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1.
Ophthalmol Ther ; 13(6): 1743-1755, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38662192

RESUMO

INTRODUCTION: Dry eye can compromise corneal astigmatism measurement repeatability during preoperative cataract surgery examination. No previous studies have analyzed the effectiveness of long-acting 3% diquafosol sodium (LA-DQS) on astigmatism measurement repeatability. This research assessed the effect of LA-DQS on astigmatism measurement repeatability in preoperative patients with cataract and short tear break-up time (TBUT) type dry eyes in both eyes of the same patient. Correlations between repeatability and TBUT, corneal high-order aberrations (HOAs), and corneal astigmatism magnitude were also analyzed. METHODS: In total, 122 eyes (61 patients) with short TBUT-type dry eye were enrolled. Preoperatively, only one eye of all patients was treated with LA-DQS for 4 weeks. TBUT and corneal HOAs were checked using CASIA 2 before and 4 weeks post-treatment. The cylindrical power and meridian of astigmatism were measured at 3- and 4-week post-treatment using IOLMaster 700. Power vectors J0 and J45 were used for astigmatism calculations. Repeatability of astigmatism measurements was assessed as the within-subject standard deviation (Sw). The relative effects of TBUT and HOAs on J0 Sw and J45 Sw were also analyzed. Comparative changes in these variables were evaluated between treated and non-treated eyes, with additional analysis of their correlations. RESULTS: Treated eyes exhibited significant improvements in TBUT, HOAs, and post-treatment measurements of J0 Sw and J45 Sw at 3 and 4 weeks. In non-treated eyes, J0 Sw and J45 Sw showed significant correlation with TBUT and corneal HOAs. HOAs showed stronger relative associations with J0 Sw and J45 Sw than TBUT. In non-treated eyes, no significant correlation was found between cylindrical power and astigmatism measurement repeatability. CONCLUSIONS: In short TBUT-type dry eye, preoperative treatment with LA-DQS significantly improved astigmatism measurement repeatability. This may improve the precision of intraocular lens (IOL) power calculations regardless of the magnitude of corneal astigmatism, especially when toric IOLs are used.

2.
Front Immunol ; 15: 1354969, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38686380

RESUMO

Background: Little is known about the relationship between the disease activity of Behçet disease (BD) and the incidence of inflammatory major organ events. Objectives: In this prospective registry study, we investigated the association between the Behçet Disease Current Activity Form (BDCAF) and incidence of inflammatory major organ events, defined as the inflammation of the ocular, central nervous, intestinal, and vascular systems in BD. Methods: We enrolled participants from Japanese multicenter prospective cohorts. The BDCAF was evaluated annually. BD-related symptoms, including inflammatory major organ events, were monitored. The association between BDCAF and inflammatory major organ events was analyzed by time-to-event analysis. An unsupervised clustering of the participants' BDCAF, therapeutic agents, and multiple serum cytokines was also performed to examine their association with inflammatory major organ events. Results: A total of 260 patients were included. The patients had a median BDCAF score of 2 [Interquartile range, 1-3] at the enrolment and remained disease active at 1- and 2-year follow-ups, indicating residual disease activity in BD. Patients with a BDCAF score of 0 had a longer inflammatory major organ event-free survival at 52 weeks than those with a score of 1 or higher (p=2.2 x 10-4). Clustering analysis revealed that patients who did not achieve remission despite treatment with tumor necrosis factor inhibitors had high serum inflammatory cytokine levels and incidences of inflammatory major organ events. Among the elevated cytokines, IL-6 was associated with inflammatory major organ events. Conclusion: This study suggests that treatment strategies targeting overall disease activity and monitoring residual serum IL-6 may help prevent inflammatory major organ events in BD.


