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Investigative Ophthalmology & Visual... Feb 2021Emmetropization is the process of adjusting ocular growth to the focal plane in order to achieve a clear image. Chromatic light may be involved as a cue to guide this...
PURPOSE
Emmetropization is the process of adjusting ocular growth to the focal plane in order to achieve a clear image. Chromatic light may be involved as a cue to guide this process. Achromats are color blind and lack normal cone function; they are often described as being hyperopic, indicating a failure to emmetropize. We aim to describe the refraction and refractive development in a population of genetically characterized achromats.
METHODS
Refractive error data were collected retrospectively from 28 medical records of CNGB3 c.1148delC homozygous achromats. The distribution of spherical equivalent refractive error (SER) and spherical error was analyzed in adults. The refractive development in children was analyzed by documenting astigmatic refractive error and calculating median SER in 1-year age groups and by analyzing the individual development when possible.
RESULTS
The distribution of SER and spherical error resembled a Gaussian distribution, indicating that emmetropization was disturbed in achromats, but we found indication of some decrease in SER during the first years of childhood. The prevalence of refractive errors was high and broadly distributed. Astigmatic refractive errors were frequent but did not seem to increase with age.
CONCLUSIONS
Refractive development in achromats is more complicated than a complete failure to emmetropize. The spread of refractive errors is larger than previously documented. Results presented here support the theory that chromatic cues and cone photoreceptors may play a role in emmetropization in humans but that it is not essential.
Topics: Accommodation, Ocular; Adolescent; Adult; Aged; Color Vision Defects; Cyclic Nucleotide-Gated Cation Channels; Female; Follow-Up Studies; Humans; Male; Middle Aged; Refraction, Ocular; Refractive Errors; Retrospective Studies; Time Factors; Young Adult
PubMed: 33560291
DOI: 10.1167/iovs.62.2.10 -
Documenta Ophthalmologica. Advances in... Dec 2015While optic neuropathy is a well-known cause of visual disturbances in linezolid-treated patients, the possibility of linezolid-related retinopathy has not been...
PURPOSE
While optic neuropathy is a well-known cause of visual disturbances in linezolid-treated patients, the possibility of linezolid-related retinopathy has not been investigated. Here, we report a case of retinopathy demonstrated by multifocal electroretinogram (mfERG) in a linezolid-treated patient.
METHOD AND RESULTS
A 61-year-old man with extensively drug-resistant pulmonary tuberculosis treated with linezolid for 5 months presented with painless loss of vision in both eyes. The patient's best corrected visual acuity was 20/50 in the right eye and 20/100 in the left eye. Fundus examination revealed mild disc edema, and color vision was defective in both eyes. Humphrey visual field tests showed a superotemporal field defect in the right eye and central and pericentral field defect in the left eye. Optical coherence tomography (OCT) revealed only mild optic disc swelling. In mfERG, central amplitudes were depressed in both eyes. Four months after the cessation of linezolid, visual acuity was restored to 20/20 right eye and 20/25 left eye. The color vision and visual field had improved. The OCT and mfEFG findings improved as well.
CONCLUSIONS
Although the clinical features were similar to linezolid-induced optic neuropathy, the mfERG findings suggest the possibility of a retinopathy through cone dysfunction.
Topics: Anti-Bacterial Agents; Color Vision Defects; Drug Resistance, Bacterial; Electroretinography; Humans; Linezolid; Male; Middle Aged; Papilledema; Retinal Cone Photoreceptor Cells; Retinal Diseases; Tomography, Optical Coherence; Tuberculosis, Pulmonary; Visual Acuity; Visual Fields
PubMed: 26526593
DOI: 10.1007/s10633-015-9518-6 -
Journal of Pediatric Ophthalmology and... Mar 2018Achromatopsia is a complex inherited retinal disease that affects the cone cell function. It is usually an autosomal-recessive disease and is characterized by pendular... (Review)
Review
Achromatopsia is a complex inherited retinal disease that affects the cone cell function. It is usually an autosomal-recessive disease and is characterized by pendular nystagmus, poor visual acuity, lack of color vision, and marked photophobia. CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, and ATF6 gene mutations have been identified as associated with this disease. New diagnostic and therapeutic tools are being studied. Optical coherence tomography and fundus autofluorescence are important imaging techniques that provide significant information about the progression of the disease. The genetic approach for these patients is a current important issue and gene therapy is an ongoing therapeutic option already being studied in clinical trials. The purpose of this review was to survey the current knowledge on diagnosis and treatment options in achromatopsia. [J Pediatr Ophthalmol Strabismus. 2018;55(2):85-92.].
