ischemic optic neuropathies

ISCHEMIC OPTIC NEUROPATHIES

DR HASIKA RAVULAFINAL YEAR PG

MS OPHTHALMOLOGY

1

Definition:

▪ Acute, painless optic neuropathy occurringpredominantly in patients over 50 years ofage

2

ISCHEMIC OPTIC NEUROPATHIES

INTRODUCTION

▪ Optic nerve ischemia most frequently occurs at the optic nerve head, where structural crowding of nerve fibers and reduction of the vascular supply may combine to impair perfusion to a critical degree and produce optic disc edema. The most common such syndrome is termed anterior ischemic optic neuropathy(AION).

▪ Generally, AION is categorized as either arteritic(associated with temporal arteritis) or nonarteritic .

3

▪ Optic nerve ischemia affects the intraorbitalportion of the nerve less frequently, with no visible disc edema, and this has been termed posterior ischemic optic neuropathy.

▪ A number of syndromes that share similar characteristics also may be ischemic in origin, such as diabetic papillopathy.

4

RELEVANT ANATOMY ANDETIOPATHOGENESIS

▪ To understand the pathogenesis completely, it is useful to review the vascular supply of optic nerve.

▪ Optic nerve receives its blood supply primarily from the posterior ciliary vessels with scant contribution from the central retinal vessels.

▪ The source and pattern of blood supply of the anterior part of the optic nerve (also called the optic nerve head, ONH) is very different from that of the posterior part.

▪ The ONH is almost entirely supplied by the posterior ciliary artery (PCA) circulation and the rest of optic nerve posterior to the ONH is supplied from several other sources.

▪ Hayreh in his pioneering work described in great detail the blood supply of the visual pathways.

▪ The blood supply of the optic nerve can be subdivided into the following parts, according to the different regions of the optic nerve:

ARTERIAL BLOOD SUPPLY OF THE ANTERIORPART OF THE OPTIC NERVE (ONH)

▪ The ONH consists of, from front to back,

(i) surface nerve fiber layer,

(ii) prelaminar region,

(iii) lamina cribrosa region, and

(iv) retro-laminar region

8

The Surface Nerve Fiber Layer

▪ This layer is mostly supplied by the retinal arterioles.

▪ In the temporal region, however, in some eyes, it may instead be supplied by the posterior ciliary artery (PCA) circulation from the deeper prelaminar region.

▪ The cilioretinal artery (an elongated posterior ciliary artery), when present, usually supplies the corresponding sector of the surface layer.

The Prelaminar Region

▪ This is situated in front of the lamina cribrosa.

▪ It is supplied by centripetal branches from the peripapillary choroid.

Lamina Cribrosa

▪ This is supplied by centripetal branches from the short PCAs, either directly or by the anastomotic arterial circle of Zinn and Haller, when that is present.

▪ Contrary to the prevalent impression, the circle of Zinn and Haller is not seen in every eye and, when seen, may be an incomplete circle.

▪ The central retinal artery gives off no branches in this region.

12

Retrolaminar Region

▪ This is the part of the ONH that lies immediately behind the lamina cribrosa.

▪ This part of the optic nerve is supplied by two vascular systems, the peripheral centripetal and the axial centrifugal systems.

Peripheral centripetal vascular system:

▪ This is seen in all nerves and forms the major source of supply to this part.

▪ It is formed by recurrent pial branches arising from the peripapillarychoroid and the circle of Zinn and Haller (when present, or the short PCAs instead).

▪ In addition, pial branches from the central retinal artery and other orbital arteries also supply this part.

▪ The pial vessels give off centripetal branches, running in the septa of the nerve.

Axial centrifugal vascular system :

▪ It is formed by inconstant branches arising from the intra-neural part of the central retinal artery.

▪ However, it is not consistently present in all the nerves.

▪ From this description of the blood supply of the ONH it becomes obvious that the main source of blood supply to the ONH is the PCA circulation via the peripapillary choroid and the short PCAs (or the circle of Zinn and Haller).

