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RATIONALE: Autosomal recessive bestrophinopathy (ARB) is a subtype of bestrophinopathy caused by biallelic mutations of the BEST1 gene, which affect the retinal pigment epithelium (RPE). Studying RPE abnormalities through imaging is essential for understanding ARB. This case series involved the use of multimodal imaging techniques, namely autofluorescence (AF) imaging at 488 nm [short-wavelength AF] and 785 nm [near-infrared AF (NIR-AF)] and polarization-sensitive optical coherence tomography (PS-OCT), to investigate RPE changes in 2 siblings with ARB. PATIENT CONCERNS: Two Japanese siblings (Case 1: male, followed for 20-23 years; Case 2: female, followed for 13-17 years) carried compound heterozygous mutations of the BEST1 gene. DIAGNOSIS: Both siblings were diagnosed with ARB. INTERVENTIONS AND OUTCOMES: Multimodal imaging techniques were used to evaluate RPE changes. Both siblings had funduscopic changes similar to those seen in the vitelliruptive stage of Best vitelliform macular dystrophy during the follow-up period. NIR-AF imaging showed hypo-AF of the entire macular lesion in both cases, and this hypo-AF remained stable over time. PS-OCT confirmed reduced RPE melanin content in these hypo-AF areas. Additionally, hyper-NIR-AF dots were observed within hypo-NIR-AF areas. Concomitant identification of focally thickened RPE melanin on PS-OCT imaging and hyper-AF on short-wavelength AF imaging at the sites containing hyper-NIR-AF dots indicated that the hyper-NIR-AF dots had originated from either stacked RPE cells or RPE dysmorphia. LESSONS: We confirmed RPE abnormalities in ARB, including diffuse RPE melanin damage in the macula alongside evidence of RPE activity-related changes. This case series demonstrates that multimodal imaging, particularly NIR-AF and PS-OCT, provides detailed insights into RPE alterations in ARB.
Asunto(s)
Bestrofinas , Enfermedades Hereditarias del Ojo , Imagen Multimodal , Enfermedades de la Retina , Epitelio Pigmentado de la Retina , Tomografía de Coherencia Óptica , Humanos , Imagen Multimodal/métodos , Masculino , Femenino , Tomografía de Coherencia Óptica/métodos , Enfermedades Hereditarias del Ojo/genética , Enfermedades Hereditarias del Ojo/diagnóstico por imagen , Enfermedades de la Retina/genética , Enfermedades de la Retina/diagnóstico por imagen , Epitelio Pigmentado de la Retina/diagnóstico por imagen , Epitelio Pigmentado de la Retina/patología , Bestrofinas/genética , Adulto Joven , Imagen Óptica/métodos , Adolescente , HermanosRESUMEN
PURPOSE: The aim of this study was to estimate the number of patients in Japan who had visited an ophthalmologist for macular dystrophy of various types, including Best vitelliform macular dystrophy (BVMD), Stargardt disease, occult macular dystrophy (OMD), cone (-rod) dystrophy, X-linked retinoschisis (XLRS), and central areolar choroid dystrophy (CACD). STUDY DESIGN: Nationwide epidemiologic survey METHODS: Questionnaires were distributed to 965 major facilities, including all the university hospitals in Japan. The aim of the questionnaire was to determine the number of patients with each type of macular dystrophy who had visited an outpatient clinic during the past 5 years (January 2015 to December 2019). RESULTS: Over 70% of the patients were diagnosed and followed up at university hospitals. The estimated annual number of newly diagnosed cases was as follows: 55.3 for BVMD, 36.7 for Stargardt disease, 35.8 for OMD, 160.6 for cone (-rod) dystrophy, 31.0 for XLRS, 29.8 for CACD, and 174.1 for other types of macular dystrophy. The total number of patients with macular dystrophy diagnosed and followed at major institutions was estimated to be 6651. CONCLUSION: This was the first nationwide survey of macular dystrophy in Japan and provided an approximate number of affected patients. The diagnosis of macular dystrophy is primarily carried out at facilities with affiliated specialists, such as university hospitals. By examining the incidence of multiple diseases simultaneously, we were able to compare the incidence of each type of macular dystrophy.
