Accelerated ischemic vascular retinopathy after intravitreally injected bevacizumab for central retinal vein occlusion in elderly patients

Abstract

Background: Ischemic changes in the retinal circulation are an uncommon but severe adverse vascular reaction to intravitreal bevacizumab (Avastin(®), Genentech, San Francisco, CA, USA/Roche, Basel, Switzerland) for central retinal vein occlusion (CRVO). In the two cases reported here, ischemic changes in the retina vasculature following intravitreal bevacizumab for CRVO were observed with the aim of describing the clinical and angiographic features of these changes.

Methods: Two elderly patients with recent-onset CRVO received one off-label intravitreal injection of bevacizumab 0.05 mL/1.25 mg.

Results: In Case 1, the patient's pre-treatment visual acuity was 20/400. At 3 weeks post injection, the patient could count fingers at a distance of 1 ft (30 cm) and fluorescein angiography showed reduction in intraretinal hemorrhages and areas of retinal non-perfusion. However, at 6 weeks these were markedly increased compared with those seen in the photograph taken 3 weeks after treatment. In Case 2, the patient's pre-treatment visual acuity was 20/200. At 1 month post injection, vision had decreased to 20/400 and fluorescein angiography showed severe macular ischemia with a remarkable capillary dropout throughout the macula.

Conclusion: Ischemic retinal injury may be an uncommon but severe adverse vascular reaction to intravitreal bevacizumab for CRVO. Although progression of retinal ischemia in CRVO could be observed shortly after intravitreal bevacizumab, whether this is a drug- or procedure-related effect or part of the natural history of the condition remains uncertain.

Keywords: Avastin; intraretinal hemorrhage; ischemia; macular infarction; retinal non-perfusion.

Figure 1

Case 1. Baseline black and white fundus photograph (A) and fluorescent angiography (FA) image (B) showing central retinal vein occlusion with diffuse intraretinal hemorrhages and edema prior to intravitreal bevacizumab injection. (C) Optical coherence tomography (OCT) image showing central macular thickening with cystoid edema. (D) FA image 3 weeks after bevacizumab injection showing a reduction of intraretinal blood and areas of retinal non-perfusion. (E) Follow-up OCT image shows reduced macular thickness with some cysts and intraretinal fluid. (F) FA image 6 weeks after injection showing areas of capillary non-perfusion and retinal ischemia markedly increased compared with at 3 weeks (see D). (G) OCT image showing spontaneous resolution of cystoid edema and macular thickening with no improvement in visual acuity. (H) Angiography image at 15 months follow-up. Pan-retinal laser photocoagulation has been performed. There is significant capillary non-perfusion at the posterior pole. (I) OCT image indicates the absence of intraretinal fluid, with multifocal points of hyperreflectivity above the retinal pigment epithelium/choriocapillaris layer. Mild sub- and intraretinal fibrosis can be observed in the fovea (arrows) as a thickened, highly reflective, yellow-green, and reddish band with loss of the overlying neurosensory retinal layers.

Figure 2

Case 2. Baseline fluorescein angiography images (A and B) of central retinal vein occlusion showing patchy areas of hypofluorescence corresponding to intraretinal hemorrhages and dye leakage from increased capillary permeability in the macula. (C) Optical coherence tomography (OCT) image showing significant cystoid edema. (D and E) Angiography images 4 weeks after injection of bevacizumab. Images show severe macular ischemia, with marked capillary dropout throughout the macula (dashed line). Acuity has dropped to 20/400. (F) OCT image at 4 weeks showing partial resolution of intraretinal fluid and cysts with reduced macular thickness. (G) Persistent fluorescein leakage and pooling of dye in the central macula 14 months post injection. (H) Angiography image at 14 months post injection showing interval increase in the extent of capillary non-perfusion temporal and inferior to the macula (dashed line). (I) OCT image showing persistent macular thickening and large cystic changes.