▪ Fluorescein angiographic studies by Hayreh SS, et al have shown a sectoral blood supply in the ONH, which goes along with the overall segmental distribution of the PCA circulation and also helps explain the segmental visual loss in AION.

ARTERIAL BLOOD SUPPLY OF THEPOSTERIOR PART OF THE OPTIC NERVE

▪ This part of the optic nerve has a peripheral and an axial vascular system.

Peripheral Centripetal Vascular System:

▪ This is always present.

▪ It is formed by the pial vessels, which come from the collateral arteries arising directly from the ophthalmic artery and some of its intraorbital branches.

Axial Centrifugal Vascular System:

▪ It is formed by branches of the central retinal artery, seen in 75 percent of cases, and the supply by the central retinal artery may extend 1 to 4 mm behind the site of penetration of the central retinal artery into the optic nerve and give rise to centrifugal branches.

Inter-individual Variation in the Blood Supply of the Optic Nerve Head

▪ There is a general impression that the pattern of blood supply of the ONH is almost identical in all eyes, and that all ischemic lesions can be explained by one standard vascular pattern.

▪ This fundamental error is responsible for a good deal of confusion.

▪ Studies by Hayreh et al have clearly shown that ONH blood supply shows a marked inter-individual variation, which is produced by the following factors:

1. Variation in the Anatomical Pattern of the Arterial Supply

▪ The usual anatomical pattern is described above.

▪ However, there are tremendous variations in the anatomical pattern and some of the differences in the vascular anatomy reported in the literature can be explained on this basis.

2. Variations in the Pattern of PCA Circulation

▪ From the account of the arterial supply of the ONH given above, it is evident that the PCAs are the main source of blood supply to the ONH.

▪ The PCAs show marked interindividual variation, which must profoundly influence the blood supply pattern of the ONH.

▪ A brief review of the work by Hayreh et al is detailed below:

(a) Variations in number of PCAs supplying an eye:

▪ There may be 1 to 5 between but usually 2 or 3 PCAs are present.

▪ The PCAs enter the eyeball usually medial and lateral to the optic nerve and hence are called medial and lateral PCAs

(b) In vivo supply by the PCAs:

▪ Hayreh et al have shown that PCAs and their branches have a segmental distribution in vivo, in the choroid as well as in the ONH.

▪ The lateral and medial PCAs supply the corresponding parts of the choroid.

▪ However, there is marked inter-individual variation in the area supplied by the PCAs in humans, both in the choroid and in the ONH.

▪ The medial PCA may supply the entire ONH, or it may take no part in the blood supply of the ONH or there may be any number of variations between these two extremes.

▪ The lateral PCA supplies the area of the ONH not supplied by the medial PCA or vice versa.

▪ When there is more than one medial or lateral PCA, the area supplied by each may be only a sector.

▪ When the superior PCA is present, it accordingly supplies a superior sector.

▪ Therefore, the inter-individual variation in number and distribution by the various PCAs produces an extremely variable pattern of distribution by the PCAs in the ONH.

▪ This is very important to keep in mind while dealing with ischemic disorders of the ONH.

25

(c) Watershed zones in the PCA distribution and their location:

▪ When a tissue is supplied by two or more end-arteries, the border between the territories of distribution of any two end-arteries is called a “watershed zone”.

▪ The significance of the watershed zones is that in the event of a fall in the perfusion pressure in the vascular bed of one or more of the end-arteries, the watershed zone, being an area of comparatively poor vascularistion is most vulnerable to ischemia.

▪ Since PCAs and their subdivisions are end-arteries in vivo, they have watershed zones between them.

▪ As discussed above, when there are two (medial and lateral) PCAs, the area of the choroid and ONH supplied by the two shows a marked inter-individual variation which results in wide variation in the location of the watershed zone between the two.

▪ When there are three or more PCAs supplying an eye, the locations of the watershed zones vary according to the number of the PCAs and their locations.

▪ The location of the watershed zone in relation to the ONH is an extremely important subject in any discussion of ischemic disorders of the ONH.

