A novel compound heterozygous variant of MYO7A in Usher syndrome type 1.

Usher syndrome (USH) is a recessive genetic disorder manifested by congenital sensorineural hearing loss and progressive retinitis pigmentosa, which leads to audiovisual impairment. We report a patient with Usher syndrome type 1 with new compound heterozygous MYO7A variants. A total of four members from the USH family were included. Medical history and retinal examinations were taken and genomic DNA from peripheral blood was extracted in the proband and other members. 381 retinal disease-associated genes were screened using targeted sequence capture array technology and Sanger sequencing was used to confirm the screening results. Scanning laser ophthalmoscope showed bone spicule pigmentary deposits in the mid-peripheral retina and whitish and thin retinal blood vessels especially in the arterioles. Optical coherence tomography showed that the centrality of the macular ellipsoid band disappeared in both eyes, and only remained near the fovea. Visual field examination showed a progressive loss of the visual field in a concentric pattern in both eyes. The electroretinography showed a significant decrease in the amplitudes of a- and b-waves in the scotopic and photopic condition. DNA sequencing identified the compound heterozygous variants including c.1003+1G > A: p. (?) and c.5957_5958del: p.G1987Lfs*50 of MYO7A, with the latter being novel. In this study, we found a novel compound heterozygous variant in MYO7A, which enriched the mutation spectrum and expanded our understanding of the heterogeneity of phenotype and genotype of Usher syndrome type 1.

RDH12-associated retinal degeneration caused by a homozygous pathogenic variant of 146C>T and literature review.

AIM: To describe the clinical, electrophysiological, and genetic features of an unusual case with an RDH12 homozygous pathogenic variant and reviewed the characteristics of the patients reported with the same variant. METHODS: The patient underwent a complete ophthalmologic examination including best-corrected visual acuity, anterior segment and dilated fundus, visual field, spectral-domain optical coherence tomography (OCT) and electroretinogram (ERG). The retinal disease panel genes were sequenced through chip capture high-throughput sequencing and Sanger sequencing was used to confirm the result. Then we reviewed the characteristics of the patients reported with the same variant. RESULTS: A 30-year male presented with severe early retinal degeneration who complained night blindness, decreased visual acuity, vitreous floaters and amaurosis fugax. The best corrected vision was 0.04 OD and 0.12 OS, respectively. The fundus photo and OCT showed bilateral macular atrophy but larger areas of macular atrophy in the left eye. Autofluorescence shows bilateral symmetrical hypo-autofluorescence. ERG revealed that the amplitudes of a- and b-wave were severely decreased. Multifocal ERG showed decreased amplitudes in the local macular area. A homozygous missense variant c.146C>T (chr14:68191267) was found. The clinical characteristics of a total of 13 patients reported with the same pathologic variant varied. CONCLUSION: An unusual patient with a homozygous pathogenic variant in the c.146C>T of RDH12 which causes late-onset and asymmetric retinal degeneration are reported. The clinical manifestations of the patient with multimodal retinal imaging and functional examinations have enriched our understanding of this disease.

The Role of OCTA in Evaluating Diabetic Retinopathy Progression: A Meta-Analysis.

Background: Diabetic retinopathy (DR) substantially threatens ocular health, necessitating the accurate and prompt assessment of its onset and progression. Optical coherence tomography angiography (OCTA) is a valuable tool for evaluating periocular microvascular indicators, offering insights crucial for diagnosing and treating DR. Objective: This meta-analysis aims to evaluate the progression of diabetic retinopathy (DR) by examining periocular microvascular indicators using optical coherence tomography angiography (OCTA). The objective is to provide substantive evidence for the future diagnosis and treatment of DR. Methods: We analyzed the relevant research retrieved from PubMed and Web of Science until January 2023. The inclusion and exclusion criteria were carefully applied to select eligible studies. Quality assessment was performed using the Newcastle-Ottawa Scale, with studies scoring 4 or less excluded. Meta-analysis was conducted using Revman 5.3 software and focused on key indicators, including peripapillary vascular length density (pVLD) and peripapillary vascular density (pVD). Heterogeneity was assessed using I2 and P values, with effect sizes determined via fixed-effect or random-effects models based on heterogeneity levels. Results: Six studies involving 839 DR-afflicted eyes and 3209 non-DR eyes were included after screening. All selected articles exhibited high reference value, with quality scores ranging from 5 to 8 points. The meta-analysis demonstrated that DR patients displayed significantly lower pVD and pVLD in the superficial (SCP) and deep capillary plexus (DCP) compared to non-DR patients (P < .05). These findings remained consistent across different effect models, reaffirming their validity. Conclusions: Patients with DR exhibit reduced levels of pVD and pVLD in the SCP and DCP compared to non-DR individuals. OCTA examination of periocular microvascular indicators emerges as an effective tool for assessing the onset and progression of DR.

Effect of COVID-19 home confinement on the efficacy of orthokeratology, 0.01% atropine and combined treatment.

