Evaluation of hyperreflective spots as a novel biomarker in patients with glaucoma

To evaluate hyperreflective spots (HRS) detected by optical coherence tomography (OCT) in healthy and glaucomatous eyes and their correlation with retinal ganglion cell (RGC) loss.

A total of 65 patients with primary open-angle glaucoma (POAG) and 65 healthy controls were enrolled, and data were collected from one eye of each participant. In glaucoma patients, the eye with better visual acuity was selected; if equal, the eye with the higher OCT image quality was included. In the control group, the eye with the higher OCT image quality was selected for analysis. OCT scans of the fovea's thinnest section were analyzed, and an area 3000 µm wide at the center was selected. HRS were defined as small spots (≤ 30 µm) with moderate reflectivity and no shadowing. HRS counts were compared between groups, and correlations with OCT parameters associated with RGC loss were assessed.

The mean age was similar between groups (glaucoma: 62.48 ± 19.77 years; control: 59.75 ± 6.65 years; P = 0.085). Inter-rater agreement for HRS counts was excellent (ICC = 0.927, 95% CI: 0.89-0.94). Glaucoma patients had significantly higher HRS counts than controls (29.65 ± 7.68 vs. 11.86 ± 5.05, P < 0.001). HRS counts positively correlated with vertical and horizontal cupping diameters (r = 0.45, P < 0.001) and negatively correlated with neuroretinal rim area (r = - 0.46, P < 0.001), total RNFL thickness (r = - 0.39, P < 0.001), and mean GCC thickness (r = - 0.43, P < 0.001). Correlation coefficients were similar after adjusting for age, intraocular pressure (IOP), and signal strength index (SSI).

HRS strongly correlate with RGC and RNFL loss in glaucoma and may serve as as a valuable biomarker in the follow-up of glaucoma.