1Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin
2University of California-Davis, Davis, California
3Center for Visual Science, University of Rochester, Rochester, New York
Commercial Relationships: J. Carroll, None; S.S. Choi, None; D.R. Williams, Optos, C; Optos, P.
Support: Research to Prevent Blindness, NIH Grants EY14749, EY01319, & EY04367, and the NSF Science and Technology Center for Adaptive Optics
Purpose:Complete achromatopsia (i.e., rod monochromacy) is a congenital vision disorder in which cone function is absent or severely diminished, due to mutations in one of 2 components of the cone phototransduction cascade (transducin or the cyclic-nucleotide gated channel). Previous histological data concerning cone structure are conflicting; suggesting anywhere from normal numbers of foveal cones to a complete absence of foveal cones. Here we sought to determine the photoreceptor complement in a genotyped achromat.
Methods:A male (ACH0016) diagnosed with complete achromatopsia (age 28) and his mother (ACH0015), a carrier (age 50), were recruited for this study. Complete ophthalmologic examinations were done on both subjects just prior to retinal imaging, which was performed over a 2-day period. Images of the photoreceptor mosaic were obtained using an adaptive optics ophthalmoscope. Color vision was assessed using a variety of tests, including the Rayleigh match, pseudoisochromatic plates (AO-HRR, Dvorine and Ishihara) and the Neitz Test of Color Vision. DNA analysis was done previously, revealing that ACH0016 was homozygous for a common CNGB3 mutation (Thr383fs) and ACH0015 was heterozygous.
Results:Behavioral and electrophysiological data from the patient (AOCH0016) were consistent with an absence of cone function. Images for ACH0016 were obtained at 1.25, 2.5, 4, and 10 degrees temporal from fixation (OD). Numerous photoreceptors are visible in all 4 images, though the photoreceptor mosaic is severely disrupted compared to images from a normal retina. The density of the photoreceptors was consistent with normal rod, not cone, densities. Images from the heterozygous carrier mother (at 1.25 and 2.5 degrees, OD) revealed no obvious disruption. An analysis of her retinal images revealed a continuous mosaic in which the photoreceptors were of a density characteristic of cones.
Conclusions:Here we presented the first in vivo images of the photoreceptor mosaic of a rod monochromat and found no evidence for structurally intact cones. The genetic and phenotypic diversity of the disease forecasts considerable variability in the relative number of residual cones in other achromats. Thus, examination of additional genetically classified patients with high-resolution retinal imaging is likely to provide valuable insight into pathogenesis of the disease as well as identify those individuals who might be most receptive to newly developed gene therapies.
Keywords: photoreceptors retinal degenerations: hereditary color vision
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