The Experts below are selected from a list of 3408 Experts worldwide ranked by ideXlab platform
Alison J. Hardcastle - One of the best experts on this subject based on the ideXlab platform.
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residual Cone structure in patients with x linked Cone Opsin mutations
Investigative Ophthalmology & Visual Science, 2018Co-Authors: Emily J Patterson, Angelos Kalitzeos, Melissa Kasilian, Jessica C Gardner, Jay Neitz, Alison J. HardcastleAbstract:Purpose To assess residual Cone structure in subjects with mutations in exon 2, 3, and 4 of the OPN1LW or OPN1MW Opsin.
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residual Cone structure in patients with x linked Cone Opsin mutations
Investigative Ophthalmology & Visual Science, 2018Co-Authors: Emily J Patterson, Angelos Kalitzeos, Melissa Kasilian, Jessica C Gardner, Jay Neitz, Alison J. HardcastleAbstract:Purpose To assess residual Cone structure in subjects with mutations in exon 2, 3, and 4 of the OPN1LW or OPN1MW Opsin. Methods Thirteen males had their OPN1LW/OPN1MW Opsin genes characterized. The Cone mosaic was imaged using both confocal and nonconfocal split-detection adaptive optics scanning light ophthalmoscopy (AOSLO), and retinal thickness was evaluated using optical coherence tomography (OCT). Six subjects completed serial imaging over a maximum period of 18 months and Cone density was measured across imaging sessions. Results Ten subjects had an OPN1LW/OPN1MW "interchange" Opsin mutation designated as LIAVA or LVAVA, which both introduce exon 3 splicing defects leading to a lack of functional photopigment in Cones expressing LIAVA and greatly reduced functional photopigment in Cones expressing LVAVA. Despite disrupted Cone reflectivity and reduced numerosity, residual inner segments could be visualized. Similar patterns were observed in individuals with an exon 2 insertion, or an exon 4 splice defect, both of which are also expected to produce Cones that are devoid of functional Opsin protein. OCT revealed variably reduced retinal thickness. A significant inverse relationship was found between the proportion of waveguiding Cones and axial length. Conclusions Split-detection imaging revealed that the altered appearance of the Cone mosaic in confocal images for subjects with exon 2, 3, and 4 mutations was generally due to disrupted waveguiding, rather than structural loss, making them possible candidates for gene therapy to restore Cone function. The relative fraction of waveguiding Cones was highly variable across subjects, which appears to influence emmetropization in these subjects.
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Cone Opsins, colour blindness and Cone dystrophy: Genotype-phenotype correlations.
South African Medical Journal, 2016Co-Authors: Jessica C Gardner, Michel Michaelides, Alison J. HardcastleAbstract:X-linked Cone photoreceptor disorders caused by mutations in the OPN1LW (L) and OPN1MW (M) Cone Opsin genes on chromosome Xq28 include a range of conditions from mild stable red-green colour vision deficiencies to severe Cone dystrophies causing progressive loss of vision and blindness. Advances in molecular genotyping and functional analyses of causative variants, combined with deep retinal phenotyping, are unravelling genetic mechanisms underlying the variability of Cone Opsin disorders.
Jay Neitz - One of the best experts on this subject based on the ideXlab platform.
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Photopigment genes, Cones, and color update: disrupting the splicing code causes a diverse array of vision disorders.
Current opinion in behavioral sciences, 2019Co-Authors: Maureen Neitz, Sara S. Patterson, Jay NeitzAbstract:The human long-wavelength and middle-wavelength sensitive Cone Opsin genes exhibit an extraordinary degree of haplotype diversity that results from recombination mechanisms that have intermixed the genes. As a first step in expression, genes—including the protein coding exons and intervening introns—are transcribed. Next, transcripts are spliced to remove the introns and join the exons to generate a mature message that codes for the protein. Important information necessary for splicing is contained within exons, and is overlaid by the protein code. Intermixing the long-wavelength and middle-wavelength sensitive Cone Opsin genes has disrupted the splicing code, leading to exclusion of some exons from the mature message and is associated with several vision disorders including nearsightedness, Cone dystrophy, and color vision deficiencies.
