Race/Ethnicity Analysis of Vascular Alterations in Optical Coherence Tomography Angiography in Diabetic Patients.

PURPOSE: Racial and ethnic minorities have a higher prevalence of diabetic retinopathy (DR) and present at advanced stages of disease. In an urban hospital population, we investigated microvascular differences in optical coherence tomography angiography (OCTA) between racial/ethnic groups while adjusting for socioeconomic status (SES). METHODS: 3 × 3 mm2 macular OCTA scans were obtained for analysis of foveal avascular zone (FAZ) area, FAZ perimeter as well as superficial (SCP) and deep capillary plexus (DCP) vessel density (VD), vessel length density (VLD), and adjusted flow index (AFI). SES was measured using the Area Deprivation Index. Multivariable regression models were used to adjust estimates for relevant confounders. RESULTS: 217 non-diabetic and 1,809 diabetic patients were included in the study, consisting of 42.2% Hispanic, 24.9% non-Hispanic (NH) Asian, 6.8% NH Black, 9.7% NH White and 16.3% Other patients. NH White was used as the reference group. Hispanic, NH Asian, and NH Black patients had significantly greater FAZ areas and FAZ perimeters, and lower DCP VD and VLD, among both non-diabetic and diabetic patients (Benjamini-Hochberg adjusted P-values <0.05). The addition of SES scores in the models did not modify any regressions significantly. CONCLUSIONS: In patients with and without diabetes, racial and ethnic minorities have significant retinal microvasculature differences when compared to NH White patients, regardless of SES. These differences are pronounced in DCP and may predispose racial/ethnic minorities to worse outcomes in DR, thus widening disparities in ophthalmic care.

Anterior Segment OCT for Detection of Narrow Angles: A Community-Based Diagnostic Accuracy Study.

PURPOSE: To assess the diagnostic accuracy of anterior segment OCT (AS-OCT) screening for detecting gonioscopically narrow angles. DESIGN: Population-based cross-sectional study. PARTICIPANTS: A stratified random sample of individuals aged ≥ 60 years, selected from a door-to-door census performed in low-lying Nepal. TESTING: Participants underwent AS-OCT, posterior segment OCT, and intraocular pressure (IOP) testing in the community. Those meeting referral criteria in either eye were invited to have a comprehensive eye examination including gonioscopy. Referral criteria included (i) the lowest 2.5% of AS-OCT measurements, (ii) retinal OCT results suggestive of glaucomatous optic neuropathy, diabetic retinopathy, or age-related macular degeneration, and (iii) elevated IOP. MAIN OUTCOME MEASURES: Sensitivity and specificity of 5 semiautomated AS-OCT parameters relative to gonioscopically narrow angles, defined as the absence of visible trabecular meshwork for ≥ 180° on nonindentation gonioscopy. RESULTS: Of 17 656 people aged ≥ 60 years enumerated from 102 communities, 12 633 (71.6%) presented for AS-OCT testing. Referral was recommended for 697 participants based on AS-OCT criteria and 2419 participants based on other criteria, of which 858 had gonioscopy performed by a glaucoma specialist. Each of the 5 AS-OCT parameters offered good diagnostic information for predicting eyes with gonioscopically narrow angles, with areas under the receiver operating characteristic curve ranging from 0.85 to 0.89. The angle opening distance at 750 µm from the scleral spur (AOD750) provided the most diagnostic information, providing an optimal sensitivity of 87% (95% confidence interval [CI], 75%-96%) and specificity of 77% (71%-83%) at a cutpoint of 367 µm, and a sensitivity of 65% (95% CI, 54%-74%) when specificity was constrained to 90% (cutpoint, 283 µm). CONCLUSIONS: On AS-OCT, the AOD750 parameter detected approximately two-thirds of cases of gonioscopically narrow angles when test specificity was set to 90%. Although such a sensitivity may not be sufficient when screening solely for narrow angles, AS-OCT requires little additional effort if posterior segment OCT is already being performed and thus could provide incremental benefit when performing OCT-based screening. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Seroreversion to Chlamydia trachomatis Pgp3 antigen among children in a hyperendemic region of Amhara, Ethiopia.

