搜索结果：Ophthalmic genetics

The eye is a recognized source of biomarkers for cardiovascular and neurodegenerative disease risk. Here we characterize the breadth of these associations and identify biological axes that may mediate them. Using UK Biobank data, we developed a multi-omic analysis pipeline integrating physiological, radiomic, metabolomic and genomic information. We trained retinal adversarial autoencoders to represent optical coherence tomography images and color fundus photographs as 256-dimensional embeddings. Retinal adversarial autoencoder-derived embeddings were associated with a range of cardiovascular and neurodegenerative diseases, including ischemic heart disease, cerebrovascular disease, Parkinson's disease and dementia. Examining associations across diverse omics datasets, we provide evidence linking ophthalmic imaging features to neurological and cardiovascular anatomy and function, lipid metabolism and gene sets associated with neurodegenerative pathology. Collectively, our findings show that ophthalmic features reflect complex, multisystem biological processes and reinforce the role of the eye as a composite indicator of systemic health.

The popularity of designer crossbreed dogs, including Labradoodles, has increased markedly in recent years. This retrospective study evaluated ophthalmic findings and the prevalence of known and presumed hereditary eye diseases (KP-HED) in Labradoodles presented for European College of Veterinary Ophthalmologists (ECVO)-certified screening in the Netherlands. ECVO Certificates from Labradoodles examined between January 2014 and December 2024 by a single ECVO diplomate were retrospectively reviewed. Screening consisted of slit-lamp biomicroscopy and indirect ophthalmoscopy following pharmacologic mydriasis. The prevalence of each KP-HED was calculated relative to the total number of dogs examined. A total of 1,182 Labradoodles (940 females, 242 males; median age 27.8 months, range 4.2-131.7 months) were included. Ninety-two dogs (7.8%) were affected by at least one KP-HED, resulting in 96 diagnoses. The most prevalent conditions were iris-to-iris persistent pupillary membrane (PPM; 4.7%) and distichiasis (2.5%), followed by cataract (0.5%), multifocal retinal dysplasia (MRD; 0.2%), and other lens opacities (0.2%). All cataracts were classified as later-onset and included cortical (0.4%), posterior polar (0.2%), and nuclear (0.08%) subtypes. The most common additional finding was the presence of tiny pigment dots on the central anterior lens capsule (3.9%). Overall, the prevalence of vision-threatening KP-HED in this population was low, indicating a generally favorable ocular health status. However, the relatively higher prevalence of iris-to-iris PPM and distichiasis compared to progenitor breeds suggests a potential influence of genetic background and breeding practices. These findings support the continued use of ophthalmic screening to guide breeding decisions.

CEP290-associated retinal diseases span a broad phenotypic spectrum, from Leber congenital amaurosis to milder retinal dystrophies to syndromic ciliopathies. Herein, we describe a non-syndromic 18-year-old woman with compound heterozygous pathogenic variants in CEP290 whose ophthalmic features are infantile-onset nystagmus, benign and stable fundus appearance, and lack of cone-mediated visual and retinal function. Serial examinations from infancy onward document stable achromatopsia-like ophthalmic features. No cone-mediated vision or retinal function was demonstrated. By optical coherence tomography, foveal architecture was preserved and central retinal thickness was stable for more than a decade (median 246 µm, range 232-257 µm). Testing for common CNGA3 and CNGB3 variants in early childhood was negative, as was further testing via an eight-gene achromatopsia panel. Trio exome sequencing identified compound heterozygous pathogenic CEP290 variants in trans: c.4723A>T (p.Lys1575Ter) and c.6277del (p.Val2093SerfsTer4). Notably, c.4723A>T is a nonsense variant previously shown to undergo nonsense-associated exon skipping, consistent with a hypomorphic effect that has been associated with milder CEP290-related retinal disease. These findings suggest a selective impairment of cone-mediated function with relative preservation of rod function.

