Exploratory optical coherence tomography (OCT) analysis in patients with geographic atrophy (GA) treated by OpRegen: Results from the Phase 1/2a trial

Abstract

Purpose : Subretinal delivery of OpRegen–a suspension of human allogeneic retinal pigment epithelial (RPE) cells–was evaluated in patients (pts) with GA secondary to age-related macular degeneration (Ph 1/2a; NCT02286089). Fundus autofluorescence (FAF) is typically used to measure GA progression, but may be limited in assessing OpRegen activity due to lack of accumulated lipofuscin given young developmental age of cells. OCT provides greater resolution and may be more effective in assessing retinal structure following OpRegen delivery. We aimed to explore the anatomical changes in the outer retina 1 yr after OpRegen delivery using OCT in cohort 4 pts.

Methods : Cohort 4 pts (n=12, BCVA 20/64-20/250) received up to 200,000 OpRegen cells via subretinal delivery. OCT and FAF at baseline and 1 yr were analyzed. On OCT, hyperreflective bands representing RPE and external limiting membrane (ELM) layers were segmented, quantified by semi-automated algorithms, and reviewed by a single masked grader. Results are presented as mean±SD.

Results : At 1 yr, minimal change in BCVA was observed in the untreated fellow eye (+1.3±6.4 letters [L]), while most pts showed an improvement or maintenance of baseline in the OpRegen-treated eye (+7.6±8.7 L), particularly among 5 pts in which atrophic areas were extensively covered by the subretinal surgical bleb containing OpRegen (+12.8 L). Rates of RPE and ELM band loss (i.e. relative quantitative gain) were slower on OCT at 1 yr in treated vs fellow eye in all pts (mm²; RPE 1.1±2.1 gain vs 1.1±1.1 loss; ELM 1.0±1.4 loss vs 1.7±1.0 loss). Improvement was most apparent in the 5 pts with extensive OpRegen coverage, resulting in maintenance and improvement of outer retina structure in treated eyes vs worsening in fellow eyes (mm²; RPE 2.6±2.5 gain vs 1.2±1.5 loss; ELM 0.2±0.6 gain vs 1.3±0.8 loss). FAF-measured GA area change (baseline to 1 yr) correlated well with the change in OCT-measured ELM loss in fellow eyes (R=0.87), but the correlation was weaker (8/11 underestimated the change) in treated eyes (R=−0.29).

Conclusions : Imaging findings suggest that OpRegen delivery has the potential to slow, halt, and reverse GA progression with improvement of retinal structure. OCT may be more suitable than FAF to assess retinal integrity post-treatment and will be further evaluated in a Ph 2a study (NCT05626114) of OpRegen.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.