New England Eye Centre New England Eye Centre Grand RoundsGrand Rounds

Wayne L. ScottWayne L. ScottApril 12, 2001April 12, 2001

New England Eye CentreNew England Eye CentreGrand Rounds - Case PresentationGrand Rounds - Case Presentation

A 38 year old man was referred to the New A 38 year old man was referred to the New England Eye centre Glaucoma service for England Eye centre Glaucoma service for evaluation of increased intraocular pressure evaluation of increased intraocular pressure in his right eye.in his right eye.

New England Eye CentreNew England Eye CentreGrand Rounds - Case PresentationGrand Rounds - Case Presentation allergies: nkdaallergies: nkda Medical history: mental retardationMedical history: mental retardation Past Ocular history:Past Ocular history:

– Keratoconus OUKeratoconus OU» OD: -20.00 +6.00 x 175OD: -20.00 +6.00 x 175» OS: -18.00 +6.50 x 180OS: -18.00 +6.50 x 180

– Contact lens intolerantContact lens intolerant– Penetrating keratoplasty OD 11/1/00Penetrating keratoplasty OD 11/1/00– Penetrating keratoplasty OS 11/7/00Penetrating keratoplasty OS 11/7/00

New England Eye CentreNew England Eye CentreGrand Rounds - Case PresentationGrand Rounds - Case Presentation Keratoplasty OD 11/1/00Keratoplasty OD 11/1/00 Follow up exam Cornea service May 24, 2000Follow up exam Cornea service May 24, 2000

– VA(sc): OD 20/30VA(sc): OD 20/30

– AT: OD 18 mm Hg AT: OD 18 mm Hg

– SLESLE» Cornea(OD): PK clearCornea(OD): PK clear

» Anterior Chamber(OD): deep and quietAnterior Chamber(OD): deep and quiet

– Medications: continued on Prednisolone Acetate 1% Medications: continued on Prednisolone Acetate 1% (Pred Forte 1%) OD BID(Pred Forte 1%) OD BID

New England Eye CentreNew England Eye CentreGrand Rounds - Case PresentationGrand Rounds - Case Presentation July 10, 2000 (6 months post penetrating July 10, 2000 (6 months post penetrating

keratoplasty)keratoplasty)– VA(sc): OD 20/40 VA(sc): OD 20/40 – AT: OD 26 mm HgAT: OD 26 mm Hg– SLESLE

» Cornea (OD): PK clear Cornea (OD): PK clear

» Anterior Chamber (OD): deep and quiet Anterior Chamber (OD): deep and quiet

– Medications: Medications: » decreased Pred Forte 1% to OD QDdecreased Pred Forte 1% to OD QD

New England Eye CentreNew England Eye CentreGrand Rounds - Case PresentationGrand Rounds - Case Presentation July 26, 2000July 26, 2000

– VA(sc): OD 20/60VA(sc): OD 20/60

– AT: OD 40 mm Hg AT: OD 40 mm Hg

– SLESLE» Cornea(OD): PK trace microcystic oedema Cornea(OD): PK trace microcystic oedema

» Anterior Chamber(OD): deep and quietAnterior Chamber(OD): deep and quiet

– MedicationsMedications» continued with Pred Forte 1% to OD QDcontinued with Pred Forte 1% to OD QD

» Add Dorzolamide HCL-Timolol Maleate (Cosopt) OD BID Add Dorzolamide HCL-Timolol Maleate (Cosopt) OD BID and Brimonidine 0.2% (Alphagan) OD BIDand Brimonidine 0.2% (Alphagan) OD BID

New England Eye CentreNew England Eye CentreGrand Rounds - Case PresentationGrand Rounds - Case Presentation August 16, 2000August 16, 2000

– VA(sc): OD 20/40VA(sc): OD 20/40– AT: OD 12 mm HgAT: OD 12 mm Hg– SLESLE

» Cornea(OD): PK clearCornea(OD): PK clear

» Anterior Chamber(OD): deep and quietAnterior Chamber(OD): deep and quiet

– Medications:Medications:» Continued with Pred-forte 1% to OD QDContinued with Pred-forte 1% to OD QD

