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Translational Vision Science &... Jun 2023To quantify visual performance of patients with achromatopsia at various contrast and luminance combinations typical for daily living conditions, in comparison to...
PURPOSE
To quantify visual performance of patients with achromatopsia at various contrast and luminance combinations typical for daily living conditions, in comparison to controls, and to measure beneficial effects of short-wavelength cutoff filter glasses used by patients with achromatopsia to reduce glare sensation.
METHODS
Best-corrected visual acuity (BCVA) was tested with Landolt rings using an automated device (VA-CAL test). The visual acuity space was assessed for each participant with and without filter glasses (transmission >550 nm) at 46 contrast-luminance combinations (18%-95%; 0-10,000 cd/m2). The BCVA differences between both conditions were calculated for each combination as absolute values and relative to individual standard BCVA.
RESULTS
Fourteen achromats (mean ± SD: 37.9 ± 17.6 years) and 14 normally sighted controls (mean ± SD: 25.2 ± 2.8 years) were included in the study. Without filter glasses, achromats' BCVA was best at 30 cd/m2 (mean ± SEM: 0.76 ± 0.046 logarithm of the minimum angle of resolution [logMAR], contrast = 89%) and worst at 10,000 cd/m2 (mean ± SEM: 1.41 ± 0.08 logMAR, contrast = 18%), a deterioration up to 0.6 logMAR due to increased luminance and decreased contrast. Filter glasses improved achromats' BCVA for almost all luminances by about 0.2 logMAR but lowered controls' BCVA by about 0.1 logMAR.
CONCLUSIONS
The VA-CAL test provides numerical proof that short-wavelength cutoff filter glasses can help patients with achromatopsia in everyday life, avoiding the common situation of severe visual impairment at certain daily object contrasts and ambient luminances.
TRANSLATIONAL RELEVANCE
The VA-CAL test discovers losses of spatial resolution in the visual acuity space not seen in standardized BCVA assessment. Filter glasses improve the patients' daily visual performance, rendering them a strongly recommended visual aid in achromatopsia.
Topics: Humans; Color Vision Defects; Social Conditions; Visual Acuity; Vision Disorders
PubMed: 37358491
DOI: 10.1167/tvst.12.6.20 -
International Medical Case Reports... 2023To describe a case of optic neuropathy after prolonged sirolimus therapy in the setting of cardiac transplant.
OBJECTIVE
To describe a case of optic neuropathy after prolonged sirolimus therapy in the setting of cardiac transplant.
BACKGROUND
Sirolimus is an immunosuppressant that inhibits Mechanistic Target of Rapamycin (mTOR) and blocks T-cell activation and B-cell differentiation by preventing response to Interleukin-2 (IL-2). Tacrolimus is another immunosuppressive agent, one of the known but uncommon side effects of which is bilateral optic neuropathy years after taking the medication. To the best of our knowledge, this is the first report of sequential optic neuropathy after years of treatment with sirolimus.
CASE PRESENTATION
A 69-year-old male with a history of cardiac transplantation presented with progressive, sequential, and painless vision loss. Visual acuity was 20/150 OD and 20/80 OS, with impaired color vision in both eyes (Ishihara 0/10) and bilateral disc pallor and mild optic disc edema in the left eye. Visual field was constricted in both eyes. The patient was on prolonged sirolimus therapy for over 7 years. Orbital MRI revealed bilateral chiasmatic thickness and FLAIR hyperintensity, without optic nerve enhancement post gadolinium. After extensive work up, other etiologies such as infectious, inflammatory, and neoplastic lesions were ruled out. Subsequently, sirolimus was substituted with cyclosporin that led to gradual improvement of vision and visual fields bilaterally.
CONCLUSION
Optic neuropathy is a rare side effect of tacrolimus, which has been seen as sudden, painless, and bilateral vision loss in post-transplant patients. Other concurrent medications influencing the cytochrome P4503A enzyme complexes may alter the pharmacokinetics of tacrolimus and increase the likelihood of toxicity. Discontinuation of offending agent has been shown to improve visual defects. We presented a rare case of optic neuropathy in a patient on sirolimus, whose visual defects improved upon discontinuation of sirolimus and switching to cyclosporin.
PubMed: 37284436
DOI: 10.2147/IMCRJ.S388481 -
Scientific Reports Jun 2023The ARR3 gene, also known as cone arrestin, belongs to the arrestin family and is expressed in cone cells, inactivating phosphorylated-opsins and preventing cone...
