Massive retinal gliosis (MRG) is a rare, benign intraocular condition resulting from reactive glial cells undergoing exaggerated repair phenomenon. A 52-year-old male presented with 6-year history of enlarging mass in the right eye, associated with progressive vision loss and worsening proptosis. He reported history of trauma to that eye secondary to a vehicular crash one year prior. Magnetic resonance imaging (MRI) of the orbits revealed an intraocular lesion with calcifications raising the possibility of a malignant tumor. Enucleation of the right globe was performed and histopathologic examination revealed the entire vitreous cavity and retina replaced by glial cells arranged in interlacing bundles and whorls with foci of calcifications, highly suspicious of MRG. This was further confirmed by a positive, diffuse, and robust cytoplasmic expression of glial fibrillary protein (GFAP). The disease is known to have favorable outcomes as no complications, such as reemergence of the mass, active bleeding, and secondary infection, were observed from the patient during subsequent visits. Distinction of MRG from other intraocular neoplasms is clinically challenging, hence biopsy is necessary. MRG should be considered as a differential diagnosis when encountering intraocular tumors, especially if there is a history of eye trauma. This is the first reported case of MRG in the Philippines.

This paper introduces the academic characteristics of Professor ZHANG Ren in treatment with acupuncture for refractory eye diseases in modern times, guided by "homotherapy for heteropathy" (same therapy for different diseases sharing the same pathogenesis). The refractory eye diseases in modern times include a variety of conditions such as glaucoma, macular degeneration, diabetic retinopathy, high myopia and its complications, dry eye, cortical visual impairment and genetic eye diseases. The same therapy is used because these diseases share the similar location and pathogenesis. Professor ZHANG optimizes the methods of acupoint selection and provides the comprehensive prescriptions, "basic prescription, prescription based on disease differentiation, and supplementary prescription". A variety of acupuncture manipulation techniques are operated in clinical practice, such as compound needling methods, penetration needling, manipulations for promoting qi movement and conducting qi flow. "Early, regular and persistent" treatment is the common requirement with "the same acupoints, the same prescription and the same acupuncture method" as well as at "the same time". It is also proposed that the treatment should be provided flexibly according to the different symptoms, "identifying the differences within similarities".
Acupuncture Therapy/methods* ; Humans ; Eye Diseases/history* ; Acupuncture Points ; History, 20th Century ; China ; History, 21st Century

Macrophages are the crucial immune cells integral to host defense and the regulation of homeostasis, exhibiting remarkable plasticity across various tissues. Upon exposure to different stimuli, they can polarize into functional subsets. The reorganization process of cellular metabolism, known as metabolic reprogramming, involves the comprehensive adjustment of intracellular metabolites, enzymes, and metabolic pathways. Recent studies have revealed the critical role of metabolic reprogramming in shaping the phenotypes and functions of macrophages. Metabolism drives and regulates macrophages by generating bioenergy and biosynthetic precursors and by altering metabolites that affect gene expression and signal transduction. This review focuses on the immunomodulatory roles of key enzymes and specific products in major metabolic pathways, such as glucose metabolism, lipid metabolism and amino acid metabolism, in macrophages. Additionally, it will highlight recent advancements in targeting metabolic regulation of macrophages in the context of ocular diseases.
Humans ; Macrophages/immunology* ; Animals ; Eye Diseases/immunology* ; Lipid Metabolism ; Glucose/metabolism* ; Metabolic Networks and Pathways ; Signal Transduction ; Metabolic Reprogramming