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Degeneración Macular , Humanos , Japón/epidemiología , Incidencia , Masculino , Femenino , Degeneración Macular/epidemiología , Degeneración Macular/diagnóstico , Persona de Mediana Edad , Adulto , Encuestas y Cuestionarios , Adolescente , Niño , Estudios Retrospectivos , Anciano , Agudeza Visual , Estudios de Seguimiento , Adulto JovenRESUMEN
PURPOSE: To clarify the genetic and clinical features of Japanese patients with ABCA4-associated retinopathy. DESIGN: Retrospective, multicenter cohort study. METHODS: Patients with retinal degeneration and biallelic ABCA4 variants were recruited from 13 different hospitals. Whole exome sequencing analysis was used for genetic testing. Comprehensive ophthalmic examinations were performed on matched patients. The primary outcome measure was identifying multimodal retinal imaging findings associated with disease progression. RESULTS: This study included 63 patients: 19 with missense/missense, 23 with missense/truncation, and 21 with truncation/truncation genotypes. In total, 62 variants were identified, including 29 novel variants. Six patients had a mild phenotype characterized by foveal-sparing or preserved foveal structure, including 4 with missense/missense and 2 with missense/truncation genotypes. The p.Arg212His variant was the most frequent in patients with mild phenotypes (4/12 alleles). Clinical findings showed a disease duration-dependent worsening of the phenotypic stage. Patients with the truncation/truncation genotype exhibited rapid retinal degeneration within a few years and definite fundus autofluorescence imaging patterns, including hyper autofluorescence at the macula and few or no flecks. CONCLUSIONS: Our results indicate that missense/missense or missense/truncation genotypes, including the p.Arg212His variant, are associated with a relatively mild phenotype. In contrast, the truncation/truncation genotype causes rapid and severe retinal degeneration in Japanese patients with ABCA4-associated retinopathy. These data are vital in predicting patient prognosis, guiding genetic counseling, and stratifying patients for future clinical trials.
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Transportadoras de Casetes de Unión a ATP , Degeneración Retiniana , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Transportadoras de Casetes de Unión a ATP/genética , Análisis Mutacional de ADN , Pueblos del Este de Asia/genética , Secuenciación del Exoma , Angiografía con Fluoresceína/métodos , Genotipo , Japón/epidemiología , Mutación Missense , Fenotipo , Degeneración Retiniana/genética , Degeneración Retiniana/diagnóstico , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodos , Agudeza Visual/fisiologíaRESUMEN
Purpose: To characterize the clinical effects of two RP1L1 hotspots in patients with East Asian occult macular dystrophy (OMD). Methods: Fifty-one patients diagnosed with OMD harboring monoallelic pathogenic RP1L1 variants (Miyake disease) from Japan, South Korea, and China were enrolled. Patients were classified into two genotype groups: group A, p.R45W, and group B, missense variants located between amino acids (aa) 1196 and 1201. The clinical parameters of the two genotypes were compared, and deep learning based on spectral-domain optical coherence tomographic (SD-OCT) images was used to distinguish the morphologic differences. Results: Groups A and B included 29 and 22 patients, respectively. The median age of onset in groups A and B was 14.0 and 40.0 years, respectively. The median logMAR visual acuity of groups A and B was 0.70 and 0.51, respectively, and the survival curve analysis revealed a 15-year difference in vision loss (logMAR 0.22). A statistically significant difference was observed in the visual field classification, but no significant difference was found in the multifocal electroretinographic classification. High accuracy (75.4%) was achieved in classifying genotype groups based on SD-OCT images using machine learning. Conclusions: Distinct clinical severities and morphologic phenotypes supported by artificial intelligence-based classification were derived from the two investigated RP1L1 hotspots: a more severe phenotype (p.R45W) and a milder phenotype (1196-1201 aa). This newly identified genotype-phenotype association will be valuable for medical care and the design of therapeutic trials.
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Inteligencia Artificial , Proteínas del Ojo , Degeneración Macular , Adolescente , Adulto , Humanos , Adulto Joven , Aminoácidos , China , Enfermedad Crónica , Pueblos del Este de Asia , Proteínas del Ojo/genética , Degeneración Macular/genética , Estudios de Asociación GenéticaRESUMEN
Occult macular dystrophy (OMD) is the most prevalent form of macular dystrophy in East Asia. Beyond RP1L1, causative genes and mechanisms remain largely uncharacterised. This study aimed to delineate the clinical and genetic characteristics of OMD syndrome (OMDS). Patients clinically diagnosed with OMDS in Japan, South Korea, and China were enrolled. The inclusion criteria were as follows: (1) macular dysfunction and (2) normal fundus appearance. Comprehensive clinical evaluation and genetic assessment were performed to identify the disease-causing variants. Clinical parameters were compared among the genotype groups. Seventy-two patients with OMDS from fifty families were included. The causative genes were RP1L1 in forty-seven patients from thirty families (30/50, 60.0%), CRX in two patients from one family (1/50, 2.0%), GUCY2D in two patients from two families (2/50, 4.0%), and no genes were identified in twenty-one patients from seventeen families (17/50, 34.0%). Different severities were observed in terms of disease onset and the prognosis of visual acuity reduction. This multicentre large cohort study furthers our understanding of the phenotypic and genotypic spectra of patients with macular dystrophy and normal fundus. Evidently, OMDS encompasses multiple Mendelian retinal disorders, each representing unique pathologies that dictate their respective severity and prognostic patterns.
