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PURPOSE: Carriers of functionally deficient mutations in the CYP39A1 gene have been recently reported to have a 2-fold increased risk of exfoliation syndrome (XFS). The aim of this study was to evaluate the risk of blindness and related clinical phenotypes of XFS patients carrying the loss-of-function CYP39A1 G204E mutation in comparison with XFS patients without any CYP39A1 mutation. DESIGN: Retrospective case study. PARTICIPANTS: A total of 35 patients diagnosed with XFS carrying the CYP39A1 G204E mutation and 150 XFS patients without any CYP39A1 mutation who were randomly selected from the Japanese XFS cohort. METHODS: Two-sided Fisher exact test with an alpha level < 0.05 was used to estimate the significance of the calculated odds ratio (OR) for all categorical measures. Comparisons between groups of subjects were performed using linear mixed effect models with group as random effect and taking possible dependence between eyes within a subject into account. MAIN OUTCOME MEASURES: Primary analysis compared the incidence of blindness (defined as visual acuity [VA] < 0.05 decimal), prevalence of exfoliation glaucoma (XFG), history of glaucoma surgery, and indices of glaucoma severity such as visual field (VF) mean deviation (MD), intraocular pressure (IOP), and vertical cup-disc ratio (CDR) between CYP39A1 G204E carriers and those without any CYP39A1 mutation. RESULTS: The overall risk for blindness was significantly higher in XFS patients carrying the CYP39A1 G204E variant (10/35 [28.6%]) compared with XFS patients without any CYP39A1 mutations (8/150 [5.4%]; odds ratio [OR], 7.1; 95% confidence interval [CI], 2.7-20.2]; P < 0.001). A higher proportion of XFS patients with the CYP39A1 G204E mutation (23/35 [65.7%]) had evidence of XFG in at least 1 eye compared with the comparison group (41/150 [27.3%]; OR, 5.1; 95% CI, 2.4-11.4]; P < 0.0001). Significantly higher peak IOP, larger vertical CDR, and worse VF MD were also found in CYP39A1 G204E variant carriers (P < 0.001). Additionally, patients with the CYP39A1 G204E mutation (18/35 [51.4%]) required more laser or glaucoma surgical interventions compared with those without any CYP39A1 mutation (32/150 [21.3%], P < 0.001). CONCLUSIONS: Patients with XFS carrying the CYP39A1 G204E mutation had significantly increased risk of blindness, higher occurrence of XFG, and more severe glaucoma compared with patients with XFS without any CYP39A1 mutation.
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Síndrome de Exfoliação , Glaucoma , Esteroide Hidroxilases , Cegueira/genética , Síndrome de Exfoliação/complicações , Síndrome de Exfoliação/genética , Glaucoma/complicações , Glaucoma/genética , Humanos , Estudos Retrospectivos , Esteroide Hidroxilases/genética , Campos VisuaisRESUMO
Importance: Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness. Objective: To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function. Design, Setting, and Participants: A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome. Exposures: Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function. Main Outcomes and Measures: The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 × 10-6. The secondary outcomes included biochemical enzymatic assays and gene expression analyses. Results: The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 × 10-7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4% [interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome. Conclusions and Relevance: In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings.
