Subtype classification of age-related macular degeneration (AMD) based on optical coherence tomography (OCT) images serves as an effective auxiliary tool for clinicians in diagnosing disease progression and formulating treatment plans. To improve the classification accuracy of AMD subtypes, this study proposes a keypoint-based, attention-enhanced residual network (KPA-ResNet). The proposed architecture adopts a 50-layer residual network (ResNet-50) as the backbone, preceded by a keypoint localization module based on heatmap regression to outline critical lesion regions. A two-dimensional relative self-attention mechanism is incorporated into convolutional layers to enhance the representation of key lesion areas. Furthermore, the network depth is appropriately increased and an improved residual module, ConvNeXt, is introduced to enable comprehensive extraction of high-dimensional features and enrich the detail of lesion boundary contours, ultimately achieving higher classification accuracy of AMD subtypes. Experimental results demonstrate that KPA-ResNet achieves significant improvements in overall classification accuracy compared with conventional convolutional neural networks. Specifically, for the wet AMD subtypes, the classification accuracies for inactive choroidal neovascularization (CNV) and active CNV reach 92.8% and 95.2%, respectively, representing substantial improvement over ResNet-50. These findings validate the superior performance of KPA-ResNet in AMD subtype classification tasks. This work provides a high-accuracy, generalizable network architecture for OCT-based AMD subtype classification and offers new insights into integrating attention mechanisms with convolutional neural networks in ophthalmic image analysis.
Tomography, Optical Coherence/methods* ; Humans ; Macular Degeneration/diagnostic imaging* ; Neural Networks, Computer

A 7-year-old girl was admitted to the hospital with rapidly progressive vision loss. Since 1 year of age, she had exhibited developmental delay accompanied by visual impairment and neutropenia. Combined with genetic testing and molecular pathogenicity analysis, she was diagnosed with Cohen syndrome (CS) caused by compound heterozygous variants in VPS13B (c.6940+1G>T and c.2911C>T). The c.6940+1G>T variant resulted in exon 38 skipping, leading to a frameshift and premature termination. Reverse transcription quantitative polymerase chain reaction revealed significantly reduced VPS13B gene expression (P<0.05). Bioinformatic analysis suggested that both variants likely produce truncated proteins. This case highlights that integrating clinical features with molecular pathogenicity assessment (DNA, RNA, and protein analysis) can improve early diagnostic accuracy for CS.
Humans ; Female ; Child ; Vesicular Transport Proteins/genetics* ; Developmental Disabilities/etiology* ; Muscle Hypotonia/etiology* ; Myopia/etiology* ; Heterozygote ; Intellectual Disability/etiology* ; Microcephaly/etiology* ; Obesity/genetics* ; Growth Disorders/etiology* ; Retinal Degeneration/genetics* ; Psychomotor Disorders/genetics* ; Fingers/abnormalities*

For HCQ retinopathy with CME, acupuncture combined with periocular injection can be used to improve the CME and protect the central vision. Subsequent research endeavors involving a more extensive cohort and extended observation periods are warranted to evaluate the effectiveness and safety profile of the intervention.
Humans ; Macular Edema/drug therapy* ; Acupuncture Therapy/methods* ; Hydroxychloroquine/therapeutic use* ; Female ; Retinal Diseases/chemically induced* ; Middle Aged ; Combined Modality Therapy ; Male