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Degeneración Macular , Distrofias Retinianas , Humanos , Estudios de Cohortes , Pueblos del Este de Asia , Electrorretinografía , Retina/patología , Degeneración Macular/patología , Distrofias Retinianas/patología , Proteínas del Ojo/genéticaRESUMEN
BACKGROUND/AIMS: To investigate genotype-phenotype associations in patients with KCNV2 retinopathy. METHODS: Review of clinical notes, best-corrected visual acuity (BCVA), molecular variants, electroretinography (ERG) and retinal imaging. Subjects were grouped according to the combination of KCNV2 variants-two loss-of-function (TLOF), two missense (TM) or one of each (MLOF)-and parameters were compared. RESULTS: Ninety-two patients were included. The mean age of onset (mean±SD) in TLOF (n=55), TM (n=23) and MLOF (n=14) groups was 3.51±0.58, 4.07±2.76 and 5.54±3.38 years, respectively. The mean LogMAR BCVA (±SD) at baseline in TLOF, TM and MLOF groups was 0.89±0.25, 0.67±0.38 and 0.81±0.35 for right, and 0.88±0.26, 0.69±0.33 and 0.78±0.33 for left eyes, respectively. The difference in BCVA between groups at baseline was significant in right (p=0.03) and left eyes (p=0.035). Mean outer nuclear layer thickness (±SD) at baseline in TLOF, MLOF and TM groups was 37.07±15.20 µm, 40.67±12.53 and 40.38±18.67, respectively, which was not significantly different (p=0.85). The mean ellipsoid zone width (EZW) loss (±SD) was 2051 µm (±1318) for patients in the TLOF, and 1314 µm (±965) for MLOF. Only one patient in the TM group had EZW loss at presentation. There was considerable overlap in ERG findings, although the largest DA 10 ERG b-waves were associated with TLOF and the smallest with TM variants. CONCLUSIONS: Patients with missense alterations had better BCVA and greater structural integrity. This is important for patient prognostication and counselling, as well as stratification for future gene therapy trials.
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The human fovea is a specialized pit structure in the central retina. Foveal hypoplasia is a condition where the foveal pit does not fully develop, and it is associated with poor vision. Autosomal dominant isolated foveal hypoplasia (FVH1) is a rare condition of foveal hypoplasia (FH) that lacks any other ocular manifestations. FVH1 is associated with hypomorphic mutations in the PAX6 gene that encodes a sequence-specific DNA-binding transcription factor for morphogenesis and evolution of the eye. We report our findings in 17 patients with PAX6 mutations associated with FVH1 or FH with aniridia and corneal opacities. Patients with three mutations, p.V78E, p.V83F and p.R128H, in the C-terminal subdomain of the paired domain (CTS) consistently have severe FH. Luciferase assays for a single reporter containing a representative PAX6 binding site indicated that the transcriptional activities of these mutations were significantly reduced, comparable to that of the truncation mutation of p.G65Rfs*5. Patients with p.P20S in the N-terminal subdomain of the paired domain, and a patient with p.N365K in the proline-serine-threonine-rich domain (PSTD) had mild FH. A patient with p.Q255L in the homeodomain had severe FH. The P20S and Q255L mutants did not affect the transcriptional activity. Mutant N365K has a retained DNA-binding activity but a reduced transcriptional activity, due to a low PSTD transactivation. These findings demonstrated that mutations associated with FVH1 underlie a functional divergence between DNA-binding ability and transcriptional activity. We conclude that a wide range of mutations in the PAX6 gene is not limited to the CST region and are responsible for FVH1.
