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Advances in Experimental Medicine and... 2018Rod monochromatism (achromatopsia) is a congenital cone photoreceptor disorder, which is rare, affecting about 1 in 30,000 individuals. These patients have normal rod... (Review)
Review
Rod monochromatism (achromatopsia) is a congenital cone photoreceptor disorder, which is rare, affecting about 1 in 30,000 individuals. These patients have normal rod function but no detectable cone function; therefore, everything they see is in shades of gray (total color blindness). Patients usually present in infancy with nystagmus and photophobia. Vision is usually about 20/200 or worse; patients have a hyperopic refractive error. Some patients show paradoxical pupillary response; that is, the pupils dilate in bright light. Fundus examination is normal, though pigmentary mottling and atrophic changes may be observed at the macula. Incomplete achromatopsia: Patients in this group have somewhat better visual acuity, about 20/80 to 20/120, with some residual functioning of cone photoreceptors. This milder form allows some color discrimination. Complete achromatopsia: It occurs in about 4-10% of Pingelapese islanders, who live on one of the Eastern Caroline Islands of Micronesia.
Topics: Color Vision Defects; Humans; Nystagmus, Pathologic; Photophobia; Retinal Cone Photoreceptor Cells; Visual Acuity
PubMed: 30578497
DOI: 10.1007/978-3-319-95046-4_24 -
Advances in Experimental Medicine and... 2018Unlike rod monochromatism, which is an autosomal recessive disease that affects all three types of cones, blue cone monochromatism (BCM) is an X-linked disease that... (Review)
Review
Unlike rod monochromatism, which is an autosomal recessive disease that affects all three types of cones, blue cone monochromatism (BCM) is an X-linked disease that affects only L-cones and M-cones. The rods and S-cones are normal. The estimated prevalence is 1 in 100,00 individuals.
Topics: Color Vision Defects; Genetic Diseases, X-Linked; Humans; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells
PubMed: 30578487
DOI: 10.1007/978-3-319-95046-4_14 -
The British Journal of Ophthalmology Jan 2016The cone dysfunction syndromes are a heterogeneous group of inherited, predominantly stationary retinal disorders characterised by reduced central vision and varying... (Review)
Review
The cone dysfunction syndromes are a heterogeneous group of inherited, predominantly stationary retinal disorders characterised by reduced central vision and varying degrees of colour vision abnormalities, nystagmus and photophobia. This review details the following conditions: complete and incomplete achromatopsia, blue-cone monochromatism, oligocone trichromacy, bradyopsia and Bornholm eye disease. We describe the clinical, psychophysical, electrophysiological and imaging findings that are characteristic to each condition in order to aid their accurate diagnosis, as well as highlight some classically held notions about these diseases that have come to be challenged over the recent years. The latest data regarding the genetic aetiology and pathological changes observed in the cone dysfunction syndromes are discussed, and, where relevant, translational avenues of research, including completed and anticipated interventional clinical trials, for some of the diseases described herein will be presented. Finally, we briefly review the current management of these disorders.
Topics: Color Vision Defects; Genotype; Humans; Phenotype; Retinal Cone Photoreceptor Cells; Retinal Diseases; Syndrome
PubMed: 25770143
DOI: 10.1136/bjophthalmol-2014-306505 -
The Journal of Gene Medicine Mar 2017The present review summarizes the current status of achromatopsia (ACHM) gene therapy-related research activities and provides an outlook for their clinical application.... (Review)
Review
The present review summarizes the current status of achromatopsia (ACHM) gene therapy-related research activities and provides an outlook for their clinical application. ACHM is an inherited eye disease characterized by a congenital absence of cone photoreceptor function. As a consequence, ACHM is associated with strongly impaired daylight vision, photophobia, nystagmus and a lack of color discrimination. Currently, six genes have been linked to ACHM. Up to 80% of the patients carry mutations in the genes CNGA3 and CNGB3 encoding the two subunits of the cone cyclic nucleotide-gated channel. Various animal models of the disease have been established and their characterization has helped to increase our understanding of the pathophysiology associated with ACHM. With the advent of adeno-associated virus vectors as valuable gene delivery tools for retinal photoreceptors, a number of promising gene supplementation therapy programs have been initiated. In recent years, huge progress has been made towards bringing a curative treatment for ACHM into clinics. The first clinical trials are ongoing or will be launched soon and are expected to contribute important data on the safety and efficacy of ACHM gene supplementation therapy.
