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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 Hereditarias de la Córnea , Humanos , Distrofias Hereditarias de la Córnea/genética , Fóvea Central , Nucleótidos , Linaje , República de CoreaRESUMEN
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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Autoanticuerpos , Metilprednisolona , Glicoproteína Mielina-Oligodendrócito , Neuritis Óptica , Humanos , Masculino , Femenino , Pronóstico , Adulto , Neuritis Óptica/diagnóstico , Neuritis Óptica/inmunología , Glicoproteína Mielina-Oligodendrócito/inmunología , Persona de Mediana Edad , Autoanticuerpos/sangre , Metilprednisolona/uso terapéutico , Neuromielitis Óptica/diagnóstico , Neuromielitis Óptica/inmunología , Acuaporina 4/inmunología , Agudeza Visual/fisiología , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/inmunología , Adulto Joven , Adolescente , AncianoRESUMEN
PURPOSE: To investigate the rate of development of symptomatic central nervous system (CNS) demyelinating attacks or recurrent optic neuritis (ON) after the first episode of ON and its risk factors for Korean pediatric patients. METHODS: This multicenter retrospective cohort study included the patients under 18 years of age (n=132) diagnosed with ON without previous or simultaneous CNS demyelinating diseases. We obtained the clinical data including the results of neuro-ophthalmological examinations, magnetic resonance images (MRIs), antibody assays, and laboratory tests. We investigated the chronological course of demyelinating disease with respect to the occurrence of neurological symptoms and/or signs, and calculated the 5-year cumulative probability of CNS demyelinating disease or ON recurrence. RESULTS: During the follow-up period (63.1±46.7 months), 18 patients had experienced other CNS demyelinating attacks, and the 5-year cumulative probability was 14.0±3.6%. Involvement of the extraorbital optic nerve or optic chiasm and asymptomatic lesions on the brain or spinal MRI at initial presentation were significant predictors for CNS demyelinating attack after the first ON. The 5-year cumulative probability of CNS demyelinating attack was 44.4 ± 24.8% in the AQP4-IgG group, 26.2±11.4% in the MOG-IgG group, and 8.7±5.9% in the double-negative group (P=0.416). Thirty-two patients had experienced a recurrence of ON, and the 5-year cumulative probability was 24.6±4.0%. In the AQP4-IgG group, the 5-year cumulative probability was 83.3±15.2%, which was significantly higher than in the other groups (P<0.001). CONCLUSIONS: A careful and multidisciplinary approach including brain/spinal imaging and antibody assay can help predict further demyelinating attacks in pediatric ON patients.
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Enfermedades Desmielinizantes , Neuromielitis Óptica , Neuritis Óptica , Humanos , Niño , Adolescente , Estudios Retrospectivos , Glicoproteína Mielina-Oligodendrócito , Neuritis Óptica/diagnóstico por imagen , Neuritis Óptica/epidemiología , Encéfalo/metabolismo , Autoanticuerpos , Inmunoglobulina G , República de Corea/epidemiología , Enfermedades Desmielinizantes/diagnóstico por imagen , Enfermedades Desmielinizantes/epidemiología , Acuaporina 4RESUMEN
Spastic paraplegia is a neurodegenerative disorder characterized by progressive leg weakness and spasticity due to degeneration of corticospinal axons. SPG7 encodes paraplegin, and pathogenic variants in the gene cause hereditary spastic paraplegia as an autosomal recessive trait. Various ophthalmological findings including optic atrophy, ophthalmoplegia, or nystagmus have been reported in patients with spastic paraplegia type 7. We report a 15-year-old male patient with a novel heterozygous variant, c.1224T>G:p.(Asp408Glu) in SPG7 (NM_003119.3) causing early onset isolated optic atrophy and infantile nystagmus prior to the onset of neurological symptoms. Therefore, SPG7 should be considered a cause of infantile nystagmus with optic atrophy.
