Worldwide multicenter ocular imaging study (EyeConic) to identify patients eligible for cone-based optogenetics therapy

Abstract

Purpose : The EyeConic study is a multicenter study, aiming to estimate the proportion of low-vision patients with preserved foveal cone photoreceptors. Previous studies showed that the cone cell body might be preserved despite outer segment loss in inherited retinal degenerations (IRDs). This ‘dormant’ cone phenotype can lead to foveal sparing, evident on ocular imaging. Thus, this dormant state creates an opportunity to resensitize cone cell bodies with optogenetic tools to restore vision in blind patients. Here we present the full dataset and update on the retrospective, cross-sectional EyeConic study.

Methods : We enrolled 436 eyes of 281 patients with generalized IRDs (study patients) from 11 centers, 20 with Stargardt disease (atrophy controls), and 80 healthy controls. Eyes with best-corrected visual acuity (BCVA) of less or equal to 20/400 were included. We developed a machine-learning-based algorithm to segment total retinal thickness in macular optical coherence tomography (OCT) scans and determined the central 350 µm rod-free volume (RFV). We created a filter to exclude hyperreflective material from volume calculation to better approximate the volume of remaining cones. The corrected RFV (cRFV) is the primary outcome measure. To allow for comparison to healthy foveal outer nuclear layer or to atrophy controls, cRFV values were normalized and expressed in z-scores.

Results : cRFVs of study patients were normally distributed and showed a wide distribution ranging from complete atrophy to well-preserved cRFVs. Mean (± s.d.) cRFV values were found to be 8.58e6 ± 4.45e6 µm³, 4.49e6 ± 1.62e6 µm³ , and 1.82e7 ± 2.14e6 µm³, for EyeConic study patients, atrophy controls and healthy controls, respectively. After normalizing cRFV to healthy individuals, we found that 37% of study patients have normal cRFV (indicated by having a z-score of at least -1.65). We also normalized the cRFV to atrophic controls and found that 58% of patients have significantly higher cRFVs than the atrophic group (indicated by having a z-score of +1.65 or above). Visual acuity did not correlate with cRFV (r=0.09; p=0.58).

Conclusions : A substantial fraction of generalized IRD patients with low vision demonstrates preserved foveal structure suggesting the presence of dormant cone photoreceptors. These patients are potential candidates for cone-based optogenetic therapy.

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