Alireza Sheikhi MD Under super vision of

EhsanAli Aliby MD and MMehdizadehMD Neuroscience Research Center

Department of Neurosurgery

Poostchi Eye Research Center

Department of Ophthalmology

Shiraz university of medical sciences

1-1 optic nerve

Optic nerve is the second pair of the cranial nerves in the human and overall it is considered as the parts of central nervous system

It is surrounded by all three meningial layers In the other word optic nerve is a part of brain which is extending into the periphery and it covers as it in the brain tissue (1 2)

Overall the optic nerve has four anatomical parts the intraocular intra orbital intra canalicular and intra cranial sections (2)

1-2 Intra ocular pressure

Intra ocular pressure (IOP) is the pressure of fluid inside the eyes (3 4) the fluid is produced by aqueous humor and drainage from trabeclar meshwork which is located in the anterior chamber angle The pressure is also influenced by thickness and rigidity of corneal

Tonometer is an acceptable method for measurement of IOP Normal IOP is defined between 10 mmHg up to 20 mmHg (Average of 155) (3 4)

With considering of direct connection of optic nerve and brain tissue it is acceptable to think about the possible correlation between intraocular pressures in the globe and intra cranial pressure in the brain

1-3 Intra Cranial Pressure

Intracranial pressure (ICP) is the fluid pressure inside the skull and on the brain tissue The pressure is mainly controlled by balance in the production and absorption of fluid CSF produced by choroid plexus and the brain float in it

(5) ICP is normally varied between 7-20 mmHg in the supine position and became negative in the vertical position (67)

There is several mechanism of increasing in ICP mass effects of tumors or abscess can directly cause increasing in ICP Increase in CSF production in meningitis idiopathic intracranial hypertension is the other cause (6)

Headache nausea and vomiting are most important symptoms in increasing in ICP Altered level of consciousness and papilledema are the signs that detected in physical examination An edemas optic nerve is a helpful sign that shows the ICP elevation (7 8)

1-4 Lamina cribrosa Lamina cribrosa works as a junction between intra

cranial and intra ocular compartments It is a Mesh-like structure This structure formed by several layers which is containing of collagen fibers

The optic nerve fibers exit the eye ball through this sclera hole in the posterior part of the globe It is helps to maintain the pressure gradient among the eye tissues and surrounding parts By increase in the intraocular pressure this component bulges outward this bulging and pressure effect on the optic nerve is considered as an important pathology in glaucoma and other disease with increasing IOP (9)

1_5CSF pressure may be equivalent to IOP in its influence on laminar pressure gradient and optic disk surface movement

The correlation of IOP and ICP was based partly to both anatomical and physiological connection between intracranial fossa in one hand and orbit in the other hand considering with the compression of posterior globe by neuro imaging in some patients with increased ICP

1_6The direct connection of optic nerve and the brain tissue suggests that there should be a possible correlation between IOP in the globe and ICP in the brain lamina cribrosa works as a junction between these two compartments and it may play an unknown role in this relation

In the other word both CSF pressure and IOP influence the laminar pressure gradient in and consequently on the optic disk surface movement The influence of CSF pressure affects the axonal transport which is known to be important in glaucoma process

1_7Based on the detection of posterior compression of the globe in some patients with increased ICP in neuro imaging studies the balance between the CSF pressure around the optic nerve and the IOP in the globe may change the position of the lamina cribrosa

So papilledema may be the results of imbalance between ICP and IOP that leads to bowing of the lamina cribrosa toward the less pressured chamber ie the vitreous cavity (10)

1_8Posterior bowing of the lamina cribrosa known as cupping in the glaucoma patients may be another presentation of this imbalance

Accordingly it was supposed that this compression of posterior of glob may lead to a transient event that may resemble as a temporary increase in IOP The increase of IOP would accordingly return to base line by any means since IOP was controlled by numerous factors

The correlation between IOP and ICP still remains un-clarified and there are controversies of presence of any correlation between IOP and ICP In this study we try to investigate the effect of iatrogenic reduction of Intraocular Pressure on Intracranial Pressure in dogs as animal models

Shiraz university of medical sciences

1_1)Berdahl JP et al study in 2008

Berdahl JP et al in 2008 via a case control study tried to compare cerebrospinal fluid (CSF) pressure in patients with primary open-angle glaucoma (POAG) and with that in nonglaucomatous patients

In this study between 1996 to 2007 Thirty-one thousand seven hundred and eighty-six subjects were underwent lumbar puncture (LP)

1-1 optic nerve

Optic nerve is the second pair of the cranial nerves in the human and overall it is considered as the parts of central nervous system

It is surrounded by all three meningial layers In the other word optic nerve is a part of brain which is extending into the periphery and it covers as it in the brain tissue (1 2)

Overall the optic nerve has four anatomical parts the intraocular intra orbital intra canalicular and intra cranial sections (2)

1-2 Intra ocular pressure

Intra ocular pressure (IOP) is the pressure of fluid inside the eyes (3 4) the fluid is produced by aqueous humor and drainage from trabeclar meshwork which is located in the anterior chamber angle The pressure is also influenced by thickness and rigidity of corneal

Tonometer is an acceptable method for measurement of IOP Normal IOP is defined between 10 mmHg up to 20 mmHg (Average of 155) (3 4)

With considering of direct connection of optic nerve and brain tissue it is acceptable to think about the possible correlation between intraocular pressures in the globe and intra cranial pressure in the brain

1-3 Intra Cranial Pressure

Intracranial pressure (ICP) is the fluid pressure inside the skull and on the brain tissue The pressure is mainly controlled by balance in the production and absorption of fluid CSF produced by choroid plexus and the brain float in it

(5) ICP is normally varied between 7-20 mmHg in the supine position and became negative in the vertical position (67)

There is several mechanism of increasing in ICP mass effects of tumors or abscess can directly cause increasing in ICP Increase in CSF production in meningitis idiopathic intracranial hypertension is the other cause (6)

Headache nausea and vomiting are most important symptoms in increasing in ICP Altered level of consciousness and papilledema are the signs that detected in physical examination An edemas optic nerve is a helpful sign that shows the ICP elevation (7 8)

1-4 Lamina cribrosa Lamina cribrosa works as a junction between intra

cranial and intra ocular compartments It is a Mesh-like structure This structure formed by several layers which is containing of collagen fibers

The optic nerve fibers exit the eye ball through this sclera hole in the posterior part of the globe It is helps to maintain the pressure gradient among the eye tissues and surrounding parts By increase in the intraocular pressure this component bulges outward this bulging and pressure effect on the optic nerve is considered as an important pathology in glaucoma and other disease with increasing IOP (9)

1_5CSF pressure may be equivalent to IOP in its influence on laminar pressure gradient and optic disk surface movement

The correlation of IOP and ICP was based partly to both anatomical and physiological connection between intracranial fossa in one hand and orbit in the other hand considering with the compression of posterior globe by neuro imaging in some patients with increased ICP

1_6The direct connection of optic nerve and the brain tissue suggests that there should be a possible correlation between IOP in the globe and ICP in the brain lamina cribrosa works as a junction between these two compartments and it may play an unknown role in this relation

In the other word both CSF pressure and IOP influence the laminar pressure gradient in and consequently on the optic disk surface movement The influence of CSF pressure affects the axonal transport which is known to be important in glaucoma process

1_7Based on the detection of posterior compression of the globe in some patients with increased ICP in neuro imaging studies the balance between the CSF pressure around the optic nerve and the IOP in the globe may change the position of the lamina cribrosa

So papilledema may be the results of imbalance between ICP and IOP that leads to bowing of the lamina cribrosa toward the less pressured chamber ie the vitreous cavity (10)

1_8Posterior bowing of the lamina cribrosa known as cupping in the glaucoma patients may be another presentation of this imbalance

Accordingly it was supposed that this compression of posterior of glob may lead to a transient event that may resemble as a temporary increase in IOP The increase of IOP would accordingly return to base line by any means since IOP was controlled by numerous factors

The correlation between IOP and ICP still remains un-clarified and there are controversies of presence of any correlation between IOP and ICP In this study we try to investigate the effect of iatrogenic reduction of Intraocular Pressure on Intracranial Pressure in dogs as animal models

Shiraz university of medical sciences

1_1)Berdahl JP et al study in 2008

Berdahl JP et al in 2008 via a case control study tried to compare cerebrospinal fluid (CSF) pressure in patients with primary open-angle glaucoma (POAG) and with that in nonglaucomatous patients

In this study between 1996 to 2007 Thirty-one thousand seven hundred and eighty-six subjects were underwent lumbar puncture (LP)

1-2 Intra ocular pressure

Intra ocular pressure (IOP) is the pressure of fluid inside the eyes (3 4) the fluid is produced by aqueous humor and drainage from trabeclar meshwork which is located in the anterior chamber angle The pressure is also influenced by thickness and rigidity of corneal

Tonometer is an acceptable method for measurement of IOP Normal IOP is defined between 10 mmHg up to 20 mmHg (Average of 155) (3 4)

With considering of direct connection of optic nerve and brain tissue it is acceptable to think about the possible correlation between intraocular pressures in the globe and intra cranial pressure in the brain

1-3 Intra Cranial Pressure

Intracranial pressure (ICP) is the fluid pressure inside the skull and on the brain tissue The pressure is mainly controlled by balance in the production and absorption of fluid CSF produced by choroid plexus and the brain float in it

(5) ICP is normally varied between 7-20 mmHg in the supine position and became negative in the vertical position (67)

There is several mechanism of increasing in ICP mass effects of tumors or abscess can directly cause increasing in ICP Increase in CSF production in meningitis idiopathic intracranial hypertension is the other cause (6)

Headache nausea and vomiting are most important symptoms in increasing in ICP Altered level of consciousness and papilledema are the signs that detected in physical examination An edemas optic nerve is a helpful sign that shows the ICP elevation (7 8)

1-4 Lamina cribrosa Lamina cribrosa works as a junction between intra

cranial and intra ocular compartments It is a Mesh-like structure This structure formed by several layers which is containing of collagen fibers

The optic nerve fibers exit the eye ball through this sclera hole in the posterior part of the globe It is helps to maintain the pressure gradient among the eye tissues and surrounding parts By increase in the intraocular pressure this component bulges outward this bulging and pressure effect on the optic nerve is considered as an important pathology in glaucoma and other disease with increasing IOP (9)

1_5CSF pressure may be equivalent to IOP in its influence on laminar pressure gradient and optic disk surface movement

The correlation of IOP and ICP was based partly to both anatomical and physiological connection between intracranial fossa in one hand and orbit in the other hand considering with the compression of posterior globe by neuro imaging in some patients with increased ICP

1_6The direct connection of optic nerve and the brain tissue suggests that there should be a possible correlation between IOP in the globe and ICP in the brain lamina cribrosa works as a junction between these two compartments and it may play an unknown role in this relation

In the other word both CSF pressure and IOP influence the laminar pressure gradient in and consequently on the optic disk surface movement The influence of CSF pressure affects the axonal transport which is known to be important in glaucoma process

1_7Based on the detection of posterior compression of the globe in some patients with increased ICP in neuro imaging studies the balance between the CSF pressure around the optic nerve and the IOP in the globe may change the position of the lamina cribrosa

So papilledema may be the results of imbalance between ICP and IOP that leads to bowing of the lamina cribrosa toward the less pressured chamber ie the vitreous cavity (10)

1_8Posterior bowing of the lamina cribrosa known as cupping in the glaucoma patients may be another presentation of this imbalance

Accordingly it was supposed that this compression of posterior of glob may lead to a transient event that may resemble as a temporary increase in IOP The increase of IOP would accordingly return to base line by any means since IOP was controlled by numerous factors

The correlation between IOP and ICP still remains un-clarified and there are controversies of presence of any correlation between IOP and ICP In this study we try to investigate the effect of iatrogenic reduction of Intraocular Pressure on Intracranial Pressure in dogs as animal models

Shiraz university of medical sciences

1_1)Berdahl JP et al study in 2008

Berdahl JP et al in 2008 via a case control study tried to compare cerebrospinal fluid (CSF) pressure in patients with primary open-angle glaucoma (POAG) and with that in nonglaucomatous patients

In this study between 1996 to 2007 Thirty-one thousand seven hundred and eighty-six subjects were underwent lumbar puncture (LP)

1-3 Intra Cranial Pressure

Intracranial pressure (ICP) is the fluid pressure inside the skull and on the brain tissue The pressure is mainly controlled by balance in the production and absorption of fluid CSF produced by choroid plexus and the brain float in it

(5) ICP is normally varied between 7-20 mmHg in the supine position and became negative in the vertical position (67)

There is several mechanism of increasing in ICP mass effects of tumors or abscess can directly cause increasing in ICP Increase in CSF production in meningitis idiopathic intracranial hypertension is the other cause (6)

Headache nausea and vomiting are most important symptoms in increasing in ICP Altered level of consciousness and papilledema are the signs that detected in physical examination An edemas optic nerve is a helpful sign that shows the ICP elevation (7 8)

1-4 Lamina cribrosa Lamina cribrosa works as a junction between intra

cranial and intra ocular compartments It is a Mesh-like structure This structure formed by several layers which is containing of collagen fibers

The optic nerve fibers exit the eye ball through this sclera hole in the posterior part of the globe It is helps to maintain the pressure gradient among the eye tissues and surrounding parts By increase in the intraocular pressure this component bulges outward this bulging and pressure effect on the optic nerve is considered as an important pathology in glaucoma and other disease with increasing IOP (9)

1_5CSF pressure may be equivalent to IOP in its influence on laminar pressure gradient and optic disk surface movement

The correlation of IOP and ICP was based partly to both anatomical and physiological connection between intracranial fossa in one hand and orbit in the other hand considering with the compression of posterior globe by neuro imaging in some patients with increased ICP

1_6The direct connection of optic nerve and the brain tissue suggests that there should be a possible correlation between IOP in the globe and ICP in the brain lamina cribrosa works as a junction between these two compartments and it may play an unknown role in this relation

In the other word both CSF pressure and IOP influence the laminar pressure gradient in and consequently on the optic disk surface movement The influence of CSF pressure affects the axonal transport which is known to be important in glaucoma process

1_7Based on the detection of posterior compression of the globe in some patients with increased ICP in neuro imaging studies the balance between the CSF pressure around the optic nerve and the IOP in the globe may change the position of the lamina cribrosa

So papilledema may be the results of imbalance between ICP and IOP that leads to bowing of the lamina cribrosa toward the less pressured chamber ie the vitreous cavity (10)

1_8Posterior bowing of the lamina cribrosa known as cupping in the glaucoma patients may be another presentation of this imbalance

