Genetic Correlations Among Corneal Biophysical Parameters and Anthropometric Traits.

Purpose: The genetic architecture of corneal dysfunction remains poorly understood. Epidemiological and clinical evidence suggests a relationship between corneal structural features and anthropometric measures. We used global and local genetic similarity analysis to identify genomic features that may underlie structural corneal dysfunction. Methods: We assembled genome-wide association study summary statistics for corneal features (central corneal thickness, corneal hysteresis [CH], corneal resistance factor [CRF], and the 3 mm index of keratometry) and anthropometric traits (body mass index, weight, and height) in Europeans. We calculated global genetic correlations (rg) between traits using linkage disequilibrium (LD) score regression and local genetic covariance using ρ-HESS, which partitions the genome and performs regression with LD regions. Finally, we identified genes located within regions of significant genetic covariance and analyzed patterns of tissue expression and pathway enrichment. Results: Global LD score regression revealed significant negative correlations between height and both CH (rg = -0.12; P = 2.0 × 10-7) and CRF (rg = -0.11; P = 6.9 × 10-7). Local analysis revealed 68 genomic regions exhibiting significant local genetic covariance between CRF and height, containing 2874 unique genes. Pathway analysis of genes in regions with significant local rg revealed enrichment among signaling pathways with known keratoconus associations, including cadherin and Wnt signaling, as well as enrichment of genes modulated by copper and zinc ions. Conclusions: Corneal biophysical parameters and height share a common genomic architecture, which may facilitate identification of disease-associated genes and therapies for corneal ectasias. Translational Relevance: Local genetic covariance analysis enables the identification of associated genes and therapeutic targets for corneal ectatic disease.

Depression in Individuals With Diabetic Retinopathy in the US National Health and Nutrition Examination Survey, 2005-2008.

PURPOSE: To examine the relationship between diabetic retinopathy (DR) and depression in the United States. DESIGN: Retrospective, cross-sectional study. METHODS: National Health and Nutrition Examination Survey (NHANES) participants between 2005 and 2008 (ages 40-85 years) were included. Prevalence of major depression among DR stages as determined by retinal imaging was estimated. Multivariable models assessed associations between depression and DR. RESULTS: Depression was more common in those with moderate to severe DR (16%) than in those with no DR (7%), mild nonproliferative diabetic retinopathy (NPDR, 6%), or proliferative DR (5%). In a model with DR stages that adjusted for demographic factors, there was an association between moderate to severe DR and depression (odds ratio [OR], 2.46, 95% CI, 1.03-5.85). CONCLUSIONS: Depression was more prevalent in those with moderate to severe NPDR than in those with no DR, mild NPDR, or proliferative DR. This relationship is statistically significant after adjustment for demographic factors.

Anthropometric Measures and Their Relationship to Steep Cornea in the United States Population.

PURPOSE: The aim of this study was to determine the relationship between anthropometric measures and steep cornea. METHODS: Participants from the 1999 to 2008 US National Health and Nutrition Examination Survey visual examination were included (20,165 subjects). Cases had a mean dioptric power, averaged across the meridians, ≥ 48.0 diopters (n = 171). Separate multivariable models assessed body mass index, height, and weight in relation to steep cornea. Analyses included both overall and sex-stratified populations. RESULTS: A relationship between BMI and steep cornea in the overall population was not detected ( P for trend = 0.78). There was a strong inverse relationship between height (adjusted for weight) and steep cornea in the overall population ( P for trend <0.0001) and in women ( P for trend <0.0001). For every 1-inch increase in height, there was a 16% reduced odds of steep cornea in the overall population (OR, 0.84; 95% CI: 0.77-0.92). A relationship between weight and steep cornea was not detected in the overall population (P for trend = 0.79). CONCLUSIONS: Greater height was associated with a lower risk of steep cornea.

Characterizing astigmatism in the United States.

