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Accurate interpretation of sequence variants in inherited retinal dystrophy (IRD) is vital given the significant genetic heterogeneity observed in this disorder. To achieve consistent and accurate diagnoses, establishment of standardized guidelines for variant interpretation is essential. The American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines for variant interpretation serve as the global "cross-disease" standard for classifying variants in Mendelian hereditary disorders. These guidelines propose a systematic approach for categorizing variants into 5 classes based on various types of evidence, such as population data, computational data, functional data, and segregation data. However, for clinical genetic diagnosis and to ensure standardized diagnosis and treatment criteria, additional specifications based on features associated with each disorder are necessary. In this context, we present a comprehensive framework outlining the newly specified ACMG/AMP rules tailored explicitly to IRD in the Japanese population on behalf of the Research Group on Rare and Intractable Diseases (Ministry of Health, Labour and Welfare of Japan). These guidelines consider disease frequencies, allele frequencies, and both the phenotypic and the genotypic characteristics unique to IRD in the Japanese population. Adjustments and modifications have been incorporated to reflect the specific requirements of the population. By incorporating these IRD-specific factors and refining the existing ACMG/AMP guidelines, we aim to enhance the accuracy and consistency of variant interpretation in IRD cases, particularly in the Japanese population. These guidelines serve as a valuable resource for ophthalmologists and clinical geneticists involved in the diagnosis and treatment of IRD, providing them with a standardized framework to assess and classify genetic variants.
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PURPOSE: This study evaluated the long-term outcomes of eyes with neovascular age-related macular degeneration (nAMD) treated with aflibercept according to a treat-and-extend (T&E) regimen for up to 5 years. Methods This retrospective study included 112 eyes of 111 patients with nAMD who received aflibercept according to the T&E regimen. The patients received 3 monthly injections of aflibercept followed by a T&E regimen for at least 12 months. Data, including best-corrected visual acuity (BCVA), treatment interval, presence of exudation, central retinal thickness, and central choroidal thickness were analyzed. RESULTS: Of the 112 consecutive eyes, 66 completed the 5-year follow-up. After 5 years of treatment, BCVA (logMAR) was significantly better than baseline (0.29 ± 0.31 at baseline and 0.18 ± 0.23 at 5 years, P < 0.01). A mean of 7.0 ± 1.5 injections in the first year and 4.9 ± 2.2 injections per year thereafter were required. In eyes with subretinal hyperreflective material (SHRM) at baseline, BCVA at baseline and 5 years were significantly worse than in eyes without SHRM at baseline and 5 years. However, the eyes with SHRM required fewer injections and exhibited greater BCVA improvement. CONCLUSION: This retrospective study demonstrated the effectiveness of the T&E regimen with aflibercept in managing nAMD over a 5-year period, maintaining significant improvements in BCVA.
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PURPOSE: Vitreous humor (VH) is used for postmortem biochemical studies because it is well protected in an uncontaminated state even after death. The goal of this research was to investigate electrolyte concentrations in the VH from human eyes with and without a history of vitrectomy surgery. METHODS: We analyzed the sodium (Na), potassium (K), chloride (Cl) and magnesium (Mg) concentrations from 34 VH samples from 34 patients. Eleven samples were from eyes with a history of vitrectomy, and the remaining 23 eyes had no history of vitrectomy. The correlations of Na, K, Cl and Mg concentrations with patient age, interval between first and second vitrectomy, and lens status (history of cataract surgery) were also evaluated. RESULTS: The Na, K, Cl and Mg concentrations in VH from vitrectomized eyes were 134.1 ± 7.9 mmol/L, 3.7 ± 0.2 mmol/L, 99.7 ± 6.7 mmol/L and 0.59 ± 0.09 mmol/L, respectively; all were significantly lower than the corresponding concentrations in VH from control eyes (lower by 5.0%, 11.0%, 11.7%, and 22.6%, respectively). Na, K, Cl and Mg concentrations in VH from vitrectomized eyes did not show significant correlations with patient ages or the interval between their first and second vitrectomies. There were no significant differences in Na, K, Cl and Mg concentrations in VH between phakic eyes and intraocular lens-implanted eyes. CONCLUSIONS: With the increasing number of vitrectomies being performed, it is necessary to consider the history of vitrectomy when using a subject's VH in forensic examination.
