{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T21:09:07Z","timestamp":1788469747185,"version":"build-2803163510"},"reference-count":33,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vision"],"abstract":"<jats:p>Background and Objectives: Primary open-angle glaucoma (POAG) is one of the leading ocular diseases leading to irreversible blindness and is often asymptomatic until advanced cases. While intraocular pressure reduction remains the cornerstone of treatment, neuroprotective strategies targeting retinal ganglion cell metabolism are actively investigated. Niacinamide (nicotinamide, vitamin B3), a precursor of NAD+, has shown neuroprotective potential in preclinical models. This exploratory study evaluated the short-term functional, structural, and electrophysiological effects of oral niacinamide supplementation in POAG. Materials and Methods: In this interventional study, patients with POAG received oral niacinamide 500 mg daily for six months. Visual field (VF) global and localized sensitivity (Mean Deviation [MD], Pattern Standard Deviation [PSD]), Optic Coherence Tomography (OCT)-derived peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC), and Visual evoked potentials (VEP) latency parameters (P2 1.4 Hz, P100 1\u00b0, and P100 15\u2032) were assessed at baseline and at six months. Because both eyes from some participants were included, primary longitudinal inference was based on clustered analyses using generalized estimating equations and linear mixed-effects models to account for inter-eye correlation. Eye-level paired analyses were used for exploratory comparison. Change\u2013change relationships across modalities were explored using Spearman correlation. Results: After accounting for inter-eye correlation, no statistically significant change in MD was detected (mean \u0394MD +0.43 dB; GEE p = 0.099; LME p = 0.101), and PSD remained stable. RNFL thickness showed a small decrease (\u22121.26 \u00b5m; GEE p = 0.046), while GCC did not change significantly. VEP P100 latencies remained stable, whereas P2 latency showed a small increase (+3.9 ms; GEE p = 0.039). Correlation analysis revealed a moderate association between changes in GCC and MD (\u03c1 = 0.44), suggesting concordance between macular structural stability and global visual field performance. Conclusions: When inter-eye correlation is appropriately accounted for, six months of niacinamide supplementation in POAG is associated with overall functional, structural, and electrophysiological stability, without evidence of clinically meaningful improvement or progression. These findings support short-term safety and highlight the importance of clustered analytical approaches and macular-centered biomarkers in future glaucoma neuroprotection trials.<\/jats:p>","DOI":"10.3390\/vision10010007","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T17:40:22Z","timestamp":1769622022000},"page":"7","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["An Exploratory Study of Six-Month Niacinamide Supplementation on Macular Structure and Electrophysiology in Primary Open-Angle Glaucoma"],"prefix":"10.3390","volume":"10","author":[{"given":"Constantin Alin","family":"Nicola","sequence":"first","affiliation":[{"name":"Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8242-8809","authenticated-orcid":false,"given":"Maria Cristina","family":"Marinescu","sequence":"additional","affiliation":[{"name":"Discipline of Medical Physiology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Alexandrescu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Marie","family":"Firan","sequence":"additional","affiliation":[{"name":"Barnsley Hospital NHS Foundation Trust, Barnsley S75 2EP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walid","family":"Alyamani","sequence":"additional","affiliation":[{"name":"Barnsley Hospital NHS Foundation Trust, Barnsley S75 2EP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9173-2976","authenticated-orcid":false,"given":"Mihaela Simona","family":"Naidin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Marketing and Management, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radu Constantin","family":"Ciuluvica","sequence":"additional","affiliation":[{"name":"Discipline of Anatomy, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radu Antoniu","family":"Patrascu","sequence":"additional","affiliation":[{"name":"Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca Maria","family":"Capraru","sequence":"additional","affiliation":[{"name":"Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1374-276X","authenticated-orcid":false,"given":"Adina","family":"Turcu-Stiolica","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Marketing and Management, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"},{"name":"Department of Health Economics and Outcomes Research, Faculty of Medicine, Iuliu Ha\u0163ieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Potop, V., Dragosloveanu, C.D.M., Cioc\u00e2lteu, A.M., Burcel, M.G., Marinescu, M.C., and D\u0103sc\u0103lescu, D.M.C. (2024). The Mirror Theory: Parallels between Open Angle and Angle Closure Glaucoma. Life, 14.","DOI":"10.3390\/life14091154"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Marinescu, M.