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Síndrome de Exfoliação/genética , Variação Genética , Esteroide Hidroxilases/genética , Idoso , Idoso de 80 Anos ou mais , Câmara Anterior/patologia , Estudos de Casos e Controles , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Feminino , Humanos , Modelos Logísticos , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Sequenciamento do ExomaRESUMO
Exfoliation syndrome (XFS) is a common, age-related, systemic fibrillinopathy. It greatly increases risk of exfoliation glaucoma (XFG), a major worldwide cause of irreversible blindness. Coding variants in the lysyl oxidase-like 1 (LOXL1) gene are strongly associated with XFS in all studied populations, but a functional role for these variants has not been established. To identify additional candidate functional variants, we sequenced the entire LOXL1 genomic locus (â¼40 kb) in 50 indigenous, black South African XFS cases and 50 matched controls. The variants with the strongest evidence of association were located in a well-defined 7-kb region bounded by the 3'-end of exon 1 and the adjacent region of intron 1 of LOXL1. We replicated this finding in US Caucasian (91 cases/1031 controls), German (771 cases/1365 controls) and Japanese (1484 cases/1188 controls) populations. The region of peak association lies upstream of LOXL1-AS1, a long non-coding RNA (lncRNA) encoded on the opposite strand of LOXL1. We show that this region contains a promoter and, importantly, that the strongly associated XFS risk alleles in the South African population are functional variants that significantly modulate the activity of this promoter. LOXL1-AS1 expression is also significantly altered in response to oxidative stress in human lens epithelial cells and in response to cyclic mechanical stress in human Schlemm's canal endothelial cells. Taken together, these findings support a functional role for the LOXL1-AS1 lncRNA in cellular stress response and suggest that dysregulation of its expression by genetic risk variants plays a key role in XFS pathogenesis.
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Aminoácido Oxirredutases/genética , Síndrome de Exfoliação/genética , RNA Longo não Codificante/genética , Idoso , Alelos , Estudos de Casos e Controles , Síndrome de Exfoliação/metabolismo , Feminino , Expressão Gênica , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Estresse Oxidativo/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras GenéticasRESUMO
Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10(-33)), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10(-8)). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.
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Glaucoma de Ângulo Aberto/genética , Polimorfismo de Nucleotídeo Único , Proteoglicanas/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Idoso , Idoso de 80 Anos ou mais , Alelos , Feminino , Variação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size =â -0.045 mm, P = 8.17 × 10(-9)). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele OR = 1.13 [95% CI: 1.06-1.22], P = 0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele OR = 1.30, P = 7.45 × 10(-9); 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions.
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Câmara Anterior/patologia , Estudo de Associação Genômica Ampla , Glaucoma de Ângulo Fechado/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Câmara Anterior/metabolismo , Povo Asiático , Glaucoma de Ângulo Fechado/patologia , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
BACKGROUND: The aim was to investigate the changes in anterior segment parameters, as assessed by anterior segment optical coherence tomography in Japanese subjects after laser peripheral iridotomy (LPI). DESIGN: This was a prospective observational study. PARTICIPANTS: The participants include 72 subjects with angle closure including primary angle closure suspect (PACS), primary angle closure (PAC), and primary angle closure glaucoma (PACG). METHODS: Anterior segment optical coherence tomography parameters was measured by customized software. Complete data of 51 subjects were available for final analysis. MAIN OUTCOME MEASURES: These were the following parameters: angle opening distance, trabecular-iris space area, anterior chamber depth, width, area and volume (iris thickness, curvature, and area, and lens vault (LV). RESULTS: A total of 25 PACS, 17 PAC and 9 PACG were included. Mean age was 74.7 ± 6.7 years, and majority were women (80.4%). Following LPI, there was a significant increase in mean gonioscopic angle width (1.16 vs. 1.93, P < 0.001) and a corresponding increase in angle opening distance, trabecular-iris space area, and angle recess area (all P < 0.001). The anterior chamber area (P < 0.001), anterior chamber volume (P < 0.001) and anterior chamber depth (P = 0.003) increased significantly; and iris curvature (P < 0.001) was significantly reduced. There were no significant changes in anterior chamber width, LV, iris thickness and area. Age-adjusted and gender-adjusted analysis for predictors of percentage change in angle opening distance 750 showed significant association with greater baseline LV (ß = 0.32, P = 0.03). No significant differences were noted in the mean percentage change in parameters between the PACS and PAC-PACG. CONCLUSIONS: An increase in anterior chamber dimensions, angle widening and iris flattening; with a constant LV, iris thickness and iris area after LPI was demonstrated in Japanese eyes with angle closure.
