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Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25×10−8), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genome-wide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value = 9.11×10−11) and 8q12 (minimum p value 1.82×10−11) previously reported for MSE and myopia age at onset. We also used an intermarker linkage- disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer et al.) and showed replication of 10 additional loci associated with myopia previously reported by Kiefer et al. This is the first replication of these loci using myopia as the trait under analysis. “Replication-level” association was also seen between hyperopia and 12 of Kiefer et al.'s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of refractive error across the distribution.

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Sixty-five patients with mild to moderate nonproliferative diabetic retinopathy who enrolled in a prospective controlled clinical trial had stereofundus photographs assessed for change over an 8-mo period. The entire study group showed a worsening of retinopathy with time (P less than 0.001). The worsening was greater in the pump-treated group (15/32) than in the conventionally treated group (9/33). The significance of this difference ranged from P = 0.67, if changes in mean retinopathy level for each patient were compared, to P = 0.177 if a grading system keyed to the worse eye was compared. The difference in rates of change between treatment groups was found to be related to the baseline mean retinopathy level (P = 0.031), but less significantly so if baseline retinopathy keyed to the worse eye was used as a covariate (P = 0.08). Worsening occurred more frequently in those patients starting with the lower retinopathy levels. Progression was associated with the appearance of retinal infarcts (cotton-wool spots, soft exudates) and/or intraretinal microvascular abnormalities, with the pump patients showing a significant increase in these individual retinal lesions compared with the conventionally treated patients over 8 mo (P less than 0.025).

The combination of multiple cerebral ischemic lesions and endocardial lesions, including valvular vegetations, suggests that these cerebral ischemic events represent cerebral emboli, and that these cerebral embolic events originate from vegetative lesions on the mitral or, less commonly, aortic valve, in association with lupus anticoagulant.

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