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Proteínas de Homeodominio , Factor de Transcripción PAX6 , Humanos , ADN/genética , Proteínas de Homeodominio/metabolismo , Mutación , Factores de Transcripción Paired Box/genética , Factor de Transcripción PAX6/genética , Proteínas Represoras/genéticaRESUMEN
PURPOSE: Bardet-Biedl Syndrome (BBS) is an autosomal recessive systemic disorder characterized by retinitis pigmentosa, polydactyly, obesity, intellectual disability, renal impairments, and hypogonadism. The purpose of this study was to determine the ocular characteristics of a boy with BBS caused by a novel homozygous variant in the ARL6 (alternative named BBS3) gene who had been originally diagnosed with retinitis punctata albescens. METHODS: This was an observational case study. The patient underwent ophthalmological examinations, electroretinography, and genetic analyses using whole-exome sequencing. RESULTS: A 7-year-old boy was examined in our hospital with complaints of a progressive reduction of his visual acuity and night blindness in both eyes. There was no family history of eye diseases and no consanguineous marriage. Fundus examinations showed numerous white spots in the deep retina and retinal pigment epithelium. Fundus autofluorescence showed hypofluorescence consistent with these spots. Both the scotopic and photopic components of the full-field electroretinographies were non-detectable. Based on these clinical findings, this boy was suspected to have retinitis punctata albescens. Subsequent genetic testing using whole-exome sequencing revealed a novel homozygous variants in the ARL6/BBS3 gene (NM_001278293.3:c.528G>A, (p.Trp176Ter)). A systemic examination by the pediatric department revealed that this boy had a history of a surgical excision of polydactyly on his left foot when he was born, and that he was mildly obese. There were no prominent intellectual or gonadal dysfunctions, no craniofacial or dental abnormalities, no congenital heart disease, and no hearing impairment. He was then clinically and genetically diagnosed with BBS. CONCLUSION AND IMPORTANCE: In children with night blindness and progressive visual dysfunction, it is important for ophthalmologists to consult clinical geneticists and pediatricians to rule out the possibility of systemic diseases such as BBS.
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Síndrome de Bardet-Biedl , Ceguera Nocturna , Polidactilia , Masculino , Niño , Humanos , Síndrome de Bardet-Biedl/diagnóstico , Síndrome de Bardet-Biedl/genética , Ceguera Nocturna/diagnóstico , Ceguera Nocturna/genética , Pueblos del Este de Asia , Factores de Ribosilacion-ADPRESUMEN
Purpose: To determine the changes in the microstructures of the photoreceptors in patients with autosomal recessive bestrophinopathy (ARB) by ultrahigh-resolution spectral-domain optical coherence tomography (UHR-SD-OCT). Methods: Five eyes of 4 patients with ARB were studied. Cross-sectional images of the fovea were recorded by the UHR-SD-OCT system with a depth resolution of <2.0 µm. Results: The UHR-SD-OCT images revealed changes in the outer retinal structures that were dependent on the severity of the photoreceptor atrophy. There was an increase in the reflectivity and appearance of small hyperreflective dots (HRDs) in the outer segments, followed by an irregularity and decrease in the length of the outer segments, then a disruption of the ellipsoid zone (EZ) band, and appearance of large HRDs corresponding to the segmented ellipsoids. Finally, there was a disappearance of the large HRDs followed by a localized thinning of the outer nuclear layer and appearance of hyperreflective foci above the region of the disrupted EZ. Conclusions: UHR-SD-OCT can record images that show detailed changes of the microstructures of the photoreceptors at different stages of ARB. These observations should help in determining the mechanisms involved in retinal pathology and should provide important information on the effectiveness of treatments.
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Inherited retinal diseases (IRDs) comprise a phenotypically and genetically heterogeneous group of ocular disorders that cause visual loss via progressive retinal degeneration. Here, we report the genetic characterization of 1210 IRD pedigrees enrolled through the Japan Eye Genetic Consortium and analyzed by whole exome sequencing. The most common phenotype was retinitis pigmentosa (RP, 43%), followed by macular dystrophy/cone- or cone-rod dystrophy (MD/CORD, 13%). In total, 67 causal genes were identified in 37% (448/1210) of the pedigrees. The first and second most frequently mutated genes were EYS and RP1, associated primarily with autosomal recessive (ar) RP, and RP and arMD/CORD, respectively. Examinations of variant frequency in total and by phenotype showed high accountability of a frequent EYS missense variant (c.2528G>A). In addition to the two known EYS founder mutations (c.4957dupA and c.8805C>G) of arRP, we observed a frequent RP1 variant (c.5797C>T) in patients with arMD/CORD.