Glaucoma is the leading cause of irreversible blindness worldwide, with disproportionately high prevalence and severity in Africans. To characterise the baseline phenotypic findings and glaucoma-related ocular features of participants with primary open-angle glaucoma (POAG, cases) and non-glaucoma controls and to report sociodemographic and medical associations of POAG in the cohort. Multicentre, cross-sectional study. 9418 adults (5189 POAG cases; 4229 controls) recruited from 16 centres in Nigeria, Ghana and Malawi. Standardised demographic, medical and ophthalmic data were collected, including visual acuity, intraocular pressure (IOP), optic disc evaluation, visual fields and central corneal thickness. Glaucoma severity, visual impairment (VI) and sociodemographic/medical associations of POAG. Compared to controls, cases were older (mean age 63.9 years vs 61.4 years, P&#x2009;<&#x2009;0.001) and more likely to be male (57.4% vs 45.2%, P&#x2009;<&#x2009;0.001). Three-quarters of cases (76.8%) were classified as having severe glaucoma in at least one eye at recruitment, with a third (34.4%) suffering severe VI or blindness. The leading causes of VI in controls were cataract (65.0%) and uncorrected refractive error (13.8%). POAG was significantly associated with older age, male sex, higher level of education, unemployment, history of alcohol consumption, African trypanosomiasis, higher maximum IOP and a positive family history of glaucoma. There is a significant glaucoma disease burden in sub-Saharan Africa. Further analyses of the cohort will identify genetic determinants of these clinical findings and reinforce the urgent need for public health interventions in sub-Saharan Africa.

Muscle eye brain (MEB) disease is a rare genetic disorder characterized by congenital muscular dystrophy, structural brain malformations and ocular abnormalities. We review the literature on ophthalmic manifestations and highlight key features that may facilitate the diagnosis of this rare condition. A literature search was conducted in the National Centre form Biotechnology Information (NCBI) PubMed, Embase, Web of Science and Scopus databases from inception through April 2026 to identify all relevant studies reporting ocular manifestations in MEB disease. The current literature on ocular manifestations in MEB disease demonstrates phenotypic variability. MEB disease is caused by homozygous or compound heterozygous mutations in the POMGnT1 gene and the clinical presentation varies in terms of age of onset, disease pattern and rate of progression. Patients with a genetically established diagnosis may present with a wide range of ocular findings, ranging from mild to severe abnormalities. The spectrum mainly includes ocular motility disorders, high myopia, glaucoma, cataract, optic nerve hypoplasia and retinal dysplastic and degenerative changes, while retinal detachment and microphthalmia are less commonly reported. The variation in phenotype and disease progression, along with the limited number of reported cases highlights the need for further research to guide clinical practice, improve risk assessment and optimize patient management. This review discusses the ocular manifestations of the disorder and emphasizes the importance of reporting additional cases of this rare condition to contribute to future research.

To assess different lots and brands of sterile preservative-free dexamethasone sodium phosphate (dexamethasone SP) for evidence of bacterial contamination via culture-dependent and independent methods, and quantify endotoxin. Broadly, the objective is to further investigate potential causes for fibrin web (FW) development after canine cataract surgery. Five samples from two lots of three brands of dexamethasone SP (30 samples total) and reagent controls were collected. All samples underwent conventional aerobic and capnophilic bacterial culture, as well as kinetic chromogenic endotoxin quantification. Deoxyribonucleic acid (DNA) extraction, 16S ribosomal ribonucleic acid (rRNA) sequencing, sequence analysis, and classification were performed on all samples. Statistical analysis assessed DNA concentration, &#x3b1; and &#x3b2; diversity, and sample biomarkers. Bacterial cultures were positive in 0/10 Auromedics, 1/10 Fresenius Kabi, and 4/10 Somerset Pharma LLC dexamethasone SP samples. The bacteria identified (Bacillus thuringiensis, Staphylococcus epidermidis, and Staphylococcus oralis) were likely present due to contaminants during plating. Endotoxin quantification was below the limit of detection of the assay (0.5 EU/mL). There were no statistically significant differences in &#x3b1; or &#x3b2; diversity between brands. Differential abundance testing found Lactococcus and Acetitomaculum as genus-level biomarkers for the Auromedics brand and Solobacterium for the Somerset brand of dexamethasone SP. The most common bacterial families recovered were Bacillaceae, Clostridiaceae, Enterobacteriaceae, Lachnospiraceae, Lactobacillaceae, Muribaculaceae, Propionilbacteriaceae, Staphylococcaeae, and Xanthobacteraceae. There were no significant dexamethasone SP brand-specific differences. Endotoxin was below the limit of detection of the assay.