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Atrofia Óptica Autosómica Dominante , Atrofia Óptica , Paraplejía Espástica Hereditaria , Humanos , Masculino , ATPasas Asociadas con Actividades Celulares Diversas/genética , Metaloendopeptidasas/genética , Mutación , Atrofia Óptica/diagnóstico , Atrofia Óptica/genética , Atrofia Óptica/patología , Paraplejía/genética , Fenotipo , Paraplejía Espástica Hereditaria/complicaciones , Paraplejía Espástica Hereditaria/diagnóstico , Paraplejía Espástica Hereditaria/genética , AdolescenteRESUMEN
Bickerstaff's brainstem encephalitis is a rare autoimmune disorder that presents with ataxia, ophthalmoplegia, disturbance of consciousness and quadriplegia. A 45-year-old man with a history of ulcerative colitis (UC) taking mesalazine (5-aminosalicylic acid) visited the emergency room presenting with ataxia, ophthalmoplegia and a progressively worsening cognitive impairment. Cerebrospinal fluid analysis showed mild elevation in protein and white blood cell count and increased intracranial pressure. Anti-GQ1b autoantibodies were found positive in the patient's serum and contrast-enhanced brain magnetic resonance imaging showed diffuse leptomeningeal enhancement and pontine lesions. Based on these findings and the patient's clinical course and history, he was diagnosed with Bickerstaff's brainstem encephalitis. Mesalazine was discontinued and high-dose steroid pulse therapy was started, followed by intravenous immunoglobulin, which resulted in gradual improvement of the neurologic symptoms. When an ulcerative colitis patient presents with progressive cognitive impairment, quadriplegia and disturbance of consciousness and gait, Bickerstaff brainstem encephalitis should be considered in the differential diagnosis and prompt immunotherapy may lead to favorable prognosis.
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Enfermedades Autoinmunes del Sistema Nervioso , Colitis Ulcerosa , Encefalitis , Oftalmoplejía , Masculino , Humanos , Persona de Mediana Edad , Tronco Encefálico/diagnóstico por imagen , Tronco Encefálico/patología , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/patología , Mesalamina , Encefalitis/complicaciones , Encefalitis/diagnóstico , Cuadriplejía , Ataxia/complicaciones , GangliósidosRESUMEN
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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Exotropía , Niño , Humanos , Estudios de Seguimiento , Resultado del Tratamiento , Exotropía/cirugía , Exotropía/etiología , Estudios Retrospectivos , Visión Binocular , Procedimientos Quirúrgicos Oftalmológicos , Músculos Oculomotores/cirugía , Enfermedad Crónica , RecurrenciaRESUMEN
Uncovering region-specific changes in the myopic retina can provide clues to the pathogenesis of myopia progression. After imposing form deprivation myopia in the right eye of 6-week-old rabbits, we investigated the proteome profile of each retinal region (central, mid-periphery, and far-periphery retina), using accurate high-resolution mass spectrometry. Protein expression was analyzed using gene ontology and network analysis compared with that of the control, the left eyes. Among 2065 proteins detected from whole retinal samples, 249 differentially expressed proteins (DEPs) were identified: 164 DEPs in the far-periphery, 39 in the mid-periphery, and 83 in the central retina. In network analysis, the far-periphery retina showed the most significant connectivity between DEPs. The regulation of coagulation was the most significant biological process in upregulated DEPs in the far-periphery retina. Proteasome was the most significant Kyoto Encyclopedia of Genes and Genomes pathway in downregulated DEPs in the central retina. Antithrombin-III, fibrinogen gamma chain, and fibrinogen beta chain were identified as hub proteins for myopia progression, which were upregulated in the far-periphery retina. Proteomic analysis in this study suggested that oxidative stress can be the primary pathogenesis of myopia progression and that the far-periphery retina plays a role as the key responder.
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Miopía , Proteoma , Animales , Conejos , Proteoma/metabolismo , Proteómica/métodos , Retina/metabolismo , Miopía/patología , Espectrometría de Masas en TándemRESUMEN
Foveal hypoplasia, optic nerve decussation defects and anterior segment dysgenesis is an autosomal recessive disorder arising from SLC38A8 mutations. SLC38A8 is a putative glutamine transporter with strong expression within the photoreceptor layer in the retina. Previous studies have been limited due to lack of quantitative data on retinal development and nystagmus characteristics. In this multi-centre study, a custom-targeted next generation sequencing (NGS) gene panel was used to identify SLC38A8 mutations from a cohort of 511 nystagmus patients. We report 16 novel SLC38A8 mutations. The sixth transmembrane domain is most frequently disrupted by missense SLC38A8 mutations. Ninety percent of our cases were initially misdiagnosed as PAX6-related phenotype or ocular albinism prior to NGS. We characterized the retinal development in vivo in patients with SLC38A8 mutations using high-resolution optical coherence tomography. All patients had severe grades of arrested retinal development with lack of a foveal pit and no cone photoreceptor outer segment lengthening. Loss of foveal specialization features such as outer segment lengthening implies reduced foveal cone density, which contributes to reduced visual acuity. Unlike other disorders (such as albinism or PAX6 mutations) which exhibit a spectrum of foveal hypoplasia, SLC38A8 mutations have arrest of retinal development at an earlier stage resulting in a more under-developed retina and severe phenotype.
