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Ophthalmology. Retina Mar 2024To examine the molecular causes of Schubert-Bornschein (S-B) congenital stationary night blindness (CSNB), clinically characterize in detail, and assess...
OBJECTIVE
To examine the molecular causes of Schubert-Bornschein (S-B) congenital stationary night blindness (CSNB), clinically characterize in detail, and assess genotype-phenotype correlations for retinal function and structure.
DESIGN
Retrospective, longitudinal, single-center case series.
PARTICIPANTS
One hundred twenty-two patients with S-B CSNB attending Moorfields Eye Hospital, United Kingdom.
METHODS
All case notes, results of molecular genetic testing, and OCT were reviewed.
MAIN OUTCOME MEASURES
Molecular genetics, presenting complaints, rates of nystagmus, nyctalopia, photophobia, strabismus, color vision defects and spherical equivalent refraction (SER). Retinal thickness, outer nuclear layer (ONL) thickness, and ganglion cell layer + inner plexiform layer (GCL+IPL) thickness from OCT imaging.
RESULTS
X-linked (CACNA1F and NYX) and autosomal recessive (TRPM1, GRM6, GPR179 and CABP4) genotypes were identified. The mean (± standard deviation) reported age of onset was 4.94 ± 8.99 years. Over the follow-up period, 95.9% of patients reported reduced visual acuity (VA), half had nystagmus, and 64.7% reported nyctalopia. Incomplete CSNB (iCSNB) patients more frequently had nystagmus and photophobia. Nyctalopia was similar for iCSNB and complete CSNB (cCSNB). Color vision data were limited but more defects were found in iCSNB. None of these clinical differences met statistical significance. There was no significant difference between groups in VA, with a mean of 0.46 logarithm of the minimum angle of resolution, and VA remained stable over the course of follow-up. Complete congenital stationary night blindness patients, specifically those with NYX and TRPM1 variants, were more myopic. CACNA1F patients showed the largest refractive variability, and the CABP4 patient was hyperopic. No significant differences were found in OCT structural analysis during the follow-up period.
CONCLUSIONS
Retinal structure in CSNB is stationary and no specific genotype-structure correlates were identified. Visual acuity seems to be relatively stable, with rare instances of progression.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
PubMed: 38522615
DOI: 10.1016/j.oret.2024.03.017 -
Vision Research May 2024EnChroma filters are aids designed to improve color vision for anomalous trichromats. Their use is controversial because the results of lab-based assessments of their...
EnChroma filters are aids designed to improve color vision for anomalous trichromats. Their use is controversial because the results of lab-based assessments of their effectiveness have so far largely failed to agree with positive anecdotal reports. However, the effectiveness of EnChroma filters will vary depending on the conditions of viewing, including whether the stimuli are broadband reflective surfaces or colors presented on RGB displays, whether illumination spectra are broadband or narrowband, the transmission spectra of particular filters, and the cone spectral sensitivity functions of the observer. We created a model of anomalous trichromatic color vision to predict the effects of EnChroma filters on the color signals impaired in anomalous trichromacy. Using the model we varied illumination, filter type and observer cone sensitivity functions, and tested the effect of presenting colors as broadband reflective surfaces or on RGB displays. We also used hyperspectral images to assess the impact of the filters on anomalous trichromats' color vision for natural scenes. Model results predicted that the filters should be broadly effective at enhancing anomalous trichromats' equivalent to L/(L + M) chromatic contrasts under a range of viewing conditions, but are substantially more effective for deuteranomals than for protanomals. The filters are predicted to be more effective for broadband reflective surfaces presented under broadband illuminants than for surfaces presented under narrowband illuminants or for colors presented on RGB displays. Since the potential impacts of contrast adaptation and perceptual learning are not considered in the model, it needs to be empirically validated. Results of empirical tests of the effects of EnChroma filters on deuteranomalous color vision in comparison with model predictions are presented in an accompanying paper (Somers et al., in prep.).
Topics: Humans; Color Perception; Color Perception Tests; Color Vision Defects; Retinal Cone Photoreceptor Cells; Color Vision; Color
PubMed: 38522412
DOI: 10.1016/j.visres.2024.108381 -
Frontiers in Neuroscience 2024Color blindness is a retinal disease that mainly manifests as a color vision disorder, characterized by achromatopsia, red-green color blindness, and blue-yellow color... (Review)
Review
Color blindness is a retinal disease that mainly manifests as a color vision disorder, characterized by achromatopsia, red-green color blindness, and blue-yellow color blindness. With the development of technology and progress in theory, extensive research has been conducted on the genetic basis of color blindness, and various approaches have been explored for its treatment. This article aims to provide a comprehensive review of recent advances in understanding the pathological mechanism, clinical symptoms, and treatment options for color blindness. Additionally, we discuss the various treatment approaches that have been developed to address color blindness, including gene therapy, pharmacological interventions, and visual aids. Furthermore, we highlight the promising results from clinical trials of these treatments, as well as the ongoing challenges that must be addressed to achieve effective and long-lasting therapeutic outcomes. Overall, this review provides valuable insights into the current state of research on color blindness, with the intention of informing further investigation and development of effective treatments for this disease.