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Distrofias de Conos y Bastones , Degeneración Macular , Enfermedades de la Retina , Humanos , Secuenciación del Exoma , Proteínas del Ojo/genética , Pueblos del Este de Asia , Mutación , Linaje , Distrofias de Conos y Bastones/diagnóstico , Distrofias de Conos y Bastones/genética , Enfermedades de la Retina/genética , Degeneración Macular/genética , Análisis Mutacional de ADNRESUMEN
Purpose: To analyze the microstructures of the photoreceptor layer in detail in eyes with occult macular dystrophy (OMD, Miyake's disease) by ultrahigh-resolution spectral-domain optical coherence tomography (UHR-SD-OCT). Observations: Twenty-eight normal subjects and 5 patients with OMD of different severities were studied. Cross-sectional images through the fovea were recorded with a UHR-SD-OCT system with a depth resolution of <2.0 µm. In patients with OMD, the UHR-SD-OCT images revealed abnormal photoreceptor microstructures which were not detected in the conventional SD-OCT images. The UHR-SD-OCT images showed that the interdigitation zone (IZ) was not present and the outer segments were hyperreflective with hyperreflective dots (HRDs) aligned like string of pearls during the earlier stages. There was a disruption of the ellipsoid zone (EZ) which appeared as clusters of larger HRDs, and these HRDs became less apparent with increasing time. The outer segments became hyporeflective and rod IZ became apparent with longer duration of the disease process. Conclusions and Importance: The UHR-SD-OCT images show detailed characteristics of the photoreceptor microstructures of different severities during the progression of OMD. These detailed observations will help in understanding the mechanisms involved in the retinal pathology and should provide important information for their treatments.
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Leber congenital amaurosis (LCA), although rare, is one of the most severe forms of early-onset inherited retinal dystrophy (IRD). Here, we review the molecular genetics and phenotypic characteristics of patients with NMNAT1-associated IRD. The longitudinal clinical and molecular findings of a Japanese girl diagnosed with LCA associated with pathogenic variants in NMNAT1 c.648delG, (p.Trp216Ter*) and c.709C>T (p.Arg237Cys) have been described to highlight the salient clinical features of NMNAT1-associated IRD.
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Amaurosis Congénita de Leber , Nicotinamida-Nucleótido Adenililtransferasa , Distrofias Retinianas , Femenino , Humanos , Japón , Amaurosis Congénita de Leber/diagnóstico , Amaurosis Congénita de Leber/genética , Mutación , Nicotinamida-Nucleótido Adenililtransferasa/genética , Nicotinamida-Nucleótido Adenililtransferasa/metabolismo , Linaje , Distrofias Retinianas/diagnósticoRESUMEN
Purpose: The purpose of this study was to investigate the perimetric features and their associations with structural and functional features in patients with RP1L1-associated occult macular dystrophy (OMD; i.e. Miyake disease). Methods: In this international, multicenter, retrospective cohort study, 76 eyes of 38 patients from an East Asian cohort of patients with RP1L1-associated OMD were recruited. Visual field tests were performed using standard automated perimetry, and the patients were classified into three perimetric groups based on the visual field findings: central scotoma, other scotoma (e.g. paracentral scotoma), and no scotoma. The association of the structural and functional findings with the perimetric findings was evaluated. Results: Fifty-four eyes (71.1%) showed central scotoma, 14 (18.4%) had other scotomata, and 8 (10.5%) had no scotoma. Central scotoma was mostly noted in both eyes (96.3%) and within the central 10 degrees (90.7%). Among the three perimetric groups, there were significant differences in visual symptoms, best-corrected visual acuity (BCVA), and structural phenotypes (i.e. severity of photoreceptor changes). The central scotoma group showed worse BCVA often with severe structural abnormalities (96.3%) and a pathogenic variant of p.R45W (72.2%). The multifocal electroretinogram (mfERG) groups largely corresponded with the perimetric groups; however, 8 (10.5%) of 76 eyes showed mfERG abnormalities preceding typical central scotoma. Conclusions: The patterns of scotoma with different clinical severity were first identified in occult macular dystrophy, and central scotoma, a severe pattern, was most frequently observed. These perimetric patterns were associated with the severity of BCVA, structural phenotypes, genotype, and objective functional characteristics which may precede in some cases.