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Segmento Anterior do Olho/patologia , Glaucoma de Ângulo Fechado/cirurgia , Iridectomia , Iris/cirurgia , Fotocoagulação a Laser , Tomografia de Coerência Óptica , Idoso , Idoso de 80 Anos ou mais , Coagulação com Plasma de Argônio , Povo Asiático/etnologia , Feminino , Glaucoma de Ângulo Fechado/etnologia , Glaucoma de Ângulo Fechado/patologia , Gonioscopia , Humanos , Pressão Intraocular , Japão/epidemiologia , Masculino , Estudos Prospectivos , Tonometria OcularRESUMO
PURPOSE: To compare anterior segment parameters in Chinese and Japanese subjects with angle closure using anterior segment optical coherence tomography (ASOCT). METHODS: One hundred and forty-two Japanese and one hundred and ninety-two Chinese subjects with primary angle closure (PAC) or primary angle-closure glaucoma (PACG) were recruited. All participants underwent A-scan biometry and ASOCT imaging (Visante, Carl Zeiss Meditec, Dublin, CA, USA). Customized software was used to measure ASOCT parameters in horizontal ASOCT scans. The parameters were compared, and multivariate analysis was performed to determine predictors of angle opening distance at 750 µm from the scleral spur (AOD750). RESULTS: Ethnic difference evaluated by multiple linear regression adjusted for age, gender, spherical equivalent, pupil diameter, and axial length showed that Japanese angle-closure subjects had significantly shallower anterior chamber depth (ACD;ß = -0.3, p < 0.001), smaller anterior chamber area (ACA; ß = -0.21, p = 0.02) and volume (ACV; ß = -0.19, p = 0.01), greater lens vault (LV, ß = 0.3, p < 0.001), lens thickness (LT; ß = 0.48, p < 0.001), greater iris area (IArea; ß = 0.19, p = 0.01), and more curved iris (ICurv; ß = 0.16, p = 0.04). The significant determinants of AOD750 were iris thickness (IT; ß = -0.21, p = 0.04), ICurv (ß = -0.17, p = 0.04), pupil diameter (PD; ß = -0.34, p = 0.001) and ACV (ß = 0.32, p < 0.001) in Japanese; and IT (ß = -0.25, p = 0.001), ACV (ß = 0.37, p < 0.001), PD (ß = -0.26, p = 0.001), and LV (ß = -0.18, p = 0.03) in Chinese. CONCLUSIONS: Compared to Chinese, Japanese angle-closure eyes have smaller and more crowded anterior segment with thicker lenses. ACV, IT, and PD are important factors for angle width in both races. These results suggest possible ethnic differences in angle-closure mechanism(s).
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Segmento Anterior do Olho/patologia , Povo Asiático/etnologia , Glaucoma de Ângulo Fechado/etnologia , Glaucoma de Ângulo Fechado/patologia , Idoso , Biometria , China/epidemiologia , Feminino , Glaucoma de Ângulo Fechado/cirurgia , Gonioscopia , Humanos , Pressão Intraocular , Iridectomia , Japão/epidemiologia , Terapia a Laser , Masculino , Tomografia de Coerência Óptica , Tonometria Ocular , Acuidade Visual/fisiologiaRESUMO
PURPOSE: A thicker lens vault (LV), measured by anterior segment optical coherence tomography (ASOCT), was recently identified as a novel risk factor for angle closure in Chinese Singaporeans. The purpose of our study was to investigate the association of LV with angle closure in Japanese subjects. DESIGN: Case-control study METHODS: One hundred and twenty-four subjects with primary angle-closure disease and 80 controls were recruited. All participants underwent ASOCT, and customized software was used to measure LV, defined as the perpendicular distance between the anterior pole of the lens and a horizontal line joining the two scleral spurs. A-scan biometry was used to measure lens thickness (LT) and to calculate lens position (LP) and relative lens position (RLP). RESULTS: Eyes with angle closure had significantly shallower anterior chamber depth (ACD), shorter axial length, greater LV and LT (p <0.001 for all), and anteriorly positioned lenses (LP, p < 0.001; RLP, p = 0.019). After multivariate analysis adjusted for age, gender, ACD, LT, and RLP, increased LV was significantly associated with angle closure (odds ratio [OR] 24.2; 95 % confidence interval [CI], 2.3-250.5, comparing lowest with highest quartile), but no association was found for LT (OR 2.59; 95 %CI, 0.48-13.85). In a sub-analysis evaluating the effect of LT on LV, LV was significantly greater in both the angle-closure group with thinner lens (LT ≤ 4.91 mm) and angle-closure group with thicker lens (LT > 4.91 mm) compared to normal controls (p < 0.001 for both). CONCLUSIONS: In Japanese eyes, LV was independently associated with angle closure. These results corroborate the recent findings from Singapore on LV as a risk factor for angle closure.
