Potential neuroprotective role of statins in glaucoma prevention and treatment: a literature review of clinical studies

Background. Glaucoma is one of the leading causes of blindness and visual impairment worldwide. As of January 1, 2022, approximately 1.2 million people with glaucoma were registered in the Russian Federation, including 101 000 individuals with visual disability. The rising prevalence of glaucoma is associated with population aging and a high burden of comorbidity in older adults. This makes the search for new approaches to preventing glaucoma-related blindness and improving glaucoma treatment particularly relevant. Purpose: To investigate the association between statin use and the development or progression of glaucoma. Materials and methods. A systematic literature search was conducted in PubMed, Google Scholar, Web of Science, Scopus, and eLibrary for publications from 2000 to 2025. The search terms were glaucoma, statins, cholesterol, and primary openangle glaucoma. Eligible publications included original studies, meta-analyses, and systematic reviews examining the association between statin use and glaucoma. Overall, 38 publications were included, of which 25 were original studies. Results. Most of the studies reviewed suggest a potential protective effect of statins in glaucoma. Long-term statin use, defi ned as treatment for more than 2–3 years, was associated with a 21–40 % lower risk of developing primary open-angle glaucoma. Several mechanisms have been proposed, including neuroprotection of retinal ganglion cells through improved microcirculation and reduced apoptosis and cytotoxicity; modulation of immune responses; and a potential reduction in intraocular pressure through improved aqueous humor outfl ow. Conclusion. This literature review indicates a complex and heterogeneous association between statin use and open-angle glaucoma development. Although most findings suggest a potential benefit, the evidence remains inconsistent. Large randomized clinical trials are needed to confirm the neuroprotective effects of statins in glaucoma. The available data may inform the development of new statin-based therapeutic strategies for glaucoma management.

1. Chuprov AD, Lositskiy AO, Trubnikov VA, Kazakovab ТN. Epidemiological features of glaucoma prevalence among the population of the Russian Federation. National Journal glaucoma. 2021;20(3):3– 10. (In Russ.) doi: 10.53432/2078-4104-2021-20-3-3-10

2. Clinical guidelines of the Russian Federation. Primary openangle glaucoma. 2024. (In Russ.) URL: https://share.google/FpoauCkxg7R3dcqHh (accessed: 10.09.2025).

3. Aprelev AE, Pidodniy EA. Primary neuroprotection of glaucoma. Orenburg medical herald. 2020; 8(2(30)):5–9. (In Russ.)

4. Killer HE, Pircher A. Normal tension glaucoma: review of current understanding and mechanisms of the pathogenesis. Eye (Lond). 2018;32(5):924–930. doi: 10.1038/s41433-018-0042-2

5. Chuprov AD, Aprelev AE, Gorbunov AA, Pidodniy EA. Neuroprotection at glaucoma. Current Issues in Science and Education. 2021;(2). (In Russ.) URL: https://science-education.ru/ru/article/view?id=30715 (accessed: 11.07.2025). doi: 10.17513/spno.30715

6. Vernazza S, Tirendi S, Bassi AM, Traverso CE, Saccà SC. Neuroinfl ammation in primary open-angle glaucoma. J Clin Med. 2020;9(10):3172. doi: 10.3390/jcm9103172

7. Charlesworth CJ, Smit E, Lee DS, Alramadhan F, Odden MC. Polypharmacy among adults aged 65 years and older in the united states: 1988–2010. J Gerontol A Biol Sci Med Sci. 2015;70(8):989–995. doi: 10.1093/gerona/glv013

8. Getmanova AM, Brezhnev AYu, Kuroyedov AV, Baranov VI, Dvornikov AS. Systemic therapy a risk factor for glaucoma development and progression. Russian journal of clinical ophthalmology. 2020;20(4):191–196. (In Russ.) doi: 10.32364/2311-7729-2020-20-4-191-196

9. Stein JD, Newman-Casey PA, Niziol LM, Gillespie BW, Lichter PR, Musch DC. Association between the use of glaucoma medications and mortality. Arch Ophthalmol. 2010;128(2):235–240. doi: 10.1001/archophthalmol.2009.378

10. Clinical guidelines of the Russian Federation. Lipid metabolism disorders. 2023 (In Russ.) URL: https://share.google/ lyAhIkEnBgwTwEzmN (accessed: 05.08.2025).