PubMed: 38298913
DOI: 10.3389/fnins.2024.1265630 -
BMC Pediatrics Jan 2024Color vision deficiency is a common X-linked genetic disorder affecting the day-to-day lives of individuals, in which school-aged children's academic performance can be...
Color vision deficiency is a common X-linked genetic disorder affecting the day-to-day lives of individuals, in which school-aged children's academic performance can be negatively affected. The aim of this study was to evaluate the prevalence and genotypic frequency of congenital color vision defects (CVD), among primary schoolchildren in Adama, Ethiopia. A school-based cross-sectional study design was used. Students were purposively selected based on their ethnicity but were randomly selected from their sections, resulting in a final sample size estimated at 846 schoolchildren who had received informed consent from their families. Data was gathered using the Ishihara color vision test, 38-plate edition. The result of the study revealed that the total prevalence of CVD was much higher (5.6%) among the male children than that of the females, which was only about 1.79%. The prevalence rates of CVD among the targeted ethnic groups were found to be the highest among Amhara (7.45%) > Oromo (5.00%) > Gurage (2.13%) children, respectively, in descending order. 62.76% of the study subjects were homozygous dominant (AA), followed by those with a heterozygous genotype (Aa) (32.51%), and the remaining 4.73% had recessive (aa) genes.
Topics: Child; Female; Humans; Male; Color Vision Defects; Ethiopia; Cross-Sectional Studies; Prevalence; Genotype; Cardiovascular Diseases
PubMed: 38254053
DOI: 10.1186/s12887-024-04529-0 -
MedRxiv : the Preprint Server For... Dec 2023Multiple Sclerosis (MS) is a neuro-inflammatory disease of the Central Nervous System (CNS) in which the body's immune system attacks and destroys myelin sheath that...
PURPOSE
Multiple Sclerosis (MS) is a neuro-inflammatory disease of the Central Nervous System (CNS) in which the body's immune system attacks and destroys myelin sheath that protects nerve fibers and causes disruption in axonal signal transmission. Demyelinating Optic Neuritis (ON) is often a manifestation of MS and involves inflammation of the optic nerve. ON can cause vision loss, pain and discomfort in the eyes, and difficulties in color perception.In this study, we developed NeuroVEP, a portable, wireless diagnostic system that delivers visual stimuli through a smartphone in a headset and measures evoked potentials at the visual cortex from near the O1, Oz, O2, O9 and O10 locations on the scalp (extended 10-20 system) using custom electroencephalography (EEG) electrodes.
METHODS
Each test session is constituted by a short 2.5-minute full-field visual evoked potentials (ffVEP) test, followed by a 12.5-minute multifocal VEP (mfVEP) test. The ffVEP test evaluates the integrity of the visual pathway by analyzing the P1 (also known as P100) component of responses from each eye, while the mfVEP test evaluates 36 individual regions of the visual field for abnormalities. Extensive signal processing, feature extraction methods, and machine learning algorithms were explored for analyzing the mfVEP responses. The results of the ffVEP test for patients were evaluated against normative data collected from a group of subjects with normal vision. Custom visual stimuli with simulated defects were used to validate the mfVEP results which yielded 91% accuracy of classification.
RESULTS
20 subjects, 10 controls and 10 with MS and/or ON were tested with the NeuroVEP device and a standard-of-care (SOC) VEP testing device which delivers only ffVEP stimuli. In 91% of the cases, the ffVEP results agreed between NeuroVEP and SOC device. Where available, the NeuroVEP mfVEP results were in good agreement with Humphrey Automated Perimetry visual field analysis. The lesion locations deduced from the mfVEP data were consistent with Magnetic Resonance Imaging (MRI) and Optical Coherence Tomography (OCT) findings.
CONCLUSION
This pilot study indicates that NeuroVEP has the potential to be a reliable, portable, and objective diagnostic device for electrophysiology and visual field analysis for neuro-visual disorders.
PubMed: 38234795
DOI: 10.1101/2023.12.26.23300405 -
Documenta Ophthalmologica. Advances in... Apr 2024Bi-allelic variants in CABP4 are associated with congenital cone-rod synaptic disorder, which has also been classified, electrophysiologically, as incomplete congenital...
