Miho Yasuda

Global prevalence and major risk factors of diabetic retinopathy

OBJECTIVE To examine the global prevalence and major risk factors for diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) among people with diabetes. RESEARCH DESIGN AND METHODS A pooled analysis using individual participant data from population-based studies around the world was performed. A systematic literature review was conducted to identify all population-based studies in general populations or individuals with diabetes who had ascertained DR from retinal photographs. Studies provided data for DR end points, including any DR, proliferative DR, diabetic macular edema, and VTDR, and also major systemic risk factors. Pooled prevalence estimates were directly age-standardized to the 2010 World Diabetes Population aged 20–79 years. RESULTS A total of 35 studies (1980–2008) provided data from 22,896 individuals with diabetes. The overall prevalence was 34.6% (95% CI 34.5–34.8) for any DR, 6.96% (6.87–7.04) for proliferative DR, 6.81% (6.74–6.89) for diabetic macular edema, and 10.2% (10.1–10.3) for VTDR. All DR prevalence end points increased with diabetes duration, hemoglobin A1c, and blood pressure levels and were higher in people with type 1 compared with type 2 diabetes. CONCLUSIONS There are approximately 93 million people with DR, 17 million with proliferative DR, 21 million with diabetic macular edema, and 28 million with VTDR worldwide. Longer diabetes duration and poorer glycemic and blood pressure control are strongly associated with DR. These data highlight the substantial worldwide public health burden of DR and the importance of modifiable risk factors in its occurrence. This study is limited by data pooled from studies at different time points, with different methodologies and population characteristics.

The Prevalence of Age-Related Macular Degeneration in Asians : A Systematic Review and Meta-Analysis

OBJECTIVE To determine the prevalence of age-related macular degeneration (AMD) in Asian populations and to compare this with prevalence in white populations. DESIGN A clear understanding of AMD prevalence in Asians is essential to meet future demands for eye health care. METHODS We searched published literature reporting AMD prevalence in Asian populations. We limited studies examined to those using standardized grading systems (either the Wisconsin Age-Related Maculopathy Grading System or the international classification proposed by the International ARM Epidemiological Study Group). We used metaanalytical methods to calculate age-specific pooled prevalence of AMD using inverse-variance weighting in a random effect model. We also calculated pooled estimates of age-standardized prevalence. A metaregression model was used to examine gender differences and differences between Asian and white populations. RESULTS We identified 9 studies reporting AMD prevalence from 4 Asian populations. Pooled prevalence estimates of early and late AMD in Asian populations aged 40 to 79 years were 6.8% (95% confidence interval [CI], 4.6%-8.9%) and 0.56% (95% CI, 0.30%-0.81%), respectively; corresponding prevalence estimates in white populations were 8.8% (95% CI, 3.8%-13.8%) and 0.59% (95% CI, 0.35%-0.84%), respectively. Reliable prevalence estimates of AMD in Asian persons aged > or =80 years were not available owing to small subject numbers in this age category. CONCLUSIONS Among persons aged 40 to 79 years, the age-specific prevalence of late AMD in Asians was comparable with that reported from white populations, but early AMD signs were less common among Asians. Further studies in Asian populations are warranted to investigate whether certain specific AMD phenotypes or subtypes, such as polypoidal choroidal vasculopathy, are more common.

Genome-wide association study identifies two susceptibility loci for exudative age-related macular degeneration in the Japanese population

Age-related macular degeneration (AMD), the leading cause of irreversible blindness in the world, is a complex disease caused by multiple environmental and genetic risk factors. To identify genetic factors that modify the risk of exudative AMD in the Japanese population, we conducted a genome-wide association study and a replication study using a total of 1,536 individuals with exudative AMD and 18,894 controls. In addition to CFH (rs800292, P = 4.23 × 10−15) and ARMS2 (rs3750847, P = 8.67 × 10−29) loci, we identified two new susceptibility loci for exudative AMD: TNFRSF10A-LOC389641 on chromosome 8p21 (rs13278062, combined P = 1.03 × 10−12, odds ratio = 0.73) and REST-C4orf14-POLR2B-IGFBP7 on chromosome 4q12 (rs1713985, combined P = 2.34 × 10−8, odds ratio = 1.30). Fine mapping revealed that rs13278062, which is known to alter TNFRSF10A transcriptional activity, had the most significant association in 8p21 region. Our results provide new insights into the pathophysiology of exudative AMD.

