This document presents a case study of a 38-year-old man referred for increased intraocular pressure in his right eye after undergoing penetrating keratoplasty in both eyes. His intraocular pressure rose due to the topical steroid medication prescribed after surgery. A trabeculectomy with 5-fluorouracil was performed to lower his pressure, which was successful. The case highlights the risk of steroid-induced glaucoma from topical corticosteroid use after ocular surgery or inflammation.

1. New England Eye Centre Grand Rounds Wayne L. Scott April 12, 2001

2. New England Eye Centre Grand Rounds - Case Presentation A 38 year old man was referred to the New England Eye centre Glaucoma service for evaluation of increased intraocular pressure in his right eye.

3. New England Eye Centre Grand Rounds - Case Presentation allergies: nkda Medical history: mental retardation Past Ocular history: Keratoconus OU OD: -20.00 +6.00 x 175 OS: -18.00 +6.50 x 180 Contact lens intolerant Penetrating keratoplasty OD 11/1/00 Penetrating keratoplasty OS 11/7/00

4. New England Eye Centre Grand Rounds - Case Presentation Keratoplasty OD 11/1/00 Follow up exam Cornea service May 24, 2000 VA(sc): OD 20/30 AT: OD 18 mm Hg SLE Cornea(OD): PK clear Anterior Chamber(OD): deep and quiet Medications: continued on Prednisolone Acetate 1% (Pred Forte 1%) OD BID

5. New England Eye Centre Grand Rounds - Case Presentation July 10, 2000 (6 months post penetrating keratoplasty) VA(sc): OD 20/40 AT: OD 26 mm Hg SLE Cornea (OD): PK clear Anterior Chamber (OD): deep and quiet Medications: decreased Pred Forte 1% to OD QD

6. New England Eye Centre Grand Rounds - Case Presentation July 26, 2000 VA(sc): OD 20/60 AT: OD 40 mm Hg SLE Cornea(OD): PK trace microcystic oedema Anterior Chamber(OD): deep and quiet Medications continued with Pred Forte 1% to OD QD Add Dorzolamide HCL-Timolol Maleate (Cosopt) OD BID and Brimonidine 0.2% (Alphagan) OD BID

7. New England Eye Centre Grand Rounds - Case Presentation August 16, 2000 VA(sc): OD 20/40 AT: OD 12 mm Hg SLE Cornea(OD): PK clear Anterior Chamber(OD): deep and quiet Medications: Continued with Pred-forte 1% to OD QD Continued Cosopt OD BID and Alphagan OD BID

8. New England Eye Centre Grand Rounds - Case Presentation September 13, 2000 VA(sc): 20/40 AT: OD 20 mm Hg continued on Alphagan, Cosopt, and Pred Forte 1% OD BID November 22, 2000 AT: OD 48 mm Hg continued on Alphagan and Cosopt added Latanoprost 0.005% (Xalatan) and Fluorometholone .1% (FML) BID OD Pred Forte 1% discontinued OD

9. New England Eye Centre Grand Rounds - Case Presentation December 6, 2000 AT: OD 34 mm Hg Questions of compliance Continued on Alphagan, Cosopt, FML December 20, 2000 Glaucoma service Medications on presentation Pred Forte QD OS Alphagan OD BID Cosopt OD BID FML OD BID VA(sc): OD 20/40 OS 20/50 AT: OD 46 mm Hg OS 18 mm Hg

10. New England Eye Centre Grand Rounds - Case Presentation SLE: Cornea: OD PK mild haze OS clear ant chamber: deep and quiet OU iris: normal OU lens: normal OU Optic nerves: healthy and intact neural retinal rims OU Fundus exam: normal macula, vessels, and periphery OU

11. New England Eye Centre Grand Rounds Disk Photo OD Disk Photo OS

12. New England Eye Centre Grand Rounds - Case Presentation Zeiss gonioscopy OD: light trabecular meshwork, broad peripheral anterior synechiae nasally and intermittent peripheral anterior synechiae to pigmented trabecular meshwork inferiorly OS: light trabecular meshwork with intermittent peripheral anterior synechiae inferiorly nasally

13. New England Eye Centre Grand Rounds – Case Presentation A 24-2 Humphrey visual field was obtained.

14. New England Eye Centre Grand Rounds HVF 24-2 OS HVF 24-2 OD

15. New England Eye Centre Grand Rounds The differential diagnosis for increased intraocular pressure in this young man is: Steroid induced Glaucoma Post-Penetrating Keratoplasty Glaucoma Primary Open Angle Glaucoma Inflammatory Glaucoma

16. New England Eye Centre Grand Rounds - Case Presentation The patient’s rise in intraocular pressure was believed to be secondary to the topical steroids he was using after the penetrating keratoplasty OD. Plan: attempt to wait out steroid response continue on present topical regimen Pred Forte QD OS Alphagan OD BID Cosopt OD BID FML OD BID added Unoprostone isopropyl 0.15% (Rescula) OD BID

17. New England Eye Centre Grand Rounds - Case Presentation January 24, 2001 Glaucoma service VA(cc): OD 20/100 OS 20/30 AT: OD 52 OS 21 SLE: Cornea: OD PK microcystic oedema OS PK clear ant chamber: deep and quiet OU iris: normal OU lens: normal OU fundus and disc OD: no change

