Quantifying Capillary Pericytes In Vivo Links Them to Retinal Vascular Leakage and Potentially Albuminuria: A Pilot...

Pericytes are vascular mural cells, critical to the formation and maintenance of tightly regulated microvascular networks, including the inner blood-retinal barrier, and their dysfunction is characteristic of many vascular diseases, including diabetic retinopathy. Although donor eye and animal studies have suggested a link between pericyte loss and retinal vascular leakage, this relationship has not been explored in living humans, nor has the role of pericytes in predicting other complications, like albuminuria, in diabetes.

In this pilot study, we utilized adaptive optics scanning laser ophthalmoscopy to image and quantify retinal capillary pericytes in humans with diabetes. Leakage was manually delineated on fluorescein angiography to calculate macular leakage (%), whereas optical coherence tomography and optical coherence tomography-angiography evaluated retinal thickness and capillary nonperfusion, respectively. In addition, urine albumin/creatinine ratios (mg/g) were extracted from charts, post hoc, to evaluate the relationship between retinal pericytes and albuminuria in a subpopulation (n=14).

The study included 24 eyes from 23 patients with a range of diabetic retinopathy severity spanning from no diabetic retinopathy to proliferative diabetic retinopathy. Notably, capillary pericyte density showed a strong, negative correlation to macular leakage (r=-0.68; P<0.001) and moderate correlation to optical coherence tomography thickness (r=-0.45; P=0.027). Receiver operating characteristics analysis identified pericyte density thresholds (≤13.2 and 13.4 pericytes per 100 µm) that showed high area under the curves for detecting macular leakage (area under the curve, 0.87) and volumetric thickness (area under the curve, 0.80). Interestingly, albumin/creatinine ratios were significantly higher in individuals with ≤13.2 retinal capillary pericyte per 100 µm compared with those above the threshold (n=14, P=0.046).

Retinal capillary pericyte density, quantified in vivo, correlates significantly with macular thickening and angiographic leakage. We identified a threshold of pericyte loss that distinguishes individuals based on macular leakage status and albuminuria, providing important insights into retinal pericytes and their potential utility as a biomarker of vascular permeability.