RESUMO
During spermatogenesis, intricate gene expression is coordinately regulated by epigenetic modifiers, which are required for differentiation of spermatogonial stem cells (SSCs) contained among undifferentiated spermatogonia. We have previously found that KMT2B conveys H3K4me3 at bivalent and monovalent promoters in undifferentiated spermatogonia. Because these genes are expressed late in spermatogenesis or during embryogenesis, we expect that many of them are potentially programmed by KMT2B for future expression. Here, we show that one of the genes targeted by KMT2B, Tsga8, plays an essential role in spermatid morphogenesis. Loss of Tsga8 in mice leads to male infertility associated with abnormal chromosomal distribution in round spermatids, malformation of elongating spermatid heads and spermiation failure. Tsga8 depletion leads to dysregulation of thousands of genes, including the X-chromosome genes that are reactivated in spermatids, and insufficient nuclear condensation accompanied by reductions of TNP1 and PRM1, key factors for histone-to-protamine transition. Intracytoplasmic sperm injection (ICSI) of spermatids rescued the infertility phenotype, suggesting competency of the spermatid genome for fertilization. Thus, Tsga8 is a KMT2B target that is vitally necessary for spermiogenesis and fertility.
Assuntos
Fertilidade , Nucleoproteínas/metabolismo , Espermátides/metabolismo , Espermatogênese , Células-Tronco/metabolismo , Animais , Feminino , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Infertilidade Masculina/genética , Infertilidade Masculina/metabolismo , Masculino , Camundongos , Camundongos Knockout , Proteína de Leucina Linfoide-Mieloide/genética , Proteína de Leucina Linfoide-Mieloide/metabolismo , Nucleoproteínas/genética , Espermatogônias/metabolismoRESUMO
PURPOSE: To investigate risk factors for increased intraocular pressure (IOP) after Descemet membrane endothelial keratoplasty (DMEK) in Asian patients. METHODS: Data from January 2015 to February 2021 were obtained from our prospective database. IOP elevation after DMEK was defined as IOP ≥ 22 mmHg or an increase in IOP of ≥ 10 mmHg from baseline. In addition, we examined maximum IOP. Using iCare, we measured IOP 1, 2, 3, and 6 months after DMEK, and every 6 months thereafter. Logistic regression and linear regression were performed to find factors predictive of IOP elevation and maximum IOP, respectively, based on the results of univariate analysis. RESULTS: We enrolled 90 eyes (mean patient age, 74.9 ± 7.5 years; mean follow-up duration, 25.6 ± 9.9 months) that underwent DMEK. IOP elevation was present in 19 eyes (21%). IOP increased from 12.6 ± 3.9 mmHg preoperatively to a postoperative maximum of 17.0 ± 5.5 mmHg up to 36 months after DMEK (p < 0.0001). In univariate logistic regression analysis for IOP elevation, only one variable, pseudoexfoliation syndrome (PEX) and preexisting glaucoma, was significant (p < 0.05). Preexisting glaucoma without PEX (OR, 19.33; 95% CI, 4.75-93.46), PEX without glaucoma (OR, 7.25; 95% CI, 1.20-41.63), and PEX glaucoma (OR, 58.00; 95% CI, 6.78-1298.29) were associated with higher risk of IOP elevation. CONCLUSIONS: In this cohort, the eyes of patients with PEX and preexisting glaucoma were found to be prone to IOP elevation after DMEK.
Assuntos
Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Glaucoma , Humanos , Idoso , Idoso de 80 Anos ou mais , Pressão Intraocular , Lâmina Limitante Posterior/cirurgia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/efeitos adversos , Glaucoma/etiologia , Glaucoma/cirurgia , Fatores de Risco , Estudos RetrospectivosRESUMO
BACKGROUND: Differences between programmed capsulorhexis diameter and actual resulting capsulorhexis diameter (ARCD) are commonly encountered in femtosecond laser-assisted cataract surgery (FLACS). The purpose of this study was to identify the preoperative ophthalmic variables influencing capsulorhexis diameter index (CDI) in FLACS for adults and create a multiple linear regression model for obtaining a more accurate capsulorhexis diameter. METHODS: This retrospective study involved sixty-seven eyes of 44 patients who received FLACS and intraocular lens implantation. The ARCD was measured using anterior segment swept-source optical coherence tomography (CASIA 2). Keratometry (K1, K2 and average K), anterior chamber depth (ACD), lens thickness (LT), anterior chamber width (ACW), white-to-white (WTW), curvature radius of anterior lens capsule (Front R) and axial length (AL) were all measured preoperatively. Based on the derived data, LT/ACW, LT/AL, LT/ACD and LT/ACW/Front R were calculated. The ratio of the programmed capsulorhexis diameter and ARCD was defined as the CDI. Correlation analysis was conducted to examine the relationship between preoperative variables listed above and the CDI. Multiple linear regression analysis was applied to select the most influential preoperative variables on CDI. RESULTS: ACD, LT, ACW, Front R, AL, LT/ACW, LT/AL, LT/ACD, and LT/ACW/Front R showed significant correlation with CDI. Front R and LT/ACW/Front R were selected as constants in the multiple linear regression model using stepwise variable selection. The following equation represents the multiple linear regression model: CDI = 1.306-4.516 × LT/ACW/FrontR-0.011 × Front R, when P < 0.0001, adjusted R-squared = 0.919, variance inflation factor = 8.389, and Durbin-Watson ratio = 1.846. Predicted postoperative capsulorhexis diameter (PPCD) equation was created based on CDI equation as follows: PPCD = programmed capsulorhexis diameter × 1.306-4.516 × LT/ACW/FrontR-0.011 × Front R. CONCLUSION: Front R and LT/ACW/Front R were found to be the most significant influencing factors of capsulorhexis size. CDI and PPCD calculation equations presented in this study may be useful in setting up more accurate programmed capsulorhexis diameter for FLACS in adults, resulting in a precise ARCD.
