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Current Biology : CB Sep 2023A new study describes a set of behavioural experiments that assess whether gene therapy can restore colour vision in patients with congenital achromatopsia.
A new study describes a set of behavioural experiments that assess whether gene therapy can restore colour vision in patients with congenital achromatopsia.
Topics: Humans; Color Vision Defects; Color Vision
PubMed: 37699345
DOI: 10.1016/j.cub.2023.07.065 -
Genetics in Medicine : Official Journal... Dec 2023CNGA3 encoding the main subunit of the cyclic nucleotide-gated ion channel in cone photoreceptors is one of the major disease-associated genes for achromatopsia. Most...
PURPOSE
CNGA3 encoding the main subunit of the cyclic nucleotide-gated ion channel in cone photoreceptors is one of the major disease-associated genes for achromatopsia. Most CNGA3 variants are missense variants with the majority being functionally uncharacterized and therefore hampering genetic diagnosis. In light of potential gene therapy, objective variant pathogenicity assessment is essential.
METHODS
We established a medium-throughput aequorin-based luminescence bioassay allowing mutant CNGA3 channel function assessment via quantification of CNGA3 channel-mediated calcium influx in a cell culture system, thereby enabling American College of Medical Genetics and Genomics/Association for Molecular Pathology-based variant re-classification.
RESULTS
We provide functional read-out obtained for 150 yet uncharacterized CNGA3 missense substitutions of which 55 were previously categorized as variants of uncertain significance (VUS) identifying 25 as functionally normal and 125 as functionally abnormal. These data enabled the American College of Medical Genetics and Genomics/ Association for Molecular Pathology-based variant re-classification of 52/55 VUS as either benign, likely benign, or likely pathogenic reaching a VUS re-classification rate of 94.5%.
CONCLUSION
Our aequorin-based bioassay allows functionally ensured clinical variant interpretation for 150 CNGA3 missense variants enabling and supporting VUS re-classification and assuring molecular diagnosis to patients affected by CNGA3-associated achromatopsia, hereby identifying patients eligible for future gene therapy trials on this disease.
Topics: Humans; Color Vision Defects; Aequorin; Retinal Cone Photoreceptor Cells; Mutation, Missense; Genomics; Cyclic Nucleotide-Gated Cation Channels
PubMed: 37689994
DOI: 10.1016/j.gim.2023.100979 -
PloS One 2023Colour-related search tasks are common in many professional fields. The study investigated whether increasing chromatic saturation can enhance the visual performance of...
BACKGROUND
Colour-related search tasks are common in many professional fields. The study investigated whether increasing chromatic saturation can enhance the visual performance of individuals with colour vision deficiency (CVD) in colour-related search tasks.
METHODS
10 normal trichromats (5M, 5F; Mean (SD) age: 23.1 (3.3) years) and 15 individuals with CVD [8 deutans and 7 protans identified by HRR plates] (14M, 1F; aged 28.6 (8.7) years) participated in this study. Four naturalistic sceneries of everyday tasks/ birds, animals and flowers of 15 different colour combinations (1 pair of colours in each combination. e.g., 'brown/black' or 'red/green') were presented in 'low' saturation, 'original' (unaltered images) and 'high' saturation condition using the Psychopy program on a colour-calibrated monitor. On each trial, the subject was asked to identify a specific-coloured target.
RESULTS
Overall, the visual search performance index (expressed as product of accuracy and a reciprocal of reaction time (%correct*s-1) of the normal trichromats [Mean (SD):77.76% correct*s-1 (16.32)] was significantly higher than CVD [45.71% correct*s-1 (18.95)] in the "original" test images (p = 0.001), but in individuals with CVD, there was no significant difference between 'original' [45.71% correct*s-1 (18.95)] and 'high' saturation condition ([47.43% correct*s-1 (20.07)]; p > 0.05). However, colour-wise, increased saturation showed improvements (≥ 10%) in protans mainly for 'red' combinations with other colours such as white (i.e., 'red/white'), purple, orange, grey, green, brown and black.
CONCLUSION
The study suggests that increasing the saturation of certain colour combinations can potentially aid in the visual search performance of individuals with CVD. This knowledge will help in better counselling and management of the patients.