PURPOSE
Bi-allelic variants in CABP4 are associated with congenital cone-rod synaptic disorder, which has also been classified, electrophysiologically, as incomplete congenital stationary night blindness (iCSNB). We describe clinical findings in a patient who demonstrated an unusual macular optical coherence tomography (OCT) phenotype, not previously reported in this condition.
METHODS
Our patient underwent multimodal retinal imaging, international standard full-field ERG testing and whole genome sequencing.
RESULTS
The patient was a 60-year-old woman with non-progressive visual impairment since birth, nystagmus and preference for dim lighting. Clinical fundus examination was unremarkable. OCT imaging revealed a hypo-reflective zone under an elevated fovea in both eyes. ERGs showed an electronegative DA10 response, with severely abnormal light-adapted responses. Whole genome sequencing revealed homozygosity for a known pathogenic variant in CABP4. No variants were found in other genes that could explain the patient's phenotype.
CONCLUSIONS
OCT findings of foveal elevation and an underlying hypo-reflective zone are novel in this condition. Whilst the clinical history was similar to achromatopsia and other cone dysfunction syndromes, ERG findings suggested disease associated with CACNA1F or CABP4. As CACNA1F is X-linked, CABP4 was more likely, and confirmed on genetic testing. The patient saw better in dim light, confirming that night blindness is not a feature of CABP4-associated disease. Our case highlights the value of ERGs in discriminating between causes of cone dysfunction, and extends the range of retinal imaging phenotypes reported in this disorder.
Topics: Female; Humans; Middle Aged; Tomography, Optical Coherence; Electroretinography; Retina; Night Blindness; Photoreceptor Cells, Vertebrate; Mutation; Calcium-Binding Proteins
PubMed: 38206458
DOI: 10.1007/s10633-023-09961-8 -
Saudi Journal of Ophthalmology :... 2023Achromatopsia is a rare stationary retinal disorder that primarily affects the cone photoreceptors. Individuals with achromatopsia present with photophobia, nystagmus,...
PURPOSE
Achromatopsia is a rare stationary retinal disorder that primarily affects the cone photoreceptors. Individuals with achromatopsia present with photophobia, nystagmus, reduced visual acuity (VA), and color blindness. Multiple genes responsible for achromatopsia have been identified (e.g. cyclic nucleotide-gated channel subunit alpha 3 [CNGA3] and activating transcription factor 6). Studies have assessed the role of gene therapy in achromatopsia. Therefore, for treatment and prevention, the identification of phenotypes and genotypes is crucial. Here, we described the clinical manifestations and genetic mutations associated with achromatopsia in patients from Saudi Arabia.
METHODS
This case series study included 15 patients with clinical presentations, suggestive of achromatopsia, who underwent ophthalmological and systemic evaluations. Patients with typical achromatopsia phenotype underwent genetic evaluation using whole-exome testing.
RESULTS
All patients had nystagmus ( = 15) and 93.3% had photophobia ( = 14). In addition, all patients ( = 15) had poor VA. Hyperopia with astigmatism was observed in 93.3% ( = 14) and complete color blindness in 93.3% of the patients ( = 14). In the context of family history, both parents of all patients ( = 15) were genetic carriers, with a high consanguinity rate (82%, = 9 families). Electroretinography showed cone dysfunction with normal rods in 66.7% ( = 10) and both cone-rod dysfunction in 33.3% ( = 5) patients. Regarding the genotypic features, 93% of patients had variants in ( = 14) categorized as pathogenic Class 1 (86.7%, = 13). Further, 66.7% ( = 10) of patients also harbored the c.661C>T DNA variant. Further, the patients were homozygous for these mutations. Three other variants were also identified: c.1768G>A (13.3%, = 2), c.830G>A (6.6%, = 1), and c. 822G >T (6.6%, = 1).
CONCLUSION
Consanguinity and belonging to the same tribe are major risk factors for disease inheritance. The most common genotype was with the c.661C>T DNA variant. We recommend raising awareness among families and providing genetic counseling for this highly debilitating disease.
