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Purpose: Achromatopsia (ACHM) is a genetically heterogenous relatively stationary congenital autosomal recessive cone disorder characterized typically by photophobia, low vision, nystagmus, hyperopia, grossly normal retinal appearance, and absent photopic responses by full-field electroretinography. Incomplete forms occur as well. This study investigates the genetic basis of clinically suspected ACHM in the United Arab Emirates., Methods: Retrospective case series (January 2016-December 2023) of patients with (1) clinically suspected ACHM or (2) mutations in ACHM-associated genes ( CNGA3 , CNGB3 , GNAT2 , PDE6C , PDE6H , AT6 )., Results: Twenty-two clinically suspected patients (19 probands) were identified. Biallelic disease genes and the number of probands were CNGA3 (9), CNGB3 (6), PDE6C (1), GNAT2 (1), RGS9BP (1), and CNNM4 (1). Some mutant alleles were recurrent across different families. Two probands had their diagnoses revised after genetic testing and phenotypic reassessment to RGS9BP -related bradyopsia and CNNM4 -related Jalili syndrome. Three additional cases (making 22 total probands) were identified from ACHM gene mutation review-one each related to PDE6C , to AT6 , and to CNGB3 in concert with CNGA3 (triallelic disease). All three presented with macular discoloration, an atypical finding for classic ACHM., Conclusion: CNGA3 was the single most frequent implicated gene. Bradyopsia and Jalili syndrome can resemble incomplete ACHM. Recurrent mutant alleles may represent founder effects. Macular discoloration on presentation can occur in PDE6C -related disease, AT6 -related disease, and triallelic CNGB3 / CNGA3 -related disease. The possibility for triallelic disease exists and requires genetic counseling beyond that of simple autosomal recessive inheritance.

Purpose: To evaluate whether colour vision normal (CVN) adults pass two Fletcher-Evans (CAM) lantern tests and to investigate the impact of imposed blur on Ishihara, CAM lantern and computerised colour discrimination test (colour assessment and diagnosis test [CAD] and Cambridge colour test [CCT]) results., Methods: In a pilot experiment, 20 (16 CVN and 4 colour vision deficient [CVD]) participants with normal VA were tested with the CAM lantern. In the main experiment, the impact of imposed dioptric blur (up to +8.00 D) on visual acuity and the Ishihara test, CAM lantern, CAD and CCT was assessed for 15 CVN participants., Results: CVN participants can fail the CAM lantern, with specificity of 81.25% (aviation mode) and 75% (clinical mode), despite following the test requirements of participants having at least 0.18 logMAR (6/9) in the better eye. With blur, test accuracy was affected. As expected, significant detrimental effects of blur on test results were found for logMAR VA and CAM lantern (aviation) with +1.00 D or higher. Ishihara, CAD and CCT results were not detrimentally affected until +8.00 D. Yellow-blue discrimination was more affected by blur for the CAD than the CCT, which was not explained by the different colour spaces used or vectors tested., Conclusion: False-positive findings on lantern colour vision tests with small apertures are likely to be increased in patients with blur due to uncorrected refractive error or ocular and visual pathway disease. Other colour vision tests with larger stimuli are more robust to blur., (© 2024 The Author(s). Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.)

Purpose: To describe the phenotype of Danish patients with genetically verified achromatopsia (ACHM) with special focus on signs of progression on structural or functional parameters, and possible genotype-phenotype correlations., Methods: Forty-eight patients were identified, with disease-causing variants in five different genes: CNGA3, CNGB3, GNAT2, PDE6C and PDE6H. Longitudinal evaluation was possible for 11 patients and 27 patients participated in a renewed in-depth phenotyping consisting of visual acuity assessment, optical coherence tomography (OCT), fundus autofluorescence, colour vision evaluation, contrast sensitivity, mesopic microperimetry and full-field electroretinography. Foveal morphology was evaluated based on OCT images for all 48 patients using a grading system based on the integrity of the hyperreflective photoreceptor band, the inner segment ellipsoid zone (ISe). Signs of progression were evaluated based on longitudinal data and correlation with age., Results: We found a statistically significant positive correlation between OCT grade and age (Spearman ρ = 0.62, p < 0.0001) and we observed changes in the foveal morphology in 2 of 11 patients with ≥5 years of follow-up. We did not find any convincing correlation between age and functional parameters (visual acuity, retinal sensitivity and contrast sensitivity) nor did we find correlation between structural and functional parameters, or any clear genotype-phenotype correlation., Conclusions: Some patients with ACHM demonstrate signs of progressive foveal changes in OCT characteristics with increasing age. This is relevant in terms of possible new treatments. However, functional characteristics, such as visual acuity, remained stable despite changing foveal structure. Thus, seen from a patient perspective, ACHM can still be considered a non-progressive condition., (© 2024 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

In natural scenes, visual discrimination of colored surfaces by individuals with X-linked dichromacy is known to be only a little poorer than in normal trichromacy. This surprising result may be related to the properties of the colors of these scenes, like the shape and orientation of the color gamut, uneven frequency, and a considerable variation in lightness. It is unclear, however, how much each of these factors contributes to the small impairment in discrimination, in particular, what is the contribution of the orientation of the gamut. We measured the discrimination of colors from natural scenes by six normal trichromats and six dichromats. Colors were drawn either from the original color gamut of the scenes or from gamut-rotated versions of the scenes. Pairs of colors were randomly drawn from hyperspectral images of one rural and one urban environment and presented on a screen. As expected, dichromats were only a little poorer than normal trichromats at discrimination but the disadvantage varied systematically with the orientation of the color gamut by a factor of about three with a minimum around a yellow-green axis. Dichromats also took longer to respond, and the response times were modulated with the orientation of the color gamut in a similar way as the loss in discrimination. For the scenes tested here, these results imply an important impact of the orientation of the gamut on discrimination. They also indicate that the predominantly yellow-blue orientation of the gamut of natural scene might not be optimal for discrimination in dichromacy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Achromatopsia is an inherited retinal disease that affects 1 in 30,000-50,000 individuals and is characterised by an absence of functioning cone photoreceptors from birth. This results in severely reduced visual acuity, no colour vision, marked sensitivity to light and involuntary oscillations of the eyes (nystagmus). In most cases, a single gene mutation prevents normal development of cone photoreceptors, with mutations in the CNGB3 or CNGA3 gene being responsible for ∼80 % of all patients with achromatopsia. There are a growing number of studies investigating recovery of cone function after targeted gene therapy. These studies have provided some promise for patients with the CNGA3 mutation, but thus far have found limited or no recovery for patients with the CNGB3 mutation. Here, we developed colour-calibrated visual stimuli designed to isolate cone photoreceptor responses. We combined these with adapted fMRI techniques and pRF mapping to identify if cortical responses to cone-driven signals could be detected in 9 adult patients with the CNGB3 mutation after receiving gene therapy. We did not detect any change in brain activity after gene therapy when the 9 patients were analysed as a group. However, on an individual basis, one patient self-reported a change in colour perception, corroborated by improved performance on a psychophysical task designed to selectively identify cone function. This suggests a level of cone sensitivity that was lacking pre-treatment, further supported by a subtle but reliable change in cortical activity within their primary visual cortex., Competing Interests: Declaration of Competing Interest Michel Michaelides consults for MeiraGTx and Jansen Pharmaceuticals and has equity in MeiraGTx., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this exploratory study is to investigate the role of S-cones in oscillatory potentials (OPs) generation by individuals with blue-cone monochromacy (BCM), retaining S-cones, and achromatopsia (ACHM), lacking cone functions., Methods: This retrospective study analyzed data from 39 ACHM patients, 20 BCM patients, and 26 controls. Central foveal thickness was obtained using spectral-domain optical coherence tomography, while amplitude and implicit time (IT) of a- and b-waves were extracted from the ISCEV Standard dark-adapted 3 cd.s.m -2 full-field ERG (ffERG). Time-frequency analysis of the same measurement enabled the extraction of OPs, providing insights into the dynamic characteristics of the recorded signal., Results: Both ACHM and BCM groups showed a significant reduction (p < .00001) of a- and b-wave amplitudes and ITs as well as the power of the OPs compared to the control groups. The comparison between ACHM and BCM didn't show any statistically significant differences in the electrophysiological parameters. The analysis of covariance revealed significantly reduced central foveal thickness in the BCM group compared to ACHM and controls (p < .00001), and in ACHM compared to controls (p < .00001), after age correction and Tukey post-hoc analysis., Conclusions: S-cones do not significantly influence OPs, and the decline in OPs' power is not solely due to a reduced a-wave. This suggests a complex non-linear network influenced by photoreceptor inputs. Morphological changes don't correlate directly with functional alterations, prompting further exploration of OPs' function and physiological role., (© 2024. The Author(s).)

