T.C. Chen

DNA sequence variants in the LOXL1 gene are associated with pseudoexfoliation glaucoma in a U.S. clinic-based population with broad ethnic diversity

BackgroundPseudoexfoliation syndrome is a major risk factor for glaucoma in many populations throughout the world. Using a U.S. clinic-based case control sample with broad ethnic diversity, we show that three common SNPs in LOXL1 previously associated with pseudoexfoliation in Nordic populations are significantly associated with pseudoexfoliation syndrome and pseudoexfoliation glaucoma.MethodsThree LOXL1 SNPs were genotyped in a patient sample (206 pseudoexfoliation, 331 primary open angle glaucoma, and 88 controls) from the Glaucoma Consultation Service at the Massachusetts Eye and Ear Infirmary. The SNPs were evaluation for association with pseudeoexfoliation syndrome, pseudoexfoliation glaucoma, and primary open angle glaucoma.ResultsThe strongest association was found for the G allele of marker rs3825942 (G153D) with a frequency of 99% in pseudoexfoliation patients (with and without glaucoma) compared with 79% in controls (p = 1.6 × 10-15; OR = 20.93, 95%CI: 8.06, 54.39). The homozygous GG genotype is also associated with pseudoexfoliation when compared to controls (p = 1.2 × 10-12; OR = 23.57, 95%CI: 7.95, 69.85). None of the SNPs were significantly associated with primary open angle glaucoma.ConclusionThe pseudoexfoliation syndrome is a common cause of glaucoma. These results indicate that the G153D LOXL1 variant is significantly associated with an increased risk of pseudoexfoliation and pseudoexfoliation glaucoma in an ethnically diverse patient population from the Northeastern United States. Given the high prevalence of pseudooexfoliation in this geographic region, these results also indicate that the G153D LOXL1 variant is a significant risk factor for adult-onset glaucoma in this clinic based population.

Polarization-sensitive spectral-domain optical coherence tomography using a single line scan camera

Polarization-sensitive optical coherence tomography can be used to measure the birefringence of biological tissue such as the human retina. Previous measurements with a time-domain polarization-sensitive optical coherence tomography system revealed that the birefringence of the human retinal nerve fiber layer is not constant, but varies as a function of location around the optic nerve head. Here we present a spectral-domain polarization-sensitive optical coherence tomography system that uses a spectrometer configuration with a single line scan camera and a Wollaston prism in the detection arm. Since only one camera has to be synchronized with other components in the system, the design is simplified considerably. This system is 60 times faster than a time-domain polarization-sensitive optical coherence tomography system. Data was acquired using concentric circular scans around the optic nerve head of a young healthy volunteer and the acquisition time for 12 circular scans was reduced from 72 s to 1.2 s. The acquired data sets demonstrate variations in retinal thickness and double pass phase retardation per unit depth that were similar to data from the same volunteer taken with a time-domain polarization-sensitive system. The double pass phase retardation per unit depth of the retinal nerve fiber layer varied between 0.18 and 0.40 degrees/mum, equivalent to a birefringence of 2.2 * 10(-4) and 4.8 * 10(-4) respectively, measured at 840 nm.

Solar Exposure and Residential Geographic History in Relation to Exfoliation Syndrome in the United States and Israel

IMPORTANCEnResidential (geographic) history and extent of solar exposure may be important risk factors for exfoliation syndrome (XFS) but, to our knowledge, detailed lifetime solar exposure has not been previously evaluated in XFS.nnnOBJECTIVEnTo assess the relation between residential history, solar exposure, and XFS.nnnDESIGN, SETTING, AND PARTICIPANTSnThis clinic-based case-control study was conducted in the United States and Israel. It involved XFS cases and control individuals (all ≥ 60-year-old white individuals) enrolled from 2010 to 2012 (United States: 118 cases and 106 control participants; Israel: 67 cases and 72 control participants).nnnMAIN OUTCOMES AND MEASURESnWeighted lifetime average latitude of residence and average number of hours per week spent outdoors as determined by validated questionnaires.nnnRESULTSnIn multivariable analyses, each degree of weighted lifetime average residential latitude away from the equator was associated with 11% increased odds of XFS (pooled odds ratio [OR], 1.11; 95% CI, 1.05-1.17; P < .001). Furthermore, every hour per week spent outdoors during the summer, averaged over a lifetime, was associated with 4% increased odds of XFS (pooled OR, 1.04; 95% CI, 1.00-1.07; P = .03). For every 1% of average lifetime summer time between 10 am and 4 pm that sunglasses were worn, the odds of XFS decreased by 2% (OR, 0.98; 95% CI, 0.97-0.99; P < .001) in the United States but not in Israel (OR, 1.00; 95% CI, 0.99-1.01; P = .92; P for heterogeneity = .005). In the United States, after controlling for important environmental covariates, history of work over water or snow was associated with increased odds of XFS (OR, 3.86; 95% CI, 1.36-10.9); in Israel, there were too few people with such history for analysis. We did not identify an association between brimmed hat wear and XFS (P > .57).nnnCONCLUSIONS AND RELEVANCEnLifetime outdoor activities may contribute to XFS. The association with work over snow or water and the lack of association with brimmed hat wear suggests that ocular exposure to light from reflective surfaces may be an important type of exposure in XFS etiology.

Correlation of localized glaucomatous visual field defects and spectral domain optical coherence tomography retinal nerve fiber layer thinning using a modified structure–function map for OCT

PurposeTo study the correlation between glaucomatous visual field (VF) defects assessed by standard automated perimetry (SAP) and peripapillary retinal nerve fiber layer (RNFL) thinning measured by spectral domain optical coherence tomography (OCT) using a modified OCT-based peripapillary RNFL structure–function map.Patients and methodsPerimetric glaucoma patients and age-matched normal control subjects were recruited from a university hospital clinic. All eyes underwent testing with the Spectralis spectral domain OCT and SAP on the same day. An OCT-based correspondence map, which correlated VF areas with peripapillary RNFL sectors was created to evaluate the relationship between glaucomatous RNFL thinning and VF loss in six nerve fiber layer bundle areas. Correlations of RNFL thinning with corresponding VF defects were examined using Spearman rank-order correlations. To demonstrate the association between localized VF defects and RNFL thickness, the theoretical curves were made according to an established log-linear model. The measured RNFL thickness values and VF defects were presented in the same scatterplot for each sector.ResultsFifty-six glaucoma patients and 85 normal subjects were included in the study. Significant association between localized VF loss and RNFL thinning was found in corresponding areas. Data from the current study fit well with established log-linear models, which compare RNFL thickness values with VF defects.ConclusionAnalysis of RNFL thinning in eyes with localized glaucomatous VF defects showed good structure–function correlation in a new OCT-based structure–function correspondence map.