Objective:To investigate the molecular characteristics and clinical heterogeneity of Usher syndrome（USH） -related gene variants in patients with hereditary hearing loss in southwest China, providing a basis for early diagnosis and clinical management. Methods:Thirteen patients from twelve families with hearing loss who attended the Affiliated Children's Hospital of Kunming Medical University between January 2017 and March 2021 were enrolled. All patients were identified as carrying USH-related gene variants through next-generation sequencing. Sanger sequencing was performed for all patients and their parents to validate the pathogenic variants. Comprehensive clinical evaluations, including medical history collection, otologic and ophthalmologic examinations, and vestibular function assessments, were conducted. Results:Among the 13 patients, 4 were diagnosed with USH type 1 and 2 with USH type 2. A total of 19 pathogenic or likely pathogenic variants were detected in USH-related genes, including MYO7A,CDH23,USH1C, and USH2A. The causative gene was MYO7A in 3 probands, CDH23 in 5, USH1C in 3, and USH2Ain 2. All patients exhibited an autosomal recessive inheritance pattern. Vestibular dysfunction was observed in 4 patients, and retinitis pigmentosa（RP） in 3 patients. Based on the genotype-phenotype correlation, 6 patients were initially diagnosed with USH, while 7 were classified as having non-syndromic hearing loss（NSHL）. Conclusion:This study revealed the clinical heterogeneity of USH-related gene variants in patients with hereditary deafness in southwest China. Although the clinical manifestations of USH are complex and there are overlapping characteristics between different subtypes, genetic testing provides an important basis for early diagnosis and precise clinical management. Especially for those with typical hearing loss, early genetic diagnosis can provide a window of time for early detection and intervention of retinitis pigmentosa.
Humans ; Usher Syndromes/genetics* ; Myosin VIIa ; Phenotype ; Male ; Female ; Myosins/genetics* ; Mutation ; Cadherins/genetics* ; Child ; Extracellular Matrix Proteins/genetics* ; Adolescent ; Pedigree ; High-Throughput Nucleotide Sequencing ; Cadherin Related Proteins ; Cytoskeletal Proteins ; Cell Cycle Proteins

OBJECTIVE: To explore the correlation between clinical manifestations and genetic variations in six Chinese Stargardt disease pedigrees. METHODS: Six Stargardt disease pedigrees due to ABCA4 gene variants that visited Shanxi Eye Hospital from June 2021 June 2023 were selected as the study subjects. A retrospective study method was used to collect the clinical and family history data of all members of these pedigrees. Peripheral venous blood samples of the examinees were collected, and genomic DNA was extracted for trio-WES. Candidate variants of the ABCA4 gene were verified by family Sanger sequencing. According to the "Standards and Guidelines for the Classification of Sequence Variants" (hereinafter referred to as the "ACMG Guidelines") formulated by American College of Medical Genetics and Genomics (ACMG), the variant sites of the ABCA4 gene were classified for pathogenicity. This study has been approved by the Medical Ethics Committee of Shanxi Eye Hospital (Ethics No. SXYYLL-20200620). RESULTS: From June 2021 to June 2023, 7 patients (patient 1 to 7) from families with Stargardt disease with ABCA4 variants were selected as the study subjects. The age of the patients was between 7 to 53 years old, and the age of onset was between their 6 to 15 years old. All patients had exhibited moderate-to-severe visual impairment with macular atrophy, and yellow white spots were seen in all patients except patient II2 in family 5. Optical coherence tomography (OCT) results showed that all patients' macular fovea was significantly thinner, with IS/OS or ellipsoid zone disappeared. Autofluorescence showed low autofluorescence in the macula, and abnormalities dot autofluorescence in the paramacular and periphery retina. ERG grouping classified three pedigrees as Group 3, two as Group 1, and one as Group 2. Genetic analysis results showed that all pedigrees had autosomal recessive inheritance, five had compound heterozygous variants in the ABCA4, and one had homozygous variants. In total 11 pathogenic mutations were detected in the ABCA4 gene, of which 3 were found for the first time, including p.Glu1704Gly, p.Gly1965Glu and p.Ser1531Phe. Patients carrying nonsense or frameshift mutations include patient 1 (family 1, II1), patient 2 (family 1, II2), patient 4 (family 3, II1), patient 6 (family 5, II2), and patient 7 (family 6, II1), whose clinical manifestations are more severe than those of patient 3 (family 2, II2) and patient 5 (family 4, II1), whom carried missense mutations in terms of best corrected visual acuity (BCVA) damage. CONCLUSION The ABCA4 gene variations may be the genetic cause of the Stargardt disease in this study, and the discovery of the ABCA4 gene p.Glu1704Gly, p.Gly1965Glu, p.Ser1531Phe variants has enriched the mutational spectrum of Stargardt disease.
Adolescent ; Adult ; Child ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; ATP-Binding Cassette Transporters/genetics* ; China ; Genetic Variation ; Macular Degeneration/congenital* ; Mutation ; Pedigree ; Retrospective Studies ; Stargardt Disease/genetics* ; East Asian People/genetics*