Topics: Animals; Chemical Phenomena; Color Vision Defects; Flowers; Humans; Male; Female; Young Adult; Adult
PubMed: 37682873
DOI: 10.1371/journal.pone.0290782 -
Documenta Ophthalmologica. Advances in... Dec 2023Biallelic mutations in the CEP290 gene cause early onset retinal dystrophy or syndromic disease such as Senior-Loken or Joubert syndrome. Here, we present an unusual...
PURPOSE
Biallelic mutations in the CEP290 gene cause early onset retinal dystrophy or syndromic disease such as Senior-Loken or Joubert syndrome. Here, we present an unusual non-syndromic case of a juvenile retinal dystrophy caused by biallelic CEP290 mutations imitating initially the phenotype of achromatopsia or slowly progressing cone dystrophy.
METHODS
We present 13 years of follow-up of a female patient who presented first with symptoms and findings typical for achromatopsia. The patient underwent functional and morphologic examinations, including fundus autofluorescence imaging, spectral-domain optical coherence tomography, electroretinography, color vision and visual field testing.
RESULTS
Diagnostic genetic testing via whole genome sequencing and virtual inherited retinal disease gene panel evaluation finally identified two compound heterozygous variants c.4452_4455del;p.(Lys1484Asnfs*4) and c.2414T > C;p.(Leu805Pro) in the CEP290 gene.
CONCLUSIONS
CEP290 mutation causes a wide variety of clinical phenotypes. The presented case shows a phenotype resembling achromatopsia or early onset slowly progressing cone dystrophy.
Topics: Humans; Female; Cone Dystrophy; Color Vision Defects; Electroretinography; Mutation; Phenotype; Retinal Dystrophies; Tomography, Optical Coherence
PubMed: 37642804
DOI: 10.1007/s10633-023-09940-z -
Die Ophthalmologie Sep 2023Achromatopsia or rod monochromatism is a congenital autosomal recessive retinal dystrophy which leads to dysfunctional cones, with decreased visual acuity, extremely...
Achromatopsia or rod monochromatism is a congenital autosomal recessive retinal dystrophy which leads to dysfunctional cones, with decreased visual acuity, extremely limited color vision, nystagmus and photophobia. Due to the initially normally appearing ocular morphology, the diagnosis is often delayed. With imaging procedures, e.g., fluorescence-autofluorescence (FAF) and optical coherence tomography (OCT), different morphological forms of achromatopsia can be discriminated that do not seem to have a differential effect on visual function. Crucial is the provision of specific edge filters. Mutations in six genes are known to cause achromatopsia. For the two most frequent genes, CNGA3 and CNGB3, gene addition therapies are currently being tested. Such future approaches should be applied before the manifestation of sensory-related amblyopia in the visual cortex. Accordingly, state of the art management of achromatopsia should provide a diagnosis in early childhood including genotyping.
Topics: Child, Preschool; Humans; Color Vision Defects; Quality of Life; Brain; Retinal Cone Photoreceptor Cells
PubMed: 37638972
DOI: 10.1007/s00347-023-01904-7 -
Ophthalmic & Physiological Optics : the... Nov 2023Colour vision deficiencies (CVDs) indicate potential genetic variations and can be important biomarkers of acquired impairment in many neuro-ophthalmic diseases....
Colour vision deficiencies (CVDs) indicate potential genetic variations and can be important biomarkers of acquired impairment in many neuro-ophthalmic diseases. However, CVDs are typically measured with tests which possess high sensitivity for detecting the presence of a CVD but do not quantify its type or severity. In this study, we introduce Foraging Interactive D-prime (FInD), a novel computer-based, generalisable, rapid, self-administered vision assessment tool and apply it to colour vision testing. This signal detection theory-based adaptive paradigm computed test stimulus intensity from d-prime analysis. Stimuli were chromatic Gaussian blobs in dynamic luminance noise, and participants clicked on cells that contained chromatic blobs (detection) or blob pairs of differing colours (discrimination). Sensitivity and repeatability of FInD colour tasks were compared against the Hardy-Rand-Rittler and the Farnsworth-Munsell 100 hue tests in 19 colour-normal and 18 inherited colour-atypical, age-matched observers. Rayleigh colour match was also completed. Detection and discrimination thresholds were higher for atypical than for typical observers, with selective threshold elevations corresponding to unique CVD types. Classifications of CVD type and severity via unsupervised machine learning confirmed functional subtypes. FInD tasks reliably detect inherited CVDs, and may serve as valuable tools in basic and clinical colour vision science.
