Longitudinal Assessment of OCT-Based Measures of Foveal Cone Structure in Achromatopsia.

Purpose: Achromatopsia (ACHM) is an autosomal recessive retinal disease associated with reduced or absent cone function. There is debate regarding the extent to which cone structure shows progressive degeneration in patients with ACHM. Here, we used optical coherence tomography (OCT) images to evaluate outer nuclear layer (ONL) thickness and ellipsoid zone (EZ) integrity over time in individuals with ACHM. Methods: Sixty-three individuals with genetically confirmed ACHM with follow-up ranging from about 6 months to 10 years were imaged using either Bioptigen or Cirrus OCT. Foveal cone structure was evaluated by assessing EZ integrity and ONL thickness. Results: A total of 470 OCT images were graded, 243 OD and 227 OS. The baseline distribution of EZ grades was highly symmetrical between eyes (P = 0.99) and there was no significant interocular difference in baseline ONL thickness (P = 0.12). The EZ grade remained unchanged over the follow-up period for 60 of 63 individuals. Foveal ONL thickness showed a clinically significant change in only 1 of the 61 individuals analyzed, although detailed adaptive optics imaging revealed no changes in cone density in this individual. Conclusions: ACHM appears to be a generally stable condition, at least over the follow-up period assessed here. As cones are the cellular targets for emerging gene therapies, stable EZ and ONL thickness demonstrate therapeutic potential for ACHM, although other aspects of the visual system need to be considered when determining the best timing for therapeutic intervention.

Statistical Evaluation of ERG Responses: A New Method to Validate Cycle-by-Cycle Recordings in Advanced Retinal Degenerations.

Purpose: To describe and evaluate a novel method to determine the validity of measurements made using cycle-by-cycle (CxC) recording techniques in patients with advanced retinal degenerations (RD) having low-amplitude flicker electroretinogram (ERG) responses. Methods: The method extends the original CxC recording algorithm introduced by Sieving et al., retaining the original recording setup and the preliminary analysis of raw data. Novel features include extended use of spectrum analysis, reduction of errors due to known sources, and a comprehensive statistical assessment using three different tests. The method was applied to ERG recordings from seven patients with RD and two patients with CNGB3 achromatopsia. Results: The method was implemented as a Windows application to processes raw data obtained from a commercial ERG system, and it features a computational toolkit for statistical assessment of ERG recordings with amplitudes as low as 1 µV, commonly found in advanced RD patients. When recorded using conditions specific for eliciting cone responses, none of the CNGB3 patients had a CxC validated response, indicating that no signal artifacts were present with our recording conditions. A comparison of the presented method with conventional 30 Hz ERG was performed. Bland-Altman plots indicated good agreement (mean difference, -0.045 µV; limits of agreement, 0.193 to -0.282 µV) between the resulting amplitudes. Within-session test-retest variability was 15%, comparing favorably to the variability of standard ERG amplitudes. Conclusions: This novel method extracts highly reliable clinical recordings of low-amplitude flicker ERGs and effectively detects artifactual responses. It has potential value both as a cone outcome variable and planning tool in clinical trials on natural history and treatment of advanced RDs.

Predicted effectiveness of EnChroma multi-notch filters for enhancing color perception in anomalous trichromats.

EnChroma filters are aids designed to improve color vision for anomalous trichromats. Their use is controversial because the results of lab-based assessments of their effectiveness have so far largely failed to agree with positive anecdotal reports. However, the effectiveness of EnChroma filters will vary depending on the conditions of viewing, including whether the stimuli are broadband reflective surfaces or colors presented on RGB displays, whether illumination spectra are broadband or narrowband, the transmission spectra of particular filters, and the cone spectral sensitivity functions of the observer. We created a model of anomalous trichromatic color vision to predict the effects of EnChroma filters on the color signals impaired in anomalous trichromacy. Using the model we varied illumination, filter type and observer cone sensitivity functions, and tested the effect of presenting colors as broadband reflective surfaces or on RGB displays. We also used hyperspectral images to assess the impact of the filters on anomalous trichromats' color vision for natural scenes. Model results predicted that the filters should be broadly effective at enhancing anomalous trichromats' equivalent to L/(L + M) chromatic contrasts under a range of viewing conditions, but are substantially more effective for deuteranomals than for protanomals. The filters are predicted to be more effective for broadband reflective surfaces presented under broadband illuminants than for surfaces presented under narrowband illuminants or for colors presented on RGB displays. Since the potential impacts of contrast adaptation and perceptual learning are not considered in the model, it needs to be empirically validated. Results of empirical tests of the effects of EnChroma filters on deuteranomalous color vision in comparison with model predictions are presented in an accompanying paper (Somers et al., in prep.).