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Vitrectomia , Corpo Vítreo , Humanos , Corpo Vítreo/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto , Eletrólitos/análise , Medicina Legal/métodos , Sódio/análise , Potássio/análise , Magnésio/análiseRESUMO
A capsular tension ring (CTR) is used for support to stabilize the capsular bag and intraocular lens (IOL) during and after cataract surgery. Although complications involving the CTR-IOL complex are not uncommon, cases of anterior displacement leading to complications are rare. This report presents a case of secondary angle closure caused by anterior displacement of the CTR-IOL complex due to aqueous misdirection and reports unique findings noted on anterior segment optical coherence tomography (AS-OCT). The patient, a 69-year-old woman, developed an acute angle closure crisis (AACC) and underwent cataract surgery with the implantation of a CTR and IOL. Post-surgery, there was an improvement in the central depth of the anterior chamber, but the patient experienced intermittent spikes in intraocular pressure. AS-OCT revealed a flat center of the iris and a closed anterior chamber angle which are plateau-iris-like findings. Secondary angle closure was caused by the CTR-IOL complex which was anteriorly displaced and pushed the peripheral iris owing to aqueous misdirection syndrome. Three weeks after the initial surgery, the patient underwent CTR removal, anterior vitrectomy, and intrascleral lens fixation. After the second surgery, intraocular pressure was normalized without any medications, and the anterior chamber angle was enlarged. This case provides a better understanding of secondary angle closure caused by the anterior displacement of the CTR-IOL complex and highlights the importance of AS-OCT in the detection of such complications.
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BACKGROUND: As gene-specific therapy for inherited retinal dystrophy (IRD) advances, unified variant interpretation across institutes is becoming increasingly important. This study aims to update the genetic findings of 86 retinitis pigmentosa (RP)-related genes in a large number of Japanese patients with RP by applying the standardised variant interpretation guidelines for Japanese patients with IRD (J-IRD-VI guidelines) built upon the American College of Medical Genetics and Genomics and the Association for Molecular Pathology rules, and assess the contribution of these genes in RP-allied diseases. METHODS: We assessed 2325 probands with RP (n=2155, including n=1204 sequenced previously with the same sequencing panel) and allied diseases (n=170, newly analysed), including Usher syndrome, Leber congenital amaurosis and cone-rod dystrophy (CRD). Target sequencing using a panel of 86 genes was performed. The variants were interpreted according to the J-IRD-VI guidelines. RESULTS: A total of 3564 variants were detected, of which 524 variants were interpreted as pathogenic or likely pathogenic. Among these 524 variants, 280 (53.4%) had been either undetected or interpreted as variants of unknown significance or benign variants in our earlier study of 1204 patients with RP. This led to a genetic diagnostic rate in 38.6% of patients with RP, with EYS accounting for 46.7% of the genetically solved patients, showing a 9% increase in diagnostic rate from our earlier study. The genetic diagnostic rate for patients with CRD was 28.2%, with RP-related genes significantly contributing over other allied diseases. CONCLUSION: A large-scale genetic analysis using the J-IRD-VI guidelines highlighted the population-specific genetic findings for Japanese patients with IRD; these findings serve as a foundation for the clinical application of gene-specific therapies.