» Continued Cosopt OD BID and Alphagan OD BIDContinued Cosopt OD BID and Alphagan OD BID

New England Eye CentreNew England Eye CentreGrand Rounds - Case PresentationGrand Rounds - Case Presentation September 13, 2000September 13, 2000

– VA(sc): 20/40VA(sc): 20/40– AT: OD 20 mm HgAT: OD 20 mm Hg– continued on Alphagan, Cosopt, and Pred Forte 1% OD continued on Alphagan, Cosopt, and Pred Forte 1% OD

BIDBID November 22, 2000November 22, 2000

– AT: OD 48 mm HgAT: OD 48 mm Hg– continued on Alphagan and Cosoptcontinued on Alphagan and Cosopt– added Latanoprost 0.005% (Xalatan) and added Latanoprost 0.005% (Xalatan) and

Fluorometholone .1% (FML) BID ODFluorometholone .1% (FML) BID OD– Pred Forte 1% discontinued ODPred Forte 1% discontinued OD

New England Eye CentreNew England Eye CentreGrand Rounds - Case PresentationGrand Rounds - Case Presentation December 6, 2000December 6, 2000

– AT: OD 34 mm HgAT: OD 34 mm Hg– Questions of complianceQuestions of compliance– Continued on Alphagan, Cosopt, FMLContinued on Alphagan, Cosopt, FML

December 20, 2000 Glaucoma serviceDecember 20, 2000 Glaucoma service– Medications on presentationMedications on presentation

» Pred Forte QD OSPred Forte QD OS» Alphagan OD BIDAlphagan OD BID» Cosopt OD BIDCosopt OD BID» FML OD BIDFML OD BID

– VA(sc): OD 20/40 OS 20/50VA(sc): OD 20/40 OS 20/50– AT: OD 46 mm Hg OS 18 mm HgAT: OD 46 mm Hg OS 18 mm Hg

New England Eye CentreNew England Eye CentreGrand Rounds - Case PresentationGrand Rounds - Case Presentation SLE:SLE:

– Cornea: OD PK mild haze OS clearCornea: OD PK mild haze OS clear– ant chamber: deep and quiet OUant chamber: deep and quiet OU– iris: normal OUiris: normal OU– lens: normal OUlens: normal OU– Optic nerves: healthy and intact neural retinal Optic nerves: healthy and intact neural retinal

rims OUrims OU– Fundus exam: normal macula, vessels, and Fundus exam: normal macula, vessels, and

periphery OUperiphery OU

New England Eye CentreNew England Eye CentreGrand RoundsGrand Rounds

Disk Photo OD Disk Photo OS

New England Eye CentreNew England Eye CentreGrand Rounds - Case PresentationGrand Rounds - Case Presentation Zeiss gonioscopyZeiss gonioscopy

– OD: light trabecular meshwork, broad OD: light trabecular meshwork, broad peripheral anterior synechiae nasally and peripheral anterior synechiae nasally and intermittent peripheral anterior synechiae to intermittent peripheral anterior synechiae to pigmented trabecular meshwork inferiorlypigmented trabecular meshwork inferiorly

– OS: light trabecular meshwork with intermittent OS: light trabecular meshwork with intermittent peripheral anterior synechiae inferiorly nasallyperipheral anterior synechiae inferiorly nasally

New England Eye CentreNew England Eye CentreGrand Rounds – Case PresentationGrand Rounds – Case Presentation A 24-2 Humphrey visual field was A 24-2 Humphrey visual field was

obtained.obtained.

New England Eye CentreNew England Eye CentreGrand RoundsGrand Rounds

HVF 24-2 OS HVF 24-2 OD

New England Eye CentreNew England Eye CentreGrand RoundsGrand Rounds

The differential diagnosis for increased The differential diagnosis for increased intraocular pressure in this young man is:intraocular pressure in this young man is:– Steroid induced GlaucomaSteroid induced Glaucoma– Post-Penetrating Keratoplasty GlaucomaPost-Penetrating Keratoplasty Glaucoma– Primary Open Angle GlaucomaPrimary Open Angle Glaucoma– Inflammatory GlaucomaInflammatory Glaucoma

New England Eye CentreNew England Eye CentreGrand Rounds - Case PresentationGrand Rounds - Case Presentation The patient’s rise in intraocular pressure was The patient’s rise in intraocular pressure was

believed to be secondary to the topical steroids he believed to be secondary to the topical steroids he was using after the penetrating keratoplasty OD. was using after the penetrating keratoplasty OD.