Assuntos
Capsulorrexe , Catarata , Humanos , Adulto , Capsulorrexe/métodos , Estudos Retrospectivos , Modelos Lineares , LasersRESUMO
Previously, we developed a chimeric adenovirus type 5 with type 35 fiber (Ad5/35), which has high tropism to dendritic cells and low hepatoxicity. For further clinical use, we constructed two recombinant vectors expressing human immunodeficiency virus 1 (HIV-1) clade C gag (Ad5/35-Cgag and MVA-Cgag). The biodistribution of the two viral vectors in a mouse model and immunity in monkeys were assessed. The mice received a single intramuscular injection with the vectors alone. The gag gene in the tissues were periodically detected using a real-time quantitative polymerase chain reaction. The distribution of Ad5/35 was also detected using an in vivo imaging system, followed by luciferase-expressing Ad5/35 administration. We found that Ad5/35-Cgag DNA and luciferase activity were detectable until 8 weeks post-administration, whereas MVA-Cgag was undetectable 72 h post-administration. Furthermore, viral administration did not increase serum aspartate aminotransferase and alanine aminotransferase levels in either mouse or monkey models. Moreover, intramuscular administration of Ad5/35-Cgag induced the gag-specific antibody level and IFNγ-secreting PBMCs, the boost with MVA-Cgag further increased the responses and lasted more than 20 weeks from the initial administration. These data demonstrate that Ad5/35 and MVA vectors are safe for in vivo use, and prime-boost with Ad5/35-MVA vaccines is suitable for clinical use against HIV-1 clade C.
Assuntos
Vacinas contra a AIDS , Infecções por Adenoviridae , HIV-1 , Vacinas de DNA , Vacínia , Humanos , Camundongos , Animais , HIV-1/genética , Adenoviridae/genética , Vacinas contra a AIDS/genética , Distribuição Tecidual , Vaccinia virus/genética , Vetores Genéticos/genética , Vacinas Sintéticas/genéticaRESUMO
OBJECTIVES: No large-scale registration study has comprehensively evaluated the activities of daily living (ADL) in patients with Behçet's disease. METHODS: The Japanese government provided us with a dataset of confirmed or suspected Behçet's disease cases derived from ongoing national registration. ADL were categorized and analysed into four categories in patients who satisfied the International Criteria for Behçet's Disease. RESULTS: Data from 2960 patients (men 38.9%, women 61.1%; median age 39 years) were assessed. While 1767 patients (59.7%) had normal ADL, the others had impaired ADL comprising limited but not assisted [n = 1058 (35.7%)], partially assisted [n = 116 (3.9%)] and fully assisted [n = 19 (0.6%)]. Logistic regression analysis showed that chronic ocular lesions [odds ratio (OR) 1.85 (95% CI 1.46, 2.35), P < 0.001], paralysis [OR 2.51 (95% CI 1.58, 3.97), P < 0.001], psychosis [OR 3.16 (95% CI 2.02, 4.95), P < 0.001] and arthritis [OR 1.69 (95% CI 1.44, 1.99), P < 0.001] led to the risk of impaired ADL. Chronic ocular lesions [OR 3.61 (95% CI 2.27, 5.72), P < 0.001], paralysis [OR 3.43 (95% CI 1.87, 6.30), P < 0.001] and psychosis [OR 3.60 (95% CI 2.00, 6.50), P < 0.001] were related to the requirement of physical assistance (partially or fully assisted), although arthritis [OR 1.39 (95% CI 0.93, 2.06), P = 0.108] was not a significant factor in this model. CONCLUSION: Ocular lesions, neurological manifestations and arthritis affected ADL. Patients with ocular lesions or neurological manifestations more frequently required physical assistance.
