Abstract
Aim: To evaluate the visual acuity outcomes with ranibizumab (RBZ) according to baseline ischaemic status in patients with macular oedema secondary to branch or central retinal vein occlusion (BRVO and CRVO) Methods: Analysis of 2 multicenter randomized clinical trials (CRUISE and BRIGHTER) Results: Data of 392 CRVO patients randomized in CRUISE and 455 BRVO patients randomized in BRIGHTER were analysed. Best-corrected visual acuity (BCVA) was measured using ETDRS charts at each visit. Presence or absence of retinal ischaemia at baseline was assessed by fluorescein angiography by the central reading centre (CRC). In CRUISE, ischaemia was defined as >30% total capillary loss in the center subfield by area. In BRIGHTER, ischaemia was defined as present if capillary loss was detected and scored as mild, moderate, severe or complete in at least one location of the center, inner or outer subfields. Baseline visual acuity, and change from baseline were reported according to ischaemic status as a post-hoc analysis over 12 months for CRUISE and as a pre-defined exploratory analysis over 6 months for BRIGHTER. In addition, data on injection requirements during the PRN phase of CRUISE (months 7-12) were analysed. Data for RBZ treatment arms (0.3mg and 0.5mg) were combined in the CRUISE analysis. Data were available for 334 patients in CRUISE (ischaemic; RBZ n=15, sham n=4: non-ischaemic; RBZ n=207, sham n=108) and 291 patients in BRIGHTER (ischaemic; RBZ n=87, RBZ + laser n=71, laser n=41: non-ischaemic; RBZ n=35, RBZ+L n=37, laser n=20). In CRUISE, the mean baseline BCVA was substantially lower for ischaemic versus non-ischaemic patients in both RBZ (37.5 vs 49.8 letters) and sham (29.5 vs 49.4 letters) treatment arms respectively. Baseline central retinal thickness and disease duration prior to enrolment were similar for all groups. In BRIGHTER, the mean baseline BCVA was slightly lower for ischaemic versus non-ischaemic patients in the RBZ+L (58.7 vs 60.4 letters) and Laser (55.6 vs 60.6 letters) respectively, but equal for RBZ (60.6 for both groups). In CRUISE and BRIGHTER, patients treated with RBZ achieved significantly greater gains in BCVA compared to the control arms irrespective of ischaemic status. In CRUISE, CRVO patients treated with RBZ achieved substantial gains in BCVA from baseline at month 6 (16.7 vs 14.4 letters) and month 12 (20.1 vs 14.7 letters) for ischaemic vs non-ischaemic patients respectively. The same was true in BRVO patients in BRIGHTER for RBZ group (14.3 vs 11.9 letters) and RBZ+L group (14.4 vs 11.8 letters) for ischaemic vs non-ischaemic patients respectively. Mean injection requirements during PRN phase of CRUISE for RBZ combined treatment arms were similar for ischaemic versus non-ischaemic patients (4.5 vs 4.1 injections respectively). Conclusions: Retinal ischaemia is a common occurrence in patients with BRVO and CRVO and clinical trial data may be helpful in exploring patient response to anti-VEGF treatment according to ischaemic status. In CRUISE, ischaemic patients had substantially lower BCVA scores yet these more severely affected patients demonstrated continuous improvements throughout the study and achieved the greater BCVA gains (mean 20 letter gain in 12 months) with the same number of injections as the non-ischaemic group. In BRIGHTER, BCVA scores at baseline were more similar and treatment with ranibizumab was highly effective in improving visual acuity outcomes comparably for both ischaemic and non-ischaemic patients. In summary, these analyses demonstrate that ranibizumab is an effective therapy for CRVO and BRVO patients irrespective of baseline ischaemic status. Vascular Diseases and Diabetic Retinopathy