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Retinose Pigmentar , Feminino , Humanos , Masculino , Distrofias de Cones e Bastonetes/genética , Distrofias de Cones e Bastonetes/patologia , População do Leste Asiático/genética , Predisposição Genética para Doença , Variação Genética , Japão , Amaurose Congênita de Leber/genética , Amaurose Congênita de Leber/patologia , Mutação , Retinose Pigmentar/genética , Retinose Pigmentar/patologia , Síndromes de Usher/genéticaRESUMO
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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Transportadores de Cassetes de Ligação de ATP , Degeneração Retiniana , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Transportadores de Cassetes de Ligação de ATP/genética , Análise Mutacional de DNA , População do Leste Asiático/genética , Sequenciamento do Exoma , Angiofluoresceinografia/métodos , Genótipo , Japão/epidemiologia , Mutação de Sentido Incorreto , Fenótipo , Degeneração Retiniana/genética , Degeneração Retiniana/diagnóstico , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Acuidade Visual/fisiologiaRESUMO
Copy-number variants (CNVs) play a substantial role in the molecular pathogenesis of hereditary disease and cancer, as well as in normal human interindividual variation. However, they are still rather difficult to identify in mainstream sequencing projects, especially involving exome sequencing, because they often occur in DNA regions that are not targeted for analysis. To overcome this problem, we developed OFF-PEAK, a user-friendly CNV detection tool that builds on a denoising approach and the use of "off-target" DNA reads, which are usually discarded by sequencing pipelines. We benchmarked OFF-PEAK on data from targeted sequencing of 96 cancer samples, as well as 130 exomes of individuals with inherited retinal disease from three different populations. For both sets of data, OFF-PEAK demonstrated excellent performance (>95% sensitivity and >80% specificity vs. experimental validation) in detecting CNVs from in silico data alone, indicating its immediate applicability to molecular diagnosis and genetic research.
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Algoritmos , Neoplasias , Humanos , Sequenciamento de Nucleotídeos em Larga Escala , Análise de Sequência de DNA , Exoma , Variações do Número de Cópias de DNA/genética , Neoplasias/genéticaRESUMO
PURPOSE: To investigate the incidence of intraocular inflammation (IOI) and its risk factors following intravitreal injections of brolucizumab for neovascular age-related macular degeneration in Japan. METHODS: A total of 1,351 Japanese consecutive patients with neovascular age-related macular degeneration who were treated with brolucizumab from May 2020 to May 2022 at 14 institutions were examined. The variables analyzed were the number of brolucizumab injections, time to onset of IOI, and risk factors. RESULTS: Intraocular inflammation developed in 152 eyes (11.3%). Retinal vasculitis and/or retinal occlusion occurred in 53 eyes (3.9%). Ninety-four patients received bilaterally, bilateral IOI occurred in five patients (5.3%). Sixteen eyes (1.2%) had irreversible visual acuity loss and nine eyes (0.67%) had visual loss of three lines or more due to retinal vasculitis and/or retinal occlusion. The cumulative IOI incidence was 4.5%, 10.3%, and 12.2% at 30, 180, and 365 days (1-year), respectively. History of IOI (including retinal vasculitis) and/or retinal occlusion (odds ratio [OR], 5.41; P = 0.0075) and female sex (OR, 1.99; P = 0.0004) were significantly associated with IOI onset. CONCLUSION: The 1-year cumulative incidence of IOI in Japanese neovascular age-related macular degeneration patients treated with brolucizumab was 12.2%. History of IOI (including retinal vasculitis) and/or retinal occlusion and female sex were significant risk factors.
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Anticorpos Monoclonais Humanizados , Degeneração Macular , Vasculite Retiniana , Uveíte , Feminino , Humanos , Inibidores da Angiogênese , Incidência , Inflamação , Injeções Intravítreas , Japão , Retina , Fatores de Risco , Transtornos da Visão , MasculinoRESUMO
PURPOSE: To clarify the abilities of circumpapillary retinal nerve fiber layer thickness (cpRNFLT) obtained by optical coherence tomography (OCT) and circumpapillary vessel density (cpVD) measured by OCT-angiography to distinguish different stages in primary open-angle glaucoma determined by 24-2 or 30-2 static visual field (VF) testing. METHODS: This retrospective study includes 25 healthy normal eyes of 25 subjects and 87 primary open-angle glaucoma eyes of 87 patients. Areas under the receiver operating characteristic curves (AUROC) were evaluated for determining glaucoma stages using cpRNFLT and cpVD. The absolute errors of the estimated mean total deviation (mTD) using optimal models with cpRNFLT and cpVD were also compared. RESULTS: The AUROCs for discriminating glaucomatous eyes from normal eyes was significantly higher for cpRNFLT than the respective AUROCs for cpVD (0.969 [95% CI 0.939 to 0.998] vs. 0.872 [95% CI 0.806 to 0.938], p = 0.006), whereas cpVD had significantly higher AUROC for discriminating severe glaucoma eyes from moderate glaucoma eyes than cpRNFLT (0.771 [95% CI 0.655 to 0.886] vs. 0.578 [95% CI 0.420 to 0.736], p = 0.022). The mean absolute error in estimating mTD using both cpRNFLT and cpVD was significantly less than the error using cpRNFLT alone (4.56 ± 3.76 dB vs. 5.39 ± 4.00 dB, p = 0.027). CONCLUSION: Our results suggest that cpVD is better for follow-ups after moderate stage. The combination of cpRNFLT and cpVD may improve VF estimation compared to cpRNFLT alone.