Accordingly it was supposed that this compression of posterior of glob may lead to a transient event that may resemble as a temporary increase in IOP The increase of IOP would accordingly return to base line by any means since IOP was controlled by numerous factors

The correlation between IOP and ICP still remains un-clarified and there are controversies of presence of any correlation between IOP and ICP In this study we try to investigate the effect of iatrogenic reduction of Intraocular Pressure on Intracranial Pressure in dogs as animal models

Shiraz university of medical sciences

1_1)Berdahl JP et al study in 2008

Berdahl JP et al in 2008 via a case control study tried to compare cerebrospinal fluid (CSF) pressure in patients with primary open-angle glaucoma (POAG) and with that in nonglaucomatous patients

In this study between 1996 to 2007 Thirty-one thousand seven hundred and eighty-six subjects were underwent lumbar puncture (LP)

There is several mechanism of increasing in ICP mass effects of tumors or abscess can directly cause increasing in ICP Increase in CSF production in meningitis idiopathic intracranial hypertension is the other cause (6)

Headache nausea and vomiting are most important symptoms in increasing in ICP Altered level of consciousness and papilledema are the signs that detected in physical examination An edemas optic nerve is a helpful sign that shows the ICP elevation (7 8)

1-4 Lamina cribrosa Lamina cribrosa works as a junction between intra

cranial and intra ocular compartments It is a Mesh-like structure This structure formed by several layers which is containing of collagen fibers

The optic nerve fibers exit the eye ball through this sclera hole in the posterior part of the globe It is helps to maintain the pressure gradient among the eye tissues and surrounding parts By increase in the intraocular pressure this component bulges outward this bulging and pressure effect on the optic nerve is considered as an important pathology in glaucoma and other disease with increasing IOP (9)

1_5CSF pressure may be equivalent to IOP in its influence on laminar pressure gradient and optic disk surface movement

The correlation of IOP and ICP was based partly to both anatomical and physiological connection between intracranial fossa in one hand and orbit in the other hand considering with the compression of posterior globe by neuro imaging in some patients with increased ICP

1_6The direct connection of optic nerve and the brain tissue suggests that there should be a possible correlation between IOP in the globe and ICP in the brain lamina cribrosa works as a junction between these two compartments and it may play an unknown role in this relation

In the other word both CSF pressure and IOP influence the laminar pressure gradient in and consequently on the optic disk surface movement The influence of CSF pressure affects the axonal transport which is known to be important in glaucoma process

1_7Based on the detection of posterior compression of the globe in some patients with increased ICP in neuro imaging studies the balance between the CSF pressure around the optic nerve and the IOP in the globe may change the position of the lamina cribrosa

So papilledema may be the results of imbalance between ICP and IOP that leads to bowing of the lamina cribrosa toward the less pressured chamber ie the vitreous cavity (10)

1_8Posterior bowing of the lamina cribrosa known as cupping in the glaucoma patients may be another presentation of this imbalance

Accordingly it was supposed that this compression of posterior of glob may lead to a transient event that may resemble as a temporary increase in IOP The increase of IOP would accordingly return to base line by any means since IOP was controlled by numerous factors

The correlation between IOP and ICP still remains un-clarified and there are controversies of presence of any correlation between IOP and ICP In this study we try to investigate the effect of iatrogenic reduction of Intraocular Pressure on Intracranial Pressure in dogs as animal models

Shiraz university of medical sciences

1_1)Berdahl JP et al study in 2008

Berdahl JP et al in 2008 via a case control study tried to compare cerebrospinal fluid (CSF) pressure in patients with primary open-angle glaucoma (POAG) and with that in nonglaucomatous patients

In this study between 1996 to 2007 Thirty-one thousand seven hundred and eighty-six subjects were underwent lumbar puncture (LP)

1-4 Lamina cribrosa Lamina cribrosa works as a junction between intra

cranial and intra ocular compartments It is a Mesh-like structure This structure formed by several layers which is containing of collagen fibers

The optic nerve fibers exit the eye ball through this sclera hole in the posterior part of the globe It is helps to maintain the pressure gradient among the eye tissues and surrounding parts By increase in the intraocular pressure this component bulges outward this bulging and pressure effect on the optic nerve is considered as an important pathology in glaucoma and other disease with increasing IOP (9)

1_5CSF pressure may be equivalent to IOP in its influence on laminar pressure gradient and optic disk surface movement

The correlation of IOP and ICP was based partly to both anatomical and physiological connection between intracranial fossa in one hand and orbit in the other hand considering with the compression of posterior globe by neuro imaging in some patients with increased ICP

1_6The direct connection of optic nerve and the brain tissue suggests that there should be a possible correlation between IOP in the globe and ICP in the brain lamina cribrosa works as a junction between these two compartments and it may play an unknown role in this relation

In the other word both CSF pressure and IOP influence the laminar pressure gradient in and consequently on the optic disk surface movement The influence of CSF pressure affects the axonal transport which is known to be important in glaucoma process

1_7Based on the detection of posterior compression of the globe in some patients with increased ICP in neuro imaging studies the balance between the CSF pressure around the optic nerve and the IOP in the globe may change the position of the lamina cribrosa

So papilledema may be the results of imbalance between ICP and IOP that leads to bowing of the lamina cribrosa toward the less pressured chamber ie the vitreous cavity (10)

1_8Posterior bowing of the lamina cribrosa known as cupping in the glaucoma patients may be another presentation of this imbalance

Accordingly it was supposed that this compression of posterior of glob may lead to a transient event that may resemble as a temporary increase in IOP The increase of IOP would accordingly return to base line by any means since IOP was controlled by numerous factors

The correlation between IOP and ICP still remains un-clarified and there are controversies of presence of any correlation between IOP and ICP In this study we try to investigate the effect of iatrogenic reduction of Intraocular Pressure on Intracranial Pressure in dogs as animal models

Shiraz university of medical sciences

1_1)Berdahl JP et al study in 2008

Berdahl JP et al in 2008 via a case control study tried to compare cerebrospinal fluid (CSF) pressure in patients with primary open-angle glaucoma (POAG) and with that in nonglaucomatous patients

In this study between 1996 to 2007 Thirty-one thousand seven hundred and eighty-six subjects were underwent lumbar puncture (LP)

1_5CSF pressure may be equivalent to IOP in its influence on laminar pressure gradient and optic disk surface movement

The correlation of IOP and ICP was based partly to both anatomical and physiological connection between intracranial fossa in one hand and orbit in the other hand considering with the compression of posterior globe by neuro imaging in some patients with increased ICP

1_6The direct connection of optic nerve and the brain tissue suggests that there should be a possible correlation between IOP in the globe and ICP in the brain lamina cribrosa works as a junction between these two compartments and it may play an unknown role in this relation

In the other word both CSF pressure and IOP influence the laminar pressure gradient in and consequently on the optic disk surface movement The influence of CSF pressure affects the axonal transport which is known to be important in glaucoma process

1_7Based on the detection of posterior compression of the globe in some patients with increased ICP in neuro imaging studies the balance between the CSF pressure around the optic nerve and the IOP in the globe may change the position of the lamina cribrosa

So papilledema may be the results of imbalance between ICP and IOP that leads to bowing of the lamina cribrosa toward the less pressured chamber ie the vitreous cavity (10)

1_8Posterior bowing of the lamina cribrosa known as cupping in the glaucoma patients may be another presentation of this imbalance

Accordingly it was supposed that this compression of posterior of glob may lead to a transient event that may resemble as a temporary increase in IOP The increase of IOP would accordingly return to base line by any means since IOP was controlled by numerous factors

The correlation between IOP and ICP still remains un-clarified and there are controversies of presence of any correlation between IOP and ICP In this study we try to investigate the effect of iatrogenic reduction of Intraocular Pressure on Intracranial Pressure in dogs as animal models

Shiraz university of medical sciences

1_1)Berdahl JP et al study in 2008

Berdahl JP et al in 2008 via a case control study tried to compare cerebrospinal fluid (CSF) pressure in patients with primary open-angle glaucoma (POAG) and with that in nonglaucomatous patients

In this study between 1996 to 2007 Thirty-one thousand seven hundred and eighty-six subjects were underwent lumbar puncture (LP)

1_6The direct connection of optic nerve and the brain tissue suggests that there should be a possible correlation between IOP in the globe and ICP in the brain lamina cribrosa works as a junction between these two compartments and it may play an unknown role in this relation

In the other word both CSF pressure and IOP influence the laminar pressure gradient in and consequently on the optic disk surface movement The influence of CSF pressure affects the axonal transport which is known to be important in glaucoma process

1_7Based on the detection of posterior compression of the globe in some patients with increased ICP in neuro imaging studies the balance between the CSF pressure around the optic nerve and the IOP in the globe may change the position of the lamina cribrosa

So papilledema may be the results of imbalance between ICP and IOP that leads to bowing of the lamina cribrosa toward the less pressured chamber ie the vitreous cavity (10)

1_8Posterior bowing of the lamina cribrosa known as cupping in the glaucoma patients may be another presentation of this imbalance

Accordingly it was supposed that this compression of posterior of glob may lead to a transient event that may resemble as a temporary increase in IOP The increase of IOP would accordingly return to base line by any means since IOP was controlled by numerous factors

The correlation between IOP and ICP still remains un-clarified and there are controversies of presence of any correlation between IOP and ICP In this study we try to investigate the effect of iatrogenic reduction of Intraocular Pressure on Intracranial Pressure in dogs as animal models

Shiraz university of medical sciences

1_1)Berdahl JP et al study in 2008

Berdahl JP et al in 2008 via a case control study tried to compare cerebrospinal fluid (CSF) pressure in patients with primary open-angle glaucoma (POAG) and with that in nonglaucomatous patients

In this study between 1996 to 2007 Thirty-one thousand seven hundred and eighty-six subjects were underwent lumbar puncture (LP)

1_7Based on the detection of posterior compression of the globe in some patients with increased ICP in neuro imaging studies the balance between the CSF pressure around the optic nerve and the IOP in the globe may change the position of the lamina cribrosa

So papilledema may be the results of imbalance between ICP and IOP that leads to bowing of the lamina cribrosa toward the less pressured chamber ie the vitreous cavity (10)

1_8Posterior bowing of the lamina cribrosa known as cupping in the glaucoma patients may be another presentation of this imbalance

Accordingly it was supposed that this compression of posterior of glob may lead to a transient event that may resemble as a temporary increase in IOP The increase of IOP would accordingly return to base line by any means since IOP was controlled by numerous factors

The correlation between IOP and ICP still remains un-clarified and there are controversies of presence of any correlation between IOP and ICP In this study we try to investigate the effect of iatrogenic reduction of Intraocular Pressure on Intracranial Pressure in dogs as animal models

Shiraz university of medical sciences

1_1)Berdahl JP et al study in 2008

Berdahl JP et al in 2008 via a case control study tried to compare cerebrospinal fluid (CSF) pressure in patients with primary open-angle glaucoma (POAG) and with that in nonglaucomatous patients

In this study between 1996 to 2007 Thirty-one thousand seven hundred and eighty-six subjects were underwent lumbar puncture (LP)

1_8Posterior bowing of the lamina cribrosa known as cupping in the glaucoma patients may be another presentation of this imbalance

Accordingly it was supposed that this compression of posterior of glob may lead to a transient event that may resemble as a temporary increase in IOP The increase of IOP would accordingly return to base line by any means since IOP was controlled by numerous factors

The correlation between IOP and ICP still remains un-clarified and there are controversies of presence of any correlation between IOP and ICP In this study we try to investigate the effect of iatrogenic reduction of Intraocular Pressure on Intracranial Pressure in dogs as animal models

Shiraz university of medical sciences

1_1)Berdahl JP et al study in 2008

Berdahl JP et al in 2008 via a case control study tried to compare cerebrospinal fluid (CSF) pressure in patients with primary open-angle glaucoma (POAG) and with that in nonglaucomatous patients

In this study between 1996 to 2007 Thirty-one thousand seven hundred and eighty-six subjects were underwent lumbar puncture (LP)

Shiraz university of medical sciences

1_1)Berdahl JP et al study in 2008

Berdahl JP et al in 2008 via a case control study tried to compare cerebrospinal fluid (CSF) pressure in patients with primary open-angle glaucoma (POAG) and with that in nonglaucomatous patients

In this study between 1996 to 2007 Thirty-one thousand seven hundred and eighty-six subjects were underwent lumbar puncture (LP)

1_1)Berdahl JP et al study in 2008

Berdahl JP et al in 2008 via a case control study tried to compare cerebrospinal fluid (CSF) pressure in patients with primary open-angle glaucoma (POAG) and with that in nonglaucomatous patients

In this study between 1996 to 2007 Thirty-one thousand seven hundred and eighty-six subjects were underwent lumbar puncture (LP)

The mean CSF pressure was 130+-42 mmHg in nonglaucomatc patients and 92+-29 mmHg in POAG patients (Plt000005) The CSF pressure was lower in POAG patients

Linear regression analysis showed that cup-to-disc ratio was correlated independently with IOP (Plt0001) CSF pressure (Plt0001) and the Trans laminar pressure difference (Plt0001)

On the other hand Multivariate analysis showed that larger cup-to-disc ratio (Plt0001) was associated with lower CSF pressure

Accordingly in his study the researchers demonstrated that CSF pressure is significantly lower in POAG patients in compare with that in nonglaucomatouscontrols

Their results support the notion that CSF pressure may play an important contributory role in the pathogenesis of POAG (11)

2_1)Dickerman RD et al study in 1998

In the study of Dickerman RD et al in 1998 the researchers tried to investigated that does Intra-ocular pressure changes during maximal isometric contraction reflect intra-cranial pressure or retinal venous pressure or not

This study was started with review of the articles which was evaluated the recent publications The researchers mentioned that the recent studies have suggested IOP may be an indirect assessment of ICP

Both IOP and ICP have similar physiologic pressure ranges and both have similar responses to changes in intra-abdominal intra-thoracic and aortic pressure

The researchers said that there are many reports that showed the intracranial hemorrhage subarachnoid hemorrhage retinal hemorrhage and retinal detachment are associated with weight lifting but there are no human study which examined the IOP changes during heavy exercises and weight lifting

So they tried to investigate the IOP changes during maximal isometric contraction

In this study Intra-ocular pressure was measured by noncontact tonometry at rest and during maximal isometric contraction

All subjects IOP were within normal ranges (mean 13 +- 28 mmHg) at rest but it was significantly (p lt 00001) elevated in each subject during maximal contraction (mean 28 +- 93 mmHg)

Linear regression analysis showed a significant linear relationship (r = 062 p lt 00001) in the net change of IOP from rest to maximal contraction for each subject