Assuntos
Síndrome de Behçet , Interleucina-6 , Sistema de Registros , Síndrome de Behçet/sangue , Síndrome de Behçet/epidemiologia , Humanos , Masculino , Feminino , Interleucina-6/sangue , Adulto , Estudos Prospectivos , Incidência , Pessoa de Meia-Idade , Inflamação/sangue , Biomarcadores/sangue , Japão/epidemiologia , Índice de Gravidade de Doença
3.
Dig Liver Dis ; 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37977914

RESUMO

BACKGROUND: Intestinal involvement in Behçet's disease (BD) is associated with poor prognosis and is more prevalent in East Asian than in Mediterranean populations. Identifying the genetic causes of intestinal BD is important for understanding the pathogenesis and for appropriate treatment of BD patients. METHODS: We performed genome-wide association studies (GWAS) and imputation/replication genotyping of human leukocyte antigen (HLA) alleles for 1,689 Korean and Turkish patients with BD (including 379 patients with intestinal BD) and 2,327 healthy controls, followed by replication using 593 Japanese patients with BD (101 patients with intestinal BD) and 737 healthy controls. Stratified cross-phenotype analyses were performed for 1) overall BD, 2) intestinal BD, and 3) intestinal BD without association of overall BD. RESULTS: We identified three novel genome-wide significant susceptibility loci including NPHP4 (rs74566205; P=1.36 × 10-8), TYW1-AUTS2 (rs60021986; P=1.14 × 10-9), and SEMA6D (rs4143322; P=5.54 × 10-9) for overall BD, and a new association with HLA-B*46:01 for intestinal BD (P=1.67 × 10-8) but not for BD without intestinal involvement. HLA peptide binding analysis revealed that Mycobacterial peptides, have a stronger binding affinity to HLA-B*46:01 compared to the known risk allele HLA-B*51:01. CONCLUSIONS: HLA-B*46:01 is associated with the development of intestinal BD; NPHP4, TYW1-AUTS2, and SEMA6D are susceptibility loci for overall BD.

4.
Sci Rep ; 13(1): 16075, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37752244

RESUMO

Corneal astigmatism is reportedly associated with polymorphisms of the platelet-derived growth factor receptor alpha (PDGFRA) gene region in Asian populations of Chinese, Malay, and Indian ancestry and populations of European ancestry. In this study, we investigated whether these PDGFRA polymorphisms are associated with corneal astigmatism in a Japanese population. We recruited 1,535 cases with corneal astigmatism (mean corneal cylinder power across both eyes: ≤ - 0.75 diopters [D]) and 842 controls (> - 0.75 D) to genotype 13 single-nucleotide polymorphisms (SNPs) in the PDGFRA gene region. We also performed imputation analysis in the region, with 179 imputed SNPs included in the statistical analyses. The PDGFRA SNPs were not significantly associated with the cases with corneal astigmatism ≤ - 0.75 D. However, the odds ratios (ORs) of the minor alleles of SNPs in the upstream region of PDGFRA, including rs7673984, rs4864857, and rs11133315, tended to increase according to the degree of corneal astigmatism, and these SNPs were significantly associated with the cases with corneal astigmatism ≤ - 1.25 D or ≤ - 1.50 D (Pc < 0.05, OR = 1.34-1.39). These results suggest that PDGFRA SNPs play a potential role in the development of greater corneal astigmatism.


Assuntos
Astigmatismo , Doenças da Córnea , Receptor alfa de Fator de Crescimento Derivado de Plaquetas , Humanos , Astigmatismo/genética , Córnea/patologia , Doenças da Córnea/genética , Topografia da Córnea , População do Leste Asiático , Polimorfismo de Nucleotídeo Único , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética
5.
Sci Rep ; 13(1): 13580, 2023 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-37604934

