Session Title: Vascular Diseases I
Session Date/Time: Friday 27/09/2013 | 08:00-10:00
Paper Time: 08:16
Venue: Hall C (Level 1)
First Author: S.Wolf SWITZERLAND
Visual impairment is common in individuals ≤50 years with myopic choroidal neovascularization (CNV). Verteporfin photodynamic therapy (vPDT) is currently the only approved treatment for myopic CNV. Anti-vascular endothelial growth factor therapies have shown promising results, and may provide rapid and sustained visual improvement in patients with myopic CNV. RADIANCE (Ranibizumab And PDT [verteporfIn] evAluation iN myopic Choroidal nEovascularization) is a pivotal phase III randomized controlled trial reporting the 12-month (M) efficacy and safety of two different dosing regimens of ranibizumab 0.5 mg versus vPDT in patients with visual impairment due to myopic CNV.
A phase III, randomized, double-masked, multicenter (involving 80 centers), active-controlled 12-month trial.
A total of 277 patients were randomized 2:2:1 to Group 1 (G1): intravitreal ranibizumab injection on Day 1, M1 and then as needed guided by best-corrected visual acuity (BCVA) stability criterion (M2-11, n=106), G2: ranibizumab on Day 1 and thereafter as needed guided by disease activity criterion (M1-11, n=116), and G3: vPDT on Day 1 and thereafter ranibizumab treatment as needed guided by disease activity criterion and/or vPDT (M3-11, n=55) as of M3. Primary objective was the superiority of ranibizumab guided by BCVA stability/disease activity retreatment criterion versus vPDT with respect to mean average BCVA change from baseline to M1 through M3. Key secondary objective was noninferiority of ranibizumab guided by disease activity criterion versus ranibizumab guided by BCVA stability criterion with respect to mean average BCVA change from baseline to M1 through M6. Secondary endpoints included mean change in BCVA from baseline to M12, proportion of patients gaining ≥10 letters, proportion of patients with CNV leakage, mean change in central retinal thickness (CRT) from baseline to M12, mean number of ranibizumab injections and safety over 12 months.
267 (96.4%) patients completed the study. Baseline mean age was 55.8 years with the majority (75.5%) being females. Mean visual acuity was 55.3 ETDRS letters. The primary endpoint was met since both ranibizumab groups were superior to vPDT group with respect to mean average BCVA change from baseline to M1 through M3 (G1: +10.5, G2: +10.6 ETDRS letters versus G3: +2.2 ETDRS letters; both p<0.00001). Ranibizumab treatment guided by disease activity criterion was noninferior to BCVA stability-guided retreatment based on mean average BCVA change (+11.7 [G2] versus +11.9 [G1] ETDRS letters; p<0.00001). Mean BCVA change from baseline to M12 were +13.8 (G1), +14.4 (G2), +9.3 ETDRS letters (G3), and 69.5%, 69.0%, 49.1% of the patients gained ≥10 letters at M12, respectively. Proportion of patients at M12 with CNV leakage (G1: 21.0%, G2: 19.0%, G3: 29.1%) decreased in >70% of the patients from baseline. CRT decreased at M12 by 66.6 (G1), 71.3 (G2) and 60.8 µm (G3). Mean number of ranibizumab injections from Day 1 to M11 were 4.6 (G1), 3.5 (G2), 3.2 (G3). No deaths or endophthalmitis cases and no new ocular/nonocular safety findings with ranibizumab were reported over 12 months.
Ranibizumab retreatment guided by BCVA stability or disease activity criterion demonstrated superior BCVA gain versus vPDT from Day 1 to M1 through M3. Ranibizumab treatment guided by disease activity criterion was noninferior to BCVA stability criterion from Day 1 to M1 through M6. The BCVA gain and decrease in myopic CNV leakage were maintained in the ranibizumab arms at M12 with low number of treatments. The ocular and nonocular safety profile was consistent with that of the already approved indications for ranibizumab.