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

Abstract

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.

Figure 1.

Optical coherence tomography angiography en face images of the superficial and deep capillary plexuses. (A) En face image of the superficial capillary plexus delineating the parafoveal region between annular rings of 1 mm and 3 mm in diameter. (B) Enface image of the deep capillary plexus. (C) Skeletonized angiography scan showing all vessels represented as 1 mm in diameter, which is used to calculate vessel length density.

Figure 2.

Boxplots of foveal avascular zone parameters across non-diabetic and diabetic individuals with varying retinopathy severity. Line inside box illustrates median. Lower and upper box boundaries show 25th and 75th quartiles, respectively. Female patients are shown in red and male patients are shown in blue for each group. DM no DR, diabetes mellitus without diabetic retinopathy; F, female; FAZ, foveal avascular zone; M, male; Mod, moderate; NPDR, nonproliferative diabetic retinopathy; PDR, proliferative diabetic retinopathy.

Figure 3.

Boxplots of vascular parameters across non-diabetic and diabetic individuals with varying retinopathy severity. Line inside box illustrates median. Lower and upper box boundaries show 25th and 75th quartiles, respectively. Female patients are shown in red and male patients are shown in blue for each group. DCP, deep capillary plexus; DM no DR, diabetes mellitus without diabetic retinopathy; F, female; FI, flow index; M, male; Mod, moderate; NPDR, nonproliferative diabetic retinopathy; PDR, proliferative diabetic retinopathy; SCP, superficial capillary plexus; VD, vessel density; VLD, vessel length density.