Their study demonstrates that IOP elevates to pathophysiologic levels during resistance exercise The increased pressures generated by power athletes during weightlifting may leads to elevations in ICP which obstruct venous outflow leading to hemorrhage and elevations in IOP (12)

Sajjadi SA et al study in 2006

In the study which was done on 2006 in Tehran university sajjadi et al evaluated the correlation between ICP and IOP Their study was performed on 77 patients The patients who had any history of glaucoma using drugs which affected IOP and abnormal ocular finding were excluded from the study

ICP of the other patients was measured by LP and IOP was measured by two scales of Schiotz tonometerin both eyes and the mean was calculated Finally they found a significant correlation between IOP and ICP (13)

Sheeran P et al study in 2000

In the study which was performed at 2000 by Sheeran P et al they demonstrated that although there is a significant correlation between intraocular pressure and intracranial pressure in neurosurgical patients change in intraocular pressure is a poor predictor of change in intracranial pressure (14)

Han Y et al study in 2008

On the other hand Han Y et al in 2008 showed there isnrsquot any correlation between intraocular pressure and intracranial pressure

They reviewed the medical records of all patients who underwent lumbar puncture between 1991 and 2007 in the neuro-ophthalmology clinic of the University of California San Francisco Data for IOP and ICP were available for 55 patients But they didnrsquot find any correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059) and accordingly mentioned that IOP measurement is not a useful substitute for ICP measurement (15)

1_The mentioned studies had several limitations for example some of these studies was performed only patients with both glaucoma and neurological problem necessitate lumber puncture that may affect the results of study by some unexpected biases

2_Nowadays the subject of any correlation between IOP and ICP remains as a sophisticated puzzle to be resolved

Since there is no animal model study in the literature as a first experience in the world the present study was designed to evaluate any relation of IOP and ICP under controlled experimental condition by inducing iatrogenic reduction of IOP in normal eyes and healthy animals and measurement of ICP in response

1-1Fifteen matured healthy out-bred dogs ( mean 10 kg) provided from laboratory animal center related to shiraz university of medical sciences were enrolled The study was approved in the university ethic committee and all procedures were performed in accordance to ARVO statement for the use of animals

In the supine position all the dogs underwent general anesthesia using Nesdonal (Sandoz Gmbh Kundl Austria )

1-2The mean IOP was recorded by double measurements in both eyes and considered as a primary IOP The animals were allocated to three groups Group 1 received Timolol ( Timolol sinadarou) one drop each 12 hours As topical anti glaucoma medication only in the right eye

Group 2 received latanoprost (Xalatan Farmacin Belgium) one drop once a day And group 3 underwent Trabeculectomy in the right eye to reduce IOP The IOP was determine using tonopen (RoichertTONO-PEN XL Applanation) for both eyes except for group 3 where the mean pressure was recorded by double measurement of IOP in the right eye (Table 3-1)

1_3To measure the ICP the hairs were clipped in the back of the head and the neck area of the dogs For cerebromedullaryapproach the land mark for midline position ( the occipital protuberance) was marked and the neck of the animal was positioned in hands and flexed up to optimal position for palpation of the space

1_4A 22 gauge needle was inserted in midline near the cranial borders of the wing of atlas (C1)When a slight loss of resistance was determined the needle was inserted further A 3 way tube was connected to the needle and when a flow of CSF was observed in the tube the CSF pressure was measured against a water column

Table 3-1 type of intervention in each group

Groups Type of intervention in

right eye

Group 1 Timolol drop 05 twice a

day

Group 2 Latanoprest(xalatan )drop

daily

Group 3 Trabeculectomy operation

1_6Trabeculectomy

Trabeculectomy was performed using Watsonrsquos modification of the Cairns technique (16) first a limbus-based conjuctival flap was prepared the sclera was exposed and a rectangular 34 mm sclera flap was made Then a 1 mm sclerosomywas made followed by peripheral iridectomy and finally the conjunctiva was closed with a continuous 10-0 nylon suture

1_7In the same manner after 2 and 4 weeks of drug administration or surgical procedure the IOP was measured with tonopen in the right eye The procedure was similarly carried out four weeks later

1_8To show the correlation between IOP and ICP all results were sorted while ignoring the methods of reduction of IOP and also the time of measurements

All the dogs underwent a same method of anesthesia and measurement of IOP and ICP was the same in all groups so bias effect of these materials will be at least

1_9An analysis of variables with repeated measure design was used to determine changes in parameters over time (day 0 14 and 28) An independent t-test was used to determine possible differences in various parameters in IOP and ICP on day 0 14 and 28

Pearson correlation coefficient was used to determine the strength of the relationship existing among various parameters On the other hand we used General linear model to evaluate ghanges in each group separately

The data were analyzed using the statistical package for social science series (SPSS 150) and ple 005 was considered as significant

1_1There were 15 skeletally mature healthy dogs enrolled in this study All dogs were remained lived till end of study The overall mean age was 21yearsplusmn 028 (range 15-25 years) with a mean weight of 175 plusmn 118 kg (16-19 kg)

The mean primary IOP was 2040plusmn 470 and that of ICP was 746plusmn 209 As is shown in table 4-1 dogs randomly allocated in 3 groups were matched in terms of weight age and also in both primary IOP and ICP (Table 4-1)

Groups Age Weight Primary IOP Primary ICP

Group A 2-25

22plusmn 027

16-19

17plusmn141

15-27

2280plusmn471

5-9

66plusmn181

Group B 15-2

190plusmn022

16-19

178plusmn109

15-27

218plusmn465

5-10

76plusmn207

Group C 2-25

220plusmn027

16-19

177plusmn109

14-20

166plusmn240

5-10

82plusmn248

P value 365 101 476 190

Table4-1 primary

measurements of the

parameters

1_3According to drug administration and trabeculectomy to changes IOP and subsequently evaluate changes in ICP multiple liner repeated measurement was performed that showed statistically considerable deference in IOP after drug administration for 2 weeks and even after 4 weeks indicative of effective application of drugs and confirmed the study to full fill our idea (Table 4-2 figure 4-1)

Groups

IOP

Primary IOP IOP after 2

weeks of drug

administration

IOP after 4

weeks of drug

administration

P value

Group A 15-27

2280plusmn471

10-19

162 plusmn370

10-18

148plusmn327

0003

Group B 15-27

218plusmn465

10-18

142plusmn389

9-14

114plusmn240

000

Group C 14-20

166plusmn240

3-6

44plusmn114

3-5

4plusmn070

000

Table 4-2 secondary

measurements of the

parameters

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

4 weeks after to drug

adminstration or surgery

2 weeks after to drug

adminstration or surgery

Prior to drug adminstration

or surgery

0

2

4

6

8

10

12

14

16

18

20

0 5 10 15 20 25 30

Intera Ocular Pressure

Inte

ra C

rani

al P

ress

ure

1_5In this regard the correlation of primary IOP and primary ICP was not statistically significant ( 1750 vs 2040 P Value 095 ) however after 2 weeks these measures become considerable ( 1106 vs 1173 P value 002 ) Subsequently after 4 weeks again results were infavor of considerable negative correlation of IOP and ICP ( 1006 vs 1183 P value 002 )

1_6On the other hand as we encounter with statistically considerable correlation between IOP and ICP in order to be able to make a model for the relation we joined all the results of IOP and ICP ignoring methods of induced IOP changes and also time of measurement in order to IOP in 45 samples

1_7Therefore according to Pearson correlation analysis there was considerable negative correlation between IOP ( v= -067 P value =000 )(fig 4-5) As was shown in table 3 felting a multiple regression model to the data where ICP was the dependent variable and IOP was the continuous predictor variable and generated the model to show correlation as follows

1_8(^ICPi) =1566 - 0337 IOP ( R2 =0448 ) and according to the table 4 the regression analysis acceptable statistically

Table 4-4 Measures was indicated that the regression analysis acceptable statistically

Model Un

standardiz

ed

coefficients

Standardiz

ed

coefficients

t Significant

Constant

IOP

B StdError Beta 242034 34939

15066 0890 -0670 16930 000

-0337 0057 -0670 -5911 000

icpiop

30

20

10

0

preiop

preicp

2 wk iop

2 wk icp

4 wk iop

4 wk icp

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

2_Nowadays the subject of any correlation between IOP and ICP remains as a sophisticated puzzle to be resolved

Since there is no animal model study in the literature as a first experience in the world the present study was designed to evaluate any relation of IOP and ICP under controlled experimental condition by inducing iatrogenic reduction of IOP in normal eyes and healthy animals and measurement of ICP in response

1-1Fifteen matured healthy out-bred dogs ( mean 10 kg) provided from laboratory animal center related to shiraz university of medical sciences were enrolled The study was approved in the university ethic committee and all procedures were performed in accordance to ARVO statement for the use of animals

In the supine position all the dogs underwent general anesthesia using Nesdonal (Sandoz Gmbh Kundl Austria )

1-2The mean IOP was recorded by double measurements in both eyes and considered as a primary IOP The animals were allocated to three groups Group 1 received Timolol ( Timolol sinadarou) one drop each 12 hours As topical anti glaucoma medication only in the right eye

Group 2 received latanoprost (Xalatan Farmacin Belgium) one drop once a day And group 3 underwent Trabeculectomy in the right eye to reduce IOP The IOP was determine using tonopen (RoichertTONO-PEN XL Applanation) for both eyes except for group 3 where the mean pressure was recorded by double measurement of IOP in the right eye (Table 3-1)

1_3To measure the ICP the hairs were clipped in the back of the head and the neck area of the dogs For cerebromedullaryapproach the land mark for midline position ( the occipital protuberance) was marked and the neck of the animal was positioned in hands and flexed up to optimal position for palpation of the space

1_4A 22 gauge needle was inserted in midline near the cranial borders of the wing of atlas (C1)When a slight loss of resistance was determined the needle was inserted further A 3 way tube was connected to the needle and when a flow of CSF was observed in the tube the CSF pressure was measured against a water column

Table 3-1 type of intervention in each group

Groups Type of intervention in

right eye

Group 1 Timolol drop 05 twice a

day

Group 2 Latanoprest(xalatan )drop

daily

Group 3 Trabeculectomy operation

1_6Trabeculectomy

Trabeculectomy was performed using Watsonrsquos modification of the Cairns technique (16) first a limbus-based conjuctival flap was prepared the sclera was exposed and a rectangular 34 mm sclera flap was made Then a 1 mm sclerosomywas made followed by peripheral iridectomy and finally the conjunctiva was closed with a continuous 10-0 nylon suture

1_7In the same manner after 2 and 4 weeks of drug administration or surgical procedure the IOP was measured with tonopen in the right eye The procedure was similarly carried out four weeks later

1_8To show the correlation between IOP and ICP all results were sorted while ignoring the methods of reduction of IOP and also the time of measurements

All the dogs underwent a same method of anesthesia and measurement of IOP and ICP was the same in all groups so bias effect of these materials will be at least

1_9An analysis of variables with repeated measure design was used to determine changes in parameters over time (day 0 14 and 28) An independent t-test was used to determine possible differences in various parameters in IOP and ICP on day 0 14 and 28

Pearson correlation coefficient was used to determine the strength of the relationship existing among various parameters On the other hand we used General linear model to evaluate ghanges in each group separately

The data were analyzed using the statistical package for social science series (SPSS 150) and ple 005 was considered as significant

1_1There were 15 skeletally mature healthy dogs enrolled in this study All dogs were remained lived till end of study The overall mean age was 21yearsplusmn 028 (range 15-25 years) with a mean weight of 175 plusmn 118 kg (16-19 kg)

The mean primary IOP was 2040plusmn 470 and that of ICP was 746plusmn 209 As is shown in table 4-1 dogs randomly allocated in 3 groups were matched in terms of weight age and also in both primary IOP and ICP (Table 4-1)

Groups Age Weight Primary IOP Primary ICP

Group A 2-25

22plusmn 027

16-19

17plusmn141

15-27

2280plusmn471

5-9

66plusmn181

Group B 15-2

190plusmn022

16-19

178plusmn109

15-27

218plusmn465

5-10

76plusmn207

Group C 2-25

220plusmn027

16-19

177plusmn109

14-20

166plusmn240

5-10

82plusmn248

P value 365 101 476 190

Table4-1 primary

measurements of the

parameters

1_3According to drug administration and trabeculectomy to changes IOP and subsequently evaluate changes in ICP multiple liner repeated measurement was performed that showed statistically considerable deference in IOP after drug administration for 2 weeks and even after 4 weeks indicative of effective application of drugs and confirmed the study to full fill our idea (Table 4-2 figure 4-1)

Groups

IOP

Primary IOP IOP after 2

weeks of drug

administration

IOP after 4

weeks of drug

administration

P value

Group A 15-27

2280plusmn471

10-19

162 plusmn370

10-18

148plusmn327

0003

Group B 15-27

218plusmn465

10-18

142plusmn389

9-14

114plusmn240

000

Group C 14-20

166plusmn240

3-6

44plusmn114

3-5

4plusmn070

000

Table 4-2 secondary

measurements of the

parameters

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

4 weeks after to drug

adminstration or surgery

2 weeks after to drug

adminstration or surgery

Prior to drug adminstration

or surgery

0

2

4

6

8

10

12

14

16

18

20

0 5 10 15 20 25 30

Intera Ocular Pressure

Inte

ra C

rani

al P

ress

ure

1_5In this regard the correlation of primary IOP and primary ICP was not statistically significant ( 1750 vs 2040 P Value 095 ) however after 2 weeks these measures become considerable ( 1106 vs 1173 P value 002 ) Subsequently after 4 weeks again results were infavor of considerable negative correlation of IOP and ICP ( 1006 vs 1183 P value 002 )

1_6On the other hand as we encounter with statistically considerable correlation between IOP and ICP in order to be able to make a model for the relation we joined all the results of IOP and ICP ignoring methods of induced IOP changes and also time of measurement in order to IOP in 45 samples

1_7Therefore according to Pearson correlation analysis there was considerable negative correlation between IOP ( v= -067 P value =000 )(fig 4-5) As was shown in table 3 felting a multiple regression model to the data where ICP was the dependent variable and IOP was the continuous predictor variable and generated the model to show correlation as follows

1_8(^ICPi) =1566 - 0337 IOP ( R2 =0448 ) and according to the table 4 the regression analysis acceptable statistically

Table 4-4 Measures was indicated that the regression analysis acceptable statistically

Model Un

standardiz

ed

coefficients

Standardiz

ed

coefficients

t Significant

Constant

IOP

B StdError Beta 242034 34939

15066 0890 -0670 16930 000

-0337 0057 -0670 -5911 000

icpiop

30

20

10

0

preiop

preicp

2 wk iop

2 wk icp

4 wk iop

4 wk icp

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1-1Fifteen matured healthy out-bred dogs ( mean 10 kg) provided from laboratory animal center related to shiraz university of medical sciences were enrolled The study was approved in the university ethic committee and all procedures were performed in accordance to ARVO statement for the use of animals

