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Ophthalmic Genetics Apr 2024ATF6-associated Achromatopsia (ACHM) is a rare autosomal recessive disorder characterized by reduction of visual acuity, photophobia, nystagmus, and poor color vision.
BACKGROUND
ATF6-associated Achromatopsia (ACHM) is a rare autosomal recessive disorder characterized by reduction of visual acuity, photophobia, nystagmus, and poor color vision.
METHODS
Detailed ophthalmological examinations were performed in a Chinese patient with ACHM. Whole exome sequencing and Sanger sequencing were performed to detect the disease-causing gene in the patient.
RESULTS
A 6-year-old girl presented photophobia, low vision and reduced color discrimination. Small yellow lesion in the macula of both eyes was observed. FAF demonstrated hypofluorescence in the macular fovea. OCT images revealed interruption of ellipsoid and interdigitation zone in the foveal area and a loss of the foveal pit. ERG showed relatively normal rod responses and unrecordable cone responses. Sequencing result identified a novel splicing variant c.354 + 6T>C in the ATF6 gene (NM_007348.4).
CONCLUSIONS
We reported detailed clinical features and genetic analysis of a new Chinese ATF6-associated patient with ACHM.
Topics: Child; Female; Humans; Activating Transcription Factor 6; China; Color Vision Defects; Photophobia; Retinal Cone Photoreceptor Cells; Tomography, Optical Coherence
PubMed: 38419580
DOI: 10.1080/13816810.2024.2322643 -
Acta Ophthalmologica Feb 2024To describe the phenotype of Danish patients with genetically verified achromatopsia (ACHM) with special focus on signs of progression on structural or functional...
PURPOSE
To describe the phenotype of Danish patients with genetically verified achromatopsia (ACHM) with special focus on signs of progression on structural or functional parameters, and possible genotype-phenotype correlations.
METHODS
Forty-eight patients were identified, with disease-causing variants in five different genes: CNGA3, CNGB3, GNAT2, PDE6C and PDE6H. Longitudinal evaluation was possible for 11 patients and 27 patients participated in a renewed in-depth phenotyping consisting of visual acuity assessment, optical coherence tomography (OCT), fundus autofluorescence, colour vision evaluation, contrast sensitivity, mesopic microperimetry and full-field electroretinography. Foveal morphology was evaluated based on OCT images for all 48 patients using a grading system based on the integrity of the hyperreflective photoreceptor band, the inner segment ellipsoid zone (ISe). Signs of progression were evaluated based on longitudinal data and correlation with age.
RESULTS
We found a statistically significant positive correlation between OCT grade and age (Spearman ρ = 0.62, p < 0.0001) and we observed changes in the foveal morphology in 2 of 11 patients with ≥5 years of follow-up. We did not find any convincing correlation between age and functional parameters (visual acuity, retinal sensitivity and contrast sensitivity) nor did we find correlation between structural and functional parameters, or any clear genotype-phenotype correlation.
CONCLUSIONS
Some patients with ACHM demonstrate signs of progressive foveal changes in OCT characteristics with increasing age. This is relevant in terms of possible new treatments. However, functional characteristics, such as visual acuity, remained stable despite changing foveal structure. Thus, seen from a patient perspective, ACHM can still be considered a non-progressive condition.
PubMed: 38348755
DOI: 10.1111/aos.16656 -
The New England Journal of Medicine Feb 2024
Topics: Humans; Color Vision Defects; Heredity; Art
PubMed: 38314808
DOI: 10.1056/NEJMp2312346 -
Acta Clinica Croatica Apr 2023Acute optic neuritis is often associated with multiple sclerosis. It is considered to be the most common ocular symptom of multiple sclerosis. In addition to acute optic...
Acute optic neuritis is often associated with multiple sclerosis. It is considered to be the most common ocular symptom of multiple sclerosis. In addition to acute optic neuritis, in patients with multiple sclerosis, subclinical optic neuritis is also described. It is characterized by slow progression and bilateral involvement, thus being unnoticed by the patient. The purpose of the present study was to assess vision impairment in multiple sclerosis patients without a history of acute optic neuritis, using a number of functional tests including visual field testing by Octopus 101 perimetry N1 program, contrast sensitivity testing by Pelli Robson chart, and color vision by Ishihara pseudoisochromatic plates. The study included 35 multiple sclerosis patients aged 18-50 years, without subjective signs of vision impairment and visual acuity 1.0 according to Snellen. Visual field defects were found in 28 patients. The most common defects of visual fields were retinal sensitivity depression in peripheral zone and nerve fiber bundle defect. Reduced contrast sensitivity was found in 30 (86%) patients. Study results indicated multiple sclerosis patients free from signs of optic neuritis to suffer vision function impairment, as demonstrated by Octopus perimetry and contrast sensitivity testing with Pelli Robson charts.