RESUMO

Immune checkpoint inhibitors (ICIs) activate anti-tumor activity by inhibiting immune checkpoint molecules that suppress inflammatory T-cell activity. However, ICIs can initiate excessive immune responses, thereby causing immune-related adverse events (irAEs). ICI-associated uveitis (ICIU) is an irAE that affects the eyes. Although Vogt-Koyanagi-Harada disease (VKH)-like uveitis is a common form of ICIU, it is unclear which factors determine the ICIU form. We retrospectively reviewed the medical records of nine ICIU cases treated with ICIs for malignancies. We also performed HLA typing in seven cases to investigate the association between HLA and disease type. Fisher's exact test was used for the statistical analysis. Five of the ICIU cases were VKH-like ICIUs, and four were non-VKH-like ICIUs. No association was found between mean age, sex, primary disease, ICI, time to onset, and disease type. Four patients with VKH-like uveitis underwent HLA genotyping and were all positive for HLA-DRB1*04:05. All 3 patients with non-VKH-like uveitis were negative for HLA-DRB1*04:05. Statistical analysis showed that HLA-DRB1*04:05 was significantly associated with developing VKH-like ICIU (P = 0.029). In ICIU, HLA-DRB1*04:05 was associated with the pathogenesis of VKH-like uveitis, suggesting that ICI-associated VKH-like uveitis has a similar pathogenesis to VKH.


Assuntos
Cadeias HLA-DRB1 , Síndrome Uveomeningoencefálica , Humanos , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB1/metabolismo , Inibidores de Checkpoint Imunológico , Estudos Retrospectivos , Síndrome Uveomeningoencefálica/induzido quimicamente , Síndrome Uveomeningoencefálica/genética
6.
Ophthalmol Ther ; 12(5): 2621-2630, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37466812

RESUMO

INTRODUCTION: Although uncommon, incomplete capsulotomy, anterior capsule tags and anterior capsule tears are still encountered during femtosecond laser-assisted cataract surgery (FLACS), resulting in surgical complications. This highlights the need to improve femtosecond laser-assisted capsulotomy technique to reduce capsulotomy-related complications. Therefore, the purpose of this study was to investigate the efficacy of a newly developed, modified technique of setting capsulotomy irradiation thickness in lowering the incidence of capsulotomy-related complications in FLACS. METHODS: This open-label prospective, comparative cohort study included 440 eyes (220 patients) treated with FLACS using the LenSx laser system (Alcon Laboratories, Inc. Fort Worth, TX, USA). Varying capsulotomy irradiation thicknesses were applied in each eye of the same patient. In Group 1, capsulotomy irradiation thickness was set between the upper edge of the highest point of the anterior capsule and the lower edge of the lowest point of the anterior capsule (modified technique). In Group 2, this was set between the center of the highest point of the anterior capsule and the center of the lowest part of the anterior capsule (conventional technique). Incidence rates of incomplete capsulotomy, anterior capsule tags and tears, and posterior capsule tears were compared. RESULTS: Preoperative baseline characteristics showed no significant differences. Mean total of the irradiation thicknesses was 877.1 ± 81.9 µm in Group 1 and 808.9 ± 80.0 in Group 2, with a statistically significant difference (P < 0.001). Incidences of incomplete capsulotomy were 1.8% and 7.7%, anterior capsule tags were 2.3% and 8.6%, and anterior capsule tears were 0% and 3.2% in Groups 1 and 2, respectively. These differences were statistically significant (P = 0.006, 0.005, and 0.015, respectively). No posterior capsule tears were reported in either group. CONCLUSION: The modified technique for capsulotomy in FLACS may significantly reduce the occurrence of capsulotomy-related complications, maximizing the benefits of FLACS.

7.
Ocul Immunol Inflamm ; : 1-7, 2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-37133403

RESUMO

PURPOSE: To investigate whether polymorphisms of GAS6 and PROS1, which each encode protein ligands for a family of tyrosine kinase receptors, are associated with Behçet's disease (BD) in a Japanese population. METHODS: We recruited 734 Japanese patients with BD and 1789 Japanese healthy controls. In all participants, we genotyped two single-nucleotide polymorphisms (SNPs) reportedly associated with BD: rs9577873 in GAS6 and rs4857037 in PROS1. RESULTS: We found that GAS6 rs9577873 was not significantly associated with BD. In contrast, PROS1 rs4857037, specifically the A allele, was associated with increased risk for BD. The A allele was also significantly associated with BD under additive and recessive genetic models. Expression analysis revealed that this allele was significantly associated with increased PROS1 expression. CONCLUSIONS: Our findings suggest that increased PROS1 expression related to the A risk allele of rs4857037 affects tyrosine kinase receptor signaling, contributing to the development of BD.