Plan: attempt to wait out steroid responsePlan: attempt to wait out steroid response– continue on present topical regimen continue on present topical regimen

» Pred Forte QD OS Pred Forte QD OS

» Alphagan OD BID Alphagan OD BID

» Cosopt OD BID Cosopt OD BID

» FML OD BID FML OD BID

– added Unoprostone isopropyl 0.15% (Rescula) OD BIDadded Unoprostone isopropyl 0.15% (Rescula) OD BID

New England Eye CentreNew England Eye CentreGrand Rounds - Case PresentationGrand Rounds - Case Presentation January 24, 2001 Glaucoma serviceJanuary 24, 2001 Glaucoma service

– VA(cc): OD 20/100VA(cc): OD 20/100 OS 20/30OS 20/30– AT: OD 52AT: OD 52 OS 21OS 21– SLE:SLE:

» Cornea: OD PK microcystic oedema OS PK clearCornea: OD PK microcystic oedema OS PK clear

» ant chamber: deep and quiet OU ant chamber: deep and quiet OU

» iris: normal OU iris: normal OU

» lens: normal OU lens: normal OU

» fundus and disc OD: no changefundus and disc OD: no change

New England Eye CentreNew England Eye CentreGrand Rounds - Case PresentationGrand Rounds - Case Presentation Plan: The decision was made to perform a Plan: The decision was made to perform a

trabeculectomy with 5-fluorouracil in an attempt trabeculectomy with 5-fluorouracil in an attempt to lower his intraocular pressure. February 7, 2001to lower his intraocular pressure. February 7, 2001

2 week s/p trab with 5-FU2 week s/p trab with 5-FU– VA(cc): OD 20/60VA(cc): OD 20/60

– IOP: OD 9 mm HgIOP: OD 9 mm Hg

– SLE: ODSLE: OD» Conjunctiva: localized elevated blebConjunctiva: localized elevated bleb

» Cornea: PK clearCornea: PK clear

» Anterior chamber: deep and trace cellAnterior chamber: deep and trace cell

New England Eye CentreNew England Eye CentreGrand Rounds - Case PresentationGrand Rounds - Case Presentation March 28, 2001March 28, 2001

– 2 months s/p trabeculectomy with 5-FU2 months s/p trabeculectomy with 5-FU– VA(cc): OD 20/50VA(cc): OD 20/50– IOP: OD 9 mm HgIOP: OD 9 mm Hg– SLE: ODSLE: OD

» Conjunctiva: low cystic bleb with microcystsConjunctiva: low cystic bleb with microcysts

» Cornea: PK clearCornea: PK clear

» Anterior chamber: deep and quietAnterior chamber: deep and quiet

New England Eye CentreNew England Eye CentreGrand Rounds – DiscussionGrand Rounds – Discussion

Elevated intraocular pressure associated with Elevated intraocular pressure associated with corticosteroid use was reported as early as the corticosteroid use was reported as early as the 1950’s but was not widely accepted until the 1950’s but was not widely accepted until the publications of Drs. Mansour Armaly and publications of Drs. Mansour Armaly and Bernard Becker in the mid 1960’s.Bernard Becker in the mid 1960’s.