In the supine position all the dogs underwent general anesthesia using Nesdonal (Sandoz Gmbh Kundl Austria )

1-2The mean IOP was recorded by double measurements in both eyes and considered as a primary IOP The animals were allocated to three groups Group 1 received Timolol ( Timolol sinadarou) one drop each 12 hours As topical anti glaucoma medication only in the right eye

Group 2 received latanoprost (Xalatan Farmacin Belgium) one drop once a day And group 3 underwent Trabeculectomy in the right eye to reduce IOP The IOP was determine using tonopen (RoichertTONO-PEN XL Applanation) for both eyes except for group 3 where the mean pressure was recorded by double measurement of IOP in the right eye (Table 3-1)

1_3To measure the ICP the hairs were clipped in the back of the head and the neck area of the dogs For cerebromedullaryapproach the land mark for midline position ( the occipital protuberance) was marked and the neck of the animal was positioned in hands and flexed up to optimal position for palpation of the space

1_4A 22 gauge needle was inserted in midline near the cranial borders of the wing of atlas (C1)When a slight loss of resistance was determined the needle was inserted further A 3 way tube was connected to the needle and when a flow of CSF was observed in the tube the CSF pressure was measured against a water column

Table 3-1 type of intervention in each group

Groups Type of intervention in

right eye

Group 1 Timolol drop 05 twice a

day

Group 2 Latanoprest(xalatan )drop

daily

Group 3 Trabeculectomy operation

1_6Trabeculectomy

Trabeculectomy was performed using Watsonrsquos modification of the Cairns technique (16) first a limbus-based conjuctival flap was prepared the sclera was exposed and a rectangular 34 mm sclera flap was made Then a 1 mm sclerosomywas made followed by peripheral iridectomy and finally the conjunctiva was closed with a continuous 10-0 nylon suture

1_7In the same manner after 2 and 4 weeks of drug administration or surgical procedure the IOP was measured with tonopen in the right eye The procedure was similarly carried out four weeks later

1_8To show the correlation between IOP and ICP all results were sorted while ignoring the methods of reduction of IOP and also the time of measurements

All the dogs underwent a same method of anesthesia and measurement of IOP and ICP was the same in all groups so bias effect of these materials will be at least

1_9An analysis of variables with repeated measure design was used to determine changes in parameters over time (day 0 14 and 28) An independent t-test was used to determine possible differences in various parameters in IOP and ICP on day 0 14 and 28

Pearson correlation coefficient was used to determine the strength of the relationship existing among various parameters On the other hand we used General linear model to evaluate ghanges in each group separately

The data were analyzed using the statistical package for social science series (SPSS 150) and ple 005 was considered as significant

1_1There were 15 skeletally mature healthy dogs enrolled in this study All dogs were remained lived till end of study The overall mean age was 21yearsplusmn 028 (range 15-25 years) with a mean weight of 175 plusmn 118 kg (16-19 kg)

The mean primary IOP was 2040plusmn 470 and that of ICP was 746plusmn 209 As is shown in table 4-1 dogs randomly allocated in 3 groups were matched in terms of weight age and also in both primary IOP and ICP (Table 4-1)

Groups Age Weight Primary IOP Primary ICP

Group A 2-25

22plusmn 027

16-19

17plusmn141

15-27

2280plusmn471

5-9

66plusmn181

Group B 15-2

190plusmn022

16-19

178plusmn109

15-27

218plusmn465

5-10

76plusmn207

Group C 2-25

220plusmn027

16-19

177plusmn109

14-20

166plusmn240

5-10

82plusmn248

P value 365 101 476 190

Table4-1 primary

measurements of the

parameters

1_3According to drug administration and trabeculectomy to changes IOP and subsequently evaluate changes in ICP multiple liner repeated measurement was performed that showed statistically considerable deference in IOP after drug administration for 2 weeks and even after 4 weeks indicative of effective application of drugs and confirmed the study to full fill our idea (Table 4-2 figure 4-1)

Groups

IOP

Primary IOP IOP after 2

weeks of drug

administration

IOP after 4

weeks of drug

administration

P value

Group A 15-27

2280plusmn471

10-19

162 plusmn370

10-18

148plusmn327

0003

Group B 15-27

218plusmn465

10-18

142plusmn389

9-14

114plusmn240

000

Group C 14-20

166plusmn240

3-6

44plusmn114

3-5

4plusmn070

000

Table 4-2 secondary

measurements of the

parameters

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

4 weeks after to drug

adminstration or surgery

2 weeks after to drug

adminstration or surgery

Prior to drug adminstration

or surgery

0

2

4

6

8

10

12

14

16

18

20

0 5 10 15 20 25 30

Intera Ocular Pressure

Inte

ra C

rani

al P

ress

ure

1_5In this regard the correlation of primary IOP and primary ICP was not statistically significant ( 1750 vs 2040 P Value 095 ) however after 2 weeks these measures become considerable ( 1106 vs 1173 P value 002 ) Subsequently after 4 weeks again results were infavor of considerable negative correlation of IOP and ICP ( 1006 vs 1183 P value 002 )

1_6On the other hand as we encounter with statistically considerable correlation between IOP and ICP in order to be able to make a model for the relation we joined all the results of IOP and ICP ignoring methods of induced IOP changes and also time of measurement in order to IOP in 45 samples

1_7Therefore according to Pearson correlation analysis there was considerable negative correlation between IOP ( v= -067 P value =000 )(fig 4-5) As was shown in table 3 felting a multiple regression model to the data where ICP was the dependent variable and IOP was the continuous predictor variable and generated the model to show correlation as follows

1_8(^ICPi) =1566 - 0337 IOP ( R2 =0448 ) and according to the table 4 the regression analysis acceptable statistically

Table 4-4 Measures was indicated that the regression analysis acceptable statistically

Model Un

standardiz

ed

coefficients

Standardiz

ed

coefficients

t Significant

Constant

IOP

B StdError Beta 242034 34939

15066 0890 -0670 16930 000

-0337 0057 -0670 -5911 000

icpiop

30

20

10

0

preiop

preicp

2 wk iop

2 wk icp

4 wk iop

4 wk icp

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1-2The mean IOP was recorded by double measurements in both eyes and considered as a primary IOP The animals were allocated to three groups Group 1 received Timolol ( Timolol sinadarou) one drop each 12 hours As topical anti glaucoma medication only in the right eye

Group 2 received latanoprost (Xalatan Farmacin Belgium) one drop once a day And group 3 underwent Trabeculectomy in the right eye to reduce IOP The IOP was determine using tonopen (RoichertTONO-PEN XL Applanation) for both eyes except for group 3 where the mean pressure was recorded by double measurement of IOP in the right eye (Table 3-1)

1_3To measure the ICP the hairs were clipped in the back of the head and the neck area of the dogs For cerebromedullaryapproach the land mark for midline position ( the occipital protuberance) was marked and the neck of the animal was positioned in hands and flexed up to optimal position for palpation of the space

1_4A 22 gauge needle was inserted in midline near the cranial borders of the wing of atlas (C1)When a slight loss of resistance was determined the needle was inserted further A 3 way tube was connected to the needle and when a flow of CSF was observed in the tube the CSF pressure was measured against a water column

Table 3-1 type of intervention in each group

Groups Type of intervention in

right eye

Group 1 Timolol drop 05 twice a

day

Group 2 Latanoprest(xalatan )drop

daily

Group 3 Trabeculectomy operation

1_6Trabeculectomy

Trabeculectomy was performed using Watsonrsquos modification of the Cairns technique (16) first a limbus-based conjuctival flap was prepared the sclera was exposed and a rectangular 34 mm sclera flap was made Then a 1 mm sclerosomywas made followed by peripheral iridectomy and finally the conjunctiva was closed with a continuous 10-0 nylon suture

1_7In the same manner after 2 and 4 weeks of drug administration or surgical procedure the IOP was measured with tonopen in the right eye The procedure was similarly carried out four weeks later

1_8To show the correlation between IOP and ICP all results were sorted while ignoring the methods of reduction of IOP and also the time of measurements

All the dogs underwent a same method of anesthesia and measurement of IOP and ICP was the same in all groups so bias effect of these materials will be at least

1_9An analysis of variables with repeated measure design was used to determine changes in parameters over time (day 0 14 and 28) An independent t-test was used to determine possible differences in various parameters in IOP and ICP on day 0 14 and 28

Pearson correlation coefficient was used to determine the strength of the relationship existing among various parameters On the other hand we used General linear model to evaluate ghanges in each group separately

The data were analyzed using the statistical package for social science series (SPSS 150) and ple 005 was considered as significant

1_1There were 15 skeletally mature healthy dogs enrolled in this study All dogs were remained lived till end of study The overall mean age was 21yearsplusmn 028 (range 15-25 years) with a mean weight of 175 plusmn 118 kg (16-19 kg)

The mean primary IOP was 2040plusmn 470 and that of ICP was 746plusmn 209 As is shown in table 4-1 dogs randomly allocated in 3 groups were matched in terms of weight age and also in both primary IOP and ICP (Table 4-1)

Groups Age Weight Primary IOP Primary ICP

Group A 2-25

22plusmn 027

16-19

17plusmn141

15-27

2280plusmn471

5-9

66plusmn181

Group B 15-2

190plusmn022

16-19

178plusmn109

15-27

218plusmn465

5-10

76plusmn207

Group C 2-25

220plusmn027

16-19

177plusmn109

14-20

166plusmn240

5-10

82plusmn248

P value 365 101 476 190

Table4-1 primary

measurements of the

parameters

1_3According to drug administration and trabeculectomy to changes IOP and subsequently evaluate changes in ICP multiple liner repeated measurement was performed that showed statistically considerable deference in IOP after drug administration for 2 weeks and even after 4 weeks indicative of effective application of drugs and confirmed the study to full fill our idea (Table 4-2 figure 4-1)

Groups

IOP

Primary IOP IOP after 2

weeks of drug

administration

IOP after 4

weeks of drug

administration

P value

Group A 15-27

2280plusmn471

10-19

162 plusmn370

10-18

148plusmn327

0003

Group B 15-27

218plusmn465

10-18

142plusmn389

9-14

114plusmn240

000

Group C 14-20

166plusmn240

3-6

44plusmn114

3-5

4plusmn070

000

Table 4-2 secondary

measurements of the

parameters

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

4 weeks after to drug

adminstration or surgery

2 weeks after to drug

adminstration or surgery

Prior to drug adminstration

or surgery

0

2

4

6

8

10

12

14

16

18

20

0 5 10 15 20 25 30

Intera Ocular Pressure

Inte

ra C

rani

al P

ress

ure

1_5In this regard the correlation of primary IOP and primary ICP was not statistically significant ( 1750 vs 2040 P Value 095 ) however after 2 weeks these measures become considerable ( 1106 vs 1173 P value 002 ) Subsequently after 4 weeks again results were infavor of considerable negative correlation of IOP and ICP ( 1006 vs 1183 P value 002 )

1_6On the other hand as we encounter with statistically considerable correlation between IOP and ICP in order to be able to make a model for the relation we joined all the results of IOP and ICP ignoring methods of induced IOP changes and also time of measurement in order to IOP in 45 samples

1_7Therefore according to Pearson correlation analysis there was considerable negative correlation between IOP ( v= -067 P value =000 )(fig 4-5) As was shown in table 3 felting a multiple regression model to the data where ICP was the dependent variable and IOP was the continuous predictor variable and generated the model to show correlation as follows

1_8(^ICPi) =1566 - 0337 IOP ( R2 =0448 ) and according to the table 4 the regression analysis acceptable statistically

Table 4-4 Measures was indicated that the regression analysis acceptable statistically

Model Un

standardiz

ed

coefficients

Standardiz

ed

coefficients

t Significant

Constant

IOP

B StdError Beta 242034 34939

15066 0890 -0670 16930 000

-0337 0057 -0670 -5911 000

icpiop

30

20

10

0

preiop

preicp

2 wk iop

2 wk icp

4 wk iop

4 wk icp

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_3To measure the ICP the hairs were clipped in the back of the head and the neck area of the dogs For cerebromedullaryapproach the land mark for midline position ( the occipital protuberance) was marked and the neck of the animal was positioned in hands and flexed up to optimal position for palpation of the space

1_4A 22 gauge needle was inserted in midline near the cranial borders of the wing of atlas (C1)When a slight loss of resistance was determined the needle was inserted further A 3 way tube was connected to the needle and when a flow of CSF was observed in the tube the CSF pressure was measured against a water column

Table 3-1 type of intervention in each group

Groups Type of intervention in

right eye

Group 1 Timolol drop 05 twice a

day

Group 2 Latanoprest(xalatan )drop

daily

Group 3 Trabeculectomy operation

1_6Trabeculectomy

Trabeculectomy was performed using Watsonrsquos modification of the Cairns technique (16) first a limbus-based conjuctival flap was prepared the sclera was exposed and a rectangular 34 mm sclera flap was made Then a 1 mm sclerosomywas made followed by peripheral iridectomy and finally the conjunctiva was closed with a continuous 10-0 nylon suture

1_7In the same manner after 2 and 4 weeks of drug administration or surgical procedure the IOP was measured with tonopen in the right eye The procedure was similarly carried out four weeks later

1_8To show the correlation between IOP and ICP all results were sorted while ignoring the methods of reduction of IOP and also the time of measurements

All the dogs underwent a same method of anesthesia and measurement of IOP and ICP was the same in all groups so bias effect of these materials will be at least

1_9An analysis of variables with repeated measure design was used to determine changes in parameters over time (day 0 14 and 28) An independent t-test was used to determine possible differences in various parameters in IOP and ICP on day 0 14 and 28

Pearson correlation coefficient was used to determine the strength of the relationship existing among various parameters On the other hand we used General linear model to evaluate ghanges in each group separately

The data were analyzed using the statistical package for social science series (SPSS 150) and ple 005 was considered as significant

1_1There were 15 skeletally mature healthy dogs enrolled in this study All dogs were remained lived till end of study The overall mean age was 21yearsplusmn 028 (range 15-25 years) with a mean weight of 175 plusmn 118 kg (16-19 kg)

The mean primary IOP was 2040plusmn 470 and that of ICP was 746plusmn 209 As is shown in table 4-1 dogs randomly allocated in 3 groups were matched in terms of weight age and also in both primary IOP and ICP (Table 4-1)

