Session Title: Vascular Diseases and Diabetic Retinopathy II
Session Date/Time: Friday 18/09/2015 | 16:30-18:00
Paper Time: 16:46
First Author: : J.Monés SPAIN
Co Author(s): :
Retinal vein occlusion (RVO) is commonly associated with retinal ischemia, which may have an impact on visual prognosis and disease management. Various interventional RVO studies have typically included assessments of retinal ischemia; however, the criteria for assessments frequently differ between studies, and limited amount of data are currently reported in relevant subgroups. Here, we report the grading criteria for ischemia and the best-corrected visual acuity (BCVA) outcomes on the basis of the patient’s baseline ischemic status from the BRIGHTER (NCT01599650) and CRYSTAL (NCT01535261) studies.
BRIGHTER and CRYSTAL were two, 24-month, phase IIIb, multicentre studies that enrolled patients with visual impairment due to macular edema secondary to branch and central RVO (BRVO and CRVO) across Europe, Australia and Canada. BRIGHTER was a randomized, active-controlled, three-arm study, whereas CRYSTAL was an open-label, single-arm study.
The BRIGHTER and CRYSTAL studies were designed to assess the long-term efficacy and safety profile of stabilization criteria-driven pro re nata (PRN) dosing regimen of ranibizumab 0.5 mg (as per the European Label) in patients with BRVO and CRVO, respectively. In the BRIGHTER study, BRVO patients (N=455) were randomized (2:2:1) to receive ranibizumab 0.5 mg (n=183), ranibizumab 0.5 mg with laser (n=180) or laser monotherapy, with an option for ranibizumab treatment to be added from Month 6 (n=92). In the CRYSTAL study, all CRVO patients (N=357) received ranibizumab 0.5 mg treatment. In both studies, patients received monthly ranibizumab until visual acuity (VA) was stable and PRN treatment thereafter until Month 12, when monitoring frequency could be reduced. Retinal ischemia, as assessed by the Vienna Central Reading Centre (CRC), was defined in both studies as capillary loss (mild, moderate, severe or completely destroyed) in at least one location of the centre, inner or outer subfield, based on the Early Treatment Diabetic Retinopathy Study (ETDRS) grading. One of the exploratory endpoints of these studies was the mean change in BCVA from baseline to Month 24 based on baseline ischemia status.
In BRIGHTER, the proportion of patients with CRC assessed ischemia at baseline was 48.3%, 39.9% and 53.0%/25.0% in the ranibizumab, ranibizumab with laser and laser monotherapy with/without ranibizumab treatment from Month 6 arms, respectively. Baseline VA by ischemia status (present/absent) was 60.6/60.6 (ranibizumab), 58.7/60.3 (ranibizumab + laser), 55.7/61.2 (laser monotherapy with ranibizumab from month 6) and 58.0/59.4 (laser monotherapy without ranibizumab from month 6). At Month 24, there was an increase in the mean BCVA with ranibizumab, ranibizumab with laser and laser monotherapy with/without ranibizumab treatment from Month 6 in ischemic patients (75.9, 74.6 and 71.1/76.2 letters), respectively. For non-ischemic patients at Month 24, mean BCVA increased with ranibizumab and ranibizumab with laser but not with laser monotherapy with/without ranibizumab treatment from Month 6 (73.4 and 74.8 and 66.4/66.6 letters), respectively. In CRYSTAL, 30% of patients had CRC assessed ischemia at baseline. Mean BCVA for ischemic/non-ischemic patients was 54.5 letters/55.5 letters at baseline. At Month 24, there was a mean BCVA letter gain of 11.1/12.9 for ischemic/non-ischemic patients to mean BCVAs of 65.5/68.5 letters, respectively.
Results from the BRIGHTER and CRYSTAL studies suggest that flexible administration of ranibizumab is an effective therapy for patients with BRVO and CRVO, regardless of their baseline ischemia status. Additional analysis on the impact of severity, location and duration of ischemia on visual gains in patients with branch and central retinal vein occlusion treated with ranibizumab is currently ongoing. Furthermore, a better understanding of retinal ischemia is needed to greater align grading and reporting of retinal perfusion status in clinical studies. THEME: Vascular Diseases and Diabetic Retinopathy