Intravitreal aflibercept versus photodynamic therapy in Chinese patients with neovascular age-related macular degeneration: outcomes of the SIGHT study / 中华眼底病杂志

Objective To assess the efficacy and safety ofintravitreal aflibercept injection (IAI) compared with photodynamic therapy (PDT) in the treatment of Chinese patients with predominantly classic subfoveal choroidal neovascularization (CNV) lesions secondary to neovascular age-related macular degeneration (nAMD).Methods A randomized,double-blind,multi-center phase-3 clinical trial lasting for 52weeks (from December 2011 to August 2014).Subjects were randomized in a 3:1 ratio to either IAI group or PDT-to-IAI group.Subjects in the IAI group received 2 mg IAI at baseline and at week 4,8,16,24,32,40,48,with sham injection at week 28,36.Subjects in the PDT-to-IAI group were forced to receive PDT once at baseline and more time at week 12,24 if PDT retreatment conditions were met.Sham injections were given in PDT-to-IAI group at baseline and at week 4,8,16 and 24,followed by 2 mg IAI at week 28,32,36,40,48.The primary outcome of efficacy were the change in mean Best Corrected Visual Acuity (BCVA) from baseline to week 28,and that of week 52.Safety evaluation included the percentage of subjects who suffered treatment emergent adverse events (TEAEs).Results Among the 304 subjects enrolled,there were 228 and 76 cases in IAI group and PDT-to-IAI group respectively.At week 28,the changes of mean BCVA in IAI group,PDT-to-IAI group compared to baseline were +14.0,+3.9 letters,respectively.At week 52,the changes of mean BCVA in two groups were + 15.2,+8.9 letters respectively with the difference of +6.2 letters (95％CI 2.6-9.9,P=0.000 9).At week 52,the mean foveal retinal thickness in the two groups decreased by-189.6,-170.0 μm,respectively.Subjects with the most BCVA increase in IAI group were those aged ＜65,and those with active CNV lesion area ＜50％ of total lesion area.The most common TEAEs in IAI group and PDT-to-IAI group are macular fibrosis [11.8％ (27/228),6.6％ (5/76)] and BCVA decline [6.6％ (15/228),21.1％ (16/76)].There were 3 cases of arterial thromboembolic events defined in the antiplatelet experimental collaboration group,but all were considered unrelated to interventions.Conclusions The efficacy of aflibercept is superior to that of PDT in nAMD patients in China.The therapeutic effect of aflibercept persisted to week 52 in all subjects.The rate of adverse events was consistent with the safety data of aflibercept known before.

Intravitreal Aflibercept for Macular Edema Following Branch Retinal Vein Occlusion: 52-Week Results of the VIBRANT Study.

PURPOSE: To determine week 52 efficacy and safety outcomes in eyes with macular edema after branch retinal vein occlusion (BRVO) treated with 2 mg intravitreal aflibercept injection (IAI) compared with grid laser. DESIGN: VIBRANT was a double-masked, randomized, phase 3 trial. PARTICIPANTS: Eyes randomized and treated in VIBRANT were followed to week 52. METHODS: In the IAI group, eyes received IAI every 4 weeks through week 24 and IAI every 8 weeks through week 48 with rescue grid laser if needed at week 36. In the grid laser group, all eyes received grid laser at baseline and, if prespecified rescue criteria were met, 1 additional laser from week 12 to 20 and IAI every 8 weeks after 3 monthly doses from week 24 onward (the laser/IAI group). MAIN OUTCOME MEASURES: The primary outcome measure was percentage of eyes with improvement from baseline best-corrected visual acuity (BCVA) letter score ≥15 at week 24. All outcome measures at week 52 were exploratory, and P values are considered nominal. RESULTS: The percentage of eyes with improvement from baseline letter score ≥15 in the IAI and laser/IAI groups was 52.7% versus 26.7% (P = 0.0003) at week 24 and 57.1% versus 41.1% (P = 0.0296) at week 52. The corresponding mean change from baseline BCVA letter score was 17.0 versus 6.9 (P < 0.0001) at week 24 and 17.1 versus 12.2 (P = 0.0035) at week 52. The mean reduction from baseline central retinal thickness was 280.5 µm versus 128.0 µm (P < 0.0001) at week 24 and 283.9 µm versus 249.3 µm (P = 0.0218) at week 52. In the IAI group, 10.6% of eyes received rescue laser at week 36, and in the laser/IAI group, 80.7% received rescue IAI from week 24 to week 48. Traumatic cataract in 1 eye (1.1%) in the IAI group was the only ocular serious adverse event. CONCLUSIONS: After 6 monthly IAI, injections every 8 weeks maintained control of macular edema and visual benefits through week 52. In the laser group, rescue IAI given from week 24 onward resulted in substantial visual improvements at week 52.

Microperimetric assessment of retinal sensitivity in eyes with diabetic macular edema from a phase 2 study of intravitreal aflibercept.

PURPOSE: To evaluate retinal sensitivity in patients with diabetic macular edema who received intravitreal aflibercept injection (IAI) or laser. METHODS: A substudy included 46 patients from DA VINCI (a randomized, double-masked Phase 2 study) receiving either laser, 0.5 mg IAI every 4 weeks, 2 mg IAI every 4 weeks, 2 mg IAI every 8 weeks after 3 monthly doses (2q8), or 2 mg IAI as-needed after 3 monthly doses for 52 weeks. Retinal sensitivity was measured in one (central), five (one central and four inner), and eight (four inner and four outer) optical coherence tomography subfields. RESULTS: Mean best-corrected visual acuity improvement in the subgroup at Week 52 was 3.3 letters with laser and ranged from 5.4 to 16.3 letters in the IAI groups. Retinal sensitivity of laser patients at Week 52 was comparable with baseline in the central optical coherence tomography subfield but decreased in the five and eight optical coherence tomography subfields. Compared with laser, retinal sensitivity significantly increased with IAI in the 2q8 and pooled IAI groups in the 5 and 8 optical coherence tomography subfields at Week 52 (P < 0.05). CONCLUSION: Intravitreal aflibercept injection improved best-corrected visual acuity and retinal sensitivity in this subgroup of patients. Laser may cause a deterioration of macular function that is not detectable with best-corrected visual acuity testing.