Monitoring trachoma transmission with antibody data requires characterization of decay in IgG to Chlamydia trachomatis antigens. In a three-year longitudinal cohort in a high transmission setting, we estimated a median IgG half-life of 3 years and a seroreversion rate of 2.5 (95% CI: 1.6, 3.5) per 100 person-years.

Association of Male Sex and Microvascular Alterations on Optical Coherence Tomography Angiography in Diabetes.

Purpose: Epidemiologically, men have a higher incidence, severity, and progression of diabetic retinopathy (DR) than women. We investigated microvascular differences between men and women with diabetes on optical coherence tomography angiography (OCTA). Methods: Three × 3 mm OCTA macula scans of non-diabetic and patients with diabetes were obtained. Vascular parameters included parafoveal vessel density (VD), vessel length density (VLD), and flow index (FI) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) as well as foveal avascular zone (FAZ) area and perimeter. Multivariable linear regression was used for statistical analysis. Results: There were 1809 patients with diabetes and 217 non-diabetic participants that were included in this study. Diabetic individuals included those with no DR (n = 1356), mild non-proliferative DR (NPDR; n = 286), moderate NPDR (n = 126), and severe NPDR/proliferative DR (PDR; n = 41). Male sex was significantly associated with smaller FAZ area/perimeter and lower DCP VLD in both non-diabetic subjects and patients with diabetes. Male sex in the diabetic group was additionally associated with lower SCP VD/VLD and DCP VD. Addition of an interaction between male sex and diabetes status in the interaction analysis showed that being male and diabetic conferred increased reduction in DCP VD and VLD compared to sex-based changes in non-diabetics. Larger FAZ perimeter, lower SCP VD/VLD, and lower DCP VLD were associated with poorer visual acuity in diabetics. Conclusions: On OCTA, male patients with diabetes may have more severe microvascular disease especially in the DCP compared to women. Translational Evidence: Sex-based alterations in diabetic microvascular disease has the potential to influence future basic and clinical studies as well as the implementation of OCTA disease markers.

Seroreversion to Chlamydia trachomatis Pgp3 antigen among children in a hyperendemic region of Amhara, Ethiopia.

Monitoring trachoma transmission with antibody data requires characterization of decay in IgG to Chlamydia trachomatis antigens. In a three-year longitudinal cohort in a high transmission setting, we estimated a median IgG half-life of 3 years and a seroreversion rate of 2.5 (95% CI: 1.6, 3.5) per 100 person-years.

Earlier Introduction to Sugar-Sweetened Beverages Associated With Lower Diet Quality Among WIC Children at Age 3 Years.

OBJECTIVE: Examine the association between the timing of sugar-sweetened beverages (SSBs) and 100% juice introduction with subsequent diet quality at age 3 years. DESIGN: Secondary analysis of a publicly available, national longitudinal dataset. PARTICIPANTS: A total of 2,218 children from the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). MAIN OUTCOME MEASURE: Dietary intakes were assessed using a 24-hour dietary recall completed by caregivers of children aged 3 years. Diet quality was assessed using the Healthy Eating Index Score-2015 (HEI-2015). ANALYSIS: Linear regression was used to assess the relationship between the timing of introduction to 100% juice and SSBs with HEI-2015. Adjustments were made for child- and maternal-related factors. RESULTS: Delayed introduction of SSBs during the first 2 years of life was associated with an increased HEI-2015 score. In adjusted analyses, for every 1-month delay in the introduction, there was a 0.09-point increase (95% confidence interval, 0.04-0.13) in the HEI-2015 score at 3 years. CONCLUSIONS AND IMPLICATIONS: Earlier introduction to SSBs may be associated with subsequent lower diet quality in WIC participants. This association may be driven by total fruit, whole grains, and added sugars HEI component scores. Further research is needed to support changes to existing WIC nutrition practices regarding SSBs and 100% juice.

