Neurofilament Light Chain in Aqueous Humor as a Marker of Neurodegeneration in Glaucoma

PURPOSE: Neurofilament light chain (NfL) is a neuronal cytoskeletal protein that has been identified as a marker of neurodegeneration in diseases of the central nervous system. In this study, we investigated whether NfL in the aqueous humor (AH) can serve as a marker of neurodegeneration in glaucoma in a racially diverse North American population. DESIGN: Single-center, case–control study. PARTICIPANTS: We enrolled patients with various types and stages of glaucoma undergoing planned ophthalmic surgery as part of their routine care and compared them with patients without glaucoma undergoing phacoemulsification for age-related cataract. METHODS: We collected AH from 39 glaucoma patients and 10 patients without glaucoma. AH NfL was quantified using the Single-Molecule Array (Simoa)(®) NF-light assay (Quanterix). Demographic information, such as age, body mass index, sex, and self-reported race, as well as clinical information, such as pre-operative intraocular pressure (IOP), maximum IOP, and number of pre-operative glaucoma medications, was obtained by reviewing the medical record. MAIN OUTCOME MEASURES: Levels of AH NfL. RESULTS: In a model controlling for age and body mass index (BMI), NfL was significantly elevated in AH from glaucoma patients (mean: 429 pg/mL; standard deviation [SD]: 1136 pg/mL) compared to AH from patients without glaucoma (mean: 3.1 pg/mL; SD: 1.9 pg/mg): P = 0.002. Higher AH NfL was associated with higher maximum IOP (R = 0.44, P = 0.005), higher pre-operative IOP (R = 0.46, P = 0.003), and more pre-operative glaucoma medications (R(s) = 0.61, P < 0.001). There was no association between AH NfL and Humphrey visual field mean deviation (R = −0.20, P = 0.220), retinal nerve fiber layer thickness as measured with optical coherence tomography (R = 0.07, P = 0.694), or glaucoma stage (R(s) = 0.015, P = 0.935). CONCLUSION: Our findings suggest that AH NfL may have clinical utility as a marker of glaucomatous neurodegeneration.