Significance: Imposing a time limit on the Farnsworth D15 test may prevent patients from compromising the test., Purpose: This study aimed to investigate the effect of test time on the Farnsworth D15 color vision test in unpracticed and practiced subjects and determine an optimal test time., Methods: Twenty-one subjects (mean/standard deviation age, 33.1/9.3 years) with a range of congenital color vision deficiency participated in the study. Pseudoisochromatic plate screening, Farnsworth D15, and anomaloscope testing were performed for classification purposes. At each of 2 visits, 10 trials of the Farnsworth D15 were performed with a range in test times from 30 seconds to 10 minutes. Between visits, subjects practiced the test. Major crossovers were used as the outcome measure. A repeated-measures analysis of variance compared the scores across trials. Post hoc Dunnett's testing analyzed the pairwise data., Results: Although no significant difference in the mean number of major crossovers was found across the 10 trials for the first visit ( F (9, 180) = 1.30, p=0.24), a significant difference was found for the second visit ( F (9, 180) = 4.77, p<0.001). The range of mean number of major crossovers for the second visit was 1.71 to 5.1, with the 30-second trial resulting in the largest number of major crossovers and the longest trial resulting in the smallest number of major crossovers. Analysis showed that a 2-minute time limit resulted in a Farnsworth D15 outcome that would be expected based on the anomaloscope for a majority of subjects., Conclusions: In this study, test time was found to affect performance in practiced subjects but not in unpracticed subjects. Based on this study, we recommend enforcing a time limit of 2 minutes to discourage those who try to pass the Farnsworth D15 through practice. Additional measures, such as recording patient behavior, can also be taken., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2024 American Academy of Optometry.)

Objective assessment of the visual system can be performed electrophysiologically using the visual evoked potential (VEP). In many clinical circumstances, this is performed using high contrast achromatic patterns or diffuse flash stimuli. These methods are clinically valuable but they may only assess a subset of possible physiological circuitries within the visual system, particularly those involved in achromatic (luminance) processing. The use of chromatic VEPs (cVEPs) in addition to standard VEPs can inform us of the function or dysfunction of chromatic pathways. The chromatic VEP has been well studied in human health and disease. Yet, to date our knowledge of their underlying mechanisms and applications remains limited. This likely reflects a heterogeneity in the methodology, analysis and conclusions of different works, which leads to ambiguity in their clinical use. This review sought to identify the primary methodologies employed for recording cVEPs. Furthermore cVEP maturation and application in understanding the function of the chromatic system under healthy and diseased conditions are reviewed. We first briefly describe the physiology of normal colour vision, before describing the methodologies and historical developments which have led to our understanding of cVEPs. We thereafter describe the expected maturation of the cVEP, followed by reviewing their application in several disorders: congenital colour vision deficiencies, retinal disease, glaucoma, optic nerve and neurological disorders, diabetes, amblyopia and dyslexia. We finalise the review with recommendations for testing and future directions., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Achromatopsia is an autosomal recessive cone dysfunction syndrome, characterized by absence of color discrimination, low visual acuity, photophobia, and nystagmus. Achromatopsia constitutes a common cause of visual impairment in children, with a prevalence of 1:30,000 worldwide., Objective: To characterize the clinical characteristics of achromatopsia, the main genes causing the disease in our population and the clinical course of the disease, with an emphasis on visual function stability with increasing age., Methods: Retrospective study based on medical charts of patients with achromatopsia. Patients were divided into two groups according to their age at last follow-up: older and younger than 10 years. A subset of patients with long term follow-up were analyzed separately, with patients being described in both age groups., Results: Seventy-six patients were included in the study. The mean age was 14.28 years. Variants in the CNGA3 gene were the most common (73.6%). Clinical characteristics included photophobia (96.2%), nystagmus (93.6%), hypermetropia (72.3%) and strabismus (51.1%). In the large cohort there was no correlation of age with visual acuity ( p  = 0.129). In the separate subset cohort with long follow-up there was a relative improvement in visual acuity with age ( p  < 0.001)., Conclusions: CNGA3 is the main gene associated with achromatopsia in our population (around ∼ 73%), which is in contrast to the distribution worldwide (∼ 25%). Most achromats suffer from photophobia and nystagmus, and the main refractive error is hypermetropia. Achromatopsia's natural course seems to be stationary, and there may even be a slight improvement in visual acuity with time., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Visual function comprises three principles: light sensation, color sensation, and minimum separable sensation. Although clinical evaluation of light sensation and visual acuity have been remarkably developed through comprehensive application of various methods, the test methods to evaluate color sensation in the clinical field have not reflected these various significant developments after their recommendation at the International Congress of Ophthalmology in 1933. To date, various research methods in color vision have been invented on the basis of clinical evaluation methods, most of which were limited to laboratory investigations and were not applied to the clinical field. In this review, the author focuses on both the currently clinical available evaluation methods and the clinically applicable methods based on the present laboratory research studies., (© 2024. Japanese Ophthalmological Society.)

Purpose: To evaluate mesopic and photopic contrast sensitivity in patients with congenital red-green color vision deficiency regarding with and without glare conditions and to compare these findings with age- and gender-matched healthy controls with normal color vision., Methods: Patients with congenital red-green color vision deficiency and age- and gender-matched healthy controls were included in this cross-sectional comparative study. Contrast sensitivity measurements were taken from all subjects in 4 different conditions; binocular mesopic-without glare, mesopic-with glare, photopic-without glare, photopic-with glare, and the results were compared., Results: Twenty one patients with color vision deficiency (13 deuteranopic, 8 protanopic) and 22 age- and gender-matched healthy controls were included in the study. The mean age was 35.2 ± 13.5 years in the protan group, 30.6 ± 7.7 years in the deutan group, 32.0 ± 8.8 years in the control group, and there was no significant difference in age between the groups (P > 0.05). The mean mesopic and photopic contrast sensitivity values of the groups at all spatial frequencies (1.5, 3, 6, 12, 18 cpd) were not statistically significant when evaluated by the multifactor repeated measures test of ANOVA to evaluate the effect of light conditions (with and without glare) (P > .05)., Conclusion: Mesopic and photopic contrast sensitivity values of patients with congenital red-green color vision deficiency were similar to healthy controls regarding with and without glare conditions., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background/aim: Congenital color vision deficiency (CCVD) is an eye disease characterized by abnormalities in the cone cells in the photoreceptor layer. Visual evoked potentials (VEPs) are electrophysiological tests that physiologically examine the optic nerve, other visual pathways, and the visual cortex. The aim of this research was to determine whether there are VEP abnormalities in CCVD patients., Methods: Patients with CCVD and healthy individuals were included in this prospective case-control study. Participants with eye disease or neurodegenerative disease were excluded from the study. Pattern reversal VEP (PVEP), flash VEP (FVEP), and optical coherence tomography were performed on all participants., Results: Twenty healthy individuals (15 male) and 21 patients with CCVD (18 male) were included in the study. The mean ages of healthy individuals and patients with CCVD were 29.8 ± 9.6 and 31.1 ± 10.9 years (p = 0.804). Retinal nerve fiber layer thickness and central macular thickness values did not differ between the two groups. In PVEP, Right P100, Left N75, P100, N135 values were delayed in CCVD patients compared to healthy individuals (p = 0.001, p = 0.032, p = 0.003, p = 0.032). At least one PVEP and FVEP abnormality was present in nine (42.9%) and six (28.6%) of the patients, respectively. PVEP or FVEP abnormalities were found in 13 (61.9%) of the patients., Conclusion: This study indicated that there may be PVEP and FVEP abnormalities in patients with CCVD., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Significance: We report on photoaversion and patient-reported quality of life in Danish patients with achromatopsia and evaluate the best optical rehabilitation. Our results contribute to the evaluation of outcome measures in therapy trials and aid in providing the best optical rehabilitation for patients with this and clinically similar conditions., Purpose: This study aimed to investigate the vision-related quality of life, the impact of photoaversion on daily living, and the best optical rehabilitation in a cohort of achromatopsia patients, including testing the hypothesis that red light-attenuating filters are generally preferred., Methods: Patients with genetically verified achromatopsia were recruited. Investigations included the 25-item Visual Function Questionnaire and supplementary questions regarding photoaversion and visual aids. Patients were evaluated by a low vision optometrist and given the choice between different light-attenuating filters. First, two specially designed red and gray filters both transmitting 6% light, and then a pre-defined broader selection of filters. Best-corrected visual acuity and contrast sensitivity were measured without filters and with the two trial filters., Results: Twenty-seven patients participated. Median 25-item Visual Function Questionnaire composite score was 73, with the lowest median score in the subscale near vision (58) and the highest in ocular pain (100). The majority of patients (88%) reported that light caused them discomfort, and 92% used aid(s) to reduce light. Ninety-six percent (26 of 27) preferred the gray filter to the red indoors; 74% (20 of 27) preferred the gray filter. Contrast sensitivity was significantly better with the gray filter compared with no filter (p=0.003) and the red filter (p=0.002)., Conclusions: Our cohort has a relatively high vision-related quality of life compared with other inherited retinal diseases, but photoaversion has a large impact on visual function. Despite what could be expected from a theoretical point of view, red filters are not generally preferred., Competing Interests: Conflict of Interest Disclosure: None of the authors have any financial conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Optometry.)