暂无摘要（点击查看详情）

Thyroid eye disease (TED) is an autoimmune orbital disorder characterized by fibroblast activation, myofibroblast differentiation, and excessive extracellular matrix production. RhoA/ROCK signaling is increasingly implicated in these fibrotic processes. This study aimed to investigate the effects of the Rho-associated protein kinase (ROCK) inhibitor netarsudil on the expression of fibrogenesis-related genes in orbital fibroblasts derived from patients with TED. Primary orbital fibroblasts were isolated from two patients with TED. Cells were treated with varying concentrations of netarsudil (ranging from 2&#x2009;&#xd7;&#x2009;10-&#x2009;2 to 2&#x2009;&#xd7;&#x2009;10-&#x2009;8 mg/mL). Gene expression of fibrogenesis markers, including TGF-&#x3b2;, &#x3b1;-SMA, ZEB1, Snail, Thy-1, and &#x3b2;-catenin, was assessed via quantitative real-time PCR. Our results demonstrated that netarsudil treatment at non-cytotoxic concentrations not only did not significantly suppress the mRNA expression of the examined fibrogenic markers, but also upregulated the expression of TGF-&#x3b2;, &#x3b1;-SMA, and ZEB1. Higher concentrations of netarsudil appeared to reduce cell viability, suggesting that apparent antifibrotic effects at elevated doses may be secondary to cytotoxicity rather than pathway-specific transcriptional repression. Our findings suggest that non-cytotoxic dose of netarsudil, is insufficient to reverse the constitutively pro-fibrotic transcriptional program in TED orbital fibroblasts. The lack of direct antifibrotic efficacy highlights the complexity of TED fibrogenesis and suggests that redundant or parallel signaling pathways may limit the impact of isolated ROCK inhibition. Further research is required to evaluate combination therapies or alternative targets in TED-related fibrosis.

Alstr&#xf6;m syndrome (AS) is a rare autosomal recessive ciliopathy caused by biallelic pathogenic variants in the ALMS1 gene. The condition is characterized by a spectrum of clinical manifestations, including cone-rod dystrophy, sensorineural hearing loss, metabolic disturbances, and progressive multiorgan involvement. Ciliopathies share considerable clinical overlap, and some cases present with features that resemble AS without meeting all diagnostic criteria. This study aims to identify the pathogenic variants in a Chinese patient with a ciliopathy resembling AS. We report a 27-year-old Chinese female with a body mass index (BMI) of 28.4&#xa0;kg/m2. The patient initially presented with progressive hearing loss at age 2&#xa0;years, followed by visual impairment beginning at age 8&#xa0;years. At age 17&#xa0;years, she developed progressive alopecia accompanied by scaly, patchy papules. By age 22&#xa0;years, she was diagnosed with polycystic ovary syndrome (PCOS) and type 2 diabetes mellitus (T2DM). Laboratory investigations revealed dyslipidemia and hyperinsulinemia. Abdominal ultrasonography demonstrated hepatic steatosis and medullary sponge kidney, while pelvic ultrasound indicated polycystic ovarian morphology. Echocardiography revealed ventricular septal thickening. Whole-exome sequencing (WES) identified that our patient was a compound heterozygote for two novel variants in the ALMS1 gene, comprising c.12114 + 1G>T and c.1856_1860dup (p.Ser621Leufs*23). Both variants were classified as likely pathogenic in accordance with the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines. Based on the clinical phenotype and molecular findings, a diagnosis of a ciliopathy resembling AS was made, although a definitive diagnosis of AS could not be confirmed due to incomplete ocular phenotyping. Disease management included metformin and pioglitazone for T2DM, continued use of hearing aids, and scheduled regular follow-up evaluations. This report describes two novel ALMS1 variants, expanding the known mutational spectrum of the gene. Genetic testing plays a supportive role in diagnosis and is valuable for familial screening and counseling, although a definitive diagnosis of AS would require complete ophthalmic phenotyping and functional validation.