Groups Age Weight Primary IOP Primary ICP

Group A 2-25

22plusmn 027

16-19

17plusmn141

15-27

2280plusmn471

5-9

66plusmn181

Group B 15-2

190plusmn022

16-19

178plusmn109

15-27

218plusmn465

5-10

76plusmn207

Group C 2-25

220plusmn027

16-19

177plusmn109

14-20

166plusmn240

5-10

82plusmn248

P value 365 101 476 190

Table4-1 primary

measurements of the

parameters

1_3According to drug administration and trabeculectomy to changes IOP and subsequently evaluate changes in ICP multiple liner repeated measurement was performed that showed statistically considerable deference in IOP after drug administration for 2 weeks and even after 4 weeks indicative of effective application of drugs and confirmed the study to full fill our idea (Table 4-2 figure 4-1)

Groups

IOP

Primary IOP IOP after 2

weeks of drug

administration

IOP after 4

weeks of drug

administration

P value

Group A 15-27

2280plusmn471

10-19

162 plusmn370

10-18

148plusmn327

0003

Group B 15-27

218plusmn465

10-18

142plusmn389

9-14

114plusmn240

000

Group C 14-20

166plusmn240

3-6

44plusmn114

3-5

4plusmn070

000

Table 4-2 secondary

measurements of the

parameters

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

4 weeks after to drug

adminstration or surgery

2 weeks after to drug

adminstration or surgery

Prior to drug adminstration

or surgery

0

2

4

6

8

10

12

14

16

18

20

0 5 10 15 20 25 30

Intera Ocular Pressure

Inte

ra C

rani

al P

ress

ure

1_5In this regard the correlation of primary IOP and primary ICP was not statistically significant ( 1750 vs 2040 P Value 095 ) however after 2 weeks these measures become considerable ( 1106 vs 1173 P value 002 ) Subsequently after 4 weeks again results were infavor of considerable negative correlation of IOP and ICP ( 1006 vs 1183 P value 002 )

1_6On the other hand as we encounter with statistically considerable correlation between IOP and ICP in order to be able to make a model for the relation we joined all the results of IOP and ICP ignoring methods of induced IOP changes and also time of measurement in order to IOP in 45 samples

1_7Therefore according to Pearson correlation analysis there was considerable negative correlation between IOP ( v= -067 P value =000 )(fig 4-5) As was shown in table 3 felting a multiple regression model to the data where ICP was the dependent variable and IOP was the continuous predictor variable and generated the model to show correlation as follows

1_8(^ICPi) =1566 - 0337 IOP ( R2 =0448 ) and according to the table 4 the regression analysis acceptable statistically

Table 4-4 Measures was indicated that the regression analysis acceptable statistically

Model Un

standardiz

ed

coefficients

Standardiz

ed

coefficients

t Significant

Constant

IOP

B StdError Beta 242034 34939

15066 0890 -0670 16930 000

-0337 0057 -0670 -5911 000

icpiop

30

20

10

0

preiop

preicp

2 wk iop

2 wk icp

4 wk iop

4 wk icp

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_4A 22 gauge needle was inserted in midline near the cranial borders of the wing of atlas (C1)When a slight loss of resistance was determined the needle was inserted further A 3 way tube was connected to the needle and when a flow of CSF was observed in the tube the CSF pressure was measured against a water column

Table 3-1 type of intervention in each group

Groups Type of intervention in

right eye

Group 1 Timolol drop 05 twice a

day

Group 2 Latanoprest(xalatan )drop

daily

Group 3 Trabeculectomy operation

1_6Trabeculectomy

Trabeculectomy was performed using Watsonrsquos modification of the Cairns technique (16) first a limbus-based conjuctival flap was prepared the sclera was exposed and a rectangular 34 mm sclera flap was made Then a 1 mm sclerosomywas made followed by peripheral iridectomy and finally the conjunctiva was closed with a continuous 10-0 nylon suture

1_7In the same manner after 2 and 4 weeks of drug administration or surgical procedure the IOP was measured with tonopen in the right eye The procedure was similarly carried out four weeks later

1_8To show the correlation between IOP and ICP all results were sorted while ignoring the methods of reduction of IOP and also the time of measurements

All the dogs underwent a same method of anesthesia and measurement of IOP and ICP was the same in all groups so bias effect of these materials will be at least

1_9An analysis of variables with repeated measure design was used to determine changes in parameters over time (day 0 14 and 28) An independent t-test was used to determine possible differences in various parameters in IOP and ICP on day 0 14 and 28

Pearson correlation coefficient was used to determine the strength of the relationship existing among various parameters On the other hand we used General linear model to evaluate ghanges in each group separately

The data were analyzed using the statistical package for social science series (SPSS 150) and ple 005 was considered as significant

1_1There were 15 skeletally mature healthy dogs enrolled in this study All dogs were remained lived till end of study The overall mean age was 21yearsplusmn 028 (range 15-25 years) with a mean weight of 175 plusmn 118 kg (16-19 kg)

The mean primary IOP was 2040plusmn 470 and that of ICP was 746plusmn 209 As is shown in table 4-1 dogs randomly allocated in 3 groups were matched in terms of weight age and also in both primary IOP and ICP (Table 4-1)

Groups Age Weight Primary IOP Primary ICP

Group A 2-25

22plusmn 027

16-19

17plusmn141

15-27

2280plusmn471

5-9

66plusmn181

Group B 15-2

190plusmn022

16-19

178plusmn109

15-27

218plusmn465

5-10

76plusmn207

Group C 2-25

220plusmn027

16-19

177plusmn109

14-20

166plusmn240

5-10

82plusmn248

P value 365 101 476 190

Table4-1 primary

measurements of the

parameters

1_3According to drug administration and trabeculectomy to changes IOP and subsequently evaluate changes in ICP multiple liner repeated measurement was performed that showed statistically considerable deference in IOP after drug administration for 2 weeks and even after 4 weeks indicative of effective application of drugs and confirmed the study to full fill our idea (Table 4-2 figure 4-1)

Groups

IOP

Primary IOP IOP after 2

weeks of drug

administration

IOP after 4

weeks of drug

administration

P value

Group A 15-27

2280plusmn471

10-19

162 plusmn370

10-18

148plusmn327

0003

Group B 15-27

218plusmn465

10-18

142plusmn389

9-14

114plusmn240

000

Group C 14-20

166plusmn240

3-6

44plusmn114

3-5

4plusmn070

000

Table 4-2 secondary

measurements of the

parameters

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

4 weeks after to drug

adminstration or surgery

2 weeks after to drug

adminstration or surgery

Prior to drug adminstration

or surgery

0

2

4

6

8

10

12

14

16

18

20

0 5 10 15 20 25 30

Intera Ocular Pressure

Inte

ra C

rani

al P

ress

ure

1_5In this regard the correlation of primary IOP and primary ICP was not statistically significant ( 1750 vs 2040 P Value 095 ) however after 2 weeks these measures become considerable ( 1106 vs 1173 P value 002 ) Subsequently after 4 weeks again results were infavor of considerable negative correlation of IOP and ICP ( 1006 vs 1183 P value 002 )

1_6On the other hand as we encounter with statistically considerable correlation between IOP and ICP in order to be able to make a model for the relation we joined all the results of IOP and ICP ignoring methods of induced IOP changes and also time of measurement in order to IOP in 45 samples

1_7Therefore according to Pearson correlation analysis there was considerable negative correlation between IOP ( v= -067 P value =000 )(fig 4-5) As was shown in table 3 felting a multiple regression model to the data where ICP was the dependent variable and IOP was the continuous predictor variable and generated the model to show correlation as follows

1_8(^ICPi) =1566 - 0337 IOP ( R2 =0448 ) and according to the table 4 the regression analysis acceptable statistically

Table 4-4 Measures was indicated that the regression analysis acceptable statistically

Model Un

standardiz

ed

coefficients

Standardiz

ed

coefficients

t Significant

Constant

IOP

B StdError Beta 242034 34939

15066 0890 -0670 16930 000

-0337 0057 -0670 -5911 000

icpiop

30

20

10

0

preiop

preicp

2 wk iop

2 wk icp

4 wk iop

4 wk icp

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

Table 3-1 type of intervention in each group

Groups Type of intervention in

right eye

Group 1 Timolol drop 05 twice a

day

Group 2 Latanoprest(xalatan )drop

daily

Group 3 Trabeculectomy operation

1_6Trabeculectomy

Trabeculectomy was performed using Watsonrsquos modification of the Cairns technique (16) first a limbus-based conjuctival flap was prepared the sclera was exposed and a rectangular 34 mm sclera flap was made Then a 1 mm sclerosomywas made followed by peripheral iridectomy and finally the conjunctiva was closed with a continuous 10-0 nylon suture

1_7In the same manner after 2 and 4 weeks of drug administration or surgical procedure the IOP was measured with tonopen in the right eye The procedure was similarly carried out four weeks later

1_8To show the correlation between IOP and ICP all results were sorted while ignoring the methods of reduction of IOP and also the time of measurements

All the dogs underwent a same method of anesthesia and measurement of IOP and ICP was the same in all groups so bias effect of these materials will be at least

1_9An analysis of variables with repeated measure design was used to determine changes in parameters over time (day 0 14 and 28) An independent t-test was used to determine possible differences in various parameters in IOP and ICP on day 0 14 and 28

Pearson correlation coefficient was used to determine the strength of the relationship existing among various parameters On the other hand we used General linear model to evaluate ghanges in each group separately

The data were analyzed using the statistical package for social science series (SPSS 150) and ple 005 was considered as significant

1_1There were 15 skeletally mature healthy dogs enrolled in this study All dogs were remained lived till end of study The overall mean age was 21yearsplusmn 028 (range 15-25 years) with a mean weight of 175 plusmn 118 kg (16-19 kg)

The mean primary IOP was 2040plusmn 470 and that of ICP was 746plusmn 209 As is shown in table 4-1 dogs randomly allocated in 3 groups were matched in terms of weight age and also in both primary IOP and ICP (Table 4-1)

Groups Age Weight Primary IOP Primary ICP

Group A 2-25

22plusmn 027

16-19

17plusmn141

15-27

2280plusmn471

5-9

66plusmn181

Group B 15-2

190plusmn022

16-19

178plusmn109

15-27

218plusmn465

5-10

76plusmn207

Group C 2-25

220plusmn027

16-19

177plusmn109

14-20

166plusmn240

5-10

82plusmn248

P value 365 101 476 190

Table4-1 primary

measurements of the

parameters

1_3According to drug administration and trabeculectomy to changes IOP and subsequently evaluate changes in ICP multiple liner repeated measurement was performed that showed statistically considerable deference in IOP after drug administration for 2 weeks and even after 4 weeks indicative of effective application of drugs and confirmed the study to full fill our idea (Table 4-2 figure 4-1)

Groups

IOP

Primary IOP IOP after 2

weeks of drug

administration

IOP after 4

weeks of drug

administration

P value

Group A 15-27

2280plusmn471

10-19

162 plusmn370

10-18

148plusmn327

0003

Group B 15-27

218plusmn465

10-18

142plusmn389

9-14

114plusmn240

000

Group C 14-20

166plusmn240

3-6

44plusmn114

3-5

4plusmn070

000

Table 4-2 secondary

measurements of the

parameters

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

4 weeks after to drug

adminstration or surgery

2 weeks after to drug

adminstration or surgery

Prior to drug adminstration

or surgery

0

2

4

6

8

10

12

14

16

18

20

0 5 10 15 20 25 30

Intera Ocular Pressure

Inte

ra C

rani

al P

ress

ure

1_5In this regard the correlation of primary IOP and primary ICP was not statistically significant ( 1750 vs 2040 P Value 095 ) however after 2 weeks these measures become considerable ( 1106 vs 1173 P value 002 ) Subsequently after 4 weeks again results were infavor of considerable negative correlation of IOP and ICP ( 1006 vs 1183 P value 002 )

1_6On the other hand as we encounter with statistically considerable correlation between IOP and ICP in order to be able to make a model for the relation we joined all the results of IOP and ICP ignoring methods of induced IOP changes and also time of measurement in order to IOP in 45 samples

1_7Therefore according to Pearson correlation analysis there was considerable negative correlation between IOP ( v= -067 P value =000 )(fig 4-5) As was shown in table 3 felting a multiple regression model to the data where ICP was the dependent variable and IOP was the continuous predictor variable and generated the model to show correlation as follows

1_8(^ICPi) =1566 - 0337 IOP ( R2 =0448 ) and according to the table 4 the regression analysis acceptable statistically

Table 4-4 Measures was indicated that the regression analysis acceptable statistically

Model Un

standardiz

ed

coefficients

Standardiz

ed

coefficients

t Significant

Constant

IOP

B StdError Beta 242034 34939

15066 0890 -0670 16930 000

-0337 0057 -0670 -5911 000

icpiop

30

20

10

0

preiop

preicp

2 wk iop

2 wk icp

4 wk iop

4 wk icp

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_6Trabeculectomy

Trabeculectomy was performed using Watsonrsquos modification of the Cairns technique (16) first a limbus-based conjuctival flap was prepared the sclera was exposed and a rectangular 34 mm sclera flap was made Then a 1 mm sclerosomywas made followed by peripheral iridectomy and finally the conjunctiva was closed with a continuous 10-0 nylon suture

1_7In the same manner after 2 and 4 weeks of drug administration or surgical procedure the IOP was measured with tonopen in the right eye The procedure was similarly carried out four weeks later

1_8To show the correlation between IOP and ICP all results were sorted while ignoring the methods of reduction of IOP and also the time of measurements

All the dogs underwent a same method of anesthesia and measurement of IOP and ICP was the same in all groups so bias effect of these materials will be at least

1_9An analysis of variables with repeated measure design was used to determine changes in parameters over time (day 0 14 and 28) An independent t-test was used to determine possible differences in various parameters in IOP and ICP on day 0 14 and 28

Pearson correlation coefficient was used to determine the strength of the relationship existing among various parameters On the other hand we used General linear model to evaluate ghanges in each group separately

The data were analyzed using the statistical package for social science series (SPSS 150) and ple 005 was considered as significant

1_1There were 15 skeletally mature healthy dogs enrolled in this study All dogs were remained lived till end of study The overall mean age was 21yearsplusmn 028 (range 15-25 years) with a mean weight of 175 plusmn 118 kg (16-19 kg)

The mean primary IOP was 2040plusmn 470 and that of ICP was 746plusmn 209 As is shown in table 4-1 dogs randomly allocated in 3 groups were matched in terms of weight age and also in both primary IOP and ICP (Table 4-1)

