Molly Munsell, MD, and Janice Ong, MD
The non-neovascular symposium “Beyond Atrophy: Restoring Vision and Redefining Care in Geographic Atrophy” panel at the American Society of Retina Specialists 2026 annual meeting was moderated by Dr. Odette Houghton, Dr. Alice Lyon, and Dr. Andre Witkin.
Vision Improvement with Sonpiretigene Isteparvovec Optogenetic Therapy in Macular Degeneration: First Direct-to Phase 2 Randomized, Controlled Trial
Dr. Jordi Mones, MD, PhD
Dr. Mones presented results from sonpiretigene isteparvovec (MCO-010, son-vec), an optogenetic therapy, for the treatment of inherited retinal degenerations and a primate model of geographic atrophy (GA). He announced an upcoming direct-to-phase 2 trial in GA in AMD patients. Son-vec is delivered via intravitreal injection of a multi-characteristic opsin transgene via AAV2 vector. Bipolar cells are transduced to express the transgenic opsin, restoring photosensitivity in areas of photoreceptor loss. In the RESTORE trial in patients with retinitis pigmentosa and baseline vision worse than 20/200, son-vec improved visual acuity by 0.3 logMAR units, corresponding to 3 ETDRS lines, at 52 weeks. In the STARLIGHT trial in patients with Stargardt disease and acuity of 20/400 or poorer, improvements in visual acuity and visual fields were seen as early as 12 weeks in the small subset of 6 patients with a macular atrophy phenotype. Dr. Mones reported results from a new non-human primate model of GA induced using OCT-guided laser targeting the outer retina. Son-vec was found to have transfected 70% of inner retinal cells in this model with no adverse events and improvements in multifocal electroretinography. GENESIS, a direct-to-phase 2 randomized controlled trial of son-vec in humans with GA due to AMD, is planned to start in 2026.
From Optical Modeling to First-in-Human Add-on Implantation of the Implantable Miniature Telescope: Translational Feasibility of a Dual-Lens System for Late-Stage AMD
Dr. Stanislao Rizzo, MD
Dr. Rizzo presented on Smaller-Incision New Generation Implantable Miniature Telescope (SING IMT), an intraocular lens (IOL) implant for AMD patients which magnifies images by 2.7 times to reduce the impact of AMD-related scotoma. SING IMT is implanted via a 6.5-7.5 mm-wide limbal incision. There are ongoing clinical trials in the US (CONCERTO) and Europe (SING PMCF). Dr. Rizzo presented the published 6-month results in 35 patients, with 97% able to read at 6 months compared to 27% at baseline. There was also a statistically significant improvement in best corrected visual acuity by less than 0.3 logMAR units. Endothelial cell density (ECD) loss at 6 months was 8% on average. In a pig model, SING IMT was successfully implanted over the top of an existing IOL. The PERSPECTIVE trial, a human safety trial in Europe for sulcus placement of SING IMT in pseudophakic patients with late AMD and baseline visual acuity between 20/80 and 20/800 as an IOL exchange or add-on IOL, is ongoing. The primary endpoint is ECD loss less than 23% at 6 months.
Liquid Biopsy Proteomics: Deciphering the Molecular Mechanisms Behind Increased Neovascular AMD Risk After Anti-complement Therapy in Geographic Atrophy
Dr. Tsai-Chu Yeh, MD, MTM
Dr. Yeh presented the results of a cross-sectional analysis of aqueous humor proteomics to better understand why some GA patients develop wet AMD after starting anticomplement therapy. They included 75 eyes in four groups: controls, and those with GA varying treatment status ranging from untreated GA eyes to those treated with pegcetacoplan, a C3 complement inhibitor, and avacincaptad pegol, a C5 complement inhibitor. Overall, they found that eyes treated with complement inhibitors showed upregulation of monocyte and macrophage-associated markers as well as activation of pro-angiogenic markers. Both C3 and C5 inhibition ultimately triggered this downstream cascade of immune activation and angiogenesis. These findings suggest also that proteomics, by identifying patients with this underlying predisposition, may also provide a means of risk-stratifying patients under consideration for anti-complement therapy in GA.
Artificial intelligence in GA: Learnings from the Pegcetacoplan Clinical Program
Dr. Paul Hahn, MD, PhD
Dr. Hahn presented the results of an AI imaging analysis of post-hoc data from the FILLY, OAKS, DERBY, and GALE trials that sought to address how retinal layer analysis using deep learning could help to risk-stratify and identify good candidate patients for anti-complement therapy. While conventional imaging endpoints focus on the total area of GA on autofluorescence, Dr. Hahn discussed how deep learning algorithms may give us a more nuanced quantification of GA extent. Deep learning algorithms were used to quantify outer retinal abnormalities including ellipsoid zone (EZ) and RPE loss. They found that progression of GA towards the fovea, which compromises central vision, was slower than extrafoveal progression, and that pegcetacoplan particularly appears to slow fovea-adjacent progression. Furthermore, they propose using the ratio of EZ to RPE losses as a new metric for GA risk stratification, highlighting a potential distinction between at-risk and lost RPE that may be helpful in identifying candidates who are most likely to benefit from anti-complement therapy. They also presented visual function data in the form of functional OCT, which integrates structural data with microperimetry, suggesting that pegcetacoplan helped to preserve macular sensitivity in at-risk zones.