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Sistemas de Transporte de Aminoácidos Neutros/genética , Segmento Anterior del Ojo/anomalías , Anomalías del Ojo/genética , Fóvea Central/anomalías , Nistagmo Congénito/genética , Factor de Transcripción PAX6/genética , Adolescente , Adulto , Segmento Anterior del Ojo/diagnóstico por imagen , Segmento Anterior del Ojo/patología , Diferenciación Celular/genética , Niño , Preescolar , Anomalías del Ojo/diagnóstico por imagen , Anomalías del Ojo/patología , Femenino , Fóvea Central/diagnóstico por imagen , Fóvea Central/patología , Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Masculino , Mutación/genética , Nistagmo Congénito/patología , Linaje , Retina/crecimiento & desarrollo , Retina/patología , Células Fotorreceptoras Retinianas Conos/patología , Tomografía de Coherencia Óptica , Agudeza Visual/genética , Agudeza Visual/fisiología , Adulto JovenRESUMEN
PURPOSE: To characterize the genotypic and phenotypic spectrum of foveal hypoplasia (FH). DESIGN: Multicenter, observational study. PARTICIPANTS: A total of 907 patients with a confirmed molecular diagnosis of albinism, PAX6, SLC38A8, FRMD7, AHR, or achromatopsia from 12 centers in 9 countries (n = 523) or extracted from publicly available datasets from previously reported literature (n = 384). METHODS: Individuals with a confirmed molecular diagnosis and availability of foveal OCT scans were identified from 12 centers or from the literature between January 2011 and March 2021. A genetic diagnosis was confirmed by sequence analysis. Grading of FH was derived from OCT scans. MAIN OUTCOME MEASURES: Grade of FH, presence or absence of photoreceptor specialization (PRS+ vs. PRS-), molecular diagnosis, and visual acuity (VA). RESULTS: The most common genetic etiology for typical FH in our cohort was albinism (67.5%), followed by PAX6 (21.8%), SLC38A8 (6.8%), and FRMD7 (3.5%) variants. AHR variants were rare (0.4%). Atypical FH was seen in 67.4% of achromatopsia cases. Atypical FH in achromatopsia had significantly worse VA than typical FH (P < 0.0001). There was a significant difference in the spectrum of FH grades based on the molecular diagnosis (chi-square = 60.4, P < 0.0001). All SLC38A8 cases were PRS- (P = 0.003), whereas all FRMD7 cases were PRS+ (P < 0.0001). Analysis of albinism subtypes revealed a significant difference in the grade of FH (chi-square = 31.4, P < 0.0001) and VA (P = 0.0003) between oculocutaneous albinism (OCA) compared with ocular albinism (OA) and Hermansky-Pudlak syndrome (HPS). Ocular albinism and HPS demonstrated higher grades of FH and worse VA than OCA. There was a significant difference (P < 0.0001) in VA between FRMD7 variants compared with other diagnoses associated with FH. CONCLUSIONS: We characterized the phenotypic and genotypic spectrum of FH. Atypical FH is associated with a worse prognosis than all other forms of FH. In typical FH, our data suggest that arrested retinal development occurs earlier in SLC38A8, OA, HPS, and AHR variants and later in FRMD7 variants. The defined time period of foveal developmental arrest for OCA and PAX6 variants seems to demonstrate more variability. Our findings provide mechanistic insight into disorders associated with FH and have significant prognostic and diagnostic value.
