Changes in Retinal Nonperfusion Associated with Suppression of Vascular Endothelial Growth Factor in Retinal Vein Occlusion

Abstract

Purpose To assess changes in retinal nonperfusion (RNP) in patients with retinal vein occlusion (RVO) treated with ranibizumab (RBZ) Design Secondary outcome measure in randomized double-masked controlled clinical trial Subjects Thirty-nine patients with central RVO (CRVO) and 42 with branch RVO (BRVO) Methods Subjects were randomized to 0.5mg or 2.0mg RBZ every month for 6 months and then re-randomized to pro re nata (prn) groups RBZ+scatter photocoagulation (laser) or RBZ alone for an additional 30 months. Main Outcome Measures Comparison of percentage of patients with increased or decreased area of RNP in patients with RVO treated with 0.5mg versus 2.0mg RBZ, during monthly injections versus prn RBZ, and in patients treated with prn RBZ versus prn RBZ+laser. Results In RVO patients given monthly injections of 0.5mg or 2.0mg RBZ for 6 months there was no significant difference in the percentage who showed reduction or increase in area of RNP. However, regardless of dose, during the 6 month period of monthly injections, a higher percentage of patients showed a reduction in area of RNP and a lower percentage showed an increase in area of RNP compared to subsequent time periods of prn RBZ treatment. After the 6 month period of monthly injections, BRVO, but not CRVO patients randomized to prn RBZ+laser showed significantly less progression of RNP compared to patients treated with prn RBZ. Conclusions Regardless of dose of ranibizumab (0.5mg or 2.0mg), monthly injections promote improvement and reduce progression of RNP compared to prn injections. Addition of scatter photocoagulation to prn RBZ may reduce progression of RNP in patients with BRVO, but a statistically significant reduction was not seen in patients with CRVO.

Changes in Retinal Microvasculature and Visual Acuity After Antivascular Endothelial Growth Factor Therapy in Retinal Vein Occlusion

“…While some reports demonstrate adverse vasoconstrictive effects on retinal perfusion that include a reduction in retinal vessel diameters and flow velocities, [31][32][33][34] there are others that demonstrate positive effects of anti-VEGF therapy on retinal perfusion, such as prevention of retinal nonperfusion. 35,36 In the current study, quantitative OCTA imaging identified that both VD and FAZ within the 3 3 3-mm area did not differ significantly during the course of anti-VEGF therapy for 12 months in patients with RVO. In addition, number of the anti-VEGF injections was not significantly associated with changes in the VD and FAZ area.…”

Reversible retinal vessel closure from VEGF-induced leukocyte plugging

“…However, measurement of area of retinal nonperfusion at several time points in RVO patients participating in clinical trials showed that progression of nonperfusion was the rule rather than the exception and that it did not occur abruptly, but rather progressed continuously through at least 24 months, the last measurement time point (30,31). In these and other clinical trials (32)(33)(34), it has been noted that subjects with substantial nonperfusion at baseline showed more rapid and often more severe worsening of nonperfusion than those with little or no nonperfusion at baseline. This suggests that all CRVOs are ischemic but to different degrees, resulting in different levels of VEGF expression, and it is eyes at the most severe end of the ischemia spectrum at baseline that tend to show the most rapid and extensive progression of retinal nonperfusion, which 5 Cyclophilin A transcripts for VCAM-1, ICAM-2, integrin β1, and integrin α4 (n in parentheses along x axis, *P < 0.05 by unpaired t tests).…”

“…In some patients, particularly those that are older, there is immediate closure of some retinal capillaries and/or arterioles, probably due to preexistent arterial disease. Regardless of the amount of retinal vessel closure that occurs immediately after thrombosis, it is frequently followed by additional closure of retinal vessels that can be reversed by VEGF suppression (32)(33)(34). In untreated eyes with CRVO, the worsening of retinal nonperfusion can be so profound that it leads to severe loss of vision due to widespread ischemic death of retinal cells, including those in the macula and/or neovascular glaucoma, a severe complication that often leads to loss of the eye.…”

“…Measurement of retinal nonperfusion in clinical trials have shown that progression of retinal nonperfusion is extremely common in untreated patients with CRVO or BRVO (30,31). Suppression of VEGF slowed progression of retinal nonperfusion and caused reopening of some previously closed retinal vessels in patients with CRVO or BRVO, whereas sham-treated patients or those in whom anti-VEGF treatment was stopped had progressive worsening of retinal nonperfusion (32)(33)(34). Some patients have nonperfusion that does not improve with VEGF suppression, and patients who show improvement in one region of nonperfusion may not in another, indicating that a substantial amount of nonperfusion is permanent, though the demonstration that some is reversible was surprising and exciting.…”

Branch Retinal Vein Occlusion – Update on Treatment Options

“…20 However, a recent study indicated that the addition of scatter photocoagulation to ranibizumab may reduce progression of retinal nonperfusion in patients with BRVO. 19 To summarise, the achievement of a potential synergistic effect by combination of different interventions requires further study.…”