Topics: Humans; Visual Acuity; Visual Fields; Vision Tests; Multiple Sclerosis; Optic Neuritis
PubMed: 38304362
DOI: 10.20471/acc.2023.62.01.24 -
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 -
Journal of Neuro-ophthalmology : the... Jan 2024The clinical characteristics of patients with polymerase gamma (POLG) mutation-associated optic neuropathy remain incompletely characterized.
BACKGROUND
The clinical characteristics of patients with polymerase gamma (POLG) mutation-associated optic neuropathy remain incompletely characterized.
METHODS
We describe the clinical characteristics of 3 patients with POLG-associated optic neuropathy. We performed a literature review of optic neuropathy cases associated with POLG mutations and compared them with our cohort.
RESULTS
Many published cases of POLG-associated optic neuropathy in our literature review lacked details regarding severity of vision loss, visual field defects, and optical coherence tomography analysis. The clinical presentation of POLG mutations remains widely variable in age (from pediatric cases to adults) and associated systemic findings. All patients in our literature review presented with systemic symptoms, most commonly muscle weakness, ptosis, and ophthalmoplegia, whereas many young patients had severe systemic symptoms. In our case series, all 3 cases had isolated optic neuropathy affecting the papillomacular bundle, with signs such as reduced visual acuity and color vision, central visual field defects, temporal retinal nerve fiber layer loss with temporal optic disc pallor, and retinal ganglion cell complex loss. In addition, 2 of the 3 cases had added mitochondrial stressors in addition to the POLG mutation.
CONCLUSIONS
Clinicians should be aware that POLG mutations can present as isolated optic neuropathy primarily affecting the papillomacular bundle. With mitochondrial failure being the likely underlying pathogenic mechanism in POLG-associated optic neuropathy, helping affected patients eliminate mitochondrial stressors may be important in reducing the risk for progressive vision loss in this otherwise currently untreatable disorder.
PubMed: 38294884
DOI: 10.1097/WNO.0000000000002089 -
Progress in Retinal and Eye Research May 2024Inherited retinal diseases (IRD) are a leading cause of blindness in the working age population and in children. The scope of this review is to familiarise clinicians... (Review)
Review
Phenotyping and genotyping inherited retinal diseases: Molecular genetics, clinical and imaging features, and therapeutics of macular dystrophies, cone and cone-rod dystrophies, rod-cone dystrophies, Leber congenital amaurosis, and cone dysfunction syndromes.
Inherited retinal diseases (IRD) are a leading cause of blindness in the working age population and in children. The scope of this review is to familiarise clinicians and scientists with the current landscape of molecular genetics, clinical phenotype, retinal imaging and therapeutic prospects/completed trials in IRD. Herein we present in a comprehensive and concise manner: (i) macular dystrophies (Stargardt disease (ABCA4), X-linked retinoschisis (RS1), Best disease (BEST1), PRPH2-associated pattern dystrophy, Sorsby fundus dystrophy (TIMP3), and autosomal dominant drusen (EFEMP1)), (ii) cone and cone-rod dystrophies (GUCA1A, PRPH2, ABCA4, KCNV2 and RPGR), (iii) predominant rod or rod-cone dystrophies (retinitis pigmentosa, enhanced S-Cone syndrome (NR2E3), Bietti crystalline corneoretinal dystrophy (CYP4V2)), (iv) Leber congenital amaurosis/early-onset severe retinal dystrophy (GUCY2D, CEP290, CRB1, RDH12, RPE65, TULP1, AIPL1 and NMNAT1), (v) cone dysfunction syndromes (achromatopsia (CNGA3, CNGB3, PDE6C, PDE6H, GNAT2, ATF6), X-linked cone dysfunction with myopia and dichromacy (Bornholm Eye disease; OPN1LW/OPN1MW array), oligocone trichromacy, and blue-cone monochromatism (OPN1LW/OPN1MW array)). Whilst we use the aforementioned classical phenotypic groupings, a key feature of IRD is that it is characterised by tremendous heterogeneity and variable expressivity, with several of the above genes associated with a range of phenotypes.
Topics: Humans; Cone-Rod Dystrophies; Eye Diseases, Hereditary; Genotype; Leber Congenital Amaurosis; Molecular Biology; Phenotype; Retinal Diseases
PubMed: 38278208
DOI: 10.1016/j.preteyeres.2024.101244 -
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