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Indian Journal of Ophthalmology Mar 2023The extended use of ethambutol beyond 2 months for treating tuberculosis has increased risk of optic neuropathy. We performed a systematic review of studies evaluating... (Review)
Review
The extended use of ethambutol beyond 2 months for treating tuberculosis has increased risk of optic neuropathy. We performed a systematic review of studies evaluating optic neuropathy in extended ethambutol use since 2010 and compared the outcome with a similar systematic review (1965-2010) by Ezer et al. Literature search was conducted in PubMed, Medline, EMBASE, and Cochrane databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Main outcome measures were visual acuity, color vision, visual field defects, optical coherence tomography (OCT), and visual evoked potential (VEP). The JBI Critical Appraisal Checklists were used for quality assessment. Twelve studies were selected (out of 639 studies) for analysis of ethambutol optic neuropathy. Visual acuity improvement after stopping ethambutol was statistically significant. Similar improvement was not noted for other outcome measures. On comparing the results of this review with those by Ezer et al., significant improvement was noted in visual acuity, color vision, and visual field defects. Moreover, more patients reported increased optic nerve toxicity, color vision defects, and visual field defects in the present review. Hence, we conclude that the extended use of ethambutol beyond 2 months results in significant optic nerve toxicity. Further randomized controlled trials with different populations are needed to understand the magnitude of this issue.
Topics: Humans; Ethambutol; Evoked Potentials, Visual; Optic Nerve Diseases; Optic Nerve; Checklist; Rare Diseases
PubMed: 36872667
DOI: 10.4103/ijo.IJO_1920_22 -
International Journal of Molecular... Feb 2023Achromatopsia is an autosomal recessive disorder, in which cone photoreceptors undergo progressive degeneration, causing color blindness and poor visual acuity, among...
Achromatopsia is an autosomal recessive disorder, in which cone photoreceptors undergo progressive degeneration, causing color blindness and poor visual acuity, among other significant eye affectations. It belongs to a group of inherited retinal dystrophies that currently have no treatment. Although functional improvements have been reported in several ongoing gene therapy studies, more efforts and research should be carried out to enhance their clinical application. In recent years, genome editing has arisen as one of the most promising tools for personalized medicine. In this study, we aimed to correct a homozygous pathogenic variant in hiPSCs derived from a patient affected by achromatopsia through CRISPR/Cas9 and TALENs technologies. Here, we demonstrate high efficiency in gene editing by CRISPR/Cas9 but not with TALENs approximation. Despite a few of the edited clones displaying heterozygous on-target defects, the proportion of corrected clones with a potentially restored wild-type PDE6C protein was more than half of the total clones analyzed. In addition, none of them presented off-target aberrations. These results significantly contribute to advances in single-nucleotide gene editing and the development of future strategies for the treatment of achromatopsia.
Topics: Humans; Color Vision Defects; CRISPR-Cas Systems; Gene Editing; Mutation; Transcription Activator-Like Effector Nucleases; Induced Pluripotent Stem Cells
PubMed: 36835061
DOI: 10.3390/ijms24043655 -
Genes Feb 2023This multicenter study aimed to characterize Korean patients with achromatopsia. The patients' genotypes and phenotypes were retrospectively evaluated. Twenty-one...
This multicenter study aimed to characterize Korean patients with achromatopsia. The patients' genotypes and phenotypes were retrospectively evaluated. Twenty-one patients (with a mean age at the baseline of 10.9 years) were enrolled and followed up for a mean of 7.3 years. A targeted gene panel or exome sequencing was performed. The pathogenic variants of the four genes and their frequencies were identified. and were equally the most prevalent genes: (N = 8, 38.1%), (N = 8, 38.1%), (N = 3, 14.3%), and (N = 2, 9.5%). The degree of functional and structural defects varied among the patients. The patients' age exhibited no significant correlation with structural defects. During the follow-up, the visual acuity and retinal thickness did not change significantly. In -achromatopsia patients, a proportion of patients with a normal foveal ellipsoid zone on the OCT was significantly higher than that of patients with other causative genes (62.5% vs. 16.7%; = 0.023). In -achromatopsia patients, the same proportion was significantly lower than that of patients with other causative genes (0% vs. 58.3%; = 0.003). Korean patients with achromatopsia showed similar clinical features but a higher prevalence of variants than those of other ethnic groups. The retinal phenotypes of the variants were more likely to be worse than those of other genes.
