Allan J. Flach

Nonsteroidal Anti-inflammatory Drugs in Ophthalmology

Nonsteroidal anti-inflammatory drugs (NSAIDs) are increasingly employed in ophthalmology to reduce miosis and inflammation, manage scleritis, and prevent and treat cystoid macular edema associated with cataract surgery. In addition, they may decrease postoperative pain and photophobia associated with refractive surgery and may reduce the itching associated with allergic conjunctivitis. In recent years, the U.S. Food and Drug Administration has approved new topical NSAIDs, and previously approved NSAIDs have been reformulated. These additions and changes result in different pharmacokinetics and dosing intervals, which may offer therapeutic advantages. For example, therapeutic effects on diabetic retinopathy and age-related macular degeneration may now be achievable. We provide an updated review on NSAIDs and a summary of their current uses in ophthalmology with attention to potential future applications.

Cyclo-oxygenase inhibitors in ophthalmology

Cyclo-oxygenase inhibitors, which are formulated as ophthalmic eyedrop preparations, have recently become commercially available for use by ophthalmologists in the United States to inhibit intraoperative miosis during cataract surgery and to prevent postoperative inflammation. In addition, they are available worldwide as ocular antiinflammatory drugs and are used in the prevention and treatment of pseudophakic and aphakic cystoid macular edema. Understanding the rationale behind the use of these agents requires an understanding of the pathophysiology of the cyclo-oxygenase inhibitors. In this review recent advances in laboratory and clinical science are emphasized. The role of COIs during and following surgery is examined.

Improvement in Visual Acuity in Chronic Aphakic and Pseudophakic Cystoid Macular Edema After Treatment With Topical 0.5% Ketorolac Tromethamine

Ketorolac tromethamine 0.5% ophthalmic solution treatment was compared to placebo treatment in 120 patients with chronic aphakic or pseudophakic cystoid macular edema (six-month or more duration of distance visual acuity of 20/40 or less and angiographic evidence of cystoid changes) during a four- to five-month double-masked, multicenter study in which patients were randomly assigned. A statistically significant improvement in distance visual acuity (two lines or more) was observed in the ketorolac-treated group as compared to the placebo-treated group after 30 days (P = .038), 60 days (P = .017), and 90 days (P = .008) of treatment. This improvement in visual acuity remained statistically significant one month after cessation of treatment (P = .001). Nine ketorolac-treated patients and two placebo-treated patients demonstrated a decrease in visual acuity one month after treatment was discontinued. Seven of the nine ketorolac-treated patients experienced an improvement in visual acuity after retreatment as compared to none of the placebo-treated patients. This study offers evidence for a more optimistic outlook in the medical treatment of chronic aphakic and pseudophakic cystoid macular edema.

Prophylaxis of Aphakic Cystoid Macular Edema without Corticosteroids: A Paired-comparison, Placebo-controlled Double-masked Study

Prior investigations have reported that topical nonsteroidal anti-inflammatory drug (NSAID) therapy prevents the development of postoperative angiographic signs of angiographic cystoid macular edema (CME). However, these studies include concurrent use of corticosteroids. The current study reports therapeutic efficacy for ketorolac ophthalmic solution (an NSAID) in the prophylaxis of angiographic aphakic CME (ACME) after cataract surgery without concurrent corticosteroids for the first time. Fifty patients with bilateral cataracts were enrolled in this placebo-controlled, paired-comparison, double-masked study. Eleven patients had evidence of angiographic ACME on postoperative day 40. Two of these patients demonstrated bilateral ACME, one patient had ACME in the NSAID-treated eye, and eight patients demonstrated ACME in the placebo-treated eye. This is a statistically significant difference favoring drug treatment. The signs of anterior ocular inflammation were greater in the eyes with ACME. This study suggests prophylactic treatment of ACME may be possible without the risks of concurrent corticosteroid toxicity. In addition, a higher incidence of ACME in black patients (22%) is observed in this study than has been recognized previously.

Topical nonsteroidal antiinflammatory drugs in ophthalmology.

Topically applied nonsteroidal antiinflammatory drugs (NSAIDs) are widely used in the management of postoperative ocular inflammation and for the prevention and treatment of cystoid macular edema (CME) after cataract surgery. In addition, they are useful for the prevention of intraoperative miosis during cataract surgery, for the relief of symptoms of seasonal allergic conjunctivitis, and for the reduction of ocular discomfort after refractive surgery. In this chapter, the current status of topically applied NSAIDs and their potential therapeutic benefit for ophthalmic disorders are summarized.

