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Purpose: Pathogenic variants in North Carolina macular dystrophy (NCMD) have rarely been reported in the East Asian population. Herein, we reported novel variants of NCMD in 2 Korean families. Methods: The regions associated with NCMD were analyzed with genome sequencing, and variants were filtered based on the minor allele frequency (0.5%) and heterozygosity. Non-coding variants were functionally annotated using multiple computational tools. Results: We identified two rare novel variants, chr6:g.99,598,914T>C (hg38; V17) and chr6:g.99,598,926G>A (hg38; V18) upstream of PRDM13 in families A and B, respectively. In Family 1, Grade 2 NCMD and a best-corrected visual acuity of 20/25 and 20/200 in the right and left eyes, respectively, were observed. In Family B, all affected individuals had Grade 1 NCMD with characteristic confluent drusen at the fovea and a best-corrected visual acuity of 20/20 in both eyes. These two variants are 10-22 bp downstream of the reported V10 variant within the DNase1 hypersensitivity site. This site is associated with progressive bifocal chorioretinal atrophy and congenital posterior polar chorioretinal hypertrophy and lies in the putative enhancer site of PRDM13. Conclusion: We identified two novel NCMD variants in the Korean population and further validated the regulatory role of the DNase1 hypersensitivity site upstream of PRDM13.
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Distrofias Hereditárias da Córnea , Humanos , Distrofias Hereditárias da Córnea/genética , Fóvea Central , Nucleotídeos , Linhagem , República da CoreiaRESUMO
BACKGROUND: Optic neuritis (ON) prognosis is influenced by various factors including attack severity, underlying aetiologies, treatments and consequences of previous episodes. This study, conducted on a large cohort of first ON episodes, aimed to identify unique prognostic factors for each ON subtype, while excluding any potential influence from pre-existing sequelae. METHODS: Patients experiencing their first ON episodes, with complete aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibody testing, and clinical data for applying multiple sclerosis (MS) diagnostic criteria, were enrolled. 427 eyes from 355 patients from 10 hospitals were categorised into four subgroups: neuromyelitis optica with AQP4 IgG (NMOSD-ON), MOG antibody-associated disease (MOGAD-ON), ON in MS (MS-ON) or idiopathic ON (ION). Prognostic factors linked to complete recovery (regaining 20/20 visual acuity (VA)) or moderate recovery (regaining 20/40 VA) were assessed through multivariable Cox regression analysis. RESULTS: VA at nadir emerged as a robust prognostic factor for both complete and moderate recovery, spanning all ON subtypes. Early intravenous methylprednisolone (IVMP) was associated with enhanced complete recovery in NMOSD-ON and MOGAD-ON, but not in MS-ON or ION. Interestingly, in NMOSD-ON, even a slight IVMP delay in IVMP by >3 days had a significant negative impact, whereas a moderate delay up to 7-9 days was permissible in MOGAD-ON. Female sex predicted poor recovery in MOGAD-ON, while older age hindered moderate recovery in NMOSD-ON and ION. CONCLUSION: This comprehensive multicentre analysis on first-onset ON unveils subtype-specific prognostic factors. These insights will assist tailored treatment strategies and patient counselling for ON.
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Autoanticorpos , Metilprednisolona , Glicoproteína Mielina-Oligodendrócito , Neurite Óptica , Humanos , Masculino , Feminino , Prognóstico , Adulto , Neurite Óptica/diagnóstico , Neurite Óptica/imunologia , Glicoproteína Mielina-Oligodendrócito/imunologia , Pessoa de Meia-Idade , Autoanticorpos/sangue , Metilprednisolona/uso terapêutico , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/imunologia , Aquaporina 4/imunologia , Acuidade Visual/fisiologia , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/imunologia , Adulto Jovem , Adolescente , IdosoRESUMO
BACKGROUND: This study evaluate the efficacy of part-time patching in preventing recurrence after bilateral lateral rectus recession (BLR) in patients with intermittent exotropia (IXT). METHODS: A total of 190 children aged 3-13 years who experienced recurrence after BLR for IXT and received part-time patching were retrospectively reviewed. The patching was prescribed for 2 h per day for more than 6 months. Patients who had a recurrence of 18 PD or more underwent reoperation. Changes in exodeviation and reoperation ratio after part-time patching were analyzed. RESULTS: A total of 34 patients (17.9%) received reoperation after part-time patching, and the reoperation ratio after 2 years was 20.3% as per the Kaplan-Meier survival analysis. Patients with a recurrence of 7 to 10 PD showed a significantly better effect compared to those with a recurrence of more than 10 PD (p < 0.001), and the reoperation ratio was also lower in the survival analysis (p = 0.004). The factor associated with reoperation in patients with part-time patching was the duration between the operation and the initiation of part-time patching (hazard ratio [HR] = 1.006, p = 0.002). CONCLUSIONS: Part-time patching was effective in maintaining the efficacy of surgery and delaying the need of reoperation after BLR. This effect was better in patients with a recurrence of ≤ 10 PD.
