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1.
Acta Diabetol ; 2019 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-31377925

RESUMO

AIMS: To summarize the effects of centralization of diabetic fundus photograph interpretation into a virtual reading center. METHODS: In 2016 Kaiser Permanente Northern California, a large, membership-based health plan with an ethnically and racially diverse population, centralized diabetic retinopathy screening into a virtual reading center. Retina screens were based on single field, 45-degree fundus photographs. We compared the accuracy of photography interpretation the year before centralization to the year after using masked reads performed by retina specialists of 1000 randomly selected screens from each time period. RESULTS: In all, 1902 patient screens with adequate quality images were included in the primary analysis. Images from pre-centralization screens were largely read by ophthalmologists (76.2%), while screens post-centralization were mainly read by optometrists (84.6%). Despite being interpreted by readers with lower levels of professional training, the sensitivity of screening increased from 43.9% (95% CI 38.0-49.8%) to 66.0% (95% CI 60.5-71.4%). CONCLUSION: A move to a centralized virtual reading center was associated with improved accuracy of diabetic retinopathy screening.

2.
N Engl J Med ; 381(3): 243-251, 2019 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-31314968

RESUMO

BACKGROUND: The relationship between outpatient systolic and diastolic blood pressure and cardiovascular outcomes remains unclear and has been complicated by recently revised guidelines with two different thresholds (≥140/90 mm Hg and ≥130/80 mm Hg) for treating hypertension. METHODS: Using data from 1.3 million adults in a general outpatient population, we performed a multivariable Cox survival analysis to determine the effect of the burden of systolic and diastolic hypertension on a composite outcome of myocardial infarction, ischemic stroke, or hemorrhagic stroke over a period of 8 years. The analysis controlled for demographic characteristics and coexisting conditions. RESULTS: The burdens of systolic and diastolic hypertension each independently predicted adverse outcomes. In survival models, a continuous burden of systolic hypertension (≥140 mm Hg; hazard ratio per unit increase in z score, 1.18; 95% confidence interval [CI], 1.17 to 1.18) and diastolic hypertension (≥90 mm Hg; hazard ratio per unit increase in z score, 1.06; 95% CI, 1.06 to 1.07) independently predicted the composite outcome. Similar results were observed with the lower threshold of hypertension (≥130/80 mm Hg) and with systolic and diastolic blood pressures used as predictors without hypertension thresholds. A J-curve relation between diastolic blood pressure and outcomes was seen that was explained at least in part by age and other covariates and by a higher effect of systolic hypertension among persons in the lowest quartile of diastolic blood pressure. CONCLUSIONS: Although systolic blood-pressure elevation had a greater effect on outcomes, both systolic and diastolic hypertension independently influenced the risk of adverse cardiovascular events, regardless of the definition of hypertension (≥140/90 mm Hg or ≥130/80 mm Hg). (Funded by the Kaiser Permanente Northern California Community Benefit Program.).


Assuntos
Pressão Sanguínea , Hipertensão/complicações , Infarto do Miocárdio/etiologia , Acidente Vascular Cerebral/etiologia , Adulto , Idoso , Isquemia Encefálica/etiologia , Diástole , Feminino , Humanos , Hemorragias Intracranianas/etiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Análise de Sobrevida , Sístole
3.
Ophthalmology ; 126(9): 1334-1335, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30980854
4.
Nat Rev Rheumatol ; 14(12): 693-703, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30401979

RESUMO

Despite advances in therapy for rheumatic diseases, hydroxychloroquine remains almost universally recommended for the treatment of systemic lupus erythematosus (SLE), and is often used in the management of other rheumatic diseases such as rheumatoid arthritis (RA). However, the major dose-limiting toxicity of hydroxychloroquine is retinopathy that can lead to loss of vision. New highly sensitive screening methods can identify early stages of retinopathy, and studies that include these modalities have indicated a substantially higher prevalence of hydroxychloroquine retinopathy than was previously recognized, resulting in revisions to ophthalmology guidelines and the recommendation of a low dose of hydroxychloroquine for many patients. However, the efficacy of low-dose hydroxychloroquine for treating SLE and other rheumatic diseases is unknown. Further studies are required to establish the effectiveness and retinal safety of the latest hydroxychloroquine treatment recommendations.

