ABSTRACT
PURPOSE: To examine the relationship between proportion of African ancestry (PAA) and proliferative diabetic retinopathy (PDR) and to identify genetic loci associated with PDR using admixture mapping in African Americans with type 2 diabetes (T2D). METHODS: Between 1993 and 2013, 1440 participants enrolled in four different studies had fundus photographs graded using the Early Treatment Diabetic Retinopathy Study scale. Cases (n = 305) had PDR while controls (n = 1135) had nonproliferative diabetic retinopathy (DR) or no DR. Covariates included diabetes duration, hemoglobin A1C, systolic blood pressure, income, and education. Genotyping was performed on the Affymetrix platform. The association between PAA and PDR was evaluated using logistic regression. Genome-wide admixture scanning was performed using ANCESTRYMAP software. RESULTS: In the univariate analysis, PDR was associated with increased PAA (odds ratio [OR] = 1.36, 95% confidence interval [CI] = 1.16-1.59, P = 0.0002). In multivariate regression adjusting for traditional DR risk factors, income and education, the association between PAA and PDR was attenuated and no longer significant (OR = 1.21, 95% CI = 0.59-2.47, P = 0.61). For the admixture analyses, the maximum genome-wide score was 1.44 on chromosome 1. CONCLUSIONS: In this largest study of PDR in African Americans with T2D to date, an association between PAA and PDR is not present after adjustment for clinical, demographic, and socioeconomic factors. No genome-wide significant locus (defined as having a locus-genome statistic > 5) was identified with admixture analysis. Further analyses with even larger sample sizes are needed to definitively assess if any admixture signal for DR is present.
Subject(s)
Black or African American/genetics , Diabetic Retinopathy/ethnology , Diabetic Retinopathy/genetics , Adult , Black or African American/statistics & numerical data , Aged , Blood Pressure/genetics , Case-Control Studies , Chromosome Mapping , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/genetics , Female , Genetic Predisposition to Disease , Genome-Wide Association Study , Genotype , Glycated Hemoglobin/analysis , Humans , Male , Middle Aged , Odds Ratio , Regression Analysis , Risk FactorsABSTRACT
PURPOSE: To assess the feasibility and potential obstacles of a departmental switch from ranibizumab (Lucentis, Genentech, South San Francisco, CA) to bevacizumab (Avastin, Genentech) for the treatment of neovascular age-related macular degeneration (AMD). METHODS: A total of 154 eyes treated for wet AMD with ranibizumab or bevacizumab were examined over a 10-month period. The treatment protocol was monthly induction therapy followed by injections as needed for macular edema or subretinal fluid on optical coherence tomography, new hemorrhage or edema on examination, worsening vision, or leakage on fluorescein angiography. Central subfield thickness and pinhole vision were the main treatment outcomes. Study windows were compared using t tests and Mann-Whitney U tests. Statistical significance was defined as a P value of <0.05. RESULTS: The majority of patients (88%) were willing to accept a bevacizumab injection. There was no difference in frequency of injection, central subfield thickness, visual outcome, or endophthalmitis rate between the ranibizumab and bevacizumab groups. A small subset of patients (4.5%) appeared to respond more favorably to ranibizumab than bevacizumab. CONCLUSIONS: Bevacizumab appears to be a cost-effective alternative to ranibizumab for the treatment of neovascular AMD. Patients previously treated with ranibizumab are typically willing to switch to bevacizumab. In the overwhelming majority of patients, there is no major decline in clinical status. However, select patients may respond better to ranibizumab injections.