Dr. Armaly and Becker published several articles Dr. Armaly and Becker published several articles on corticosteroids' intraocular pressure effects on corticosteroids' intraocular pressure effects upon both normal and glaucomatous eyes.upon both normal and glaucomatous eyes.1,2,3,51,2,3,5

New England Eye CentreNew England Eye CentreGrand Rounds – DiscussionGrand Rounds – Discussion

Several case reports have confirmed that Several case reports have confirmed that intraocular pressure may rise with topical, intraocular pressure may rise with topical, systemic, periocular and inhaled systemic, periocular and inhaled administration of corticosteroids.administration of corticosteroids.6,76,7

Clinically, steroid induced glaucoma Clinically, steroid induced glaucoma resembles open-angle glaucoma with an resembles open-angle glaucoma with an open and normal anterior chamber angle open and normal anterior chamber angle and no symptomsand no symptoms

New England Eye CentreNew England Eye CentreGrand Rounds – DiscussionGrand Rounds – Discussion

Corticosteroids raise intraocular pressure by Corticosteroids raise intraocular pressure by lowering the facility of outflow by way of several lowering the facility of outflow by way of several mechanisms.mechanisms.– Inhibit catabolism of glycosaminoglycans(GAG)Inhibit catabolism of glycosaminoglycans(GAG)

» The GAG then accumulate in the trabecular meshwork The GAG then accumulate in the trabecular meshwork obstructing outflow.obstructing outflow.

– corticosteroids stabilize lysosomal membranes, corticosteroids stabilize lysosomal membranes, inhibiting release of enzymes which breakdown inhibiting release of enzymes which breakdown glycosaminoglycans.glycosaminoglycans.

– Inhibit phagocytosis of foreign material by trabecular Inhibit phagocytosis of foreign material by trabecular endothelial cells, blocking outflow channelsendothelial cells, blocking outflow channels

New England Eye CentreNew England Eye CentreGrand Rounds – DiscussionGrand Rounds – Discussion

Who is at risk for developing steroid Who is at risk for developing steroid induced glaucoma?induced glaucoma?– Primary open angle glaucomaPrimary open angle glaucoma– High myopiaHigh myopia– DiabeticsDiabetics

New England Eye CentreNew England Eye CentreGrand Rounds - DiscussionGrand Rounds - Discussion

– Careful history taking of current and past medications Careful history taking of current and past medications is vital in its diagnosisis vital in its diagnosis

– A rise in intraocular pressure may occur as early as one A rise in intraocular pressure may occur as early as one week after initiating treatment or many months to years week after initiating treatment or many months to years afterwards.afterwards.

– Latency period may depend upon a few factorsLatency period may depend upon a few factors88::» Potency of the drugPotency of the drug

» route of administrationroute of administration

» Dose and frequency of drugDose and frequency of drug

» patient individual responsepatient individual response

» Presence of other ocular diseasesPresence of other ocular diseases

New England Eye CentreNew England Eye CentreGrand Rounds – DiscussionGrand Rounds – Discussion

Corticosteroids- family of compounds Corticosteroids- family of compounds derived from cholesterol molecule.derived from cholesterol molecule.99

– Addition of double bonds, side group Addition of double bonds, side group modifications and creation of derivative modifications and creation of derivative compounds can change effect and potency of compounds can change effect and potency of the drug.the drug.

– Derivative compounds may change effect of the Derivative compounds may change effect of the base molecule by affecting penetration into the base molecule by affecting penetration into the eye, release and degradation rate.eye, release and degradation rate.

New England Eye CentreNew England Eye CentreGrand Rounds - DiscussionGrand Rounds - Discussion

– Several types of corticosteroids are less likely Several types of corticosteroids are less likely to cause intraocular elevation but are less to cause intraocular elevation but are less effective in controlling inflammation.effective in controlling inflammation.

» Rimexolone (Vexol)Rimexolone (Vexol)

» Flourometholone(FML)Flourometholone(FML)

» Loteprednol(Lotemax)Loteprednol(Lotemax)

New England Eye CentreNew England Eye CentreGrand Rounds – DiscussionGrand Rounds – Discussion

ManagementManagement– Obtain baseline intraocular pressure before Obtain baseline intraocular pressure before

starting corticosteroid therapy. starting corticosteroid therapy. – Check IOP every 2-3 weeks for first few Check IOP every 2-3 weeks for first few

months, then every 2-3 months if chronic months, then every 2-3 months if chronic treatment is needed.treatment is needed.

– There is no time period beyond which a patient There is no time period beyond which a patient is incapable of developing corticosteroid is incapable of developing corticosteroid induced glaucoma.induced glaucoma.