Topics: Color Vision; Color Vision Defects; Disease Management; Electroretinography; Fluorescein Angiography; Fundus Oculi; Humans; Phenotype; Retinal Cone Photoreceptor Cells; Tomography, Optical Coherence
PubMed: 29257187
DOI: 10.3928/01913913-20171117-01 -
Indian Journal of Ophthalmology May 2021Color vision deficiency (CVD) is a condition that results in individuals being unable to distinguish differences between certain colors. Occupational color vision... (Review)
Review
Color vision deficiency (CVD) is a condition that results in individuals being unable to distinguish differences between certain colors. Occupational color vision standards were introduced in aviation in 1919 by The Aeronautical Commission of the International Civil Air Navigation Authority. Concern has been expressed during the last few years that the current color vision standards in aviation may be too stringent and, at the same time, also variable across the world. The tests employed do not always reflect the tasks pilots encounter in today's aviation environment. This ambiguity leads to the possible exclusion of deserving applicants for selection as aircrew. The compatibility of CVD with aircraft crew is assessed by medical personnel using clinical diagnosis tests on the ground level. These clinical tests were developed specifically to detect the presence, nature, and severity of CVD. No clinical tests yet provide a measure of operational performance in operating an aircraft. Arbitrary pass marks have been assigned to clinical tests such that a failing candidate will either be subject to operational restrictions or excluded completely. The prescribed clinical tests and associated pass marks vary considerably between regulators. While an individual may be subject to no restrictions in one jurisdiction, they may be excluded in another. This article highlights newer diagnostic techniques adopted by different countries for assessing color vision to see for the scope of evidence-based guidelines for minimum color vision requirements for flight crew as well as for civil aviation in India.
Topics: Aviation; Color Perception Tests; Color Vision; Color Vision Defects; Humans; India
PubMed: 33913828
DOI: 10.4103/ijo.IJO_2252_20 -
Genes Mar 2023Achromatopsia is a rare congenital condition with cone photoreceptor dysfunction causing color blindness, reduced vision, nystagmus and photophobia. New treatments are...
Achromatopsia is a rare congenital condition with cone photoreceptor dysfunction causing color blindness, reduced vision, nystagmus and photophobia. New treatments are being developed, but the current evidence is still conflicting regarding possible progression over time, and there is no clear genotype-phenotype correlation. This natural history study aimed to further explore the course of disease and potential clinical differences between various genotypes. The retrospective design allowed for the study of a large cohort with a long follow-up. Patients were identified from the Danish national registries. If not already available, genetic analysis was offered to the patient. Clinical data from 1945-2022 were retrieved from medical records and included best-corrected visual acuity (BCVA), color vision, refractive error, nystagmus, visual fields and fundoscopic findings. We identified variants believed to be disease causing in five of the known achromatopsia genes: ; ; ; and ; and novel variants were identified in and . Progressive deterioration of BCVA only attributable to achromatopsia was found in three of 58 patients. Progressive phenotype was seen with variants in and The results indicate that myopia could be more frequently occurring with variants in , and and support the evidence that achromatopsia is a predominantly stationary condition with respect to BCVA. Although a clear genotype-phenotype correlation can still not be concluded, there may be differences in phenotypical characteristics with variants in different genes.
