RESUMEN
Purpose: To investigate sex-based differences in inflammation-related biomarkers on spectral-domain OCT. Design: Cross-sectional study. Participants: Patients with diabetic macular edema (DME) between February 1, 2019, and March 31, 2023, without intravitreal anti-VEGF injection within the previous 6 months. Methods: We reviewed each patient's medical record for age, biological sex, race and ethnicity, most recent glycated hemoglobin A1c (HbA1c) level, visual acuity (VA), and central macular thickness (CMT). OCT biomarkers that have been found in literature to be associated with inflammation, including disorganization of retinal inner layers (DRIL), retinal hyperreflective retinal foci (HRFs), hyperreflective choroidal foci (HCFs), subfoveal neuroretinal detachment (SND), and perturbation in retinal nerve fiber layer thickness, ganglion cell layer thickness, and inner nuclear layer (INL) thickness were evaluated by graders masked to the clinical characteristics of the patients. We performed multivariable regression analyses with the OCT biomarkers as the outcome variables and sex, age, HbA1c, and CMT as independent variables. Main Outcome Measures: OCT inflammation-related biomarkers, as listed above. Results: Female patients were, on average, 2 years older than male patients (P = 0.041). There were no significant differences in race and ethnicity, HbA1c, VA, or CMT between male and female patients. After controlling for age, HbA1c, and CMT, we found male sex to be associated with more HRF (incidence rate ratio [IRR] = 1.19; 95% confidence interval [CI] = 1.10-1.29), more HCF (odds ratio = 2.01; 95% CI = 1.12-3.64), and thicker INL (7 µm thicker in males; 95% CI = 2-12). Sex was not a significant predictor for either DRIL or SND in the multivariable regression models. Patients with higher HbA1c were more likely to have more HRF (IRR = 1.02 per 1 point increase; 95% CI = 1.00-1.04) after controlling for other factors. Conclusions: Male sex was correlated with more inflammation-related biomarkers on OCT including more HRF, more HCF, and thicker INL, after accounting for age, glycemic control, and amount of DME. Further studies are needed to evaluate the potential implications of these sex-based differences for individualized treatment. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
RESUMEN
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.