Single-cell analyses identify dysfunctional CD16+ CD8 T cells in smokers.

Tobacco smoke exposure contributes to the global burden of communicable and chronic diseases. To identify immune cells affected by smoking, we use single-cell RNA sequencing on peripheral blood from smokers and nonsmokers. Transcriptomes reveal a subpopulation of FCGR3A (CD16)-expressing Natural Killer (NK)-like CD8 T lymphocytes that increase in smokers. Mass cytometry confirms elevated CD16+ CD8 T cells in smokers. Inferred as highly differentiated by pseudotime analysis, NK-like CD8 T cells express markers characteristic of effector memory re-expressing CD45RA T (TEMRA) cells. Indicative of immune aging, smokers' CD8 T cells are biased toward differentiated cells and smokers have fewer naïve cells than nonsmokers. DNA methylation-based models show that smoking dose is associated with accelerated aging and decreased telomere length, a biomarker of T cell senescence. Immune aging accompanies T cell senescence, which can ultimately lead to impaired immune function. This suggests a role for smoking-induced, senescence-associated immune dysregulation in smoking-mediated pathologies.

Smoking-associated AHRR demethylation in cord blood DNA: impact of CD235a+ nucleated red blood cells.

BACKGROUND: Numerous studies have demonstrated that DNA methylation levels in the aryl hydrocarbon receptor repressor (AHRR) gene measured in cord blood are significantly associated with prenatal tobacco smoke exposure and can be used as a fetal exposure biomarker. The mechanism driving this demethylation has not been determined and it is unclear if all cord blood cell types are impacted. Nucleated red blood cells (nRBCs/CD235a+ cells) are developmentally immature RBCs that display genome-wide hypomethylation and are observed at increased frequency in the cord blood of smoking mothers. We tested if AHRR methylation levels in CD235a+ nRBCs or nRBC counts influenced AHRR methylation in whole cord blood. METHODS: Cord blood was collected from smoking (n = 34) and nonsmoking (n = 19) mothers and DNA was prepared from whole cord blood, isolated CD235a+ nRBCs, and CD14+ monocytes. AHRR methylation in cord blood DNA was measured using Illumina 850K arrays (cg05575921, chr5:373378). Pyrosequencing was used to compare methylation levels among cord blood, CD235a+, and CD14+ cells. We measured nRBC percentages using conventional complete blood counts and estimated percent nRBCs by a deconvolution model. RESULTS: Methylation levels in AHRR were significantly lower in nRBCs relative to whole cord blood and CD14+ monocytes. While AHRR methylation levels in the cell types were significantly correlated across all subjects, methylation values at the chr5:373378 CpG averaged 14.6% lower in nRBCs (range 0.4 to 24.8%; p = 3.8E-13) relative to CD14+, with nonsmokers showing a significantly greater hypomethylation (- 4.1%, p = 1.8E-02). Methylation level at the AHRR chr5:373378 CpG was strongly associated with self-reported smoking in both CD14+ monocytes (t test p = 5.7E-09) and nRBCs (p = 4.8E-08), as well as cotinine levels (regression p = 1.1E-07 and p = 3.6E-04, respectively). For subjects with whole blood 850K data, robust linear regression models adjusting for estimated cell type composition, either including nRBCs counts or estimates, modestly increased the association between smoking and cg05575921 methylation. CONCLUSIONS: Prenatal smoke exposure was highly significantly associated with AHRR methylation in cord blood, CD14+ monocytes, and CD235a+ nRBCs. AHRR methylation levels in nRBCs and nRBC counts had minimal effect on cord blood methylation measurements. However, regression models using estimated nRBCs or actual nRBC counts outperformed those lacking these covariates.