Topics: Humans; Color Vision Defects; Retrospective Studies; Cyclic Nucleotide-Gated Cation Channels; Republic of Korea
PubMed: 36833446
DOI: 10.3390/genes14020519 -
Optics Express Feb 2023This cross-sectional and observational study includes 50 eyes of subjects with color blindness and 50 eyes of control subjects. Visual function (visual acuity, contrast... (Observational Study)
Observational Study
This cross-sectional and observational study includes 50 eyes of subjects with color blindness and 50 eyes of control subjects. Visual function (visual acuity, contrast sensitivity, and color vision) and neuroretinal structure were assessed in all subjects using optical coherence tomography (OCT). Significant thinning of the retinal nerve fiber layer, ganglion cell layer, and retina were observed in the color blindness group. Significant thinning was also recorded in layers that involve photoreceptor nuclei (between the outer limiting layer and the Bruch membrane and between the outer plexiform layer and the outer limiting membrane). OCT evaluation based on retinal segmentation is a rapid (5-10 minutes) non-invasive technique and seems to be a good biomarker of color blindness.
Topics: Humans; Color Vision; Color Vision Defects; Cross-Sectional Studies; Retina; Visual Acuity; Tomography, Optical Coherence
PubMed: 36823837
DOI: 10.1364/OE.461872 -
Scientific Reports Feb 2023Achromatopsia is an autosomal recessive cone photoreceptor disease that is frequently caused by pathogenic variants in the CNGA3 gene. Here, we present a systematic...
Achromatopsia is an autosomal recessive cone photoreceptor disease that is frequently caused by pathogenic variants in the CNGA3 gene. Here, we present a systematic functional analysis of 20 CNGA3 splice site variants detected in our large cohort of achromatopsia patients and/or listed in common variant databases. All variants were analyzed by functional splice assays based on the pSPL3 exon trapping vector. We demonstrated that ten variants, both at canonical and non-canonical splice sites, induced aberrant splicing, including intronic nucleotide retention, exonic nucleotide deletion and exon skipping, resulting in 21 different aberrant transcripts. Of these, eleven were predicted to introduce a premature termination codon. The pathogenicity of all variants was assessed based on established guidelines for variant classification. Incorporation of the results of our functional analyses enabled re-classification of 75% of variants previously classified as variants of uncertain significance into either likely benign or likely pathogenic. Our study is the first in which a systematic characterization of putative CNGA3 splice variants has been performed. We demonstrated the utility of pSPL3 based minigene assays in the effective assessment of putative splice variants. Our findings improve the diagnosis of achromatopsia patients, who may thus benefit from future gene-based therapeutic strategies.
Topics: Humans; Color Vision Defects; RNA Splicing; Exons; Nucleotides; RNA Splice Sites; Mutation; Cyclic Nucleotide-Gated Cation Channels
PubMed: 36801918
DOI: 10.1038/s41598-023-29452-9 -
Neuro-ophthalmology (Aeolus Press) 2023Colour vision is an important aspect of visual function that might help individuals in doing daily activities. Some occupations require and test for good colour...
Colour vision is an important aspect of visual function that might help individuals in doing daily activities. Some occupations require and test for good colour discrimination. We describe a case of a 20-year-old man who was referred to our centre to establish if he had colour vision deficiency (CVD). He had been tested for this twice as part of his assessment to enter the police force. At the first examination, he had normal colour vision, while the second examination revealed CVD, thus the patient was referred for confirmation. Colour vision tests using the Ishihara plates showed normal results with each eye, while a Roth test revealed an unspecified CVD in the right eye and deuteranopia in the left eye. During the evaluation, we noticed he was using a red-tinted contact lens in the right eye, and was wearing a red mask with transparent red plastic in the upper part. After removal of the contact lens and mask, he was asked to repeat the examinations and it revealed deuteranopia in both eyes. A tinted contact lens is a corrective device that can help to enhance colour discrimination in CVD subjects. However, in this case the tinted contact lens was used inappropriately to manipulate the colour vision examination. We highlight the case to raise awareness that the use of red contact lenses and red filters can mask CVD.
