Elevated Neurodegeneration Markers in the Aqueous Humor of Primary Open Angle and Normal Tension Glaucoma Patients Correlate With Disease Severity

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Purpose: Glaucoma, a degenerative condition of the optic nerve, results in irreversible blindness. Intraocular monitoring of neurodegeneration markers will help in early diagnosis, prognostication, and unravelling novel disease mechanisms. Thus, we evaluated neurodegeneration markers in patients with glaucoma and correlated them with clinical parameters. Methods: Aqueous humor (AH) from patients with primary open angle glaucoma (POAG; 26 eyes), normal tension glaucoma (NTG; 10 eyes), and non-glaucomatous controls (18 eyes) were collected at the time of trabeculectomy and/or cataract surgery. The levels of amyloid-beta (Aβ)40, Aβ42, β-synuclein, glial fibrillary acidic protein (GFAP), neurofilament heavy chain (NfH), neurofilament light chain (NfL), total Tau (t-Tau), and ubiquitin C-terminal hydrolase L1 (UCHL1) were measured in AH using microfluidic cartridge-based multiplex ELISA. Results: The levels of Aβ40, Aβ42, β-synuclein, GFAP, NfH, NfL, and t-Tau in the AH were significantly (P < 0.0001) higher in patients with POAG compared with the healthy controls. Whereas, Aβ40, Aβ42, and NfH were significantly (P < 0.05) higher in patients with NTG compared with controls. Area under the curve (AUC) analysis demonstrated that, in patients with POAG, Aβ40, Aβ42, GFAP, and NfH exhibited AUC values of 0.949, 0.929, 0.944, and 0.955, respectively, with 80% to 100% sensitivity and specificity (P < 0.0001). In patients with NTG, only NfH showed a comparable AUC of 0.944 with similar diagnostic accuracy. GFAP, Aβ42, and t-Tau levels were observed to be inversely associated with visual field index and/or retinal nerve fiber layer thickness of patients with POAG and/or NTG. Conclusions: Increased intraocular levels of neurodegeneration markers and their association with clinical parameters in patients with POAG and/or NTG indicate their potential as biomarkers or therapeutic targets in the management of glaucoma.

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