Primary congenital glaucoma is a rare disease that occurs in early birth and can lead to low vision. Evaluating affected children is challenging and there is a lack of studies regarding color vision in pediatric glaucoma patients. This cross-sectional study included 21 eyes of 13 children with primary congenital glaucoma who were assessed using the Farnsworth D-15 test to evaluate color vision discrimination and by spectral domain optical coherence tomography to measure retinal fiber layer thickness. Age, visual acuity, cup-to-disc ratio and spherical equivalent data were also collected. Global and sectional circumpapillary and macular retinal fiber layer thicknesses were measured and compared based on color vision test performance. Four eyes (19%) failed the color vision test with diffuse dyschromatopsia patterns. Only age showed statistical significance in color vision test performance. Global and sectional circumpapillary and macular retinal fiber layer thicknesses were similar between the color test outcomes dyschromatopsia and normal. While the color vision test could play a role in assessing children with primary congenital glaucoma, further studies are needed to correlate it with damage to retinal fiber layer thickness., (© 2024. The Author(s).)

Purpose: Non-human primates (NHPs) are useful models for human retinal disease. Chromatic pupillometry has been proposed as a noninvasive method of identifying inherited retinal diseases (IRDs) in humans; however, standard protocols employ time-consuming dark adaptation. We utilized shortened and standard dark-adaptation protocols to compare pupillary light reflex characteristics following chromatic stimulation in rhesus macaques with achromatopsia to wild-type (WT) controls with normal retinal function., Methods: Nine rhesus macaques homozygous for the p.R656Q mutation (PDE6C HOMs) and nine WT controls were evaluated using chromatic pupillometry following 1-minute versus standard 20-minute dark adaptations. The following outcomes were measured and compared between groups: pupil constriction latency, peak constriction, pupil constriction time, and constriction velocity., Results: Pupil constriction latency was significantly longer in PDE6C HOMs with red-light (P = 0.0002) and blue-light (P = 0.04) stimulation versus WT controls. Peak constriction was significantly less in PDE6C HOMs with all light stimulation compared to WT controls (P < 0.0001). Pupil constriction time was significantly shorter in PDE6C HOMs versus WT controls with red-light (P = 0.04) and white-light (P = 0.003) stimulation. Pupil constriction velocity was significantly slower in PDE6C HOMs versus WT controls with red-light (P < 0.0001), blue-light (P < 0.0001), and white-light (P = 0.0002) stimulation. Dark adaptation time only significantly affected peak (P = 0.008) and time of pupil constriction (P = 0.02) following blue-light stimulation., Conclusions: Chromatic pupillometry following 1- and 20-minute dark adaptation is an effective tool for screening NHPs for achromatopsia., Translational Relevance: Rapid identification of NHPs with IRDs will provide animal research models to advance research and treatment of achromatopia in humans.

Hue and luminance contrast are basic visual features. Here we use multivariate analyses of magnetoencephalography data to investigate the timing of the neural computations that extract them, and whether they depend on common neural circuits. We show that hue and luminance-contrast polarity can be decoded from MEG data and, with lower accuracy, both features can be decoded across changes in the other feature. These results are consistent with the existence of both common and separable neural mechanisms. The decoding time course is earlier and more temporally precise for luminance polarity than hue, a result that does not depend on task, suggesting that luminance contrast is an updating signal that separates visual events. Meanwhile, cross-temporal generalization is slightly greater for representations of hue compared to luminance polarity, providing a neural correlate of the preeminence of hue in perceptual grouping and memory. Finally, decoding of luminance polarity varies depending on the hues used to obtain training and testing data. The pattern of results is consistent with observations that luminance contrast is mediated by both L-M and S cone sub-cortical mechanisms., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Purpose: To explore the relationship of color vision deficiency with myopia progression and axial elongation in Chinese primary school children during a five-year cohort study., Methods: A total of 2849 grade 1 students (aged 7.1 ± 0.4 years) from 11 primary schools were enrolled and followed up for five years. Cycloplegic autorefraction and axial length were measured annually. Color vision testing was performed using Ishihara's test and the City University color vision test., Results: The prevalence of color vision deficiency was 1.68%, with 2.81% in boys and 0.16% in girls. Color-deficient cases consisted of 91.6% deutan and 8.3% protan. Over the five years, the cumulative incidence of myopia was 35.4% (17/48) in the color-vision deficiency group, which was lower than the 56.7% (1017/1794) in the color normal group (P = 0.004). Over the five-year study period, the change in spherical equivalent refraction in the color vision-deficiency group (-1.81 D) was also significantly lower than that in the color normal group (-2.41 D) (P = 0.002)., Conclusions: The lower incidence and slower progression of myopia in children with color-vision deficiency over the five-year follow-up period suggest that color-deficient individuals are less susceptible to myopia onset and development.

Background : Bornholm eye disease (BED) is a rare X-linked cone dysfunction disorder with high myopia, amblyopia, and color vision defects. Materials and methods: Visual and ocular outcomes in a family where two of five siblings had molecularly confirmed BED are reported. Ophthalmological assessments included best-corrected visual acuity (BCVA), color vision test, and optical coherence tomography (OCT). Medical records, electroretinography (ERG), and genetic analyses were re-evaluated. Results: Two male siblings had confirmed BED with myopia and protanopia. The younger brother had high myopia, subnormal BCVA, and ocular fundi that showed tilted discs, crescent shaped peripapillary atrophy, and visible choroidal vessels. OCT confirmed retinal and choroidal atrophy. The older brother was lightly myopic with normal/subnormal BCVA and subtle findings in the fundi. Both brothers had abnormal ERG recordings with a decreased cone response. They also had a structurally intact OPN1LW/OPN1MW gene cluster. The OPN1LW gene was shown to carry a deleterious variant combination in exon 3 known to result in mis-splicing of opsin mRNA and acknowledged as LIAVA amino acid delineation (Leu153-Ile171-Ala174-Val178-Ala180), while the OPN1MW gene exon 3 showed a non-pathogenic variant combination (MVVVA). Another normal-sighted brother carried another wildtype variant combination (LVAIS) in exon 3 of the OPN1LW gene. Conclusions: The two affected brothers demonstrated a large variability in their phenotypes even though the genotypes were identical. They presented a disease-associated haplotype in exon 3 of OPN1LW that has been described as the molecular cause of BED.

The ability of the adult human brain to develop function following correction of congenital deafferentation is controversial. Specifically, cases of recovery from congenital visual deficits are rare. CNGA3 -achromatopsia is a congenital hereditary disease caused by cone-photoreceptor dysfunction, leading to impaired acuity, photoaversion, and complete color blindness. Essentially, these patients have rod-driven vision only, seeing the world in blurry shades of gray. We use the uniqueness of this rare disease, in which the cone-photoreceptors and afferent fibers are preserved but do not function, as a model to study cortical visual plasticity. We had the opportunity to study two CNGA3 -achromatopsia adults (one female) before and after ocular gene augmentation therapy. Alongside behavioral visual tests, we used novel fMRI-based measurements to assess participants' early visual population receptive-field sizes and color regions. Behaviorally, minor improvements were observed, including reduction in photoaversion, marginal improvement in acuity, and a new ability to detect red color. No improvement was observed in color arrangement tests. Cortically, pretreatment, patients' population-receptive field sizes of early visual areas were untypically large, but were decreased following treatment specifically in the treated eye. We suggest that this demonstrates cortical ability to encode new input, even at adulthood. On the other hand, no activation of color-specific cortical regions was demonstrated in these patients either before or up to 1 year post-treatment. The source of this deficiency might be attributed either to insufficient recovery of cone function at the retinal level or to challenges that the adult cortex faces when computing new cone-derived input to achieve color perception. SIGNIFICANCE STATEMENT The possibility that the adult human brain may regain or develop function following correction of congenital deafferentation has fired the imagination of scientists over the years. In the visual domain, cases of recovery from congenital deficits are rare. Gene therapy visual restoration for congenital CNGA3 -achromatopsia, a disease caused by cone photoreceptor dysfunction, gave us the opportunity to examine cortical function, to the best of our knowledge for the first time, both before and after restorative treatment. While behaviorally only minor improvements were observed post-treatment, fMRI analysis, including size algorithms of population-receptive fields, revealed cortical changes, specifically receptive field size decrease in the treated eyes. This suggests that, at least to some degree, the adult cortex is able to encode new input., (Copyright © 2021 the authors.)