▪ This is because in the event of fall of perfusion pressure in the PCAs or their branches, the part of the ONH located in the watershed zone becomes vulnerable to ischemia.

Fluorescein fundus angiograms of four eye with AION showing different locations of the watershed zone (vertical dark bands) in relation to the optic disk. (A) Right eye with the watershed zone lying temporal to the optic disk. (B) Right eye with the watershed zone passing through the temporal part of the disk and adjacent temporal peripapillary choroid. (C) Left eye with the optic disk lying in the center of the watershed zone. (D) Left eye with the watershed zone passing through the nasal part of thedisk and adjacent nasal peripapillary choroid

(d) Difference in blood flow in various PCAs as well as short PCAs:

▪ Clinical and experimental studies by Hayreh et al have indicated that the mean blood pressure (BP) in the various PCAs may be different in health and in disease.

▪ In the event of a fall of perfusion pressure, the vascular bed supplied by one artery may be affected earlier and more than the others.

▪ Optic nerve ischemia most frequently occurs at the optic nerve head, where structural crowding of nerve fibers and reduction of vascular supply may combine to impair perfusion to a critical degree.

▪ The blood flow in the optic nerve head depends upon several factors, the most important of which is the blood pressure in its vessels.

▪ The blood flow in the ONH is calculated by using the following formula (Hayreh et al):

Perfusion pressure = Mean BP – intraocular pressure (IOP).

Mean BP = Diastolic BP + 1/3 (systolic minus diastolic BP).

▪ From this formula, it is evident that the blood flow depends upon (a) resistance to blood flow, (b) BP and (c) IOP.

▪ Therefore, a reduction in blood flow may develop consequent to alterations in one of these three factors.

▪ Transient poor circulation or loss of circulation in the optic nerve head can occur due to a transient fall of blood pressure below a critical level in its vessels, which in turn, in susceptible persons, would produce AION.

▪ It is extremely important to remember that in this mode of development of AION there is no actual blockage of the posterior ciliary arteries.

▪ A fall of the blood pressure below the critical level in the capillaries of the optic nerve head may be caused either by a marked fall in blood pressure or by a rise in the eye pressure, or a combination of these factors.

▪ Normally an autoregulation mechanism operates in the optic nerve and helps compensate for any decrease in the blood flow but autoregulation operates only over a critical range of perfusion pressure so that with a rise or fall of perfusion pressure beyond the critical range, the autoregulationbecomes ineffective and breaks down

Autoregulation in relation to the optic nerve blood flow

▪ Factors that lead to the derangement of the autoregulationin the ONH include some well known and some partly known, systemic and local causes, including aging arterial Hypertension, diabetes mellitus, marked arterial hypotension due to any cause, arteriosclerosis, atherosclerosis, hypercholesterolemia, and hyperhomocysteinemia.

▪ Thus, from the above discussion, it is evident that many ocular and systemic risk factors may predispose to the development of NAAION.

a. Ocular : Elevated IOP, small disk, presence of disk edema

b. Local vascular : Occlusion or stenosis of posterior ciliary artery or ophthalmic artery (atherosclerosis, giant cell arteritis).

c. Systemic : Hypotension, diabetes, hypertension, leukemia, intake of contraceptive pills, hematological disorders like polycythemia, sickle cell disease.

ANTERIOR ISCHEMIC OPTIC NEUROPATHY (AION)

▪ Epidemiology

▪ Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common acute optic neuropathy in patients over 50 years of age, with an estimated annual incidence in the United States of 2.3–10.2 per 100 000 population.

▪ No gender predisposition exists, but the disease occurs with significantly higher frequency in White than in Black or Hispanic populations.

▪ The incidence of arteritic anterior ischemic optic neuropathy (AAION) is significantly lower (0.36 per 100 000 population annually in patients over 50 years of age).

38

Ocular Manifestations

▪ AION presents with rapid onset of painless, unilateral visual loss manifested by decreased visual acuity, visual field, or both.

▪ The level of visual acuity impairment varies widely, from minimal loss to no light perception, and the visual field loss may conform to any pattern of deficit related to the optic disc.