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Glaucoma de Ângulo Fechado/etiologia , Doenças do Cristalino/complicações , Cristalino/patologia , Idoso , Biometria , Estudos de Casos e Controles , Feminino , Humanos , Pressão Intraocular , Japão , Doenças do Cristalino/diagnóstico , Masculino , Fatores de Risco , Tomografia de Coerência Óptica , Tonometria OcularRESUMO
Symptom overlap between meibomian gland dysfunction (MGD) and dry eye (DE) makes it difficult to distinguish between these two conditions on the basis of symptoms alone. We searched for characteristic symptoms that might help to distinguish MGD from DE on the basis of a population-based study. Subjects comprised 311 residents of Takushima island (18 to 96 years), including 117 individuals with MGD and 114 with DE. Responses to a symptom-related questionnaire (19 items) were subjected to factor analysis, and univariate regression analysis was performed to identify ocular surface parameters associated with characteristic symptoms of MGD. Factor analysis revealed aggregation of symptoms according to three factors: Factor 1 related to Symptom Score, Factor 2 to DE, and Factor 3 to MGD. Symptoms associated with DE included 11 items, whereas the only item related to MGD was tearing sensation. Pearson's correlation analysis revealed that tearing sensation was associated with tear meniscus height (TMH), noninvasive tear-film breakup time, fluorescein staining score, meiboscore, meibum grade, and Schirmer value. Subjects with MGD experienced significantly more tearing and had a larger TMH than did those without MGD (p = 0.0334). Tearing sensation may thus be a characteristic symptom of MGD. Physicians should suspect MGD who complain of tearing sensation.
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Intervention studies have shown that n-3 polyunsaturated fatty acid (PUFA) supplementation is effective for the treatment of meibomian gland dysfunction (MGD). Ointment containing an analog of vitamin D has also been found to improve symptoms and signs of MGD. We have now evaluated the relation of MGD prevalence to dietary intake of fatty acids (FAs) and vitamin D among a Japanese population. Subjects comprised 300 adults aged 20 to 92 years residing on Takushima Island. MGD was diagnosed on the basis of subjective symptoms, lid margin abnormalities, and meibomian gland obstruction. Dietary FA and vitamin D intake was estimated with a brief-type self-administered diet history questionnaire. MGD prevalence was 35.3%. Multivariate adjusted odds ratios (95% confidence intervals) between extreme quintiles of intake for MGD prevalence were 0.40 (0.16-0.97) for total fat, 0.40 (0.17-0.97) for saturated FAs, 0.40 (0.17-0.97) for oleic acid, 0.52 (0.23-1.18) for n-3 PUFAs, 0.63 (0.27-1.49) for n-6 PUFAs, 1.32 (0.59-2.95) for the n-6/n-3 PUFA ratio, and 0.38 (0.17-0.87) for vitamin D. Total fat, saturated FA, oleic acid, and vitamin D intake may thus be negatively associated with MGD prevalence in the Japanese.