Objective:The prevalence of seasonal allergic rhinitis （AR） and its combined diseases have been increasing recently. The purpose was to investigate the clinical characteristics and treatment of seasonal AR in northern China. Methods:A cross-sectional study was conducted in AR patients. The Visual analogue scale （VAS）, combined diseases, clinical features, allergic pollen and treatments were analyzed. Results:Of the 789 AR subjects included, 54.1% had a family history of atopic disease. The mian course wa s（7.4±5.9） years. 95.4% of the subjects had moderate to severe AR. The prevalence rates of allergic conjunctivitis （AC）, allergic asthma （AA）, and pollen food allergy syndrome （PFAS） were 71.1%, 19.0%, and 39.5% respectively. Among the patients, 13.8% presented with only AR, while 39.3% had an AR combined with other disease, and 1.9% exhibited comorbidity involving five different diseases. VAS was positively correlated with the number of comorbidities（r=0.186, P<0.001）. The mugwort exhibited the highest rate of pollen sensitization （48.9%）, closely followed by cypress （48.3%）. The prevalence of mono-sensitization to pollen was 20.2%, while the positive rates for double-sensitized pollens and more than three sensitized pollens were 17.4% and 62.4%, respectively. Among the study participants, 19.9% did not receive any form of treatment, while 66.2% were administered oral medication and 27.5% underwent nasal steroid spray therapy. The proportion of individuals receiving anti-IgE monoclonal antibodies was 4.3%, and allergen immunotherapy （AIT） treatment was undergone by 11.8%. Meanwhile, 41.2% of patients undergoing anti-IgE monoclonal antibody treatment also received AIT. The distribution of therapy types among patients was as follows: 44.7% received a single type, 22.2% received two types, and 9.8% received three types of therapy. Additionally, there was a subset of patients（1%） who were undergoing five distinct forms of treatment. The VAS score exhibited a significant negative correlation with no treatment（r=-0.199, P<0.001）, while it showed a positive association with the number of treatment modalities（r=0.245, P<0.001）. Conclusion:Mugwort and cypress are the predominant allergenic pollens responsible for seasonal AR in northern China. The majority of cases present with moderate to severe AR, often accompanied by various comorbidities, necessitating consideration of diverse treatment modalities. However, the current rate of adoption for AIT remains relatively insufficient.
Humans ; China/epidemiology* ; Cross-Sectional Studies ; Rhinitis, Allergic, Seasonal/therapy* ; Pollen/immunology* ; Adult ; Male ; Female ; Young Adult ; Adolescent ; Middle Aged ; Child ; Prevalence ; Allergens/immunology* ; Asthma/epidemiology* ; Conjunctivitis, Allergic

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 clinical characteristics and genetic cause of a child with gastrointestinal hemorrhage and Cerebroretinal microangiopathy with calcifications and cysts (CRMCC) and to review the literature. METHODS: Clinical data of a child with gastrointestinal hemorrhage with CRMCC admitted to the Hepatology Department of Hunan Children's Hospital in September 2019 were collected, and peripheral blood DNA of the child and his parents were analyzed by whole exome sequencing. Candidate variants were validated by Sanger sequencing, followed by bioinformatics analysis, American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants pathogenicity classification, and protein structure prediction. A literature search with "Coats Plus syndrome" or "Cerebroretinal microangiopathy with calcifications and cysts" as keywords was conducted at PubMed, China National Knowledge Infrastructure and Wanfang databases to include recently published studies (up to December 2023). This study has been approved by the Ethics Committee of Hunan Children's Hospital (Ethics No. KY2020-07). Informed consent for clinical research was obtained from the guardian of the child. RESULTS: The proband was a 10-year-10-month-old boy. The clinical manifestations were intrauterine and postnatal growth retardation, gastrointestinal hemorrhage, liver fibrosis, panhemopenia, bilateral exudative retinopathy, intracranial lesions and facial pigmentation. WES and Sanger sequencing revealed two novel heterozygous variants in the CTC1 gene: c.787G>A (p.Val263Met) in exon 5 and c.2930C>G (p.Ser977Cys) in exon 17, which were inherited from his mother and father, respectively. According to ACMG pathogenicity classification, both missense variants were classified as variants of uncertain significance (VUS). Protein structure prediction showed the absence of LIG_SH3_3 motif and LIG_SH3_3 motif, and the p.Ser977Cys mutation may affect the binding between CST (CTC1-STN1-TEN) complex and DNA strand. The child had continued to experience recurrent gastrointestinal bleeding episodes despite propranolol treatment, but the condition was controlled after liver transplantation. According to the predefined literature search strategy of this study, a total of 10 relevant articles on pediatric CRMCC patients were retrieved, involving 11 children with gastrointestinal bleeding. Pharmacological and endoscopic therapies play a certain role in the management of CRMCC children complicated with gastrointestinal bleeding. CONCLUSION The CTC1 gene c.787G>A and c.2930C>G variants probably underlay CRMCC in this child. This study has broadened the variation spectrum of CTC1-related diseases and provided a basis for genetic counseling. Liver transplantation may be an important treatment for gastrointestinal hemorrhage in children who do not respond well to medication and endoscopic therapy.
Humans ; Male ; Gastrointestinal Hemorrhage/genetics* ; Child ; Calcinosis/genetics* ; Cysts/genetics* ; Central Nervous System Cysts/genetics* ; Mutation ; Exome Sequencing ; Leukoencephalopathies ; Retinal Diseases ; Seizures ; Muscle Spasticity ; Brain Neoplasms ; Ataxia

