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Emily J Patterson, James Tee, Jay Neitz, Christopher S Langlo, Alfredo Dubra, Maureen Neitz, Adam M Dubis, Alison J Hardcastle, Michel Michaelides, Joseph Carroll; Assessing cone mosaic disruption in patients with X-linked cone dysfunction. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):88. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Cone dysfunction syndromes are typically associated with reduced color vision and have been linked to the OPN1LW and OPN1MW genes on the X chromosome. How mutations in these genes affect cone photoreceptor integrity remains an important question as we seek to elucidate a deeper understanding of the genotype-phenotype relationship in these conditions. Here we used adaptive optics scanning light ophthalmoscopy (AOSLO) to characterize cone structure in subjects with mutations in the OPN1LW and OPN1MW genes.
Six males (aged 11-37 years) with OPN1LW and OPN1MW mutations were recruited. All subjects were dichromatic (5 protanopic, 1 deuteranopic). Images of the cone mosaic were obtained using AOSLO (both confocal and non-confocal split-detection). Cone density was measured at parafoveal regions of interest (ROIs) using semi-automated cone-counting software and compared to published normative data. In five subjects, we compared cone density across the confocal and non-confocal split-detection modalities. Confocal cone density was assessed over time for two subjects (follow up = 2 or 4 years).
Three subjects had the previously reported LIAVA haplotype encoded by either the OPN1LW or OPN1MW gene, while two others had an insertion in exon 2 of the OPN1LW gene resulting in a 32bp repeat. The final subject had no OPN1LW gene, and one of his two OPN1MW genes encoded either the LIAVA or MIAVA haplotype. Subjects showed variable reduction in cone density compared to normal observers using both confocal (range = 26-90%) and split detection (range = 7-87%) images. In most ROIs, we observed greater cone density using split-detection rather than confocal images (p = .70), indicating that the low cone density in confocal images was due partly to altered cone reflectivity, rather than complete loss of cones. No change in cone density was observed for the two subjects for whom serial images were acquired (p = .30 and .42).
There is striking variability in the cone mosaic phenotype in individuals with OPN1LW and OPN1MW mutations. The combined use of confocal and split-detection AOSLO imaging allows for a more thorough assessment of residual cone structure in these patients. It remains to be seen whether the variable degree of cone loss observed here correlates with variable functional deficits.
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