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Aqueous-deficient dry eye (ADDE) and meibomian gland dysfunction (MGD) can be refractory to therapy. Intense pulsed light (IPL) was recently introduced as an effective treatment for MGD. We here evaluated the efficacy of IPL combined with MG expression (MGX) compared with MGX alone (n = 23 and 20, respectively) for patients with refractory ADDE with mild MGD at three sites. Symptom score, visual acuity (VA), noninvasive breakup time (NIBUT) and lipid layer thickness (LLT) of the tear film, lid margin abnormalities, fluorescein BUT (FBUT), fluorescein staining, tear meniscus height (TMH), meibum grade, meiboscore, and Schirmer's test value were assessed at baseline and 1 and 3 months after treatment. LLT, plugging, vascularity, FBUT and NIBUT were improved only in the IPL-MGX group at three months compared with baseline. All parameters with the exception of VA, meiboscore, TMH, Schirmer's test value were also improved in the IPL-MGX group compared with the control group at three months, as was VA in patients with central corneal epitheliopathy. Although IPL-MGX does not affect aqueous layer, the induced improvement in quality and quantity of the lipid layer may increase tear film stability and ameliorate symptoms not only for evaporative dry eye but for ADDE.
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PURPOSE: To evaluate the prevalence and risk factors of and the relationship between meibomian gland dysfunction (MGD) and dry eye (DE) in Japan. DESIGN: A population-based cross-sectional study. METHODS: Participants filled in questionnaires regarding ocular symptoms, systemic diseases, and lifestyle factors. Meibomian gland-related parameters and tear film-related parameters were evaluated. Risk factors for MGD and DE were analyzed by using univariate and multivariate logistic regression. Age-specific prevalence of MGD and DE was estimated by using a general additive model with degree-3 natural splines. The structural relation between MGD and DE was assessed by factor analysis using the principal components method and promax rotation. RESULTS: A total of 356 residents of Takushima Island (133 males, 223 females) at the mean ± SD age of 55.5 ± 22.4 years (range, 6-96 years) were enrolled. The prevalence of MGD and DE was 32.9% and 33.4%, respectively, with a coexistence rate of 12.9%. The prevalence of MGD was associated with male sex (odds ratio [OR], 2.42), age (OR per decade increment,1.53), and oral intake of lipid-lowering agents (OR, 3.22). The prevalence of DE was associated with female sex (OR, 3.36), contact lens wear (OR, 2.84), conjunctivochalasis (OR, 2.57), and lid margin abnormalities (OR, 3.16). The age-specific prevalence of MGD and DE differed, and factor analysis for 16 parameters showed that MGD and DE had independent hidden sources (interfactor correlation, -0.017). CONCLUSIONS: MGD and DE are common in this population. Although their ocular symptoms are similar, the pathogenesis of MGD differs from that of DE.
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Síndromes do Olho Seco/epidemiologia , Disfunção da Glândula Tarsal/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Síndromes do Olho Seco/etiologia , Análise Fatorial , Feminino , Humanos , Japão/epidemiologia , Modelos Logísticos , Masculino , Disfunção da Glândula Tarsal/etiologia , Pessoa de Meia-Idade , Fatores de Risco , Distribuição por Sexo , Adulto JovemRESUMO
PURPOSE: The purpose of this study was to evaluate the efficacy of 360-degree suture trabeculotomy (360S-LOT) ab interno for treating open-angle glaucoma (OAG). Risk factors of surgical failure were examined. PATIENTS AND METHODS: 360S-LOT ab interno alone was performed for patients with uncontrolled OAG, and combined 360S-LOT ab interno/phacoemulsification was performed for patients with controlled OAG with a visually significant cataract between March 2014 and September 2015 at a single center. The patients were prospectively followed for 2 years. The main outcome measures included 2-year intraocular pressure (IOP), number of anti-glaucoma medications used, postoperative complications, and predictive factors of surgical failure. Kaplan-Meier analysis was performed, with surgical success (with or without medication use) defined as postoperative IOP ≤15 mmHg and IOP reduction ≥20% (criterion A) or IOP ≤12 mmHg and IOP reduction ≥30% (criterion B). Predictive factors were evaluated using Cox proportional hazard ratios. RESULTS: A total of 64 eyes of 64 patients were included, and 50 (78%) eyes of 64 eyes underwent a phacoemulsification combination procedure. Surgery significantly reduced IOP from 18.4 ± 2.9 mmHg before surgery to 13.4 ± 3.0 mmHg after surgery (P < 0.001). Patients used an average of 1.8 ± 1.5 medications before surgery and 1.3 ± 1.5 medications after surgery (P = 0.101). No serious postoperative complications were observed. The probability of surgical success was 49.2% and 16.0% using criteria A and B, respectively. No risk factors of surgical failure were identified. CONCLUSION: The 360S-LOT ab interno procedure is a favorable option for treating eyes with mild or moderate OAG.