Topics: Humans; Color Vision Defects; Retrospective Studies; Cyclic Nucleotide-Gated Cation Channels; Denmark
PubMed: 36980963
DOI: 10.3390/genes14030690 -
Advances in Experimental Medicine and... 2016Colour vision is only achieved in the presence of healthy and functional cone photoreceptors found in the retina. It is an essential component of human vision and... (Review)
Review
Colour vision is only achieved in the presence of healthy and functional cone photoreceptors found in the retina. It is an essential component of human vision and usually the first complaint patients undergoing vision degeneration have is the loss of daylight colour vision. Therefore, an understanding of the biology and basic mechanisms behind cone death under the degenerative state of retinal dystrophies and how the activation of the apoptotic pathway is triggered will provide valuable knowledge. It will also have broader applications for a spectrum of visual disorders and will be critical for future advances in translational research.
Topics: Animals; Apoptosis; Color Vision; Color Vision Defects; Disease Models, Animal; Genetic Predisposition to Disease; Humans; Mutation; Retinal Cone Photoreceptor Cells; Retinal Degeneration
PubMed: 26427416
DOI: 10.1007/978-3-319-17121-0_31 -
Investigative Ophthalmology & Visual... Mar 2020The purpose of this study was to report GNAT2-associated achromatopsia (GNAT2-ACHM) natural history, characterize photoreceptor mosaic, and determine a therapeutic...
PURPOSE
The purpose of this study was to report GNAT2-associated achromatopsia (GNAT2-ACHM) natural history, characterize photoreceptor mosaic, and determine a therapeutic window for potential intervention.
METHODS
Patients with GNAT2-ACHM were recruited from a single tertiary referral eye center (Moorfields Eye Hospital, London, UK). We performed longitudinal clinical evaluation and ophthalmic examination, and multimodal retinal imaging, including adaptive optics scanning light ophthalmoscopy, quantitative analysis of the cone mosaic, and outer nuclear layer (ONL) thickness, including cone densities evaluation in selected regions of interest and comparison with reported healthy controls.
RESULTS
All nine subjects (3 women) presented with nystagmus, decreased visual acuity (VA), light sensitivity, and highly variable color vision loss. One patient had normal color vision and better VA. Mean VA was 1.01 (±0.10) logarithms of the minimal angle of resolution (LogMAR) at baseline, and 1.04 (±0.10) LogMAR after a mean follow-up (range) of 7.6 years (1.7-12.8 years). Optical coherence tomography showed preservation of the foveal ellipsoid zone (EZ; n = 8; 88.9%), and EZ disruption (n = 1; 11.1%). Mean ONL thickness (range, ± SD) was 84.72 µm (28.57-113.33, ± 25.46 µm) and 86.47 µm (28.57-113.33, ± 24.65 µm) for right and left eyes, respectively. Mean cone densities (±SD) at 190 µm, 350 µm, and 500 µm from the foveal center, were 48.4 (±24.6), 37.8 (±14.7), and 30.7 (±9.9), ×103 cones/mm2, respectively. Mean cone densities were lower than these of unaffected individuals, but with an overlap.
CONCLUSIONS
The cone mosaic in GNAT2-ACHM is relatively well preserved, potentially allowing for a wide therapeutic window for cone-directed interventions.
Topics: Adolescent; Adult; Child; Color Perception Tests; Color Vision Defects; Electroretinography; Female; Follow-Up Studies; GTP-Binding Protein gamma Subunits; Humans; Male; Middle Aged; Multimodal Imaging; Nystagmus, Pathologic; Ophthalmoscopy; Optical Imaging; Pedigree; Phenotype; Retinal Cone Photoreceptor Cells; Tomography, Optical Coherence; Visual Acuity; Young Adult
PubMed: 32203983
DOI: 10.1167/iovs.61.3.40 -
Investigative Ophthalmology & Visual... Dec 2019To perform deep phenotyping of subjects with PDE6C achromatopsia and examine disease natural history.
PURPOSE
To perform deep phenotyping of subjects with PDE6C achromatopsia and examine disease natural history.
