Duke University

Vanderbilt University

Eric Postel

Cynthia A Toth

Ronald F Overaker

Brian C Dodge

Margaret A Pericak-Vance

Brooks W McCuen

Michael Hauser

Jonathan L Haines

Silke Schmidt

Anita Agarwal

William K Scott

Age-related macular degeneration (AMD) is a leading cause of visual impairment and blindness in the elderly whose etiology remains largely unknown. Previous studies identified chromosome 1q32 as harboring a susceptibility locus for AMD, but it was not identified. We identified a strongly associated haplotype in two independent data sets. DNA sequencing of the complement factor II gene (CFII) within this haplotype revealed a coding variant, Y402II, that significantly increases the risk for AMD with odds ratios between 2.45 and 5.57. This identifies Complement factor II as involved in pathogenesis of AMD. This single variant alone is so common that it likely explains 43 percent of AMD in older adults. In addition, we have replicated and refined previous reports implicating a coding change in LOC387715 as the second major AMD susceptibility allele. The effect of rs10490924 appears to be completely independent of the Y402H variant in the CFH gene. The joint effect of these two susceptibility genes is consistent with a multiplicative model, and together, they may explain as much as 65% of the PAR of AMD. In contrast, the effect of rs10490924 appears to be strongly modified by cigarette smoking. Smoking and LOC387715 together may explain as much as 34% of AMD. Our data indicate that variant genotypes at rs10490924 confer a substantially larger AMD risk to cigarette smokers than non-smokers. This observation is supported by traditional case-control modeling, by ordered subset linkage analysis (OSA) incorporating pack-years of cigarette smoking as a covariate, and by family-based association analysis using a more homogeneous set of families as defined by OSA.

Genetic variants increase the risk of age-related macular degeneration

Surgical instruments, especially for opthalmological surgical procedures, have a smooth, bulbous arcuate tip that surrounds the distal end of a lumen. The tip may be translucent and flexible. Most preferably, the tip is formed of a compliant, yet self-supporting, material, such as medical grade transparent silicone elastomer. The bulbous arcuate tip may take various geometric forms, for example, generally spherical, ellipsoid or the like. The bulbous arcuate tip may be symmetrical about the elongate axis of the instrument or may be asymmetrical (i.e., angularly disposed) relative to such longitudinal axis. The surgical instruments of this invention are most preferably made by first adhering a length of compliant tubing (e.g., silicone) onto a distal end of a rigid tube (e.g., a section of a stainless steel needle). The proximal rigid tube section is preferably coaxially sleeved over, and affixed to, the distal compliant tube section. A forming wire may then be inserted into the aligned lumens of the proximal rigid tube and distal compliant tube sections so that a terminal end section of the forming wire extends beyond the distal end of the compliant tube section. A bolus of curable liquid elastomer is then applied onto the distal end of compliant tube section around the forming wire protruding therefrom. By rotating and otherwise manipulating the tube sections during curing of the liquid elastomer, a bulbous arcuate tip may be formed. Once the elastomer tip is cured (solidified), the forming wire may be withdrawn thereby forming a through lumen which terminates at the tip. The tip may alternatively be constructed using injection-molding techniques.

Miniaturized surgical instruments especially useful for the opthalmologic surgical procedures and methods of making the same

Growing community of inventors

Durham, NC, United States of America

Eric Postel