8.
BMC Ophthalmol ; 23(1): 19, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36631785

RESUMO

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 , Lasers
9.
Rheumatology (Oxford) ; 62(4): 1451-1459, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-36069626

RESUMO

OBJECTIVES: With the increased use of immune checkpoint inhibitors (ICIs) in cancer patients, arthralgia has been the most commonly reported musculoskeletal immune-related adverse event (irAE). We aimed to characterize arthralgia and its association with overall survival (OS). MATERIAL AND METHODS: Randomized controlled trials (RCTs) reporting on data for ICI-induced arthralgia from four online databases were comprehensively investigated. Odds ratios (ORs) with 95% CIs were calculated for arthralgia using a random-effects model meta-analysis. Individual patient data were reconstructed from RCTs assessing OS in patients with or without ICI-induced arthralgia. We also retrospectively collected data on the clinical features and outcomes of ICI-induced arthralgia in the Yokohama City University (YCU) registry. RESULTS: We analysed 14 377 patients from 24 RCTs. The OR of ICI-induced arthralgia was 1.37 (95% CI 1.20, 1.56). Of the 369 patients in the YCU registry, 50 (13.6%) developed ICI-induced arthralgia. Among them, 30 had other grade ≥2 irAEs, which was noticeably more frequent than in those without arthralgia (OR 1.92, 95% CI 1.04, 3.52). By irAE types, a significant difference was found for relative adrenal insufficiency (OR 3.88, 95% CI 1.80, 8.39). In the YCU registry, patients with (vs without) ICI-induced arthralgia had better OS (log-rank, P < 0.001). OS results were validated from RCT patients with matched cancer types, drugs, and time to arthralgia onset (hazard ratio 0.34, 95% CI 0.17, 0.65, P < 0.001). CONCLUSIONS: If arthralgia develops after ICIs, another irAE, such as relative adrenal insufficiency, may have developed. The incidence of arthralgia was associated with better OS, and the condition of patients with irAEs must be carefully evaluated to determine optimal management.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Artralgia/induzido quimicamente , Coleta de Dados , Bases de Dados Factuais , Neoplasias/tratamento farmacológico
10.
Ophthalmol Ther ; 11(4): 1479-1491, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35588046

RESUMO

INTRODUCTION: The present study aimed to compare the effects of rebamipide and artificial tears during the perioperative period of cataract surgery on the postoperative visual outcomes. METHODS: Seventy-two eyes from 36 patients with a cataract were enrolled. Rebamipide (group R) was administered in one eye and Mytear® artificial tear ophthalmic solution (group A) in the other eye from 4 weeks preoperatively to 3 months postoperatively. Tear breakup time (TBUT), high-order aberrations (HOAs), superficial punctate keratopathy in the central part of the cornea (C-SPK), and corrected distance visual acuity (CDVA) were assessed at baseline, 1 week, 1 month, and 3 months after cataract surgery with trifocal intraocular lens (IOL) implantation. Contrast sensitivity and disability glare with visual angle values compatible with spatial frequencies of 1.1, 1.8, 2.9, 4.5, 7.1, and 10.2 cycles/degree (CPD) were evaluated postoperatively. Between-group differences of all variables were analyzed. RESULTS: At baseline, no significant differences in the variables were noted between the two groups. Mean TBUT was significantly higher, while mean C-SPK and HOAs were significantly lower in group R than in group A at each assessment. Mean CDVA was significantly higher at 1 week and 1 month postoperatively in group R compared with group A; this value was not significant at 3 months. Between-group differences in contrast sensitivity and disability glare were statistically significant at all spatial frequencies, 1 week and 1 month postoperatively. At 3 months postoperatively, there were significant differences in contrast sensitivity and disability glare at most spatial frequencies. CONCLUSION: Dry eye management with rebamipide in the perioperative period of cataract surgery with trifocal IOL implantation was significantly more effective than artificial tears in improving ocular surface condition, contrast sensitivity, and disability glare postoperatively.