METHODS
Eight subjects with disease-causing variants in PDE6C were assessed in detail, including clinical phenotype, best-corrected visual acuity, fundus autofluorescence, and optical coherence tomography. Six subjects also had confocal and nonconfocal adaptive optics scanning light ophthalmoscopy, axial length, international standard pattern and full-field electroretinography (ERG), short-wavelength flash (S-cone) ERGs, and color vision testing.
RESULTS
All subjects presented with early-onset nystagmus, decreased best-corrected visual acuity, light sensitivity, and severe color vision loss, and five of them had high myopia. We identified three novel disease-causing variants and provide phenotype data associated with nine variants for the first time. No subjects had foveal hypoplasia or residual ellipsoid zone (EZ) at the foveal center; one had an absent EZ, three had a hyporeflective zone, and four had outer retinal atrophy. The mean width of the central EZ lesion on optical coherence tomography at baseline was 1923 μm. The mean annual increase in EZ lesion size was 48.3 μm. Fundus autofluorescence revealed a central hypoautofluorescence with a surrounding ring of increased signal (n = 5). The mean hypoautofluorescent area at baseline was 3.33 mm2 and increased in size by a mean of 0.13 mm2/year. Nonconfocal adaptive optics scanning light ophthalmoscopy revealed residual foveal cones in only one of two cases. Full-field ERGs were consistent with severe generalized cone system dysfunction but with relative preservation of S-cone sensitivity.
CONCLUSIONS
PDE6C retinopathy is a severe cone dysfunction syndrome often presenting as typical achromatopsia but without foveal hypoplasia. Myopia and slowly progressive maculopathy are common features. There are few (if any) residual foveal cones for intervention in older adults.
Topics: Adolescent; Adult; Child; Color Vision; Color Vision Defects; Cyclic Nucleotide Phosphodiesterases, Type 6; Electroretinography; Eye Proteins; Female; Follow-Up Studies; Forecasting; Humans; Male; Middle Aged; Ophthalmoscopy; Phenotype; Tomography, Optical Coherence; Visual Acuity; Young Adult
PubMed: 31826238
DOI: 10.1167/iovs.19-27761 -
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 -
Expert Opinion on Biological Therapy Jan 2018The eye is a target for investigational gene therapy due to the monogenic nature of many inherited retinal and optic nerve degenerations (IRD), its accessibility, tight... (Review)
Review
INTRODUCTION
The eye is a target for investigational gene therapy due to the monogenic nature of many inherited retinal and optic nerve degenerations (IRD), its accessibility, tight blood-ocular barrier, the ability to non-invasively monitor for functional and anatomic outcomes, as well as its relative immune privileged state.Vectors currently used in IRD clinical trials include adeno-associated virus (AAV), small single-stranded DNA viruses, and lentivirus, RNA viruses of the retrovirus family. Both can transduce non-dividing cells, but AAV are non-integrating, while lentivirus integrate into the host cell genome, and have a larger transgene capacity.
AREAS COVERED
This review covers Leber's congenital amaurosis, choroideremia, retinitis pigmentosa, Usher syndrome, Stargardt disease, Leber's hereditary optic neuropathy, Achromatopsia, and X-linked retinoschisis.
EXPERT OPINION
Despite great potential, gene therapy for IRD raises many questions, including the potential for less invasive intravitreal versus subretinal delivery, efficacy, safety, and longevity of response, as well as acceptance of novel study endpoints by regulatory bodies, patients, clinicians, and payers. Also, ultimate adoption of gene therapy for IRD will require widespread genetic screening to identify and diagnose patients based on genotype instead of phenotype.
Topics: Choroideremia; Clinical Trials as Topic; Color Vision Defects; Dependovirus; Genetic Therapy; Genetic Vectors; Humans; Lentivirus; Macular Degeneration; Nerve Degeneration; Stargardt Disease; Usher Syndromes; cis-trans-Isomerases
PubMed: 29057663
DOI: 10.1080/14712598.2018.1389886