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Human Gene Therapy. Clinical Development Mar 2015Spontaneous canine models exist for several inherited retinal dystrophies. This review will summarize the models and indicate where they have been used in translational... (Review)
Review
Spontaneous canine models exist for several inherited retinal dystrophies. This review will summarize the models and indicate where they have been used in translational gene therapy trials. The RPE65 gene therapy trials to treat childhood blindness are a good example of how studies in dogs have contributed to therapy development. Outcomes in human clinical trials are compared and contrasted with the result of the preclinical dog trials.
Topics: Animals; Blindness; Color Vision Defects; Disease Models, Animal; Dogs; Genetic Therapy; Humans; Leber Congenital Amaurosis; Macular Degeneration; Retinal Dystrophies; cis-trans-Isomerases
PubMed: 25671556
DOI: 10.1089/humc.2014.155 -
American Journal of Ophthalmology Sep 2023To assess the safety and efficacy of AAV8-hCARp.hCNGB3 in participants with CNGB3-associated achromatopsia (ACHM). (Clinical Trial)
Clinical Trial
PURPOSE
To assess the safety and efficacy of AAV8-hCARp.hCNGB3 in participants with CNGB3-associated achromatopsia (ACHM).
DESIGN
Prospective, phase 1/2 (NCT03001310), open-label, nonrandomized clinical trial.
METHODS
The study enrolled 23 adults and children with CNGB3-associated ACHM. In the dose-escalation phase, adult participants were administered 1 of 3 AAV8-hCARp.hCNGB3 dose levels in the worse-seeing eye (up to 0.5 mL). After a maximum tolerated dose was established in adults, an expansion phase was conducted in children ≥3 years old. All participants received topical and oral corticosteroids. Safety and efficacy parameters, including treatment-related adverse events and visual acuity, retinal sensitivity, color vision, and light sensitivity, were assessed for 6 months.
RESULTS
AAV8-hCARp.hCNGB3 (11 adults, 12 children) was safe and generally well tolerated. Intraocular inflammation occurred in 9 of 23 participants and was mainly mild or moderate in severity. Severe cases occurred primarily at the highest dose. Two events were considered serious and dose limiting. All intraocular inflammation resolved following topical and systemic steroids. There was no consistent pattern of change from baseline to week 24 for any efficacy assessment. However, favorable changes were observed for individual participants across several assessments, including color vision (n = 6/23), photoaversion (n = 11/20), and vision-related quality-of-life questionnaires (n = 21/23).
CONCLUSIONS
AAV8-hCARp.hCNGB3 for CNGB3-associated ACHM demonstrated an acceptable safety and tolerability profile. Improvements in several efficacy parameters indicate that AAV8-hCARp.hCNGB3 gene therapy may provide benefit. These findings, with the development of additional sensitive and quantitative end points, support continued investigation.
Topics: Humans; Adult; Child; Child, Preschool; Color Vision Defects; Prospective Studies; Cyclic Nucleotide-Gated Cation Channels; Genetic Therapy; Inflammation
PubMed: 37172884
DOI: 10.1016/j.ajo.2023.05.009 -
Eye (London, England) Aug 2021In the absence of pre-admission testing for colour blindness, many of the currently practicing ophthalmologists are colour blind, accordingly their accuracy of...
PURPOSE
In the absence of pre-admission testing for colour blindness, many of the currently practicing ophthalmologists are colour blind, accordingly their accuracy of distinguishing fine diabetic retinopathy (DR) changes is still unknown. This study aims to assess the accuracy of diagnosing and staging diabetic retinopathy and macular oedema among protonopic, deutronopic and tritanopic ophthalmologists.
METHODS
Cross-sectional assessment of fundus images that were prepared to simulate the appearance in cases of colour blindness. We assessed the accuracy of staging diabetic retinopathy and macular oedema by a retina specialist on colour-blind simulated images. We used randomiser.org to randomly select images to be simulated by the previously validated Vischeck colour blindness simulator.
RESULTS
A total of 150 simulated images were reviewed, 50 images for each of simulated protanopia, deuteranopia and tritanopia. We found that the accuracy for staging DR and macular oedema for protanope grader were 50% and 60%, respectively. Accuracy within one stage difference for DR and macular oedema were 88% and 90%, respectively. For deuteranopes, 56% and 64% accuracy for DR and macular oedema, respectively. Accuracy within one stage difference for DR and macular oedema were 86% and 90%, respectively. For Tritanope, 62% and 84% accuracy for DR and macular oedema, respectively.