5.
Arthritis Res Ther ; 20(1): 133, 2018 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-29976231

RESUMO

BACKGROUND: Hydroxychloroquine (HCQ) retinopathy may be more common than previously recognized; recent ophthalmology guidelines have revised recommendations from ideal body weight (IBW)-based dosing to actual body weight (ABW)-based dosing. However, contemporary HCQ prescribing trends in the UK remain unknown. METHODS: We examined a UK general population database to investigate HCQ dosing between 2007 and 2016. We studied trends of excess HCQ dosing per ophthalmology guidelines (defined by exceeding 6.5 mg/kg of IBW and 5.0 mg/kg of ABW) and determined their independent predictors using multivariable logistic regression analyses. RESULTS: Among 20,933 new HCQ users (78% female), the proportions of initial HCQ excess dosing declined from 40% to 36% using IBW and 38% to 30% using ABW, between 2007 and 2016. Among these, 47% of women were excess-dosed (multivariable OR 12.52; 95% CI 10.99-14.26) using IBW and 38% (multivariable OR 1.98; 95% CI,1.81-2.15) using ABW. Applying IBW, 37% of normal and 44% of obese patients were excess-dosed; however, applying ABW, 53% of normal and 10% of obese patients were excess-dosed (multivariable ORs = 1.61 and 0.1 (reference = normal); both p < 0.01). Long-term HCQ users showed similar excess dosing. CONCLUSION: A substantial proportion of HCQ users in the UK, particularly women, may have excess HCQ dosing per the previous or recent weight-based guidelines despite a modest decline in recent years. Over half of normal-BMI individuals were excess-dosed per the latest guidelines. This implies the potential need to reduce dosing for many patients but also calls for further research to establish unifying evidence-based safe and effective dosing strategies.

6.
Nat Commun ; 9(1): 2278, 2018 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-29891935

RESUMO

Primary open-angle glaucoma (POAG) is a leading cause of irreversible vision loss, yet much of the genetic risk remains unaccounted for, especially in African-Americans who have a higher risk for developing POAG. We conduct a multiethnic genome-wide association study (GWAS) of POAG in the GERA cohort, with replication in the UK Biobank (UKB), and vice versa, GWAS in UKB with replication in GERA. We identify 24 loci (P < 5.0 × 10-8), including 14 novel, of which 9 replicate (near FMNL2, PDE7B, TMTC2, IKZF2, CADM2, DGKG, ANKH, EXOC2, and LMX1B). Functional studies support intraocular pressure-related influences of FMNL2 and LMX1B, with certain Lmx1b mutations causing high IOP and glaucoma resembling POAG in mice. The newly identified loci increase the proportion of variance explained in each GERA race/ethnicity group, with the largest gain in African-Americans (0.5-3.1%). A meta-analysis combining GERA and UKB identifies 24 additional loci. Our study provides important insights into glaucoma pathogenesis.

7.
Ophthalmology ; 125(6): e40-e41, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29784100
8.
Clin Rheumatol ; 37(7): 1853-1859, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29696437

