Analysis of potential ischemic effect of intravitreal bevacizumab on unaffected retina in treatment-naïve macular edema due to branch retinal vein occlusion: A prospective, interventional case-series

Background To study potential ischemic effects of intravitreal Bevacizumab (IVB) on unaffected retina in treatment-naive eyes with macular edema secondary to branch retinal vein occlusion (BRVO) and contralateral eyes secondary to systemic absorption. Methods and Findings Prospective, interventional series included 27 treatment-naive eyes with BRVO and macular edema. Exclusion criteria: Eyes with diabetic retinopathy, glaucoma, vasculitides, papilledema or systemic neurologic condition. Subjects underwent complete ophthalmological examination including fluoroscein angiography (FA), optical coherence tomography (OCT) and multifocal electroretinogram (mf-ERG). All subjects received single 1.25 mg/0.05ml IVB injection. Two observers measured all parameters; inter-observer agreements were expressed as kappa values. Paired t-test was used to compare values at baseline and follow-up. The statistical analysis was done using SPSS for Windows, Version 14.0. (Chicago, SPSS Inc.) Presenting mean CFT (central foveal thickness) was 499.5(+/-229.7) μm, mean BCVA (best corrected visual acuity) was 0.64(+/-0.41) logMAR. At last followup, mean CFT was 267.9(+/-159.3) μm (P<0.001), 95% CI [127.18, 422.32]; mean BCVA was 0.28(+/-0.24) logMAR. Respectively, mean N1 and P1 amplitudes of mfERG in 'unaffected quadrant' at presentation were -6.10(+/-4.00) nV/deg2 and 17.17(+/-11.54)nV/deg2 ; and -5.33(+/-1.30)nV/deg2 and 15.29(+/-4.69)nV/deg2 at final follow-up (P = 0.631 and 0.197, respectively), (95% CIs [-0.93, 1.42] and [-4.22, 1.08] respectively). In fundus quadrant of fellow eyes corresponding to unaffected quadrant in treated eyes, mean N1 and P1 amplitudes at presentation were -5.39(+/-1.56)nV/deg2 and 15.89(+/-3.89)nV/deg2 ; and -5.39(+/-1.90)nV/deg2 and 15.9(+/-5.52)nV/deg2 (P = 0.380 and 0.208), (95% CIs [-0.57, 1.28] and [-4.1, 1.1]) at last follow-up, respectively. Limitations: This study analysed the effects with a single injection of bevacizumab. However, whether ischemic adverse effects will emerge with repeated IVB injections as a consequence of cumulative dosing needs further investigation. The setting of our study being a tertiarycare centre, the numbers of fresh BRVO cases without prior intervention were limited. Thus, the limitations of our study include a small sample size with a small follow-up period. No major ocular/systemic adverse event was observed in the study period. Conclusion No evidence of progressive ischaemia attributable to single bevacizumab treatment was observed in this study. However, a larger prospective study involving subjects with cumulative dosing of bevacizumab and a longer follow-up could provide a better understanding of the potential ischaemic effects of bevacizumab or other anti-VEGF agents.