Intravitreal aflibercept for macular edema following branch retinal vein occlusion: the 24-week results of the VIBRANT study.

PURPOSE: To compare the efficacy and safety of intravitreal aflibercept injection (IAI) with macular grid laser photocoagulation for the treatment of macular edema after branch retinal vein occlusion (BRVO). DESIGN: The VIBRANT study was a double-masked, active-controlled, randomized, phase III trial. PARTICIPANTS: Treatment-naïve eyes with macular edema after BRVO were included in the study if the occlusion occurred within 12 months and best-corrected visual acuity (BCVA) was between ≤73 and ≥24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (20/40-20/320 Snellen equivalent). METHODS: Eyes (1 eye per patient) received either IAI 2 mg every 4 weeks (n=91) from baseline to week 20 or grid laser (n=92) at baseline with a single grid laser rescue treatment, if needed, from weeks 12 through 20. MAIN OUTCOME MEASURES: The primary outcome measure was the proportion of eyes that gained ≥15 ETDRS letters from baseline BCVA at week 24. Secondary end points included mean change from baseline BCVA and central retinal thickness (CRT) at week 24. RESULTS: The proportion of eyes that gained ≥15 ETDRS letters from baseline at week 24 was 52.7% in the IAI group compared with 26.7% in the laser group (P=0.0003). The mean improvement from baseline BCVA at week 24 was 17.0 ETDRS letters in the IAI group and 6.9 ETDRS letters in the laser group (P<0.0001). The mean reduction in CRT from baseline at week 24 was 280.5 µm in the IAI group and 128.0 µm in the laser group (P<0.0001). Traumatic cataract in an IAI patient was the only ocular serious adverse event (SAE) that occurred. There were no cases of intraocular inflammation or endophthalmitis. The incidence of nonocular SAEs was 8.8% in the IAI group and 9.8% in the laser group. One Anti-Platelet Trialists' Collaboration-defined event of nonfatal stroke (1.1%) and 1 death (1.1%) due to pneumonia occurred during the 24 weeks of the study, both in patients in the laser group. CONCLUSIONS: Monthly IAI provided significantly greater visual benefit and reduction in CRT at 24 weeks than grid laser photocoagulation in eyes with macular edema after BRVO.

Intravitreal aflibercept injection for macular edema due to central retinal vein occlusion: two-year results from the COPERNICUS study.

PURPOSE: To evaluate the efficacy and safety of intravitreal aflibercept injection (IAI) for the treatment of macular edema secondary to central retinal vein occlusion (CRVO). DESIGN: Randomized, double-masked, phase 3 trial. PARTICIPANTS: A total of 188 patients with macular edema secondary to CRVO. METHODS: Patients received IAI 2 mg (IAI 2Q4) (n = 114) or sham injections (n = 74) every 4 weeks up to week 24. During weeks 24 to 52, patients from both arms were evaluated monthly and received IAI as needed, or pro re nata (PRN) (IAI 2Q4 + PRN and sham + IAI PRN). During weeks 52 to 100, patients were evaluated at least quarterly and received IAI PRN. MAIN OUTCOME MEASURES: The primary efficacy end point was the proportion of patients who gained ≥ 15 letters in best-corrected visual acuity (BCVA) from baseline to week 24. This study reports week 100 results. RESULTS: The proportion of patients gaining ≥ 15 letters was 56.1% versus 12.3% (P<0.001) at week 24, 55.3% versus 30.1% (P<0.001) at week 52, and 49.1% versus 23.3% (P<0.001) at week 100 in the IAI 2Q4 + PRN and sham + IAI PRN groups, respectively. The mean change from baseline BCVA was also significantly higher in the IAI 2Q4 + PRN group compared with the sham + IAI PRN group at week 24 (+17.3 vs. -4.0 letters; P<0.001), week 52 (+16.2 vs. +3.8 letters; P<0.001), and week 100 (+13.0 vs. +1.5 letters; P<0.0001). The mean reduction from baseline in central retinal thickness was 457.2 versus 144.8 µm (P<0.001) at week 24, 413.0 versus 381.8 µm at week 52 (P = 0.546), and 390.0 versus 343.3 µm at week 100 (P = 0.366) in the IAI 2Q4 + PRN and sham + IAI PRN groups, respectively. The mean number (standard deviation) of PRN injections in the IAI 2Q4 + PRN and sham + IAI PRN groups was 2.7 ± 1.7 versus 3.9 ± 2.0 during weeks 24 to 52 and 3.3 ± 2.1 versus 2.9 ± 2.0 during weeks 52 to 100, respectively. The most frequent ocular serious adverse event from baseline to week 100 was vitreous hemorrhage (0.9% vs. 6.8% in the IAI 2Q4 + PRN and sham + IAI PRN groups, respectively). CONCLUSIONS: The visual and anatomic improvements after fixed dosing through week 24 and PRN dosing with monthly monitoring from weeks 24 to 52 were diminished after continued PRN dosing, with a reduced monitoring frequency from weeks 52 to 100.