Assuntos
Atividades Cotidianas , Síndrome de Behçet/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: This study aimed to determine the clinical efficacy of apremilast for oral ulcers (OUs), extra-oral manifestations, and overall disease activity in patients with Behçet's disease (BD). METHODS: A systematic literature search was performed in PubMed, Embase, Cochrane Library, and Web of Science Core Collection. Studies assessing the treatment effects of apremilast in BD were included. The odds ratios (ORs) of being symptom-free for individual manifestations and mean difference (MD) of Behçet's Disease Current Activity Form (BDCAF) scores were calculated with 95% confidence intervals (CIs) at 12 and 24 weeks using a random-model meta-analysis. RESULTS: Of 259 screened articles, eight were included. After 12 weeks of apremilast treatment the OR of symptom-free was as followings: OUs, 45.76 (95% CI, 13.23-158.31); genital ulcers, 4.56 (95% CI, 2.47-8.44); erythema nodosum, 3.59 (95% CI, 1.11-11.61); pseudofolliculitis, 2.81 (95% CI, 1.29-6.15); and arthritis, 3.55 (95% CI, 1.71-7.40). Furthermore, BDCAF scores at 12 weeks were significantly reduced (MD=-1.38; -1.78 to -0.99). However, the proportion of oral-ulcer-free patients increased at 24 weeks (OR = 14.88; 4.81 to 46.07). CONCLUSIONS: The currently accumulated data indicate an improvement in mucocutaneous and articular symptoms by short-term apremilast treatment in patients with BD.
Assuntos
Artrite , Síndrome de Behçet , Úlceras Orais , Úlcera Cutânea , Síndrome de Behçet/complicações , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamento farmacológico , Genitália , Humanos , Úlceras Orais/tratamento farmacológico , Úlceras Orais/etiologia , Talidomida/análogos & derivados , ÚlceraRESUMO
Takayasu arteritis (TAK) is a systemic vasculitis with severe complications that affects the aorta and its large branches. HLA-B*52 is an established susceptibility locus to TAK. To date, there are still only a limited number of reports concerning non-HLA susceptibility loci to TAK. We conducted a genome-wide association study (GWAS) and a follow-up study in a total of 633 TAK cases and 5,928 controls. A total of 510,879 SNPs were genotyped, and 5,875,450 SNPs were imputed together with HLA-B*52. Functional annotation of significant loci, enhancer enrichment, and pathway analyses were conducted. We identified four unreported significant loci, namely rs2322599, rs103294, rs17133698, and rs1713450, in PTK2B, LILRA3/LILRB2, DUSP22, and KLHL33, respectively. Two additional significant loci unreported in non-European GWAS were identified, namely HSPA6/FCGR3A and chr21q.22. We found that a single variant associated with the expression of MICB, a ligand for natural killer (NK) cell receptor, could explain the entire association with the HLA-B region. Rs2322599 is strongly associated with the expression of PTK2B Rs103294 risk allele in LILRA3/LILRB2 is known to be a tagging SNP for the deletion of LILRA3, a soluble receptor of HLA class I molecules. We found a significant epistasis effect between HLA-B*52 and rs103294 (P = 1.2 × 10-3). Enhancer enrichment analysis and pathway analysis suggested the involvement of NK cells (P = 8.8 × 10-5, enhancer enrichment). In conclusion, four unreported TAK susceptibility loci and an epistasis effect between LILRA3 and HLA-B*52 were identified. HLA and non-HLA regions suggested a critical role for NK cells in TAK.
Assuntos
Epistasia Genética , Antígeno HLA-B52/genética , Polimorfismo de Nucleotídeo Único , Receptores Imunológicos/genética , Arterite de Takayasu/genética , Estudos de Casos e Controles , Células Cultivadas , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/patologia , Arterite de Takayasu/patologiaRESUMO
OBJECTIVE: To determine the real-world short-term efficacy and safety of apremilast for Behçet's disease (BD). METHODS: The study included patients who received apremilast for refractory oral ulcers in addition to meeting International Study Group criteria for BD or the revised International Criteria for Behçet's Disease. To assess the efficacy of apremilast, Behçet's disease current activity form (BDCAF) and patients' self-perception of their disease activity were monitored for three months. The disease phenotypes, laboratory data, concomitant medication use, and adverse events were also investigated. RESULTS: Fourteen BD patients were included in the study. Concomitant drug use were as follows: colchicine 92.9%, prednisolone 21.4%, immunosuppressants 28.6%, and tumor-necrosis inhibitor 14.3%. Oral ulcers and BDCAF scores at 3 months showed significant improvement compared to baseline. Adverse events during the study were diarrhea (n = 3, 21.4%), nausea (n = 3, 21.4%), music hallucination (n = 1, 7.1%), and branch retinal vein occlusion (n = 1, 7.1%). Apremilast was discontinued in 1 patient (7.1%) due to nausea. CONCLUSION: Significant improvement in oral ulcer and BDCAF with apremilast was confirmed in real-world BD patients after 3 months. The combination of colchicine and apremilast appears to be well tolerated in BD in the short-term.