Empirical tests of the effectiveness of EnChroma multi-notch filters for enhancing color vision in deuteranomaly.

Manufacturers of notch filter-based aids for color vision claim that their products can enhance color perception for people with anomalous trichromacy, a form of color vision deficiency (CVD). Anecdotal reports imply that people with CVD can have radically enhanced color vision when using the filters. However, existing empirical research largely focussed on the effect of notch filters on performance on diagnostic tests for CVD has not found that they have any substantial effect. Informed by a model of anomalous trichromatic color vision, we selected stimuli predicted to reveal the effects of EnChroma filters. Using these stimuli, we tested the ability of EnChroma filters to enhance color vision for 10 deuteranomalous trichromats in three experiments: 1. asymmetric color matching between test and control filter conditions, 2. color discrimination measured using four alternative forced-choice, and 3. color appearance measured using dissimilarity ratings to reconstruct subjective color spaces using multidimensional scaling. To investigate potential effects of long-term adaptation or perceptual learning, participants completed all three experiments at two time points, on first exposure to the filters, and after a week of regular use. We found a significant effect of the filters on color matches in the direction predicted by the model at both time points, implying that the filters can enhance the anomalous trichromatic color gamut. However, we found minimal effect of the filters on color discrimination at threshold. We found a significant effect of the filters in enhancing the appearance of colors along the red-green axis at the first time point, and a trend in the same direction at the second time point. Our results provide the first quantitative experimental evidence that notch filters can enhance color perception for anomalous trichromats.

Should Colour Vision Deficiency be a Factor for Considering Admission to Nursing Education Programs?

Null.

Novel ATF6 homozygous variant in a Chinese patient with achromatopsia.

BACKGROUND: ATF6-associated Achromatopsia (ACHM) is a rare autosomal recessive disorder characterized by reduction of visual acuity, photophobia, nystagmus, and poor color vision. METHODS: Detailed ophthalmological examinations were performed in a Chinese patient with ACHM. Whole exome sequencing and Sanger sequencing were performed to detect the disease-causing gene in the patient. RESULTS: A 6-year-old girl presented photophobia, low vision and reduced color discrimination. Small yellow lesion in the macula of both eyes was observed. FAF demonstrated hypofluorescence in the macular fovea. OCT images revealed interruption of ellipsoid and interdigitation zone in the foveal area and a loss of the foveal pit. ERG showed relatively normal rod responses and unrecordable cone responses. Sequencing result identified a novel splicing variant c.354 + 6T>C in the ATF6 gene (NM_007348.4). CONCLUSIONS: We reported detailed clinical features and genetic analysis of a new Chinese ATF6-associated patient with ACHM.

Prevalence and genotypic frequency of color vision defects among primary schoolchildren in Adama Town, Eastern Ethiopia.

Color vision deficiency is a common X-linked genetic disorder affecting the day-to-day lives of individuals, in which school-aged children's academic performance can be negatively affected. The aim of this study was to evaluate the prevalence and genotypic frequency of congenital color vision defects (CVD), among primary schoolchildren in Adama, Ethiopia. A school-based cross-sectional study design was used. Students were purposively selected based on their ethnicity but were randomly selected from their sections, resulting in a final sample size estimated at 846 schoolchildren who had received informed consent from their families. Data was gathered using the Ishihara color vision test, 38-plate edition. The result of the study revealed that the total prevalence of CVD was much higher (5.6%) among the male children than that of the females, which was only about 1.79%. The prevalence rates of CVD among the targeted ethnic groups were found to be the highest among Amhara (7.45%) > Oromo (5.00%) > Gurage (2.13%) children, respectively, in descending order. 62.76% of the study subjects were homozygous dominant (AA), followed by those with a heterozygous genotype (Aa) (32.51%), and the remaining 4.73% had recessive (aa) genes.