RESUMO

We aimed to assess the impact of ophthalmology weight-based hydroxychloroquine (HCQ) dosing guidelines on prescribing patterns. We examined initial HCQ prescription dosing between 2007 and 2016 and determined independent predictors for HCQ dosing above the previous (2011) recommended ≤ 6.5 mg/kg of ideal body weight (IBW)/day and the latest (2016) recommended ≤ 5.0 mg/kg of actual body weight (ABW)/day using logistic regression. Among 17,797 patients (82% female), the proportion of 400 mg prescribed daily dosing declined sharply from 80% in 2007-2011 to nearly 40% in 2014, whereas the proportions of 200- and 300-mg daily doses showed the opposite trends during the same periods. Accordingly, the risk of HCQ dosing above the guideline recommendations declined by more than 60%. While 36% of normal body mass index (BMI) individuals were classified as dosing above the IBW-based guideline, 66% would have received dosing above the latest ABW-based guideline. The risk of excess dosing was associated with female patients and dermatology prescribers (adjusted odds ratios ≥ 2 according to IBW- or ABW-based guidelines). There has been a sharp decline in HCQ dosing following ophthalmology weight-based guidelines in recent years. While this trend is likely helpful in reducing the risk of retinopathy, its potential impact on HCQ efficacy remains to be clarified.


Assuntos
Antirreumáticos/administração & dosagem , Cálculos da Dosagem de Medicamento , Hidroxicloroquina/administração & dosagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Antirreumáticos/efeitos adversos , Feminino , Fidelidade a Diretrizes , Humanos , Hidroxicloroquina/efeitos adversos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Doenças Retinianas/induzido quimicamente , Doenças Retinianas/prevenção & controle
10.
J Allergy Clin Immunol ; 141(3): 991-1001, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29030101

RESUMO

BACKGROUND: Peanut allergy (PA) is a complex disease with both environmental and genetic risk factors. Previously, PA loci were identified in filaggrin (FLG) and HLA in candidate gene studies, and loci in HLA were identified in a genome-wide association study and meta-analysis. OBJECTIVE: We sought to investigate genetic susceptibility to PA. METHODS: Eight hundred fifty cases and 926 hyper-control subjects and more than 7.8 million genotyped and imputed single nucleotide polymorphisms (SNPs) were analyzed in a genome-wide association study to identify susceptibility variants for PA in the Canadian population. A meta-analysis of 2 phenotypes (PA and food allergy) was conducted by using 7 studies from the Canadian, American (n = 2), Australian, German, and Dutch (n = 2) populations. RESULTS: An SNP near integrin α6 (ITGA6) reached genome-wide significance with PA (P = 1.80 × 10-8), whereas SNPs associated with Src kinase-associated phosphoprotein 1 (SKAP1), matrix metallopeptidase 12 (MMP12)/MMP13, catenin α3 (CTNNA3), rho GTPase-activating protein 24 (ARHGAP24), angiopoietin 4 (ANGPT4), chromosome 11 open reading frame (C11orf30/EMSY), and exocyst complex component 4 (EXOC4) reached a threshold suggestive of association (P ≤ 1.49 × 10-6). In the meta-analysis of PA, loci in or near ITGA6, ANGPT4, MMP12/MMP13, C11orf30, and EXOC4 were significant (P ≤ 1.49 × 10-6). When a phenotype of any food allergy was used for meta-analysis, the C11orf30 locus reached genome-wide significance (P = 7.50 × 10-11), whereas SNPs associated with ITGA6, ANGPT4, MMP12/MMP13, and EXOC4 and additional C11orf30 SNPs were suggestive (P ≤ 1.49 × 10-6). Functional annotation indicated that SKAP1 regulates expression of CBX1, which colocalizes with the EMSY protein coded by C11orf30. CONCLUSION: This study identifies multiple novel loci as risk factors for PA and food allergy and establishes C11orf30 as a risk locus for both PA and food allergy. Multiple genes (C11orf30/EMSY, SKAP1, and CTNNA3) identified by this study are involved in epigenetic regulation of gene expression.

