Sex Differences in Inflammation-Related Biomarkers Detected with OCT in Patients with Diabetic Macular Edema

Abstract

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.

Keywords: Biomarker; Diabetic retinopathy; Inflammation; OCT; Sex difference.

Figure 1

Representative examples of several inflammation-related biomarkers. A, Disorganization of retinal inner layers. The extent of disorganization of retinal inner layers (dashed line) was measured in the 1-mm-wide area centered on the foveal depression. B, Retinal hyperreflective retinal foci marked with white arrows. C, Hyperreflective choroidal foci marked with white arrows. D, Subfoveal neuroretinal detachment with margins marked by white arrows.

Figure 2

Flow diagram of patients included and excluded in the study. CPT = Current Procedural Terminology; ICD = International Classification of Diseases; OCT = Optical Coherence Tomography; VEGF = vascular endothelial growth factor.