Groups Age Weight Primary IOP Primary ICP

Group A 2-25

22plusmn 027

16-19

17plusmn141

15-27

2280plusmn471

5-9

66plusmn181

Group B 15-2

190plusmn022

16-19

178plusmn109

15-27

218plusmn465

5-10

76plusmn207

Group C 2-25

220plusmn027

16-19

177plusmn109

14-20

166plusmn240

5-10

82plusmn248

P value 365 101 476 190

Table4-1 primary

measurements of the

parameters

1_3According to drug administration and trabeculectomy to changes IOP and subsequently evaluate changes in ICP multiple liner repeated measurement was performed that showed statistically considerable deference in IOP after drug administration for 2 weeks and even after 4 weeks indicative of effective application of drugs and confirmed the study to full fill our idea (Table 4-2 figure 4-1)

Groups

IOP

Primary IOP IOP after 2

weeks of drug

administration

IOP after 4

weeks of drug

administration

P value

Group A 15-27

2280plusmn471

10-19

162 plusmn370

10-18

148plusmn327

0003

Group B 15-27

218plusmn465

10-18

142plusmn389

9-14

114plusmn240

000

Group C 14-20

166plusmn240

3-6

44plusmn114

3-5

4plusmn070

000

Table 4-2 secondary

measurements of the

parameters

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

4 weeks after to drug

adminstration or surgery

2 weeks after to drug

adminstration or surgery

Prior to drug adminstration

or surgery

0

2

4

6

8

10

12

14

16

18

20

0 5 10 15 20 25 30

Intera Ocular Pressure

Inte

ra C

rani

al P

ress

ure

1_5In this regard the correlation of primary IOP and primary ICP was not statistically significant ( 1750 vs 2040 P Value 095 ) however after 2 weeks these measures become considerable ( 1106 vs 1173 P value 002 ) Subsequently after 4 weeks again results were infavor of considerable negative correlation of IOP and ICP ( 1006 vs 1183 P value 002 )

1_6On the other hand as we encounter with statistically considerable correlation between IOP and ICP in order to be able to make a model for the relation we joined all the results of IOP and ICP ignoring methods of induced IOP changes and also time of measurement in order to IOP in 45 samples

1_7Therefore according to Pearson correlation analysis there was considerable negative correlation between IOP ( v= -067 P value =000 )(fig 4-5) As was shown in table 3 felting a multiple regression model to the data where ICP was the dependent variable and IOP was the continuous predictor variable and generated the model to show correlation as follows

1_8(^ICPi) =1566 - 0337 IOP ( R2 =0448 ) and according to the table 4 the regression analysis acceptable statistically

Table 4-4 Measures was indicated that the regression analysis acceptable statistically

Model Un

standardiz

ed

coefficients

Standardiz

ed

coefficients

t Significant

Constant

IOP

B StdError Beta 242034 34939

15066 0890 -0670 16930 000

-0337 0057 -0670 -5911 000

icpiop

30

20

10

0

preiop

preicp

2 wk iop

2 wk icp

4 wk iop

4 wk icp

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_7In the same manner after 2 and 4 weeks of drug administration or surgical procedure the IOP was measured with tonopen in the right eye The procedure was similarly carried out four weeks later

1_8To show the correlation between IOP and ICP all results were sorted while ignoring the methods of reduction of IOP and also the time of measurements

All the dogs underwent a same method of anesthesia and measurement of IOP and ICP was the same in all groups so bias effect of these materials will be at least

1_9An analysis of variables with repeated measure design was used to determine changes in parameters over time (day 0 14 and 28) An independent t-test was used to determine possible differences in various parameters in IOP and ICP on day 0 14 and 28

Pearson correlation coefficient was used to determine the strength of the relationship existing among various parameters On the other hand we used General linear model to evaluate ghanges in each group separately

The data were analyzed using the statistical package for social science series (SPSS 150) and ple 005 was considered as significant

1_1There were 15 skeletally mature healthy dogs enrolled in this study All dogs were remained lived till end of study The overall mean age was 21yearsplusmn 028 (range 15-25 years) with a mean weight of 175 plusmn 118 kg (16-19 kg)

The mean primary IOP was 2040plusmn 470 and that of ICP was 746plusmn 209 As is shown in table 4-1 dogs randomly allocated in 3 groups were matched in terms of weight age and also in both primary IOP and ICP (Table 4-1)

Groups Age Weight Primary IOP Primary ICP

Group A 2-25

22plusmn 027

16-19

17plusmn141

15-27

2280plusmn471

5-9

66plusmn181

Group B 15-2

190plusmn022

16-19

178plusmn109

15-27

218plusmn465

5-10

76plusmn207

Group C 2-25

220plusmn027

16-19

177plusmn109

14-20

166plusmn240

5-10

82plusmn248

P value 365 101 476 190

Table4-1 primary

measurements of the

parameters

1_3According to drug administration and trabeculectomy to changes IOP and subsequently evaluate changes in ICP multiple liner repeated measurement was performed that showed statistically considerable deference in IOP after drug administration for 2 weeks and even after 4 weeks indicative of effective application of drugs and confirmed the study to full fill our idea (Table 4-2 figure 4-1)

Groups

IOP

Primary IOP IOP after 2

weeks of drug

administration

IOP after 4

weeks of drug

administration

P value

Group A 15-27

2280plusmn471

10-19

162 plusmn370

10-18

148plusmn327

0003

Group B 15-27

218plusmn465

10-18

142plusmn389

9-14

114plusmn240

000

Group C 14-20

166plusmn240

3-6

44plusmn114

3-5

4plusmn070

000

Table 4-2 secondary

measurements of the

parameters

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

4 weeks after to drug

adminstration or surgery

2 weeks after to drug

adminstration or surgery

Prior to drug adminstration

or surgery

0

2

4

6

8

10

12

14

16

18

20

0 5 10 15 20 25 30

Intera Ocular Pressure

Inte

ra C

rani

al P

ress

ure

1_5In this regard the correlation of primary IOP and primary ICP was not statistically significant ( 1750 vs 2040 P Value 095 ) however after 2 weeks these measures become considerable ( 1106 vs 1173 P value 002 ) Subsequently after 4 weeks again results were infavor of considerable negative correlation of IOP and ICP ( 1006 vs 1183 P value 002 )

1_6On the other hand as we encounter with statistically considerable correlation between IOP and ICP in order to be able to make a model for the relation we joined all the results of IOP and ICP ignoring methods of induced IOP changes and also time of measurement in order to IOP in 45 samples

1_7Therefore according to Pearson correlation analysis there was considerable negative correlation between IOP ( v= -067 P value =000 )(fig 4-5) As was shown in table 3 felting a multiple regression model to the data where ICP was the dependent variable and IOP was the continuous predictor variable and generated the model to show correlation as follows

1_8(^ICPi) =1566 - 0337 IOP ( R2 =0448 ) and according to the table 4 the regression analysis acceptable statistically

Table 4-4 Measures was indicated that the regression analysis acceptable statistically

Model Un

standardiz

ed

coefficients

Standardiz

ed

coefficients

t Significant

Constant

IOP

B StdError Beta 242034 34939

15066 0890 -0670 16930 000

-0337 0057 -0670 -5911 000

icpiop

30

20

10

0

preiop

preicp

2 wk iop

2 wk icp

4 wk iop

4 wk icp

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_8To show the correlation between IOP and ICP all results were sorted while ignoring the methods of reduction of IOP and also the time of measurements

All the dogs underwent a same method of anesthesia and measurement of IOP and ICP was the same in all groups so bias effect of these materials will be at least

1_9An analysis of variables with repeated measure design was used to determine changes in parameters over time (day 0 14 and 28) An independent t-test was used to determine possible differences in various parameters in IOP and ICP on day 0 14 and 28

Pearson correlation coefficient was used to determine the strength of the relationship existing among various parameters On the other hand we used General linear model to evaluate ghanges in each group separately

The data were analyzed using the statistical package for social science series (SPSS 150) and ple 005 was considered as significant

1_1There were 15 skeletally mature healthy dogs enrolled in this study All dogs were remained lived till end of study The overall mean age was 21yearsplusmn 028 (range 15-25 years) with a mean weight of 175 plusmn 118 kg (16-19 kg)

The mean primary IOP was 2040plusmn 470 and that of ICP was 746plusmn 209 As is shown in table 4-1 dogs randomly allocated in 3 groups were matched in terms of weight age and also in both primary IOP and ICP (Table 4-1)

Groups Age Weight Primary IOP Primary ICP

Group A 2-25

22plusmn 027

16-19

17plusmn141

15-27

2280plusmn471

5-9

66plusmn181

Group B 15-2

190plusmn022

16-19

178plusmn109

15-27

218plusmn465

5-10

76plusmn207

Group C 2-25

220plusmn027

16-19

177plusmn109

14-20

166plusmn240

5-10

82plusmn248

P value 365 101 476 190

Table4-1 primary

measurements of the

parameters

1_3According to drug administration and trabeculectomy to changes IOP and subsequently evaluate changes in ICP multiple liner repeated measurement was performed that showed statistically considerable deference in IOP after drug administration for 2 weeks and even after 4 weeks indicative of effective application of drugs and confirmed the study to full fill our idea (Table 4-2 figure 4-1)

Groups

IOP

Primary IOP IOP after 2

weeks of drug

administration

IOP after 4

weeks of drug

administration

P value

Group A 15-27

2280plusmn471

10-19

162 plusmn370

10-18

148plusmn327

0003

Group B 15-27

218plusmn465

10-18

142plusmn389

9-14

114plusmn240

000

Group C 14-20

166plusmn240

3-6

44plusmn114

3-5

4plusmn070

000

Table 4-2 secondary

measurements of the

parameters

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

4 weeks after to drug

adminstration or surgery

2 weeks after to drug

adminstration or surgery

Prior to drug adminstration

or surgery

0

2

4

6

8

10

12

14

16

18

20

0 5 10 15 20 25 30

Intera Ocular Pressure

Inte

ra C

rani

al P

ress

ure

1_5In this regard the correlation of primary IOP and primary ICP was not statistically significant ( 1750 vs 2040 P Value 095 ) however after 2 weeks these measures become considerable ( 1106 vs 1173 P value 002 ) Subsequently after 4 weeks again results were infavor of considerable negative correlation of IOP and ICP ( 1006 vs 1183 P value 002 )

1_6On the other hand as we encounter with statistically considerable correlation between IOP and ICP in order to be able to make a model for the relation we joined all the results of IOP and ICP ignoring methods of induced IOP changes and also time of measurement in order to IOP in 45 samples

1_7Therefore according to Pearson correlation analysis there was considerable negative correlation between IOP ( v= -067 P value =000 )(fig 4-5) As was shown in table 3 felting a multiple regression model to the data where ICP was the dependent variable and IOP was the continuous predictor variable and generated the model to show correlation as follows

1_8(^ICPi) =1566 - 0337 IOP ( R2 =0448 ) and according to the table 4 the regression analysis acceptable statistically

Table 4-4 Measures was indicated that the regression analysis acceptable statistically

Model Un

standardiz

ed

coefficients

Standardiz

ed

coefficients

t Significant

Constant

IOP

B StdError Beta 242034 34939

15066 0890 -0670 16930 000

-0337 0057 -0670 -5911 000

icpiop

30

20

10

0

preiop

preicp

2 wk iop

2 wk icp

4 wk iop

4 wk icp

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_9An analysis of variables with repeated measure design was used to determine changes in parameters over time (day 0 14 and 28) An independent t-test was used to determine possible differences in various parameters in IOP and ICP on day 0 14 and 28

Pearson correlation coefficient was used to determine the strength of the relationship existing among various parameters On the other hand we used General linear model to evaluate ghanges in each group separately

The data were analyzed using the statistical package for social science series (SPSS 150) and ple 005 was considered as significant

1_1There were 15 skeletally mature healthy dogs enrolled in this study All dogs were remained lived till end of study The overall mean age was 21yearsplusmn 028 (range 15-25 years) with a mean weight of 175 plusmn 118 kg (16-19 kg)

The mean primary IOP was 2040plusmn 470 and that of ICP was 746plusmn 209 As is shown in table 4-1 dogs randomly allocated in 3 groups were matched in terms of weight age and also in both primary IOP and ICP (Table 4-1)

Groups Age Weight Primary IOP Primary ICP

Group A 2-25

22plusmn 027

16-19

17plusmn141

15-27

2280plusmn471

5-9

66plusmn181

Group B 15-2

190plusmn022

16-19

178plusmn109

15-27

218plusmn465

5-10

76plusmn207

Group C 2-25

220plusmn027

16-19

177plusmn109

14-20

166plusmn240

5-10

82plusmn248

P value 365 101 476 190

Table4-1 primary

measurements of the

parameters

1_3According to drug administration and trabeculectomy to changes IOP and subsequently evaluate changes in ICP multiple liner repeated measurement was performed that showed statistically considerable deference in IOP after drug administration for 2 weeks and even after 4 weeks indicative of effective application of drugs and confirmed the study to full fill our idea (Table 4-2 figure 4-1)

Groups

IOP

Primary IOP IOP after 2

weeks of drug

administration

IOP after 4

weeks of drug

administration

P value

Group A 15-27

2280plusmn471

10-19

162 plusmn370

10-18

148plusmn327

0003

Group B 15-27

218plusmn465

10-18

142plusmn389

9-14

114plusmn240

000

Group C 14-20

166plusmn240

3-6

44plusmn114

3-5

4plusmn070

000

Table 4-2 secondary

measurements of the

parameters

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

4 weeks after to drug

adminstration or surgery

2 weeks after to drug

adminstration or surgery

Prior to drug adminstration

or surgery

0

2

4

6

8

10

12

14

16

18

20

0 5 10 15 20 25 30

Intera Ocular Pressure

Inte

ra C

rani

al P

ress

ure

1_5In this regard the correlation of primary IOP and primary ICP was not statistically significant ( 1750 vs 2040 P Value 095 ) however after 2 weeks these measures become considerable ( 1106 vs 1173 P value 002 ) Subsequently after 4 weeks again results were infavor of considerable negative correlation of IOP and ICP ( 1006 vs 1183 P value 002 )

1_6On the other hand as we encounter with statistically considerable correlation between IOP and ICP in order to be able to make a model for the relation we joined all the results of IOP and ICP ignoring methods of induced IOP changes and also time of measurement in order to IOP in 45 samples

1_7Therefore according to Pearson correlation analysis there was considerable negative correlation between IOP ( v= -067 P value =000 )(fig 4-5) As was shown in table 3 felting a multiple regression model to the data where ICP was the dependent variable and IOP was the continuous predictor variable and generated the model to show correlation as follows

1_8(^ICPi) =1566 - 0337 IOP ( R2 =0448 ) and according to the table 4 the regression analysis acceptable statistically

Table 4-4 Measures was indicated that the regression analysis acceptable statistically

