Maureen Neitz

The human opsin gene cluster at Xq28 contains highly similar OPN1LW and OPN1MW genes essential for red-green color vision. Current molecular methods cannot accurately analyze this complex locus, limiting diagnosis of color vision deficiencies (CVD) and detection of carrier status. We performed Nanopore long-read sequencing of 206 individuals, comparing alignment-based analysis with targeted de novo assembly. Alignment-based methods performed poorly, whereas targeted assembly achieved 99% concordance for OPN1LW and 92% for OPN1MW copy numbers and resolved gene order in all XY individuals and 87% of XX individuals. This approach detected CVD in 3.2% of XY individuals and identified 8% of XX individuals as carriers, consistent with population estimates. Moreover, it molecularly explained the phenotypic severity in a family with Bornholm eye disease and clarified carrier status in an XX individual suspected of carrying two CVD haplotypes. Our approach provides a comprehensive, reference-free method for accurate analysis of expressed opsin genes and reliable CVD carrier detection.

Red–green color vision deficiency (CVD) is the most common single-locus genetic disorder in humans, but our ability to accurately diagnose the subtype and severity of red–green CVD in the clinic is limited. The most widely used diagnostic tools are subject to both Type I and Type II errors, while highly accurate tests are expensive, time-consuming, and not widely available. In this study, we present an iPhone-based color matching test that uses a combination of optics and software to achieve the diagnostic accuracy of an anomaloscope and the convenience of pseudoisochromatic plates. In validation testing, the device correctly diagnosed 100% of participants, as verified by genetic testing.

Aims: To evaluate the myopia control efficacy of Diffusion Optics Technology (DOT) spectacle lenses in children over a 4-year treatment period. Methods: CYPRESS Part 1 (NCT03623074) was a 3-year multicentre, randomised, controlled, double-masked trial comparing two investigational spectacle lens DOT designs (Test 1, Test 2) and standard single vision Control lenses in 256 North American children aged 6–10 years. Children completing Part 1 (n=200) were invited to enrol in CYPRESS Part 2 (NCT04947735) for an additional 1-year period. In Part 2, Test 1 (n=35) and Control groups (n=42) continued with their original lens assignment and the Test 2 group (n=21) were crossed over to Test 1 (DOT 0.2) lenses. The co-primary endpoints were change from baseline in axial length (AL) and cycloplegic spherical equivalent refraction (cSER). Results: Test 1 spectacle lenses demonstrated superiority to the Control in both co-primary endpoints: with a difference between means (Test 1−Control) of −0.13 mm for AL (p=0.018) and 0.33 D for cSER (p=0.008) in Part 1 and −0.05 mm for AL (p=0.038) and 0.13 D for cSER (p=0.043) in Part 2. Comparing treatment effects in Part 1 and 2 suggests that COVID-19 public health restrictions negatively impacted treatment efficacy in study years 2 and 3. Conclusion: DOT 0.2 spectacle lenses are safe and effective at reducing myopia progression, with additional benefit evident in year 4 of wear. These results support the hypothesis that a mild reduction in retinal contrast can slow myopia progression in young children. The unprecedented disruption in participant schooling and lifestyle during the COVID-19 pandemic may have depressed treatment efficacy in Part 1.

We are writing to address errors of misrepresentation in the article “ON and OFF receptive field processing in the presence of optical scattering” [ Biomed. Opt. Express 14, 2618 (2023)10.1364/BOE.489117 ]. In their investigation of predictions of “contrast theory” to explain the efficacy of diffusion optics technology (DOT), a myopia control lens design [ Br. J. Ophthalmol. 107, 1709 (2023)10.1136/bjo-2021-321005 ], Breher et al. incorrectly indicated that our contrast theory proposed that the association between cone opsin gene splicing defects and myopia was due to differential involvement in ON- and OFF-visual pathways. In addition, the Authors write that we have “hypothesized enhanced ON contrast sensitivity in myopes,” but we predict the opposite.

The irreducible unique hues—red, green, blue, and yellow—remain one of the great mysteries of vision science. Attempts to create a physiologically parsimonious model that can predict the spectral locations of the unique hues all rely on at least one post hoc adjustment to produce appropriate loci for unique green and unique red, and struggle to explain the non-linearity of the Blue/Yellow system. We propose a neurobiological color vision model that overcomes these challenges by using physiological cone ratios, cone-opponent normalization to equal-energy white, and a simple adaptation mechanism to produce color-opponent mechanisms that accurately predict the spectral locations and variability of the unique hues.

As commercially available glasses for color vision deficiency (CVD) are classified as low risk, they are not subject to stringent marketing regulations. We investigate how EnChroma and VINO glasses affect performance on the Colour Assessment and Diagnosis (CAD) test in individuals with CVD. Data were obtained from 51 individuals with red-green CVD. Blood or saliva samples were collected to examine the structure of the OPN1LW/OPN1MW array. Individuals completed the CAD test twice without glasses and once with each pair of glasses. Although there was a statistically significant effect of both glasses, only that of VINO could be considered functionally meaningful.

Nearsightedness (myopia) is a global health problem of staggering proportions that has driven the hunt for environmental and genetic risk factors in hopes of gaining insight into the underlying mechanism and providing new avenues of intervention. Myopia is the dominant risk factor for leading causes of blindness, including myopic maculopathy and retinal detachment. The fundamental defect in myopia—an excessively elongated eyeball—causes blurry distance vision that is correctable with lenses or surgery, but the risk of blindness remains. Haplotypes of the long-wavelength and middle-wavelength cone opsin genes (OPN1LW and OPN1MW, respectively) that exhibit profound exon-3 skipping during pre-messenger RNA splicing are associated with high myopia. Cone photoreceptors expressing these haplotypes are nearly devoid of photopigment. Conversely, cones in the same retina that express non-skipping haplotypes are relatively full of photopigment. We hypothesized that abnormal contrast signals arising from adjacent cones differing in photopigment content stimulate axial elongation, and spectacles that reduce contrast may significantly slow myopia progression. We tested for an association between spherical equivalent refraction and OPN1LW haplotype in males of European ancestry as determined by long-distance PCR and Sanger sequencing and identified OPN1LW exon 3 haplotypes that increase the risk of common myopia. We also evaluated the effects of contrast-reducing spectacles lenses on myopia progression in children. The work presented here provides new insight into the cause and prevention of myopia progression.

Red–green color vision deficiency (CVD) is the most common single locus genetic disorder in humans, affecting approximately 8% of males and 0.4% of females [G. H. M. Waaler, Acta Ophthalmol. 5, 309 (2009)10.1111/j.1755-3768.1927.tb01016.x ]; however, only about 1/4 of CVD individuals are dichromats who rely on only two cone types for color vision. The remaining 3/4 are anomalous trichromats whose CVD is milder, being based on three cone types, and who still perform remarkably well on many color-based tasks. To illustrate this, we have developed an algorithm that computes the relative loss of color discrimination in red-green CVD individuals with varying degrees of deficiency and accurately simulates their color experience for color normal observers. The resulting simulation illustrates the large gap in color discrimination between dichromats and even the most severe anomalous trichromats, showing that, relative to dichromats, the majority of anomalous trichromats can function without aids for color vision deficiency.