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Albinismo Ocular , Albinismo Oculocutáneo , Albinismo , Defectos de la Visión Cromática , Albinismo Ocular/diagnóstico , Albinismo Ocular/genética , Albinismo Oculocutáneo/diagnóstico , Albinismo Oculocutáneo/genética , Defectos de la Visión Cromática/diagnóstico , Defectos de la Visión Cromática/genética , Proteínas del Citoesqueleto , Fóvea Central/anomalías , Humanos , Proteínas de la Membrana , Trastornos de la Visión/diagnósticoRESUMEN
BACKGROUND: During the surgical resection of petroclival meningiomas, preserving the cranial nerves is crucial. The abducens nerve is particularly vulnerable during surgery. However, the preoperative risk factors and postoperative prognosis of abducens nerve palsy (ANP) are poorly understood. METHODS: We retrospectively analyzed 70 patients who underwent surgery for petroclival meningiomas between May 2010 and December 2019, divided into gross-total resection (GTR) and subtotal resection (STR) groups. The relationship of preoperative clinical factors with the incidence and recovery of postoperative ANP was analyzed. RESULTS: Postoperative ANP was observed in 23 patients (32.9%). Multivariable logistic regression revealed that the tumor-to-cerebellar peduncle T2 imaging intensity index (TCTI) (P < 0.001) and internal auditory canal invasion (P = 0.033) contributed to postoperative ANP. GTR was achieved in 37 patients (52.9%), and 10 (27.0%) of them showed ANP. STR was achieved in 33 patients (47.1%), and 13 (39.4%) of them showed ANP. Recovery from ANP took a median of 6.6 months (range, 4.5-20.3 months). At 6 months after the operation, recovery of the abducens nerve function was observed in 16 patients (69.0%); of whom, 4 (40.0%) were in the GTR group and 12 (92.3%) were in the STR group (P = 0.025). CONCLUSIONS: TCTI and internal auditory canal invasion were the risk factors for postoperative ANP. Although intentional STR did not prevent ANP immediately after the operation, recovery of the abducens nerve function after surgery was observed more frequently in the STR group than in the GTR group.
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Enfermedades del Nervio Abducens , Neoplasias Meníngeas , Meningioma , Neoplasias de la Base del Cráneo , Humanos , Enfermedades del Nervio Abducens/diagnóstico , Enfermedades del Nervio Abducens/etiología , Enfermedades del Nervio Abducens/cirugía , Neoplasias Meníngeas/complicaciones , Neoplasias Meníngeas/cirugía , Meningioma/complicaciones , Meningioma/cirugía , Procedimientos Neuroquirúrgicos/efectos adversos , Procedimientos Neuroquirúrgicos/métodos , Estudios Retrospectivos , Neoplasias de la Base del Cráneo/complicaciones , Resultado del TratamientoRESUMEN
The PAX6 is essential for ocular morphogenesis and is known to be highly sensitive to changes in gene expression, where neither over- nor under-expression ensures normal ocular development. Two unrelated probands with classical aniridia who were previously considered "PAX6-negative", were studied by whole-genome sequencing. Through the use of multiple in silico deep learning-based algorithms, we identified two novel putative causal mutations, c.-133_-132del in the 5' untranslated region (5'-UTR) and c.-52 + 5G>A in an intron upstream of the PAX6 gene. The luciferase activity was significantly increased and VAX2 binding was disrupted with the former 5'-UTR variant compared with wild-type sequence, which resulted in a striking overexpression of PAX6. The minigene assay showed that the c.-52 + 5G>A mutation caused defective splicing, which resulted in the formation of truncated transcripts.
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Aniridia/genética , Mutación , Factor de Transcripción PAX6/genética , Regiones no Traducidas 5'/genética , Algoritmos , Causalidad , Aprendizaje Profundo , Ensayo de Cambio de Movilidad Electroforética , Ojo/embriología , Regulación de la Expresión Génica , Genes Reporteros , Proteínas de Homeodominio/metabolismo , Humanos , Intrones/genética , Anotación de Secuencia Molecular , Factor de Transcripción PAX6/biosíntesis , Factor de Transcripción PAX6/fisiología , Proteínas Recombinantes/genética , Eliminación de Secuencia , Secuenciación Completa del GenomaRESUMEN
Purpose: We comprehensively evaluated the mutational spectrum of Leber congenital amaurosis (LCA) and investigated the molecular diagnostic rate and genotype-phenotype correlation in a Korean cohort. Methods: This single-center retrospective case series included 50 Korean patients with LCA between June 2015 and March 2019. Molecular analysis was conducted using targeted panel-based next-generation sequencing, including deep intronic and regulatory variants or whole exome sequencing. The molecular diagnosis was made based on the inheritance pattern, zygosity, and pathogenicity. Results: Among the 50 patients, 27 patients (54%) were male, and 11 (22%) showed systemic features. Genetic variants highly likely to be causative were identified in 78% (39/50) of cases and segregated into families. We detected two pathogenic or likely pathogenic variants in a gene linked to a recessive trait without segregation analysis in three cases (6.0%). GUCY2D (20%), NMNAT1 (18%), and CEP290 (16%) were the most frequently mutated genes in Korean LCA. Copy number variations were found in three patients, which accounted for 6% of LCA cases. A possible dual molecular diagnosis (Senior-Løken syndrome along with Leigh syndrome, and Joubert syndrome with transposition of the great arteries) was made in two patients (4%). Three of 50 patients were medically or surgically actionable: one patient for RPE65 gene therapy and two patients with WDR19 Senior-Løken syndrome for early preparation for kidney and liver transplantations. Conclusions: This study demonstrated that approximately 4% of patients may have dual molecular diagnoses, and 6% were surgically or medically actionable in LCA. Therefore, accurate molecular diagnosis and careful interpretation of next-generation sequencing results can be of great help in patients with LCA.