-C., Dascalescu, D.-M.-C., Constantin, M.-M., Coviltir, V., Potop, V., Stanila, D., Constantin, F., Alexandrescu, C., Ciuluvica, R.-C., and Voinea, L.-M. (2023). Particular Anatomy of the Hyperopic Eye and Potential Clinical Implications. Medicina, 59.","DOI":"10.3390\/medicina59091660"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1097\/IJG.0000000000002083","article-title":"Primary Open Angle Glaucoma Prevalence in Europe: A Systematic Review and Meta-Analysis","volume":"31","author":"Aiello","year":"2022","journal-title":"J. Glaucoma"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1016\/j.ophtha.2025.06.002","article-title":"Prevalence of Glaucoma in Europe and Projections to 2050: Findings from the European Eye Epidemiology (E3) Consortium","volume":"132","author":"Stuart","year":"2025","journal-title":"Ophthalmology"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Coviltir, V., Burcel, M.G., Balt\u0103, G., and Marinescu, M.C. (2024). Interplay Between Ocular Ischemia and Glaucoma: An Update. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252212400"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Wang, L.-H., Huang, C.-H., and Lin, I.-C. (2024). Advances in Neuroprotection in Glaucoma: Pharmacological Strategies and Emerging Technologies. Pharmaceuticals, 17.","DOI":"10.3390\/ph17101261"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s44324-025-00067-0","article-title":"The Role of NAD+ Metabolism and Its Modulation of Mitochondria in Aging and Disease","volume":"3","author":"Yusri","year":"2025","journal-title":"Npj Metab. Health Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/s41580-020-00313-x","article-title":"NAD+ Metabolism and Its Roles in Cellular Processes during Ageing","volume":"22","author":"Covarrubias","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Waddell, J., Khatoon, R., and Kristian, T. (2023). Cellular and Mitochondrial NAD Homeostasis in Health and Disease. Cells, 12.","DOI":"10.3390\/cells12091329"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1089\/ars.2017.7269","article-title":"Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic Targets for Age-Related Degenerative Diseases: Rationale, Biochemistry, Pharmacokinetics, and Outcomes","volume":"30","author":"Braidy","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101988","DOI":"10.1016\/j.redox.2021.101988","article-title":"Nicotinamide Provides Neuroprotection in Glaucoma by Protecting against Mitochondrial and Metabolic Dysfunction","volume":"43","author":"Tribble","year":"2021","journal-title":"Redox Biol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Nicola, C.A., Marinescu, M.C., Firan, A.M., Naidin, M.S., Ciuluvica, R.C., Rosu, M.M., Meca, A.-D., Bogdan, M., and Turcu-Stiolica, A. (2024). Systematic Review and Meta-Analysis on the Association Between Daily Niacin Intake and Glaucoma. Nutrients, 16.","DOI":"10.3390\/nu16213604"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1097\/IJG.0000000000000767","article-title":"Glaucoma as a Metabolic Optic Neuropathy: Making the Case for Nicotinamide Treatment in Glaucoma","volume":"26","author":"Williams","year":"2017","journal-title":"J. Glaucoma"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.ogla.2025.01.002","article-title":"American Glaucoma Society-American Academy of Ophthalmology Position Statement on Nicotinamide Use for Glaucoma Neuroprotection","volume":"8","author":"Shukla","year":"2025","journal-title":"Ophthalmol. Glaucoma"},{"key":"ref_15","unstructured":"Ruia, S., and Tripathy, K. (2025). Humphrey Visual Field. StatPearls, StatPearls Publishing."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"306","DOI":"10.4103\/sjopt.sjopt_143_24","article-title":"Visual Field Patterns in Glaucoma: A Systematic Review","volume":"38","author":"Vandersnickt","year":"2024","journal-title":"Saudi J. Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1146\/annurev-vision-100419-111350","article-title":"Optical Coherence Tomography and Glaucoma","volume":"7","author":"Geevarghese","year":"2021","journal-title":"Annu. Rev. Vis. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"15","DOI":"10.22336\/rjo.2020.4","article-title":"Visual Evoked Potential in the Early Diagnosis of Glaucoma. Literature Review","volume":"64","author":"Firan","year":"2020","journal-title":"Rom. J. Ophthalmol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Nicola, C.A., Marinescu, M.C., Firan, A.M., Tartea, G., Naidin, M.S., Ciuluvica, R.C., Dimulescu, M.D., Voicu, N.M., Mihailescu, C.M., and Meca, A.-D. (2025). Changes in Quality of Life Among Glaucoma Patients Following Six Months of Niacinamide Supplementation. Nutrients, 17.","DOI":"10.3390\/nu17172775"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1097\/IJG.0b013e3181752c83","article-title":"Assessing Quality of Life in Patients with Glaucoma Using the Glaucoma Quality of Life-15 (GQL-15) Questionnaire","volume":"18","author":"Goldberg","year":"2009","journal-title":"J. Glaucoma"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10633-016-9553-y","article-title":"ISCEV standard for clinical visual evoked potentials: (2016 update)","volume":"133","author":"Odom","year":"2016","journal-title":"Doc. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.ogla.2020.12.001","article-title":"Predicting Global Test-Retest Variability of Visual Fields in Glaucoma","volume":"4","author":"Choi","year":"2020","journal-title":"Ophthalmol. Glaucoma"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1111\/ceo.13818","article-title":"Improvement in Inner Retinal Function in Glaucoma with Nicotinamide (vitamin B3) Supplementation: A Crossover Randomized Clinical Trial","volume":"48","author":"Hui","year":"2020","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ha, A., Kim, Y.K., Lee, C.K., Williams, P.A., Morgan, J.E., Shin, Y.I., Kim, E., Kim, M., and Rho, S. (2025). Effects of Nicotinamide Supplementation in Normal-Tension Glaucoma: A Crossover Placebo-Controlled Randomised Clinical Trial. Br. J. Ophthalmol.","DOI":"10.1136\/bjo-2025-328096"},{"key":"ref_25","first-page":"11","article-title":"Nicotinamide and Pyruvate for Neuroenhancement in Open-Angle Glaucoma: A Phase 2 Randomized Clinical Trial","volume":"140","author":"John","year":"2021","journal-title":"JAMA Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1016\/j.clinph.2009.08.014","article-title":"High Test-Retest Reliability of Checkerboard Reversal Visual Evoked Potentials (VEP) over 8 Months","volume":"120","author":"Sarnthein","year":"2009","journal-title":"Clin. Neurophysiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1167\/tvst.14.5.13","article-title":"Normative Variability in Retinal Nerve Fiber Layer Thickness: Does It Matter Where the Peaks Are?","volume":"14","author":"Gowrisankaran","year":"2025","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e109","DOI":"10.1097\/IJG.0000000000000203","article-title":"Test-Retest Variability of Retinal Nerve Fiber Layer Thickness and Macular Ganglion Cell-Inner Plexiform Layer Thickness Measurements Using Spectral-Domain Optical Coherence Tomography","volume":"24","author":"Wadhwani","year":"2015","journal-title":"J. Glaucoma"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"100549","DOI":"10.1016\/j.xops.2024.100549","article-title":"Biological and Methodological Variability in Retinal Nerve Fiber Layer OCT: The Framingham Heart Study","volume":"4","author":"Almidani","year":"2024","journal-title":"Ophthalmol. Sci."},{"key":"ref_30","first-page":"2010","article-title":"24-2 Visual Field Progression Rates Better Correlate with GCL than RNFL Rate of Change in Glaucoma","volume":"64","author":"Xing","year":"2023","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1007\/s11845-025-03980-x","article-title":"The potential of visual evoked potentials latency and amplitude to be a subclinical predictor of clinical prognosis in multiple sclerosis","volume":"194","author":"Soker","year":"2025","journal-title":"Ir. J. Med. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/eye.2016.281","article-title":"Targeting retinal ganglion cell recovery","volume":"31","author":"Crowston","year":"2017","journal-title":"Eye"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kosior-Jarecka, E., and Grzybowski, A. (2024). Retinal Ganglion Cell Replacement in Glaucoma Therapy: A Narrative Review. J. Clin. Med., 27.","DOI":"10.3390\/jcm13237204"}],"container-title":["Vision"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2411-5150\/10\/1\/7\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T10:37:13Z","timestamp":1770115033000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2411-5150\/10\/1\/7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,28]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["vision10010007"],"URL":"https:\/\/doi.org\/10.3390\/vision10010007","relation":{},"ISSN":["2411-5150"],"issn-type":[{"value":"2411-5150","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,28]]}}}