Assuntos
Síndrome de Behçet/tratamento farmacológico , Úlceras Orais/tratamento farmacológico , Talidomida/análogos & derivados , Adulto , Colchicina/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Estudos Prospectivos , Talidomida/efeitos adversos , Talidomida/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
BACKGROUND: How HLA-A26 modulates Behçet's disease (BD) ocular lesions such as iridocyclitis and retinochorioiditis has not been scrutinized. METHODS: Ministry of Health, Labour and Welfare of Japan provided us a database of BD patients who were registered from 2003 to 2014. We selected patients who satisfied International Criteria for BD and whose data for HLA-A26 was available. RESULTS: Eligible 557 patients consisting of 238 men (42.7%) and 319 women (57.3%), whose median age was 38 years old (interquartile range 29-47) were analyzed. Prevalence of general ocular lesions, iridocyclitis, retinochorioiditis, and chronic lesions were 43.1%, 30.7%, 34.1%, and 17.4%, respectively. The prevalence of ocular lesions was higher among HLA-A26 carriers compared to that among HLA-A26 non-carriers with odds ratio (OR) of 2.5 (95% confidence interval (95% CI) 1.8-3.5, p < .001) for general ocular lesions, OR of 2.5 (95% CI 1.7-3.6, p < .001) for iridocyclitis, OR of 2.8 (95% CI 1.9-4.0, p < .001) for retinochorioiditis, and OR of 2.7 (95% CI 1.7-4.3, p < .001) for 'chronic ocular lesion following iridocyclitis or retinochorioiditis'. The HLA-A26 had a similar impact on ocular lesions between HLA-B51 positive and negative cases (Breslow-Day test, p > .05). However, the HLA-A26 had a larger impact on iridocyclitis for men compared to women (Breslow-Day test, p = .040). The male HLA-A26 carriers had higher risk of iridocyclitis with OR of 3.4 (95% CI 2.0-5.9, p < .001), while the OR for women was 1.5 (95% CI 0.9-2.6, p = .146). CONCLUSION: HLA-A26 carriers had higher risk for iridocyclitis and retinochorioiditis. However, the impact was more prominent for men.
Assuntos
Síndrome de Behçet/genética , Antígenos HLA-A/genética , Antígeno HLA-B51/genética , Adulto , Síndrome de Behçet/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de RiscoRESUMO
PURPOSE: To identify novel susceptibility loci for high myopia. DESIGN: Genome-wide association study (GWAS) followed by replication and meta-analysis. PARTICIPANTS: A total of 14 096 samples from East and Southeast Asian populations (2549 patients with high myopia and 11 547 healthy controls). METHODS: We performed a GWAS in 3269 Japanese individuals (1668 with high myopia and 1601 control participants), followed by replication analysis in a total of 10 827 additional samples (881 with high myopia and 9946 control participants) from Japan, Singapore, and Taiwan. To confirm the biological role of the identified loci in the pathogenesis of high myopia, we performed functional annotation and Gene Ontology (GO) analyses. MAIN OUTCOME MEASURES: We evaluated the association of single nucleotide polymorphisms with high myopia and GO terms enriched among genes identified in the current study. RESULTS: We identified 9 loci with genome-wide significance (P < 5.0 × 10-8). Three loci were previously reported myopia-related loci (ZC3H11B on 1q41, GJD2 on 15q14, and RASGRF1 on 15q25.1), and the other 6 were novel (HIVEP3 on 1p34.2, NFASC/CNTN2 on 1q32.1, CNTN4/CNTN6 on 3p26.3, FRMD4B on 3p14.1, LINC02418 on 12q24.33, and AKAP13 on 15q25.3). The GO analysis revealed a significant role of the nervous system related to synaptic signaling, neuronal development, and Ras/Rho signaling in the pathogenesis of high myopia. CONCLUSIONS: The current study identified 6 novel loci associated with high myopia and demonstrated an important role of the nervous system in the disease pathogenesis. Our findings give new insight into the genetic factors underlying myopia, including high myopia, by connecting previous findings and allowing for a clarified interpretation of the cause and pathophysiologic features of myopia at the molecular level.