CONCLUSION
Colour vision is important for distinguishing fine details during retina assessment in diabetic retinopathy patients. Colour blindness is associated with low accuracy in staging diabetic retinopathy and macular oedema, particularly among protonopic graders, and to a lesser extent in tritanopic graders.
Topics: Color; Color Vision Defects; Cross-Sectional Studies; Diabetes Mellitus; Diabetic Retinopathy; Humans; Ophthalmologists
PubMed: 33106610
DOI: 10.1038/s41433-020-01232-z -
Investigative Ophthalmology & Visual... Feb 2021Psychophysical and genetic testing provide substantial information about color vision phenotype and genotype. However, neither reveals how color vision phenotypes and...
PURPOSE
Psychophysical and genetic testing provide substantial information about color vision phenotype and genotype. However, neither reveals how color vision phenotypes and genotypes manifest themselves in individual cones, where color vision and its anomalies are thought to originate. Here, we use adaptive-optics phase-sensitive optical coherence tomography (AO-PSOCT) to investigate these relationships.
METHODS
We used AO-PSOCT to measure cone function-optical response to light stimulation-in each of 16 human subjects with different phenotypes and genotypes of color vision (five color-normal, three deuteranopic, two protanopic, and six deuteranomalous trichromatic subjects). We classified three spectral types of cones (S, M, and L), and we measured cone structure-namely cone density, cone mosaic arrangement, and spatial arrangement of cone types.
RESULTS
For the different phenotypes, our cone function results show that (1) color normals possess S, M, and L cones; (2) deuteranopes are missing M cones but are normal otherwise; (3) protanopes are missing L cones but are normal otherwise; and (4) deuteranomalous trichromats are missing M cones but contain evidence of at least two subtypes of L cones. Cone function was consistent with the subjects' genotype in which only the first two M and L genes in the gene array are expressed and was correlated with the estimated spectral separation between photopigments, including in the deuteranomalous trichromats. The L/M cone ratio was highly variable in the color normals. No association was found between cone density and the genotypes and phenotypes investigated, and the cone mosaic arrangement was altered in the dichromats.
CONCLUSIONS
AO-PSOCT is a novel method for assessing color vision phenotype and genotype in single cone cells.
Topics: Adult; Color Perception; Color Vision; Color Vision Defects; Female; Genotype; Humans; Male; Middle Aged; Phenotype; Retinal Cone Photoreceptor Cells; Retinal Pigments; Tomography, Optical Coherence; Young Adult
PubMed: 33544131
DOI: 10.1167/iovs.62.2.8 -
Clinical & Experimental Optometry Jul 2004All people with abnormal colour vision, except for a few mildly affected deuteranomals, report that they experience problems with colour in everyday life and at work.... (Review)
Review
All people with abnormal colour vision, except for a few mildly affected deuteranomals, report that they experience problems with colour in everyday life and at work. Contemporary society presents them with increasing problems because colour is now so widely used in printed materials and in computer displays. Equal opportunity law gives them protection against unfair discrimination in employment, so a decision to exclude a person from employment on the grounds of abnormal colour vision must now be well supported by good evidence and sound argument. This paper reviews the investigations that have contributed to understanding the nature and consequences of the problems they have. All those with abnormal colour vision are at a disadvantage with comparative colour tasks that involve precise matching of colours or discrimination of fine colour differences either because of their loss of colour discrimination or anomalous perception of metamers. The majority have problems when colour is used to code information, in man-made colour codes and in naturally occurring colour codes that signal ripeness of fruit, freshness of meat or illness. They can be denied the benefit of colour to mark out objects and organise complex visual displays. They may be unreliable when a colour name is used as an identifier. They are slower and less successful in search when colour is an attribute of the target object or is used to organise the visual display. Because those with the more severe forms of abnormal colour vision perceive a very limited gamut of colours, they are at a disadvantage in the pursuit and appreciation of those forms of art that use colour.
Topics: Color Vision Defects; Disabled Persons; Humans
PubMed: 15312030
DOI: 10.1111/j.1444-0938.2004.tb05056.x -
Clinical & Experimental Optometry Jul 2004The author describes his experiences due to his inherited colour vision deficiency, as a child, as student and as a medical practitioner, when he had certain... (Review)
Review
The author describes his experiences due to his inherited colour vision deficiency, as a child, as student and as a medical practitioner, when he had certain difficulties in clinical work. He quotes from the literature on the clinical skills of physicians with this deficiency and gives an account of his own research that involved meeting and testing other doctors of medicine. This revealed a wide range of difficulties experienced by colour vision defective doctors in their practice of medicine with a potentiality for errors. Although there is a number of publications on this subject, the profession has made little response to them. This suggests that it is facing a dilemma that is inhibiting appropriate action. It is suggested that colour vision scientists and medical practitioners need more understanding of each other's discipline if progress is to be made. The advantages of screening of medical students and advising those found to have a deficiency are discussed and lines of research are proposed.
