-
International Journal of Molecular... Feb 2021Achromatopsia (ACHM) is a rare genetic disorder of infantile onset affecting cone photoreceptors. To determine the extent of progressive retinal changes in... (Observational Study)
Observational Study
Achromatopsia (ACHM) is a rare genetic disorder of infantile onset affecting cone photoreceptors. To determine the extent of progressive retinal changes in achromatopsia, we performed a detailed longitudinal phenotyping and genetic characterization of an Italian cohort comprising 21 ACHM patients (17 unrelated families). Molecular genetic testing identified biallelic pathogenic mutations in known ACHM genes, including four novel variants. At baseline, the patients presented a reduced best corrected visual acuity (BCVA), reduced macular sensitivity (MS), normal dark-adapted electroretinogram (ERG) responses and undetectable or severely reduced light-adapted ERG. The longitudinal analysis of 16 patients (mean follow-up: 5.4 ± 1.0 years) showed a significant decline of BCVA (0.012 logMAR/year) and MS (-0.16 dB/year). Light-adapted and flicker ERG responses decreased below noise level in three and two patients, respectively. Only two patients (12.5%) progressed to a worst OCT grading during the follow-up. Our findings corroborate the notion that ACHM is a progressive disease in terms of BCVA, MS and ERG responses, and affects slowly the structural integrity of the retina. These observations can serve towards the development of guidelines for patient selection and intervention timing in forthcoming gene replacement therapies.
Topics: Adolescent; Adult; Biomarkers; Child, Preschool; Color Vision Defects; Cyclic Nucleotide Phosphodiesterases, Type 6; Cyclic Nucleotide-Gated Cation Channels; DNA Mutational Analysis; Eye Proteins; Female; Heterotrimeric GTP-Binding Proteins; Humans; Longitudinal Studies; Male; Mutation; Pedigree; Phenotype; Prognosis; Retrospective Studies; Tomography, Optical Coherence; Young Adult
PubMed: 33562422
DOI: 10.3390/ijms22041681 -
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 -
Scientific Reports Feb 2022Color blindness, or color vision deficiency (CVD), is an ocular disease that suppresses the recognition of different colors. Recently, tinted glasses and lenses have...
Color blindness, or color vision deficiency (CVD), is an ocular disease that suppresses the recognition of different colors. Recently, tinted glasses and lenses have been studied as hopeful devices for color blindness correction. In this study, 2D biocompatible and flexible plasmonic contact lenses were fabricated using polydimethylsiloxane (PDMS) and a low-cost, and simple design based on the soft nano-lithography method and investigated for correction of red-green (deuteranomaly) color blindness. In addition, the stability test of the fabricated plasmonic contact lenses was investigated into the phosphate buffered saline (PBS) solution and the proposed lens offers an excellent stability into the PBS solution. The plasmonic contact lens proposed herein is based on the plasmonic surface lattice resonance (SLR) phenomenon and offers a good color filter for color blindness correction. The biocompatibility, low cost, stability, and simple fabrication of these contact lenses can offer new insights for applications of color blindness correction.
Topics: Biocompatible Materials; Buffers; Color; Color Perception; Color Vision Defects; Contact Lenses; Dimethylpolysiloxanes; Humans; Phosphates; Pliability; Saline Solution; Vision, Ocular
PubMed: 35132172
DOI: 10.1038/s41598-022-06089-8 -
BMC Ophthalmology Sep 2022Alström Syndrome (AS) is an autosomal recessive hereditary disease with the characteristics of multiorgan dysfunction. Due to the heterogeneity of clinical...
PURPOSE
Alström Syndrome (AS) is an autosomal recessive hereditary disease with the characteristics of multiorgan dysfunction. Due to the heterogeneity of clinical manifestations of AS, genetic testing is crucial for the diagnosis of AS. Herein, we used whole-exome sequencing (WES) to determine the genetic causes and characterize the clinical features of three affected patients in two Chinese families with Alström Syndrome.
MATERIALS AND METHODS
Three affected patients (initially diagnosed as achromatopsia). and five asymptomatic members were recruited for both genetic and clinical tests. The complete ophthalmic examinations and systemic examinations were performed on all participants. Whole exome sequencing (WES) was performed for mutation detection. The silico analysis was also applied to predict the pathogenesis of identified pathogenic variants.