11.
Ophthalmology ; 125(2): 169-178, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28951074

RESUMO

PURPOSE: To compare the accuracy of intraocular lens (IOL) calculation formulas (Barrett Universal II, Haigis, Hoffer Q, Holladay 1, Holladay 2, Olsen, and SRK/T) in the prediction of postoperative refraction using a single optical biometry device. DESIGN: Retrospective consecutive case series. PARTICIPANTS: A total of 13 301 cataract operations with an AcrySof SN60WF implant and 5200 operations with a SA60AT implant (Alcon Laboratories, Inc., Fort Worth, TX). METHODS: All patients undergoing cataract surgery between July 1, 2014, and December 31, 2015, with Lenstar 900 optical biometry were eligible. A single eye per patient was included in the final analysis, resulting in a total of 18 501 cases. We compared the performance of each formula with respect to the error in predicted spherical equivalent and evaluated the effect of applying the Wang-Koch (WK) adjustment for eyes with axial length >25.0 mm on 4 of the formulas. RESULTS: For the SN60WF, the standard deviation of the prediction error, in order of lowest to highest, was the Barrett Universal II (0.404), Olsen (0.424), Haigis (0.437), Holladay 2 (0.450), Holladay 1 (0.453), SRK/T (0.463), and Hoffer Q (0.473), and the results for the SA60AT were similar. The Barrett formula was significantly better than the other formulas in postoperative refraction prediction (P < 0.01) for both IOL types. Application of the WK axial length modification generally resulted in a shift from hyperopic to myopic outcomes in long eyes. CONCLUSIONS: Overall, the Barrett Universal II formula had the lowest prediction error for the 2 IOL models studied.


Assuntos
Biometria/métodos , Hiperopia/reabilitação , Lentes Intraoculares , Miopia/reabilitação , Óptica e Fotônica/instrumentação , Refração Ocular/fisiologia , Idoso , Feminino , Humanos , Hiperopia/fisiopatologia , Masculino , Miopia/fisiopatologia , Período Pós-Operatório , Estudos Retrospectivos
13.
Ophthalmology ; 124(3): e29-e30, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28219514
15.
Ophthalmology ; 123(6): 1386-94, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26992838

RESUMO

BACKGROUND: The American Academy of Ophthalmology recommendations on screening for chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy are revised in light of new information about the prevalence of toxicity, risk factors, fundus distribution, and effectiveness of screening tools. PATTERN OF RETINOPATHY: Although the locus of toxic damage is parafoveal in many eyes, Asian patients often show an extramacular pattern of damage. DOSE: We recommend a maximum daily HCQ use of ≤5.0 mg/kg real weight, which correlates better with risk than ideal weight. There are no similar demographic data for CQ, but dose comparisons in older literature suggest using ≤2.3 mg/kg real weight. RISK OF TOXICITY: The risk of toxicity is dependent on daily dose and duration of use. At recommended doses, the risk of toxicity up to 5 years is under 1% and up to 10 years is under 2%, but it rises to almost 20% after 20 years. However, even after 20 years, a patient without toxicity has only a 4% risk of converting in the subsequent year. MAJOR RISK FACTORS: High dose and long duration of use are the most significant risks. Other major factors are concomitant renal disease, or use of tamoxifen. SCREENING SCHEDULE: A baseline fundus examination should be performed to rule out preexisting maculopathy. Begin annual screening after 5 years for patients on acceptable doses and without major risk factors. SCREENING TESTS: The primary screening tests are automated visual fields plus spectral-domain optical coherence tomography (SD OCT). These should look beyond the central macula in Asian patients. The multifocal electroretinogram (mfERG) can provide objective corroboration for visual fields, and fundus autofluorescence (FAF) can show damage topographically. Modern screening should detect retinopathy before it is visible in the fundus. TOXICITY: Retinopathy is not reversible, and there is no present therapy. Recognition at an early stage (before any RPE loss) is important to prevent central visual loss. However, questionable test results should be repeated or validated with additional procedures to avoid unnecessary cessation of valuable medication. COUNSELING: Patients (and prescribing physicians) should be informed about risk of toxicity, proper dose levels, and the importance of regular annual screening.


