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Rebecca Russ Soares, Jason Hsu; Ocular Tolerability of Intravitreal Defibrotide Sodium Injections in Brown Norway Rats. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1302.
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Currently, no treatment for lysing the thrombus in central retinal vein occlusion (CRVO) has been proven to be effective. The pleotropic effects of defibrotide sodium on clot lysis and inflammation make it a candidate for treatment of ischemic CRVO. The purpose of this study was to evaluate the tolerability of defibrotide delivered by intravitreal injection (IVI) at various concentrations in Brown Norway (BN) rats.
Five BNs assigned to one of four groups (balanced salt solution [BSS] or defibrotide 20 mg/ml, 50 mg/ml, or 80 mg/ml) received a single 5ml IVI of test article to the right eye. BNs then underwent ocular exams, optical coherence tomography (OCT), fundus imaging (clinical signs scored from 0 [none]-4 [severe]), and electroretinography (ERG) at baseline, Day 2 and Day 7. Animals were euthanized at Day 7, and eyes fixed and H&E stained. Data were analyzed with ANOVA or t-test with Dunnett’s post-test.
Ocular exams showed no significant difference in clinical scores between groups or right vs. left eye at Day 7 for hyperemia (p=0.0627) or chemosis p=0.42. Fundus exam showed similar mild venous tortuosity in all right eyes on Day 2 which resolved by Day 7. OCT showed mild vitritis in the BSS, 20 mg/ml, and 50 mg/ml but not the 80mg/ml group. At Day 7 the 80mg/mL concentration group had a mean clinical score of 0 for vitritis, significantly lower than the mean clinical score of 0.3± 0.1 for the BSS group (p= 0.03). ERG showed systematic reduction in dark- and light-adapted amplitudes in both eyes for all groups. Both eyes in the 20mg/ml defibrotide group had a significant pairwise reduction in b-wave amplitudes at maximum light intensity from Day 0 to 7 (p=0.03, p=0.002). Untreated left eyes in this group had a significantly greater mean reduction (-350.0±72.7mV) compared to right eyes (-248.8±93.5mV, p=0.02). Histologic sections taken at Day 7 showed no structural or cellular changes.
No significant durable adverse effects of IVI defibrotide at any concentration on clinical exam, OCT, or histology was found. Venous tortuosity was transient in nature in all eyes receiving IVI, including BSS control, possibly related to the volume of injection and increase in intraocular pressure. Systematic reduction in ERG wave amplitudes was possibly random or a result of stress [JH1] [RS2] from IVI. Additional testing is needed, as nonsignificant comparisons may be underpowered.
This is a 2020 ARVO Annual Meeting abstract.
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