▪ An altitudinal field defect is most common, but generalized depression, broad arcuate scotomas, and cecocentral defects also are seen.

▪ A relative afferent pupillary defect invariably is present with monocular optic neuropathy.

▪ The optic disc is edematous at onset, and edema occasionally precedes visual loss by weeks to months.

39

40

▪ Although pallid edema has been described as the hallmark of AION, it is common to see hyperemic swelling, particularly in the nonarteritic form.

▪ The disc most often is swollen diffusely, but a segment of more prominent involvement frequently is present, and either focal or diffuse surface telangiectasia is not unusual and may be quite pronounced.

▪ Commonly, flame hemorrhages are located adjacent to the disc, and the peripapillary retinal arterioles frequently are narrowed.

41

42

43

44

Arteritic anterior ischemic optic neuropathy

▪ In 5–10% of cases, AION may occur as a manifestation of the vasculitis associated with temporal arteritis.

▪ Patients with the arteritic form usually note other symptoms of the disease – headache (most common), jaw claudication, and temporal artery or scalp tenderness are those aligned most frequently with a final diagnosis of temporal arteritis.

▪ Malaise, anorexia, weight loss, fever, proximal joint arthralgia, and myalgia also are noted commonly; however, the disease occasionally manifests with visual loss in the absence of overt systemic symptoms, so-called occult temporal arteritis.

45

▪ Typically, AAION develops in elderly patients, with a mean age of 70 years, with severe visual loss (visual acuity < 20/200 (6/60) in the majority).

▪ It may be preceded by transient visual loss similar to that of carotid artery disease; this finding is extremely unusual in the nonarteritic form and, when present, is highly suggestive of arteritis.

▪ Pallor, which may be severe, chalky-white, is associated with the edema of the optic disc more frequently in AAION than in the nonarteritic form.

▪ Choroidal ischemia may be associated with the optic neuropathy and produces peripapillary pallor and edema deep to the retina.

▪ The disc of the fellow eye is of normal diameter most frequently, with a normal physiological cup.

46

Nonarteritic anterior ischemic optic neuropathy

▪ In 90–95% of cases, AION is unrelated to temporal arteritis.

▪ The nonarteritic form of the disease occurs in a relatively younger age group (mean age of 60 years) and usually is associated with less severe visual loss.

▪ Frequently, visual impairment is reported upon awakening, possibly related to nocturnal systemic hypotension.

▪ The initial course of visual loss may be static (with little or no fluctuation of visual level after the initial loss) or progressive (with either episodic or visual loss that declines steadily over weeks to months prior to eventual stabilization).

47

▪ The progressive form has been reported in 22% to 37% of NAION cases. Usually, no associated systemic symptoms occur, although periorbital pain is described occasionally.

▪ Fellow eye involvement is estimated to occur in 12–19% by 5 years after onset.

▪ Recurrent episodes of visual loss that result from NAION in the same eye are unusual and occur most often in younger patients.

48

▪ The optic disc edema in NAION may be diffuse or segmental, hyperemic or pale, but pallor occurs less frequently than it does in AAION.

▪ A focal region of more severe swelling often is seen and typically displays an altitudinal distribution, but it does not correlate consistently with the sector of visual field loss.

▪ Diffuse or focal telangiectasia of the edematous disc may be present.

▪ This finding may represent microvascular shunting from ischemic to nonischemic regions of the optic nerve head, so-called luxury perfusion.

49

▪ The optic disc in the contralateral eye typically is small in diameter and demonstrates a small or absent physiological cup.

▪ The disc appearance in such fellow eyes has been described as the disc at risk, with postulated structural crowding of the axons at the level of the cribriform plate, associated mild disc elevation, and disc margin blurring without overt edema.

50

(A) Fundus photograph of the right eye shows prominent swelling of the disc with a disc rim hemorrhage. (B) Fundus photograph of the left eye shows a healthy appearing but crowded disc with a cup-to-disc ratio of 0.2.