Gillespie syndrome (GS) is a rare congenital disorder with ocular and neurological defects. Classically, it has been noted to have a triad of cerebellar ataxia, variable absence of iris but always with a scalloped edge and intellectual disability. This scalloped iris edge is essential to make a diagnosis of GS. Both autosomal dominant and recessive inheritance have been reported with de novo pathogenic variants in the inositol 1,4,5-trisphosphate receptor type 1 gene (ITPR1). We report a novel variant of ITPR1 gene causing Gillespie syndrome in multiple members of a family. A retrospective chart review of a single pedigree was performed. Three pediatric patients and a parent underwent complete ophthalmic examinations. Molecular genetic testing was pursued where clinically indicated. Two siblings (one male, one female) were being evaluated for ataxia. Genetic testing identified a paternally inherited ITPR1 variant, c.5970A>C, p.Gln1990His, in both siblings. A third sibling (female) was later evaluated and also found to have the familial ITPR1 variant. On ophthalmic examination, all three siblings and their father had characteristic iris hypoplasia confirming the diagnosis of Gillespie syndrome. We report a new variant of ITPR1 gene causing Gillespie syndrome in the described family. Clinical and molecular analyses and their correlation helped to establish the clinical relevance of this variant.

To describe the ocular and extraocular findings in two unrelated Turkish families with type 1 Stickler syndrome carrying two novel truncating COL2A1 variants and to emphasize the marked intrafamilial phenotypic variability. Seven affected individuals from the two families underwent detailed ophthalmic examination including BCVA, slit-lamp biomicroscopy with vitreous phenotype assessment, fundus evaluation, and multimodal retinal imaging. Systemic evaluation included craniofacial, pediatric, orthopedic, and audiological assessments. Index cases underwent clinical exome sequencing; targeted NGS confirmed segregation in family members. Variants were classified as per ACMG criteria. In Family 1, a novel nonsense COL2A1 variant, c.3910C>T (p.Gln1304Ter), was identified as the father and three sons. Ocular findings ranged from mild myopia and epiretinal membranes to bilateral retinal detachment and macular holes. The membranous vitreous anomaly of type 1 Stickler syndrome was present in all; one child had Pierre Robin sequence and another had cleft palate. In Family 2, a novel nonsense COL2A1 variant, c.3016A>T (p.Lys1006Ter), was detected in the proband along with her mother and brother. The proband had rhegmatogenous retinal detachment; affected relatives showed milder phenotypes including isolated high myopia and high myopia with retinal detachment. Marked intrafamilial phenotypic variability was observed in both families. These two novel truncating COL2A1 variants expand the mutational spectrum of type 1 Stickler syndrome. This case series illustrates the broad clinical variability of the disease, from isolated high myopia to severe vitreoretinal complications, and supports early molecular diagnosis, family screening, and preventive ophthalmic surveillance.

To investigate the genetic mutation profiles of gene-related retinal detachment (RD) and evaluate the utility of The American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) pathogenicity classification system with emphasis on variants of uncertain significance (VUS) in a young Chinese cohort. A consecutive cohort of 28 patients under 30y with RD and clinical features suggesting genetic etiology was enrolled between September 2024 and August 2025 at Zhongshan Ophthalmic Center. All patients underwent comprehensive ophthalmic examinations, genetic testing, and surgical repair. Genetic variants were interpreted via the ACMG/AMP criteria. The cohort consisted of 21 males and 7 females, with a mean age of 15.1&#xb1;6.71y (ranged: 4-29). The predominant etiologies were Stickler syndrome (10/28, 35.7%), familial exudative vitreoretinopathy (FEVR; 6/28, 21.4%), and Marfan syndrome (4/28, 14.3%). A total of 30 disease-associated variants were identified, among which 60.0% (18/30) were classified as pathogenic/likely pathogenic (P/LP) and 40.0% (12/30) as VUS per ACMG/AMP criteria. The primary factors contributing to VUS classification included high population allele frequency (33.3%), variant novelty (33.3%), and discrepant in silico predictions (25.0%). Patients with P/LP variants exhibited a significantly higher prevalence of high myopia (<-6 D; 93.8% vs 50.0%, P=0.027) and tessellated fundus (87.5% vs 50.0%, P=0.044) compared to those with VUS/not available (NA) variants. Stickler syndrome, FEVR, and Marfan syndrome are the leading causes of gene-related RD in the Chinese Han cohort. A high VUS rate (40.0%) poses diagnostic challenges, primarily due to population-specific frequency differences, novel variants, and insufficient functional evidence. By integrating clinical history, phenotypic manifestations, and family history, a clear diagnosis can be established in 66.7% of VUS cases. Ethnically tailored genomic databases and expanded multicenter cohorts are needed to improve VUS resolution and enhance the clinical utility of genetic testing in young RD individuals.