11.
Gene ; 820: 146212, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35143941

RESUMO

BACKGROUND: IgG4-related disease (IgG4-RD) is an immune-mediated disorder characterized by high serum IgG4 concentration and IgG4-bearing plasma cell infiltration in affected organs. IgG4-related periaortitis/periarteritis is a recently identified disease entity in IgG4-RD that affects the cardiovascular system. Since the genetic factors related to disease onset are unclear, we examined the genetic associations with IgG4-related periaortitis/periarteritis susceptibility. METHODS: A small scale of genome-wide association analysis identified that interleukin 1 receptor type 1 (IL1R1) gene variants were correlated with the development of IgG4-related periaortitis/periarteritis in 75 patients with IgG4-RD. Accordingly, 8 single nucleotide polymorphisms (SNPs) in the IL1R1 gene were selected and genotyped in 124 patients with IgG4-RD (43 with periaortitis/periarteritis and 81 without periaortitis/periarteritis) and 344 healthy subjects. RESULTS: The minor allele frequencies of 6 SNPs (rs2287049, rs3917273, rs2160227, rs951192, rs3917318, rs7582198) were significantly increased in IgG4-related periaortitis/periarteritis patients compared with those without periaortitis/periarteritis (corrected P < 0.05). In addition, the frequency of the AGAAA haplotype, comprised of 5 SNPs (rs3917273, rs2160227, rs951192, rs3917318, rs7582198), was significantly higher in patients with periaortitis/periarteritis (OR = 2.41, 95% CI:1.42-4.10). CONCLUSION: Our findings indicated that IL1R1 genetic polymorphisms contributed to IgG4-related periaortitis/periarteritis and the possibility of certain genetic factors influencing the risk of specific IgG4-RD manifestations.


Assuntos
Arterite/genética , Doença Relacionada a Imunoglobulina G4/genética , Polimorfismo de Nucleotídeo Único , Receptores Tipo I de Interleucina-1/genética , Fibrose Retroperitoneal/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Suscetibilidade a Doenças , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Imunoglobulina G/sangue , Inflamação , Masculino , Pessoa de Meia-Idade
12.
Sci Rep ; 12(1): 2879, 2022 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-35190604

RESUMO

Refractive changes are reportedly affected by age, sex, and current refractive error. To clarify the pattern of refractive changes in a Japanese population, we conducted a 5-year follow-up longitudinal analysis of spherical equivalent (SE) refractive changes with stratification by sex, age, and SE in 593,273 eyes from Japanese individuals ages 3-91 years. The 5-year SE change with myopic shift dramatically increased over time after age 4 years, and the largest change was observed in both males and females who were age 8 years at baseline [males: - 2.654 ± 0.048 diopters (D); females: - 3.110 ± 0.038 D]. During school age, the 5-year myopic change was greater in females than in males, and emmetropic and low-to-moderate myopic eyes underwent larger myopic changes than hyperopic and high-to-severe myopic eyes. After the peak at age 8 years, the 5-year myopic change gradually declined with age and fell below - 0.25 D at age 27 in males and age 26 years in females. The 5-year SE changes transitioned from a myopic to a hyperopic shift at age 51 in both sexes, and hyperopization advanced more quickly in hyperopic eyes. Our findings highlight the importance of myopia prevention in school-aged children.