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The association between L:M Cone ratio, Cone Opsin genes and myopia susceptibility.
Vision Research, 2019Co-Authors: Lene Aarvelta Hagen, Jay Neitz, Maureen Neitz, James A. Kuchenbecker, Solveig Arnegard, Stuart J. Gilson, Rigmor C. BaraasAbstract:Abstract In syndromic forms of myopia caused by long (L) to middle (M) wavelength (L/M) interchange mutations, erroneous contrast signals from ON-bipolar cells activated by Cones with different levels of Opsin expression are suggested to make the eye susceptible to increased growth. This susceptibility is modulated by the L:M Cone ratio. Here, we examined L and M Opsin genes, L:M Cone ratios and their association with common refractive errors in a population with low myopia prevalence. Cycloplegic autorefraction and ocular biometry were obtained for Norwegian genetically-confirmed normal trichromats. L:M Cone ratios were estimated from spectral sensitivity functions measured with full-field ERG, after adjusting for individual differences in the wavelength of peak absorption deduced from Cone Opsin genetics. Mean L:M Cone ratios and the frequency of alanine at L Opsin position 180 were higher in males than what has been reported in males in populations with high myopia prevalence. High L:M Cone ratios in females were associated with lower degree of myopia, and myopia was more frequent in females who were heterozygous for L Opsin exon 3 haplotypes than in those who were homozygous. The results suggest that the L:M Cone ratio, combined with milder versions of L Opsin gene polymorphisms, may play a role in common myopia. This may in part explain the low myopia prevalence in Norwegian adolescents and why myopia prevalence was higher in females who were heterozygous for the L Opsin exon 3 haplotype, since females are twice as likely to have genetic polymorphisms carried on the X-chromosome.
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residual Cone structure in patients with x linked Cone Opsin mutations
Investigative Ophthalmology & Visual Science, 2018Co-Authors: Emily J Patterson, Angelos Kalitzeos, Melissa Kasilian, Jessica C Gardner, Jay Neitz, Alison J. HardcastleAbstract:Purpose To assess residual Cone structure in subjects with mutations in exon 2, 3, and 4 of the OPN1LW or OPN1MW Opsin.
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residual Cone structure in patients with x linked Cone Opsin mutations
Investigative Ophthalmology & Visual Science, 2018Co-Authors: Emily J Patterson, Angelos Kalitzeos, Melissa Kasilian, Jessica C Gardner, Jay Neitz, Alison J. HardcastleAbstract:Purpose To assess residual Cone structure in subjects with mutations in exon 2, 3, and 4 of the OPN1LW or OPN1MW Opsin. Methods Thirteen males had their OPN1LW/OPN1MW Opsin genes characterized. The Cone mosaic was imaged using both confocal and nonconfocal split-detection adaptive optics scanning light ophthalmoscopy (AOSLO), and retinal thickness was evaluated using optical coherence tomography (OCT). Six subjects completed serial imaging over a maximum period of 18 months and Cone density was measured across imaging sessions. Results Ten subjects had an OPN1LW/OPN1MW "interchange" Opsin mutation designated as LIAVA or LVAVA, which both introduce exon 3 splicing defects leading to a lack of functional photopigment in Cones expressing LIAVA and greatly reduced functional photopigment in Cones expressing LVAVA. Despite disrupted Cone reflectivity and reduced numerosity, residual inner segments could be visualized. Similar patterns were observed in individuals with an exon 2 insertion, or an exon 4 splice defect, both of which are also expected to produce Cones that are devoid of functional Opsin protein. OCT revealed variably reduced retinal thickness. A significant inverse relationship was found between the proportion of waveguiding Cones and axial length. Conclusions Split-detection imaging revealed that the altered appearance of the Cone mosaic in confocal images for subjects with exon 2, 3, and 4 mutations was generally due to disrupted waveguiding, rather than structural loss, making them possible candidates for gene therapy to restore Cone function. The relative fraction of waveguiding Cones was highly variable across subjects, which appears to influence emmetropization in these subjects.