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Anomalías Múltiples/genética , Cerebelo/anomalías , Ciliopatías/genética , Variaciones en el Número de Copia de ADN/genética , Anomalías del Ojo/genética , Enfermedades Renales Quísticas/genética , Amaurosis Congénita de Leber/diagnóstico , Amaurosis Congénita de Leber/genética , Enfermedad de Leigh/genética , Atrofias Ópticas Hereditarias/genética , Retina/anomalías , Anomalías Múltiples/diagnóstico , Adolescente , Adulto , Antígenos de Neoplasias/sangre , Antígenos de Neoplasias/genética , Proteínas de Ciclo Celular/sangre , Proteínas de Ciclo Celular/genética , Niño , Preescolar , Ciliopatías/diagnóstico , Proteínas del Citoesqueleto/sangre , Proteínas del Citoesqueleto/genética , Anomalías del Ojo/diagnóstico , Femenino , Estudios de Asociación Genética , Terapia Genética , Guanilato Ciclasa/sangre , Guanilato Ciclasa/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Péptidos y Proteínas de Señalización Intracelular/genética , Enfermedades Renales Quísticas/diagnóstico , Amaurosis Congénita de Leber/diagnóstico por imagen , Amaurosis Congénita de Leber/terapia , Enfermedad de Leigh/diagnóstico , Masculino , Mutación , Nicotinamida-Nucleótido Adenililtransferasa/sangre , Nicotinamida-Nucleótido Adenililtransferasa/genética , Atrofias Ópticas Hereditarias/diagnóstico , Trasplante de Órganos , Linaje , Receptores de Superficie Celular/sangre , Receptores de Superficie Celular/genética , República de Corea , Estudios Retrospectivos , Transposición de los Grandes Vasos/genética , cis-trans-Isomerasas/genéticaRESUMEN
PURPOSE: To determine the age- and sex-specific prevalence and incidence of demyelinating optic neuritis and the risk of multiple sclerosis (MS) in pediatric and adult populations in South Korea. DESIGN: A nationwide, population-based, retrospective study using data from the Korean National Health Claims database from 2010 to 2016. PARTICIPANTS: The entire South Korean population aged 65 years of age or younger (n = 44 700 564). All patients with optic neuritis from the entire Korean population were included. METHODS: Patients aged 14 years of age or younger were classified as pediatric patients, and those aged 15 to 65 years were classified as adults. Each group was analyzed separately. Patients with optic neuritis had a subsequent diagnosis, including idiopathic, MS, neuromyelitis optica (NMO), and acute disseminated encephalomyelitis. Prevalence and incidence, conversion rate to MS, and treatment modalities (steroids, plasmapheresis, interferon-ß, and immunosuppressants) were estimated. MAIN OUTCOME MEASURES: Prevalence and incidence of optic neuritis, and conversion rate to MS. RESULTS: Among 44 700 564 individuals, 531 pediatric patients (50.7% female) and 7183 adults (53.3% female) were identified as having optic neuritis. Annual incidence was 1.04 (95% confidence interval [CI], 1.01-1.07) per 100 000 pediatric individuals and 3.29 (95% CI, 3.28-3.30) per 100 000 adults. Peak incidence was observed at 10 to 14 years in the pediatric population and at 30 to 34 years and 50 to 54 years in the adult population. Conversion rate to MS was 13.8% in the pediatric population and 11.4% in the adult population. Fourteen percent of all patients were treated with chronic immunosuppressants, 38% of patients with NMO underwent plasmapheresis, and 50% of patients with MS were treated with interferon-ß. CONCLUSIONS: This is a nationwide epidemiologic study of optic neuritis in individuals of all ages in South Korea. The incidence of optic neuritis and subsequent risk of MS in the pediatric population are comparable to those reported in western countries but are lower in the adult population than in western countries. The incidence rate in adults was 3.2-fold higher than in the pediatric population, and the overall MS conversion rate in the entire Korean population was estimated to be 10.6%.