Hydrocephalus is an etiologically heterogeneous disorder that may result from acquired insults or monogenic causes. More than 100 genes have been implicated in congenital and early-onset hydrocephalus, but MAP7D3 has not previously been associated with disturbances of cerebrospinal fluid (CSF) circulation. We report an adult patient with obstructive hydrocephalus in whom a novel frameshift variant in MAP7D3 was identified by exome sequencing. A 38-year-old woman presented with a 6-month history of progressive predominantly occipital headache without nausea, vomiting, or diplopia. Neurological examination was normal, whereas neuro-ophthalmic assessment showed unilateral right optic disc swelling consistent with papilledema. Brain MRI demonstrated ventriculomegaly of the lateral and third ventricles with depression of the third-ventricle floor and a partially empty sella, without mass lesion, venous sinus thrombosis, or parenchymal abnormalities. Cine phase-contrast MRI revealed impaired CSF flow through the aqueduct, and there was no clinical or radiological evidence of prior intracranial hemorrhage or central nervous system infection. The patient had no relevant comorbidities, was not taking anticoagulants or antiplatelet agents, and reported no family history of hydrocephalus, macrocephaly, intraventricular hemorrhage, or monogenic neurodevelopmental disorders. Endoscopic third ventriculostomy performed in 04/2022 led to improvement in headache intensity (visual analogue scale 6 to 3) and a decrease in Evans index from 0.40 to 0.36 at 12-month follow-up, with stable ophthalmic findings at approximately 24 months. Research exome sequencing identified a novel frameshift variant in MAP7D3 (c.30_40delinsCGTCTCT; p.Gly11ValfsTer5), absent from population databases and predicted to result in loss of function. Based on ACMG/AMP criteria and the current literature, we classified this variant as a strong candidate variant of uncertain significance. This case illustrates how a carefully phenotyped adult patient with obstructive hydrocephalus and no identifiable acquired cause may benefit from exploratory exome sequencing, which can reveal rare variants in emerging candidate genes such as MAP7D3. Although a causal role for MAP7D3 loss-of-function in hydrocephalus has not yet been established, our findings support further functional studies and highlight the need for cautious interpretation of single-patient variants of uncertain significance.

This study characterizes the clinical and genetic features of ABCA4-associated inherited retinal diseases (IRDs) in eight unrelated probands from the three provinces of Northeast China. All patients harbored biallelic pathogenic ABCA4 variants, with detailed variant profiles provided in Table&#xa0;2. Eight unrelated Chinese pedigrees (31 individuals, including 8 probands and 23 family members) with ABCA4-related IRDs. All participants underwent comprehensive ophthalmic examinations. Genetic variants were identified using a targeted next-generation sequencing (NGS) panel for IRDs. For all candidate pathogenic variants, in silico pathogenicity predictions were performed using REVEL, PolyPhen-2, MutationTaster, SIFT, and LRT (Likelihood Ratio Test). The pathogenicity of the variants was classified in accordance with the guidelines of the American College of Medical Genetics and Genomics (ACMG), integrating computational evidence and segregation analysis. All candidate variants were validated by bidirectional Sanger sequencing, and co-segregation analysis was performed in available family members. Sixteen ABCA4 variants were identified, including six novel potentially deleterious variants (three predicted loss-of-function). ACMG classifications comprised six pathogenic variants, eight likely pathogenic variants, and two variants of uncertain significance (VUS). Phenotypically, six probands presented with Stargardt disease type 1 (STGD1), one with early-onset severe retinal dystrophy (EOSRD, compound heterozygous ABCA4 variants), and one with an unclassified IRD. The three provinces of Northeast China STGD1 patients displayed a higher proportion of mild-severity variants yet presented with an earlier median onset age (10.6&#x2009;years) and more severe visual impairment (77.2% with best-corrected visual acuity <&#x2009;0.1) when compared to global cohorts. However, this observation may reflect referral bias to a tertiary center and requires validation in larger, multi-ethnic cohorts. Targeted NGS identified six potentially novel ABCA4 variants in the Northeast Chinese population, including three predicted loss-of-function variants. This study reports a case of ABCA4 associated EOSRD, thereby broadening the documented ABCA4 variant spectrum in this population.