RESULTS
In family 1, the proband showed low vision, hyperopia, photophobia, nystagmus, and total color blindness. DNA analysis revealed that she carried a compound heterozygote with two novel pathogenic variants in the ALMS1 gene NM_015120.4:c.10379del (NP_055935.4:p.(Asp2252Tyr)) and NM_015120.4:c.11641_11642del (NP_055935.4:p.(Val3881ThrfsTer11)). Further systemic examinations showed short stature, acanthosis nigricans, and sensorineural hearing loss. In family 2, two affected siblings presented the low vision, hyperopia, photophobia, nystagmus, and total color blindness. DNA analysis revealed that they carried a same compound heterozygote with two novel pathogenic variants in the ALMS1 gene NM_015120.4:c.10379del (NP_055935.4:p.(Asn3460IlefsTer49)), NM_015120.4:c.10819C > T (NP_055935.4:p.(Arg3607Trp)). Further systemic examinations showed obesity and mild abnormalities of lipid metabolism. According to the genetic testing results and further systemic analysis, the three affected patients were finally diagnosed as Alström Syndrome (AS).
CONCLUSIONS
We found two new compound heterozygous pathogenic variants of the ALMS1 gene and determined the diagnosis as Alström Syndrome in three patients of two Chinese families. Our study extends the genotypic and phenotypic spectrums for ALMS1 -AS and emphasizes the importance of gene testing in assisting the clinical diagnosis for cases with phenotypic diversities, which would help the AS patients with early diagnosis and treatment to reduce future systemic damage.
Topics: Alstrom Syndrome; Cell Cycle Proteins; China; Color Vision Defects; DNA; Female; Humans; Hyperopia; Mutation; Pedigree; Photophobia; Vision, Low
PubMed: 36162988
DOI: 10.1186/s12886-022-02597-3 -
Scientific Reports Jan 2021To evaluate the changes in functional vision in patients with resolved endophthalmitis. This was a cross-sectional study. The study included 20 patients with resolved...
To evaluate the changes in functional vision in patients with resolved endophthalmitis. This was a cross-sectional study. The study included 20 patients with resolved endophthalmitis and best-corrected visual acuity of 20/100 or better. Visual acuity (VA), contrast threshold (CT), red/green (RG) and yellow/blue (YB) colour vision and 15 Hz flicker modulation threshold (FMT) were assessed using standard psychophysical techniques. The median age was 54 years. The median visual acuity was 0.27 (~ 20/40-Snellen Equivalent) ((interquartile range [IQR]), 0.30) logMAR). The median log contrast threshold (CT) was - 1.13 (IQR, 0.36) log units (normative value for age-matched CT: - 1.61 log units). The median red/green (RG) and yellow/blue (YB) thresholds were 11.52 (IQR, 26.19) and 9.45 (IQR, 16.20) CAD units respectively, which were at least 5 times higher than age-matched normative RG and YB thresholds. The median central cone- mediated FMT was 17.64% (IQR, 23.40%), which was much higher compared to age-matched FMT (5.48% [IQR, 3.47]). Linear regression revealed significant relationship between contrast thresholds and foveal thickness (y = 0.001x-1.47, R = 0.20, p = 0.048). Though endophthalmitis may resolve with a good visual acuity, deficits in visual functions like chromatic discrimination, cone-mediated flicker and contrast sensitivity persist.
Topics: Adolescent; Adult; Color Vision Defects; Contrast Sensitivity; Cross-Sectional Studies; Endophthalmitis; Female; Humans; Male; Middle Aged; Visual Acuity; Young Adult
PubMed: 33504844
DOI: 10.1038/s41598-021-81530-y -
Ceska a Slovenska Oftalmologie :... 2016The aim of this review is to provide a comprehensive summary of current gene therapy clinical trials for monogenic and optic nerve disorders.The number of genes for... (Review)
Review
The aim of this review is to provide a comprehensive summary of current gene therapy clinical trials for monogenic and optic nerve disorders.The number of genes for which gene-based therapies are being developed is growing. At the time of writing this review gene-based clinical trials have been registered for Leber congenital amaurosis 2 (LCA2), retinitis pigmentosa 38, Usher syndrome 1B, Stargardt disease, choroideremia, achromatopsia, Leber hereditary optic neuropathy (LHON) and X-linked retinoschisis. Apart from RPE65 gene therapy for LCA2 and MT-ND4 for LHON which has reached phase III, all other trials are in investigation phase I and II, i.e. testing the efficacy and safety.Because of the relatively easy accessibility of the retina and its ease of visualization which allows monitoring of efficacy, gene-based therapies for inherited retinal disorders represent a very promising treatment option. With the development of novel therapeutic approaches, the importance of establishing not only clinical but also molecular genetic diagnosis is obvious.Key words: gene therapy, monogenic retinal diseases, optic nerve atrophy, mitochondrial disease.
Topics: Eye Diseases, Hereditary; Genetic Therapy; Humans; Optic Nerve Diseases; Retinal Diseases
PubMed: 27860478
DOI: No ID Found -
Scientific Reports May 2022We set out to develop a simple objective test of functional colour vision based on eye movements made in response to moving patterns. We exploit the finding that while...