Assuntos
Antirreumáticos/toxicidade , Cloroquina/toxicidade , Hidroxicloroquina/toxicidade , Doenças Retinianas/diagnóstico , Transtornos da Visão/diagnóstico , Academias e Institutos , Adulto , Antirreumáticos/administração & dosagem , Grupo com Ancestrais do Continente Asiático/etnologia , Cloroquina/administração & dosagem , Eletrorretinografia/efeitos dos fármacos , Feminino , Angiofluoresceinografia , Humanos , Hidroxicloroquina/administração & dosagem , Concentração Máxima Permitida , Pessoa de Meia-Idade , Oftalmologia/organização & administração , Doenças Retinianas/induzido quimicamente , Doenças Retinianas/etnologia , Fatores de Risco , Tomografia de Coerência Óptica , Estados Unidos , Transtornos da Visão/induzido quimicamente , Transtornos da Visão/etnologia , Acuidade Visual/efeitos dos fármacos , Acuidade Visual/fisiologia , Testes de Campo Visual , Campos Visuais/efeitos dos fármacos , Campos Visuais/fisiologia
16.
Eur J Hum Genet ; 24(7): 1049-55, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26733291

RESUMO

Age-related macular degeneration (AMD) risk variants in the complement system point to the important role of immune response and inflammation in the pathogenesis of AMD. Although the human leukocyte antigen (HLA) region has a central role in regulating immune response, previous studies of genetic variation in HLA genes and AMD have been limited by sample size or incomplete coverage of the HLA region by first-generation genotyping arrays and imputation panels. Here, we conducted a large-scale HLA fine-mapping study with 4841 AMD cases and 23 790 controls of non-Hispanic white ancestry from the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging cohort. Genotyping was conducted using custom Affymetrix Axiom arrays, with dense coverage of the HLA region. Classic HLA polymorphisms were imputed using SNP2HLA, which utilizes a large reference panel to provide improved imputation accuracy of variants in this region. We examined a total of 6937 SNPs and 172 classical HLA alleles, conditioning on established AMD risk variants, which revealed novel associations with two non-synonymous SNPs in perfect linkage disequilibrium, rs9274390 and rs41563814 (odds ratio (OR)=1.21; P=1.4 × 10(-11)) corresponding to amino-acid changes at position 66 and 67 in HLA-DQB1, respectively, and the DQB1*02 classical HLA allele (OR=1.22; P=3.9 × 10(-10)) with the risk of AMD. We confirmed these association signals, again conditioning on established risk variants, in the MMAP data set of subjects with advanced AMD (rs9274390/rs41563814: OR=1.28; P=1.30 × 10(-3), DQB1*02: OR=1.32; P=9.00 × 10(-4)). These findings support a role of HLA class II alleles in the risk of AMD.


Assuntos
Cadeias beta de HLA-DQ/genética , Degeneração Macular/genética , Mutação de Sentido Incorreto , Polimorfismo de Nucleotídeo Único , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Humanos , Desequilíbrio de Ligação , Degeneração Macular/patologia , Masculino
17.
Ophthalmology ; 123(2): 287-94, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26459998

RESUMO

PURPOSE: Intracameral injection is an effective method for preventing infection, but no controlled study has been published in the United States. DESIGN: We conducted an observational, longitudinal cohort study to examine the effect of topical and injected antibiotics on risk of endophthalmitis. PARTICIPANTS: We identified 315 246 eligible cataract procedures in 204 515 members of Kaiser Permanente, California, 2005-2012. METHODS: The study used information from the membership, medical, pharmacy, and surgical records from the electronic health record. MAIN OUTCOME MEASURES: The adjusted odds ratio (OR) and 95% confidence interval (CI) for the association of antibiotic prophylaxis (route and agent) with risk of endophthalmitis was estimated using logistic regression analysis. RESULTS: We confirmed 215 cases of endophthalmitis (0.07% or 0.7/1000). Posterior capsular rupture was associated with a 3.68-fold increased risk of endophthalmitis (CI, 1.89-7.20). Intracameral antibiotic was more effective than topical agent alone (OR, 0.58; CI, 0.38-0.91). Combining topical gatifloxacin or ofloxacin with intracameral agent was not more effective than using an intracameral agent alone (compared with intracameral only: intracameral plus topical, OR, 1.63; CI, 0.48-5.47). Compared with topical gatifloxacin, prophylaxis using topical aminoglycoside was ineffective (OR, 1.97; CI, 1.17-3.31). CONCLUSIONS: Surgical complication remains a key risk factor for endophthalmitis. Intracameral antibiotic was more effective for preventing post-cataract extraction endophthalmitis than topical antibiotic alone. Topical antibiotic was not shown to add to the effectiveness of an intracameral regimen.


Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Endoftalmite/prevenção & controle , Infecções Oculares Bacterianas/prevenção & controle , Facoemulsificação , Administração Tópica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aminoglicosídeos/administração & dosagem , Aminoglicosídeos/uso terapêutico , Antibacterianos/administração & dosagem , Cefalosporinas/administração & dosagem , Cefalosporinas/uso terapêutico , Bases de Dados Factuais , Endoftalmite/epidemiologia , Endoftalmite/microbiologia , Infecções Oculares Bacterianas/epidemiologia , Infecções Oculares Bacterianas/microbiologia , Feminino , Fluoroquinolonas/administração & dosagem , Fluoroquinolonas/uso terapêutico , Seguimentos , Humanos , Injeções Intraoculares , Complicações Intraoperatórias/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Resultado do Tratamento
18.
Am J Epidemiol ; 183(2): 147-55, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26608880

RESUMO

Although type 2 diabetes (T2D) predicts glaucoma, the potential for unmeasured confounding has hampered causal conclusions. We performed separate sample genetic instrumental variable analyses using the Genetic Epidemiology Research Study on Adult Health and Aging cohort (n = 69,685; 1995-2013) to estimate effects of T2D on primary open-angle glaucoma (POAG; 3,554 cases). Genetic instrumental variables for overall and mechanism-specific (i.e., linked to T2D via influences on adiposity, ß-cell function, insulin regulation, or other metabolic processes) T2D risk were constructed by using 39 genetic polymorphisms established to predict T2D in other samples. Instrumental variable estimates indicated that T2D increased POAG risk (odds ratio = 2.53, 95% confidence interval: 1.04, 6.11). The instrumental variable for ß-cell dysregulation also significantly predicted POAG (odds ratioß-cell = 5.26, 95% confidence interval: 1.75, 15.85), even among individuals without diagnosed T2D, suggesting that metabolic dysregulation may increase POAG risk prior to T2D diagnosis. The T2D risk variant in the melatonin receptor 1B gene (MTNR1B) predicted risk of POAG independently of T2D status, indicating possible pleiotropic physiological functions of melatonin, but instrumental variable effect estimates were significant even excluding MTNR1B variants. To our knowledge, this is the first genetic instrumental variable study of T2D and glaucoma, providing a novel approach to evaluating this hypothesized relationship. Our findings substantially bolster observational evidence that T2D increases POAG risk.


Assuntos
Diabetes Mellitus Tipo 2/genética , Glaucoma de Ângulo Aberto/genética , Idoso , California , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Células Secretoras de Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo Genético , Receptor MT2 de Melatonina/genética , Fatores de Risco
19.
Ophthalmology ; 123(1): 92-101, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26260281