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Esclerosis Múltiple/epidemiología , Neuritis Óptica/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Niño , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prevalencia , República de Corea/epidemiología , Estudios Retrospectivos , Adulto JovenRESUMEN
PURPOSE: To describe characteristics of recurrent intermittent exotropia after bilateral lateral rectus (BLR) recession, and identify factors associated with poor outcome after unilateral medial rectus (MR) resection for recurrent intermittent exotropia. METHODS: We retrospectively reviewed 124 patients who have undergone unilateral MR resection for recurrent intermittent exotropia after BLR recession. Patients were followed for at least 2 years after MR resection. Clinical characteristics and risk factors associated with poor outcome after unilateral MR resection were evaluated. Successful outcome was defined as distant deviation within the range of 4 prism diopters (PD) esotropia and 10 PD exotropia at last visit after MR resection. RESULTS: Among 124 patients, 50 patients (41.1%) were male, and the mean age at the time of MR resection was 9.5 ± 3.1 years. The average follow-up period after MR resection was 43.8 ± 23.7 months. Forty-seven patients (37.9%) were classified to have poor outcome at last visit, and 29 patients (23.4%) underwent third operation. None of the patients was overcorrected after MR resection. Multiple logistic regression analyses showed that distant deviation at post-operative 3 months and male gender were associated with poor outcome (OR 1.49; 95% CI 1.27-1.73; P < 0.001, and OR 5.19; 95% CI 1.42-18.98; P = 0.013, respectively). CONCLUSION: Ocular deviation at 3 months after unilateral MR resection for recurrent intermittent exotropia may play a valuable role in anticipating poor outcome. Patients whose exotropia exceeded 9 PD at distance at 3 months' follow-up tended to recur while those whose exotropia remained below 9 PD at distance showed a stable disease course.
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Exotropía/cirugía , Movimientos Oculares/fisiología , Músculos Oculomotores/cirugía , Procedimientos Quirúrgicos Oftalmológicos/efectos adversos , Complicaciones Posoperatorias , Refracción Ocular/fisiología , Niño , Preescolar , Exotropía/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Músculos Oculomotores/fisiopatología , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: The visual prognosis in Leber hereditary optic neuropathy (LHON) is generally poor. However, some individuals can have spontaneous visual recovery (VR) in one or both eyes by a mechanism that is not yet clearly understood. The purpose of this study was to determine whether certain clinical and optic disc features are associated with VR in patients with LHON. METHODS: We retrospectively examined 80 eyes of 40 patients with LHON using clinical databases, fundus photographs, and high-definition spectral-domain optical coherence tomography (OCT) images. VR was defined as a gain of 3 or more lines of logarithm of the minimum angle of resolution (logMAR)-scaled visual acuity from nadir; this represents a doubling of the visual angle. Patients were divided into VR and nonrecovery (NR) groups. Using fundus photographs, we measured optic disc size and evaluated for the presence of optic disc features, including peripapillary telangiectasia, disc hyperemia, and swelling. We also measured the disc area, cup-to-disc ratio, and rim area of the optic disc using OCT. RESULTS: Twenty-one of 80 eyes (26%) had a VR. The VR occurred within 2 years after onset in 81% of cases. The VR group showed younger age at onset (21 vs 29 years, P = 0.017) and better visual acuity at the nadir (1.39 vs 2.16 logMAR, P < 0.001) compared with the NR group. Optic disc features, particularly peripapillary telangiectasia (P = 0.027) and disc hyperemia (P = 0.006), were more prominent in the NR group. The cup-to-disc ratio was significantly smaller (0.64 vs 0.71, P = 0.004) and the rim area was significantly greater (1.17 vs 0.85 mm, P < 0.001) in the VR group compared with the NR group. CONCLUSIONS: A younger age at onset and a less severe reduction of visual acuity at the nadir were associated with a higher probability of VR. Presence of peripapillary telangiectasia and optic disc hyperemia may serve as predictive factors for poor visual prognosis in patients with LHON.