PURPOSE: To study astigmatism and astigmatism rule by (1) determining changes in prevalence in the United States between 1971 to 1975 and 1999 to 2008 and (2) identifying associations with demographic factors. SETTING: National survey. DESIGN: Retrospective cross-sectional study. METHODS: Participants of the 1971 to 1975 and 1999 to 2008 National Health and Nutrition Examination Survey (NHANES) aged 20 to 74 years representing the U.S population were included. The 1971 to 1975 NHANES measured astigmatism in participants using an algorithm based on presenting visual acuity, lensometry, and objective refraction. Similar methods were implemented using the 1999 to 2008 NHANES data for comparison. Prevalence of clinically significant astigmatism (≥1.0 diopters [D]) was identified, and logistic regression models were used to assess demographic associations with rule of astigmatism. RESULTS: A total of 3371 and 13 10 participants were included from the 1970s and 2000s NHANES. Main outcomes were prevalence estimates of astigmatism and odds ratios estimating associations with demographic characteristics. There was an increase in astigmatism from the 1970s to 2000s (14% [95% CI: 13.2-14.5] vs 24% [22.8-24.6], which was more pronounced in men (12% [10.8-12.7] vs 23% [21.9-24.2]) than in women (16% [14.9-16.8] vs 24% [23.0-25.7]). In adjusted analysis of the 2000s cohort, myopic patients had 8.34 (CI: 7.30-9.54) times greater odds of astigmatism than nonmyopic patients. In the 2000s, there was increased odds of against-the-rule (ATR) astigmatism in men (odds ratio [OR], 1.4; 95% CI: 1.1-1.8) compared with women, in nonmyopic patients (OR, 2.3; 95% CI: 1.7-3.1) compared with myopic patients, and in patients aged 60 to 74 years (OR, 3.7; 95% CI: 2.7-5.1) compared with those aged 20 to 39 years. CONCLUSIONS: There is greater prevalence of astigmatism and ATR astigmatism in 1999 to 2008 compared with 30 years before in the U.S. Factors associated with ATR astigmatism were being male, White, and nonmyopic.

Integrated Home- and Community-Based Services Improve Community Survival Among Independence at Home Medicare Beneficiaries Without Increasing Medicaid Costs.

OBJECTIVES: To determine the effect of home-based primary care (HBPC) for frail older adults, operating under Independence at Home (IAH) incentive alignment on long-term institutionalization (LTI). DESIGN: Case-cohort study using HBPC site, Medicare administrative data, and National Health and Aging Trends Study (NHATS) benchmarks. SETTING: Three IAH-participating HBPC sites in Philadelphia, PA, Richmond, VA, and Washington, DC. PARTICIPANTS: HBPC integrated with long-term services and supports (LTSS) cases (n = 721) and concurrent comparison groups (HBPC not integrated with LTSS: n = 82; no HBPC: n = 573). Cases were eligible if enrolled at one of the three HBPC sites from 2012 to 2015. Independence at Home-qualified (IAH-Q) concurrent comparison groups were selected from Philadelphia, PA; Richmond, VA; and Washington, DC. INTERVENTION: HBPC integrated with LTSS under IAH demonstration incentives. MEASUREMENTS: Measurements include LTI rate and mortality rates, community survival, and LTSS costs. RESULTS: The LTI rate in the three HBPC programs (8%) was less than that of both concurrent comparison groups (IAH-Q beneficiaries not receiving HBPC, 16%; patients receiving HBPC but not in the IAH demonstration practices, 18%). LTI for patients at each HBPC site declined over the three study years (9.9%, 9.4%, and 4.9%, respectively). Costs of home- and community-based services (HCBS) were nonsignificantly lower among integrated care patients ($2151/mo; observed-to-expected ratio = .88 [.68-1.09]). LTI-free survival in the IAH HBPC group was 85% at 36 months, extending average community residence by 12.8 months compared with IAH-q participants in NHATS. CONCLUSION: HBPC integrated with long-term support services delays LTI in frail, medically complex Medicare beneficiaries without increasing HCBS costs.