Model Un

standardiz

ed

coefficients

Standardiz

ed

coefficients

t Significant

Constant

IOP

B StdError Beta 242034 34939

15066 0890 -0670 16930 000

-0337 0057 -0670 -5911 000

icpiop

30

20

10

0

preiop

preicp

2 wk iop

2 wk icp

4 wk iop

4 wk icp

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_1There were 15 skeletally mature healthy dogs enrolled in this study All dogs were remained lived till end of study The overall mean age was 21yearsplusmn 028 (range 15-25 years) with a mean weight of 175 plusmn 118 kg (16-19 kg)

The mean primary IOP was 2040plusmn 470 and that of ICP was 746plusmn 209 As is shown in table 4-1 dogs randomly allocated in 3 groups were matched in terms of weight age and also in both primary IOP and ICP (Table 4-1)

Groups Age Weight Primary IOP Primary ICP

Group A 2-25

22plusmn 027

16-19

17plusmn141

15-27

2280plusmn471

5-9

66plusmn181

Group B 15-2

190plusmn022

16-19

178plusmn109

15-27

218plusmn465

5-10

76plusmn207

Group C 2-25

220plusmn027

16-19

177plusmn109

14-20

166plusmn240

5-10

82plusmn248

P value 365 101 476 190

Table4-1 primary

measurements of the

parameters

1_3According to drug administration and trabeculectomy to changes IOP and subsequently evaluate changes in ICP multiple liner repeated measurement was performed that showed statistically considerable deference in IOP after drug administration for 2 weeks and even after 4 weeks indicative of effective application of drugs and confirmed the study to full fill our idea (Table 4-2 figure 4-1)

Groups

IOP

Primary IOP IOP after 2

weeks of drug

administration

IOP after 4

weeks of drug

administration

P value

Group A 15-27

2280plusmn471

10-19

162 plusmn370

10-18

148plusmn327

0003

Group B 15-27

218plusmn465

10-18

142plusmn389

9-14

114plusmn240

000

Group C 14-20

166plusmn240

3-6

44plusmn114

3-5

4plusmn070

000

Table 4-2 secondary

measurements of the

parameters

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

4 weeks after to drug

adminstration or surgery

2 weeks after to drug

adminstration or surgery

Prior to drug adminstration

or surgery

0

2

4

6

8

10

12

14

16

18

20

0 5 10 15 20 25 30

Intera Ocular Pressure

Inte

ra C

rani

al P

ress

ure

1_5In this regard the correlation of primary IOP and primary ICP was not statistically significant ( 1750 vs 2040 P Value 095 ) however after 2 weeks these measures become considerable ( 1106 vs 1173 P value 002 ) Subsequently after 4 weeks again results were infavor of considerable negative correlation of IOP and ICP ( 1006 vs 1183 P value 002 )

1_6On the other hand as we encounter with statistically considerable correlation between IOP and ICP in order to be able to make a model for the relation we joined all the results of IOP and ICP ignoring methods of induced IOP changes and also time of measurement in order to IOP in 45 samples

1_7Therefore according to Pearson correlation analysis there was considerable negative correlation between IOP ( v= -067 P value =000 )(fig 4-5) As was shown in table 3 felting a multiple regression model to the data where ICP was the dependent variable and IOP was the continuous predictor variable and generated the model to show correlation as follows

1_8(^ICPi) =1566 - 0337 IOP ( R2 =0448 ) and according to the table 4 the regression analysis acceptable statistically

Table 4-4 Measures was indicated that the regression analysis acceptable statistically

Model Un

standardiz

ed

coefficients

Standardiz

ed

coefficients

t Significant

Constant

IOP

B StdError Beta 242034 34939

15066 0890 -0670 16930 000

-0337 0057 -0670 -5911 000

icpiop

30

20

10

0

preiop

preicp

2 wk iop

2 wk icp

4 wk iop

4 wk icp

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

Groups Age Weight Primary IOP Primary ICP

Group A 2-25

22plusmn 027

16-19

17plusmn141

15-27

2280plusmn471

5-9

66plusmn181

Group B 15-2

190plusmn022

16-19

178plusmn109

15-27

218plusmn465

5-10

76plusmn207

Group C 2-25

220plusmn027

16-19

177plusmn109

14-20

166plusmn240

5-10

82plusmn248

P value 365 101 476 190

Table4-1 primary

measurements of the

parameters

1_3According to drug administration and trabeculectomy to changes IOP and subsequently evaluate changes in ICP multiple liner repeated measurement was performed that showed statistically considerable deference in IOP after drug administration for 2 weeks and even after 4 weeks indicative of effective application of drugs and confirmed the study to full fill our idea (Table 4-2 figure 4-1)

Groups

IOP

Primary IOP IOP after 2

weeks of drug

administration

IOP after 4

weeks of drug

administration

P value

Group A 15-27

2280plusmn471

10-19

162 plusmn370

10-18

148plusmn327

0003

Group B 15-27

218plusmn465

10-18

142plusmn389

9-14

114plusmn240

000

Group C 14-20

166plusmn240

3-6

44plusmn114

3-5

4plusmn070

000

Table 4-2 secondary

measurements of the

parameters

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

4 weeks after to drug

adminstration or surgery

2 weeks after to drug

adminstration or surgery

Prior to drug adminstration

or surgery

0

2

4

6

8

10

12

14

16

18

20

0 5 10 15 20 25 30

Intera Ocular Pressure

Inte

ra C

rani

al P

ress

ure

1_5In this regard the correlation of primary IOP and primary ICP was not statistically significant ( 1750 vs 2040 P Value 095 ) however after 2 weeks these measures become considerable ( 1106 vs 1173 P value 002 ) Subsequently after 4 weeks again results were infavor of considerable negative correlation of IOP and ICP ( 1006 vs 1183 P value 002 )

1_6On the other hand as we encounter with statistically considerable correlation between IOP and ICP in order to be able to make a model for the relation we joined all the results of IOP and ICP ignoring methods of induced IOP changes and also time of measurement in order to IOP in 45 samples

1_7Therefore according to Pearson correlation analysis there was considerable negative correlation between IOP ( v= -067 P value =000 )(fig 4-5) As was shown in table 3 felting a multiple regression model to the data where ICP was the dependent variable and IOP was the continuous predictor variable and generated the model to show correlation as follows

1_8(^ICPi) =1566 - 0337 IOP ( R2 =0448 ) and according to the table 4 the regression analysis acceptable statistically

Table 4-4 Measures was indicated that the regression analysis acceptable statistically

Model Un

standardiz

ed

coefficients

Standardiz

ed

coefficients

t Significant

Constant

IOP

B StdError Beta 242034 34939

15066 0890 -0670 16930 000

-0337 0057 -0670 -5911 000

icpiop

30

20

10

0

preiop

preicp

2 wk iop

2 wk icp

4 wk iop

4 wk icp

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_3According to drug administration and trabeculectomy to changes IOP and subsequently evaluate changes in ICP multiple liner repeated measurement was performed that showed statistically considerable deference in IOP after drug administration for 2 weeks and even after 4 weeks indicative of effective application of drugs and confirmed the study to full fill our idea (Table 4-2 figure 4-1)

Groups

IOP

Primary IOP IOP after 2

weeks of drug

administration

IOP after 4

weeks of drug

administration

P value

Group A 15-27

2280plusmn471

10-19

162 plusmn370

10-18

148plusmn327

0003

Group B 15-27

218plusmn465

10-18

142plusmn389

9-14

114plusmn240

000

Group C 14-20

166plusmn240

3-6

44plusmn114

3-5

4plusmn070

000

Table 4-2 secondary

measurements of the

parameters

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

4 weeks after to drug

adminstration or surgery

2 weeks after to drug

adminstration or surgery

Prior to drug adminstration

or surgery

0

2

4

6

8

10

12

14

16

18

20

0 5 10 15 20 25 30

Intera Ocular Pressure

Inte

ra C

rani

al P

ress

ure

1_5In this regard the correlation of primary IOP and primary ICP was not statistically significant ( 1750 vs 2040 P Value 095 ) however after 2 weeks these measures become considerable ( 1106 vs 1173 P value 002 ) Subsequently after 4 weeks again results were infavor of considerable negative correlation of IOP and ICP ( 1006 vs 1183 P value 002 )

1_6On the other hand as we encounter with statistically considerable correlation between IOP and ICP in order to be able to make a model for the relation we joined all the results of IOP and ICP ignoring methods of induced IOP changes and also time of measurement in order to IOP in 45 samples

1_7Therefore according to Pearson correlation analysis there was considerable negative correlation between IOP ( v= -067 P value =000 )(fig 4-5) As was shown in table 3 felting a multiple regression model to the data where ICP was the dependent variable and IOP was the continuous predictor variable and generated the model to show correlation as follows

1_8(^ICPi) =1566 - 0337 IOP ( R2 =0448 ) and according to the table 4 the regression analysis acceptable statistically

Table 4-4 Measures was indicated that the regression analysis acceptable statistically

Model Un

standardiz

ed

coefficients

Standardiz

ed

coefficients

t Significant

Constant

IOP

B StdError Beta 242034 34939

15066 0890 -0670 16930 000

-0337 0057 -0670 -5911 000

icpiop

30

20

10

0

preiop

preicp

2 wk iop

2 wk icp

4 wk iop

4 wk icp

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

Groups

IOP

Primary IOP IOP after 2

weeks of drug

administration

IOP after 4

weeks of drug

administration

P value

Group A 15-27

2280plusmn471

10-19

162 plusmn370

10-18

148plusmn327

0003

Group B 15-27

218plusmn465

10-18

142plusmn389

9-14

114plusmn240

000

Group C 14-20

166plusmn240

3-6

44plusmn114

3-5

4plusmn070

000

Table 4-2 secondary

measurements of the

parameters

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

4 weeks after to drug

adminstration or surgery

2 weeks after to drug

adminstration or surgery

Prior to drug adminstration

or surgery

0

2

4

6

8

10

12

14

16

18

20

0 5 10 15 20 25 30

Intera Ocular Pressure

Inte

ra C

rani

al P

ress

ure

1_5In this regard the correlation of primary IOP and primary ICP was not statistically significant ( 1750 vs 2040 P Value 095 ) however after 2 weeks these measures become considerable ( 1106 vs 1173 P value 002 ) Subsequently after 4 weeks again results were infavor of considerable negative correlation of IOP and ICP ( 1006 vs 1183 P value 002 )

1_6On the other hand as we encounter with statistically considerable correlation between IOP and ICP in order to be able to make a model for the relation we joined all the results of IOP and ICP ignoring methods of induced IOP changes and also time of measurement in order to IOP in 45 samples

1_7Therefore according to Pearson correlation analysis there was considerable negative correlation between IOP ( v= -067 P value =000 )(fig 4-5) As was shown in table 3 felting a multiple regression model to the data where ICP was the dependent variable and IOP was the continuous predictor variable and generated the model to show correlation as follows

1_8(^ICPi) =1566 - 0337 IOP ( R2 =0448 ) and according to the table 4 the regression analysis acceptable statistically

Table 4-4 Measures was indicated that the regression analysis acceptable statistically

Model Un

standardiz

ed

coefficients

Standardiz

ed

coefficients

t Significant

Constant

IOP

B StdError Beta 242034 34939

15066 0890 -0670 16930 000

-0337 0057 -0670 -5911 000

icpiop

30

20

10

0

preiop

preicp

2 wk iop

2 wk icp

4 wk iop

4 wk icp

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

4 weeks after to drug

adminstration or surgery

2 weeks after to drug

adminstration or surgery

Prior to drug adminstration

or surgery

0

2

4

6

8

10

12

14

16

18

20

0 5 10 15 20 25 30

Intera Ocular Pressure

Inte

ra C

rani

al P

ress

ure

1_5In this regard the correlation of primary IOP and primary ICP was not statistically significant ( 1750 vs 2040 P Value 095 ) however after 2 weeks these measures become considerable ( 1106 vs 1173 P value 002 ) Subsequently after 4 weeks again results were infavor of considerable negative correlation of IOP and ICP ( 1006 vs 1183 P value 002 )

1_6On the other hand as we encounter with statistically considerable correlation between IOP and ICP in order to be able to make a model for the relation we joined all the results of IOP and ICP ignoring methods of induced IOP changes and also time of measurement in order to IOP in 45 samples

1_7Therefore according to Pearson correlation analysis there was considerable negative correlation between IOP ( v= -067 P value =000 )(fig 4-5) As was shown in table 3 felting a multiple regression model to the data where ICP was the dependent variable and IOP was the continuous predictor variable and generated the model to show correlation as follows

1_8(^ICPi) =1566 - 0337 IOP ( R2 =0448 ) and according to the table 4 the regression analysis acceptable statistically

Table 4-4 Measures was indicated that the regression analysis acceptable statistically

Model Un

standardiz

ed

coefficients

Standardiz

ed

coefficients

t Significant

Constant

IOP

B StdError Beta 242034 34939

15066 0890 -0670 16930 000

-0337 0057 -0670 -5911 000

icpiop

30

20

10

0

preiop

preicp

2 wk iop

2 wk icp

4 wk iop

4 wk icp

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

0

5

10

15

20

25

30Intera Ocular Pressure

Intera Cranial Pressure

Prior to drug adminstration

or surgery

2 weeks after to drug

adminstration or surgery

4 weeks after to drug

adminstration or surgery

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

4 weeks after to drug

adminstration or surgery

2 weeks after to drug

adminstration or surgery

Prior to drug adminstration

or surgery

0

2

4

6

8

10

12

14

16

18

20

0 5 10 15 20 25 30

Intera Ocular Pressure

Inte

ra C

rani

al P

ress

ure

1_5In this regard the correlation of primary IOP and primary ICP was not statistically significant ( 1750 vs 2040 P Value 095 ) however after 2 weeks these measures become considerable ( 1106 vs 1173 P value 002 ) Subsequently after 4 weeks again results were infavor of considerable negative correlation of IOP and ICP ( 1006 vs 1183 P value 002 )

1_6On the other hand as we encounter with statistically considerable correlation between IOP and ICP in order to be able to make a model for the relation we joined all the results of IOP and ICP ignoring methods of induced IOP changes and also time of measurement in order to IOP in 45 samples

1_7Therefore according to Pearson correlation analysis there was considerable negative correlation between IOP ( v= -067 P value =000 )(fig 4-5) As was shown in table 3 felting a multiple regression model to the data where ICP was the dependent variable and IOP was the continuous predictor variable and generated the model to show correlation as follows

1_8(^ICPi) =1566 - 0337 IOP ( R2 =0448 ) and according to the table 4 the regression analysis acceptable statistically

Table 4-4 Measures was indicated that the regression analysis acceptable statistically