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Atrofia Óptica Hereditaria de Leber/diagnóstico por imagen , Disco Óptico/diagnóstico por imagen , Recuperación de la Función/fisiología , Agudeza Visual/fisiología , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Atrofia Óptica Hereditaria de Leber/fisiopatología , Pronóstico , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Adulto JovenRESUMEN
PURPOSE: Leber congenital amaurosis (LCA) is a hereditary retinal dystrophy with wide genetic heterogeneity. Next-generation sequencing (NGS) targeting multiple genes can be a good option for the diagnosis of LCA, and we tested a clinical exome panel in patients with LCA. METHODS: A total of nine unrelated Korean patients with LCA were sequenced using the Illumina TruSight One panel, which targets 4,813 clinically associated genes, followed by confirmation using Sanger sequencing. Patients' clinical information and familial study results were obtained and used for comprehensive interpretation. RESULTS: In all nine patients, we identified pathogenic variations in LCA-associated genes: NMNAT1 (n=3), GUCY2D (n=2), RPGRIP1 (n=2), CRX (n=1), and CEP290 or SPATA7. Six patients had one or two mutations in accordance with inheritance patterns, all consistent with clinical phenotypes. Two patients had only one pathogenic mutation in recessive genes (NMNAT1 and RPGRIP1), and the clinical features were specific to disorders associated with those genes. Six patients were solved for genetic causes, and it remains unclear for three patients with the clinical exome panel. With subsequent targeted panel sequencing with 113 genes associated with infantile nystagmus syndrome, a likely pathogenic allele in CEP290 was detected in one patient. Interestingly, one pathogenic variant (p.Arg237Cys) in NMNAT1 was present in three patients, and it had a high allele frequency (0.24%) in the general Korean population, suggesting that NMNAT1 could be a major gene responsible for LCA in Koreans. CONCLUSIONS: We confirmed that a commercial clinical exome panel can be effectively used in the diagnosis of LCA. Careful interpretation and clinical correlation could promote the successful implementation of clinical exome panels in routine diagnoses of retinal dystrophies, including LCA.
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Exoma/genética , Proteínas del Ojo/genética , Amaurosis Congénita de Leber/diagnóstico , Amaurosis Congénita de Leber/genética , Análisis de Secuencia de ADN , Adulto , Antígenos de Neoplasias/genética , Proteínas de Ciclo Celular , Proteínas del Citoesqueleto , Análisis Mutacional de ADN , Proteínas de Unión al ADN/genética , Femenino , Estudios de Asociación Genética , Guanilato Ciclasa/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Proteínas de Homeodominio/genética , Humanos , Lactante , Masculino , Mutación , Proteínas de Neoplasias/genética , Nicotinamida-Nucleótido Adenililtransferasa/genética , Linaje , Proteínas/genética , Receptores de Superficie Celular/genética , Transactivadores/genéticaRESUMEN
PURPOSE: To compare segmented retinal layer thicknesses between patients with idiopathic infantile nystagmus (IIN) and controls. METHODS: This retrospective case-control study included 66 patients with IIN and 66 age-matched controls. The retinal layers were examined using spectral domain optical coherence tomography with autosegmentation. Central foveal thickness (CFT), outer nuclear layer (ONL), and outer segment length (OSL) thickness were measured at the fovea center. Mean values for retinal nerve fiber layer, ganglion cell inner plexiform layer (GCIPL), inner nuclear layer, outer plexiform-outer nuclear layer (OPNL) thicknesses were calculated at two measurement points (nasal and temporal hump points at the macula area). RESULTS: There were no significant between-group differences in age, gender, or refraction error. The CFT was thicker in the IIN group compared with the control group (225.0 µm vs. 217.8 µm, P = 0.017) and OSL was shorter in IIN than in controls (40.0 µm vs. 43.7 µm., P < 0.001). The ONL thickness at the central fovea was not statistically different between the two groups. At the nasal and temporal position where the ganglion cell density was thickest, the GCIPL thickness was thinner in the IIN group compared to the controls (99.5 µm vs. 102.8 µm, P = 0.010). The GCIPL thickness was negatively correlated with logMAR visual acuity (Spearman's rho = -0.502, P < 0.001). CONCLUSIONS: The foveal pit was shallower, OSL was shorter, and the GCIPL thicknesses at macular humps were decreased in the patients with IIN compared with that of controls. The faulty development of the macula may be related to unknown pathophysiologic mechanism during fovea maturation in IIN or continuous eye movement itself interrupt fovea development.