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Glaucoma de Ângulo Aberto , Glaucoma , Disco Óptico , Humanos , Glaucoma de Ângulo Aberto/diagnóstico , Disco Óptico/irrigação sanguínea , Campos Visuais , Estudos Retrospectivos , Pressão Intraocular , Densidade Microvascular , Vasos Retinianos , Células Ganglionares da Retina , Tomografia de Coerência Óptica/métodos , Fibras NervosasRESUMO
Toxoplasmosis is a major infectious disease, affecting approximately one-third of the world's population; its main clinical manifestation, ocular toxoplasmosis (OT), is a severe sight-threatening disease. Nevertheless, the diagnosis of OT is based on clinical findings, which needs improvement, even with biochemical tests, such as polymerase chain reaction and antibody detections. Furthermore, the efficacy of OT-targeted treatment is limited; thus, additional measures for diagnosis and treatments are needed. Here, we for the first time report a significantly reduced iron concentration in the vitreous humor (VH) of human patients infected with OT. To obtain further insights into molecular mechanisms, we established a mouse model of T. gondii infection, in which intravitreally injected tracer 57Fe, was accumulated in the neurosensory retina. T. gondii-infected eyes showed increased lipid peroxidation, reduction of glutathione peroxidase-4 expression and mitochondrial deformity in the photoreceptor as cristae loss. These findings strongly suggest the involvement of ferroptotic process in the photoreceptor of OT. In addition, deferiprone, an FDA-approved iron chelator, reduced the iron uptake but also ameliorated toxoplasma-induced retinochoroiditis by reducing retinal inflammation. In conclusion, the iron levels in the VH could serve as diagnostic markers and iron chelators as potential treatments for OT.
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Coriorretinite , Ferroptose , Toxoplasma , Toxoplasmose Ocular , Animais , Camundongos , Humanos , Toxoplasmose Ocular/diagnóstico , Coriorretinite/diagnóstico , Retina , FerroRESUMO
BACKGROUND: Nanophthalmos (NNO) is a rare condition with significantly shorter axial length than normal. Several genes are known to cause NNO, among them the MFRP and PRSS56 genes have been reported to cause majority of NNOs. The purpose of this study was to determine the genetic basis of Japanese patients with NNO. MATERIALS AND METHODS: We studied seven patients with NNO. Whole exome sequencing (WES) and Sanger sequencing were performed to determine the variants causing the NNO. We also reviewed the medical charts of the patients to determine the phenotype of these seven patients. RESULTS: WES revealed that four patients from three families carried homozygous frameshift variants of the PRSS56 gene (c.1066dupC). Two novel variants of the MFRP gene were detected in the other two patients: one proband had a homozygous missense variant (c.1486 G>A) and the other had a compound heterozygous variant (c.1486 G>A and c.662_663insT). The axial length of the eight eyes with the PRSS56 variant was 15.69 ± 0.48 mm (mean ± SD) and that for the 4 eyes with the MFRP variant was 15.63 ± 0.69 mm. Three of the six cases with the PRSS56 or MFRP variant had the uveal effusion syndrome. CONCLUSIONS: NNOs in Japanese patients are caused by variants of the PRSS56 and MFRP genes as in other ethnic populations. In addition, two new variants of the MFRP gene were found in our cohort. The phenotypes and anomalies in Japanese patients with NNO were similar to those reported for other ethnic populations.
