Sustained and targeted episcleral delivery of celecoxib in a rabbit model of retinal and choroidal neovascularization

BACKGROUND: To evaluate the efficacy of selective episcleral delivery of celecoxib formulated in a sustained-release episcleral exoplant on a model of retinal and choroidal neovascularization induced in rabbits by subretinal injection of matrigel combined with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). METHODS: Nine New Zealand white rabbits were randomly assigned to three groups (episcleral celecoxib exoplant, intravitreal bevacizumab injection and control group). The bFGF was mixed with matrigel at a concentration of 10 ug/0.1 mL, and VEGF was mixed with matrigel at a concentration of 2 ug/0.1 mL. Animals assigned to celecoxib or intravitreal bevacizumab groups were treated within 03 days from matrigel injection. Fluorescein angiography (FA) and electroretinography (ERG) were performed 5 days, 2, 4 and 8 weeks after matrigel injection. Persistence or regression of three clinical features (subretinal hyperfluorescence, retinal vascular tortuosity and retinal fibrotic spots) was independently evaluated in each study group at all follow-up periods. Statistical analysis using Fisher’s exact test was performed to compare the frequency of findings at each time point between treated groups and control. RESULTS: In all study eyes, matrigel induced the appearance of subretinal blebs and the development of retinal and subretinal neovascularization characterized by progressive and late hyperfluorescence on FA. Persistence of subretinal hyperfluorescence was higher in non-treated (control) animals compared to celecoxib (p = 0.0238) treated animals. The mean b-wave amplitude ratios of ERG recordings did not reveal statistically significant differences between the study groups. Control animals retained in average 40% (± 7%) of the pre-treatment recorded b-wave amplitude, compared to 53% (± 29%) after bevacizumab and 53% (± 17%) after celecoxib treatment. CONCLUSION: In this rabbit model of retinal and subretinal neovascularization, episcleral celecoxib delivery was demonstrated to significantly inhibit neovascularization. It was also noticed, although not statistically significant, an apparent effect of episcleral celecoxib on preventing tractional retinal detachment secondary to epiretinal fibrovascular proliferation. The transscleral delivery of celecoxib combined with sustained-release strategy may have impact in the treatment of retinal and choroidal proliferative diseases.