Structural and functional rescue of cones carrying the most common cone opsin C203R missense mutation.

An arginine to cysteine substitution at amino acid position 203 (C203R) is the most common missense mutation in human cone opsin. Linked to color blindness and blue cone monochromacy (BCM), C203 is involved in a crucial disulfide bond required for proper folding. It has previously been postulated that expression of mutant C203R cone opsin exerts a toxic effect on cone photoreceptors, similar to some well-characterized missense mutations in rhodopsin that lead to protein misfolding. In this study, we generated and characterized a BCM mouse model carrying the equivalent C203R mutation (Opn1mwC198R Opn1sw-/-) to investigate the disease mechanism and develop a gene therapy approach for this disorder. Untreated Opn1mwC198R Opn1sw-/- cones phenocopied affected cones in human patients with the equivalent mutation, exhibiting shortened or absent cone outer segments and loss of function. We determined that gene augmentation targeting cones specifically yielded robust rescue of cone function and structure when Opn1mwC198R Opn1sw-/- mice were treated at early ages. Importantly, treated cones displayed elaborated outer segments and replenished expression of crucial cone phototransduction proteins. Interestingly, we were unable to detect OPN1MWC198R mutant opsin at any age. We believe this is the first proof-of-concept study exploring the efficacy of gene therapy in BCM associated with a C203R mutation.

Colour perception develops throughout childhood with increased risk of deficiencies in children born prematurely.

AIM: To quantify the impact of prematurity on chromatic discrimination throughout childhood, from 2 to 15 years of age. METHODS: We recruited two cohorts of children, as part of the TrackAI Project, an international project with seven different study sites: a control group of full-term children with normal visual development and a group of children born prematurely. All children underwent a complete ophthalmological exam and an assessment of colour discrimination along the three colour axes: deutan, protan and trytan using a DIVE device with eye tracking technology. RESULTS: We enrolled a total of 1872 children (928 females and 944 males) with a mean age of 6.64 years. Out of them, 374 were children born prematurely and 1498 were full-term controls. Using data from all the children born at term, reference normative curves were plotted for colour discrimination in every colour axis. Pre-term children presented worse colour discrimination than full-term in the three colour axes (p < 0.001). Even after removing from the comparison, all pre-term children with any visual disorder colour discrimination outcomes remained significantly worse than those from full-term children. CONCLUSION: While colour perception develops throughout the first years of life, children born pre-term face an increased risk for colour vision deficiencies.

Rationally blind? Rationality polarizes policy support for colour blindness versus multiculturalism.

Do White Americans prefer society to be 'colour-blind' by rising above racial identities, or 'multicultural' by openly discussing and considering them? We developed an ideology-rationality model to understand support for these diversity perspectives. Specifically, since people endorse a diversity perspective in line with their ideological values, we hypothesized that conservatism is related to a relative preference for colour blindness over multiculturalism. However, since colour blindness and multiculturalism are complex and multi-layered ideologies, we further hypothesized that the relationship between conservatism and a preference for colour blindness over multiculturalism is especially pronounced under higher levels of rationality. Results confirmed the hypotheses, either when rationality was operationalized within a dual process theory (Study 1, N = 496) or experimentally induced within a tripartite model of cognition (Study 2, N = 497). Higher levels of rationality guided White Americans high in conservatism towards a stronger preference for colour-blindness, but those low in conservatism towards a stronger preference for multiculturalism. These results suggest that among White Americans the endorsement of colour blindness versus multiculturalism stems from the interplay between ideological orientation and rationality and that rational considerations about racial policies may further divide rather than unify along ideological lines.

Comparison of Two Printed Pseudoisochromatic Tests for Color Vision Assessment.