Assuntos
Povo Asiático/genética , Loci Gênicos , Predisposição Genética para Doença/genética , Miopia Degenerativa/genética , Doenças do Sistema Nervoso/genética , Polimorfismo de Nucleotídeo Único , Feminino , Estudo de Associação Genômica Ampla , Técnicas de Genotipagem , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Singapura , TaiwanRESUMO
BACKGROUND: Despite the surge in the number of cataract surgeries, there is limited information available regarding the influence of pupil dilation on predicted postoperative refraction and its comparison with recommended various intraocular lens power calculated using the different parameters. We used three different IOL power calculation formulas: Barrett Universal II (Barrett) (5-variable formula), Haigis (3-variable formula), and SRK/T (2-variable formula), in order to investigate the potential effect of pupil dilation on the predicted postoperative refraction (PPR) and recommended intraocular lens (IOL) power calculation. METHODS: This retrospective study included 150 eyes. All variables were measured and calculated using a ZEISS IOL Master 700. The following variables were measured before and after dilation: anterior chamber depth (ACD), lens thickness (LT), white-to-white (WTW). PPR and recommended IOL power were calculated by Barrett, Haigis, and SRK/T IOL calculation formulas. The change in each variable before and after dilation, and the correlations between all changes were analyzed using the Wilcoxon signed-rank test and the Spearman's rank-order correlation test, respectively. RESULTS: The mean absolute change (MAC) in PPR before and after dilation was found to be highest in the Barrett formula. Significant differences were found between each MAC (P < 0.0001). Significant changes were observed before and after dilation in ACD and LT (P < 0.0001), but not in WTW. Using the Barrett and Haigis formulas, there was a significant positive correlation between the change in PPR and change in ACD (P < 0.0001), and a negative correlation between change in PPR and change in LT (P < 0.0001). The correlations were strongest with the Barret formula followed by the Haigis, particularly in terms of LT. Changes in PPR determined by the Barrett formula also demonstrated a significant positive correlation with changes in WTW (P = 0.022). The recommended IOL power determined using Barrett and Haigis changed before and after dilation in 23.3 and 19.3% cases respectively, while SRK/T showed no change. CONCLUSIONS: In terms of PPR and recommended IOL power, pupil dilation influenced mostly the Barrett formula. Given the stronger correlation between the changes in PPR when using Barrett and the changes in ACD, LT, and WTW, changes in ACD, LT, and WTW significantly affect how dilation influences the Barrett formula. Determining how dilation influences each formula and other variables is key to improving the accuracy of IOL calculations.
Assuntos
Lentes Intraoculares , Pupila , Biometria , Humanos , Implante de Lente Intraocular , Óptica e Fotônica , Refração Ocular , Estudos RetrospectivosRESUMO
OBJECTIVES: To evaluate the efficacy of a mydriatic agent for posterior synechiae after phacoemulsification and intraocular lens (IOL) implantation followed by Descemet membrane endothelial keratoplasty (staged DMEK). METHODS: In this prospective study, the outcomes of DMEK with or without mydriasis (0.5% tropicamide and 0.5% phenylephrine hydrochloride [Mydrin-P; Santen, Osaka, Japan]) after the DMEK procedure were analyzed. Patients underwent IOL implantation approximately 4 weeks before DMEK. Six months after DMEK, the iris posterior synechiae severity score was evaluated based on the extent of posterior synechiae affecting the eight areas (45° each) of the pupillary rim (posterior synechiae score; grades 0-8). Best spectacle-corrected visual acuity, central corneal thickness, endothelial cell density, axial length, and the amount of air at the end of the surgery were also evaluated. RESULTS: Fifteen eyes of 15 patients (mydriatic: n=8, control: n=7) were eligible for inclusion. Iris posterior synechiae were detected in all seven eyes (100.0%) in the control group, whereas they were noted in two eyes in the mydriatic group (25%). The mean iris posterior synechiae score was 0.69±1.20 in the mydriatic group and was significantly lower than that in the control group (4.57±0.90; P<0.001). There was no significant difference in other clinical factors. Although the incidence and scores of posterior synechiae in the control group were higher, the incidence was significantly reduced with the use of a mydriatic agent (in the mydriatic group). CONCLUSIONS: Use of a mydriatic agent is an effective measure to prevent postoperative synechiae after DMEK.
Assuntos
Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/efeitos adversos , Doenças da Íris/prevenção & controle , Doenças do Cristalino/prevenção & controle , Midriáticos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/etnologia , Combinação de Medicamentos , Feminino , Humanos , Doenças da Íris/etnologia , Doenças da Íris/etiologia , Japão/epidemiologia , Doenças do Cristalino/etnologia , Doenças do Cristalino/etiologia , Implante de Lente Intraocular , Masculino , Pessoa de Meia-Idade , Facoemulsificação , Fenilefrina/uso terapêutico , Estudos Prospectivos , Aderências Teciduais/etnologia , Aderências Teciduais/etiologia , Aderências Teciduais/prevenção & controle , Tropicamida/uso terapêutico , Acuidade Visual/fisiologiaRESUMO
Objectives: To scrutinize the influence of HLA-B51 to each clinical manifestation of patients with Behçet's disease (BD) using a database of the Ministry of Health, Labour and Welfare of Japan.Methods: The database of newly registered patients with BD was obtained from the Japanese Ministry of Health, Labour and Welfare. Patients who met International Criteria for Behçet's Disease (ICBD) and had data for HLA-B51 were selected and analyzed.Results: Among the 3044 analyzable cases, 1334 (43.8%) were men and 1710 (56.2%) were women; the median age was 38 years (IQR 29-48). HLA-B51 was positive for 1334 (44.5%). Prevalence of selected manifestations was 98.5% for oral ulceration, 85.5% for skin lesion, 42.1% for ocular lesion, 69.1% for genital ulceration, and 29.0% for gastrointestinal symptom. HLA-B51-positive patients had higher risk for ocular lesion (OR 1.59, 95%CI: 1.37-1.84; p < .001) and lower risk for genital ulceration (OR 0.72, 95%CI: 0.62-0.84; p < .001) and gastrointestinal symptom (OR 0.65, 95%CI: 0.55-0.77; p < .001). No significant difference was observed for other organ involvement; oral ulceration, skin lesion, positive pathergy test, arthritis, epididymitis, vascular lesion, or neurological manifestation. Subgroup analyses revealed that HLA-B51 was not related to genital ulceration in the cases with an ICBD score of 6 or higher and that HLA-B51 tended to more largely affect the risk of three manifestations for men compared to that for women.Conclusion: HLA-B51 positive is a risk factor for ocular lesion and vice versa for genital ulceration and gastrointestinal symptoms in patients with Japanese BD.