Prevalence and risk factors for myopic retinopathy in a japanese population: The hisayama study

PURPOSE To examine the prevalence of myopic retinopathy and its risk factors in a general Japanese population. DESIGN Population-based, cross-sectional study. PARTICIPANTS In 2005, a total of 1969 Hisayama residents aged ≥ 40 years consented to participate in this study. Of these, 1892 subjects with adequate data were enrolled. METHODS Each participant underwent comprehensive physical and eye examinations that included measurements of refractive error, axial lengths, and color fundus photography. Myopic retinopathy was defined as the presence of diffuse chorioretinal atrophy, patchy chorioretinal atrophy, lacquer cracks, or macular atrophy. MAIN OUTCOME MEASURES Prevalence of myopic retinopathy. RESULTS Thirty-three participants had myopic retinopathy and the prevalence was 1.7% (2.2% in women and 1.2% in men). The prevalence of myopic retinopathy increased significantly with advancing age. Diffuse chorioretinal atrophy, patchy chorioretinal atrophy, lacquer cracks, and macular atrophy were present in 1.7%, 0.4%, 0.2%, and 0.4% of subjects, respectively. In multivariate analysis, myopic retinopathy was significantly associated with older age (per 1 year: odds ratio [OR], 1.12; 95% confidence interval [CI], 1.07-1.18), female gender (OR, 3.29; 95% CI, 1.09-9.92), and longer axial length (per 1 mm: OR, 4.20; 95% CI, 3.03-5.83). CONCLUSIONS The prevalence of myopic retinopathy was 1.7% in a general Japanese population. Older age, female gender, and longer axial length were significant risk factors for myopic retinopathy.

Original articlePrevalence and Risk Factors for Myopic Retinopathy in a Japanese Population: The Hisayama Study

PURPOSE To examine the prevalence of myopic retinopathy and its risk factors in a general Japanese population. DESIGN Population-based, cross-sectional study. PARTICIPANTS In 2005, a total of 1969 Hisayama residents aged ≥ 40 years consented to participate in this study. Of these, 1892 subjects with adequate data were enrolled. METHODS Each participant underwent comprehensive physical and eye examinations that included measurements of refractive error, axial lengths, and color fundus photography. Myopic retinopathy was defined as the presence of diffuse chorioretinal atrophy, patchy chorioretinal atrophy, lacquer cracks, or macular atrophy. MAIN OUTCOME MEASURES Prevalence of myopic retinopathy. RESULTS Thirty-three participants had myopic retinopathy and the prevalence was 1.7% (2.2% in women and 1.2% in men). The prevalence of myopic retinopathy increased significantly with advancing age. Diffuse chorioretinal atrophy, patchy chorioretinal atrophy, lacquer cracks, and macular atrophy were present in 1.7%, 0.4%, 0.2%, and 0.4% of subjects, respectively. In multivariate analysis, myopic retinopathy was significantly associated with older age (per 1 year: odds ratio [OR], 1.12; 95% confidence interval [CI], 1.07-1.18), female gender (OR, 3.29; 95% CI, 1.09-9.92), and longer axial length (per 1 mm: OR, 4.20; 95% CI, 3.03-5.83). CONCLUSIONS The prevalence of myopic retinopathy was 1.7% in a general Japanese population. Older age, female gender, and longer axial length were significant risk factors for myopic retinopathy.