11. Gordeev IG, Taratukhin EO. Prospects of the statin treatment: review of current studies. Russian Heart Journal. 2016;15(6(92)):398–403. (In Russ.) doi: 10.18087/RHJ.2016.6.2271

12. Schmeer C, Kretz A, Isenmann S. Statin-mediated protective effects in the central nervous system: general mechanisms and putative role of stress proteins. Restor Neurol Neurosci. 2006;24(2):79–95.

13. Makogon SI, Ivanova DI. The relationship of the metabolic syndrome and its correction with the development and progression of glaucoma. National Journal glaucoma. 2024;23(1):65–74. (In Russ.) doi: 10.53432/2078-4104-2024-23-1-65-74

14. Kang JH, Boumenna T, Stein JD, Khawaja A, Rosner BA, Wiggs JL, Pasquale LR. Association of statin use and high serum cholesterol levels with risk of primary open-angle glaucoma. JAMA Ophthalmol. 2019;137(7):756–765. doi: 10.1001/jamaophthalmol.2019.0900

15. McGwin GJr, McNeal S, Owsley C, Girkin C, Epstein D, Lee PP. Statins and other cholesterol-lowering medications and the presence of glaucoma. Arch Ophthalmol. 2004;122(6):822– 826. doi: 10.1001/archopht.122.6.822

16. Marcus MW, Müskens RP, Ramdas WD, Wolfs RC, De Jong PT, Vingerling JR, Hofman A, Stricker BH, Jansonius NM. Cholesterol-lowering drugs and incident open-angle glaucoma: a population-based cohort study. PLoS One. 2012;7(1):e29724. doi: 10.1371/journal.pone.0029724

17. De Castro DK, Punjabi OS, Bostrom AG, Stamper RL, Lietman TM, Ray K, Lin SC. Effect of statin drugs and aspirin on progression in open-angle glaucoma suspects using confocal scanning laser ophthalmoscopy. Clin Exp Ophthalmol. 2007;35(6):506–513. doi: 10.1111/j.1442-9071.2007.01529.x

18. Whigham B, Oddone EZ, Woolson S, Coffman C, Allingham RR, Shieh C, Muir KW. The influence of oral statin medications on progression of glaucomatous visual field loss: A propensity score analysis. Ophthalmic Epidemiol. 2018;25(3):207–214. doi: 10.1080/09286586.2017.1399427

19. Stein JD, Newman-Casey PA, Talwar N, Nan B, Richards JE, Musch DC. The relationship between statin use and open-angle glaucoma. Ophthalmology. 2012;119(10):2074–2081. doi: 10.1016/j.ophtha.2012.04.029

20. Leung DY, Li FC, Kwong YY, Tham CC, Chi SC, Lam DS. Simvastatin and disease stabilization in normal tension glaucoma: a cohort study. Ophthalmology. 2010;117(3):471–476. doi: 10.1016/j.ophtha.2009.08.016

21. Yokoyama S, Nakagawa C, Hosomi K. Association between statin use and open-angle glaucoma: a nested case-control study using the Japanese claims database. Sci Rep. 2023;13(1):11677. doi: 10.1038/s41598-023-38957-2

22. Chen HY, Hsu SY, Chang YC, Lin CC, Sung FC, Chen WC, Kao CH. Association between statin use and open-angle glaucoma in hyperlipidemia patients: a Taiwanese population-based case-control study. Medicine (Baltimore). 2015;94(45):e2018. doi: 10.1097/MD.0000000000002018

23. Yuan Y, Wang W, Shang X, Xiong R, Ha J, Zhang L, Zhu Z, He M. Association between statin use and the risks of glaucoma in Australia: a 10-year cohort study. Br J Ophthalmol. 2023;107(1):66–71. doi: 10.1136/bjophthalmol-2021-318789

24. Wang S, Xu L, Jonas JB, You QS, Wang YX, Yang H. Dyslipidemia and eye diseases in the adult Chinese population: the Beijing eye study. PLoS One. 2012;7(3):e26871. doi: 10.1371/journal.pone.0026871

25. Newman-Casey PA, Talwar N, Nan B, Musch DC, Stein JD. The relationship between components of metabolic syndrome and open-angle glaucoma. Ophthalmology. 2011;118(7):1318– 1326. doi: 10.1016/j.ophtha.2010.11.022