51

Feature Arteritic AION Nonarteritic AION

Age (mean years) 70 60

Sex ratio Female > male Male = female

Associated symptoms Headache, scalptenderness, jaw

claudication

Pain occasionally noted

Visual acuity Up to 76% < 20/200(6/60)

Up to 61% > 20/200(6/60)

Disc Pale > hyperemic edemaCup normal

Hyperemic > pale edemaCup small

Mean erythrocytesedimentation rate

(mm/hour)

70 20–40

Fluorescein angiogram Disc and choroidfilling delay

Disc filling delay

Natural history Improvement rareFellow eye in up to 95%

Improvement inup to 43%

Fellow eye in < 30%

Treatment Corticosteroids None proved52

53

FUNDUS FLUORESCEIN ANGIOGRAPHY

▪ In non-arteritic AION, during the very early stages of the disease, angiography may show filling defects in the optic disk.

▪ In contrast, peripapillary choroidal filling is not delayed.

▪ In arteritic AION this test is extremely helpful in making the diagnosis because it shows that both the choroid and the optic disk in the area supplied by the involved posterior ciliary artery do not fill.

▪ Since, arteritic and non-arteritic forms of the ischemic optic neuropathy differ in the underlying risk factors, it is extremely important to distinguish between the two forms of the disease.

Diagnosis and Ancillary Testing

▪ The most important early step in the management of AION is the differentiation of the arteritic from the nonarteritic form of the disease.

▪ Measurement of the erythrocyte sedimentation rate (ESR) is standard.

▪ Active temporal arteritis usually is associated with an elevation of ESR to 70–120 mm/hour, and in acute AION that is associated with other typical features, this finding suggests the arteriticform; in most cases, it should prompt immediate corticosteroid therapy and confirmatory temporal artery biopsy.

▪ The test has significant limitations, however, with normal measurements found in an estimated 16% of biopsy-proved cases.

56

▪ Conversely, abnormally high readings occur normally with increasing age and with other diseases, most commonly occult malignancy, other inflammatory disease, and diabetes.

▪ Measurement of serum C-reactive protein (CRP), another acute-phase plasma protein, may aid in diagnosis.

▪ Hayreh et al.reported 97% specificity for temporal arteritis in cases of AION in which both ESR > 47 mm/hour and CRP > 2.45mg/dL were found.

57

▪ Confirmation of the diagnosis of temporal arteritis by superficial temporal artery biopsy is recommended in any case of AION in which a clinical suspicion of arteritis exists based on age, associated systemic symptoms, severity of visual loss, and elevated ESR and CRP levels.

▪ Positive biopsy findings, such as intimal thickening, internal limiting lamina fragmentation, and chronic inflammatory infiltrate with giant cells, provide support for long-term systemic corticosteroid therapy.

58

▪ A negative biopsy result, however, does not rule out arteritis; both discontinuous arterial involvement (“skip lesions”) and solely contralateral temporal artery inflammation may result in false-negative results.

▪ In the face of negative initial biopsy, consideration is given to contralateral biopsy in cases with high clinical suspicion of temporal arteritis.

59

60

Differential Diagnosis

▪ The differential diagnosis of AION includes idiopathic optic neuritis, particularly in patients under 50 years of age; other forms of optic nerve inflammation, such as those related to syphilis or sarcoidosis; infiltrative optic neuropathies; anterior orbital lesions that produce optic nerve compression; and diabetic papillopathy.

▪ Optic neuritis may resemble AION with regard to rate of onset, pattern of visual field loss, and optic disc appearance.

▪ In most cases, however, the patient’s age, lack of pain with eye movement, and pallor or segmental configuration of the disc edema enables differentiation.

▪ Early disc filling delay on fluorescein angiography may confirm ischemia.

61

▪ Syphilitic or sarcoid-associated optic neuritis often is associated with other intraocular inflammatory signs, which should prompt further testing.

▪ Orbital lesions typically produce gradually progressive visual loss.

▪ Associated signs of orbital disease, such as mild exophthalmos, lid abnormalities, or eye movement limitation, may suggest the use of neuroimaging to detect anterior orbital inflammation or tumor.

