OBJECTIVETo 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 METHODSA 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.RESULTSA 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.CONCLUSIONSThere 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.
Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly with limited therapeutic options. Here, we report on a study of >12 million variants including 163,714 directly genotyped, most rare, protein-altering variant. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5×10–8) distributed across 34 loci. While wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first signal specific to wet AMD, near MMP9 (difference-P = 4.1×10–10). Very rare coding variants (frequency < 0.1%) in CFH, CFI, and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.
Background
A comprehensive evaluation of the independent and combined associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality is required for assessment of the impact of kidney function on risk in the general population, with implications for improving the definition and staging of chronic kidney disease (CKD).
Methods
A collaborative meta-analysis of general population cohorts was undertaken to pool standardized data for all-cause and cardiovascular mortality. The two kidney measures and potential confounders from 14 studies (105,872 participants; 730,577 person-years) with urine albumin-to-creatinine ratio (ACR) measurements and seven studies (1,128,310 participants; 4,732,110 person-years) with urine protein dipstick measurements were modeled.
Findings
In ACR studies, mortality risk was unrelated to eGFR between 75-105 ml/min/1·73 m2 and increased at lower eGFR. Adjusted hazard ratios (HRs) for all-cause mortality at eGFR 60, 45, and 15 (versus 95) ml/min/1·73 m2 were 1·18 (95% CI: 1·05-1·32), 1·57 (1·39-1·78), and 3·14 (2·39-4·13), respectively. ACR was associated with mortality risk linearly on the log-log scale without threshold effects. Adjusted HRs for all-cause mortality at ACR 10, 30, and 300 (versus 5) mg/g were 1·20 (1·15-1·26), 1·63 (1·50-1·77), and 2·22 (1·97-2·51). eGFR and ACR were multiplicatively associated with mortality without evidence of interaction. Similar findings were observed for cardiovascular mortality and in dipstick studies.
Interpretation
Lower eGFR (<60 ml/min/1·73 m2) and higher albuminuria (ACR ≥10 mg/g) were independent predictors of mortality risk in the general population. This study provides quantitative data for using both kidney measures for risk evaluation and CKD definition and staging.
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