RESUMO

PURPOSE: To evaluate the association between refractive error and the prevalence of glaucoma by race or ethnicity. DESIGN: Cross-sectional study. PARTICIPANTS: Kaiser Permanente Northern California Health Plan members with refractive error measured at 35 years of age or older between 2008 and 2014 and with no history of cataract surgery, refractive surgery, or a corneal disorder. METHODS: We identified 34 040 members with glaucoma or ocular hypertension (OHTN; cases) and 403 398 members without glaucoma (controls). Glaucoma cases were classified as primary angle-closure glaucoma (PACG); 1 of the 4 forms of open-angle glaucoma: primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), pigmentary glaucoma (PIGM), and pseudoexfoliation glaucoma (PEX); or OHTN. Refractive error, expressed as spherical equivalent (SE), was coded as a continuous trait and also as categories. Logistic regression analyses were used to estimate the association between refractive error and the prevalence of glaucoma overall and in specific racial or ethnic groups. MAIN OUTCOME MEASURES: The association between refractive error and glaucoma subtypes evaluated as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: In controls, the mean SE was -0.59 diopters (D) (standard deviation, 2.62 D). Each 1-D reduction in SE was associated with a 22% decrease in the odds of PACG (OR, 0.78; 95% CI, 0.77-0.80) and with increases in the odds of open-angle glaucoma ranging from 1.23 (95% CI, 1.20-1.26) for PIGM, to 1.07 (95% CI, 1.03-1.11) for PEX, and to 1.05 (95% CI, 1.04-1.06) for OHTN. In addition, we observed a stronger association between myopia and POAG among non-Hispanic whites (OR, 1.12; 95% CI, 1.11-1.13) and NTG among Asians (OR, 1.17; 95% CI, 1.15-1.20) and non-Hispanic whites (OR, 1.19; 95% CI, 1.15-1.22). CONCLUSIONS: Myopia was associated with an increased prevalence of all forms of open-angle glaucoma and OHTN, whereas hyperopia was associated with a substantially increased prevalence of PACG. Although high myopia is a strong risk factor for glaucoma subtypes, low and moderate myopia also have a significant effect on glaucoma risk. Additionally, there were moderate racial differences in the association of myopia with the risk of POAG and NTG.


Assuntos
Grupos Étnicos , Glaucoma/etnologia , Refração Ocular/fisiologia , Erros de Refração/etnologia , Adulto , Idoso , California/epidemiologia , Estudos Transversais , Feminino , Glaucoma/complicações , Glaucoma/fisiopatologia , Humanos , Incidência , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Erros de Refração/etiologia , Erros de Refração/fisiopatologia , Estudos Retrospectivos
20.
Invest Ophthalmol Vis Sci ; 56(8): 4290-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26176866

RESUMO

PURPOSE: We compared across age-related macular degeneration (AMD) subtypes the effect of AMD risk variants, their predictive power, and heritability. METHODS: The prevalence of AMD was estimated among active non-Hispanic white Kaiser Permanente Northern California members who were at least 65 years of age as of June 2013. The genetic analysis included 5,170 overall AMD cases ascertained from electronic health records (EHR), including 1,239 choroidal neovascularization (CNV) cases and 1,060 nonexudative AMD cases without CNV, and 23,130 controls of non-Hispanic white ancestry from the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. Imputation was based on the 1000 Genomes Project reference panel. RESULTS: The narrow-sense heritability due to common autosomal single nucleotide polymorphisms (SNPs) was 0.37 for overall AMD, 0.19 for AMD unspecified, 0.20 for nonexudative AMD, and 0.60 for CNV. For the 19 previously reported AMD risk loci, the area under the receiver operating characteristic (ROC) curve was 0.675 for overall AMD, 0.640 for AMD unspecified, 0.678 for nonexudative AMD, and 0.766 for CNV. The individual effects on the risk of AMD for 18 of the 19 SNPs were in a consistent direction with those previously reported, including a protective effect of the APOE ε4 allele. Conversely, the risk of AMD was significantly increased in carriers of the ε2 allele. CONCLUSIONS: These findings provide an independent confirmation of many of the previously identified AMD risk loci, and support a potentially greater role of genetic factors in the development of CNV. The replication of established associations validates the use of EHR in genetic studies of ophthalmologic traits.


Assuntos
Predisposição Genética para Doença , Degeneração Macular/genética , Polimorfismo Genético , Idoso , Alelos , California/epidemiologia , Feminino , Genótipo , Humanos , Degeneração Macular/epidemiologia , Masculino , Fenótipo , Prevalência , Estudos Retrospectivos , Fatores de Risco
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