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Deletion of the X-linked Opsin gene array locus control region (LCR) results in disruption of the Cone mosaic.
Vision Research, 2010Co-Authors: Joseph Carroll, Ethan A Rossi, Jay Neitz, Jason Porter, Austin Roorda, David R. Williams, Maureen NeitzAbstract:Blue Cone monochromacy (BCM) is an X-linked condition in which long- (L) and middle- (M) wavelength-sensitive Cone function is absent. Due to the X-linked nature of the condition, female carriers are spared from a full manifestation of the associated defects but can show visual symptoms, including abnormal Cone electroretinograms. Here we imaged the Cone mosaic in four females carrying an L/M array with deletion of the locus control region, resulting in an absence of L/M Opsin gene expression (effectively acting as a Cone Opsin knockout). On average, they had Cone mosaics with reduced density and disrupted organization compared to normal trichromats. This suggests that the absence of Opsin in a subset of Cones results in their early degeneration, with X-inactivation the likely mechanism underlying phenotypic variability in BCM carriers.
Maureen Neitz - One of the best experts on this subject based on the ideXlab platform.
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Photopigment genes, Cones, and color update: disrupting the splicing code causes a diverse array of vision disorders.
Current opinion in behavioral sciences, 2019Co-Authors: Maureen Neitz, Sara S. Patterson, Jay NeitzAbstract:The human long-wavelength and middle-wavelength sensitive Cone Opsin genes exhibit an extraordinary degree of haplotype diversity that results from recombination mechanisms that have intermixed the genes. As a first step in expression, genes—including the protein coding exons and intervening introns—are transcribed. Next, transcripts are spliced to remove the introns and join the exons to generate a mature message that codes for the protein. Important information necessary for splicing is contained within exons, and is overlaid by the protein code. Intermixing the long-wavelength and middle-wavelength sensitive Cone Opsin genes has disrupted the splicing code, leading to exclusion of some exons from the mature message and is associated with several vision disorders including nearsightedness, Cone dystrophy, and color vision deficiencies.
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The association between L:M Cone ratio, Cone Opsin genes and myopia susceptibility.
Vision Research, 2019Co-Authors: Lene Aarvelta Hagen, Jay Neitz, Maureen Neitz, James A. Kuchenbecker, Solveig Arnegard, Stuart J. Gilson, Rigmor C. BaraasAbstract:Abstract In syndromic forms of myopia caused by long (L) to middle (M) wavelength (L/M) interchange mutations, erroneous contrast signals from ON-bipolar cells activated by Cones with different levels of Opsin expression are suggested to make the eye susceptible to increased growth. This susceptibility is modulated by the L:M Cone ratio. Here, we examined L and M Opsin genes, L:M Cone ratios and their association with common refractive errors in a population with low myopia prevalence. Cycloplegic autorefraction and ocular biometry were obtained for Norwegian genetically-confirmed normal trichromats. L:M Cone ratios were estimated from spectral sensitivity functions measured with full-field ERG, after adjusting for individual differences in the wavelength of peak absorption deduced from Cone Opsin genetics. Mean L:M Cone ratios and the frequency of alanine at L Opsin position 180 were higher in males than what has been reported in males in populations with high myopia prevalence. High L:M Cone ratios in females were associated with lower degree of myopia, and myopia was more frequent in females who were heterozygous for L Opsin exon 3 haplotypes than in those who were homozygous. The results suggest that the L:M Cone ratio, combined with milder versions of L Opsin gene polymorphisms, may play a role in common myopia. This may in part explain the low myopia prevalence in Norwegian adolescents and why myopia prevalence was higher in females who were heterozygous for the L Opsin exon 3 haplotype, since females are twice as likely to have genetic polymorphisms carried on the X-chromosome.
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Deletion of the X-linked Opsin gene array locus control region (LCR) results in disruption of the Cone mosaic.
