Revakinagene taroretcel-lwey

Macular telangiectasia type 2 is a genetically complex disorder with variable penetrance and expressivity. Although several causative genes have been identified, the genetic basis remains unknown in most affected individuals. Genetic and metabolomic studies have implicated dysregulated serine and lipid metabolism in disease pathogenesis. Serine deficiency promotes the accumulation of cytotoxic 1-deoxysphingolipids, which damage Müller cells, photoreceptors, and retinal pigment epithelium. Emerging evidence suggests that the retinal pigment epithelium plays a more important role in disease development than previously recognized. Macular telangiectasia type 2 has traditionally been considered a primary neurodegenerative disorder with secondary vascular abnormalities. However, optical coherence tomography angiography findings have indicated that vascular changes may occur earlier than previously appreciated and may develop in parallel with neurodegeneration rather than as a secondary consequence. Furthermore, there is a strong structure–function correlation between ellipsoid zone loss on optical coherence tomography and retinal sensitivity measured using microperimetry. This relationship supported the acceptance by the US Food and Drug Administration of ellipsoid zone loss area, a structural surrogate endpoint, for the approval of the ciliary neurotrophic factor implant (revakinagene taroretcel-Lwey) in macular telangiectasia type 2 patients. Several therapeutic strategies targeting the underlying metabolic abnormalities are also under investigation. These include serine supplementation, fenofibrate to reduce 1-deoxysphingolipid production, and gene replacement therapy. In addition, growing evidence suggests that mitochondrial dysfunction and impaired cellular energy metabolism contribute to disease pathogenesis and warrant further investigation as potential therapeutic targets.

To report a case of 13-year long progression of geographic atrophy (GA) from dry age-related macular degeneration (AMD) with ciliary neurotrophic factor (CNTF) implant, NT-501, in one eye, compared with the untreated contralateral eye.

Using sequential images from 2012 to 2024, the macular GA and peripapillary atrophy was identified as areas of definitely decreased autofluorescence on fundus autofluorescence (FAF) and clearly delineated areas of hyperreflectivity on near infrared reflectance (NIR-R). Optical coherence tomography B scans confirmed areas of complete retinal pigment epithelium and outer retinal atrophy to support FAF grading.

A 76-year-old man received the CNTF implant in the right eye in August 2011. Macular GA area on short wavelength FAF exhibited growth from 4.51 mm 2 (8/2012) to 14.46 mm 2 (6/2020), in the treated right eye, and from 3.2 mm 2 to 14.92 mm 2 , in the untreated left eye. The linearized growth rates were 0.21 mm/year (right) and 0.26 mm/year (left), showing a 16.3% difference. A similar pattern was seen on green laser FAF from 2018 to 2024, with peripapillary atrophy progression rates of 0.2 mm 2 /year (right) and 1.03 mm 2 /year (left).

Notably, the implanted eye exhibited less progression of macular GA and peripapillary atrophy. While acknowledging the limitations of a single case, we highlight the potential benefits of using the CNTF implant, a one-time surgical procedure, in reducing the treatment burden for atrophic patients with AMD. We hope to see further reports from other sites that participated in this compassionate use protocol for NT-501 in atrophic AMD.