Taku Wakabayashi, MD, PhD
Retina Research Fellow
Wills Eye Hospital
Day 2 of Retina Society 2021 started off with an exciting surgical retina session moderated by Drs. David Zacks and Julia Haller.
The session started off with Dr. Rajeev Muni from the University of Toronto who presented a post-hoc analysis from the PIVOT trial, focusing on the incidence and impact of outer retinal folds on visual outcomes after pneumatic retinopexy versus pars plana vitrectomy for macula-off RRDs. He found that the incidence of outer retinal folds was more common in the PPV group (34%) than pneumatic group (14%) (p=0.03). Although outer retinal folds spontaneously disappeared, outer retinal folds present at 1 months were significantly associated with worse visual acuity at 1 year. Dr. Muni concluded that not only is the retinal reattachment important but also “quality of the reattachment” is important as well.
Following Dr. Muni were two presentations from the DRCR network. First was Dr. Clement Chan from Southern California Desert Retina Consultants who presented data from the DRCR Retina Network Protocol AG, a multi-center randomized clinical trial comparing pneumatic vitreolysis using C3F8 gas versus observation for eyes with vitreomacular traction. At 24 weeks, 18 of 23 eyes in the pneumatic vitreolysis group (78%) versus 2 of 22 eyes in the sham group (9%) achieved central vitreomacular traction release without rescue vitrectomy (P< 0.001). However, there was no difference in the mean visual change from baseline at 24 weeks between the two groups (6.7 vs 6.1 letters).
Dr. Calvin Mein from Retina Consultants of Texas then presented data from the DRCR Retina Network Protocol AH, a single-arm study on pneumatic vitreolysis using C3F8 gas for small macular holes (≤250 µm at the minimum diameter). He found that only 10 of 35 eyes (29%) achieved macular hole closure without rescue vitrectomy at 8 weeks. The mean visual change from baseline at 8 weeks was -1.5 letters.
It must be noted that both protocols AG and AH were terminated early because of safety concerns related to a high rate of retinal detachments and retinal tears in the pneumatic vitreolysis cohorts. The rate of retinal detachment and tears was 12% (7/59 eyes) when combining the two cohorts from AG and AH.
One of the most anticipated sessions of Retina Society this year was the Thursday morning presentations of Phase III Pivotal trials. The session was moderated by the lively Dr. Judy Kim. Dr. Jeff Heier from Ophthalmic Consultants of Boston presented the 12 month results of the Phase 3 DERBY and OAKS trial, which examined the efficacy and safety of intravitreal pegcetacoplan compared to sham in patients with geographic atrophy. Pegcetacoplan inhibits C3 as well as downstream C5. In these studies, patients with foveal and extrafoveal GA (≥2.5 and ≤17.5 mm2 in size) were randomized to: intravitreal pegcetacoplan (15mg/0.1mL) monthly, intravitreal pegcetacoplan (15mg/0.1mL) every other month, sham monthly, or sham every other month. The primary endpoint at 12 months was change in GA lesions as seen on autofluorescence imaging.
Pegcetacoplan met the primary endpoint in OAKS. The rate of GA progression was reduced by 22% in the monthly arm, and 16% in the every other month arm, both statistically significant. In contrast, pegcetacoplan did not meet the primary endpoint in DERBY. The rate of GA progression was reduced by 12% in the monthly arm, and 11% in the every other month arm, both not statistically significant.
Prespecified analysis revealed that pegcetacoplan demonstrated greater efficacy in patients with extrafoveal lesions at baseline. Both OAKS and DERBY showed consistent efficacy in treated eyes versus untreated fellow eyes.
Why the results were inconsistent between OAKS and DERBY trials? Regional differences and imbalances in baseline characteristics such as lesion location and size may have influenced the GA progression. Dr. Heier said investigation is still ongoing to understand the disparities between OAKS and DERBY trials.
Dr. Charles Wykoff from Retina Consultants of Texas presented the safety results of the Phase 3 DERBY and OAKS trial. Overall, pegcetacoplan administered monthly and every other month was well tolerated. The rate of intraocular inflammation was 2.1% (9/419 eyes) in the monthly arm, and 1.0% (4/420 eyes) in the every other month arm (OAKS and DERBY combined). The majority of cases were mild and most patients resumed intravitreal pegcetacoplan administration. Infectious endophthalmitis occurred in 0.2% (1/419 eyes) in the monthly arm, and 0.5% (2/420 eyes) in the every other month arm, which was in line with previous prospective pivotal trials of intravitreal therapeutics. New-onset exudative AMD was developed in 6.0%, 4.1%, and 2.4% of patients in the monthly, every other month, and sham groups. Those patients continued treatment with pegcetacoplan and received anti-VEGF treatment. Based on the presentations, pegcetacoplan certainly has the potential to become the first treatment option in eyes with GA. We all look forward to seeing 24 months results in the near future.