18. New England Eye Centre Grand Rounds - Case Presentation Plan: The decision was made to perform a trabeculectomy with 5-fluorouracil in an attempt to lower his intraocular pressure. February 7, 2001 2 week s/p trab with 5-FU VA(cc): OD 20/60 IOP: OD 9 mm Hg SLE: OD Conjunctiva: localized elevated bleb Cornea: PK clear Anterior chamber: deep and trace cell

19. New England Eye Centre Grand Rounds - Case Presentation March 28, 2001 2 months s/p trabeculectomy with 5-FU VA(cc): OD 20/50 IOP: OD 9 mm Hg SLE: OD Conjunctiva: low cystic bleb with microcysts Cornea: PK clear Anterior chamber: deep and quiet

20. New England Eye Centre Grand Rounds – Discussion Elevated intraocular pressure associated with corticosteroid use was reported as early as the 1950’s but was not widely accepted until the publications of Drs. Mansour Armaly and Bernard Becker in the mid 1960’s. Dr. Armaly and Becker published several articles on corticosteroids' intraocular pressure effects upon both normal and glaucomatous eyes. 1,2,3,5

21. New England Eye Centre Grand Rounds – Discussion Several case reports have confirmed that intraocular pressure may rise with topical, systemic, periocular and inhaled administration of corticosteroids. 6,7 Clinically, steroid induced glaucoma resembles open-angle glaucoma with an open and normal anterior chamber angle and no symptoms

22. New England Eye Centre Grand Rounds – Discussion Corticosteroids raise intraocular pressure by lowering the facility of outflow by way of several mechanisms. Inhibit catabolism of glycosaminoglycans(GAG) The GAG then accumulate in the trabecular meshwork obstructing outflow. corticosteroids stabilize lysosomal membranes, inhibiting release of enzymes which breakdown glycosaminoglycans. Inhibit phagocytosis of foreign material by trabecular endothelial cells, blocking outflow channels

23. New England Eye Centre Grand Rounds – Discussion Who is at risk for developing steroid induced glaucoma? Primary open angle glaucoma High myopia Diabetics

24. New England Eye Centre Grand Rounds - Discussion Careful history taking of current and past medications is vital in its diagnosis A rise in intraocular pressure may occur as early as one week after initiating treatment or many months to years afterwards. Latency period may depend upon a few factors 8 : Potency of the drug route of administration Dose and frequency of drug patient individual response Presence of other ocular diseases

25. New England Eye Centre Grand Rounds – Discussion Corticosteroids- family of compounds derived from cholesterol molecule. 9 Addition of double bonds, side group modifications and creation of derivative compounds can change effect and potency of the drug. Derivative compounds may change effect of the base molecule by affecting penetration into the eye, release and degradation rate.

26. New England Eye Centre Grand Rounds - Discussion Several types of corticosteroids are less likely to cause intraocular elevation but are less effective in controlling inflammation. Rimexolone (Vexol) Flourometholone(FML) Loteprednol(Lotemax)

27. New England Eye Centre Grand Rounds – Discussion Management Obtain baseline intraocular pressure before starting corticosteroid therapy. Check IOP every 2-3 weeks for first few months, then every 2-3 months if chronic treatment is needed. There is no time period beyond which a patient is incapable of developing corticosteroid induced glaucoma.

28. New England Eye Centre Grand Rounds – Discussion Management Use steroid preparations that are less likely to increase intraocular pressure when possible Once a pressure rise is noted, attempt stopping or tapering the corticosteroid for a decrease of the intraocular pressure to baseline If the pressure is too high, add glaucoma medications in addition to tapering corticosteroids A filtering procedure may need to be performed if severe or prolonged intraocular pressure elevation is potentially damaging to the optic nerve.

29. New England Eye Centre Grand Rounds - Bibliography Armaly MF. Effect of corticosteroids on intraocular pressure and fluid dynamics. I. The effect of dexamethasone in the normal eye. Arch Ophthalmol 1963;70: 482-491 Armaly MF. Effect of corticosteroids on intraocular pressure and fluids dynamics. I. The effect of dexamethasone in the glaucomatous eye. Arch Ophthalmol 1963; 70: 492-499. Armaly MF. Statistical attributes of the steroid hypertensive response in the clinically normal eye. Invest Ophthalmol Vis Sci. 1965:4; 187- 197. Ayyala RS. Penetrating Keratoplasty and Glaucoma. Surv Ophthalmol 45:91-105, 2000.

30. New England Eye Centre Grand Rounds – Bibliography Becker B. Intraocular pressure response to topical corticosteroids. Invest Ophthalmol Vis Sci. 1965; 4:198-205. Cubey RB Glaucoma following the application of corticosteroid to the skin of the eyelids British Journal of Dermatology. 1976 95; 207-208 Dryer EB. Inhaled steroid use and glaucoma. New England J. Med. 1993; 329: 1822 Kass MA, Johnson T, Corticosteroid induced Glaucoma. In: The Glaucomas Editors: Ritch, Shields, Krupin. Chapter 64. Pp. 1161-1167.

31. New England Eye Centre Grand Rounds – Bibliography Pappa, K. Corticosteroid Drugs. In. Havener’s Ocular Pharmacology. Editor Laurel Craven chapter 7, section 3: pp. 364-429.