PURPOSE: To investigate the effect of COVID-19 home confinement on the efficacy of the interventions for controlling myopia, and to select effective therapies to control myopia during COVID-19 confinement. METHOD: Children (n = 164) aged 8-12 years with spherical equivalent refraction of -1.00 to -6.00 diopters were stratified into two age subgroups and randomly allocated into the control, 0.01% atropine, orthokeratology (ortho-k) and atropine combined ortho-k (ACO) groups. Axial length (AL) was measured at baseline, 6-, 12-, 18- and 24-month visits. The follow-up spanned the period before the COVID-19 outbreak, the period of the home confinement, and the period of the school reopening. Hence, the AL change in different periods was collected and compared. Data analysis was performed following the criteria of intention to treat (ITT). RESULTS: All 164 children were involved in the ITT analysis. Compared to control, all interventions can still reduce the AL elongation during the COVID-19 home confinement period (all p < 0.05). However, the efficacy was compromised: individuals experienced more AL elongation during the COVID-19 home confinement period in the control, 0.01% atropine and ACO groups (all p < 0.05). Interestingly, in the ortho-k group, the difference was insignificant (p = 0.178), and the interaction between the intervention type (control vs. ortho-k) and the confinement severity was significant (p for interaction = 0.041), which is different from the atropine (p for interaction = 0.248) or ACO group (p for interaction = 0.988). These results were stable after being adjusted by other variables based on the multivariable regression model. CONCLUSION: Ortho-k was less affected by the COVID-19 home confinement, which is potentially a better therapy for children in this high-risk environment. Further investigations are warranted to validate this issue.

The molecular genetics of anterior segment dysgenesis.

Anterior segment dysgenesis is a severe developmental eye disorder that leads to blindness in children. The exact mechanisms underlying this condition remain elusive. Recently, an increasing amount of studies have focused on genes and signal transduction pathways that affect anterior segment dysgenesis;these factors include transcription factors, developmental regulators, extracellular matrix genes, membrane-related proteins, cytoskeleton proteins and other associated genes. To date, dozens of gene variants have been found to cause anterior segment dysgenesis. However, there is still a lack of effective treatments. With a broader and deeper understanding of the molecular mechanisms underlying anterior segment development in the future, gene editing technology and stem cell technology may be new treatments for anterior segment dysgenesis. Further studies on the mechanisms of how different genes influence the onset and progression of anterior segment dysgenesis are still needed.

Association between prediabetes/hyperglycemia and retinal diseases: A meta-analysis.

PURPOSE: To explore the effect of prediabetes/hyperglycemia on the incidence of retinopathy. METHODS: PubMed and EMBASE databases were retrieved to screen case-control studies or prospective cohort studies of retinopathy in prediabetic patients from January, 2004 to December, 2019. After quality evaluation by two evaluators according to inclusion and exclusion criteria, RevMan 5.3 software was used for meta-analysis. RESULTS: A total of 18 articles were included. Meta-analysis showed that there have been more incidents of retinal diseases in patients with prediabetes/hyperglycemia [MD (mean difference) = 2.50, 95% CI (1.74 to 3.6)] than those in normal controls (p < 0.05). The incidence of macular diseases [MD = 1.36, 95% CI (1.05 to 1.76)] was significantly higher in prediabetic patients than that of the control group (p < 0.05). No significant differences in DR-like retinopathy were found between both groups [MD = 2.02, 95% CI (0.84 to 4.85)] (p > 0.05). In neonates, hyperglycemia was associated with an increased risk of ROP [MD = 3.6, 95% CI (1.89 to 6.86)] (p < 0.001). CONCLUSIONS: Prediabetes/hyperglycemia is associated with an increased risk of retinal diseases. Retinal diseases screening such as macular diseases among people with prediabetes should be warranted. But no significant differences in DR-like retinopathy were found. However, more further studies are needed to clarify the details between prediabetes/hyperglycemia and different kinds of retinal diseases.

Latest progress in the study of nanoparticle-based delivery of the CRISPR/Cas9 system.

The CRISPR/Cas9 system has been harnessed to cleave a targeted DNA fragment via its Cas nuclease activity under the direction of guide RNA for rendering gene insertions, deletions, and point mutations in basic research and clinical applications. There are a number of vehicles, including lipofectamine, viruses, and nanoparticles, that can deliver the CRISPR/Cas9 system, but all these methods face numerous challenges during their application in life science contexts. Here, we focus on the delivery of CRISPR/Cas9 via nanoparticles because this method has shown great advantages in terms of safety, simplicity and flexibility.

New compound heterozygous CYP4V2 mutations in bietti crystalline corneoretinal dystrophy.

Bietti crystalline corneoretinal dystrophy (BCD) is an autosomal recessive retinal dystrophy which is caused by the mutations of CYP4V2, usually progressing to legal blindness by the 5th or 6th decade of life. Here we identified CYP4V2 compound heterozygous mutations in two female siblings with BCD without subjective symptoms. After 381 pathogenic genes related to retinal diseases were screened by targeted sequence capture array techniques and confirmed by Sanger sequencing, two compound heterozygous mutations in CYP4V2 were found. One was missense mutation c.1198C>T (p.R400C) and the other was frameshift mutation c.802-8_810delinsGC (p.V268_E329del). Optical coherence tomography (OCT) showed that the ellipsoid zone was absent in the macular regions and electroretinogram (ERG) revealed poor cone and rod responses. Compound heterozygous mutations in CYP4V2 are related to the BCD. Our study expands our knowledge of heterogenic phenotypes and genotypes through genetic diagnosis of the BCD patients.