Anomalous trichromacy is a common form of congenital color deficiency resulting from a genetic alteration in the photopigments of the eye's light receptors. The changes reduce sensitivity to reddish and greenish hues, yet previous work suggests that these observers may experience the world to be more colorful than their altered receptor sensitivities would predict, potentially indicating an amplification of post-receptoral signals. However, past evidence suggesting such a gain adjustment rests on subjective measures of color appearance or salience. We directly tested for neural amplification by using fMRI to measure cortical responses in color-anomalous and normal control observers. Color contrast response functions were measured in two experiments with different tasks to control for attentional factors. Both experiments showed a predictable reduction in chromatic responses for anomalous trichromats in primary visual cortex. However, in later areas V2v and V3v, chromatic responses in the two groups were indistinguishable. Our results provide direct evidence for neural plasticity that compensates for the deficiency in the initial receptor color signals and suggest that the site of this compensation is in early visual cortex., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the validity, reproducibility, and feasibility of the "Color Vision Evaluation Test" (CVET) for the diagnosis of congenital dyschromatopsia., Design: Prospective, monocentric, sensitivity, and specificity analysis study comparing the CVET with the Farnsworth 15 Hue standard test (15 Hue STF)., Methods: A total of 155 children from the Paediatric University Hospital of Nice were screened (both eyes) using Ishihara's pseudoisochromatic cards, which allowed dividing them into a dyschromatic group and a control group. All children underwent twice the 15 Hue STF and the CVET with at least 7 days between both series of tests., Results: Patients' mean age was 7.56 ± 3.51 years in the dyschromatic group and 8.92 ± 2.9 years in the control group. At the first evaluation, the sensitivity and specificity were 95.7% and 96.4%, respectively, for the CVET and 75% and 58.9%, respectively, for the 15 Hue STF (P < .001). The reproducibility of the CVET was 100%, whereas that of the 15 Hue STF was 88.4% (P = .01). The mean test explanation duration was 18.8 seconds for the CVET and 17.7 seconds for the 15 Hue STF (P = .3). In the dyschromatic group, the mean duration of the CVET was always significantly longer than that of the 15 Hue STF (P < .001). The children subjectively preferred to undergo the CVET rather than the 15 Hue STF in 84.6% of cases (P < .001)., Conclusions: The CVET is a rapid, reliable, and reproducible test for the diagnosis of congenital dyschromatopsia. It is accessible to young children., (Copyright © 2020 Elsevier Inc. All rights reserved.)

To evaluate the changes in functional vision in patients with resolved endophthalmitis. This was a cross-sectional study. The study included 20 patients with resolved endophthalmitis and best-corrected visual acuity of 20/100 or better. Visual acuity (VA), contrast threshold (CT), red/green (RG) and yellow/blue (YB) colour vision and 15 Hz flicker modulation threshold (FMT) were assessed using standard psychophysical techniques. The median age was 54 years. The median visual acuity was 0.27 (~ 20/40-Snellen Equivalent) ((interquartile range [IQR]), 0.30) logMAR). The median log contrast threshold (CT) was - 1.13 (IQR, 0.36) log units (normative value for age-matched CT: - 1.61 log units). The median red/green (RG) and yellow/blue (YB) thresholds were 11.52 (IQR, 26.19) and 9.45 (IQR, 16.20) CAD units respectively, which were at least 5 times higher than age-matched normative RG and YB thresholds. The median central cone- mediated FMT was 17.64% (IQR, 23.40%), which was much higher compared to age-matched FMT (5.48% [IQR, 3.47]). Linear regression revealed significant relationship between contrast thresholds and foveal thickness (y = 0.001x-1.47, R 2  = 0.20, p = 0.048). Though endophthalmitis may resolve with a good visual acuity, deficits in visual functions like chromatic discrimination, cone-mediated flicker and contrast sensitivity persist.

Some aspects of vision after correcting the longitudinal chromatic aberration (LCA) of the eye are not yet completely understood. For instance, correcting the LCA notably alters the through focus visual acuity (VA) curve, but it does not improve the best VA obtained for the natural case. In this work, vision with corrected LCA is further investigated by using an adaptive optics visual simulator (AOVS). VA was measured continuously during 20 minutes in 5 subjects under both natural and corrected LCA conditions to explore possible adaptation effects. Low contrast VA as a function of time exhibited a consistent and significant boost of 0.19 in decimal scale after an average time of 10.9 minutes of continuous testing. For high contrast, only one subject showed a similar increase in VA. These results suggest that some LCA neural adaptation may exist, particularly for low contrast. This adaptation impacts the performance of vision under corrected LCA, and possibly prevents measurement for immediate visual benefit. The results have practical implications for the design and visual testing of optical aids, especially those correcting, or altering, the LCA.

Significance: The options that can help patients with congenital color vision defect, to a better professional and leisure adaptation, are very limited. Different haploscopic lenses can be considered, and their effects need to be investigated in patients with different defects., Purpose: The purpose of this study was to present and discuss the effect of a pair of asymmetric long-pass filters fitted for deuteranopia, with the result of a 60% improvement in distinguishing red-green plates when compared with baseline., Case Report: We report the case of a 51-year-old man with congenital deuteranopia fitted with haploscopic ChromaGen filters. During the 2-month follow-up, we observed a decrease in left-eye logMAR visual acuity and contrast sensitivity with an increased ability to discriminate the plates of different color vision tests (Ishihara, Farnsworth, and Hardy-Rand-Rittler). The visual outcomes are discussed considering the spectral sensitivity curves of each filter, measured with a spectrophotometric device., Conclusions: This report describes an improvement in the ability to resolve color vision plates after using asymmetric haploscopic filters showing a left-eye decrease in logMAR visual acuity and contrast sensitivity function. Subjects with a history of color vision deficiency might benefit from using haploscopic filters that selectively minimize the transmittance within a specific bandwidth to improve the color discrimination in deutan color vision deficiency. The simultaneous analysis of the color vision outcomes and transmittance spectrum of the haploscopic filters might contribute to a better understanding of the mechanisms behind the claimed efficacy of these devices.

Purpose: To describe a patient with combined central serous chorioretinopathy and achromatopsia., Methods: Clinical examination, enhanced depth imaging- optical coherence tomography, fundus autofluorescence, fluorescein angiography and electroretinography were used to study a 33-year-old female presented with the complaint of poor vision since childhood in both eyes, which worsened in the left eye (LE) recently., Results: In slit-lamp examination, there was a macular elevation in the LE and macular pigmentary change as well as optic disk pallor in both eyes. Enhanced depth imaging optical coherence tomography revealed central inner/outer segment (IS/OS) disruptions, subretinal fluid and thick choroid. Accessory tests included the full-field ERG with severe reduced photopic response (with relatively normal scotopic responses) and fluorescein angiography (FA), which found distinct leakage points in OD and barely visible hyperfluorescent spots in OS. Based on the history of nystagmus, lifelong stable poor vision, loss of foveal cone thickness with IS/OS disruption and severe reduced photopic response with relatively normal scotopic responses, we determined that the diagnosis was most consistent with achromatopsia (ACHM). On the other hand, OCT and FA findings show the simultaneous occurrence of pachychoroid-related central serous chorioretinopathy in this patient., Conclusion: This case highlights a case of CSC and ACHM.

Achromatopsia is an inherited retinal disease characterized by loss of cone photoreceptor function. Day blind CNGA3 mutant Improved Awassi sheep provide a large animal model for achromatopsia. This study measured refractive error and axial length parameters of the eye in this model and evaluated chromatic pupillary light reflex (cPLR) testing as a potential screening test for loss of cone function. Twenty-one CNGA3 mutant, Improved Awassi, 12 control Afec-Assaf and 12 control breed-matched wild-type (WT) Awassi sheep were examined using streak retinoscopy and B-mode ocular ultrasonography. Four CNGA3 mutant and four Afec-Assaf control sheep underwent cPLR testing. Statistical tests showed that day-blind sheep are significantly more myopic than both Afec-Assaf and WT Awassi controls. Day-blind sheep had significantly longer vitreous axial length compared to WT Awassi (1.43 ± 0.13 and 1.23 ± 0.06 cm, respectively, p < 0.0002) and no response to bright red light compared to both controls. Lack of response to bright red light is consistent with cone dysfunction, demonstrating that cPLR can be used to diagnose day blindness in sheep. Day-blind sheep were found to exhibit myopia and increased vitreous chamber depth, providing a naturally occurring large animal model of myopia.