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Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Fibras Nerviosas/patología , Nistagmo Congénito/diagnóstico , Células Ganglionares de la Retina/patología , Tomografía de Coherencia Óptica/métodos , Agudeza Visual , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios Retrospectivos , Campos Visuales , Adulto JovenRESUMEN
BACKGROUND: The authors report a case of a rare complication that occurred after botulinum toxin injection to the extraocular muscle, which was easily overlooked and successfully corrected by surgery. CASE PRESENTATION: A 34-year-old female patient visited our clinic for diplopia and ocular motility disorder after removal of an epidermoid tumor of the brain. At her initial visit, her best-corrected visual acuity (BCVA) was 20/20 for both eyes. An alternate cover test showed 45 prism-diopter esotropia and 3 prism-diopter hypertropia in the right eye. Following 6 months of observation, the deviation of the strabismus did not improve, and botulinum toxin was injected into the right medial rectus (RMR). After 6 days, she visited our clinic with decreased visual acuity of her right eye. The BCVA was found to be 20/50 for her right eye. Funduscopic examination presented a retinal tear inferonasal to the optic disc with preretinal hemorrhage. Subretinal fluid nasal to the fovea was seen on optical coherence tomography (OCT). Barrier laser photocoagulation was done around the retinal tear; however, her visual acuity continued to decrease, and vitreous hemorrhage and subretinal fluid at the lesion did not improve. In addition, a newly developed epiretinal membrane was seen on OCT. An alternate cover test presented 30 prism-diopter right esotropia. 19 weeks after RMR botulinum toxin injection, she received pars plana vitrectomy, membranectomy, endolaser barrier photocoagulation, and intravitreal bevacizumab (Avastin®) injection. After 4 months, her visual acuity improved to 20/20, and only 4 prism-diopter of right hypertropia and 3 prism-diopter of exotropia were noted. Vitreous opacity and the epiretinal membrane were completely removed, as confirmed by funduscopic and examination. CONCLUSIONS: Sudden loss of vision after injection of botulinum toxin into the extraocular muscle may suggest a serious complication, and a prompt, thorough ophthalmic examination should be performed. If improvements are not observed, rapid surgical intervention is recommended to prevent additional complications.
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Toxinas Botulínicas/efectos adversos , Neurotoxinas/efectos adversos , Desprendimiento de Retina/inducido químicamente , Hemorragia Vítrea/inducido químicamente , Adulto , Femenino , Humanos , Inyecciones Intramusculares/efectos adversos , Inyecciones Intraoculares/efectos adversosRESUMEN
BACKGROUND AND PURPOSE: Our aim was to evaluate the risk of subsequent stroke development after retinal artery occlusion (RAO). METHODS: National registry data were collected from the Korean National Health Insurance Service, comprised 1 025 340 random subjects. Patients diagnosed with RAO in 2002 and 2003 were excluded. The RAO group was composed of patients with an initial diagnosis of either central or other RAO between January 2004 and December 2013 (n=401). The comparison group was composed of randomly selected patients (5 per RAO patient; n=2003) who were matched to the RAO group according to sociodemographic factors and year of RAO diagnosis. Each sampled patient was tracked until 2013. Cox proportional hazard regression was used. RESULTS: Stroke occurred in 15.0% of the RAO group and in 8.0% of the comparison group (P < 0.001). RAO was associated with an increased risk of stroke occurrence (hazard ratio, 1.78; 95% confidence interval, 1.32-2.41). The magnitude of the RAO effect for stroke was larger among younger adults aged <65 years (hazard ratio, 3.11) than older adults aged ≥65 years (hazard ratio, 1.26). However, the risk of subsequent stroke was significantly increased in older adults aged ≥65 years at the 4-year follow-up (hazard ratio, 1.58; 95% confidence interval, 1.01-2.48). CONCLUSIONS: RAO was significantly associated with subsequent stroke after adjusting for comorbidities and sociodemographic factors. These findings are limited by uncontrolled confounding factors and need to be replicated by other observational studies.