Assuntos
Artrite/epidemiologia , Síndrome de Behçet/complicações , Gastroenteropatias/epidemiologia , Antígeno HLA-B51/sangue , Úlcera/epidemiologia , Adulto , Síndrome de Behçet/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
Purpose: Lattice degeneration of the retina is a vitreoretinal disorder characterized by a visible fundus lesion that predisposes the patient to retinal detachment. It has been suggested that collagen type II alpha 1 (COL2A1) gene variants may contribute to the development of disorders associated with retinal detachment. Here we investigated whether COL2A1 gene variants were associated with the risk of lattice degeneration of the retina. Methods: We recruited 634 Japanese patients with lattice degeneration of the retina and 1694 Japanese healthy controls. We genotyped 13 tagging single-nucleotide polymorphisms (SNPs) in COL2A1. We also performed imputation analysis to evaluate the potential association of un-genotyped COL2A1 SNPs, involving the imputation of 65 SNPs. Results: Two intronic SNPs-rs1793954 and rs1635533-were significantly associated with lattice degeneration of the retina. The SNP rs1793954 showed the strongest association, with its C allele carrying an increased disease risk (p = 0.0016, corrected p = 0.021, OR = 1.25). The rs1793954 and rs1635533 SNPs were in strong linkage disequilibrium with each other (r 2 = 0.99), and conditional analysis revealed that rs1793954 could account for the association between rs1635533 and the disease. Conclusions: Our results suggested that COL2A1 gene variants may contribute to the development of lattice degeneration of the retina. Further genetic and functional analyses of COL2A1 variants are needed to clarify the present findings.
Assuntos
Povo Asiático/genética , Colágeno Tipo II/genética , Predisposição Genética para Doença , Mutação/genética , Degeneração Retiniana/genética , Alelos , Humanos , Japão , Desequilíbrio de Ligação/genética , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
BACKGROUND: To evaluate the clinical outcomes and features of Descemet's membrane endothelial keratoplasty (DMEK) for eyes with pseudoexfoliation syndrome (PEX). METHODS: In this retrospective study, 37 DMEK cases were reviewed from available medical records. Patients who exhibited endothelial dysfunction derived from PEX or Fuchs endothelial corneal dystrophy (FECD) and successfully underwent cataract surgery about four weeks before DMEK were enrolled. The best spectacle-corrected visual acuity (BSCVA), central corneal thickness (CCT), endothelial cell density (ECD), and incidence of intra-operative/post-operative complications of DMEK were analyzed. RESULTS: This study included 14 eyes of 14 patients (PEX: n = 6, FECD: n = 8). There was no primary graft failure. In the PEX group, BSCVA improved from 0.67 ± 0.28 at the preoperative point to 0.43 ± 0.14 at 1 month, 0.27 ± 0.10 at 3 months, and 0.19 ± 0.08 at 6 months after DMEK. The donor corneal ECD was 2704 ± 225 cells/mm2 at the preoperative point and decreased to 1691 ± 498 cells/mm2 at 1 month, 1425 ± 366 cells/mm2 at 3 months, and 1281 ± 340 cells/mm2 (52.7 ± 11.7% less than ECD of the donor graft) at 6 months after DMEK. None of the patients required rebubbling. When compared with the FECD group, no statistical difference was observed in CCT (p = 0.821); BSCVA (p = 0.001) and the reduction rate of ECD (p = 0.010) were relatively worse. CONCLUSIONS: DMEK is effective for the treatment of endothelial dysfunction due to PEX.