High Serum Bilirubin Levels and Diabetic Retinopathy : The Hisayama Study

PURPOSE To assess the association between serum total bilirubin levels and diabetic retinopathy prevalence in participants of the Hisayama Study who had diabetes and impaired glucose metabolism. DESIGN Population-based, cross-sectional study. PARTICIPANTS Of 3119 participants of the Hisayama Study Eye Examinations in 2007, Japan, 1672 aged ≥40 years with either diabetes or impaired glucose metabolism (defined by a 75-g oral glucose tolerance test) were enrolled in the present study. METHODS Diabetic retinopathy was assessed via ophthalmic examination after pupil dilatation. The presence and the severity of diabetic retinopathy were determined by grading of color fundus photographs using the modified Airlie House classification system. Association of diabetic retinopathy with serum bilirubin quartiles was assessed using logistic regression model adjusting for age and known risk factors for diabetic retinopathy. MAIN OUTCOME MEASURES Prevalent diabetic retinopathy. RESULTS Diabetic retinopathy was present in 70 of 1672 (4.2%) participants. The prevalence of diabetic retinopathy in persons with the highest bilirubin quartile (≥0.9 mg/dL) was 2.7%, compared with the prevalence of 3.4%, 5.1%, and 5.1% in those with the first (<0.6 mg/dL), second (0.6-0.69 mg/dL), and third quartiles (0.7-0.89 mg/dL). After adjusting for factors known to be associated with diabetic retinopathy, the prevalence was significantly lower among persons with the highest bilirubin quartile compared with those with the lowest quartile (odds ratio [OR], 0.25; 95% confidence interval [CI], 0.09-0.72) or compared with those in the 3 lower quartiles (OR, 0.25; 95% CI, 0.11-0.58). CONCLUSIONS Elevated serum bilirubin levels may be protective against diabetic retinopathy among persons with either diabetes or impaired glucose metabolism, independent of known risk factors for diabetic retinopathy.

Nine-Year Incidence and Risk Factors for Retinal Vein Occlusion in a General Japanese Population: The Hisayama Study

PURPOSE To estimate the long-term cumulative incidence and risk factors for retinal vein occlusion (RVO) in a population-based cohort study of Japanese. METHODS In 1998, a total of 1775 individuals aged 40 years or older underwent a baseline eye examination. Of those, 1369 subjects (77.1%) took part in the follow-up eye examination in 2007 and were enrolled in the present study. Each participant underwent a comprehensive examination. The diagnosis of RVO, including branch (BRVO) and central RVO (CRVO), was determined by grading color fundus photographs. Logistic regression analysis was performed to determine risk factors for RVO. RESULTS The 9-year cumulative incidence of RVO was 3.0% (2.7% for BRVO and 0.3% for CRVO). The age-specific cumulative incidence of RVO significantly increased with age (P for trend = 0.03). After adjusting for age and sex, higher diastolic blood pressure and chronic kidney disease (CKD) were significantly associated with RVO. In multivariate analysis, higher diastolic blood pressure (per 10 mm Hg) (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.14 to 2.01) and CKD (OR, 2.23; 95% CI, 1.02 to 4.89) remained independently significant risk factors for RVO. In stratified analysis, the risk of RVO was higher in subjects with CKD than that in subjects without CKD in both the nonhypertension and the hypertension groups. CONCLUSIONS These findings suggest that the incidence of RVO is higher in Japanese than that in other Asians and Caucasians, and that higher blood pressure and CKD are independent risk factors for RVO in the Japanese.

Prevalence and Systemic Risk Factors for Retinal Vein Occlusion in a General Japanese Population: The Hisayama Study

