Safety of intravitreal ketorolac and diclofenac: An electroretinographic and histopathologic study

OBJECTIVE: To determine the clinical, histologic, and electroretinographic effects in the rabbit retina of escalating doses of two intravitreally delivered nonsteroidal anti-inflammatory drugs (NSAIDs): ketorolac and diclofenac. METHODS: Right eyes received a single 0.1 mL injection of either ketorolac (500-6000 μg/0.1 mL) or diclofenac (300-1500 μg/0.1 mL) prepared in balanced salt solution (BSS). Left eyes served as controls and received BSS. Dark- and light-adapted electroretinograms (ERG) were obtained at baseline and 4 and 8 weeks postinjection. Enucleated eyes were examined histologically. RESULTS: Ophthalmic examinations demonstrated no signs of intraocular inflammation or retinal toxicity. Intraocular pressure measurements remained similar between NSAID injected and control eyes. Histologic and ERG studies of eyes injected with 6000 μg ketorolac and ≥500 μg diclofenac demonstrated toxicity. In contrast, doses up to 3000 μg ketorolac demonstrated enhanced b-wave amplitude responses. Delayed drug toxicity was observed for the highest doses of both NSAIDs. CONCLUSIONS: Intravitreal 3000 μg ketorolac and 300 μg diclofenac were nontoxic in this animal study, and may offer an effective and safer alternative to intravitreal corticosteroids.