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

Purpose: 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. Methods: This study included 65 primary open-angle glaucoma (POAG) patients and 65 healthy controls. 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 glaucoma severity were assessed. Results: 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). Conclusions: HRS strongly correlate with RGC and RNFL loss in glaucoma and may serve as as a valuable biomarker in the follow-up of glaucoma.