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Degeneración Macular/fisiopatología , Escotoma/fisiopatología , Campos Visuales/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Electrorretinografía , Proteínas del Ojo/genética , Asia Oriental , Femenino , Genotipo , Humanos , Degeneración Macular/diagnóstico por imagen , Degeneración Macular/genética , Masculino , Persona de Mediana Edad , Fenotipo , Estudios Retrospectivos , Escotoma/diagnóstico por imagen , Escotoma/genética , Tomografía de Coherencia Óptica , Agudeza Visual/fisiología , Pruebas del Campo Visual , Adulto JovenRESUMEN
2p15p16.1 microdeletion syndrome is a recently recognized congenital disorder characterized by developmental delay and dysmorphic features. RP2-associated retinal disorder (RP2-RD) is an X-linked inherited retinal disease with a childhood onset caused by a loss-of-function variant in the RP2 gene. Here, we describe a 14-year-old boy with double diagnoses of 2p15p16.1 microdeletion syndrome and RP2-RD. The recurrence risk of each condition and the indication for potential therapeutic options for RP2-RD are discussed.
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Peripherin-2 (PRPH2) is one of the causative genes of inherited retinal dystrophy. While the gene is relatively common in Caucasians, reports from Asian ethnicities are limited. In the present study, we report 40 Japanese patients from 30 families with PRPH2-associated retinal dystrophy. We identified 17 distinct pathogenic or likely pathogenic variants using next-generation sequencing. Variants p.R142W and p.V200E were relatively common in the cohort. The age of onset was generally in the 40's; however, some patients had earlier onset (age: 5 years). Visual acuity of the patients ranged from hand motion to 1.5 (Snellen equivalent 20/13). The patients showed variable phenotypes such as retinitis pigmentosa, cone-rod dystrophy, and macular dystrophy. Additionally, intrafamilial phenotypic variability was observed. Choroidal neovascularization was observed in three eyes of two patients with retinitis pigmentosa. The results demonstrate the genotypic and phenotypic variations of the disease in the Asian cohort.
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Periferinas/genética , Fenotipo , Distrofias Retinianas/genética , Adulto , Anciano , Femenino , Frecuencia de los Genes , Humanos , Japón , Masculino , Persona de Mediana Edad , Mutación Missense , Distrofias Retinianas/patologíaRESUMEN
PURPOSE: To assess the validity of retinal surface wrinkling (RSW) as an indicator to select patients relevant for internal limiting membrane peeling during vitrectomy for rhegmatogenous retinal detachment, to prevent postoperative visual decline due to epiretinal membrane growth. METHODS: This was a prospective, interventional case series of 78 consecutive eyes that underwent initial vitrectomy to repair rhegmatogenous retinal detachments and were followed for 6 months. The presence/absence of RSW was evaluated presurgically on en face optical coherence tomographic images. The internal limiting membrane was peeled if RSW was identified. The main outcome measure was the prevalence of postsurgical epiretinal membrane growth that caused a visual decline of 0.2 or more in logarithm of the minimum angle of resolution unit. RESULTS: The internal limiting membrane was peeled for RSW appearance in 22 eyes (28.2%). Mild epiretinal membranes developed in 8 of the 56 internal limiting membrane-unpeeled eyes (10.3% of total, 6 eyes at stage 1 in the classification of Govetto); however, visual decline occurred in none of them with the mean visual acuity of these 8 eyes maintained at -0.08 ± 0.11 in logarithm of the minimum angle of resolution (≈20/16). CONCLUSION: Visual decline due to epiretinal membrane growth after rhegmatogenous retinal detachment repair was entirely prevented by peeling the internal limiting membrane in about 30% of cases selected for the presence of RSW.