Ocular melanoma (OM) incidence varies worldwide, but the relative impact of geographic latitude versus pigmentation genetics remains debated. We investigated whether the country-level frequency of the rs12913832 derived (G) blue-eye allele (G allele frequency), or latitude better explains international differences in OM incidence. We performed an observational ecological study of 29 countries using age-standardized OM incidence data from the International Agency for Research on Cancer (IARC), G allele frequencies from publicly available databases, and population-weighted centroids derived from nighttime lights data. We conducted correlation, linear regression, and mediation analyses to assess the associations among latitude, G allele frequency, and OM incidence. In univariate analyses, both latitude and the G allele frequency were positively associated with OM incidence. In multivariate regression, latitude was no longer significant, whereas the G allele frequency explained substantially more variance and uniquely accounted for 61 times more variance (partial r2) than latitude. Mediation analysis indicated that about 92% of latitude's effect on incidence was mediated through G allele frequency. At the population level, the G allele frequency is a markedly stronger predictor of OM incidence than geographic latitude. As an ecological analysis, this study identifies a population-level association rather than individual-level genetic risk and suggests that pigmentation genetics underlie much of the international variation in OM incidence.

Near-infrared (NIR) and red light photobiomodulation (PBM) has gained increasing interest as a non-invasive therapeutic approach for a variety of medical conditions including ocular diseases. The eye represents a particularly suitable target for light-based therapies owing to its optical accessibility and the high mitochondrial demand of various tissues such as the retina and optic nerve. Ocular aging and several ophthalmic disorders are associated with mitochondrial dysfunction, oxidative stress, and chronic inflammation, providing a biological rationale for the use of PBM as a potential adjunctive approach. This narrative review provides an evidence-weighted, indication-specific synthesis of NIR and red-light PBM in ophthalmology, emphasizing device- and protocol-dependence, differences between multiwavelength PBM and repeated low-level red-light therapy, study-design limitations, safety considerations, and clinical translation gaps. A structured literature search was conducted using major scientific databases to identify relevant experimental studies, clinical trials, and observational reports. The review focuses on proposed mitochondria-centered mechanisms of action, including cytochrome c oxidase-mediated signaling, nitric oxide release, reactive oxygen species-driven hormetic responses, and downstream anti-inflammatory effects. Particular emphasis is reserved to dry age-related macular degeneration, for which literature is more relevant, and to dry eye disease owing to meibomian gland dysfunction and myopia, for which a body of evidence is progressively growing. For other ocular indications, data remain preliminary or exploratory. Overall, available data support biological plausibility and suggest possible functional or anatomical signals in selected ocular diseases, but the clinical evidence remains heterogeneous, with substantial variability in devices, wavelengths, dosimetry, treatment protocols, and study design, and remains insufficient to define PBM as established therapy for most indications. However, the clinical evidence remains heterogeneous, with substantial variability in devices, wavelengths, dosimetry, and treatment protocols. Although available studies generally report favorable short-term tolerability, long-term safety and the role of PBM in routine ophthalmic practice remain insufficiently defined. Well-designed, adequately randomized controlled trials with standardized treatment parameters are required to determine efficacy, optimal protocols, and long-term clinical relevance.

Manual segmentation of the whole anterior visual pathway (aVP) from high-resolution magnetic resonance imaging (MRI) is time-consuming and prone to inter-rater variability. We developed and validated a fully automated deep learning framework, "aVP-seg," to perform rapid, multiclass segmentation of the optic nerves, chiasm, and optic tracts in healthy volunteers and multiple sclerosis (MS) patients. We developed and validated a cascaded two-stage three-dimensional convolutional neural network (principal segmentation + refinement) for automated multiclass segmentation of the aVP from 0.6-mm isotropic three-dimensional constructive interference in steady state (CISS) MRI. The model was trained and evaluated in 34 healthy controls and 46 MS patients. Ground truth was derived from manual segmentations by two expert radiologists. Spatial agreement metrics included Dice similarity coefficient (DSC), 95th percentile Hausdorff distance (HD95), and volumetric similarity. Agreement with the ground truth for the whole aVP was high (DSC 0.86&#x2009;&#xb1;&#x2009;0.03, mean&#x2009;&#xb1;&#x2009;standard deviation; 95% confidence interval (CI) 0.85-0.86). Boundary alignment was strong (HD95 1.18&#x2009;mm &#xb1; 0.54; 95% CI 1.06-1.30) and volumetric similarity was high (0.96&#x2009;&#xb1;&#x2009;0.04; 95% CI 0.95-0.97). Accuracy was consistent for the left and right optic nerves (DSC 0.85-0.86&#x2009;&#xb1;&#x2009;0.05-0.04) and chiasm (DSC 0.83&#x2009;&#xb1;&#x2009;0.09), but lower for the left and right optic tracts (DSC 0.74-0.75&#x2009;&#xb1;&#x2009;0.07-0.07). The aVP-seg provided accurate, automated multiclass segmentation of the whole aVP from high-resolution CISS MRI. This tool may standardize and accelerate the extraction of quantitative biomarkers of aVP integrity in neuro-ophthalmic conditions. Automated multiclass segmentation of the entire anterior visual pathway enables standardized and reproducible preparation of MRI data for quantitative analysis. This approach facilitates future assessment of optic pathway involvement in MS and other neuro-ophthalmic disorders. aVP-seg enabled fully automated segmentation of the entire anterior visual pathway from high-resolution CISS MRI data. Automated segmentation reduces processing time and operator-dependent variability. aVP-seg shows robust performance across both healthy subjects and MS patients.