Assuntos
Erros de Refração/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Miopia/prevenção & controle , Refração Ocular , Erros de Refração/fisiopatologia , Fatores Sexuais , Fatores de Tempo , Adulto Jovem
13.
Ophthalmol Ther ; 11(2): 603-611, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35064909

RESUMO

INTRODUCTION: Refractive accuracy is crucial for increasing patient satisfaction after cataract surgery. Tear film instability caused by dry eye can lead to inaccurate measurement of corneal power, which is one of the most important factors for postoperative refractive calculation. This study investigated the effect of 2% rebamipide ophthalmic suspension on the predicted refractive accuracy for cataract surgery in patients with dry eye. METHODS: This single-center, prospective, open-label study included 35 dry eyes (with tear breakup time < 5 s) who underwent cataract surgery. The patients were treated with rebamipide for 4 weeks before the preoperative examination. In addition to the usual evaluation of biometric variables essential for cataract surgery, tear breakup time (TBUT), superficial punctate keratopathy in the central part of the cornea (C-SPK), corneal higher-order aberrations (HOAs), and predicted postoperative spherical equivalent (P-SE) were evaluated at baseline and 4 weeks after dry eye treatment. The patients' subjective spherical equivalent (S-SE) was evaluated 1 month postoperatively. The difference between S-SE and P-SE was used to assess the accuracy of the P-SE. Improvement in TBUT, C-SPK, HOA, and the accuracy of P-SE after dry eye treatment were analyzed. RESULTS: The accuracy of the biometry readings for the achieved P-SE was within 0.25 D in 42.9% and 54.3%; within 0.5 D in 71.4% and 88.6%; and within 0.75 D in 88.6% and 97.1% of eyes before and after rebamipide treatment, respectively (p < 0.01). TBUT, C-SPK, and HOAs significantly improved after rebamipide treatment (p < 0.01). CONCLUSION: Rebamipide significantly improved the corneal surface condition and accuracy of the predicted postoperative refraction in dry eyes.

14.
Int Rev Immunol ; 41(2): 84-106, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33258398

RESUMO

Behçet's disease (BD) is a systemic and inflammatory disease, characterized mainly by recurrent oral and genital ulcers, eye involvement, and skin lesions. Although the exact etiopathogenesis of BD remains unrevealed, a bulk of studies have implicated the genetic contributing factors as critical players in disease predisposition. In countries along the Silk Road, human leukocyte antigen (HLA)-B51 has been reported as the strongest genetically associated factor for BD. Genome-wide association studies, local genetic polymorphism studies, and meta-analysis of combined data from Turkish, Iranian, and Japanese populations have also identified new genetic associations with BD. Among these, other HLA alleles such as HLA-B*15, HLA-B*27, HLA-B*57, and HLA-A*26 have been found as independent risk factors for BD, whereas HLA-B*49 and HLA-A*03 are independent protective alleles for BD. Moreover, other genes have also reached the genome-wide significance level of association with BD susceptibility, including IL10, IL23R-IL12RB2, IL12A, CCR1-CCR3, STAT4, TNFAIP3, ERAP1, KLRC4, and FUT2. Also, several rare nonsynonymous variants in TLR4, IL23R, NOD2, and MEFV genes have been reported to be involved in BD pathogenesis. According to genetic determinants in the loci outside the MHC region that are contributed to the host defense, immunity, and inflammation pathways, it is suggested that immune responses to the pathogen as an important environmental factor and mucosal immunity contribute to BD susceptibility.