OBJECTIVE: To explore the clinical phenotype, genotype and genetic characteristics for a patient with unilateral Pigmented paravenous retinochoroidal atrophy (PPRCA) and Retinitis pigmentosa (RP) in the contralateral eye. METHODS: A PPRCA pedigree which had presented at the Department of Medical Genetics of the Eye Hospital of Wenzhou Medical University in August 2021 was selected as the study subject. Clinical data of the family members were collected. The proband underwent wide-field fundus photography, wide-field autofluorescence, full-field electroretinogram (ff-ERG), visual field testing, optical coherence tomography (OCT), and fundus angiography (FFA and ICGA). Blood samples were collected from the proband and family members (parents and two sisters), and buccal mucosal cells were collected from the proband's daughter, and genomic DNA was extracted for each family member. Whole exome sequencing (WES) was performed on the proband. Candidate variants were verified using Sanger sequencing and pathogenicity analysis. This study was approved by the Medical Ethics Committee of the Eye Hospital of Wenzhou Medical University (Ethics No. 2019-134). RESULTS: Wide-angle fundus photography and autofluorescence showed that the right eye was consistent with PPRCA and the left eye with RP. OCT showed that the outer layer of the fovea was intact in the right eye, while disorganized outer segment was found in the fovea of the left eye, and outer segment atrophies outside the fovea were found in both eyes. The amplitudes of ff-ERG decreased significantly in both eyes, and the amplitudes in right eye were slightly higher than those of the left eye. Visual field showed a paracentral arcuate scotoma in the right eye and severe centripetal contraction in the left eye. FFA showed hyperfluorescence in the retinal vein distribution area caused by atrophy of retinal pigment epithelium of the right eye and hypofluorescence related to bone spicule pigmentation, in addition with mottled hypofluorescence of choroid in the left eye. ICGA showed mild paravenous retinochroidal atrophy of the right eye and diffuse choroid capillaries atrophy in the middle and peripheral area of the left eye. WES revealed that the proband had a heterozygous c.2234C>T (p.Thr745Met) variant of the CRB1 gene. Sanger sequencing confirmed that the proband and family members except the father of the proband carried the same CRB1 gene variant. Based on the criteria and guidelines for the classification of genetic variation and related consensus from the American College of Medical Genetics and Genomics (ACMG), this variant was classified as pathogenic (PM3_VeryStrong+PM1+PM2_Supporting +PP3). CONCLUSION The heterozygous c.2234C>T (p.Thr745Met) variant of the CRB1 gene may underlay the unilateral PPRCA with contralateral eye RP in this proband. Above findings have enriched the mutational spectrum of the CRB1 gene.
Humans ; Electroretinography ; Exome Sequencing ; Eye Proteins/genetics* ; Membrane Proteins/genetics* ; Mutation ; Nerve Tissue Proteins/genetics* ; Pedigree ; Phenotype ; Retinitis Pigmentosa/genetics* ; Tomography, Optical Coherence ; Retinal Degeneration ; Eye Diseases, Hereditary