62

Systemic Associations

▪ AAION is known to be a manifestation of temporal arteritis.

▪ NAION has been reported in association with a number of diseases that could predispose to reduced perfusion pressure or increased resistance to flow within the optic nerve head.

▪ Systemic hypertension has been documented in up to 47% of patients who have NAION and diabetes in up to 24%.

63

▪ Diabetics in particular show a predisposition to NAION at a young age.

▪ Carotid occlusive disease, itself, does not appear to be associated directly with NAION in most cases.

▪ However, indirect evidence shows increased central nervous system, small vessel, ischemic disease in patients who have NAION, based on magnetic resonance imaging (MRI) data.

64

▪ Early reports did not indicate that the incidence of prior or subsequent cerebrovascular or cardiovascular events is increased, but more recent studies indicate that they are both more common than in the normal population, particularly in patients who have hypertension or diabetes.

▪ Subsequent mortality, however, is not affected.

65

▪ Also, NAION has been reported in association with multiple forms of vasculitis, acute systemic hypotension, migraine, optic disc drusen, and idiopathic vaso-occlusive diseases.

▪ Other risk factors, such as hyperopia, smoking, the presence of human lymphocyte antigen A, and hyperlipidemia have been proposed.

▪ Recent reports of the association of hyperhomocystinemiawith AION, particularly in patients under 50, are inconclusive.

▪ Prothrombotic risk factors, such as protein C and S and antithrombin III deficiencies, factor V Leiden mutation, and cardiolipin antibodies, do not seem to be associated with AION.

66

Treatment

Arteritic anterior ischemic optic neuropathy

▪ Early treatment of AAION is essential and must be instituted immediately in any suspected case of temporal arteritis.

▪ High-dose systemic corticosteroids are standard; the use of intravenous methylprednisolone at 1 g/day for the first 3 days has been recommended for AAION when the patient is in the acute phase of severe involvement, because this mode of therapy produces higher blood levels of medication more rapidly.

▪ Oral prednisone in the range of 60–100 mg/day may be used initially and for follow-up to intravenous pulse therapy; alternate day regimens do not suppress the disease effectively.

67

▪ Treatment usually reduces systemic symptoms within several days.

▪ A positive response is so typical that if it does not occur, an alternate disease process should be considered.

▪ Treatment is usually continued at high dose for several months before beginning taper.

68

Nonarteritic anterior ischemic optic neuropathy

▪ There is no proven effective therapy for NAION.

▪ Oral corticosteroids at standard dosage (1 mg/kg per day) are not beneficial, and megadose intravenous therapy has not been evaluated systematically.

▪ Optic nerve sheath decompression (ONSD) surgery has been attempted, based on the theory that reduction of perineuralsubarachnoid cerebrospinal fluid pressure might improve local vascular flow or axoplasmic transport in the optic nerve head, and thus reduce tissue injury in reversibly damaged axons.

▪ The Ischemic Optic Neuropathy Decompression Trial compared ONSD surgery in 119 patients with no treatment in 125 controls.

69

▪ The study revealed no significant benefit for treatment and a possible, although not proven, harmful effect; it was recommended that ONSD not be performed for NAION.

▪ Hyperbaric oxygen, by marked elevation of the dissolved oxygen content in the blood, provides increased tissue oxygenation that might reduce damage in reversibly injured axons.

▪ A controlled clinical pilot study of hyperbaric oxygen in 22 patients who had acute NAION, however, has shown no beneficial effect.

70

▪ Johnson et al.reported a beneficial effect for oral levodopaon the visual outcome for NAION, but the study was controversial, and the effect is considered unproved.

▪ Neuroprotective agents have shown a beneficial effect in animal models of optic nerve damage, but are not proven to be effective in NAION.

▪ The effect of aspirin in reducing risk of fellow eye involvement is unclear.

71

Course and Outcome

Arteritic anterior ischemic optic neuropathy

▪ The major goal of therapy in AAION is to prevent visual loss in the fellow eye.

