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Lucas Janeschitz-Kriegl, Giacomo Calzetti, Michel Michaelides, Jose Alain Sahel, Zoltán Nagy, Katarina Stingl, Jin Zi-Bing, Jacque L Duncan, Eyal Banin, Byron L Lam, Michalis Georgiou, Boris Rosin, Viktória Szabo, Potyra Rosa, Bence György, Hendrik P Scholl; Worldwide multicenter ocular imaging study (EyeConic) to identify patients eligible for cone-based optogenetics therapy. Invest. Ophthalmol. Vis. Sci. 2022;63(7):455.
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We are developing a cone-based optogenetic vision restoration approach that aims to resensitize dormant cone photoreceptors in patients with low vision. In a subset of patients with inherited retinal dystrophies (IRDs), cones lose their light-sensitive outer segments but remain alive in a dormant stage. This creates an opportunity to resensitize them through targeted optogenetic tools. However, the true proportion of low vision patients harboring dormant, non-functional cones, is currently unknown. The worldwide multicenter retrospective study (EyeConic) aims to estimate the proportion of low vision patients with remaining cone cell bodies for the first time.
We have enrolled 276 eyes of 174 patients with generalized IRDs (study patients) from 7 centers, 15 patients with Stargardt macular dystrophy (STGD) and 15 healthy individuals. Eyes of patients with generalized IRDs and best-corrected visual acuity (BCVA) less than 20/400 were included. We developed a machine-learning-based algorithm to segment total retina in study participants based on macular optical coherence tomography (OCT) scans and calculated the volume of the central foveolar hypercylinder (350 µm diameter). This value is used as a proxy for the remaining cone mass and is expressed as normalized z scores of healthy outer nuclear layer volume.
Foveal hypercylinder volumes of study patients followed a normal distribution and were highly variable ranging from complete atrophy to normal volumes. We found that 31% and 39% of study patients had foveolar hypercylinder volumes within 2 and 3 z scores (indicating 2 and 3 standard deviations from the normal), respectively. There was no correlation between foveolar hypercylinder volume of study patients and BCVA (r=0.04). The highest z-scores were observed in patients harboring biallelic mutations in CEP78, IFT140, CEP290, CRX and TULP1.
A substantial number of patients with generalized IRDs show a foveal hypercylinder volume that is within the range of a healthy cone volume. Such structure-function dissociation provides an opportunity for cone-based optogenetic vision restoration. A significant fraction of patients with low vision are thus candidates for cone-based optogenetics therapy.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
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