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Membrana Basal/cirugía , Complicaciones Posoperatorias/prevención & control , Desprendimiento de Retina/cirugía , Tomografía de Coherencia Óptica/métodos , Agudeza Visual , Vitrectomía/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Desprendimiento de Retina/diagnósticoRESUMEN
BACKGROUND/AIMS: To investigate the utility of a data-driven deep learning approach in patients with inherited retinal disorder (IRD) and to predict the causative genes based on fundus photography and fundus autofluorescence (FAF) imaging. METHODS: Clinical and genetic data from 1302 subjects from 729 genetically confirmed families with IRD registered with the Japan Eye Genetics Consortium were reviewed. Three categories of genetic diagnosis were selected, based on the high prevalence of their causative genes: Stargardt disease (ABCA4), retinitis pigmentosa (EYS) and occult macular dystrophy (RP1L1). Fundus photographs and FAF images were cropped in a standardised manner with a macro algorithm. Images for training/testing were selected using a randomised, fourfold cross-validation method. The application program interface was established to reach the learning accuracy of concordance (target: >80%) between the genetic diagnosis and the machine diagnosis (ABCA4, EYS, RP1L1 and normal). RESULTS: A total of 417 images from 156 Japanese subjects were examined, including 115 genetically confirmed patients caused by the three prevalent causative genes and 41 normal subjects. The mean overall test accuracy for fundus photographs and FAF images was 88.2% and 81.3%, respectively. The mean overall sensitivity/specificity values for fundus photographs and FAF images were 88.3%/97.4% and 81.8%/95.5%, respectively. CONCLUSION: A novel application of deep neural networks in the prediction of the causative IRD genes from fundus photographs and FAF, with a high prediction accuracy of over 80%, was highlighted. These achievements will extensively promote the quality of medical care by facilitating early diagnosis, especially by non-specialists, access to care, reducing the cost of referrals, and preventing unnecessary clinical and genetic testing.
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Transportadoras de Casetes de Unión a ATP/genética , Aprendizaje Profundo , Proteínas del Ojo/genética , Angiografía con Fluoresceína/métodos , Enfermedades de la Retina/diagnóstico , Segmento Externo de la Célula en Bastón/patología , Transportadoras de Casetes de Unión a ATP/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Niño , Proteínas del Ojo/metabolismo , Femenino , Estudios de Seguimiento , Fondo de Ojo , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Enfermedades de la Retina/genética , Enfermedades de la Retina/metabolismo , Estudios Retrospectivos , Segmento Externo de la Célula en Bastón/metabolismo , Adulto JovenRESUMEN
PURPOSE: To describe the detailed retinal phenotype of KCNV2-associated retinopathy. STUDY DESIGN: Multicenter international retrospective case series. METHODS: Review of retinal imaging including fundus autofluorescence (FAF) and optical coherence tomography (OCT), including qualitative and quantitative analyses. RESULTS: Three distinct macular FAF features were identified: (1) centrally increased signal (n = 35, 41.7%), (2) decreased autofluorescence (n = 27, 31.1%), and (3) ring of increased signal (n = 37, 44.0%). Five distinct FAF groups were identified based on combinations of those features, with 23.5% of patients changing the FAF group over a mean (range) follow-up of 5.9 years (1.9-13.1 years). Qualitative assessment was performed by grading OCT into 5 grades: (1) continuous ellipsoid zone (EZ) (20.5%); (2) EZ disruption (26.1%); (3) EZ absence, without optical gap and with preserved retinal pigment epithelium complex (21.6%); (4) loss of EZ and a hyporeflective zone at the foveola (6.8%); and (5) outer retina and retinal pigment epithelium complex loss (25.0%). Eighty-six patients had scans available from both eyes, with 83 (96.5%) having the same grade in both eyes, and 36.1% changed OCT grade over a mean follow-up of 5.5 years. The annual rate of outer nuclear layer thickness change was similar for right and left eyes. CONCLUSIONS: KCNV2-associated retinopathy is a slowly progressive disease with early retinal changes, which are predominantly symmetric between eyes. The identification of a single OCT or FAF measurement as an endpoint to determine progression that applies to all patients may be challenging, although outer nuclear layer thickness is a potential biomarker. Findings suggest a potential window for intervention until 40 years of age.