PubMed: 38155673
DOI: 10.4103/sjopt.sjopt_108_23 -
Progress in Retinal and Eye Research Jan 2024The endoplasmic reticulum (ER) is the largest intracellular organelle carrying out a broad range of important cellular functions including protein biosynthesis, folding,... (Review)
Review
The endoplasmic reticulum (ER) is the largest intracellular organelle carrying out a broad range of important cellular functions including protein biosynthesis, folding, and trafficking, lipid and sterol biosynthesis, carbohydrate metabolism, and calcium storage and gated release. In addition, the ER makes close contact with multiple intracellular organelles such as mitochondria and the plasma membrane to actively regulate the biogenesis, remodeling, and function of these organelles. Therefore, maintaining a homeostatic and functional ER is critical for the survival and function of cells. This vital process is implemented through well-orchestrated signaling pathways of the unfolded protein response (UPR). The UPR is activated when misfolded or unfolded proteins accumulate in the ER, a condition known as ER stress, and functions to restore ER homeostasis thus promoting cell survival. However, prolonged activation or dysregulation of the UPR can lead to cell death and other detrimental events such as inflammation and oxidative stress; these processes are implicated in the pathogenesis of many human diseases including retinal disorders. In this review manuscript, we discuss the unique features of the ER and ER stress signaling in the retina and retinal neurons and describe recent advances in the research to uncover the role of ER stress signaling in neurodegenerative retinal diseases including age-related macular degeneration, inherited retinal degeneration, achromatopsia and cone diseases, and diabetic retinopathy. In some chapters, we highlight the complex interactions between the ER and other intracellular organelles focusing on mitochondria and illustrate how ER stress signaling regulates common cellular stress pathways such as autophagy. We also touch upon the integrated stress response in retinal degeneration and diabetic retinopathy. Finally, we provide an update on the current development of pharmacological agents targeting the UPR response and discuss some unresolved questions and knowledge gaps to be addressed by future research.
Topics: Humans; Retinal Degeneration; Diabetic Retinopathy; Unfolded Protein Response; Endoplasmic Reticulum Stress; Retina; Endoplasmic Reticulum; Homeostasis
PubMed: 38092262
DOI: 10.1016/j.preteyeres.2023.101231 -
JCI Insight Jan 2024An arginine to cysteine substitution at amino acid position 203 (C203R) is the most common missense mutation in human cone opsin. Linked to color blindness and blue cone...
An arginine to cysteine substitution at amino acid position 203 (C203R) is the most common missense mutation in human cone opsin. Linked to color blindness and blue cone monochromacy (BCM), C203 is involved in a crucial disulfide bond required for proper folding. It has previously been postulated that expression of mutant C203R cone opsin exerts a toxic effect on cone photoreceptors, similar to some well-characterized missense mutations in rhodopsin that lead to protein misfolding. In this study, we generated and characterized a BCM mouse model carrying the equivalent C203R mutation (Opn1mwC198R Opn1sw-/-) to investigate the disease mechanism and develop a gene therapy approach for this disorder. Untreated Opn1mwC198R Opn1sw-/- cones phenocopied affected cones in human patients with the equivalent mutation, exhibiting shortened or absent cone outer segments and loss of function. We determined that gene augmentation targeting cones specifically yielded robust rescue of cone function and structure when Opn1mwC198R Opn1sw-/- mice were treated at early ages. Importantly, treated cones displayed elaborated outer segments and replenished expression of crucial cone phototransduction proteins. Interestingly, we were unable to detect OPN1MWC198R mutant opsin at any age. We believe this is the first proof-of-concept study exploring the efficacy of gene therapy in BCM associated with a C203R mutation.
Topics: Humans; Animals; Mice; Retinal Cone Photoreceptor Cells; Mutation, Missense; Cone Opsins; Rhodopsin; Color Vision Defects
PubMed: 38060327
DOI: 10.1172/jci.insight.172834 -
Stem Cell Research & Therapy Nov 2023Inherited retinal diseases (IRDs) can induce severe sight-threatening retinal degeneration and impose a considerable economic burden on patients and society, making... (Review)
Review
Inherited retinal diseases (IRDs) can induce severe sight-threatening retinal degeneration and impose a considerable economic burden on patients and society, making efforts to cure blindness imperative. Transgenic animals mimicking human genetic diseases have long been used as a primary research tool to decipher the underlying pathogenesis, but there are still some obvious limitations. As an alternative strategy, patient-derived induced pluripotent stem cells (iPSCs), particularly three-dimensional (3D) organoid technology, are considered a promising platform for modeling different forms of IRDs, including retinitis pigmentosa, Leber congenital amaurosis, X-linked recessive retinoschisis, Batten disease, achromatopsia, and best vitelliform macular dystrophy. Here, this paper focuses on the status of patient-derived iPSCs and organoids in IRDs in recent years concerning disease modeling and therapeutic exploration, along with potential challenges for translating laboratory research to clinical application. Finally, the importance of human iPSCs and organoids in combination with emerging technologies such as multi-omics integration analysis, 3D bioprinting, or microfluidic chip platform are highlighted. Patient-derived retinal organoids may be a preferred choice for more accurately uncovering the mechanisms of human retinal diseases and will contribute to clinical practice.
Topics: Animals; Humans; Induced Pluripotent Stem Cells; Retina; Retinal Degeneration; Retinitis Pigmentosa; Organoids
PubMed: 38012786
DOI: 10.1186/s13287-023-03564-5