Assuntos
Síndrome de Behçet , Aminopeptidases/genética , Síndrome de Behçet/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígeno HLA-B51/genética , Humanos , Irã (Geográfico) , Antígenos de Histocompatibilidade Menor , Pirina/genética
15.
Arthritis Rheumatol ; 74(4): 671-681, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34652073

RESUMO

OBJECTIVE: To explore susceptibility loci associated with uveitis in Behçet's disease (BD). METHODS: We conducted a 2-stage study, consisting of a genome-wide association study (GWAS) stage and a replication stage, in a Chinese population. The GWAS stage included 978 cases with BD-related uveitis and 4,388 controls, and the replication stage included 953 cases with BD-related uveitis and 2,129 controls. Luciferase reporter analysis and chromatin immunoprecipitation assay were performed to explore the functional role of susceptibility genetic variants near ZMIZ1. RESULTS: Three independent HLA alleles (HLA-B51 [3.75 × 10-190 ], HLA-A26 [1.50 × 10-18 ], and HLA-C0704 [3.44 × 10-16 ]) were identified as having a genome-wide association with BD-related uveitis. In the non-HLA region, in addition to confirming 7 previously reported loci, we identified 22 novel susceptibility variants located in 16 loci. Meta-analysis of the Chinese cohort consisting of 1,931 cases and 6,517 controls and a published Japanese cohort of 611 cases and 737 controls showed genome-wide significant associations with ZMIZ1, RPS6KA4, IL10RA, SIPA1-FIBP-FOSL1, and VAMP1. Functional experiments demonstrated that genetic variants of ZMIZ1 were associated with enhanced transcription activity and increased expression of ZMIZ1. CONCLUSION: This GWAS study identified a novel set of genetic variants that are associated with susceptibility to uveitis in BD. These findings enrich our understanding of the contribution of genetic factors to the disease.


Assuntos
Síndrome de Behçet , Uveíte , Povo Asiático/genética , Síndrome de Behçet/genética , Proteínas de Transporte/genética , China , Estudo de Associação Genômica Ampla , Humanos , Proteínas de Membrana/genética , Uveíte/genética
16.
Rheumatology (Oxford) ; 61(3): 1133-1140, 2022 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-34146088

RESUMO

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 Questionários
17.
Clin Ophthalmol ; 15: 4141-4152, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34703200

RESUMO

PURPOSE: Halos are a chief source of patient dissatisfaction after multifocal intraocular lens (IOL) implantation. The primary purpose of this study was to investigate the influence of age, postoperative refraction, and pre- and postoperative pupil size on postoperative halo size with a trifocal diffractive IOL (AcrySof IQ PanOptix) and extended depth-of-focus (EDOF) IOL (TECNIS Symfony) to determine whether these factors could predict postoperative halo size. PATIENTS AND METHODS: This single-center, open-label study conducted between October 2018 and April 2020 in Yokosuka, Japan included 160 patients: 80 with PanOptix and 80 with Symfony IOLs. Size and intensity of the halos were examined binocularly using a computer-based simulator (Eyeland Design Network GmbH) and scored from 0 (minimum) to 10 (maximum) at 1, 3, and 6 months postoperatively, along with the change in each variable for both IOLs. The respective correlations of halo size with age, postoperative refraction, pre- and postoperative pupil size, and discomfort level due to the halo were also investigated 6 months postoperatively. RESULTS: Halo size and intensity were significantly mitigated between 1, 3, and 6 months postoperatively. Throughout the observation period, halo size was significantly larger with PanOptix than with Symphony (P < 0.05), and halo intensity was significantly higher with Symphony than with PanOptix (P < 0.05). The pre- and postoperative pupil size correlated positively with halo size, while age and postoperative refraction were negatively correlated, for both IOLs. CONCLUSION: Understanding the features and predictive preoperative factors of halos in different types of multifocal IOLs may be useful in improving patient satisfaction.

