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Using NSAIDS to Treat Macular Edema
NSAIDs can be a first line of therapy for patients with CME
BY JUAN ORELLANA, M.D., M.S., F.A.C.S.

Topical diclofenac (Voltaren, Novartis), ketorolac (Acular and Acular LS, Allergan), nepafenac (Nevanac, Alcon) and bromfenac (Xibrom, ISTA Pharmaceuticals) all belong to the NSAIDs class of medications. As an anti-inflammatory class, they function by inhibiting the enzyme cyclooxygenase, which blocks the synthesis of prostaglandins. A reduction in prostaglandin formation results in a decrease in inflammation. Inflammation functions to make the blood-retinal barrier more permeable.

It appears that the principle pathway involved in pain and inflammation is the COX-2 pathway where NSAIDs seem to play a significant role. The current uses for topical NSAIDs have been somewhat limited to the
prevention of intraoperative miosis during phacoemulsification,1,2 relief of postoperative pain, inflammation and photophobia,3 therapy for ocular atopy4 and the reduction of post-cataract cystoid macular edema (CME).3 Many cataract surgeons have used NSAIDs, such as diclofenac, preoperatively to block the formation of CME.5 For patients who develop a persistent postop CME, NSAIDs have been dispensed to reduce postop edema and improve the patient's vision.

Figure 1. The OCT demonstrates an increased thickness that correlates with her BCVA of 20/400.

Case History/Presentation

An 85-year-old female underwent cataract surgery in her left eye. She had undergone cataract surgery in the right eye 10 months previously and was diagnosed with CME by fluorescein angiography 1 month after phacoemulsification. Her acuity at diagnosis was 20/400 in the postop right eye and 20/200 in the phakic nuclear sclerotic left eye.

Intense topical prednisolone acetate was initiated; however, after 2 weeks of therapy, her IOP was noted to be 32 mm Hg. Her BCVA remained unchanged. In our office, her BVA in the right eye was 20/400. The intraocular lens was in place without any signs of vitreous in the anterior chamber. The OCT and angiogram demonstrated CME (Figure 1). Because prednisolone acetate caused her IOP to rise, a course of NSAIDs was recommended.

She began bromfenac therapy b.i.d. in her right eye. After 4 weeks of treatment, her acuity in her right eye had improved to 20/60 (Fig. 2). Both the angiogram and OCT demonstrated significant changes as well. She continued treatment and returned to the referring physician after 6 weeks of therapy. Her acuity was 20/25-2 in the right eye. It was suggested that she continue therapy for another 2 weeks, making a total of 8 weeks of treatment.

Post-Cataract CME Syndrome

Figure 2. After 4 weeks of b.i.d. bromfenac therapy, OCT shows decreased thickness, correlating with improved BCVA of 20/60.

Several factors have been implicated in the development of the Irvine-Gass or post-cataract CME syndrome.6 The principal culprit in the development of CME has been the development of an inflammatory process whereby prostaglandins are released. Physiologically, prostaglandins cause vasodilation and an increase permeability of the blood-retinal barrier. This increased permeability is manifested as a weakening of the tight junctions between capillary endothelial cells and a slowing of the active retinal fluid pumping mechanism of the pigment epithelium.

A risk factor for the development of CME after cataract surgery includes uveitis or any ocular inflammatory conditions such as intermediate uveitis, or sarcoid.6 Corticosteroids, either topical, parenterally, retrobulbar (sub-Tenon's) or intravenously,7 have been accepted as treatment for post-cataract CME. Corticosteroids are usually successful in ameliorating the condition; however, some patients will either not respond to treatment or demonstrate an increase in their IOP. For this reason, alternative therapies have been sought.

Because NSAIDs and prednisolone acetate block prostaglandin synthesis via the same pathway, NSAIDs have been evaluated and found to be helpful in both preventing and treating CME.5,8-10 One study has demonstrated that q.i.d. ketorolac is as effective as b.i.d. bromfenac in the treatment of pseudophakic CME.8 Patient compliance with a b.i.d. regimen is generally better than that with a q.i.d. regimen. Bromfenac is the only topical NSAID with a b.i.d.-dosing schedule. Recent studies have also demonstrated that bromfenac remains in an effective concentration in the aqueous humor for 12 hours and persists in the choroid and retina.11

Treatment with NSAIDs can certainly be a first line of therapy for patients with CME. Treatment can be a long process and caution is advised because NSAIDs can retard wound healing. The same can also be said for topical prednisolone. In my experience, patients appreciate the alternative of NSAID-therapy and adhere to its regimen when bromfenac is used.

My experience with NSAIDs and retinal disorders such as CME, central serous retinopathy and leakage from confluent retinal drusen or macular edema from vascular occlusions or diabetes mellitus has been extremely encouraging. That bromfenac can be found throughout the eye suggests adequate penetration, which may explain the efficacy seen in treating several retinal disorders. To some extent, ocular inflammation may be a contributing cause of the macular edema we see in both CME and other retinal conditions such as diabetic maculopathy.

Juan Orellana, M.D., M.S., F.A.C.S., is founder of Orellana Retina Associates, PLLC in Raleigh, N.C. He is also a clinical associate professor at the University of North Carolina-Chapel Hill.

References

1. Ohara K, Ohbuto A, Miyamoto T, Miyakubo H, Nezu N. Prevention of miosis during cataract surgery by topical bromfenac sodium. Jpn J Clin Ophthalmol. 2004;58:1325-1328.

2. Data on file. ISTA Pharmaceuticals Xibrom US Phase 111 Trials.

3. Seward MS, Cooke DL, Grillone LR, Sacks RM, Bromfenac Study Group. Topical Xibrom 0.09% Significantly Reduced Ocular Pain Following Cataract Surgery. Presented at ARVO, Fort Lauderdale, Florida 2006. Poster B600. April 30, 2006.

4. Miyake K, Masuda K, Shirato S, Oshika T, Eguchi K, Hoshi H, Majima Y, Kimura W, Hayashi F. Comparison of diclofenac and fluorometholone in preventing cystoid macular edema after small incision cataract surgery: a multicentered prospective trial. Jpn J Ophthalmol. 2000;44:58-67.

5. Schainus R. Topical nonsteroidal anti-inflammatory therapy in Ophthalmology. Ophthalmologica. 2003;217:89-98.

6. Gass JD. Stereo Atlas of Macular Diseases. Diagnosis and treatment. CV Mosby Company Third Edition. P380,1987.

7. Abe T, Hayasaka S, Nagaki Y. Pseudophakic cystoid macular edema treated with NSAIDS. J Cataract Refract Surg. 1999;25:1286-1288.

8. Rho DS. Treatment of acute pseudophakic cystoid macular edema: Diclofenac versus ketorolac. J Cataract Refract Surg. 2003;29:2378-2384.

9. Holekamp NM. Treatment of Pseudophakic CME. Ocul Immunol Inflamm. 1998;6:121-123.

10. Italian Diclofenac Study Group. Efficacy of diclofenac eyedrops in preventing postoperative inflammation and long-term cystoid macular edema. J Cataract Refract Surg. 1997;23:1183-1189.

11. McNamara T, Baklayan GA, Deshmukh HM, Patterson HM, Gow JA. Concentrations of Radioactivity in Ocular Tissues Following a Single Topical Ocular Dose of 14C-Bromfenac Ophthalmic Solution (Xibrom). Presented at ARVO, Fort Lauderdale, Florida 2006. Poster B484, May 4, 2006.