▪ Untreated, such involvement occurs in 54–95% of cases, typically within 4 months.

▪ With corticosteroid therapy, the rate of such breakthrough is reduced to an estimated 13%.

▪ Prognosis for visual recovery in the affected eye that has treatment generally is poor, but recent reports suggest a 15–34% improvement rate, which is higher with intravenous than with oral therapy.

▪ Worsening of vision in spite of therapy has been reported in 9–17% of cases. 72

Nonarteritic anterior ischemic optic neuropathy

▪ The course of untreated NAION varies considerably.

▪ Reports indicate that 24–43% of cases demonstrate spontaneous improvement of visual acuity by three Snellenlines or more.

▪ Even in the progressive form, improvement has been reported to occur in roughly 30%.

▪ Whether NAION is static or progressive, visual acuity and field stabilize after several months.

73

▪ Within 6 weeks, occasionally sooner, the optic disc becomes visibly atrophic, either in a sectorial or diffuse pattern.

▪ Further progression or recurrent episodes are extremely rare after 2 months and, if present, should prompt evaluation for another cause of optic neuropathy.

74

75

POSTERIOR ISCHEMIC OPTIC NEUROPATHY

▪ Ischemia of the optic nerve that does not involve the optic nerve head is termed posterior ischemic optic neuropathy (PION).

▪ It presents with acute visual loss associated with signs of optic neuropathy (afferent pupillary defect and visual field loss) in one or both eyes, with initially normal appearance of the optic disc, which subsequently becomes atrophic.

76

The diagnosis of PION is most often made in one of two settings:

▪ 1. Vasculitis, most importantly giant cell arteritis (GCA); evaluation for GCA should be the primary consideration with this presentation in the elderly, or

▪ 2. The combination of systemic hypotension and anemia, usually related to blood loss either from surgery (coronary artery bypass and lumbar spine procedures most commonly),gastrointestinal bleed, or trauma.

77

▪ The differential diagnosis includes compressive, inflammatory, and infiltrative optic neuropathies, although the onset in PION is typically more abrupt.

▪ In most cases, neuroimaging is indicated to rule out these possibilities.

78

▪ Sadda et al.reported a multicenter, retrospective review of 72 patients with PION, adding a third classification paralleling the nonarteritic form of AION.

▪ The nonarteritic PION group accounted for 38 of the 72 patients, exhibited similar risk factors, and followed a clinical course precisely like that of NAION.

▪ In contrast to perioperative and arteritic PION, which were characterized by severe visual loss with little or no recovery, nonarteritic PION was less severe and showed improvement in 34% of patients.

79

▪ It is important to recognize this nonarteritic form in patients with acute optic neuropathy but no optic disc edema, a scenario that may be mistaken for retrobulbar optic neuritis.

▪ Such patients, particularly those with ischemic white-matter lesions on MRI, might be incorrectly begun on immunomodulatory therapy to reduce the risk of MS.

▪ PION differs from optic neuritis by its occurrence in older age groups, with lack of pain on eye movements.

80

DIABETIC PAPILLOPATHY

PATHOGENESIS

▪ The pathogenesis of diabetic papillopathy is unclear.

▪ Early investigators postulated either a toxic effect on the optic nerve secondary to abnormal glucose metabolism or a vascular disturbance of the inner disc surface, similar to that which produces retinal edema, with the resultant microvascular leakage into the disc.

▪ The most commonly proposed theory suggests diabetic papillopathy to be a mild form of NAION, with reversible ischemia of both the prelaminar and inner surface layers of the optic nerve head.

▪ Edema of the optic nerve head in the absence of significant visual dysfunction and not secondary to elevated intracranial pressure occurs in several presumed vascular disorders as follows:

81

▪ Asymptomatic optic disc edema, which evolves to typical NAION weeks to months after initial symptoms.

▪ Asymptomatic disc edema of the fellow eye in patients who have NAION, which may either progress to NAION or resolve spontaneously.