PubMed: 36798862
DOI: 10.1080/01658107.2022.2086582 -
The American Journal of Medicine May 2023
Topics: Humans; Color Vision Defects; Biomedical Research
PubMed: 36754131
DOI: 10.1016/j.amjmed.2023.01.019 -
Irish Journal of Medical Science Oct 2023Emergency service vehicle (ESV) drivers are an important part of the health, fire and police services. ESV driving is associated with increased crash risk, but little... (Review)
Review
BACKGROUND
Emergency service vehicle (ESV) drivers are an important part of the health, fire and police services. ESV driving is associated with increased crash risk, but little guidance exists in the literature on relevant medical conditions among drivers and their potential for adding to higher crash risks.
AIMS
We undertook a narrative review to examine the role of medical and other conditions in crash risk of ESV drivers.
METHOD
A literature search was conducted using the ScienceDirect and Transport Research International Documentation (TRID) databases. There was no time frame for the search, and results were restricted to review and research articles.
RESULTS
Of 570 papers identified, 13 remained after screening and full-text review. A range of factors have been shown to have an impact on increased crash risk, including the nature of the task, physical features of the equipment, training, experience, environmental conditions and secondary tasks. There was scant information on medical conditions other than alcohol use disorders.
CONCLUSIONS
Given issues of speed, vehicle and environment, it would seem prudent to mandate levels of medical fitness to drive similar to and sometimes exceeding (i.e. colour blindness for traffic signals and alerts, hearing impairment as first responders) those for group 2 drivers with extra stipulations relating to specific service needs such as enhanced visual (such as colour blindness and contrast sensitivity) and auditory function. Further research is needed on the prevalence and emergence of relevant medical conditions among ESV drivers, with due consideration of their application to the driving tasks in each service.
Topics: Humans; Automobile Driving; Accidents, Traffic; Alcoholism; Color Vision Defects; Ambulances
PubMed: 36752949
DOI: 10.1007/s11845-023-03301-0 -
Translational Vision Science &... Jan 2023Blue cone monochromacy (BCM) is an X-linked retinopathy due to mutations in the OPN1LW/OPN1MW gene cluster. Symptoms include reduced visual acuity and disturbed color...
PURPOSE
Blue cone monochromacy (BCM) is an X-linked retinopathy due to mutations in the OPN1LW/OPN1MW gene cluster. Symptoms include reduced visual acuity and disturbed color vision. We studied BCM color vision to determine outcome measures for future clinical trials.
METHODS
Patients with BCM and normal-vision participants were examined with Farnsworth-Munsell (FM) arrangement tests and the Color Assessment and Diagnosis (CAD) test. A retrospective case series in 36 patients with BCM (ages 6-70) was performed with the FM D-15 test. A subset of six patients also had Roth-28 Hue and CAD tests.
RESULTS
All patients with BCM had abnormal results for D-15, Roth-28, and CAD tests. With D-15, there was protan-deutan confusion and no bimodal tendency. Roth-28 results reinforced that finding. There was symmetry in color vision metrics between the two eyes and coherence between sessions with the arrangement tests and CAD. Severe abnormalities in red-green sensitivity with CAD were expected. Unexpected were different levels of yellow-blue results with two patterns of abnormal thresholds: moderate elevation in two younger patients and severe elevation in four patients ≥35 years. Coefficients of repeatability and intersession means were tabulated for all test modalities.
CONCLUSIONS
Given understanding of advantages, disadvantages, and complexities of interpretation of results, both an arrangement test and CAD should be useful monitors of color vision through a clinical trial in BCM.
TRANSLATIONAL RELEVANCE
Our pilot studies in BCM of arrangement and CAD tests indicated both were clinically feasible and interpretable in the context of this cone gene disease.
Topics: Humans; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Color Vision; Retrospective Studies; Color Vision Defects; Outcome Assessment, Health Care
PubMed: 36692456
DOI: 10.1167/tvst.12.1.25