Asunto(s)
Canales de Potasio con Entrada de Voltaje , Enfermedades de la Retina , Angiografía con Fluoresceína , Fondo de Ojo , Humanos , Fenotipo , Retina , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/genética , Estudios Retrospectivos , Tomografía de Coherencia ÓpticaRESUMEN
PURPOSE: To investigate the genotype and long-term clinical phenotype of patients with Bietti crystalline dystrophy (BCD) in Korea and Japan. DESIGN: Retrospective case series. PARTICIPANTS: We analyzed 62 patients with clinical features of BCD who harbor pathogenic biallelic CYP4V2 variants in their homozygote or compound heterozygote. METHODS: Data were collected from patient charts, including age, best-corrected visual acuity (BCVA), Goldmann perimetry results, fundus photography, OCT findings, fundus autofluorescence results, and electroretinography findings. We compared the clinical course of the patients with homozygous c.802-8_810de117insGC [exon7del], the most common mutation in the East Asian population, with those of the patients with other genotypes. MAIN OUTCOME MEASURES: Best-corrected visual acuity, visual field (VF), and their changes during follow-up. RESULTS: The mean age at the first visit was 55.2 years, with a mean follow-up of 7.1 years. The mean BCVAs at the first and last visits were 0.28 logarithm of the minimum angle of resolution (logMAR) and 0.89 logMAR, respectively. In genetic testing, c.802-8_810de117insGC was detected in 86 of 124 alleles of the patients, and 36 patients were homozygous for this mutation. The age, BCVA, VF area, central foveal thickness, and abnormal hypoautofluorescent area at either the first or last visit were not different between the exon7del homozygotes and the others. The mean BCVA changes per year were 0.089 logMAR in the exon7del homozygotes and 0.089 logMAR in the others. An age- and gender-adjusted linear regression analysis showed no association between the exon7del homozygote status and the rate of vision loss. Characteristic crystalline deposits in the posterior pole were generally observed in younger patients and disappeared over time along with progressive retinochoroidal atrophy. CONCLUSIONS: Patients with BCD and a homozygote for c.802-8_810de117insGC accounted for more than 50% of this cohort of Korean and Japanese patients, and the clinical effect of this deleterious variant was not severe in the spectrum of CYP4V2 retinopathy.
Asunto(s)
Distrofias Hereditarias de la Córnea/genética , Familia 4 del Citocromo P450/genética , ADN/genética , Angiografía con Fluoresceína/métodos , Mutación , Enfermedades de la Retina/genética , Tomografía de Coherencia Óptica/métodos , Distrofias Hereditarias de la Córnea/diagnóstico , Distrofias Hereditarias de la Córnea/epidemiología , Análisis Mutacional de ADN , Electrorretinografía , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , República de Corea/epidemiología , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/epidemiología , Estudios Retrospectivos , Factores de TiempoRESUMEN
PURPOSE: To compare the visual outcomes and prevalence of epiretinal membrane (ERM) growth postoperatively between eyes treated with and without internal limiting membrane peeling during vitrectomy for macula-sparing rhegmatogenous retinal detachment. METHODS: Fifty-five consecutive cases who underwent vitrectomy for macula-sparing rhegmatogenous retinal detachment were reviewed retrospectively. The inclusion criteria were a minimal 6-month follow-up postoperatively and spectral domain optical coherence tomographic images available at follow-up. Cases with any pre-existing macular condition possibly affecting the visual prognosis were excluded. All cases were divided into two groups: 22 cases without internal limiting membrane peeling (Group 1) and 33 cases with internal limiting membrane peeling (Group 2). The two groups were compared using the Mann-Whitney U test and Fisher exact test in terms of the best-corrected visual acuity (BCVA) (logarithm of the minimum angle of resolution) before vitrectomy, postoperative BCVA, and the presence of postoperative ERM growth. Postoperative BCVA and ERM growth were determined at 6 months, 12 months, and the last visit. The visual outcomes were also analyzed between cases with and without postoperative symptomatic ERM growth, which caused visual impairment and required surgical removal. RESULTS: The mean postoperative BCVAs were 0.00, -0.08, and -0.08 logarithm of the minimum angle of resolution in Group 1, and -0.08, -0.08, and -0.08 logarithm of the minimum angle of resolution in Group 2 at 6 months, 12 months, and the last visit, respectively, and did not differ significantly between the 2 groups at each time point except for at 12 months (P = 0.027). An ERM developed in 14 cases in Group 1, 7 of which were symptomatic. No cases in Group 2 had ERM growth. The prevalence of ERM growth was significantly (P < 0.001) higher in Group 1 than Group 2. The BCVA was significantly worse at 6 months (P = 0.011), 12 months (P = 0.003), and the last visit (P = 0.019) in 7 cases with symptomatic ERMs (median, 0.30, 0.15, and 0.10 logarithm of the minimum angle of resolution, respectively) than in 48 cases without symptomatic ERMs (median, -0.08, -0.08, and -0.08 logarithm of the minimum angle of resolution, respectively). CONCLUSION: Internal limiting membrane peeling did not result in decreased visual acuity postoperatively in cases with a macula-sparing rhegmatogenous retinal detachment, and the procedure significantly prevented postsurgical ERM growth. Symptomatic ERMs led to decreased visual acuity even after surgical removal. These results support the validity and efficacy of internal limiting membrane peeling for preventing ERM growth after rhegmatogenous retinal detachment repair.