Vision Research, 2010Co-Authors: Joseph Carroll, Ethan A Rossi, Jay Neitz, Jason Porter, Austin Roorda, David R. Williams, Maureen NeitzAbstract:Blue Cone monochromacy (BCM) is an X-linked condition in which long- (L) and middle- (M) wavelength-sensitive Cone function is absent. Due to the X-linked nature of the condition, female carriers are spared from a full manifestation of the associated defects but can show visual symptoms, including abnormal Cone electroretinograms. Here we imaged the Cone mosaic in four females carrying an L/M array with deletion of the locus control region, resulting in an absence of L/M Opsin gene expression (effectively acting as a Cone Opsin knockout). On average, they had Cone mosaics with reduced density and disrupted organization compared to normal trichromats. This suggests that the absence of Opsin in a subset of Cones results in their early degeneration, with X-inactivation the likely mechanism underlying phenotypic variability in BCM carriers.
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Cone photoreceptor mosaic disruption associated with Cys203Arg mutation in the M-Cone Opsin.
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Joseph Carroll, Melissa Wagner-Schuman, Cory a Siebe, Christina Sloan, Summer Thompson, Jungtae Rha, David H. Foster, Jessica I W Morgan, Rigmor C. Baraas, Diane M. Tait, Jay Neitz, D.r. Williams, Maureen NeitzAbstract:Missense mutations in the Cone Opsins have been identified as a relatively common cause of red/green color vision defects, with the most frequent mutation being the substitution of arginine for cysteine at position 203 (C203R). When the corresponding cysteine is mutated in rhodOpsin, it disrupts proper folding of the pigment, causing severe, early onset retinitis pigmentosa. While the C203R mutation has been associated with loss of Cone function in color vision deficiency, it is not known what happens to Cones expressing this mutant Opsin. Here, we used high-resolution retinal imaging to examine the Cone mosaic in two individuals with genes encoding a middle-wavelength sensitive (M) pigment with the C203R mutation. We found a significant reduction in Cone density compared to normal and color-deficient controls, accompanying disruption in the Cone mosaic in both individuals, and thinning of the outer nuclear layer. The C203R mosaics were different from that produced by another mutation (LIAVA) previously shown to disrupt the Cone mosaic. Comparison of these mosaics provides insight into the timing and degree of Cone disruption and has implications for the prospects for restoration of vision loss associated with various Cone Opsin mutations.
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Adaptive optics retinal imaging reveals S-Cone dystrophy in tritan color-vision deficiency
Journal of the Optical Society of America A, 2007Co-Authors: Rigmor C. Baraas, K L Gunther, David H. Foster, D.r. Williams, Joseph Carroll, M. Chung, Maureen NeitzAbstract:Tritan color-vision deficiency is an autosomal dominant disorder associated with mutations in the short-wavelength-sensitive- (S-) Cone-pigment gene. An unexplained feature of the disorder is that individuals with the same mutation manifest different degrees of deficiency. To date, it has not been possible to examine whether any loss of S-Cone function is accompanied by physical disruption in the Cone mosaic. Two related tritan subjects with the same novel mutation in their S-Cone-Opsin gene, but different degrees of deficiency, were examined. Adaptive optics was used to obtain high-resolution retinal images, which revealed distinctly different S-Cone mosaics consistent with their discrepant phenotypes. In addition, a significant disruption in the regularity of the overall Cone mosaic was observed in the subject completely lacking S-Cone function. These results taken together with other recent findings from molecular genetics indicate that, with rare exceptions, tritan deficiency is progressive in nature.
Jessica C Gardner - One of the best experts on this subject based on the ideXlab platform.
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residual Cone structure in patients with x linked Cone Opsin mutations
Investigative Ophthalmology & Visual Science, 2018Co-Authors: Emily J Patterson, Angelos Kalitzeos, Melissa Kasilian, Jessica C Gardner, Jay Neitz, Alison J. HardcastleAbstract:Purpose To assess residual Cone structure in subjects with mutations in exon 2, 3, and 4 of the OPN1LW or OPN1MW Opsin.