18.
Ophthalmol Ther ; 10(4): 989-1002, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34478122

RESUMO

INTRODUCTION: Understanding the relationship between postoperative intraocular lens (IOL) shift and refractive change is crucial for the accuracy of predicted postoperative refraction (PPR). We assessed the relationships between different IOL fixation methods, haptic designs, and several metrics. METHODS: Single-center, open-label study which included 69 eyes. We preoperatively measured the anterior chamber depth (ACD), lens thickness (LT), axial length (AL), and PPR. AcrySof IQ (n = 27) and FineVision (n = 24) were fixed in the bag, and FEMTIS (n = 18) was fixed in capsulorhexis. At 1 day, 1 week, and 1 month postoperatively, we checked the IOL position and refraction and compared the IOL shift, refraction change, and the margin of error of the predicted PPR (PR-PPR difference). We also analyzed the correlation between postoperative and preoperative variables. RESULTS: FEMTIS showed the highest stability in terms of IOL shift and refraction. The in-the-bag-fixated IOLs showed a significant forward shift between 1 day and 1 week postoperatively. There were significant differences in the PR-PPR difference between the IOLs. ACD and AL showed significant positive correlations, and LT showed a significant negative correlation with IOL shift and change in PR between 1 day and 1 week, but not between 1 week and 1 month postoperatively. CONCLUSION: The relationship between postoperative IOL shift and refraction change varied according to IOLs with different haptic types. Capsulorhexis fixation may be more stable than in-the-bag fixation. Furthermore, preoperative ACD, LT, and AL may be useful factors to predict IOL shift, change in PR, and to a lesser extent the degree of the margin of error in clinical practice. Our findings may improve the accuracy of PPR and refractive outcomes.

19.
Ophthalmol Ther ; 10(4): 891-904, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34292514

RESUMO

INTRODUCTION: This study investigated the effect of rebamipide on discrepancies in the power and axis of astigmatism between two intra-patient keratometric measurements in patients with dry eyes. METHODS: Fifty-eight dry eyes (with a short tear breakup time [TBUT] of less than 5 s) were analyzed. Patients with dry eye were treated with 2% rebamipide ophthalmic suspension (group R) or Mytear® artificial tear ophthalmic solution (group M) for 4 weeks. TBUT and corneal higher-order aberrations (HOAs) were evaluated at baseline and 4 weeks after treatment. Astigmatism power and axis were measured twice during both evaluations, at 5-min intervals. Baseline and post-treatment measurements were compared. Changes in TBUT and HOAs, and intra-patient discrepancies in astigmatism power and axis measurements were evaluated. RESULTS: HOAs showed significant positive correlations with intra-patient differences in astigmatism power and axis (P < 0.001). At the 4-week post-treatment follow-up, TBUT increased, and HOAs and astigmatism power and axis discrepancies decreased in a significant number of patients in group R (P < 0.001). In group M, only differences in astigmatism power decreased in a significant number of cases (P = 0.005). The degree of change in the intra-patient difference in astigmatism power between the two post-treatment keratometric measurements was significantly greater in group R than in group M (P < 0.001). In group R, baseline HOAs exhibited a significant positive correlation with changes in HOAs and intra-patient differences in astigmatism power (both P < 0.001). In group M, baseline HOAs were only significantly correlated with changes in intra-patient differences in astigmatism power (P = 0.030). CONCLUSION: In dry eyes with short TBUTs, rebamipide significantly improved the corneal surface condition and significantly reduced intra-patient discrepancies in astigmatism power and axis measurements. Rebamipide may improve the accuracy of intraocular lens (IOL) power calculations in dry eyes, particularly when toric IOLs are implanted.


This study investigated the effect of rebamipide on discrepancies in power and axis of astigmatism between two intra-patient keratometric measurements in patients with dry eyes. Short tear break-up time and corneal high-order aberrations were evaluated at baseline and 4 weeks after treatment. Astigmatism power and axis were measured twice at both evaluations. Baseline and post-treatment measurements were compared, and changes in short tear break-up time and high-order aberrations, as well as intra-patient discrepancies in astigmatism power and axis measurements, were evaluated. High-order aberrations at baseline showed significant positive correlations with intra-patient differences in astigmatism power and axis. Rebamipide significantly improved the corneal surface condition and significantly reduced intra-patient discrepancies in astigmatism power and axis measurements. Rebamipide may improve the accuracy of intraocular lens power calculations in dry eyes, particularly when toric intraocular lenses are implanted.

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