We set out to develop a simple objective test of functional colour vision based on eye movements made in response to moving patterns. We exploit the finding that while the motion of a colour-defined stimulus can be cancelled by adding a low-contrast luminance-defined stimulus moving in the opposite direction, the "equivalent luminance contrast" required for such cancellation is reduced when colour vision is abnormal. We used a consumer-grade infrared eye-tracker to measure eye movements made in response to coloured patterns drifting at different speeds. An automated analysis of these movements estimated individuals' red-green equiluminant point and their equivalent luminance contrast. We tested 34 participants: 23 colour vision normal controls, 9 deuteranomalous and 2 protanomalous individuals. We obtained reliable estimates of strength of directed eye movements (i.e. combined optokinetic and voluntary tracking) for stimuli moving at 16 deg/s and could use these data to classify participants' colour vision status with a sensitivity rate of 90.9% and a specificity rate of 91.3%. We conclude that an objective test of functional colour vision combining a motion-nulling technique with an automated analysis of eye movements can diagnose and assess the severity of protanopia and deuteranopia. The test places minimal demands on patients (who simply view a series of moving patterns for less than 90 s), requires modest operator expertise, and can be run on affordable hardware.
Topics: Color Perception; Color Vision; Color Vision Defects; Contrast Sensitivity; Eye Movements; Humans; Motion Perception
PubMed: 35562176
DOI: 10.1038/s41598-022-11152-5 -
Scientific Reports May 2023Effects of type 2 diabetes on achromatic and chromatic contrast sensitivity (CS) are still controversial. In this study, we aimed to investigate CS in patients without...
Effects of type 2 diabetes on achromatic and chromatic contrast sensitivity (CS) are still controversial. In this study, we aimed to investigate CS in patients without diabetic retinopathy (no-DR) and in those with non-proliferative DR (NPDR) and proliferative DR (PDR) using psychophysical methods with transient and sustained achromatic stimuli and color patches. Achromatic CS was measured with the pulsed pedestal (PP) paradigm (7, 12, and 19 cd/m) and pedestal-△-pedestal (P-△-P) paradigm (11.4, 18, and 28.5 cd/m). A chromatic discrimination paradigm that assesses protan, deutan, and tritan color vision was adopted. Forty-two patients (no-DR n = 24, NPDR n = 12, PDR = 6; male n = 22, mean age = 58.1 y/o) and 38 controls (male n = 18, mean age = 53.4 y/o) participated. In patients, mean thresholds were higher than in controls and linear trends were significant in most conditions. For the PP paradigm, differences were significant in the PDR and NPDR groups in the 7 and 12 cd/m condition. For the P-△-P paradigm, differences were only significant in the PDR group in the 11 cd/m condition. Chromatic contrast loss was significant in the PDR group along the protan, deutan and tritan axes. The results suggest independent involvements of achromatic and chromatic CS in diabetic patients.
Topics: Humans; Male; Middle Aged; Female; Contrast Sensitivity; Diabetes Mellitus, Type 2; Color Vision Defects; Color Vision; Diabetic Retinopathy
PubMed: 37156848
DOI: 10.1038/s41598-023-34407-1 -
Digital Journal of Ophthalmology : DJO 2023We present a case of presumed topiramate-induced retinopathy in a 58-year-old woman who presented with progressive, bilateral visual loss following a 3- to 4-year...
We present a case of presumed topiramate-induced retinopathy in a 58-year-old woman who presented with progressive, bilateral visual loss following a 3- to 4-year history of oral topiramate intake for migraine. She reported difficulty with light adaptation, hemeralopia, and color desaturation. Her best-corrected visual acuity was 1/60 (20/1200) in the right eye and 6/18 (20/60) in the left eye, and she performed poorly on Ishihara color plate testing. Anterior segment examination was normal; dilated funduscopy showed mild macular pigmentary changes. Optical coherence tomography revealed subtle thinning and reduced reflectivity of the subfoveal ellipsoid zone and interdigitation zone bilaterally, associated with increased foveal autofluorescence. Humphrey visual field 24-2 revealed central defects. Electrodiagnostic testing showed a reduced and delayed b-wave and a normal a-wave on photopic full-field electroretinogram (ERG), with normal scotopic responses; multifocal ERG revealed reduced responses in the inner 10° in both eyes. She underwent extensive investigations including whole-body computed tomography and positron emission tomography scan, magnetic resonance imaging of the brain, uveitis screening, retinal autoantibody testing, and genetic testing on the retinal dystrophy panel to rule-out other causes for her presentation, all of which were normal or negative.
Topics: Female; Humans; Middle Aged; Electroretinography; Migraine Disorders; Retina; Retinal Dystrophies; Topiramate
PubMed: 37727465
DOI: 10.5693/djo.02.2023.01.004