Comparative effects of ketorolac 0.5% or diclofenac 0.1% ophthalmic solutions on inflammation after cataract surgery

OBJECTIVE Ketorolac tromethamine 0.5% and diclofenac sodium 0.1% ophthalmic solutions are approved for use by the U.S. Food and Drug Administration to avoid excessive postoperative inflammation after cataract surgery and implantation of an intraocular lens. This study compares the efficacy and toxicity of these nonsteroidal anti-inflammatory drugs for the first time. DESIGN Randomized, double-masked, prospective clinical trial. PARTICIPANTS A total of 120 patients assigned in equal numbers to 1 of the 2 treatment regimens. INTERVENTION Treatment with either ketorolac 0.5% or diclofenac 0.1% ophthalmic solutions instilled four times daily for 30 days beginning the first postoperative day after surgery. MAIN OUTCOME MEASURES Objective (Kowa FC 1000 laser cell and flare meter) and subjective (slit-lamp biomicroscope) measurements of inflammation and toxicity were made and compared at three separate post-operative visits. RESULTS The anti-inflammatory effects of the two treatment regimens were not statistically different at any of the postoperative visits. Patients tolerated both treatments equally well. CONCLUSIONS This study shows diclofenac sodium 0.1% and ketorolac tromethamine 0.5% ophthalmic solutions are equally effective and safe for the control of postoperative inflammation after uncomplicated cataract surgery performed by phacoemulsification followed by the implantation of a foldable intraocular lens.

Episcleritis, Conjunctivitis, and Keratitis as Ocular Manifestations of Lyme Disease

A 35-year-old woman presented with a bilateral palpebral follicular conjunctivitis. Subsequently, she developed a bilateral keratitis and, on a separate occasion, an episcleritis that was associated with a recrudescence of Lyme disease and poor compliance with the antibiotic regimen. Both the keratitis and episcleritis cleared completely after topical corticosteroid therapy and reinstitution of appropriate antibiotic treatment. This report emphasizes the importance of collaboration between internal medicine and ophthalmologic specialists during the long-term management of Lyme disease.

Local Ocular Hypotensive Effect of Topically Applied Acetazolamide

Acetazolamides usefulness in the treatment of the glaucomas is limited by the systemic side effects that often accompany its oral administration, and topical administration was initially thought to have no effect upon the intraocular pressures of human and rabbit eyes. Recent studies, however, have shown the usefulness of water-loading tests for screening drugs with potential antiglaucomatous activity. We found evidence that topical acetazolamide has the ability to lessen the increase in intraocular pressure after water-loading in pigmented rabbits and correlated this observation with low levels (0.0 to 0.7 microgram/ml) of plasma acetazolamide. Further, a separate study showed that 10% topical acetazolamide can enhance the ocular hypotensive effects of systemically administered acetazolamide in normal pigmented rabbits, suggesting that topically applied acetazolamide can have a local effect on intraocular pressure.

Stevens-Johnson syndrome associated with methazolamide treatment reported in two Japanese-American women.

BACKGROUND Systemic acetazolamide treatment has been reported in association with Stevens-Johnson syndrome (SJS). This is the first report of this syndrome associated with methazolamide treatment. The association is reported in two Japanese-American women. METHOD AND RESULTS Two patients with SJS, which developed during treatment with methazolamide, are described. Other potential associations are discussed. CONCLUSIONS Systemically administered carbonic anhydrase inhibitors, including both acetazolamide and methazolamide can be associated with SJS.

Efficacy of low concentrations of ketorolac tromethamine in animal models of ocular inflammation.

PURPOSE To determine if topical ophthalmic application of ketorolac tromethamine concentrations below 0.5% can block the biochemical and physiological processes associated with chemically induced ocular inflammation in rabbits. METHODS Ocular inflammation was induced in rabbits by intravenous (i.v.) injection of endotoxin (2.5 microg/kg) isolated from Salmonella typhimurium, or by a topical application of arachidonic acid (1.0%). The effect of ketorolac (at concentrations ranging from 0.001%-0.5%) on ocular inflammation was determined by measuring changes in the blood-aqueous barrier, using fluorophotometry (dextran-isothiocyanate-fluorescein; FITC-dextran 2%) and by measuring changes in aqueous humor protein concentrations. Changes in aqueous humor prostaglandin E(2) (PGE(2)) concentrations were also measured. RESULTS Ketorolac 0.01%-0.5% produced substantial decreases in endotoxin-induced fluorescein leakage into the aqueous humor. The decrease produced by ketorolac 0.1% was comparable to that produced by ketorolac 0.5%. Ketorolac 0.1%-0.5% produced substantial decreases in endotoxin-induced increases in prostaglandin concentrations in the aqueous humor, and in arachidonic acid-induced protein leakage into the aqueous humor. CONCLUSIONS Topical application of ketorolac concentrations as low as 0.01%-0.1% significantly reduce chemically induced ocular inflammation in rabbits.