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OBJECTIVE: We performed a pilot trial to evaluate the 24-month safety and efficacy of 360-degree suture trabeculotomy ab interno with phacoemulsification used to treat mild to moderate open-angle glaucoma coexisting with cataract. METHODS AND ANALYSIS: We randomly assigned 18 eyes with open-angle glaucoma and coexisting cataract to undergo 360-degree suture trabeculotomy ab interno with phacoemulsification (combined) or phacoemulsification alone (control) (1:1 ratio) and followed up patients for 24 months. Main outcome measures were mean postoperative intraocular pressure (IOP) and success probabilities based on Kaplan-Meier life table analyses. Surgical success was defined as follows: criterion A: IOP value ≥6 mm Hg and ≤15 mm Hg, with ≥20 % reduction without medication; criterion B: IOP value ≥6 mm Hg and ≤12 mm Hg, with ≥30% reduction without medication. Secondary outcome measures included the number of medications, complications and best-corrected visual acuity. RESULTS: Mean IOP values (number of medications), which were 18.4 mm Hg (0.9) and 17.1 mm Hg (1.3) at baseline, showed significant reductions to 11.8 mm Hg (1.0) and 14.6 mm Hg (1.5) at 24 months postoperatively in the combined and control groups, respectively (p=0.0003 and 0.0192, respectively). Success rates for criterion A in the combined and control groups were 77.8% and 11.1%, respectively (p=0.0110) and those for criterion B in the combined and control groups were 46.7% and 0%, respectively (p=0.0036). Both groups had a similar overall occurrence of postoperative complications. CONCLUSION: Using 360-degree suture trabeculotomy ab interno with phacoemulsification appeared to be a more beneficial option for mild to moderate open-angle glaucoma with coexisting cataract than phacoemulsification alone. TRIAL REGISTRATION NUMBER: UMIN000021170, date of registration: 2016/03/01.
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PURPOSE: To evaluate the efficacy of intense pulsed light (IPL) therapy combined with meibomian gland expression (MGX) for refractory meibomian gland dysfunction (MGD) in a prospective study conducted at 3 sites in Japan. METHODS: Patients with refractory obstructive MGD were enrolled and underwent 4 to 8 IPL-MGX treatment sessions at 3-week intervals. Clinical assessment included the Standard Patient Evaluation of Eye Dryness questionnaire; noninvasive breakup time of the tear film and interferometric fringe pattern as determined by tear interferometry; lid margin abnormalities, fluorescein breakup time of the tear film, corneal and conjunctival fluorescein staining (CFS), and meibum grade as evaluated with a slit-lamp microscope; meibomian gland morphology (meiboscore); and tear production as measured by the Schirmer test without anesthesia. RESULTS: Sixty-two eyes of 31 patients (17 women, 14 men; mean age ± SD, 47.6 ± 16.8 years) were enrolled. The Standard Patient Evaluation of Eye Dryness score (P < 0.001), noninvasive breakup time (P < 0.001), and interferometric fringe pattern (P < 0.001) were significantly improved after therapy, with 74% of eyes showing a change in the interferometric fringe pattern from 1 characteristic of lipid deficiency to the normal condition. Meibum grade, lid margin abnormality scores, fluorescein breakup time, and CFS were also significantly improved (P < 0.001, P < 0.001, P < 0.001, and P = 0.002, respectively) after treatment, whereas the meiboscore and Schirmer test value remained unchanged. CONCLUSIONS: IPL-MGX ameliorated symptoms and improved the condition of the tear film in patients with refractory MGD and is therefore a promising treatment option for this disorder.