Topics: Animals; Clinical Trials as Topic; Color Vision Defects; Cyclic Nucleotide-Gated Cation Channels; Dependovirus; Disease Models, Animal; Drug Evaluation, Preclinical; Genetic Predisposition to Disease; Genetic Therapy; Genetic Vectors; Humans; Mutation; Transgenes; Treatment Outcome
PubMed: 28095637
DOI: 10.1002/jgm.2944 -
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 -
Handbook of Experimental Pharmacology 2017As our understanding of the genetic basis for inherited retinal disease has expanded, gene therapy has advanced into clinical development. When the gene mutations... (Review)
Review
As our understanding of the genetic basis for inherited retinal disease has expanded, gene therapy has advanced into clinical development. When the gene mutations associated with inherited retinal dystrophies were identified, it became possible to create animal models in which individual gene were altered to match the human mutations. The retina of these animals were then characterized to assess whether the mutated genes produced retinal phenotypes characteristic of disease-affected patients. Following the identification of a subpopulation of patients with the affected gene and the development of techniques for the viral gene transduction of retinal cells, it has become possible to deliver a copy of the normal gene into the retinal sites of the mutated genes. When this was performed in animal models of monogenic diseases, at an early stage of retinal degeneration when the affected cells remained viable, successful gene augmentation corrected the structural and functional lesions characteristic of the specific diseases in the areas of the retina that were successfully transduced. These studies provided the essential proof-of-concept needed to advance monogenic gene therapies into clinic development; these therapies include treatments for: Leber's congenital amaurosis type 2, caused by mutations to RPE65, retinoid isomerohydrolase; choroideremia, caused by mutations to REP1, Rab escort protein 1; autosomal recessive Stargardt disease, caused by mutations to ABCA4, the photoreceptor-specific ATP-binding transporter; Usher 1B disease caused by mutations to MYO7A, myosin heavy chain 7; X-linked juvenile retinoschisis caused by mutations to RS1, retinoschisin; autosomal recessive retinitis pigmentosa caused by mutations to MERTK, the proto-oncogene tyrosine-protein kinase MER; Leber's hereditary optic neuropathy caused by mutations to ND4, mitochondrial nicotinamide adenine dinucleotide ubiquinone oxidoreductase (complex I) subunit 4 and achromatopsia, caused by mutations to CNGA3, cyclic nucleotide-gated channel alpha 3 and CNGB3, cyclic nucleotide-gated channel beta 3. This review includes a tabulated summary of treatments for these monogenic retinal dystrophies that have entered into clinical development, as well as a brief summary of the preclinical data that supported their advancement into clinical development.
Topics: Color Vision Defects; Humans; Leber Congenital Amaurosis; Optic Atrophy, Hereditary, Leber; Proto-Oncogene Mas; Retinal Dystrophies; Retinitis Pigmentosa
PubMed: 28035529
DOI: 10.1007/164_2016_91 -
Wilderness & Environmental Medicine Dec 2023This Lessons from History article uses science, aviation, medicine, and mountaineering sources to describe some of the effects of hypoxia, illumination, and other...
This Lessons from History article uses science, aviation, medicine, and mountaineering sources to describe some of the effects of hypoxia, illumination, and other environmental conditions on the eye, the central nervous system, and light and color perception. The historical perspective is augmented by an analysis of an informal observation of the altered perception of red color on a deck of playing cards while climbing Mera Peak in the Himalaya. The appearance of a grayer red color on the cards was initially attributed to the effects of hypoxia alone. Instead, analysis of cards in combination with the low incidence of protan color vision defects at altitude indicated that glare and contrast effects in the extremely bright lighting environment combined with hypoxia likely caused the perception of a grayer red. The incident provides an educational opportunity for review, analysis, and commentary about some of the complex elements that impact color vision.
Topics: Humans; Color Vision; Color Perception; Altitude; Color Vision Defects; Hypoxia
PubMed: 37775373
DOI: 10.1016/j.wem.2023.08.003 -
Ophthalmic Research 2015Achromatopsia (ACHM) is a rare autosomal recessive inherited retinal disorder with an incidence of approximately 1 in 30,000. It presents at birth or early infancy and... (Review)
Review
Achromatopsia (ACHM) is a rare autosomal recessive inherited retinal disorder with an incidence of approximately 1 in 30,000. It presents at birth or early infancy and is typically characterized by reduced visual acuity, nystagmus, photophobia, and very poor or absent color vision. The symptoms arise from isolated cone dysfunction, which can be caused by mutations in the crucial components of the cone phototransduction cascade. Although ACHM is considered a functionally nonprogressive disease affecting only the cone system, recent studies have described progressive age-dependent changes in retinal architecture. Currently, no specific therapy is available for ACHM; however, gene replacement therapy performed on animal models for three ACHM genes has shown promising results. Accurate genetic and clinical diagnosis of patients may therefore enhance and enable therapeutic intervention in the near future. This short review summarizes the genetic background, pathophysiology, clinical findings, diagnostics, and therapeutic perspectives in ACHM.
Topics: Animals; Color Vision Defects; Disease Models, Animal; Drug Evaluation, Preclinical; Electroretinography; Eye Proteins; Genetic Therapy; Humans; Mutation; Pedigree; Retinal Cone Photoreceptor Cells; Retinal Degeneration
PubMed: 26304472
DOI: 10.1159/000435957 -
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 -
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