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Michalis Georgiou, Anthony G Robson, Nashila Hirji, Navjit Singh, Thomas Kane, Alfredo Dubra, Joseph Carroll, Andrew Webster, Angelos Kalitzeos, Michel Michaelides; Deep Phenotyping of PDE6C-Associated Retinopathy. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5167. doi: https://doi.org/.
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To examine disease natural history and perform deep-phenotyping of subjects with PDE6C-associated retinopathy.
Eight subjects with disease-causing variants in PDE6C were assessed in detail, including clinical phenotype, visual acuity (VA), fundus autofluorescence (FAF), and optical coherence tomography (OCT). Multiple parameters were monitored. Six subjects also had confocal and non-confocal Adaptive Optics Scanning Light Ophthalmoscopy (AOSLO), axial length, color vision, International-standard pattern and full-field electroretinography (PERG; ERG) and additional S-cone testing.
All eight subjects (7 females) presented with early-onset nystagmus, decreased VA, light sensitivity, and severe color vision loss. We identified 10 disease-causing variants; 9 of which are novel. Foveal hypoplasia was absent in all subjects, in contrast to other achromatopsia (ACHM) genotypes (Fisher’s Exact Test, p=0.0003). No subjects had residual ellipsoid zone (EZ) at the foveal center; 1 had an absent EZ, 3 had a hyporeflective zone, and 4 had outer retinal atrophy. The width of the EZ lesion at baseline was 1923μm (range, ±SD; 503-4087μm, ±1359μm). Mean age±SD at baseline OCT was 36±8 years. Seven patients had a mean follow-up (FU) of 5.6 years for OCT. The mean (range,±SD) annual rate of EZW loss was 48.3μm (1.7-178, ±61.7); with all subjects progressing at variable rates. A central hypoautofluorescence with a surrounding ring of increased signal was present in five subjects (mean age±SD; 34±7.8years); who had 6.5 years of FU (Fig.1). The mean hypofluorescent area at baseline was 3.33 mm2 and increased in size by a mean of 0.13 mm2/year. The mean hyperautofluorescent ring area at baseline was 2.03 mm2 and increased centrifugally by 0.14 mm2/year. Axial length was varying greatly (range: 22.50-27.88 mm, SD: 2.18 mm) and for all subjects available was used for correcting the measurements. Non-confocal AOSLO was analyzable in 2 subjects and revealed a lack of foveal cones. The electrophysiology was consistent with severe macular and generalised cone system dysfunction, but with relative preservation of short-wavelength sensitivity. Older patients had also rod photoreceptor dysfunction.
PDE6C-associated retinopathy is a severe and very slowly progressive condition, often presenting as typical ACHM, without foveal hypoplasia, with few (if any) residual foveal cones for intervention.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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