Purpose: To evaluate the colour vision severity classification standard 'CIE 143:2001 International recommendations for colour vision requirements in transport' (CIE 143:2001), which has become out of date because of the lack of commercial availability of required colour vision tests., Methods: One-hundred-five subjects had colour vision tested and colour vision severity classified according to a modified CIE 143:2001 algorithm that included pseudoisochromatic plates (Ishihara's test and Hardy Rand Rittler (HRR) 4th edition), Optec 900 lantern and Farnsworth D-15. Subject's results and colour vision severity classification were compared to performance and colour vision severity classification on the computerized 'Colour Assessment and Diagnosis' (CAD) test., Results: According to CIE 143:2001, using Ishihara's test, Optec lantern and Farnsworth D 15, 11 subjects (10%) were category I (normal), 16 (15%) were category II (mild), 48 (46%) were category III (poor), and 30 (29%) were category IV (severe). Classified by CAD score, 10 (10%) were category I, 11 (10%) were category II, 41 (39%) were category III, and 43 (41%) were category IV. The correlation between the two estimates of the severity of colour vision loss (i.e. CIE 143:2001 and CAD) was high, with a Kendall's Tau test of 0.81 (τ = 0.81 p < 0.001). A suggested CIE 143:2001 classification including new CAD score limits improves the classification correlation to 0.90 (τ = 0.90 p < 0.001) for all diagnoses., Conclusion: The colour vision severity classification standard 'CIE 143:2001 International recommendations for colour vision requirements in transport', has not implemented new diagnostic tools with better accuracy. We propose three possible revisions to the CIE 143:2001 algorithm, based on the availability of CAD: (1) Replacing the current CIE 143:2001 algorithm using new CAD threshold limits, (2) Use of CAD as a secondary test to Ishihara's test and HRR or (3) Revising the current CIE 143:2001 algorithm using Ishihara's test, HRR, Optec 900 and FD15., (© 2020 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Many studies have examined how color and luminance information are processed in the visual system. It has been observed that chromatic noise masked luminance discrimination in trichromats and that luminance thresholds increased as a function of noise saturation. Here, we aimed to compare chromatic noise inhibition on the luminance thresholds of trichromats and subjects with severe deutan or protan losses. Twenty-two age-matched subjects were evaluated, 12 trichromats and 10 with congenital color vision impairment: 5 protanopes/protanomalous, and 5 deuteranopes/deuteranomalous. We used a mosaic of circles containing chromatic noise consisting of 8 chromaticities around protan, deutan, and tritan confusion lines. A subset of the circles differed in the remaining circles by the luminance arising from a C-shaped central target. All the participants were tested in 4 chromatic noise saturation conditions (0.04, 0.02, 0.01, 0.005 u'v' units) and 1 condition without chromatic noise. We observed that trichromats had an increasing luminance threshold as a function of chromatic noise saturation under all chromatic noise conditions. The subjects with color vision deficiencies displayed no changes in the luminance threshold across the different chromatic noise saturations when the noise was composed of chromaticities close to their color confusion lines (protan and deutan chromatic noise). However, for tritan chromatic noise, they were found to have similar results to the trichromats. The use of chromatic noise masking on luminance threshold estimates could help to simultaneously examine the processing of luminance and color information. A comparison between luminance contrast discrimination obtained from no chromatic and high-saturated chromatic noise conditions could be initially undertaken in this double-duty test.

Purpose: Genetic variation in PDE6C is associated with achromatopsia and cone dystrophy, with only a few reports of cone-rod dystrophy in the literature. We describe two pediatric and two adult patients with PDE6C related cone and cone-rod dystrophy and the first longitudinal data of a pediatric patient with PDE6C-related cone dystrophy., Methods: This cohort of four patients underwent comprehensive ophthalmologic evaluation at the National Eye Institute's Ophthalmic Genetics clinic, including visual field testing, retinal imaging and electroretinogram (ERG). Next-generation sequencing-based genetic testing was performed and subsequent analysis of the variants was done through three-dimensional protein models generated by Phyre2 and Chimera., Results: All cases shared decreased best-corrected visual acuity and poor color discrimination. Three of the four patients had a cone-rod dystrophy, presenting with an ERG showing decreased amplitude on both photopic and scotopic waveforms and a mild to moderately constricted visual field. One of the children was diagnosed with cone dystrophy, having a preserved peripheral field. The children had none to minor structural retinal changes, whereas the adults had clear macular dystrophy., Conclusions: PDE6C-related cone-rod dystrophy consists of a severe phenotype characterized by early-onset nystagmus, decreased best-corrected visual acuity, poor color discrimination, progressive constriction of the visual field, and night blindness. Our work contributes with valuable information toward understanding the visual prognosis and allelic heterogeneity of PDE6C-related cone and cone-rod dystrophy.

Purpose: Chromatic visual evoked potentials (cVEP) primarily reflect the parvocellular visual pathway function, which has been shown to be predominantly affected in demyelinating disease (DD). The purpose of this study was to evaluate cVEP responses and to compare them with other structural and functional findings in young patients with DD., Methods: Thirty patients (8-28 years of age) with DD with or without a history of optic neuritis (ON) were investigated. Twenty-five eyes had at least one episode of ON (ON-group) and 35 eyes had no clinically evident episode of ON (nON-group). OCT imaging was performed using a high-resolution spectral-domain OCT (SD-OCT), measuring retinal nerve fiber layer (RNFL) thickness. Pattern reversal electroretinography (PERG) and visual evoked potentials (VEP) were recorded according to the ISCEV standard, and chromatic visual evoked potentials (cVEP) were recorded to isoluminant red-green (R-G) and blue-yellow (B-Y) 7° circle stimuli, composed of horizontal sinusoidal gratings with spatial frequency 2 cycles/°, 90% chromatic contrast and onset-offset (300:700 ms) mode of stimulation. Structural and functional measures were analyzed and compared between the groups., Results: Both general (G) and temporal (T) RNFL thicknesses were reduced below normal limits in most of the eyes. However, in the ON-group (G: 77.5 ± 20.6, T: 51.4 ± 23.4 µm), the thinning was more significant (p < 0.001) than in the nON-group (G: 95.4 ± 12.1, T: 70.1 ± 11.5 µm). PERG N95 was within normal limits in the nON-group, while it was significantly more affected in the ON-group (7.4 ± 1.0 vs. 5.1 ± 2.0 μV; p < 0.0001). Similarly, also VEP P100 latency and amplitude showed a greater percentage of abnormality in the ON-group, the latency being longer (117.2 ± 16.9 vs. 99.4 ± 4.6 ms; p < 0.0001) and the amplitude lower (9.1 ± 5.1 vs. 16.4 ± 7.5 μV; p < 0.0001). The cVEP N-wave amplitude to R-G and B-Y stimuli was reduced below normal limits in both ON- and nON-groups; however, cVEP to B-Y stimulation were slightly more affected in the ON-group (4.0 ± 3.8 vs. 5.9 ± 3.3 µm; p = 0.02). A positive correlation between cVEP amplitude and RNFL thickness and between cVEP amplitude and PERG N95 amplitude, as well as a strong negative correlation between cVEP amplitude and P100 latency was observed., Conclusions: These findings demonstrate that cVEP indicate early abnormality of parvocellular pathway function in eyes with or without a history of optic neuritis and can be used together with other structural and functional parameters to evaluate visual pathway integrity of young patients with DD.

Some doctors with severe congenital colour vision deficiency (CCVD) may experience difficulty in colour discrimination that can affect their decision-making. In the absence of evidence-based guidelines, learners with CCVD are arbitrarily debarred from specialising in some disciplines. This cross-sectional, anonymous, questionnaire-based study asked specialists from all over the country if doctors with CCVD should avoid specialising in their respective disciplines. Of 218 responses, 80 (36.7%) said they should avoid it, citing colour discrimination as critical. The 32 (14.7%) participants who were unsure and 106 (48.6%) who said that CCVD would not be a problem gave reasons that mirrored those in the literature: the degree of deficiency is variable; experience helps; automation, history-taking, close observation, good illumination, contrast, touch, and peer-corroboration can reduce dependency on colour. Awareness of the deficiency and finding ways to compensate for it during training may mitigate errors and safeguard patients. Instead of blocking people with CCVD from admission to some specialties, specialists should consider these findings and support learners who are aware of their deficiency and still wish to specialise in a particular discipline.