OBJECTIVE: To investigate the clinical features and pathogenesis of a child with Stargardt disease caused by variants of ABCA4 gene. METHODS: A child presented at Shenzhen Eye Hospital between September 5, 2020, and April 3, 2023 was selected as the study subject. Clinical data of the child were collected. Whole exome sequencing was performed on peripheral blood samples from the child and his parents. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of Shenzhen Eye Hospital (Ethics No.: 2022KYPJ072). RESULTS: The child was a 10-year-old male presenting with uncorrected visual acuity of 0.1 in both eyes without improvement with refractive correction. Fundus photography showed diffusely distributed yellow-white flecks in the macular region. FAF revealing central hypofluorescence surrounded by a hyperfluorescent ring, and OCT demonstrating significant foveal thinning (right eye: 45 μm; left eye: 50 μm) with ellipsoid zone disruption. Whole exome sequencing and Sanger sequencing revealed that the child has harbored compound heterozygous variants of the ABCA4 gene, namely c.2384G>T (p.Gly795Val) and c.2903G>A (p.Arg968Glu), which were inherited from his phenotypically normal parents and consistent with an autosomal recessive inheritance. This specific combination of the variants was previously unreported. According to the guidelines from the American College of Medical Genetics and Genomics (ACMG) guidelines, both variants were classified as likely pathogenic (PM2_Supporting+PM3+PP3+PP4; PM1+PM2_Supporting+PP3+PP4). CONCLUSION The novel compound heterozygous variants of the ABCA4 gene probably underlay the genetic etiology of Stargardt disease type 1 in this child. Above finding has expanded the mutational spectrum of the ABCA4 gene among the Chinese population and provided further evidence for understanding the genetic heterogeneity and genotype-phenotype correlation of the Stargardt disease.
Humans ; Male ; Child ; ATP-Binding Cassette Transporters/genetics* ; Stargardt Disease/genetics* ; Heterozygote ; Mutation ; Exome Sequencing ; Macular Degeneration/congenital*

OBJECTIVE: To explore the clinical phenotype and genetic characteristics in two children with Knobloch syndrome (KNO) due to variants of COL18A1 gene. METHODS: Two children presented at the Genetic Eye Disease Clinic of the Eye Hospital of Wenzhou Medical University in October 2023 for ocular lesions were selected as the study subjects. Relevant clinical data and peripheral venous blood samples were collected from the children and their parents. Following genomic DNA extraction, whole-exome sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing of the family members. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2021-212-K-185). RESULTS: Both children exhibited characteristic ocular features of KNO including nystagmus, high myopia, and leopard spot fundus. Additionally, child 1 also presented with congenital occipital bone dysplasia and occipital encephalocele, while child 2 was diagnosed with vitreoretinochoroidopathy and bilateral high myopia. WES has identified compound heterozygous variants of the COL18A1 gene in both children, including a c.3013+3A>C splice-site variant and a c.2743C>T (p.Arg915Ter) nonsense variant in child 1, and a novel c.1702-1G>A splice-site variant and a c.3836C>T (p.Ser1279Leu) missense variant in child 2. A comprehensive literature review has identified 63 domestic and international articles involving 167 patients with KNO whom can be classified into three subtypes, with KNO type I being the most common and caused by pathogenic variants in the COL18A1 gene. Both probands in this study were children with KNO type I. Analysis of the genotype-phenotype correlations and population distribution characteristics revealed that the KNO patients exhibited significant clinical and genetic heterogeneity, along with a broad geographic distribution, with a relatively greater number of cases reported in Brazil and China. and a broad geographic distribution, with the highest numbers reported in Brazil and China. While no significant difference in genotype distribution was observed between Chinese and non-Chinese patients, phenotypic disparities were noted, with the non-Chinese cohort showing significantly higher rates of retinal detachment and developmental delay (P < 0.05), whereas Chinese patients exhibited a greater proportion of macular hypoplasia (P < 0.05). CONCLUSION The main clinical manifestations of KNO include high myopia, vitreoretinal dystrophy, and occipital encephalocele. The novel c.1702-1G>A splice-site variant identified in the COL18A1 gene has expanded the mutational spectrum of KNO type I and provided valuable insights for genetic diagnosis, counseling, and clinical management of the disease.
Humans ; Retinal Detachment/congenital* ; Male ; Female ; Child ; Encephalocele/genetics* ; Exome Sequencing ; Collagen Type XVIII/genetics* ; Phenotype ; Retinal Degeneration/genetics* ; Mutation ; Child, Preschool