Retinitis pigmentosa (RP) is an inherited retinal disease (IRD), whereby each affected individual typically harbours pathogenic variants in a single causative gene, yet the disorder exhibits marked genetic heterogeneity, with more than 100 genes reported to underlie RP. Dual-gene defect constellations are rare but may modify disease presentation, complicating diagnosis, prognosis and therapeutic decision-making. This study aimed to characterize the clinical and genetic effects of dual-gene variants in patients with RP as the lead diagnosis. We retrospectively analysed 10 affected individuals and their parents from eight families with confirmed dual-genotype constellations in RP-associated genes. Ophthalmic evaluation included best-corrected visual acuity (BCVA), visual fields, multimodal imaging, electroretinography (ERG) and full-field stimulus threshold testing (FST). Genetic analyses comprised whole genome sequencing and targeted segregation studies; for the latter, long-read sequencing was used to clarify cis/trans variant configuration. Genes involved were CEP290, RCBTB1, ABCA4, PDE6A, CRB1, EYS, PRPH2, MYO7A, RS1, USH2A, MT-TL1, RHO and BEST1, in various genotype constellations. Phenotypes ranged from early-onset severe rod-cone dystrophy to late-onset mild RP, largely reflecting gene-specific effects (e.g. EYS&#x2009;>&#x2009;CRB1&#x2009;>&#x2009;PRPH2) and their interactions. Long-read sequencing revealed ABCA4 variants in cis, explaining asymptomatic carriers and informing gene therapy eligibility. Functional retinal testing highlighted gene-specific patterns, including macular preservation in EYS-driven RP and Best disease-associated macular changes. Dual-gene variant constellations contribute to heterogeneous RP phenotypes. Integrating comprehensive genetic analysis with detailed clinical assessment is critical to define gene-specific contributions, inform prognosis, guide clinical management and determine eligibility for emerging gene-based therapies.

Rotavirus remains a major cause of mortality among young children worldwide, underscoring the urgent need for new vaccines. The present study evaluated the repeated-dose toxicity and immunogenicity of a bivalent rotavirus subunit candidate vaccine PP-P[6]/P[8]-VP8 Mix (containing equal amounts of P[6]-VP8 and P[8]-VP8 chimeric antigens) based on norovirus P particles in cynomolgus monkeys. The monkeys (5 per sex per group) were randomly assigned to a blank control group, an adjuvant control group, and low- and high-dose vaccine groups (60 &#x3bc;g/monkey and 120 &#x3bc;g/monkey). The animals received four intramuscular injections at 4-week intervals, followed by a 6-week recovery period. General behavior, body temperature, body weight, food intake, hematology, serum biochemistry, ophthalmic examination, electrocardiogram, urine analysis, immunogenicity parameters, and pathological examination of the animals were detected. No toxicologically significant abnormalities were observed throughout the study. Histopathological examination showed that there were deposition foci of aluminum hydroxide adjuvant and mild subacute inflammatory reactions at the injection site in the vaccine group. Lymphoid follicle hyperplasia and lymph sinus histiocytosis were observed in the draining lymph nodes, which are typical local immune response manifestations of aluminum adjuvant vaccines. No other adverse pathological changes were found. Our regulatory toxicology study has demonstrated the safety and immunogenicity of PP-P[6]/P[8] - VP8 Mix under the experimental conditions, supporting its entry into clinical research.