Significance: Enchroma glasses were designed to improve color vision among color-blind individuals. The putative aid of such optic filters in alleviating color blindness remains to be demonstrated. Our study shows that the beneficial impacts on color discrimination are quite small in comparison to the undesirable effects., Purpose: Congenital color blindness is a common genetic anomaly, and there is still no effective aid for affected people. Enchroma glasses are selective filters designed to enhance color discrimination among red-green color-blind individuals. However, there is a lack of data supporting their efficiency. The present study aimed to characterize the effect of Enchroma filters on color discrimination., Methods: Colorimetric coordinates of figures from a pseudoisochromatic (American Optical Hardy-Rand-Rittler [AO H-R-R]) test were measured. Nine color-blind and five control adult participants performed the AO H-R-R test and a color-naming task using monochromatic stimuli. All data were collected with and without Enchroma filters., Results: Colorimetric coordinates of AO H-R-R figures were shifted out of their respective pseudoisochromatic line. The AO H-R-R error scores of participants with color blindness were not clearly improved by the filters except for the protanopic subgroup. However, the filters promoted a change in the classification of the defect, specifically by increasing protan errors in deutan participants. In the color-naming task, Enchroma filters impaired perception in all participants, specifically for cyan stimuli., Conclusions: Enchroma filters may affect the nature of a color vision deficiency without necessarily alleviating its severity. Although the performance of protan participants increased in the pseudoisochromatic task with Enchroma filters, this was the only improvement observed across tasks and subgroups. In summary, this study does not support the efficacy of Enchroma filters in correcting color discrimination in color-blind individuals.

Purpose: To characterize the progression of optical gaps and expand the known etiologies of this phenotype., Design: Retrospective cohort study., Methods: Thirty-six patients were selected based on the identification of an optical gap on spectral-domain optical coherence tomography (OCT) from a large cohort of patients (N = 746) with confirmed diagnoses of inherited retinal dystrophy. The width and height of the gaps in 70 eyes of 36 patients were measured by 2 independent graders using the caliper tool on Heidelberg Explorer. Measurements of outer and central retinal thickness were also evaluated and correlated with gap dimensions., Results: Longitudinal analysis confirmed the progressive nature of optical gaps in patients with Stargardt disease, achromatopsia, occult macular dystrophy, and cone dystrophies (P < .003). Larger changes in gap width were noted in patients with Stargardt disease (78.1 μm/year) and cone dystrophies (31.9 μm/year) compared with patients with achromatopsia (16.2 μm/year) and occult macular dystrophy (15.4 μm/year). Gap height decreased in patients with Stargardt disease (6.5 μm/year; P = .02) but increased in patients with achromatopsia (3.3 μm/year) and occult macular dystrophy (1.2 μm/year). Gap height correlated with measurements of central retinal thickness at the fovea (r = 0.782, P = .00012). Interocular discordance of the gap was observed in 7 patients. Finally, a review of all currently described etiologies of optical gap was summarized., Conclusion: The optical gap is a progressive phenotype seen in an increasing number of etiologies. This progressive nature suggests a use as a biomarker in the understanding of disease progression. Interocular discordance of the phenotype may be a feature of Stargardt disease and cone dystrophies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To investigate the long-term natural history of retinal function of achromatopsia (ACHM)., Methods: Subjects with molecularly confirmed ACHM were recruited in a prospective cohort study of mesopic microperimetry. Coefficient of repeatability and intraclass correlation coefficient (ICC) of mean sensitivity (MS) were calculated. Best-corrected visual acuity (BCVA), bivariate contour ellipse area (BCEA), contrast sensitivity (CS), MS, total volume (VTOT), and central field volume (V5°) from volumetric and topographic analyses were acquired. Correlation of functional parameters with structural findings from optical coherence tomography (OCT) was performed., Results: Eighteen subjects were recruited. Mean follow-up was 7.2 years. The MS test-retest repeatability coefficient was 1.65 decibels (dB), and the ICC was 0.973 (95% confidence interval, 0.837-0.98). Mean MS was similar for right and left eyes (16.97dB and 17.14dB, respectively). A negative significant correlation between logMAR BCVA and the retinal sensitivity indices (MS, VTOT, V5°) was found. A significant negative correlation between logCS and MS, VTOT, and V5° was also observed. BCVA and BCEA improved during follow-up. Mean CS, MS, VTOT, and V5° at final follow-up were similar to baseline. MS was similar between CNGA3- and CNGB3-ACHM. Patients with and without the presence of a foveal ellipsoid zone on OCT had similar MS (16.64 dB and 17.17 dB, respectively)., Conclusions: We demonstrate a highly reproducible assessment of MS. Retinal function including MS, volumetric indices, and CS are stable in ACHM. Improvement of fixation stability and small changes of BCVA over time may be part of the natural history of the disease.

For over 150 years, spectrally selective filters have been proposed to improve the vision of observers with color vision deficiencies [1]. About 6% of males and <1% of females have anomalies in their gene arrays coded on the X chromosome that result in significantly decreased spectral separation between their middle- (M-) and long- (L-) wave sensitive cone photoreceptors [2]. These shifts alter individuals' color-matching and chromatic discrimination such that they are classified as anomalous trichromats [3, 4]. Broad-band spectrally selective filters proposed to improve the vision of color-deficient observers principally modify the illuminant and are largely ineffective in enhancing discrimination or perception because they do not sufficiently change the relative activity of M- and L-photoreceptors [5, 6]. Properly tailored notch filters, by contrast, might increase the difference of anomalous M- and L-cone signals. Here, we evaluated the effects of long-term usage of a commercial filter designed for this purpose on luminance and chromatic contrast response, estimated with a signal detection-based scaling method. We found that sustained use over two weeks was accompanied by increased chromatic contrast response in anomalous trichromats. Importantly, these improvements were observed when tested without the filters, thereby demonstrating an adaptive visual response. Normal observers and a placebo control showed no such changes in contrast response. These findings demonstrate a boosted chromatic response from exposure to enhanced chromatic contrasts in observers with reduced spectral discrimination. They invite the suggestion that modifications of photoreceptor signals activate a plastic post-receptoral substrate that could potentially be exploited for visual rehabilitation., Competing Interests: Declaration of Interests KK holds shares in EnChroma®. The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: To evaluate the effects of the ChromaGen contact lens (CCL) on best-corrected visual acuity, contrast sensitivity and pseudoisochromatic test plate performance in patients with congenital colour vision deficiency (CVD)., Methods: CCLs were inserted into 50 eyes of 25 patients with congenital red-green CVD. The patients were tested with the Ishihara and Hardy-Rand-Rittler test plates before and after the insertion of Magenta 2, Magenta 3, and Violet 3 CCLs. The patients' mean numbers of recognised symbols were calculated and the most appropriate CCL was determined for each eye. The best-corrected visual acuity for both far and near vision and contrast sensitivity were evaluated before and after the insertion of the appropriate CCLs, and the results were compared., Results: The mean age of the patients was 26.56 ± 10.30 years. While all CCLs increased the mean numbers of recognised symbols on the Ishihara (p < 0.001 for all), Magenta 3 was observed to be the most useful CCL. On the other hand, while all CCLs increased the mean numbers of recognised symbols on Hardy-Rand-Rittler (p < 0.001 for all), Magenta 2 and Magenta 3 were detected as the most useful CCLs. After insertion of the most appropriate CCL for each eye, the mean best-corrected visual acuity for both far and near vision were decreased (p < 0.001 for both). Statistically significant alterations were also detected at some spatial frequencies of contrast sensitivity measurements., Conclusion: CCLs decrease the far and near best-corrected visual acuity, and static and dynamic contrast sensitivity at some spatial frequencies, and invalidate the pass criteria of pseudoisochromatic test plates by increasing the number of recognised symbols., (© 2019 Optometry Australia.)

Background: The clinical phenotyping of patients with achromatopsia harboring variants in phosphordiesterase 6C (PDE6C) has poorly been described in the literature. PDE6C encodes the catalytic subunit of the cone phosphodiesterase, which hydrolyzes the cyclic guanosine monophosphate that proceeds with the hyperpolarization of photoreceptor cell membranes, as the final step of the phototransduction cascade., Methods: In the current study, two patients from a consanguineous family underwent full ophthalmologic examination and molecular investigations including WES. The impact of the variant on the functionality of the protein has been analyzed using in silico molecular modeling., Results: The patients identified with achromatopsia segregated a homozygous missense variant (c.C1775A:p.A592D) in PDE6C gene located on chromosome 10q23. Molecular modeling demonstrated that the variant would cause a protein conformational change and result in reduced phosphodiesterase activity., Conclusion: Our data extended the phenotypic spectrum of retinal disorders caused by PDE6C variants and provided new clinical and genetic information on achromatopsia.