26. Ho H, Shi Y, Chua J, Tham YC, Lim SH, Aung T, Wong TY, Cheng CY. Association of systemic medication use with intraocular pressure in a multiethnic Asian population: the Singapore epidemiology of eye diseases study. JAMA Ophthalmol. 2017;135(3):196–202. doi: 10.1001/jamaophthalmol.2016.5318

27. Song XY, Chen YY, Liu WT, Cong L, Zhang JL, Zhang Y, Zhang YY. Atorvastatin reduces IOP in ocular hypertension in vivo and suppresses ECM in trabecular meshwork perhaps via FGD4. Int J Mol Med. 2022;49(6):76. doi: 10.3892/ijmm.2022.5132

28. Arroyo JG. The manifold actions of statins. Comment on “Effects of systemic administration of simvastatin on retinal circulation”, by T. Nagaoka, A. Takahashi, E. Sato, et al. Arch Ophthalmol. 124:665–670, 2006. Surv Ophthalmol. 2006;51(5):526–527. doi: 10.1016/j.survophthal.2006.06.016

29. Lin CH, Lin HI, Chen ML, Lai TT, Cao LP, Farrer MJ, Wu RM, Chien CT. Lovastatin protects neurite degeneration in LRRK2-G2019S parkinsonism through activating the Akt/Nrf pathway and inhibiting GSK3β activity. Hum Mol Genet. 2016;25(10):1965–1978. doi: 10.1093/hmg/ddw068

30. Bibbins-Domingo K, Grossman DC, Curry S, et al. Statin use for the primary prevention of cardiovascular disease in adults: US preventive services task force recommendation statement. JAMA. 2016;316(19):1997–2007. doi: 10.1001/jama.2016.15450

31. Talwar N, Musch DC, Stein JD. Association of daily dosage and type of statin agent with risk of open-angle glaucoma. JAMA Ophthalmol. 2017;135(3):263–267. doi: 10.1001/jamaophthalmol.2016.5406

32. Cong L, Fu S, Zhang J, Zhao J, Zhang Y. Effects of atorvastatin on porcine aqueous humour outfl ow and trabecular meshwork cells. Exp Ther Med. 2018;15(1):210–216. doi: 10.3892/ etm.2017.5353

33. Honjo M, Tanihara H, Nishijima K, Kiryu J, Honda Y, Yue BY, Sawamura T. Statin inhibits leukocyte-endothelial interaction and prevents neuronal death induced by ischemia-reperfusion injury in the rat retina. Arch Ophthalmol. 2002;120(12):1707–1713. doi: 10.1001/archopht.120.12.1707

34. Bösel J, Gandor F, Harms C, Synowitz M, Harms U, Djoufack PC, Megow D, Dirnagl U, Hörtnagl H, Fink KB, Endres M. Neuroprotective effects of atorvastatin against glutamate-induced excitotoxicity in primary cortical neurones. J Neurochem. 2005;92(6):1386–1398. doi: 10.1111/j.1471-4159.2004.02980.x

35. Unlu M, Aktas Z, Gocun PU, Ilhan SO, Hasanreisoglu M, Hasanreisoglu B. Neuroprotective effect of systemic and/ or intravitreal rosuvastatin administration in rat glaucoma model. Int J Ophthalmol. 2016;9(3):340–347. doi: 10.18240/ijo.2016.03.03

36. Nagaoka T, Takahashi A, Sato E, Izumi N, Hein TW, Kuo L, Yoshida A. Effect of systemic administration of simvastatin on retinal circulation. Arch Ophthalmol. 2006;124(5):665– 670. doi: 10.1001/archopht.124.5.665

37. Terai N, Spoerl E, Fischer S, Hornykewycz K, Haustein M, Haentzschel J, Pillunat LE. Statins affect ocular microcirculation in patients with hypercholesterolaemia. Acta Ophthalmol. 2011;89(6):e500–504. doi: 10.1111/j.1755-3768.2011.02154.x

38. Yuan Y, Xiong R, Wu Y, Ha J, Wang W, Han X, He M. Associations of statin use with the onset and progression of open-angle glaucoma: A systematic review and meta-analysis. EClinicalMedicine.