AOphthalmology, BBiophysics, 1Medical College of Wisconsin, Milwaukee, Wisconsin
2Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
3UCL Institute of Ophthalmology, London, United Kingdom
4Moorfields Eye Hospital, London, United Kingdom
ACenter for Visual Science, BOphthalmology, 5University of Rochester, Rochester, New York
Commercial Relationships: J. Carroll, None; E. Banin, None; D.M. Hunt, None; R. Martin, None; M. Michaelides, None; L. Mizrahi-Meissonnier, None; A.T. Moore, None; D. Sharon, None; D.R. Williams, Optos, C; U.S. Patents #5,777,719, #5,949,521, #6,095,651, #6,379,005, #6,948,818, #6,199,986, #6,299,311, #6,827,444, #6,264,328, #6,338,559, P; A. Dubra, None.
Support: NIH EY001931 & EY017607, Alfredo Dubra-Suarez, Ph.D., holds a Career Award at the Scientific Interface from the Burroughs Welcome Fund.
Purpose:The purpose of this study was to evaluate the photoreceptor mosaic in 3 affected males and 3 carrier females with blue cone monochromacy (BCM).
Methods:Genetic analysis was performed to determine the structure and sequence of the L/M gene array. We obtained high-resolution retinal images using spectral domain optical coherence tomography (SD-OCT), adaptive optics ophthalmoscopy (AOO), and adaptive optics scanning laser ophthalmoscopy (AOSLO). The AOO and AOSLO were equipped with 52- and 97-channel magnetic deformable mirrors, respectively. Retinal thickness and outer nuclear layer (ONL) thickness were compared to data from 167 normals. Cone spacing and regularity were measured and compared to previously published values from normal retinas as well as normative data from our lab.
Results:In all 3 males, BCM was due to a 2-step mutational pathway; one male had a rare opsin variant (LIAVS) and the other 2 had the C203R mutation in a single hybrid gene. SD-OCT revealed significant ONL and retinal thinning in the affected males, but not the female carriers. Cone spacing was normal in the carrier females, though there were disruptions in the regularity of the cone mosaic. In the affected males, a sparse mosaic of photoreceptors likely to represent S-cones was observed in the foveal region. In the peripheral retina, contiguous patches of the rod mosaic were observed, with individual rods being easily resolved. This was interleaved by an array of dark spots (presumed non-functioning cones). In two of the affected males, the foveal S-cone free area could be clearly resolved on both the AOSLO images and the SD-OCT images.
Conclusions:In both the LIAVS and C203R BCM mosaics, L/M cone structure is compromised to the point where they do not waveguide; however the appearance of the photoreceptor mosaic suggests that a significant number of cones remain in the parafoveal and peripheral retina. This has important implications for the potential restoration of visual function in some BCM patients, and underscores the importance of developing high-resolution genotype-phenotype maps in conditions such as BCM.
Keywords: imaging/image analysis: clinical color pigments and opsins photoreceptors
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