Background: Abnormalities and contrast sensitivity have already been studied in schizophrenia. However, the relationship between symptom severity in schizophrenia and colour vision sensitivity has not been studied systematically. Aim: Our objective was to evaluate colour discrimination in patients with schizophrenia compared to controls and examine if this colour discrimination is correlated with schizophrenia symptoms' severity. Methods: This case-control study, performed between January and April 2017, included 50 schizophrenic patients and 50 healthy controls matched for age and sex. The Positive and Negative Symptoms Scale (PANSS) was used to determine the schizophrenia symptoms' severity. Colour discrimination was evaluated using the total error score (TES) generated using the Farnsworth D-15 test. The higher the TES, the more severe colourblindness. Results: A significantly higher mean TES was found in schizophrenics (30.32) compared to healthy patients (13.07) ( p  < 0.001). Colour blindness was correlated to the severity of schizophrenic symptoms only in the subgroup of patients with severe schizophrenia. Conclusion: Colour vision defect is a common feature in schizophrenia, and may be more significant when related to psychotic symptoms.KEY POINTSA significantly higher mean TES was found in schizophrenics compared to healthy patients.Colour blindness was correlated to the severity of schizophrenic symptoms only in the subgroup of patients with severe schizophrenia.Colour vision defect is a common feature in schizophrenia, and may be more significant when related to psychotic symptoms.

Color provides valuable information about the environment, yet the exact mechanisms explaining how colors appear to us remain poorly understood. Retinal signals are processed in the visual cortex through high-level mechanisms that link color perception with top-down expectations and knowledge. Here, we review the neuroimaging evidence about color processing in the brain, and how it is affected by acquired brain lesions in humans. Evidence from patients with brain-damage suggests that high-level color processing may be divided into at least three modules: perceptual color experience, color naming, and color knowledge. These modules appear to be functionally independent but richly interconnected, and serve as cortical relays linking sensory and semantic information, with the final goal of directing object-related behavior. We argue that the relations between colors and their objects are key mechanisms to understand high-level color processing.

Importance: Achromatopsia linked to variations in the CNGA3 gene is associated with day blindness, poor visual acuity, photophobia, and involuntary eye movements owing to lack of cone photoreceptor function. No treatment is currently available., Objective: To assess safety and vision outcomes of supplemental gene therapy with adeno-associated virus (AAV) encoding CNGA3 (AAV8.CNGA3) in patients with CNGA3-linked achromatopsia., Design, Setting, and Participants: This open-label, exploratory nonrandomized controlled trial tested safety and vision outcomes of gene therapy vector AAV8.CNGA3 administered by subretinal injection at a single center. Nine patients (3 per dose group) with a clinical diagnosis of achromatopsia and confirmed biallelic disease-linked variants in CNGA3 were enrolled between November 5, 2015, and September 22, 2016. Data analysis was performed from June 6, 2017, to March 12, 2018., Intervention: Patients received a single unilateral injection of 1.0 × 1010, 5.0 × 1010, or 1.0 × 1011 total vector genomes of AAV8.CNGA3 and were followed up for a period of 12 months (November 11, 2015, to October 10, 2017)., Main Outcomes and Measures: Safety as the primary end point was assessed by clinical examination of ocular inflammation. Systemic safety was assessed by vital signs, routine clinical chemistry testing, and full and differential blood cell counts. Secondary outcomes were change in visual function from baseline in terms of spatial and temporal resolution and chromatic, luminance, and contrast sensitivity throughout a period of 12 months after treatment., Results: Nine patients (mean [SD] age, 39.6 [11.9] years; age range, 24-59 years; 8 [89%] male) were included in the study. Baseline visual acuity letter score (approximate Snellen equivalent) ranged from 34 (20/200) to 49 (20/100), whereas baseline contrast sensitivity log scores ranged from 0.1 to 0.9. All 9 patients underwent surgery and subretinal injection of AAV8.CNGA3 without complications. No substantial safety problems were observed during the 12-month follow-up period. Despite the congenital deprivation of cone photoreceptor-mediated vision in achromatopsia, all 9 treated eyes demonstrated some level of improvement in secondary end points regarding cone function, including mean change in visual acuity of 2.9 letters (95% CI, 1.65-4.13; P = .006, 2-sided t test paired samples). Contrast sensitivity improved by a mean of 0.33 log (95% CI, 0.14-0.51 log; P = .003, 2-sided t test paired samples)., Conclusions and Relevance: Subretinal gene therapy with AAV8.CNGA3 was not associated with substantial safety problems and was associated with cone photoreceptor activation in adult patients, as reflected by visual acuity and contrast sensitivity gains., Trial Registration: ClinicalTrials.gov Identifier: NCT02610582.

Significance: This research shows that some color-vision-defective patients could identify railway signal lights correctly if they are working in the yard where sighting distances for signal lights are shorter., Purpose: When interpreting railway signal lights, sighting distance can vary depending on the employee's location and job requirements. Individuals with a color-vision-defect may pass railroad employment color vision testing for positions with shorter sighting distances, despite failing to qualify for positions with longer sighting distances. The CN Lantern (CNLan) simulates railway signal lights. We evaluated performance and repeatability on CNLan at different viewing distances in color-normal and color-deficient individuals., Methods: Fifty-six subjects with normal color vision and 63 subjects with a red-green color-vision-defect participated. The CNLan test was performed at 4.6-, 2.3-, 1.15-, and 0.57-m viewing distance. The test was repeated after 10 days., Results: All individuals with normal color vision passed the CNLan at all distances at both visits without errors. For the group with a color-vision-defect, the pass rate increased from 12% at 4.6 m to 62% at 0.57 m. The repeatability of the CNLan between visits for the color-vision-defective group was very good with AC1 agreement values greater than 0.85., Conclusions: An increase in retinal illumination was likely responsible for the improved performance as the test distance was decreased. Typical sighting distances in railway yards correspond to the 0.57-m test distance in our study. The results of this study suggest that 62% of the individuals with a red-green color-vision-defect may correctly identify colored signal lights in a railway yard where sighting distances are less than 100 m.

Significance: This research will help clinicians in advising their color-vision-defective patients regarding their career options., Purpose: In Canadian railways, individuals with a color-vision-defect (CVD) may qualify for positions at shorter sighting distance from signal lights. The railway companies' medical units use the CN Lantern (CNLan) test, and there is little information available as to whether clinical color-vision tests (CCVTs) can predict the CNLan results. This study determines the ability of some CCVTs to predict the CNLan performance to assist clinicians in advising their CVD patients regarding career options., Methods: The CNLan viewing distance was varied between 4.6 and 0.57 m using a geometric progression. The CCVTs were the Hardy, Rand, and Rittler; Ishihara; ColorDx pseudoisochromatic plate (PIP); the Rabin Cone Contrast Test; Color Assessment and Diagnosis; Cambridge Color Vision Test; U.S. Air Force Operational Based Vision Assessment Cone Contrast Test; Farnsworth Munsell D15; and ColorDx D15. Fifty-six normal-color-vision and 63 CVD subjects participated in this study., Results: Failure of either the Farnsworth Munsell D15 or ColorDx D15 essentially guarantees failure on the CNLan at the 4.6-m distance. The agreement values decreased as the viewing distance decreased., Conclusions: To counsel patients regarding a career as a locomotive engineer, clinicians should have either the Hardy, Rand, and Rittler or ColorDx PIP and a D15 test. For patients applying for a position in the yard, a mild-to-moderate classification CVD on HRR or ColorDx PIP indicates a high probability of passing CNLan.