Topics: Humans; Color Vision Defects; Color Vision; Vision Tests; Machine Learning; Cardiovascular Diseases; Color Perception
PubMed: 37589437
DOI: 10.1111/opo.13210 -
Ophthalmology Dec 2023To describe the largest, most phenotypically and genetically diverse cohort of patients with inherited retinal disease (IRD)-related Coats-like vasculopathy (CLV).
PURPOSE
To describe the largest, most phenotypically and genetically diverse cohort of patients with inherited retinal disease (IRD)-related Coats-like vasculopathy (CLV).
DESIGN
Multicenter retrospective cohort study.
PARTICIPANTS
A total of 67 patients with IRD-related CLV.
METHODS
Review of clinical notes, ophthalmic imaging, and molecular diagnosis from 2 international centers.
MAIN OUTCOME MEASURES
Visual function, retinal imaging, management, and response to treatment were evaluated and correlated.
RESULTS
The prevalence of IRD-related CLV was 0.5%; 54% of patients had isolated retinitis pigmentosa (RP), 21% had early-onset severe retinal dystrophy, and less frequent presentations were syndromic RP, sector RP, cone-rod dystrophy, achromatopsia, PAX6-related dystrophy, and X-linked retinoschisis. The overall age of patients at CLV diagnosis was 30.7 ± 16.9 years (1-83). Twenty-one patients (31%) had unilateral CLV, and the most common retinal features were telangiectasia, exudates, and exudative retinal detachment (ERD) affecting the inferior and temporal retina. Macular edema/schisis was observed in 26% of the eyes, and ERD was observed in 63% of the eyes. Fifty-four patients (81%) had genetic testing, 40 of whom were molecularly solved. Sixty-six eyes (58%) were observed, 17 eyes (15%) were treated with a single modality, and 30 eyes (27%) had a combined approach. Thirty-five eyes (31%) were "good responders," 42 eyes (37%) were "poor responders," 22 eyes (19%) had low vision at baseline and were only observed, and 12 eyes (11%) did not have longitudinal assessment. Twenty-one observed eyes (62%) responded well versus 14 (33%) treated eyes. Final best-corrected visual acuity was significantly worse than baseline (P = 0.002); 40 patients (60%) lost 15 ETDRS letters or more over follow-up in 1 or both eyes, and 21 patients (31%) progressed to more advanced stages of visual impairment.
CONCLUSIONS
Inherited retinal disease-related CLV is rare, sporadic, and mostly bilateral; there is no gender predominance, and it can occur in diverse types of IRD at any point of the disease, with a mean onset in the fourth decade of life. Patients with IRD-related CLV who have decreased initial visual acuity, ERD, CLV changes affecting 2 or more retinal quadrants, and CRB1-retinopathy may be at higher risk of a poor prognosis.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Humans; Infant; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Prevalence; Retrospective Studies; Retina; Retinal Detachment; Retinal Dystrophies; Retinitis Pigmentosa; Cone-Rod Dystrophies; Vision, Low; Eye Proteins; Membrane Proteins; Nerve Tissue Proteins
PubMed: 37544434
DOI: 10.1016/j.ophtha.2023.07.027 -
Sensors (Basel, Switzerland) Jul 2023Ensuring the quality of color contact lenses is vital, particularly in detecting defects during their production since they are directly worn on the eyes. One...
Ensuring the quality of color contact lenses is vital, particularly in detecting defects during their production since they are directly worn on the eyes. One significant defect is the "center deviation (CD) defect", where the colored area (CA) deviates from the center point. Measuring the extent of deviation of the CA from the center point is necessary to detect these CD defects. In this study, we propose a method that utilizes image processing and analysis techniques for detecting such defects. Our approach involves employing semantic segmentation to simplify the image and reduce noise interference and utilizing the Hough circle transform algorithm to measure the deviation of the center point of the CA in color contact lenses. Experimental results demonstrated that our proposed method achieved a 71.2% reduction in error compared with existing research methods.