Model Un

standardiz

ed

coefficients

Standardiz

ed

coefficients

t Significant

Constant

IOP

B StdError Beta 242034 34939

15066 0890 -0670 16930 000

-0337 0057 -0670 -5911 000

icpiop

30

20

10

0

preiop

preicp

2 wk iop

2 wk icp

4 wk iop

4 wk icp

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

0

5

10

15

20

25

30

Intera Ocular Pressure

Intera Cranial Pressure

4 weeks after to drug

adminstration or surgery

2 weeks after to drug

adminstration or surgery

Prior to drug adminstration

or surgery

0

2

4

6

8

10

12

14

16

18

20

0 5 10 15 20 25 30

Intera Ocular Pressure

Inte

ra C

rani

al P

ress

ure

1_5In this regard the correlation of primary IOP and primary ICP was not statistically significant ( 1750 vs 2040 P Value 095 ) however after 2 weeks these measures become considerable ( 1106 vs 1173 P value 002 ) Subsequently after 4 weeks again results were infavor of considerable negative correlation of IOP and ICP ( 1006 vs 1183 P value 002 )

1_6On the other hand as we encounter with statistically considerable correlation between IOP and ICP in order to be able to make a model for the relation we joined all the results of IOP and ICP ignoring methods of induced IOP changes and also time of measurement in order to IOP in 45 samples

1_7Therefore according to Pearson correlation analysis there was considerable negative correlation between IOP ( v= -067 P value =000 )(fig 4-5) As was shown in table 3 felting a multiple regression model to the data where ICP was the dependent variable and IOP was the continuous predictor variable and generated the model to show correlation as follows

1_8(^ICPi) =1566 - 0337 IOP ( R2 =0448 ) and according to the table 4 the regression analysis acceptable statistically

Table 4-4 Measures was indicated that the regression analysis acceptable statistically

Model Un

standardiz

ed

coefficients

Standardiz

ed

coefficients

t Significant

Constant

IOP

B StdError Beta 242034 34939

15066 0890 -0670 16930 000

-0337 0057 -0670 -5911 000

icpiop

30

20

10

0

preiop

preicp

2 wk iop

2 wk icp

4 wk iop

4 wk icp

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

0

2

4

6

8

10

12

14

16

18

20

0 5 10 15 20 25 30

Intera Ocular Pressure

Inte

ra C

rani

al P

ress

ure

1_5In this regard the correlation of primary IOP and primary ICP was not statistically significant ( 1750 vs 2040 P Value 095 ) however after 2 weeks these measures become considerable ( 1106 vs 1173 P value 002 ) Subsequently after 4 weeks again results were infavor of considerable negative correlation of IOP and ICP ( 1006 vs 1183 P value 002 )

1_6On the other hand as we encounter with statistically considerable correlation between IOP and ICP in order to be able to make a model for the relation we joined all the results of IOP and ICP ignoring methods of induced IOP changes and also time of measurement in order to IOP in 45 samples

1_7Therefore according to Pearson correlation analysis there was considerable negative correlation between IOP ( v= -067 P value =000 )(fig 4-5) As was shown in table 3 felting a multiple regression model to the data where ICP was the dependent variable and IOP was the continuous predictor variable and generated the model to show correlation as follows

1_8(^ICPi) =1566 - 0337 IOP ( R2 =0448 ) and according to the table 4 the regression analysis acceptable statistically

Table 4-4 Measures was indicated that the regression analysis acceptable statistically

Model Un

standardiz

ed

coefficients

Standardiz

ed

coefficients

t Significant

Constant

IOP

B StdError Beta 242034 34939

15066 0890 -0670 16930 000

-0337 0057 -0670 -5911 000

icpiop

30

20

10

0

preiop

preicp

2 wk iop

2 wk icp

4 wk iop

4 wk icp

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_5In this regard the correlation of primary IOP and primary ICP was not statistically significant ( 1750 vs 2040 P Value 095 ) however after 2 weeks these measures become considerable ( 1106 vs 1173 P value 002 ) Subsequently after 4 weeks again results were infavor of considerable negative correlation of IOP and ICP ( 1006 vs 1183 P value 002 )

1_6On the other hand as we encounter with statistically considerable correlation between IOP and ICP in order to be able to make a model for the relation we joined all the results of IOP and ICP ignoring methods of induced IOP changes and also time of measurement in order to IOP in 45 samples

1_7Therefore according to Pearson correlation analysis there was considerable negative correlation between IOP ( v= -067 P value =000 )(fig 4-5) As was shown in table 3 felting a multiple regression model to the data where ICP was the dependent variable and IOP was the continuous predictor variable and generated the model to show correlation as follows

1_8(^ICPi) =1566 - 0337 IOP ( R2 =0448 ) and according to the table 4 the regression analysis acceptable statistically

Table 4-4 Measures was indicated that the regression analysis acceptable statistically

Model Un

standardiz

ed

coefficients

Standardiz

ed

coefficients

t Significant

Constant

IOP

B StdError Beta 242034 34939

15066 0890 -0670 16930 000

-0337 0057 -0670 -5911 000

icpiop

30

20

10

0

preiop

preicp

2 wk iop

2 wk icp

4 wk iop

4 wk icp

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_6On the other hand as we encounter with statistically considerable correlation between IOP and ICP in order to be able to make a model for the relation we joined all the results of IOP and ICP ignoring methods of induced IOP changes and also time of measurement in order to IOP in 45 samples

1_7Therefore according to Pearson correlation analysis there was considerable negative correlation between IOP ( v= -067 P value =000 )(fig 4-5) As was shown in table 3 felting a multiple regression model to the data where ICP was the dependent variable and IOP was the continuous predictor variable and generated the model to show correlation as follows

1_8(^ICPi) =1566 - 0337 IOP ( R2 =0448 ) and according to the table 4 the regression analysis acceptable statistically

Table 4-4 Measures was indicated that the regression analysis acceptable statistically

Model Un

standardiz

ed

coefficients

Standardiz

ed

coefficients

t Significant

Constant

IOP

B StdError Beta 242034 34939

15066 0890 -0670 16930 000

-0337 0057 -0670 -5911 000

icpiop

30

20

10

0

preiop

preicp

2 wk iop

2 wk icp

4 wk iop

4 wk icp

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_7Therefore according to Pearson correlation analysis there was considerable negative correlation between IOP ( v= -067 P value =000 )(fig 4-5) As was shown in table 3 felting a multiple regression model to the data where ICP was the dependent variable and IOP was the continuous predictor variable and generated the model to show correlation as follows

1_8(^ICPi) =1566 - 0337 IOP ( R2 =0448 ) and according to the table 4 the regression analysis acceptable statistically

Table 4-4 Measures was indicated that the regression analysis acceptable statistically

Model Un

standardiz

ed

coefficients

Standardiz

ed

coefficients

t Significant

Constant

IOP

B StdError Beta 242034 34939

15066 0890 -0670 16930 000

-0337 0057 -0670 -5911 000

icpiop

30

20

10

0

preiop

preicp

2 wk iop

2 wk icp

4 wk iop

4 wk icp

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_8(^ICPi) =1566 - 0337 IOP ( R2 =0448 ) and according to the table 4 the regression analysis acceptable statistically

Table 4-4 Measures was indicated that the regression analysis acceptable statistically

Model Un

standardiz

ed

coefficients

Standardiz

ed

coefficients

t Significant

Constant

IOP

B StdError Beta 242034 34939

15066 0890 -0670 16930 000

-0337 0057 -0670 -5911 000

icpiop

30

20

10

0

preiop

preicp

2 wk iop

2 wk icp

4 wk iop

4 wk icp

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

Table 4-4 Measures was indicated that the regression analysis acceptable statistically

Model Un

standardiz

ed

coefficients

Standardiz

ed

coefficients

t Significant

Constant

IOP

B StdError Beta 242034 34939

15066 0890 -0670 16930 000

-0337 0057 -0670 -5911 000

icpiop

30

20

10

0

preiop

preicp

2 wk iop

2 wk icp

4 wk iop

4 wk icp

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

icpiop

30

20

10

0

preiop

preicp

2 wk iop

2 wk icp

4 wk iop

4 wk icp

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_1According to what mentioned in the introduction and review of the articles it seems that the compression of posterior of glob may led to a transient event which can temporary causes increased in the IOP

In contrast IOP may have some effects in the ICP As the best of our knowledge IOP can controlled by many factors in this study we tried to investigate this relation and also the effect of decreasing in the IOP on ICP

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_2The relation of ICP and IOP is a subject of controversy till now Sajjadi and colleagues claimed that there was a strong positive correlation between IOP and ICP (r= 0955) and introduced IOP measurement as a reliable non invasive procedure for evaluation of ICP in patients with neurosurgical problems

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_3The mechanism painted out by Saladin et al for direct correlation of IOP and ICP was attributed to the anatomical and physiological connection between intracranial fosse and orbit by detection of the compression of posterior globe by neuro imaging in some patients with increased ICP however as was mentioned this rising of IOP if actually happened was only a transient event with rapid reversal to baseline since there was no increasing of IOP was observed in response to increase of ICP in other studies

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_4One of them was the study was designed by Han Y et al 2008 on records of 55 patients underwent concomitant measurement IOP and ICP between 1991 and 2007 in the neuro-ophthalmology clinic at the University of California San Francisco

Their results were indicative of no correlation between IOP and ICP (Pearson correlation coefficient r = 007 p = 059)and they implied that IOP measurement is not a useful substitute for ICP measurement

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_5As a promising new finding was Berdahl et al study which was the new detection of low CSF pressure in patients with open angle glaucoma and they suggested that low CSF Pressure may work in concert with IOP to produce an unacceptably high Tran laminar pressure gradient (a pressure difference across the lamina cribrosa)

they introduced this event as a disrupting pathway for retinal ganglion cell axoplasmic flow ultimately leading to retinal ganglion cell apoptosis and visual loss in patients with glaucoma

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_6Since then many letters are published giving variable arguments on the results of this study and to finding a way for interpretation of their results

One of the pitfall points pertained to that study was the selection of patients with neurological problem which may have confounding effect and can be considered as an obstacle to generalize the results to all conditions

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_7The present study was the first animal model study to show the pattern of correlation of ICP in response to iatrogenic reduction of IOP in healthy mature dogs The superiority of this study to others is the selection of normal eyes to be enabled to measure purely the effect of IOP on ICP

Since IOP can be changed in stressful conditions even in animals and also to measure both IOP and ICP in all subjected in a similar stable condition all dogs were received general anesthesia and measurements began in a moments after intubations

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_8We refused to use Ketamin as a known drug to affect IOP and ICP

Instead we use pento barbital and we consumed that since we measured all parameters in all dogs in the same condition with the same medication any possible confounding effect of anesthesia would be eliminated

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_9Also two different drugs with different mechanisms for reduction of IOP as well as surgical procedure with another alternate mechanism for lowering IOP was used to overcome other possible biases in this study

Our results were confirmed the subject reported by Berdahl et al in a way that IOP was correlated with ICP with a statistically significant negative standardize coefficient ieabout ndash 067 pv =000

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_10Also the regression formula estimated this relation to be ^ICPi = 1506 ndash 0337 IOP (Rsup2 =0448)The question to be addressed in this subject is the mechanism this relation could be interpreted as was expected by Berdahl et al study

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_11There might be some unknown receptors in the lamina crirosa that function as detectors of any changes in both IOP and ICP Their attempts will be toward measurements of the sum of IOP and ICP to be constant

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_12Therefore any reduction or elevation in pressure of IOP or ICP would result in the inverse changes of the counterpart to hold this summation unchanged

In the other words in a case of glaucoma while the receptors detected high IOP they work toward reduction of IOP but because of the presence of malfunction and pathology behind glaucoma process they could reduce only in ICP

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_13Conversely in the patients with low IOP their activation would result in an increase in ICP The same mechanism will work toward any reduction in IOP as shown in this study

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1_14In conclusion there was a negative linear correlation between IOP and ICP when the multiple regression formula was applied to make a model

As reduction of IOP in a single eye considerably affected ICP it is reasonable that changes in IOP in both eyes may have more effects on ICP

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

1-Hayreh SS Posterior ischaemic optic neuropathy clinical features pathogenesis and management Eye (Lond) 2004 181188

2-Sadda SR Nee M Miller NR Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol 2001 132743

3-Lomoriello DS Lombardo M Tranchina L Oddone F Serrao S Ducoli P Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry Graefes Arch Clin Exp Ophthalmol 2011249(3)429-34

4-Vinciguerra P Albegrave E Mahmoud AM Trazza S Hafezi F Roberts CJ Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking J Refract Surg 201026(9)669-76

5-Murad A Ghostine S Colohan AR Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH Acta Neurochir Suppl 2011110(Pt 2)183-7

6-Gard G An investigation into the regulation of intra-cranial pressure and its influence upon the surrounding cranial bones J Bodyw Mov Ther 200913(3)246-54

7-Hannerz J Ericson K The relationship between idiopathic intracranial hypertension and obesity Headache 200949(2)178-84

8-Bruce DA Alavi A Bilaniuk L Diffuse cerebral swelling following head injuries in children the syndrome of malignant brain edema J Neurosurg 1981 54170

9-Morgan-Davies M Taylor N Hill A R Aspinall P OrsquoBrien C J Azuara-Blanco A Three dimensional analysis of the lamina cribrosa in glaucoma Br J Ophthalmol 2004 88(10)1299ndash1304

10- Pasquale LR Low intracranial pressure a tipping point in our understanding of primary open-angle glaucoma Ophthalmology 2008 May115(5)761-2

11-Berdahl JP Allingham RR Johnson DH Cerebrospinal fluid pressure is decreased in primary open-angle glaucoma Ophthalmology 2008 115(5)763-8

12-Dickerman RD Smith GH Langham-Roof L McConathy WJ East JW Smith AB Intra-ocular pressure changes during maximal isometric contraction does this reflect intra-cranial pressure or retinal venous pressure Neurol Res 199921(3)243-6

13-Sajjadi SA Harirchian MH Sheikhbahaei N Mohebbi MR Malekmadani MH Saberi H The relation between intracranial and intraocular pressures study of 50 patients Ann Neurol200659(5)867-70

14-Sheeran P Bland JM Hall GM Intraocular pressure changes and alterations in intracranial pressure Lancet 2000 11355(9207)899

15-Han Y McCulley TJ Horton JC No correlation between intraocular pressure and intracranial pressure Ann Neurol 2008 64(2)221-4

16- Chen HS Ritch R Krupin T Hsu WC Control of filtering bleb structure through tissue bioengineering An animal model Invest Ophthalmol Vis Sci 200647(12)5310-4

17- Saladin LK Bruni JE The effects of intracerebroventricular versus intravenous administration of vasopressin on intracranial pressure in the rat Neurol Res 199315(3)198-203