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Microftalmia , Humanos , Microftalmia/genética , Microftalmia/patologia , População do Leste Asiático , Olho , Mutação da Fase de Leitura , Família , Mutação , Proteínas de Membrana/genética , Serina Proteases/genéticaRESUMO
PURPOSE: To determine the correlation between the presence of torque teno virus (TTV) in the aqueous humor of patients with uveitis and clinical information, including immunodeficiency history. DESIGN: Multicenter, retrospective, cross-sectional study. METHODS: Fifty-eight patients with uveitis with a suspected infectious etiology and 24 controls with cataract or age-related macular degeneration were included. We used quantitative polymerase chain reaction to test all subjects for TTV and multiplex polymerase chain reaction to test uveitis subjects for common ocular pathogens. When possible, both serum and aqueous humor samples were tested. Ocular TTV positivity was compared with age, sex, and a history of systemic immunodeficiency with logistic analysis. RESULTS: Ocular TTV positivity was found in 23%, 11%, and 0% of patients with herpetic uveitis, nonherpetic uveitis, and controls, respectively. Among patients with herpes infection, positivity for ocular TTV was found in 43%, 8%, 14%, and 50% of patients with cytomegalovirus retinitis, iridocyclitis, acute retinal necrosis, and Epstein-Barr virus-positive uveitis, respectively. Patients with cytomegalovirus retinitis showed a significantly higher rate of ocular TTV infection than controls (P = .008). Serum analysis revealed TTV positivity in 90% of patients with uveitis and in 100% of controls. Age- and gender-adjusted logistic analysis revealed a correlation between ocular TTV positivity and systemic immunodeficiency (P = .01), but no correlations between ocular TTV and age, gender, or viral pathogenic type. CONCLUSIONS: These findings suggest that positivity for ocular TTV was correlated with a clinical history of systemic immunodeficiency.
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Retinite por Citomegalovirus , Infecções por Vírus Epstein-Barr , Torque teno virus , Uveíte , Humanos , Estudos Transversais , DNA Viral/análise , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Herpesvirus Humano 4/genética , Estudos Retrospectivos , Torque teno virus/genética , Uveíte/complicações , Uveíte/diagnóstico , Masculino , FemininoRESUMO
PURPOSE: To determine the factors significantly associated with the amplitudes and implicit times of the flicker electroretinograms (ERGs) recorded with the RETeval system by analyzing the comprehensive data obtained during a health checkup screening. METHODS: Flicker ERGs were recorded with the RETeval system from 373 individuals who had a normal fundus and optical coherence tomography images. The sex, age, anthropometric, ophthalmologic, and hematologic data were collected from all participants who were 40- to 89-years-of-age. Univariable and multivariable linear mixed effects regression analyses were performed to identify factors that were significantly associated with the implicit times and amplitudes of the RETeval flicker ERGs. RESULTS: Univariable linear mixed effects regression analysis showed significant correlations between the implicit times and the best-corrected visual acuity, the age, the axial length, the blood sugar level, and the blood urea nitrogen level. Analyses by multivariable linear mixed effects regression identified that the axial length (ß = 0.28), the age (ß = 0.24), and the blood sugar level (ß = 0.092) were three independent factors that were significantly correlated with the implicit times of the RETeval flicker ERGs. Univariable linear mixed effects regression analysis also showed significant correlations between the amplitudes of the RETeval flicker ERGs and the age, the platelet count, and the creatinine level. Multivariable linear mixed effects regression models identified the age (ß = -0.092), the platelet count (ß = 0.099), and the creatinine level (ß = -0.12) as three independent factors that were significantly correlated with the amplitudes of the RETeval flicker ERGs. However, the smoking habits, body mass index, and the blood pressure were not significantly correlated with either the implicit times or amplitudes of the RETeval flicker ERGs. CONCLUSIONS: Our results indicate that the age and some ophthalmologic and hematologic findings but not the anthropometric findings were significantly associated with the implicit times and amplitudes of the RETeval flicker ERGs. Thus, clinicians should remember these factors when analyzing the RETeval flicker ERGs.
