Inhibition of Choroidal Neovascularization by Intravitreal Ketorolac

Abstract

To determine the inhibitory effect of intravitreal nonsteroidal anti-inflammatory drugs on choroidal neovascularization (CNV) in an animal model of age-related macular degeneration.Methods: Six laser burns of sufficient power to rupture the Bruch membrane were induced in the peripapillary area of each eye of 18 adult Brown Norway rats. Both eyes of each animal received the same 5-µL intravitreal injection of 30 mg/mL of ketorolac tromethamine, 40 mg/mL of triamcinolone acetonide, or balanced salt solution. Fluorescein angiography was performed on days 14 and 21 after injection, animals were euthanized, and retinal pigment epithelium-choroidsclera (choroidal) flat mounts were prepared. Areas of abnormal vascular leakage on fluorescein angiography and vascular budding on choroidal mounts were measured and quantified using an image analysis program.Results: Intravitreal ketorolac significantly reduced CNV leakage on fluorescein angiography at 2 (P Ͻ.001) and 3 (P=.006) weeks compared with eyes injected with balanced salt solution, but intravitreal triamcinolone was a more potent inhibitor of CNV leakage than ketorolac (P Ͻ.001). Vascular budding on choroidal mounts was almost entirely suppressed with triamcinolone (PϽ.001) and significantly inhibited with ketorolac (P =.009). Conclusion:Intravitreal ketorolac significantly reduced laser-induced CNV leakage and vascular budding as determined by fluorescein angiography and choroidal flat mounts, respectively, although this effect was less than that of triamcinolone.Clinical Relevance: Intravitreal nonsteroidal antiinflammatory drugs may be useful in the treatment of CNV owing to age-related macular degeneration or other causes and offer distinct clinical advantages over corticosteroids because of their lack of association with cataract formation or glaucoma.

Topical Bromfenac as an Adjunctive Treatment With Intravitreal Ranibizumab for Exudative Age-Related Macular Degeneration

“…11,12 However, to date, the addition of PDT to ranibizumab treatment has not conferred a benefit in visual outcomes. 13 Because several experimental studies have shown that NSAIDs inhibit CNV in animals by downregulating VEGF, [14][15][16] using NSAIDs to treat AMD seemed 3. Changes in CRT.…”

Pharmacokinetic Comparison of Ketorolac After Intracameral, Intravitreal, and Suprachoroidal Administration in Rabbits

“…11 In recent studies, the experimental efficacy of ketorolac in the inhibition of ocular neovascularization has been evaluated. 12,13 Ketorolac has obvious clinical advantages over corticosteroids in terms of cataract formation, ocular infections, and increase of intraocular pressure. [14][15][16] Nowadays, treatment of posterior segment of eyes remains a challenge because it is hard for drugs to cross the ocular barriers to the posterior chamber by topical administration of eye drops.…”

Current Choroidal Neovascularization Treatment

“…A study showed that topical bromfenac adjunctive ranibizumab might reduce the frequency of treatment over 6 months in eyes with relatively small AMD lesions [61]. Another study reported that intravitreal ketorolac significantly inhibited CNV leakage and vascular budding in an animal model of CNV, although the effect was less than that of triamcinolone [62]. This effect may be related to the COX enzymes and the anti-stress protein, Nrf2 [63].…”