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Túnica Conjuntiva/metabolismo , Doenças Palpebrais/terapia , Terapia de Luz Pulsada Intensa/métodos , Glândulas Tarsais/metabolismo , Lágrimas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Túnica Conjuntiva/patologia , Doenças Palpebrais/diagnóstico , Doenças Palpebrais/epidemiologia , Feminino , Humanos , Incidência , Interferometria , Japão/epidemiologia , Masculino , Glândulas Tarsais/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: To evaluate the efficacy and safety of 0.05% epinastine and 0.1% olopatadine eye drop preparations as seasonal and preseasonal treatments in patients with seasonal allergic conjunctivitis (SAC). SUBJECTS AND METHODS: This was a prospective, randomized, case-control study involving two institutions. The subjects were patients diagnosed with SAC at two institutions between February and March in 2014. To examine the clinical effects of seasonal treatment, 0.05% epinastine and 0.1% olopatadine were administered, and their effects were investigated every 2 weeks (Stage 1). To evaluate the clinical effects of preseasonal therapy, in January 2015, the same eye drop preparations as adopted in Stage 1 were administered to patients who had participated in Stage 1 and provided consent to participate in this study, and their effects were investigated every month (Stage 2). RESULTS: In Stage 1, the 0.05% epinastine group consisted of 43 patients, and the 0.1% olopatadine group consisted of 42 patients. There were significant improvements in the total symptom and objective finding scores at each time point after administration in comparison with those before its baseline, but there were no significant differences between the two groups. In Stage 2, the 0.05% epinastine group consisted of 15 patients, and the 0.1% olopatadine group consisted of 14 patients. The rate of change in the total symptom score in comparison with that at the baseline of preseasonal treatment was significantly higher in the 0.1% olopatadine group 1 month after the start of treatment, suggesting symptom deterioration (P=0.025). There was no significant difference in the rate of change in the total objective finding score between the two groups. CONCLUSION: Seasonal treatment with 0.05% epinastine or 0.1% olopatadine was equally effective for patients with allergic conjunctivitis. However, for preseasonal therapy, 0.05% epinastine was more effective than 0.1% olopatadine.
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PURPOSE: We measured tear film parameters, including the morphology and function of meibomian glands, in junior high school students at 15 years of age. METHODS: A total of 111 eyes of 111 students (56 males and 55 females) were enrolled in the study. The ocular symptom score (0-14), after-school study time, lipid layer thickness (LLT) of the tear film, partial blink rate, lid margin abnormalities (0-4), tear film breakup time, corneal and conjunctival epithelial damage (fluorescein staining score, 0-9), meiboscore as determined by noncontact meibography (0-6), Schirmer test value, and meibum grade (0-3) were determined. The relationships between parameters were evaluated with the Spearman correlation coefficient (ρ). RESULTS: The meiboscore was 2.8 ± 1.2, and the meibum grade was 1.8 ± 1.2. The meiboscore significantly correlated with the meibum grade (ρ = 0.272, P = 0.004), Schirmer test value (ρ = -0.220, P = 0.021), and LLT (ρ = -0.264, P = 0.005). The breakup time significantly correlated with LLT (ρ = 0.261, P = 0.006), meibum grade (ρ = -0.338, P < 0.001), and fluorescein staining score (ρ = -0.214, P = 0.025). The partial blink rate significantly correlated with the Schirmer test value (ρ = -0.240, P = 0.011). The meiboscore (P < 0.001) and meibum grade (P = 0.032) were significantly greater in males than in females. CONCLUSIONS: The morphology and function of meibomian glands are altered even at 15 years of age, with the changes being more prominent in males than in females.
