AOphthalmology, BCell Biology, Neurobiology & Anatomy, 1Medical College of Wisconsin, Milwaukee, Wisconsin
2Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois
3The Chicago Lighthouse for People Who Are Blind or Visually Impaired, Chicago, Illinois
4Psicologia Experimental, Universidade de Sao Paulo, Sao Paulo, Brazil
5Ophthalmology, University of Washington, Seattle, Washington
Commercial Relationships: Jungtae Rha, None; Mohamed A. Genead, None; Daniela M. Bonci, None; Adam M. Dubis, None; Brett Schroeder, None; Maureen Neitz, None; Gerald A. Fishman, None; Joseph Carroll, None
Support: Research to Prevent Blindness, CAPES, NIH grants P30EY001931, P30EY001730, P30EY001792, R01EY017607, Hope for Vision, Foundation Fighting Blindness, and Grant Healthcare Foundation.
Purpose:To characterize the integrity of the photoreceptor mosaic in human patients with achromatopsia, as this may be of predictive value for potential future therapeutic trials.
Methods:Eleven achromatopsia patients (8 male & 3 female) were recruited in the current study. Photoreceptor images were obtained using an adaptive optics (AO) ophthalmoscope. Cross-sectional images of the retina were obtained using SD-OCT. All patients were screened for mutations in GNAT2, CNGA3, and CNGB3 genes.
Results:The AO images showed significantly disrupted photoreceptor mosaics. In most patients we found evidence of residual cone structures, manifest as dark spots surrounded by visible rod photoreceptors. We interpreted the dark spots as a non-waveguiding cone inner segments, which likely have malformed or absent cone outer segments. We found significant variability in the macular appearance on SD-OCT that ranged from a focal disruption of the IS/OS to a complete disruption of the IS/OS with RPE atrophy. The presence of an intraretinal "bubble" was also consistent with some previous reports, though we observed older individuals without this "bubble". We found that 7/11 patients had significant retinal thinning in the outer ETDRS-like ring, 10/11 had significant retinal thinning in the inner ETDRS-like ring, and 4/11 had significant retinal thinning of the central foveal subfield. We saw no significant age-dependent decline in total retinal thickness at the fovea. Four patients were homozygous and one was heterozygous for a 1 base pair deletion (1148 del C) in the CNGB3 gene. One patient was compound heterozygous for mutations in the CNGA3 and CNGB3 genes, and one patient was homozygous for a CNGA3 mutation. Mutations were not found in the remaining 4 patients.
Conclusions:Cone structures are highly variable in patients with achromatopsia, which should be considered when selecting patients as candidates for gene therapy intervention. The variability persisted even within patients with the same genotype. Our preliminary results do not support a general age-related decline in cone structures.
Keywords: photoreceptors imaging/image analysis: clinical color vision
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