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Glicemia , Retina , Humanos , Creatinina , Eletrorretinografia/métodos , Tomografia de Coerência Óptica , Regulador Transcricional ERGRESUMO
PURPOSE: To assess the effects of half-dose photodynamic therapy (PDT) combined with an intravitreous aflibercept (IVA) injection for pachychoroid neovasculopathy (PNV) and its predictive factors. METHODS: Clinical information of 43 patients (43 eyes) with PNV obtained before and 6 months after treatment with half-dose PDT combined with IVA was retrospectively analyzed. Patients were categorized into the sufficient (25 eyes, 58.1%) or insufficient (18 eyes, 41.9%) group based on resolution or persistence/recurrence of subretinal fluid (SRF), respectively, and clinical data were compared. Macular neovascularization (MNV) change was studied in 30 cases with available pre- and post-treatment optical coherence tomography angiography images. RESULTS: The sufficient group included younger patients with better baseline best-corrected visual acuity (BCVA), more treatment-naïve eyes, and smaller MNV lesions at baseline than the insufficient group (all, P < 0.047). Complete SRF resolution was 81.8% in treatment-naïve eyes and only 33.3% in previously treated eyes. MNV expanded after half-dose PDT was combined with IVA regardless of the treatment outcome (P = 0.003). CONCLUSION: Half-dose PDT combined with IVA was effective for PNV treatment, especially for younger patients with good baseline BCVA, treatment-naïve eyes, and small MNV sizes at baseline. MNV expanded after treatment regardless of the treatment outcomes.
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Fotoquimioterapia , Receptores de Fatores de Crescimento do Endotélio Vascular , Humanos , Estudos Retrospectivos , Fundo de Olho , Tomografia de Coerência Óptica , Fotoquimioterapia/métodos , Angiofluoresceinografia/métodosRESUMO
Introduction: Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are two groups of inherited retinal diseases (IRDs) where the rod photoreceptors degenerate followed by the cone photoreceptors of the retina. A genetic diagnosis for IRDs is challenging since >280 genes are associated with these conditions. While whole exome sequencing (WES) is commonly used by diagnostic facilities, the costs and required infrastructure prevent its global applicability. Previous studies have shown the cost-effectiveness of sequence analysis using single molecule Molecular Inversion Probes (smMIPs) in a cohort of patients diagnosed with Stargardt disease and other maculopathies. Methods: Here, we introduce a smMIPs panel that targets the exons and splice sites of all currently known genes associated with RP and LCA, the entire RPE65 gene, known causative deep-intronic variants leading to pseudo-exons, and part of the RP17 region associated with autosomal dominant RP, by using a total of 16,812 smMIPs. The RP-LCA smMIPs panel was used to screen 1,192 probands from an international cohort of predominantly RP and LCA cases. Results and discussion: After genetic analysis, a diagnostic yield of 56% was obtained which is on par with results from WES analysis. The effectiveness and the reduced costs compared to WES renders the RP-LCA smMIPs panel a competitive approach to provide IRD patients with a genetic diagnosis, especially in countries with restricted access to genetic testing.
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PURPOSE: To examine the morphologic changes in macular neovascularization (MNV) secondary to age-related macular degeneration after 2 years of aflibercept treatment under a treat-and-extend (T&E) regimen. METHODS: This retrospective study analyzed the medical records for 26 eyes of 25 patients diagnosed with treatment-naive neovascular age-related macular degeneration and treated with aflibercept under a treat-and-extend regimen for 2 years. The areas of the MNV and vascular structures were assessed using swept-source optical coherence tomography angiography at baseline and after 2 years of treatment. RESULTS: The mean MNV area increased significantly from 0.65 ± 0.42 mm 2 at baseline to 0.78 ± 0.45 mm 2 at 2 years. At 2 years, the mean change in the MNV area from baseline was 22% (interquartile range: 4%-60%). The baseline MNV area was negatively correlated with the change ratio of the MNV areas at 2 years and baseline ( R = -0.68, P < 0.001). Nine of the 26 eyes (34.6%) showed newly formed mature vessels, and 7 eyes (26.9%) showed prominently developing preexisting mature vessels. CONCLUSION: Macular neovascularization expanded and showed vascular maturation under aflibercept treatment with a treat-and-extend regimen. The smaller the MNV at baseline, the greater is its expansion in 2 years.