SIGNIFICANCE: The Waggoner PIP24 is a pseudoisochromatic test with a pattern similar to the Ishihara test. This study determined that the W-PIP24 can be used clinically to yield screening results (or sensitivity and specificity) comparable with the Ishihara. PURPOSE: This study aimed to determine whether the W-PIP24 is equivalent to the Ishihara 38 edition pseudoisochromatic test in detecting red-green color vision defects. Also, the performance of each plate of the W-PIP24 in detecting the color vision defects relative to the Ishihara test was determined. METHODS: Sixty-three individuals with congenital red-green color vision defects and 57 with normal trichromacy were recruited. Participants were tested with both the Ishihara and W-PIP24. The first-order agreement coefficients were calculated for the Ishihara and W-PIP24. The results were also analyzed using specificity, sensitivity, efficiency, and predictive pass and fail values. RESULTS: The agreement between the W-PIP24 and Ishihara test using the recommended criterion of using all plates was perfect. The sensitivity, specificity, predictive pass, and predictive fail were 1.00 (95% confidence interval, 0.94 to 1.00). CONCLUSIONS: This study showed that the W-PIP24 using a failure criterion of three or more errors on screening plates 1 to 15 is equivalent to the Ishihara test while screening for red-green color vision deficiency using a failure criterion of three or more errors on screening plates 1 to 17 of the Ishihara 38 edition.

Prevalence of Congenital Color Vision Deficiency in Southern Taiwan and Detection of Female Carriers by Visual Pigment Gene Analysis.

This study aimed to investigate the prevalence of color vision deficiencies (CVDs) and determine whether carriers could be detected by analyzing the visual pigment genes. Materials and Methods: The data of students who underwent routine CVD screening using the Ishihara color test in Kaohsiung, Southern Taiwan were analyzed. Furthermore, the DNA samples of 80 randomly selected females and four obligate carriers were analyzed. The most upstream genes, downstream genes, and the most downstream genes in the red/green pigment gene arrays were amplified separately using polymerase chain reaction (PCR), and exon 5 of each gene was analyzed. The prevalence of congenital red-green CVD in this study was 3.46% in males and 0.14% in females. The PCR analysis of the first gene, downstream gene, and last gene revealed normal patterns in 73 normal cases. Seven unusual patterns were detected in two proton carriers and five deutan carriers. Among the randomly selected females, 8.8% (7/80) were CVD carriers. The prevalence of CVD among male Taiwanese students in this study was 3.46%. Female carriers of congenital CVD can be identified by molecular analysis of the visual pigment genes. The proportion of CVD carriers among the randomly selected females was 8.8%, which was slightly higher than expected and further studies are warranted.

Color perception on Ishihara plates with red lenses in subjects with low vision due to retinal diseases.

Purpose: This study aimed to evaluate color perception (CP) changes on Ishihara plates following red-tinted contact lenses in subjects with low vision (LV) from retinal diseases. Methods: A cross-sectional observational study without control involved 84 subjects, aged 20-70 years, having LV from retinal diseases to examine CP changes following wearing red-tinted contact lenses. The subjects viewed Ishihara plates, with each eye separately, before and after wearing red lenses in two categories: "plates 1-21" and "plates 22-25". Change in CP with the use of a red lens was the primary outcome measure. Results: There was a significant increase in the number of plates read in both categories, that is, plates 1-21 (P = 0.002) and plates 22-25 (P = 0.032), the latter being used to diagnose the red-green defects. Although 70 eyes could read both digits on plates 22-25 and appeared to have normal color vision (CV) at baseline, this number rose to 99 eyes following the use of red-tinted lenses. There was a significant change in the type of CP (red defect/green defect/normal/undefined defect) (P = 0.022) with the application of a red-tinted lens. Conclusions: The use of red-tinted lenses caused a significant increase in the number of plates read, increased the number of subjects who appeared normal on plates 22-25, and significantly changed CP of LV subjects. These lenses can be a valuable aid for LV subjects. Although Ishihara plates can diagnose only red-green defects, further studies on CV testing techniques that detect both red-green and blue-yellow CV defects are recommended.

Achromatopsia-Visual Cortex Stability and Plasticity in the Absence of Functional Cones.