▪ Disc edema in association with systemic hypertension, which resolves without sequelae as blood pressure is normalized.

82

▪ Diabetic papillopathy fits this category, as well.

▪ The prominent surface telangiectasias may represent vascular shunting from prelaminar to ischemic vascular beds.

▪ The frequent occurrence of a crowded optic disc in the fellow eye,as in NAION, also supports an ischemic mechanism.

83

OCULAR MANIFESTATIONS

▪ Early reports of diabetic papillopathy depicted the acute onset of unilateral or bilateral disc edema in young, type 1 diabetics, without the usual defects in visual field and pupillary function associated with NAION or optic neuritis;a recent report included a substantial number of older patients with type 2 diabetes.

▪ The currently accepted criteria for the diagnosis of diabetic papillopathy include:

84

Presence of diabetes (approximately 70% type 1, 30% type 2).

Optic disc edema (unilateral in roughly 60%).

Only mild optic nerve dysfunction.

▪ The absence of ocular inflammation or elevated intracranial pressure also is essential to the diagnosis.

85

▪ Although younger patients predominate (approximately 75% of those reported are under the age of 50 years), those affected may be of any age and typically experience either no visual complaints or vague, nonspecific visual disturbance, such as mild blurring or distortion; transient visual obscuration has been reported rarely.

▪ Visual acuity is usually only mildly impaired; over 75% of reported cases measured 20/40 (6/12) or better. Macular edema contributes to visual acuity loss in many cases.

▪ Pain is absent, as are other ocular or neurological symptoms.

86

▪ The involved optic discs may demonstrate either nonspecific hyperemic edema or, in approximately 55% of cases, marked telangiectasia of the inner surface microvasculature; pale swelling typically has been a criterion for exclusion and suggests AION.

▪ The surface telangiectasia is so prominent in many cases that it may be mistaken for neovascularization.

▪ True disc neovascularization occasionally is superimposed on the edema of diabetic papillopathy. The fellow eye frequently demonstrates crowding, with a small cup-to-disc ratio similar to the configuration seen in patients who have NAION.

87

OPTIC DISC IN DIABETIC PAPILLOPATHY

(A) Nonspecific hyperemic disc edema. 88

(B) Surface vessels show marked telangiectasia, in which dilated vesselsgenerally follow a radial distribution.

89

(C) Contrast with diabetic optic disc neovascularization; notethe irregular, random branching pattern of surface vessels. 90

▪ Diabetic retinopathy usually is present (in more than 80% of reported cases) at the time of onset of papillopathy, but it varies in severity.

▪ It is associated with cystoid macular edema in about 25% of cases and neovascularization in approximately 9%.

91

DIFFERENTIAL DIAGNOSIS

▪ Conditions that may simulate diabetic papillopathy include papilledema (elevated intracranial pressure), hypertensive papillopathy, optic disc neovascularization, papillitis, and NAION.

▪ Symptoms of elevated intracranial pressure usually differentiate papilledema, and in bilateral cases with such symptoms, neuroimagingand lumbar puncture must be considered.

▪ Disc edema related to systemic hypertension typically does not demonstrate prominent telangiectasia and usually is associated with hypertensive retinopathy; blood pressure measurement is important in suspected cases.

▪ Papillitis and NAION both demonstrate significant optic nerve dysfunction, as evidenced by afferent pupillary defect and visual field loss.

92

COURSE AND OUTCOME

▪ Although systemic corticosteroids have been used in isolated cases, no proven therapy exists for this disorder.

▪ Untreated, the optic disc edema gradually resolves over a period of 2–10 months, to leave minimal optic atrophy in about 20% of cases and subtle, if any, visual field loss.

▪ Visual acuity at the time of resolution of edema is 20/40 (6/12) or better in about 80% of cases; the remainder of patients suffer visual impairment because of maculopathy.

▪ The long-term visual prognosis for patients who have diabetic papillopathy, however, is limited by the associated diabetic retinopathy.

▪ Proliferative changes, with attendant complications, develop in approximately 25% of cases.

93

THANK YOU….

94

95

96