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Degeneração Macular , Degeneração Macular Exsudativa , Humanos , Inibidores da Angiogênese/uso terapêutico , Angiofluoresceinografia , Injeções Intravítreas , Degeneração Macular/diagnóstico , Neovascularização Patológica/tratamento farmacológico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Degeneração Macular Exsudativa/tratamento farmacológicoRESUMO
PURPOSE: To investigate the genetic architecture of age-related macular degeneration (AMD) in a Japanese population. DESIGN: Genome-wide association study (GWAS). PARTICIPANTS: Three thousand seven hundred seventy-two patients with AMD and 16 770 control participants from the Japanese population were enrolled in the association analyses. METHODS: We conducted a meta-analysis of 2 independent GWASs that included a total of 2663 patients with AMD and 9471 control participants using the imputation reference panel for genotype imputation specified for the Japanese population (n = 3541). A replication study was performed using an independent set of 1109 patients with AMD and 7299 control participants. MAIN OUTCOME MEASURES: Associations of genetic variants with AMD. RESULTS: A meta-analysis of the 2 GWASs identified 6 loci significantly associated with AMD (P < 5.0 × 10-8). Of these loci, 4 were known to be associated with AMD (CFH, C2/FB, TNFRSF10A, and ARMS2), and 2 were novel (rs4147157 near WBP1L and rs76228488 near GATA5). The newly identified associations were confirmed in a replication study (P < 0.01). After the meta-analysis of all datasets, we observed strong associations in these loci (P = 1.88 × 10-12 and P = 1.35 × 10-9 for meta-analysis for rs4147157 and rs76228488, respectively). When we looked up the associations in the reported central serous chorioretinopathy (CSC) GWAS conducted in the Japanese population, both loci were associated significantly with CSC (P = 4.86 × 10-3 and P = 4.28 × 10-3 for rs4147157 and rs76228488, respectively). We performed a genetic colocalization analysis for these loci and estimated that the posterior probabilities of shared causal variants between AMD and CSC were 0.39 and 0.60 for WBP1L and GATA5, respectively. Genetic correlation analysis focusing on the epidemiologically suggested clinical risk factors implicated shared polygenic architecture between AMD and smoking cessation (rg [the measure of genetic correlation] = -0.33; P = 0.01; false discovery rate, 0.099). CONCLUSIONS: Our findings imply shared genetic components conferring the risk of both AMD and CSC. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
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Coriorretinopatia Serosa Central , Degeneração Macular , Humanos , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença , Coriorretinopatia Serosa Central/diagnóstico , Coriorretinopatia Serosa Central/genética , Degeneração Macular/genética , Genótipo , Polimorfismo de Nucleotídeo Único , Loci GênicosRESUMO
PURPOSE: To assess the effects of half-dose photodynamic therapy on subretinal fluid and macular neovascularization (MNV) using optical coherence tomography angiography in patients with chronic central serous chorioretinopathy. METHODS: Clinical information on 168 patients (168 eyes) with chronic central serous chorioretinopathy obtained before and 6 months after treatment with half-dose photodynamic therapy was retrospectively analyzed. Patients were categorized into a success (145 eyes) or failure (23 eyes) group based on the absence or presence of subretinal fluid, respectively, and clinical data were compared between them. Macular neovascularization was studied in 147 cases with available optical coherence tomography angiography images. P < 0.05 indicated statistical significance. RESULTS: The success group showed a younger patient age, better posttreatment best-corrected visual acuity, and thicker pretreatment central choroidal thickness (all, P < 0.047) than did the failure group. Regarding MNV analysis, nine, eight, and 130 eyes had definite, possible, and no MNV, respectively, at baseline; among them, 100.0%, 75.0%, and 2.3%, respectively, had MNV at 6 months posttreatment. Patients with definite MNV at baseline were less likely to show successful subretinal fluid resolution. CONCLUSION: Although half-dose photodynamic therapy is generally effective for the treatment of chronic central serous chorioretinopathy, coexisting MNV may compromise the outcome; thus, optical coherence tomography angiography-based assessment of chronic central serous chorioretinopathy is important.