New England Eye CentreNew England Eye CentreGrand Rounds – DiscussionGrand Rounds – Discussion

ManagementManagement– Use steroid preparations that are less likely to increase Use steroid preparations that are less likely to increase

intraocular pressure when possibleintraocular pressure when possible– Once a pressure rise is noted, attempt stopping or Once a pressure rise is noted, attempt stopping or

tapering the corticosteroid for a decrease of the tapering the corticosteroid for a decrease of the intraocular pressure to baselineintraocular pressure to baseline

– If the pressure is too high, add glaucoma medications in If the pressure is too high, add glaucoma medications in addition to tapering corticosteroidsaddition to tapering corticosteroids

– A filtering procedure may need to be performed if A filtering procedure may need to be performed if severe or prolonged intraocular pressure elevation is severe or prolonged intraocular pressure elevation is potentially damaging to the optic nerve.potentially damaging to the optic nerve.

New England Eye CentreNew England Eye CentreGrand Rounds - BibliographyGrand Rounds - Bibliography1.1. Armaly MF. Effect of corticosteroids on intraocular Armaly MF. Effect of corticosteroids on intraocular

pressure and fluid dynamics. I. The effect of pressure and fluid dynamics. I. The effect of dexamethasone in the normal eye. Arch Ophthalmol dexamethasone in the normal eye. Arch Ophthalmol 1963;70: 482-4911963;70: 482-491

2.2. Armaly MF. Effect of corticosteroids on intraocular Armaly MF. Effect of corticosteroids on intraocular pressure and fluids dynamics. I. The effect of pressure and fluids dynamics. I. The effect of dexamethasone in the glaucomatous eye. Arch dexamethasone in the glaucomatous eye. Arch Ophthalmol 1963; 70: 492-499.Ophthalmol 1963; 70: 492-499.

3.3. Armaly MF. Statistical attributes of the steroid Armaly MF. Statistical attributes of the steroid hypertensive response in the clinically normal eye. hypertensive response in the clinically normal eye. Invest Ophthalmol Vis Sci. 1965:4; 187- 197.Invest Ophthalmol Vis Sci. 1965:4; 187- 197.

4.4. Ayyala RS. Penetrating Keratoplasty and Glaucoma. Ayyala RS. Penetrating Keratoplasty and Glaucoma. Surv Ophthalmol 45:91-105, 2000.Surv Ophthalmol 45:91-105, 2000.

New England Eye CentreNew England Eye CentreGrand Rounds – BibliographyGrand Rounds – Bibliography5.5. Becker B. Intraocular pressure response to topical Becker B. Intraocular pressure response to topical

corticosteroids. Invest Ophthalmol Vis Sci. 1965; corticosteroids. Invest Ophthalmol Vis Sci. 1965; 4:198-205.4:198-205.

6.6. Cubey RB Glaucoma following the application of Cubey RB Glaucoma following the application of corticosteroid to the skin of the eyelids British Journal corticosteroid to the skin of the eyelids British Journal of Dermatology. 1976 95; 207-208of Dermatology. 1976 95; 207-208

7.7. Dryer EB. Inhaled steroid use and glaucoma. New Dryer EB. Inhaled steroid use and glaucoma. New England J. Med. 1993; 329: 1822England J. Med. 1993; 329: 1822

8.8. Kass MA, Johnson T, Corticosteroid induced Kass MA, Johnson T, Corticosteroid induced Glaucoma. In: The Glaucomas Editors: Ritch, Shields, Glaucoma. In: The Glaucomas Editors: Ritch, Shields, Krupin. Chapter 64. Pp. 1161-1167.Krupin. Chapter 64. Pp. 1161-1167.

New England Eye CentreNew England Eye CentreGrand Rounds – BibliographyGrand Rounds – Bibliography9.9. Pappa, K. Corticosteroid Drugs. In. Havener’s Pappa, K. Corticosteroid Drugs. In. Havener’s

Ocular Pharmacology. Editor Laurel Craven Ocular Pharmacology. Editor Laurel Craven chapter 7, section 3: pp. 364-429.chapter 7, section 3: pp. 364-429.