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residual Cone structure in patients with x linked Cone Opsin mutations
Investigative Ophthalmology & Visual Science, 2018Co-Authors: Emily J Patterson, Angelos Kalitzeos, Melissa Kasilian, Jessica C Gardner, Jay Neitz, Alison J. HardcastleAbstract:Purpose To assess residual Cone structure in subjects with mutations in exon 2, 3, and 4 of the OPN1LW or OPN1MW Opsin. Methods Thirteen males had their OPN1LW/OPN1MW Opsin genes characterized. The Cone mosaic was imaged using both confocal and nonconfocal split-detection adaptive optics scanning light ophthalmoscopy (AOSLO), and retinal thickness was evaluated using optical coherence tomography (OCT). Six subjects completed serial imaging over a maximum period of 18 months and Cone density was measured across imaging sessions. Results Ten subjects had an OPN1LW/OPN1MW "interchange" Opsin mutation designated as LIAVA or LVAVA, which both introduce exon 3 splicing defects leading to a lack of functional photopigment in Cones expressing LIAVA and greatly reduced functional photopigment in Cones expressing LVAVA. Despite disrupted Cone reflectivity and reduced numerosity, residual inner segments could be visualized. Similar patterns were observed in individuals with an exon 2 insertion, or an exon 4 splice defect, both of which are also expected to produce Cones that are devoid of functional Opsin protein. OCT revealed variably reduced retinal thickness. A significant inverse relationship was found between the proportion of waveguiding Cones and axial length. Conclusions Split-detection imaging revealed that the altered appearance of the Cone mosaic in confocal images for subjects with exon 2, 3, and 4 mutations was generally due to disrupted waveguiding, rather than structural loss, making them possible candidates for gene therapy to restore Cone function. The relative fraction of waveguiding Cones was highly variable across subjects, which appears to influence emmetropization in these subjects.
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Cone Opsins, colour blindness and Cone dystrophy: Genotype-phenotype correlations.
South African Medical Journal, 2016Co-Authors: Jessica C Gardner, Michel Michaelides, Alison J. HardcastleAbstract:X-linked Cone photoreceptor disorders caused by mutations in the OPN1LW (L) and OPN1MW (M) Cone Opsin genes on chromosome Xq28 include a range of conditions from mild stable red-green colour vision deficiencies to severe Cone dystrophies causing progressive loss of vision and blindness. Advances in molecular genotyping and functional analyses of causative variants, combined with deep retinal phenotyping, are unravelling genetic mechanisms underlying the variability of Cone Opsin disorders.
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Three different Cone Opsin gene array mutational mechanisms with genotype-phenotype correlation and functional investigation of Cone Opsin variants.
Human mutation, 2014Co-Authors: Jessica C Gardner, Hisao Ueyama, Gerald Liew, Yinghua Quan, Burcu Ermetal, Alice E. Davidson, Nele Schwarz, Naheed Kanuga, Ravinder K. Chana, Eamonn R. MaherAbstract:Mutations in the OPN1LW (L-) and OPN1MW (M-)Cone Opsin genes underlie a spectrum of Cone photoreceptor defects from stationary loss of color vision to progressive retinal degeneration. Genotypes of 22 families with a range of Cone disorders were grouped into three classes: deletions of the locus control region (LCR); missense mutation (p.Cys203Arg) in an L-/M-hybrid gene; and exon 3 single-nucleotide polymorphism (SNP) interchange haplotypes in an otherwise normal gene array. Moderate-to-high myopia was observed in all mutation categories. Individuals with LCR deletions or p.Cys203Arg mutations were more likely to have nystagmus and poor vision, with disease progression in some p.Cys203Arg patients. Three disease-associated exon 3 SNP haplotypes encoding LIAVA, LVAVA, or MIAVA were identified in our cohort. These patients were less likely to have nystagmus but more likely to show progression, with all patients over the age of 40 years having marked macular abnormalities. Previously, the haplotype LIAVA has been shown to result in exon 3 skipping. Here, we show that haplotypes LVAVA and MIAVA also result in aberrant splicing, with a residual low level of correctly spliced Cone Opsin. The OPN1LW/OPN1MW:c.532A>G SNP, common to all three disease-associated haplotypes, appears to be principally responsible for this mutational mechanism.