Assuntos
Coriorretinopatia Serosa Central , Fotoquimioterapia , Humanos , Coriorretinopatia Serosa Central/diagnóstico , Coriorretinopatia Serosa Central/tratamento farmacológico , Fotoquimioterapia/métodos , Tomografia de Coerência Óptica/métodos , Angiofluoresceinografia/métodos , Estudos Retrospectivos , Fármacos Fotossensibilizantes/uso terapêutico , Acuidade Visual , Neovascularização Patológica/tratamento farmacológicoRESUMO
BACKGROUND/AIMS: The accuracy of pattern deviation (PD) in estimating the damage to the glaucomatous visual field (VF) in the central 10° in eyes with glaucoma and cataract is unclear. METHODS: This retrospective study includes 63 eyes of 52 glaucoma patients who successfully underwent cataract surgery or cataract surgery plus iStent implantation. Using the Humphrey Field Analyser 10-2 test, VF was measured within 6 months preoperatively and postoperatively (VFpre and VFpost, respectively). The mean total deviation values in VFpost (mTDpost) indicates glaucomatous damage without cataract and the difference between this value and mean PD values in VFpre (mPDpre) was evaluated (εmPD). The effect of cataract was then evaluated as the difference between mTDpost and mTDpre (ΔmTD), while the effects of mTDpost and ΔmTD on εmPD were also assessed. In addition, based on preoperative visual acuity (VApre) and VFpre, the optimal model for predicting mTDpost was identified. The error of this method (εOptimalModel) was estimated as the difference against mTDpost, which was compared with εmPD. RESULTS: Compared with mTDpre, there was a significant improvement in mTDpost (p=0.028). A significant difference was observed between mPDpre and mTDpost (p<0.001). Further, εmPD significantly increased with the increase of mTDpost or ΔmTD (p<0.001 and p=0.0444, respectively). The absolute εOptimalModel was significantly smaller than the absolute εmPD (p<0.001). CONCLUSIONS: This study warns clinicians that PD of the central 10° VF might underestimate the glaucomatous VF damage with the progression of glaucoma and overestimate it as a cataract progresses.
RESUMO
This retrospective study aimed to evaluate choroidal hemodynamics after half-dose photodynamic therapy (PDT) for central serous chorioretinopathy (CSC) and the effects of smoking using laser speckle flowgraphy. This study included 29 eyes of 29 patients treated with half-dose PDT for CSC, who were followed-up for at least 6 months. The mean blur rate (MBR) in the PDT irradiation area (whole area), the pachyvessel (PV) area, non-PV (NPV) area, and filling delay (FD) area were assessed at baseline and 1, 3, and 6 months post-PDT, respectively. The MBR was also assessed by smoking status. The MBR significantly decreased from baseline in the whole, PV, NPV, and FD areas at all time points (P < 0.001). Of the 29 patients, 6 were never smokers, 13 were past smokers, and 10 were current smokers. At baseline, no significant difference was found in the MBR in the whole, PV, NPV, and FD areas among never, past, and current smokers. The MBR changes showed a significantly smaller decrease in current smokers than in never smokers in the whole (P = 0.021), PV (P = 0.009), and NPV (P = 0.034) areas, but not in the FD area (P = 0.172). Half-dose PDT for CSC reduced choroidal blood flow in the PDT-irradiated area, which was blunted by current smoking status.