Purpose: Achromatopsia is a rare inherited disorder rendering retinal cone photoreceptors nonfunctional. As a consequence, the sizable foveal representation in the visual cortex is congenitally deprived of visual input, which prompts a fundamental question: is the cortical representation of the central visual field in patients with achromatopsia remapped to take up processing of paracentral inputs? Such remapping might interfere with gene therapeutic treatments aimed at restoring cone function. Methods: We conducted a multicenter study to explore the nature and plasticity of vision in the absence of functional cones in a cohort of 17 individuals affected by autosomal recessive achromatopsia and confirmed biallelic disease-causing CNGA3 or CNGB3 mutations. Specifically, we tested the hypothesis of foveal remapping in human achromatopsia. For this purpose, we applied two independent functional magnetic resonance imaging (fMRI)-based mapping approaches, i.e. conventional phase-encoded eccentricity and population receptive field mapping, to separate data sets. Results: Both fMRI approaches produced the same result in the group comparison of achromatopsia versus healthy controls: sizable remapping of the representation of the central visual field in the primary visual cortex was not apparent. Conclusions: Remapping of the cortical representation of the central visual field is not a general feature in achromatopsia. It is concluded that plasticity of the human primary visual cortex is less pronounced than previously assumed. A pretherapeutic imaging workup is proposed to optimize interventions.

Pro-Con Debate: Perioperative Research Should Be Color-Blind.

Profound racial and ethnic disparities have been documented in health and health care outcomes in recent decades. Some researchers have erroneously ascribed these inequities to biological variations, prompting debate as to how, or even if, race and ethnicity should be included as an outcome variable. Color blindness is a racial ideology with roots in constitutional law that posits that equality is best achieved by disregarding the racial and ethnic characteristics of the individual. Color consciousness, in contrast, approaches disparities with the knowledge that experiences related to one's race and ethnicity influence an individual's health and well-being. In this Pro-Con commentary article, we discuss the concept of color blindness and debate its use as an approach in medicine and research.

Test UD Interferencia: Creación y validación de un nuevo instrumento de resistencia a la interferencia. Normalización y estandarización en población española / UD Interference Test: Creation and validation of a new instrument of resistance to interference. Normalization and standardization for Spanish population

Introducción: El test UD Interferencia evalúa la velocidad de procesamiento y la atención, y está basado en el concepto de interferencia del test de Stroop. El objetivo principal de este estudio es proporcionar una versión alternativa del test de Stroop que evite algunas de las limitaciones de versiones anteriores, relacionadas con el daltonismo y las dificultades de lectura en personas mayores, y obtener datos normativos y estandarizados para este test, adaptados a población española. Métodos: El estudio se enmarca dentro del proyecto Normacog, para el cual se evaluó a 905 participantes (18-93 años). Se analizó la fiabilidad y la validez concurrente y de constructo del test. Se analizaron el efecto de la edad, nivel educativo y sexo sobre el rendimiento en UD Interferencia y se crearon percentiles y puntuaciones escalares ajustadas por edad y nivel educativo. Resultados: El test muestra buena fiabilidad (α = 0,875) y validez concurrente (r de 0,443 a 0,725; p < 0,001) y de constructo (r de 0,472 a 0,737; p < 0,001). Se observó un efecto significativo de la edad y el nivel educativo sobre el rendimiento en UD Interferencia, explicando del 12 al 40% de la varianza. El sexo únicamente presentó un efecto significativo en la variable índice de resistencia a la interferencia. Conclusiones: Se presenta una versión alternativa del test de Stroop que presenta algunas ventajas sobre anteriores versiones. Se aportan baremos estandarizados y normalizados para población española que permiten corregir el test teniendo en cuenta la edad y educación de la persona evaluada.(AU)

Introduction: The UD Interference Test measures processing speed and attention, and is based on the concept of interference of the Stroop Test. The main purpose of the study is to provide an alternative version of the Stroop Test that overcomes some of the limitations of previous versions in assessing individuals with daltonism or age-related reading difficulties, and to obtain normative and standardised data for the Spanish population. Methods: This study is part of the Normacog project. We evaluated 905 individuals (age range, 18-93 years) to analyse the test's reliability and concurrent and construct validity. We evaluated the effect of age, sex, and level of education on UD Interference Test performance and calculated percentiles and age- and education-adjusted scaled scores. Results: The test has good reliability (α = 0.875) and concurrent (r = 0.443-0.725; p < .001) and construct validity (r = 0.472-0.737; p < .001). We observed age and educational level to have a significant effect on UD Interference Test scores, explaining 12-40% of variance. Sex only had a significant effect on the resistance to interference index. Conclusions: We present an alternative version of the Stroop Color and Word Test with some advantages over previous versions. We provide standardised and normalised data for the Spanish population to correct the test according to the subject's age and level of education.(AU)