Topics: Attitude of Health Personnel; Attitude to Health; Color Vision Defects; Humans; India; Japan; Physician Impairment; Physicians; Taiwan
PubMed: 15312038
DOI: 10.1111/j.1444-0938.2004.tb05065.x -
British Journal of Industrial Medicine Oct 1972460-461. Blue-grey vision due to the effect of certain amines on the eye is a recognized but generally little known phenomenon. We review previous accounts of the...
460-461. Blue-grey vision due to the effect of certain amines on the eye is a recognized but generally little known phenomenon. We review previous accounts of the condition and describe our experience of its occurrences. We consider the condition should be known as `glaucopsia'.
Topics: Amines; Color Vision Defects; Ethylamines; Humans; Morpholines; Occupational Diseases; Piperidines; Retinal Pigments
PubMed: 4539087
DOI: 10.1136/oem.29.4.460 -
The National Medical Journal of India 2018
Topics: Color Vision Defects; Education, Medical; Health Personnel; Humans; India; Prevalence; Students, Medical; Visually Impaired Persons; Workplace
PubMed: 30829218
DOI: 10.4103/0970-258X.253161 -
Communications Biology Mar 2022Numerous missense mutations in cyclic nucleotide-gated (CNG) channels cause achromatopsia and retinitis pigmentosa, but the underlying pathogenic mechanisms are often...
Numerous missense mutations in cyclic nucleotide-gated (CNG) channels cause achromatopsia and retinitis pigmentosa, but the underlying pathogenic mechanisms are often unclear. We investigated the structural basis and molecular/cellular effects of R410W, an achromatopsia-associated, presumed loss-of-function mutation in human CNGA3. Cryo-EM structures of the Caenorhabditis elegans TAX-4 CNG channel carrying the analogous mutation, R421W, show that most apo channels are open. R421, located in the gating ring, interacts with the S4 segment in the closed state. R421W disrupts this interaction, destabilizes the closed state, and stabilizes the open state. CNGA3_R410W/CNGB3 and TAX4_R421W channels are spontaneously active without cGMP and induce cell death, suggesting cone degeneration triggered by spontaneous CNG channel activity as a possible cause of achromatopsia. Our study sheds new light on CNG channel allosteric gating, provides an impetus for a reevaluation of reported loss-of-function CNG channel missense disease mutations, and has implications for mutation-specific treatment of retinopathy.
Topics: Color Vision Defects; Cyclic Nucleotide-Gated Cation Channels; Humans; Light Signal Transduction; Mutation, Missense; Retinal Cone Photoreceptor Cells
PubMed: 35233102
DOI: 10.1038/s42003-022-03120-6 -
Sensors (Basel, Switzerland) Apr 2021In this paper, a novel method to modify color images for the protanopia and deuteranopia color vision deficiencies is proposed. The method admits certain criteria, such...
In this paper, a novel method to modify color images for the protanopia and deuteranopia color vision deficiencies is proposed. The method admits certain criteria, such as preserving image naturalness and color contrast enhancement. Four modules are employed in the process. First, fuzzy clustering-based color segmentation extracts key colors (which are the cluster centers) of the input image. Second, the key colors are mapped onto the CIE 1931 chromaticity diagram. Then, using the concept of confusion line (i.e., loci of colors confused by the color-blind), a sophisticated mechanism translates (i.e., removes) key colors lying on the same confusion line to different confusion lines so that they can be discriminated by the color-blind. In the third module, the key colors are further adapted by optimizing a regularized objective function that combines the aforementioned criteria. Fourth, the recolored image is obtained by color transfer that involves the adapted key colors and the associated fuzzy clusters. Three related methods are compared with the proposed one, using two performance indices, and evaluated by several experiments over 195 natural images and six digitized art paintings. The main outcomes of the comparative analysis are as follows. (a) Quantitative evaluation based on nonparametric statistical analysis is conducted by comparing the proposed method to each one of the other three methods for protanopia and deuteranopia, and for each index. In most of the comparisons, the Bonferroni adjusted -values are <0.015, favoring the superiority of the proposed method. (b) Qualitative evaluation verifies the aesthetic appearance of the recolored images.
Topics: Cluster Analysis; Color; Color Perception; Color Vision Defects; Humans
PubMed: 33924510
DOI: 10.3390/s21082740