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Exotropia , Criança , Humanos , Seguimentos , Resultado do Tratamento , Exotropia/cirurgia , Exotropia/etiologia , Estudos Retrospectivos , Visão Binocular , Procedimentos Cirúrgicos Oftalmológicos , Músculos Oculomotores/cirurgia , Doença Crônica , RecidivaRESUMO
BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disorder associated with various systemic and ocular complications. This study aimed to investigate the prevalence, risk factors, and clinical characteristics of ocular complications in a cohort of Korean AD patients. METHODS: A retrospective review of medical records was conducted for AD patients who visited the dermatology and ophthalmology clinics at the same institution. Demographic data, clinical characteristics, and types of ocular complications were recorded. Logistic regression analysis was performed to identify factors associated with ocular complications. RESULTS: A total of 212 AD patients were included in the study. The intraocular complications had a prevalence of 1.9%, whereas ocular surface diseases were observed more frequently, with prevalence of 13.2%. Among the ocular complications, blepharitis was the most prevalent, followed by atopic keratoconjunctivitis. Subcapsular cataract, atrophic hole, and retinal detachment were also observed. The head and neck score in the Eczema Area and Severity Index (EASI) emerged as a significant predictor for intraocular complications, independent of age, gender, total EASI score, and family history. No significant association was found between total EASI score and ocular surface disease. CONCLUSION: This study provides insights into the prevalence and risk factors of ocular complications in Korean AD patients. The head and neck score in EASI was identified as a significant predictor for intraocular complications. These findings emphasize the importance of comprehensive evaluation and interdisciplinary care for AD patients, particularly in identifying and managing potential vision-threatening complications.
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Dermatite Atópica , Índice de Gravidade de Doença , Humanos , Dermatite Atópica/epidemiologia , Dermatite Atópica/complicações , Masculino , Feminino , República da Coreia/epidemiologia , Estudos Retrospectivos , Adulto , Prevalência , Adulto Jovem , Pessoa de Meia-Idade , Adolescente , Fatores de Risco , Criança , Blefarite/epidemiologia , Blefarite/etiologia , Pré-Escolar , Oftalmopatias/epidemiologia , Oftalmopatias/etiologia , Catarata/epidemiologia , Ceratoconjuntivite/epidemiologia , Idoso , Conjuntivite Alérgica/epidemiologia , Conjuntivite Alérgica/complicaçõesRESUMO
Inherited retinal degenerations are blinding genetic disorders characterized by high genetic and phenotypic heterogeneity. The implementation of next-generation sequencing in routine diagnostics, together with advanced clinical phenotyping including multimodal retinal imaging, have contributed to the increase of reports describing novel genotype-phenotype associations and phenotypic expansions. In this study, we describe sixteen families with early-onset non-syndromic retinal degenerations in which affected probands carried rare bi-allelic variants in CFAP410, a ciliary gene previously associated with syndromic recessive Jeune syndrome. The most common retinal phenotypes were cone-rod and rod-cone dystrophies, but the clinical presentations were unified by their early onset as well as the severe impact on central visual function. Twelve variants were detected (three pathogenic, seven likely pathogenic, two of uncertain significance), eight of which were novel. One deep intronic change, c.373+91A>G, led to the creation of a cryptic splice acceptor site in intron four, followed by the inclusion of a 200- base pair pseudoexon and subsequent premature stop codon formation. To our knowledge this is the first likely pathogenic deep-intronic variant identified in this gene. Meta-analysis of all published and novel CFAP410 variants revealed no clear correlation between the severity of the CFAP410-associated phenotypes and the identified causal variants. This is supported by the fact that the frequently encountered missense variant p.(Arg73Pro), often found in syndromic cases, was also associated with non-syndromic retinal degeneration. This study expands the current knowledge of CFAP410-associated ciliopathy by enriching its mutational landscape and supports its association with non-syndromic retinal degeneration.
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Importance: Despite advances in next-generation sequencing (NGS), a significant proportion of patients with inherited retinal disease (IRD) remain undiagnosed after initial genetic testing. Exome sequencing (ES) reanalysis in the clinical setting has been suggested as one method for improving diagnosis of IRD. Objective: To investigate the association of clinician-led reanalysis of ES data, which incorporates updated clinical information and comprehensive bioinformatic analysis, with the diagnostic yield in a cohort of patients with IRDs in Korea. Design, Setting, and Participants: This was a multicenter prospective cohort study involving 264 unrelated patients with IRDs, conducted in Korea between March 2018 and February 2020. Comprehensive ophthalmologic examinations and ES analyses were performed, and ES data were reanalyzed by an IRD specialist for single nucleotide variants, copy number variants, mobile element insertions, and mitochondrial variants. Data were analyzed from March to July 2023. Main Outcomes and Measures: Diagnostic rate of conventional bioinformatic analysis and clinician-driven ES reanalysis. Results: A total of 264 participants (151 [57.2%] male; mean [SD] age at genetic testing, 33.6 [18.9] years) were enrolled, including 129 patients (48.9%) with retinitis pigmentosa and 26 patients (9.8%) with Stargardt disease or macular dystrophy. Initial bioinformatic analysis diagnosed 166 patients (62.9%). Clinician-driven reanalysis identified the molecular cause of diseases in an additional 22 patients, corresponding to an 8.3-percentage point increase in diagnostic rate. Key factors associated with new molecular diagnoses included clinical phenotype updates (4 patients) and detection of previously overlooked variation, such as structural variants (9 patients), mitochondrial variants (3 patients), filtered or not captured variants (4 patients), and noncanonical splicing variants (2 patients). Among the 22 patients, variants in 7 patients (31.8%) were observed in the initial analysis but not reported to patients, while those in the remaining 15 patients (68.2%) were newly detected by the ES reanalysis. Conclusions and Relevance: In this cohort study, clinician-centered reanalysis of ES data was associated with improved molecular diagnostic yields in patients with IRD. This approach is important for uncovering missed genetic causes of retinal disease.