OBJECTIVE: To explore the genetic basis for a boy affected with Cohen syndrome. METHODS: A boy admitted to Children's Hospital of Nanjing Medical University in January 2021 was selected as the study subject. Genome DNA was extracted from peripheral blood samples from the child and his parents. Whole exome sequencing (WES) was carried out. And candidate variants were verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 202106060-1). RESULTS: WES revealed that the child has harbored compound heterozygous variants of the VPS13B gene, namely c.1563+1G>A and c.3007insC (p.A1003Afs*13), which were inherited from his mother and father, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rates as pathogenic. The c.3007insC (p.A1003Afs*13) was unreported previously. CONCLUSION The compound heterozygous variants c.1563+1G>A and c.3007insC (p.A1003Afs*13) of the VPS13B gene probably underlay the pathogenesis of Cohen syndrome in this child. Above finding has enriched the mutational spectrum of VPS13B gene.
Humans ; Male ; Vesicular Transport Proteins/genetics* ; Intellectual Disability/genetics* ; Muscle Hypotonia/genetics* ; Microcephaly/genetics* ; Fingers/abnormalities* ; Myopia/genetics* ; Obesity/genetics* ; Developmental Disabilities/genetics* ; Mutation ; Exome Sequencing ; Child ; Heterozygote ; Retinal Degeneration

Background and Objective: The Philippines does not have a national congenital rubella syndrome (CRS) surveillance or registry. Regular monitoring of CRS cases in hospitals, including in a Philippine tertiary hospital, helped in the past to provide clinico-epidemiologic data on CRS. This study aimed to continue providing clinico-epidemiologic data on CRS cases seen in the Philippine tertiary hospital from 2009-2012 and 2019-2022 and compare the cases seen from said timelines. Methods: A cross-sectional study was used, employing chart review of patients newly diagnosed with CRS from 2009-2012 and 2019-2022 in the Department of Ophthalmology and Visual Sciences at the Philippine tertiary hospital. Results: Forty-two patients newly diagnosed with CRS from 2009-2012 and 2019-2022 were included. Only 14 (33%) were serologically-confirmed cases (albeit qualitatively). Median age (first and third interquartile ranges) at consult was 1 year (0.4, 2.5). Twenty-four (57%) patients had maternal history of rashes and/or fever. Trimester of pregnancy when mother became symptomatic was not significantly correlated with chief complaint (p=0.20) and numbers of ophthalmic (p=0.68) and systemic manifestations (p=0.32). Cataract was the most common ophthalmic manifestation present in 40 (95%) patients. Twenty-six (62%) patients had other associated systemic findings of which hearing loss was the most common. Only 29 of 40 patients with cataract underwent lensectomy, with 23 patients having poor visual prognosis prior to surgery (5 with nystagmus alone, 10 with nystagmus and strabismus, and 8 with strabismus alone). Discussion: Using ophthalmic manifestations as primary indicator, this study provided an update on the CRS cases in the country. Laboratory confirmation remains a challenge in diagnosing CRS as the tests are costly and not widely available. There was increase from 2009-2012 compared to 2019-2022 in number of patients who underwent surgical treatment for cataract but visual outcomes were suboptimal due to delay in consultation. Although there was a decrease in number of CRS cases seen in the Philippine tertiary hospital, this cannot be attributed to increased rubella-containing vaccine (RCV) coverage alone. Conclusion Provision of data from individual hospital-based studies similar to this highlights the need for a national CRS surveillance system or registry. This can better gauge the burden of CRS and identify the gap in RCV coverage.
Rubella Syndrome, Congenital ; Retinitis Pigmentosa