OBJECTIVE: To explore the genetic etiology of a child with Brain small vessel disease 1 with ocular anomalies. METHODS: A child who was admitted to Ningbo Women and Children's Hospital on May 28, 2022 was selected for the study. Clinical data were collected, and peripheral blood samples from the child and her parents were obtained for genomic DNA extraction. Whole exome sequencing (WES) was performed to screen for pathogenic variants. Candidate variants were validated via Sanger sequencing and subjected to bioinformatic analysis. This study was approved by the Medical Ethics Committee of Ningbo Women and Children's Hospital (Ethics No. EC2020-014). RESULTS: The child was a 7-year-old female with a diagnosis of epilepsy. WES revealed that she has carried a heterozygous missense variant in the COL4A1 gene: c.1792G>A (p.Gly598Ser). Sanger sequencing confirmed that her parents both had the wild-type genotype for this variant. Based on American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants, the variant were predicted to be a likely pathogenic (PS2+PM1+PM2_Supporting+PP3). Bioinformatics predicted that amino acid 598 was highly conserved in different species, formed hydrogen bond with Asp599 after becoming Ser598. CONCLUSION The heterozygous missense variant of the COL4A1 gene c.1792T>C (p.G598S) could be the pathogenic cause of this child with Brain small vessel disease 1 with ocular anomalies.
Humans ; Female ; Child ; Collagen Type IV/genetics* ; Eye Abnormalities/genetics* ; Exome Sequencing ; Mutation, Missense ; Cerebral Small Vessel Diseases/genetics*

OBJECTIVE: To explore the genetic etiology of a Chinese pedigree with recurrent Joubert syndrome with negative results by whole-exome sequencing in the prior proband. METHODS: Chinese pedigree which opted elective abortion at the Women and Children's Hospital Affiliated to Chongqing Medical University in December 2024 was selected as the study subject. Whole-genome sequencing was carried out on fetal tissue after termination of pregnancy. Candidate variants were validated by Sanger sequencing and interpreted, while non-coding variant was analyzed using in silico prediction tools. RNA sequencing and cDNA sequencing were conducted on fetal brain tissue. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.2024YL045-02). RESULTS: Both the fetus and the affected child were found to harbor compound heterozygous variants of the CEP290 gene, namely c.7341dup (p.Leu2448fs*8) (pathogenic, maternally inherited) and c.1523-408G>A (likely pathogenic, paternally inherited). Both in silico analysis and fetal brain RNA sequencing confirmed aberrant RNA splicing caused by the intronic variant. CONCLUSION This case has highlighted the value of combining whole-genome sequencing with RNA functional validation. Above results not only enriched the spectrum of CEP290 gene mutations but also underscored its diagnostic value in resolving complex prenatal cases, providing critical clues for the prenatal diagnosis and recurrence risk assessment in genetic counseling.
Female ; Humans ; Pregnancy ; Abnormalities, Multiple/genetics* ; Antigens, Neoplasm/genetics* ; Cell Cycle Proteins/genetics* ; Cerebellum/abnormalities* ; Cytoskeletal Proteins/genetics* ; Eye Abnormalities/genetics* ; Introns/genetics* ; Kidney Diseases, Cystic/diagnosis* ; Pedigree ; Retina/abnormalities* ; Sequence Analysis, RNA/methods* ; Whole Genome Sequencing/methods* ; Child

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 analyze genetic factors and phenotype characteristics in pediatric population with slight-to-moderate sensorineural hearing loss. Methods:Children with slight-to-moderate sensorineural hearing loss of and their parents, enrolled from the Chinese Deafness Genome Project, were studied. Hearing levels were assessed using pure tone audiometry, behavioral audiometry, auditory steady state response（ASSR）, auditory brainstem response（ABR） thresholds, and deformed partial otoacoustic emission（DPOAE）. Classification of hearing loss is according to the 2022 American College of Medical Genetics and Genomics（ACMG） Clinical Practice Guidelines for Hearing Loss. Whole exome sequencing（WES） and deafness gene Panel testing were performed on peripheral venous blood from probands and validations were performed on their parents by Sanger sequencing. Results:All 134 patients had childhood onset, exhibiting bilateral symmetrical slight-to-moderate sensorineural hearing loss, as indicated by audiological examinations. Of the 134 patients, 29（21.6%） had a family history of hearing loss, and the rest were sporadic patients. Genetic causative genes were identified in 66（49.3%） patients. A total of 11 causative genes were detected, of which GJB2 was causative in 34 cases（51.5%）, STRC in 10 cases（15.1%）, MPZL2 gene in six cases（9.1%）, and USH2A in five cases（7.6%）.The most common gene detected in slight-to-moderate hearing loss was GJB2, with c. 109G>A homozygous mutation found in 16 cases（47.1%） and c. 109G>A compound heterozygous mutation in 9 cases（26.5%）. Conclusion:This study provides a crucial genetic theory reference for early screening and detection of mild to moderate hearing loss in children, highlighting the predominance of recessive inheritance and the significance of gene like GJB2, STRC, MPZL2, USH2A.
Humans ; Child ; Connexins/genetics* ; Connexin 26/genetics* ; Hearing Loss, Sensorineural/diagnosis* ; Mutation ; Usher Syndromes ; Hearing Loss, Bilateral ; Audiometry, Pure-Tone ; Intercellular Signaling Peptides and Proteins