Assuntos
Lâmina Limitante Posterior/cirurgia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Síndrome de Exfoliação/cirurgia , Distrofia Endotelial de Fuchs/cirurgia , Idoso , Idoso de 80 Anos ou mais , Perda de Células Endoteliais da Córnea/patologia , Endotélio Corneano/patologia , Feminino , Humanos , Masculino , Análise de Regressão , Estudos Retrospectivos , Acuidade Visual/fisiologiaRESUMO
OBJECTIVES: This study aimed to identify patients with high-probability of ocular involvement of Behçet's disease (BD). METHODS: The Japanese Ministry of Health, Labour and Welfare provided dataset of ongoing nationwide BD registration project. A patient who had confirmed BD and who was suspected to have BD was registered. We mainly analyzed newly registered patients who had the data for all demographic and diagnostic parameters regardless of fulfilment of any diagnostic criteria. RESULTS: Among 3213 patients with confirmed or possible BD, 1382 (43.0%) were men and 1831 (57.0%) were women with a median age of 38 years (interquartile range (IQR) 30-49 years). The median duration between onset and registration was 0 year (IQR 0-3). A binomial multivariable logistic regression analysis revealed that being female (odds ratio (OR) 0.63, 95% confidence interval (CI) 0.53-0.75, p < .001), duration since onset (OR 1.33 per 10 years, 95% CI 1.18-1.51, p < .001), genital ulceration (OR 0.28, 95% CI 0.23-0.34, p < .001), and gastrointestinal symptoms (OR 0.36, 95% CI 0.30-0.44, p < .001) were related to the ocular lesion. Analyses based on data of 2800 patients who satisfied International criteria of BD, age-, sex-, duration-based subgroup analyses, analyses targeting iridocyclitis and retino-uveitis, and analysis including patients with missing data confirmed that the four factors were associated with the probability of eye involvement. CONCLUSION: The ocular involvement did not accompany with genital ulcer or gastrointestinal symptoms at the early stage of BD.
Assuntos
Síndrome de Behçet , Gastroenteropatias , Genitália , Úlcera , Uveíte , Adulto , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/epidemiologia , Síndrome de Behçet/fisiopatologia , Correlação de Dados , Feminino , Gastroenteropatias/diagnóstico , Gastroenteropatias/etiologia , Humanos , Japão/epidemiologia , Masculino , Razão de Chances , Sistema de Registros/estatística & dados numéricos , Fatores Sexuais , Úlcera/diagnóstico , Úlcera/etiologia , Uveíte/diagnóstico , Uveíte/epidemiologia , Uveíte/etiologiaRESUMO
Background: Clinical data of patients with entro-, vasculo-, and neuro-variant possible Behçet's disease (BD) based on Japanese criteria has not yet comprehensively reported. Methods: This ongoing nation-wide registration has been carried out by the Japanese Ministry of Health, Labour and Welfare. The Ministry asked physicians who diagnosed a patient with confirmed or possible BD to register the patient data by filling out a registration form. The Ministry provided us with the dataset after unlinkable anonymization. We analyzed 2003-2014 database generated from the early stage new cases. Results: Among the 7950 analyzable cases, 694 (8.7%) had variant-type possible BD without satisfying complete/incomplete criteria. Of the 694 patients, 479, 46, and 169 had entero-, vasculo-, and neuro-variant possible BD, respectively. Out of these 694 patients, 35 (5.0%) and 154 (22.2%) satisfied the International Study Group criteria and the International Criteria of BD, respectively. Entero-variant possible patients rarely (1.8%) had ocular lesions. Patients with vasculo-variant possible BD were featured by low genital ulceration risk (6.8%) and frequent positive HLA-B51 (60.0%). Neuro-variant possible BD was featured by high median age at registration (48 year). Vasculo- (69.6%) and neuro-variant (68.6%) BD patients showed clear male dominance. Epididymitis was very rare among variant-type possible BD men. Conclusion: We analyzed 694 early-stage variant-type possible BD cases. We believe the data from our study will contribute to further international discussion regarding BD diagnostic criteria and clarification of the clinical presentations of the Japanese variant-type possible BD patients.
Assuntos
Síndrome de Behçet/patologia , Adulto , Síndrome de Behçet/epidemiologia , Bases de Dados Factuais , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: Sarcoidosis is a major cause of granulomatous uveitis but rarely manifests as multiple choroidal granulomas. This report describes the use of enhanced depth imaging optical coherence tomography (EDI-OCT) to visualize changes occurring in multiple choroidal granulomas during treatment. METHODS: The patient was a 36-year-old Japanese man with histopathologically confirmed sarcoidosis, who was examined using EDI-OCT and showed multiple yellowish-white subretinal lesions in the peripapillary region and the arcade of the right eye. RESULTS: EDI-OCT revealed homogeneous hyporeflective choroidal lesions with choriocapillaris thinning, consistent with a diagnosis of choroidal granulomas. Subretinal fluid adjacent to one of the peripapillary choroidal lesions was also apparent. EDI-OCT during oral prednisolone administration revealed a decrease in lesion size at as early as 3 weeks and complete resolution of the lesions after 6 months of treatment. However, 2 months after prednisolone discontinuation, EDI-OCT revealed recurrence of choroidal granulomas in the peripapillary region and the arcade of the right eye. After injection of triamcinolone acetonide into the posterior sub-Tenon's capsule (sub-Tenon's injection), EDI-OCT demonstrated a reduction in granuloma lesion size within 3 months of the injection. CONCLUSION: EDI-OCT allowed detailed morphologic visualization of the choroidal granulomas caused by sarcoidosis. This imaging technique was useful for monitoring changes in granuloma size in response to steroid administration and for early detection of recurrence. Injection of triamcinolone acetonide into the posterior sub-Tenon's capsule was as effective as oral prednisolone for the treatment of choroidal granulomas.
