Abstract
Purpose: :
Dexamethasone intravitreal implant (Ozurdex) is an intravitreal biodegradable polymeric implant that contains the potent corticosteroid dexamethasone. It is approved for the treatment of macula edema associated with retinal vein occlusion. The purpose of this study was to evaluate the efficacy of the DEX Implant in an animal model of chronic retinal neovascularization (RNV) created by intravitreal injection of the gliotoxin, DL-α-aminoadipic acid (DL-AAA).
Methods: :
All procedures were done in conscious animals. Sixteen pigmented rabbits weighing 2.0-2.5 kg were dosed unilaterally with 0.1 ml of 0.05 M DL-AAA intravitreally. After 18 months, rabbits were stratified into 2 groups (n=8/group) with an equal distribution of RNV. One group was given the DEX Implant and the other a sham injection, with follow-up at baseline, 1, 2 and 4 weeks. Retinal assessments were performed on conscious animals. Retinal fluorescein angiography was done by IV administration of 5% NaF via the marginal ear vein. RNV angiographic leak was assessed by 2 methods: 1) Image analysis of the leak area based on brightness of an optic disc blood vessel, and 2) subjective masked scoring (0=no leak, 1=minimal leak 2=mild leak, 3=moderate leak, 4=severe leak) by 3 observers.
Results: :
DL-AAA produced retinal disorganization, retinal atrophy, and variable RNV in 4-8 weeks, which was still present 18 months later. Pre-intervention baseline leak areas (mean ± SEM) were 114648 ± 22779 and 155530 ± 44769 sq pixels in sham and DEX Implant groups, respectively; corresponding subjective scores were 2.96 ± 0.3 and 3.21 ± 0.34. At 1 week after dosing, as a % of baseline, leak area in the sham and DEX Implant groups were 98% ± 10% and 27% ± 13% (P=0.0009); subjective scores were 97% ± 8% and 53% ± 16% (P=0.02). At 2 weeks, leak area were 102% ± 9% and 28% ± 13% (p=0.0003); subjective scores were 97 ± 14% and 45 ± 14% (p=0.03). At 4 weeks, leak area were 107% ± 12% and 28% ± 13% (P=0.0005); subjective scores were 107% ± 9% and 45% ± 15% (P=0.005).
Conclusions: :
Dex Implant was effective at reducing angiographic leak in a rabbit model of chronic RNV.
Keywords: neovascularization • corticosteroids • macula/fovea