PURPOSE To examine the prevalence of retinal vein occlusion (RVO) and its systemic relevant factors in a general Japanese population aged 40 years or older. METHODS In 1998, 1775 Hisayama residents consented to participate in the study. Each participant underwent a comprehensive examination that included ophthalmic testing. RVO was determined by grading color fundus photographs. Logistic regression analysis was performed to determine risk factors for RVO. RESULTS Of the 1775 subjects examined, 38 had RVO. The prevalence of RVO was 2.1% (2.0% for branch RVO and 0.2% for central RVO). After adjustment for age and sex, it was found that systolic and diastolic blood pressures, hypertension, and hematocrit were significantly associated with RVO. In multivariate analysis, age (per 10 years; odds ratio [OR], 1.47; 95% confidence interval [CI], 1.04-2.08), hypertension (OR, 4.25; 95% CI, 1.82-9.94), and hematocrit (per 10%; OR, 3.09; 95% CI, 1.10-1.22) remained independently significant risk factors for RVO. Both high-normal blood pressure and hypertension were significantly associated with RVO. Furthermore, compared with normotensive subjects without high hematocrit, the likelihood of RVO was markedly high in subjects having both high blood pressure and high hematocrit (age- and sex-adjusted OR, 36.0; 95% CI, 4.43-292). CONCLUSIONS The findings suggest that the prevalence of RVO is higher in the Japanese than in other Asians or Caucasians and that older age, higher hematocrit, and both hypertension and high-normal blood pressure are significant risk factors for RVO in the Japanese.

Antiangiogenic shift in vitreous after vitrectomy in patients with proliferative diabetic retinopathy

PURPOSE We determined whether the concentrations of VEGF, erythropoietin, and endostatin in the vitreous are altered after vitrectomy in patient with proliferative diabetic retinopathy (PDR). METHODS We measured the levels of VEGF, erythropoietin, and endostatin by sandwich ELISA in vitreous samples collected from 38 eyes of 33 patients with PDR before pars plana vitrectomy (without IOL implantation) and the same 38 eyes during IOL implantation 3.1 to 25.7 (mean 6.7) months after the initial vitrectomy. RESULTS The mean vitreous levels of VEGF (964.5 pg/mL) and erythropoietin (1359.5 pg/mL) in the samples collected before vitrectomy were significantly higher in patients with PDR than in the control patients (0.68 and 70.7 pg/mL, respectively; P < 0.01). The levels of VEGF (292.5 pg/mL) and erythropoietin (557.9 pg/mL) in the samples from eyes with PDR collected at the time of IOL implantation were significantly lower than those collected before vitrectomy (P < 0.01). In contrast, the changes in the level of endostatin were not significant after vitrectomy. The VEGF and erythropoietin levels in the vitreous fluid from patients with PDR were correlated inversely with the interval between the initial vitrectomy and the time of the IOL implantation. CONCLUSIONS The significant decrease in the intravitreal concentration of VEGF and erythropoietin, and an absence of a significant change in the endostatin indicated a shift in the antiangiogenic balance in the vitreous of patients with PDR after successful vitrectomy.

Low-frequency coding variants in CETP and CFB are associated with susceptibility of exudative age-related macular degeneration in the Japanese population.

Age-related macular degeneration (AMD) is a major cause of blindness in the elderly. Previous sequencing studies of AMD susceptibility genes have revealed the association of rare coding variants in CFH, CFI, C3 and C9 in European population; however, the impact of rare or low-frequency coding variants on AMD susceptibility in other populations is largely unknown. To identify the role of low-frequency coding variants on exudative AMD susceptibility in a Japanese population, we analysed the association of coding variants of 34 AMD candidate genes in the two-stage design by a multiplex PCR-based target sequencing method. We used a total of 2,886 (1st: 827, 2nd: 2,059) exudative AMD cases including typical AMD, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation and 9,337 (1st: 3,247 2nd: 6,090) controls. Gene-based analysis found a significant association of low-frequency variants (minor allele frequency (MAF) < 0.05) in CETP, C2 and CFB. The association of CETP remained after conditioned with all known genome-wide association study (GWAS) associated variants. In addition, when we included only disruptive variants, enrichment of rare variants (MAF < 0.01) was also observed after conditioned with all GWAS associated variants (P = 1.03 × 10−6, odds ratio (OR) = 2.48). Haplotype and conditional analysis of the C2-CFB-SKIV2L locus showed a low-frequency variant (R74H) in CFB would be individually associated with AMD susceptibility independent of the GWAS associated SNP. These findings highlight the importance of target sequencing to reveal the impact of rare or low-frequency coding variants on disease susceptibility in different ethnic populations.