Assuntos
Doenças da Coroide/diagnóstico , Granuloma/diagnóstico por imagem , Sarcoidose/complicações , Adulto , Corioide/patologia , Doenças da Coroide/tratamento farmacológico , Granuloma/tratamento farmacológico , Humanos , Masculino , Tomografia de Coerência Óptica/métodos , Triancinolona Acetonida/administração & dosagemRESUMO
Objective: This report aimed to scrutinize the prevalence of Behçet's disease (BD)-related clinical manifestations based on age- and sex-specific subgroups using a Japanese nationwide registration database. Methods: The database of newly registered BD was obtained from the Japanese Ministry of Health, Labour and Welfare. Patients who met the International Criteria for Behçet's Disease were selected and analysed. Results: Among 6627 International Criteria for Behçet's Disease cases, 2651 (40.0%) were men and 3976 (60.0%) were women with a median age of 39 years (interquartile range: 31-50 years). Ocular lesion was more common in male [odds ratio (male: female) 2.64 (95% CI: 2.35, 2.95, P < 0.001)] and genital ulceration was more common in female (odds ratio = 0.29, 95% CI: 0.25, 0.32, P < 0.001). Ocular lesion (P < 0.001), arthritis (P < 0.001) and vascular lesions (P < 0.001) were more frequently observed in elderly registered patients. Contrarily, genital ulceration (P < 0.001), epididymitis of males (P = 0.023) and oral ulceration (P = 0.003) were more common in younger patients. Simultaneous assessment of sex and age revealed that male predominance of ocular involvement was found in the young adult generation, but not in patients over 70 year of age. A female predominance of genital ulcer was prominently observed in patients 20-59 year of age; however, the sex difference was not found in patients over 60 years of age. Sensitivity analysis using International Study Group criteria replicated the results. Conclusion: We showed that clinical phenotype in early phase of BD was different depending on onset age and sex.
Assuntos
Síndrome de Behçet/fisiopatologia , Sistema de Registros , Adolescente , Adulto , Fatores Etários , Idoso , Artrite/etiologia , Artrite/fisiopatologia , Síndrome de Behçet/complicações , Síndrome de Behçet/genética , Criança , Bases de Dados Factuais , Epididimite/etiologia , Epididimite/fisiopatologia , Oftalmopatias/etiologia , Oftalmopatias/fisiopatologia , Feminino , Gastroenteropatias/etiologia , Gastroenteropatias/fisiopatologia , Doenças dos Genitais Femininos/etiologia , Doenças dos Genitais Femininos/fisiopatologia , Doenças dos Genitais Masculinos/etiologia , Doenças dos Genitais Masculinos/fisiopatologia , Antígeno HLA-B51/genética , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/fisiopatologia , Razão de Chances , Úlceras Orais/etiologia , Úlceras Orais/fisiopatologia , Fenótipo , Fatores Sexuais , Úlcera Cutânea/etiologia , Úlcera Cutânea/fisiopatologia , Doenças Vasculares/etiologia , Doenças Vasculares/fisiopatologia , Adulto JovemRESUMO
We here describe three different clinical manifestations of tubulointerstitial nephritis and uveitis (TINU) syndrome. We examined and diagnosed the following 3 patients: a 15-year-old boy with bilateral anterior uveitis (Case 1), a 14-year-old girl with bilateral papilledema (Case 2), and a 49-year-old woman with panuveitis (Case 3). The findings are presented herein. Case 1: The patient had bilateral anterior uveitis. Urinalysis revealed markedly increased ß2-microglobulin and N-acetyl-ß-D-glucosaminidase levels. As the patient was pathologically diagnosed with tubulointerstitial nephritis (TIN), we diagnosed TINU based on the presence of both uveitis and TIN. He was treated with oral corticosteroids. Case 2: This patient showed anterior uveitis and papilledema in both eyes. On initial examination, the urine test results did not show any abnormality. Three months later, high ß2-microglobulin and N-acetyl-ß-D-glucosaminidase levels were detected. As the patient was clinically diagnosed with TIN, we subsequently diagnosed TINU. Both the ocular and renal findings improved without treatment. Case 3: The patient developed bilateral panuveitis, retinal vasculitis, and macular edema, which were initially suspected to be sarcoidosis. However, she was pathologically diagnosed with TIN 12 months before the onset of uveitis; therefore, she was finally diagnosed with TINU. She recovered with local corticosteroid administration only. TINU may present with fundal features in addition to anterior uveitis. Detailed history taking and urinalysis are important to determine the presence of tubular disorders in similar patients.