The ARR3 gene, also known as cone arrestin, belongs to the arrestin family and is expressed in cone cells, inactivating phosphorylated-opsins and preventing cone signals. Variants of ARR3 reportedly cause X-linked dominant female-limited early-onset (age < 7 years old) high myopia (< - 6D). Here, we reveal a new mutation (c.228T>A, p.Tyr76*) in ARR3 gene that can cause early-onset high myopia (eoHM) limited to female carriers. Protan/deutan color vision defects were also found in family members, affecting both genders. Using ten years of clinical follow-up data, we identified gradually worsening cone dysfunction/color vision as a key feature among affected individuals. We present a hypothesis that higher visual contrast due to the mosaic of mutated ARR3 expression in cones contributes to the development of myopia in female carriers.
Topics: Child; Female; Humans; Male; Arrestin; Color Vision; Color Vision Defects; Mutation; Myopia; Retinal Cone Photoreceptor Cells
PubMed: 37268727
DOI: 10.1038/s41598-023-36141-0 -
Indian Journal of Ophthalmology May 2023To investigate the quality of life (QoL) in a sample of color vision deficit (CVD) patients in India and how color vision deficiency affects them psychologically,...
PURPOSE
To investigate the quality of life (QoL) in a sample of color vision deficit (CVD) patients in India and how color vision deficiency affects them psychologically, economically, and in productivity related to their work and occupation.
METHODS
A descriptive and case-control study design using a questionnaire was conducted on N = 120 participants, of whom 60 were patients of CVD (52 male and eight female) who visited two eye facilities in Hyderabad between 2020 and 2021 and 60 were age-matched normal color vision participants who served as controls. We validated English-Telugu adapted version of CVD-QoL, developed by Barry et al. in 2017 (CB-QoL). The CVD-QoL consists of 27 Likert-scale items with factors (lifestyle, emotions, and work). Color vision was assessed using the Ishihara and Cambridge Mollen color vision tests. A six-point Likert scale was used, with lower scores indicating poor QoL (from 1 = severe issue to 6 = no problem).
RESULTS
The CVD-QoL questionnaire's reliability and internal consistency were measured, including Cronbach's α (α =0.70-0.90). There was no significance between the group in age (t = -1.2, P = 0.67) whereas the Ishihara colour vision test, scores showed a significant difference (t = 4.50, P < 0.001). The QoL scores showed a significant difference towards lifestyle, emotions and work (P = 0.001). The CVD group had a poorer QoL score than the normal color vision group odds ratio [OR] =0.31, 95% confidence interval [CI], (P = 0.002, CI = 0.14-0.65, Z = 3.0) . In this analysis, a low CI indicated that the OR was more precise.
CONCLUSION
Color vision deficiency affects Indians' QoL, according to this study. The mean scores of lifestyle, emotions, and work were lower than the UK sample.Since CVD is underreported and possibly affects developing countries more, advocacy for a new health care plan on CVD is essential. Increasing public understanding and awareness could also help diagnosing the CVD population.
Topics: Humans; Male; Female; Quality of Life; Color Vision; Color Vision Defects; Case-Control Studies; Reproducibility of Results; Surveys and Questionnaires; Cardiovascular Diseases
PubMed: 37202949
DOI: 10.4103/ijo.IJO_1975_22 -
Nigerian Medical Journal : Journal of... 2023To objectively measure visual function amongst Primary Open Angle Glaucoma (POAG) patients and compare these with age and sex-matched controls by describing the...
BACKGROUND
To objectively measure visual function amongst Primary Open Angle Glaucoma (POAG) patients and compare these with age and sex-matched controls by describing the characteristics of visual function in relation to the severity of POAG.
METHODOLOGY
A case-control study was carried out among 106 POAG patients and an equal number of age-sex matched controls attending Asokoro District Hospital, Abuja, and Eye Foundation Hospital Abuja from Nov 2012 to April 2013. The objective measures of visual function assessed include visual acuity (VA), contrast sensitivity (CS), colour vision (CV), and visual fields (MD) in the better eye (BE)].
RESULTS
All measures of visual function were found to be reduced comparing cases to controls and this was statistically significant. VABE (0.39±0.73; 0.0017±0.02p<0.001); MDBE (-8.02±6.80; 0.17±0.3P<0.001); CSBE (1.46±0.59; 1.90±0.16p<0.001): Colour vision defects (54.7%; 6.6% p<0.001). In comparing mild; moderate; severe glaucoma: VABE (0.0053±0.03; 0.057±0.08; 0.766±0.90 p<0.001); MDBE (-3.46±1.93;-8.17±3.55;-16.43±6.01p <0.001); CSBE (1.88±0.26; 1.69± 0.37; 1.11±0.59 p<0.001): Color vision defects (20.6%; 31.6%; 86.9%) respectively (BE: Better Eye). While looking at the two independent groups above, mild and moderate were not statistically significant except for the visual field, but comparing mild with severe and moderate with severe, they had a statistically significant relationship across all the visual functions tested. In comparing controls with mild, color vision and visual field had a statistically significant difference. Comparing the groups with mild and moderate glaucoma, only visual fields as a visual function were statistically significant. Whereas comparing both groups with the severe group independently, they had statistically significant in all the visual functions tested.