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A Novel Missense Mutation in Both OPN1LW and OPN1MW Cone Opsin Genes Causes X-Linked Cone Dystrophy (XLCOD5)
Retinal Degenerative Diseases, 2011Co-Authors: Jessica C Gardner, Naheed Kanuga, Tom R. Webb, Anthony G. Robson, Graham E. Holder, Andrew Stockman, Caterina Ripamonti, Neil D. Ebenezer, Olufunmilola A. Ogun, Sophie DeveryAbstract:X-linked Cone and Cone-rod dystrophies (XLCOD and XLCORD) are an inherited group of retinal disorders primarily involving Cone photoreceptors. The most common cause is mutation of RPGR. In a British family with XLCOD, we mapped the disorder to Xq26.1-qter, excluding RPGR and other known retinal degeneration genes. The Cone Opsin gene array on Xq28 was a positional candidate locus. A novel missense mutation (c.529T > C; p.W177R) was identified in exon 3 of both the long wavelength-sensitive (OPN1LW; LW, red) and medium wavelength-sensitive (OPN1MW; MW, green) Cone Opsin genes, which segregated with disease. Exon 3 sequences of both genes were identical, derived from the OPN1MW gene by partial gene conversion. The amino acid W177 is conserved in all Opsins across species. We have shown that W177R in MW Opsin results in protein misfolding and retention in the endoplasmic reticulum (ER). Mutations in the OPN1LW /OPN1MW Cone Opsin gene array can therefore cause a spectrum of phenotypes, from colour blindness to progressive Cone dystrophy (XLCOD5).
Angelos Kalitzeos - One of the best experts on this subject based on the ideXlab platform.
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residual Cone structure in patients with x linked Cone Opsin mutations
Investigative Ophthalmology & Visual Science, 2018Co-Authors: Emily J Patterson, Angelos Kalitzeos, Melissa Kasilian, Jessica C Gardner, Jay Neitz, Alison J. HardcastleAbstract:Purpose To assess residual Cone structure in subjects with mutations in exon 2, 3, and 4 of the OPN1LW or OPN1MW Opsin.
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residual Cone structure in patients with x linked Cone Opsin mutations
Investigative Ophthalmology & Visual Science, 2018Co-Authors: Emily J Patterson, Angelos Kalitzeos, Melissa Kasilian, Jessica C Gardner, Jay Neitz, Alison J. HardcastleAbstract:Purpose To assess residual Cone structure in subjects with mutations in exon 2, 3, and 4 of the OPN1LW or OPN1MW Opsin. Methods Thirteen males had their OPN1LW/OPN1MW Opsin genes characterized. The Cone mosaic was imaged using both confocal and nonconfocal split-detection adaptive optics scanning light ophthalmoscopy (AOSLO), and retinal thickness was evaluated using optical coherence tomography (OCT). Six subjects completed serial imaging over a maximum period of 18 months and Cone density was measured across imaging sessions. Results Ten subjects had an OPN1LW/OPN1MW "interchange" Opsin mutation designated as LIAVA or LVAVA, which both introduce exon 3 splicing defects leading to a lack of functional photopigment in Cones expressing LIAVA and greatly reduced functional photopigment in Cones expressing LVAVA. Despite disrupted Cone reflectivity and reduced numerosity, residual inner segments could be visualized. Similar patterns were observed in individuals with an exon 2 insertion, or an exon 4 splice defect, both of which are also expected to produce Cones that are devoid of functional Opsin protein. OCT revealed variably reduced retinal thickness. A significant inverse relationship was found between the proportion of waveguiding Cones and axial length. Conclusions Split-detection imaging revealed that the altered appearance of the Cone mosaic in confocal images for subjects with exon 2, 3, and 4 mutations was generally due to disrupted waveguiding, rather than structural loss, making them possible candidates for gene therapy to restore Cone function. The relative fraction of waveguiding Cones was highly variable across subjects, which appears to influence emmetropization in these subjects.