Assuntos
Pálpebras/fisiologia , Glândulas Tarsais/fisiologia , Lágrimas/fisiologia , Adolescente , Estudos Transversais , Feminino , Fluoresceína/metabolismo , Corantes Fluorescentes/metabolismo , Voluntários Saudáveis , Humanos , Aparelho Lacrimal/fisiologia , Lipídeos/fisiologia , Masculino , Estudos Prospectivos , Coloração e RotulagemRESUMO
Although lysyl oxidase-like 1 (LOXL1) is known as the principal genetic risk factor for pseudoexfoliation (PEX) syndrome, a major cause of glaucoma and cardiovascular complications, no functional variants have been identified to date. Here, we conduct a genome-wide association scan on 771 German PEX patients and 1,350 controls, followed by independent testing of associated variants in Italian and Japanese data sets. We focus on a 3.5-kb four-component polymorphic locus positioned spanning introns 1 and 2 of LOXL1 with enhancer-like chromatin features. We find that the rs11638944:C>G transversion exerts a cis-acting effect on the expression levels of LOXL1, mediated by differential binding of the transcription factor RXRα (retinoid X receptor alpha) and by modulating alternative splicing of LOXL1, eventually leading to reduced levels of LOXL1 mRNA in cells and tissues of risk allele carriers. These findings uncover a functional mechanism by which common noncoding variants influence LOXL1 expression.
Assuntos
Processamento Alternativo , Aminoácido Oxirredutases/genética , Síndrome de Exfoliação/diagnóstico , Síndrome de Exfoliação/genética , Predisposição Genética para Doença , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , Cromatina/química , Elementos Facilitadores Genéticos , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Alemanha , Glaucoma/complicações , Glaucoma/genética , Humanos , Íntrons , Itália , Japão , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Ligação Proteica , Receptor X Retinoide alfa/genéticaRESUMO
Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 × 10-14) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 × 10-8). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.
Assuntos
Aminoácido Oxirredutases/genética , Síndrome de Exfoliação/genética , Estudo de Associação Genômica Ampla , Mutação de Sentido Incorreto , Mutação Puntual , Idoso de 80 Anos ou mais , Alelos , Aminoácido Oxirredutases/fisiologia , Substituição de Aminoácidos , Povo Asiático/genética , Canais de Cálcio/genética , Adesão Celular , Síndrome de Exfoliação/etnologia , Matriz Extracelular/metabolismo , Olho/metabolismo , Feminino , Perfilação da Expressão Gênica , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Chaperonas Moleculares/biossíntese , Chaperonas Moleculares/genética , RNA Mensageiro/biossíntese , Esferoides CelularesRESUMO
BACKGROUND: In this paper, we describe 360° suture trabeculotomy (360°LOT) ab interno and the short-term course in patients who underwent this procedure. METHODS: We prospectively studied 12 patients (12 eyes) with open-angle glaucoma who underwent 360°LOT ab interno at the Sato Eye Clinic between February and July 2014. The surgical procedure involved making a 1.7 mm temporal corneal incision, exposing an approximately 15° opening in the inner wall of Schlemm's canal (nasal side) using a Trabectome with a gonioscope, and inserting a 5-0 nylon suture rounded at the tip into Schlemm's canal opened via the anterior chamber. The suture was then threaded around Schlemm's canal, and the tip of the suture that emerged on the other side was then advanced through the opening to make a circumferential incision. Intraocular pressure (IOP), number of anti-glaucoma medications used, complications, and the surgery completion rate were prospectively studied. RESULTS: Mean IOP, which was 19.4 mmHg at baseline, showed a significant decrease at each of the monthly observation points, reaching 13.8 mmHg at 6 months after surgery (P=0.0004, paired t-test). The mean number of anti-glaucoma medications decreased from 3.2 at baseline to 1.1 at 6 months after surgery. IOP spikes ≥30 mmHg were seen in 25% of patients, but there were no other serious complications and the surgery completion rate was 92%. CONCLUSION: The 360°LOT ab interno procedure preserves the conjunctiva and sclera, and has a high surgery completion rate when using the anterior chamber approach, and could therefore be an effective short-term treatment of open-angle glaucoma.