PubMed: 37514827
DOI: 10.3390/s23146533 -
Journal of Personalized Medicine Jul 2023(1) Background: Achromatopsia is a rare disease of which the natural course and impact on life are still unknown to this date. We aimed to assess the morphological,...
(1) Background: Achromatopsia is a rare disease of which the natural course and impact on life are still unknown to this date. We aimed to assess the morphological, functional characteristics, and quality of life in a large sample size of patients with achromatopsia. (2) A total of 94 achromats were included in this retrospective cohort study. Sixty-four were patients of the Department of Ophthalmology, Saarland University Medical Centre in Homburg/Saar, Germany, between 2008 and 2021. Thirty further participants with achromatopsia from the national support group were included using an online questionnaire, which is available under 'Supplementary data'. Statistical analysis was performed using SPSS Version 25; (3) The 94 patients (37 males (39.4%) and 57 females (60.6%)) showed a mean age of 24.23 ± 18.53 years. Visual acuity was stable (SD ± 0.22 logMAR at 1.0 logMAR) over a time of observation from 2008 to 2021. Edge filter glasses were the most used optical aids, while enlarged reading glasses were the most used low vision aids. (4) Conclusions: Our findings give an insight into describing the natural process and the quality of life of achromatopsia. The results demonstrate that achromatopsia is a predominantly stationary disease. The individual prescription of edge filters and low-vision aids is essential following a personalised fitting.
PubMed: 37511719
DOI: 10.3390/jpm13071106 -
Photodiagnosis and Photodynamic Therapy Sep 2023This study aimed to examine the color discrimination ability of patients with transfusion-dependent beta-thalassemia (TDβ-T) in detail using the Farnsworth Munsell (FM)...
Investigation of the color discrimination ability using the Farnsworth-Munsell 100-hue test and structural changes by SS-OCT in patients with transfusion-dependent beta-thalassemia.
AIM
This study aimed to examine the color discrimination ability of patients with transfusion-dependent beta-thalassemia (TDβ-T) in detail using the Farnsworth Munsell (FM) 100-hue test and to evaluate structural changes by swept source-optical coherence tomography (SS-OCT).
MATERIAL AND METHODS
This prospective, sectional study included 40 patients (79 eyes) with TDβ-T and 21 controls (42 eyes). The volunteers underwent a detailed ophthalmological examination and SS-OCT (DRI-OCT, Triton) imaging. Excluded were those with congenital color vision defects detected with the Ishihara pseudoisochromatic test. The patients' color vision was examined using the FM 100-hue test. The total error score (TES), the blue-yellow local error score (b-y LES), and the red-green local error score (r-g LES) were calculated. p <0.05 was considered significant.
RESULTS
The mean age was 30.34±6.94 years in the patient group and 32.26±6.43 years in the control group (p = 0.078). The patient group had a significantly lower hemoglobin level (9.25±0.87 g/dL vs. 14±1.79 g/dL, p <0.001) and a significantly higher ferritin level (2665.56±2658.05 μg/L vs. 52.87±69.59 μg/L, p<0.001) compared to the control group. The mean TES, b-y LES, and r-g LES were higher in the patients than in the controls (64.84±30.18 vs. 28.45±16.55, p<0.001, 34.21±17.54 vs. 15.67±10.07, p <0.001, and 29.32±15.72 vs. 12.12±7.94, p<0.001, respectively). The patients had a higher b-y LES than r-g LES (34.21±17.54 vs. 29.32±15.72, p = 0.015). Choroidal thickness was lower in the patients than in the controls (284.34±63.55 µm vs. 324.98±88.05 µm, p = 0.043).
CONCLUSION
We found that the color discrimination ability of the patients with TDβ-T was reduced in both the r-g and b-y color axes compared to the controls, and their color discrimination ability in the b-y color axis was more affected than in the r-g axis.
Topics: Humans; Young Adult; Adult; Color Perception; Prospective Studies; Tomography, Optical Coherence; beta-Thalassemia; Photochemotherapy; Photosensitizing Agents
PubMed: 37481147
DOI: 10.1016/j.pdpdt.2023.103716