Chromatic vision and structural assessment in primary congenital glaucoma.

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.

Association Between Color Vision Deficiency and Myopia in Chinese Children Over a Five-Year Period.

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.

Temporal dynamics of the neural representation of hue and luminance polarity.

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.

Cortical Visual Mapping following Ocular Gene Augmentation Therapy for Achromatopsia.

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.

Visual and ocular findings in a family with X-linked cone dysfunction and protanopia.

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.

Visual function deficits in eyes with resolved endophthalmitis.

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, R2 = 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.

Color Compensation in Anomalous Trichromats Assessed with fMRI.

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.

Evaluation of a New Test for the Diagnosis of Congenital Dyschromatopsia in Children: the Color Vision Evaluation Test.

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.

Adaptation to the eye's chromatic aberration measured with an adaptive optics visual simulator.

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.

Case Report: Effect of Haploscopic Filter on Contrast Sensitivity Function and Color Vision Tests.

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.

Naturally-occurring myopia and loss of cone function in a sheep model of achromatopsia.

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.

Specificity of the chromatic noise influence on the luminance contrast discrimination to the color vision phenotype.

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.

Characterizing the Effects of Enchroma Glasses on Color Discrimination.

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.

PDE6C: Novel Mutations, Atypical Phenotype, and Differences Among Children and Adults.

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.

Long-Term Investigation of Retinal Function in Patients with Achromatopsia.

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.

Medical legal validity of the use of the anomaloscope in the dyschromatopsia of aspiring civil and military aircraft pilots.

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.

Adaptive Changes in Color Vision from Long-Term Filter Usage in Anomalous but Not Normal Trichromacy.

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.

Central serous chorioretinopathy and achromatopsia: a case report.

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.

Optical Gap Biomarker in Cone-Dominant Retinal Dystrophy.

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.

Tritan color vision deficiency may be associated with an OPN1SW splicing defect and haploinsufficiency.

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.