CONCLUSION
In conclusion, visual function was reduced in glaucoma patients as compared to controls. Visual acuity, contrast sensitivity and colour vision differed significantly in comparing mild with severe and moderate with severe. Color vision differed significantly in comparing mild to controls.
PubMed: 38887442
DOI: No ID Found -
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 -
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 -
Stem Cell Research Jun 2023Cone dystrophy with supernormal rod response (CDSRR) is associated with pathogenic variants of the KCNV2 gene that result in severe symptoms, including color vision...
Cone dystrophy with supernormal rod response (CDSRR) is associated with pathogenic variants of the KCNV2 gene that result in severe symptoms, including color vision defects, decreased visual acuity, and specific changes in electroretinogram responses. Two iPSC lines were obtained from two patients in the same family with different types of mutations in the KCNV2 gene. These lines could serve as a useful model for studying the pathogenetic mechanism and treatment development for CDSRR. PBMCs from donors have been reprogrammed into iPSC lines. Derived clones were characterized with mutation sequencing, analysis of common pluripotency-associated markers at the protein levels, and in vitro differentiation studies.
Topics: Humans; Cone Dystrophy; Induced Pluripotent Stem Cells; Retinal Rod Photoreceptor Cells; Mutation; Potassium Channels, Voltage-Gated
PubMed: 37121194
DOI: 10.1016/j.scr.2023.103099 -
Investigative Ophthalmology & Visual... Apr 2023Specific haplotypes (LVAVA, LIVVA, and LIAVA) formed by five polymorphisms (p.L153M, p.V171I, p.A174V, p.I178V, and p.S180A in exon 3 of OPN1LW) that cause partial or...
PURPOSE
Specific haplotypes (LVAVA, LIVVA, and LIAVA) formed by five polymorphisms (p.L153M, p.V171I, p.A174V, p.I178V, and p.S180A in exon 3 of OPN1LW) that cause partial or complete exon skipping have been reported as unique genetic causes of high myopia with or without colorblindness. This study aimed to identify the contribution of OPN1LW to early-onset high myopia (eoHM) and the molecular basis underlying eoHM with or without colorblindness.
METHODS
Comparative analysis of exome sequencing data was conducted for 1226 families with eoHM and 9304 families with other eye conditions. OPN1LW variants detected by targeted or whole exome sequencing were confirmed by long-range amplification and Sanger sequencing, together with segregation analysis. The clinical data were thoroughly analyzed.
RESULTS
Unique haplotypes and truncation variants in OPN1LW were detected exclusively in 68 of 1226 families with eoHM but in none of the 9304 families with other visual diseases (P = 1.63 × 10-63). Four classes of variants were identified: haplotypes causing partial splicing defects in OPN1LW (LVAVA or LIVVA in 31 families), LVAVA in OPN1LW-OPN1MW hybrid gene (in 3 families), LIAVA in OPN1LW (in 29 families), and truncations in OPN1LW (in 5 families). The first class causes partial loss of red photopigments, whereas the latter three result in complete loss of red photopigments. This is different from the replacement of red with green owing to unequal re-arrangement causing red-green colorblindness alone. Of the 68 families, 42 affected male patients (31 families) with the first class of variants (LVAVA or LIVVA in OPN1LW) had eoHM alone, whereas 37 male patients with the latter 3 classes had eoHM with protanopia. Adaptive optics retinal imaging demonstrated reduced cone regularity and density in men with eoHM caused by OPN1LW variants compared to those patients with eoHM and without OPN1LW variants.
CONCLUSION
Based on the 68 families with unique variants in OPN1LW, our study provides firm evidence that the two different phenotypes (eoHM with or without colorblindness) are caused by two different classes of variants (partial splicing-effect haplotypes or complete splicing-effect haplotypes/truncation variants, respectively). The contribution of OPN1LW to eoHM (isolated and syndromic) was characterized by OPN1LW variants found in 5.5% (68/1226) of the eoHM families, making it the second most common cause of monogenic eoHM alone (2.4%) and a frequent cause of syndromic monogenic eoHM with colorblindness. Such haplotypes, in which each individual variant alone is considered a benign polymorphism, are potential candidates for other hereditary diseases with causes of missing genetic defects.
Topics: Humans; Male; Color Vision Defects; Haplotypes; Mutation; Myopia; Pedigree
PubMed: 37097228
DOI: 10.1167/iovs.64.4.29