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Jonathan B Lin,1 Kristen M Pitts,1 Hani El Helwe,1 Cameron Neeson,1 Nathan E Hall,1 Henisk Falah,1 Stephanie A Schultz,2 Silas L Wang,1 Kristine Lo,1 Christian Song,1 Milica A Margeta,1,* David Solá-Del Valle1,* 1Department of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear, Boston, MA, USA; 2Department of Neurology, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA*These authors contributed equally to this workCorrespondence: David Solá-Del Valle; Milica A Margeta, Assistant Professor of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, 243 Charles Street, Boston, MA, 02114, USA, Email david_sola-delvalle@meei.harvard.edu; milica_margeta@meei.harvard.eduPurpose: 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 (Rs = 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 (Rs = 0.015, P = 0.935).Conclusion: Our findings suggest that AH NfL may have clinical utility as a marker of glaucomatous neurodegeneration.Keywords: neurofilament light chain, glaucoma, neurodegeneration, biomarker |
