Automated Cell Density Mapping of Macular Surface Macrophages in Diabetic Maculopathy

Abstract

Purpose : Retinal macrophages play key roles in vascular inflammatory regulation and angiogenesis. A novel automated density mapping technique and clinical OCT was used to examine the relationship between surface macrophages density and perfused capillary density in the maculae of healthy and diabetic eyes.

Methods : 49 patients with diabetic retinopathy (DR) and 14 controls were imaged using clinical SD-OCT(Avanti RTVue-XR; Optovue). Ten 3x3mm scans centered at the fovea were acquired and averaged (PMID: 28068370). Ocular magnification of each image was corrected for axial length . Foveal avascular zone (FAZ) border was outlined manually on the OCT-A scan. Automated surface macrophage cell density measurements within the FAZ were performed on the 3µm OCT-Reflectance (OCT-R) slab above the ILM surface using MATLAB (Fig. A1 & B1) (PMID: 32574351). Surface macrophage cell density maps were also generated for each subject. OCT-Angiography (OCT-A) full vascular slab, fromthe ILM to 9μm below the posterior boundary of the outer plexiform layer OPL, was used to measure capillary density (Fig. A2 & B2) (PMID: 31106029).

Results : Maculae of control eyes revealed a few slender, ramified surface macrophage cells . Diabetic maculae showed more cells which were rounder with fewer protrusions, irregularly distributed. Surface macrophage cells within the FAZ were found in 14% of controls and 80% of diabetic eyes (Fig. A3 & B3). Statistically significant differences were observed between control and DR groups in surface macrophage cell density (Kruskal-Wallis tests, P= 0.0005) with mean±SDs of 1±4, 12±16, 15±12, and 17±16 cells/mm² in the controls, diabetes without DR, NPDR, and PDR, respectively. Linear regression showed significant correlation between surface macrophage cell densities within the FAZ and surrounding perifoveal perfused capillary densities (R= -0.36, P= 0.005).

Conclusions : Clinical OCT is capable of detecting and mapping the density of macular surface macrophage cells in control and diabetic eyes. Our findings suggest that these cells migrate towards the center of the FAZ in diabetic eyes as compared to control eyes. Higher surface macrophage cell density within the FAZ appears to correlate with progressive reduction of perfused capillary density as DR worsens. Density mapping of surface macrophage cells may provide a useful clinical biomarker of progressive retinal vascular disease or response to therapy.

This is a 2021 ARVO Annual Meeting abstract.