Purpose: To evaluate structural grading and quantitative segmentation of foveal hypoplasia using handheld OCT, versus preferential looking (PL), as predictors of future vision in preverbal children with infantile nystagmus., Design: Longitudinal cohort study., Participants: Forty-two patients with infantile nystagmus (19 with albinism, 17 with idiopathic infantile nystagmus, and 6 with achromatopsia) were examined., Methods: Spectral-domain handheld OCT was performed in preverbal children up to 36 months of age. Foveal tomograms were graded using our 6-point grading system for foveal hypoplasia and were segmented for quantitative analysis: photoreceptor length, outer segment (OS) length, and foveal developmental index (FDI; a ratio of inner layers versus total foveal thickness). Patients were followed up until they could perform chart visual acuity (VA) testing. Data were analyzed using linear mixed regression models. Visual acuity predicted by foveal grading was compared with prediction by PL, the current gold standard for visual assessment in infants and young children., Main Outcome Measures: Grade of foveal hypoplasia, quantitative parameters (photoreceptor length, OS length, FDI), and PL VA were obtained in preverbal children for comparison with future chart VA outcomes., Results: We imaged 81 eyes from 42 patients with infantile nystagmus of mean age 19.8 months (range, 0.9-33.4 months; standard deviation [SD], 9.4 months) at the first handheld OCT scan. Mean follow-up was 44.1 months (range, 18.4-63.2 months; SD, 12.0 months). Structural grading was the strongest predictor of future VA (grading: r = 0.80, F = 67.49, P < 0.0001) compared with quantitative measures (FDI: r = 0.74, F = 28.81, P < 0.001; OS length: r = 0.65; F = 7.94, P < 0.008; photoreceptor length: r = 0.65; F = 7.94, P < 0.008). Preferential looking was inferior to VA prediction by foveal grading (PL: r = 0.42, F = 3.12, P < 0.03)., Conclusions: Handheld OCT can predict future VA in infantile nystagmus. Structural grading is a better predictor of future VA than quantitative segmentation and PL testing. Predicting future vision may avert parental anxiety and may optimize childhood development., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the effect of colour discrimination ability on the stereoscopic acuity by comparing individuals having congenital colour vision deficiency (CCVD) with healthy individuals., Design: A comparative study., Participants: The study included 53 binocular males, of whom 26 (mean age, 36.04 ± 9.30 years) were in the healthy group and 27 (mean age, 33.04 ± 9.81 years) were in the CCVD group., Methods: The following tests were used: the Ishihara pseudo-isochromatic plate test for detecting CCVD, the Farnsworth Munsell 100 (FM100) hue test for colour discrimination ability, the TNO and Titmus stereo tests for stereoscopic acuity., Results: In the CCVD group, 20 males were deutan and 7 males were protan. According to the FM100 hue test, total error score (TES), blue/yellow (b/y) local error score (LES), and red/green LES were significantly lower in the healthy group (30.23 ± 18.78, 15.15 ± 10.38, and 13.88 ± 11.93, respectively) than in the CCVD group (133.59 ± 67.45, 41.15 ± 22.03, and 89.15 ± 52.16, respectively) (p < 0.01 for each). The stereo test scores revealed significantly higher stereoscopic acuity in the healthy group (43.85 ± 33.92 arcsec for the TNO test and 40.00 ± 0.00 arcsec for the Titmus test) than in the CCVD group (93.33 ± 90.51 arcsec for TNO stereo test and 52.96 ± 24.62 arcsec for the Titmus test) (p < 0.05 for each). The TNO test score was significantly and positively correlated with the TES (r = 0.390, p = 0.049) and b/y LES (r = 0.490, p = 0.011) in the healthy group., Conclusions: Colour discrimination ability affected stereoscopic acuity. Moreover, stereoscopic acuity increased with increasing colour discrimination ability, which could be originated from the b/y colour region., (Copyright © 2019 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Here we present evidence implicating disrupted RNA splicing as a potential cause of inherited tritan color vision. Initially we tested 51 subjects for color vision deficiencies. One made significant tritan errors; the others were classified as normal trichromats. The putative tritan subject was the only one of the 51 subjects found to be heterozygous for an OPN1SW gene mutation that disrupts RNA splicing in an in vitro assay. In order to gather further support for the role of the splicing mutation in tritan color vision, the putative tritan subject's mother and sister were examined. They also made tritan errors and had the same OPN1SW gene mutation.

Color blindness is a condition of altered color perception, scientifically defined as "dyschromatopsia". Color blindness affects 8% of the world population. Color blindness is caused by an alteration of the cones that influences the vision of the color self (red, green, blue). A comparative study was conducted in dischromatopsic subjects identified during the course of the ordinary investigations directed towards the civil aero-navigating personnel by the Ophthalmology Department of the Air Force, between March 2019 and January 2020, at "Aldo Di Loreto" Institute of Aeronautical and Space Medicine of Rome. 10 subjects aged 20 to 50, with dyschromatopsia found at Ishihara's pseudoisochromatic tables, were submitted to Oculus HMC-Anomaloscope with a manual execution program and then a CAD test. Thus, in 2 out of 10 cases of dyschromatopsia, the Anomaloscope would have guided the medical judgement, while the CAD test would have oriented towards a judgment of full fitness despite the same lack of chromatic sensitivity however, underlined by both tests. In conclusion, the CAD test confirmed a highly sensitive and specific method of determining the presence and depth of the chromatic perception deficit but also the method was able to prevent the unjust refusal of certain air navigation activities to the aspirant staff., (©Romanian Society of Ophthalmology.)

We embed large-scale, plasmonic metasurfaces into off-the-shelf rigid gas permeable contact lenses and study their ability to serve as visual aids for color vision deficiency. In this study, we specifically address deuteranomaly, which is the most common class of color vision deficiency. This condition is caused by a redshift of the medium-type cone photoreceptor and leads to ambiguity in the color perception of red and green and their combinations. The effect of the metasurface-based contact lenses on the color perception was simulated using Commission Internationale de l'Eclairage (CIE) color spaces and conventional models of the human color-sensitive photoreceptors. Comparison between normal color vision and uncorrected and corrected deuteranomaly by the proposed element demonstrates the ability offered by the nanostructured contact lens to shift back incorrectly perceived pigments closer to the original pigments. The maximal improvement in the color perception error before and after the proposed correction for deuteranomaly is up to a factor of $\sim{10}$∼10. In addition, an Ishihara-based color test was also simulated, showing the contrast restoration achieved by the element, for deuteranomaly conditions.

Purpose: To investigate feasibility, reliability and discriminative validity of pseudoisochromatic (PIC) colour vision tests, the Mollon-Reffin minimalist (MRM) test and the Cambridge Colour Test (CCT) among children (3-10 years) with reduced visual acuity., Methods: Thirty-three patients with reduced visual acuity and 38 healthy control subjects with age-related normal visual acuity were recruited for this prospective study. Visual acuity in patients was reduced due to amblyopia, binocular maculopathy, or optic neuropathy. Tests were performed in a single 1-hr session., Results: All but two children successfully completed the PIC and MRM tests. Success rate for the CCT was lower, 87%, CI [72%, 96%] for control subjects and 79%, CI [61%, 91%] for patients, with a strong positive effect of age on the odds of successful completion (OR 5.63, p = 0.007). Reliability was high in PIC and MRM tests but comparably lower in CCT. The rate of correct answers in PIC tests was between 88% and 100%. One proband was diagnosed with deuteranomaly with an average Ishihara score of 21%. All children (with the exception of one daltonian) scored at least two points in the MRM test. Sensitivity thresholds in CCT decreased with age with a strong effect size in control subjects and weak to moderate effect size in patients., Conclusions: Pseudoisochromatic and MRM tests show sufficient feasibility in young children with reduced visual acuity. For CCT feasibility in 3-5-year olds is reduced, most probably due to the longer test duration. Consistent with earlier findings, colour discrimination thresholds decrease with age independent on visual acuity status., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose. This study was performed to determine achromatic contrast sensitivity and color vision in lead and zinc mine workers. Methods. A total of 230 male workers, who had been working in mine and had been in contact with minerals for at least 1 year, were considered as the case group, and the age of 90 years matched men who have not been in contact with minerals, being regarded as the control group. Contrast sensitivity was assessed using the Freiburg test at three frequencies of 1, 5 and 15 cycles of degree and under low mesopic light condition by two gratings and Landolt C stimuli. Color vision was assessed using the Farnsworth D-15 test under high mesopic light condition. Both tests were carried out monocularly. Data were analyzed using version 22 SPSS software. Results. There was a significant difference between studied groups with Landolt C stimulus in all three frequencies 1, 5 and 15 cycles per degree (p=0.009, p=0.016 and p=0.003). With Grating stimulus, there was a significant difference between the two groups in frequencies of 1 and 15 cycles per degree but at frequency of 5 cycles per degree, there was a border difference (p<0.0001, p=0.051 and p=0.008). A significant difference was observed between color confusion indexes of the two groups (p<0.0001). Conclusion. Chronic exposure to mineral in lead and zinc mine may cause color vision deficiency and decrease in contrast sensitivity. It is recommended that Farnsworth D-15 and Freiburg contrast sensitivity tests would be involved in the early diagnosis of neurodegenerative and visual disorders in workers exposed to minerals., (©Romanian Society of Ophthalmology.)