Preview

Russian Ophthalmological Journal

Advanced search

Feasibility of a prostaglandin-timolol fixed combination first-line treatment of primary glaucoma

https://doi.org/10.21516/2072-0076-2025-18-4-190-195

Abstract

Glaucoma is the most common cause of irreversible blindness worldwide. The reasons for the high and growing level of blindness due to glaucoma are low diagnostic population coverage, the incorrect hypotensive therapy and low glaucoma patient’s adherence. In practice, the recommended initial monotherapy does not allow achieving target IOP at moderate and advanced glaucoma with a high IOP level, which, according to clinical guidelines, is an indication for the initial combination therapy. Starting with a latanoprost-timolol fixed combination allows achieving a significant IOP decrease and increasing patient compliance by optimizing the number of instillations, reducing the total treatment cost, the total preservative volume, the absence of a washout effect and waiting between instillation of two drugs.

About the Authors

S. Yu. Petrov
Helmholtz National Medical Research Center of Eye Diseases
Russian Federation

Sergey Yu. Petrov — Dr. of Med. Sci., head of the glaucoma department

14/19, Sadovaya-Chernogryazskaya St., Moscow, 105062



O. I. Markelova
Helmholtz National Medical Research Center of Eye Diseases
Russian Federation

Oksana I. Markelova — junior researcher, glaucoma department

14/19, Sadovaya-Chernogryazskaya St., Moscow, 105062



References

1. Quigley H.A., Broman A.T. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006; 90 (3): 262–7. doi: 10.1136/bjo.2005.081224

2. Stuart KV, de Vries VA, Schuster AK, et al. Prevalence of glaucoma in Europe and projections to 2050: Findings from the European Eye Epidemiology (E3) Consortium. Ophthalmology. 2025 Oct; 132 (10): 1114–24. doi: 10.1016/j.ophtha.2025.06.002

3. Jonas J.B., Aung T., Bourne R.R., et al. Glaucoma. Lancet. 2017; 390 (10108): 2183–93. doi: 10.1016/S0140-6736(17)31469-1

4. World report on vision. World Health Organization. 2019 [29.02.2024]. Available from: https://cdn.who.int/media/docs/default-source/blindness-and-visualimpairment/9789241516570-eng.pdf?sfvrsn=dd15adbb_3

5. Tham YC, Li X, Wong TY, et al. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology. 2014; 121 (11): 2081–90. doi: 10.1016/j.ophtha.2014.05.013

6. Neroev V.V., Mikhaylova L.A., Malishevskaya T.N., Petrov S.Yu., Filippova O.M. Glaucoma epidemiology in the Russian Federation. Russian ophthalmological journal. 2024; 17 (3): 7–12 (In Russ.). doi: 10.21516/2072-0076-2024-17-3-7-12

7. Asia Pacific Glaucoma Guidelines: Kugler Publications; 2016. https://www.apglaucomasociety.org/2024-asia-pacific-glaucoma-guidelines

8. ICO Guidelines for Glaucoma Eye Care: International Council of Ophthalmology; 2015. https://icoph.org/eye-care-delivery/glaucoma/

9. Gedde SJ, Vinod K, Wright MM, et al. Primary open-angle glaucoma preferred practice pattern (R). Ophthalmology. 2021; 128(1): 71-150. doi: 10.1016/j.ophtha.2020.10.022

10. Vrijens B, De Geest S, Hughes DA, et al. A new taxonomy for describing and defining adherence to medications. Br J Clin Pharmacol. 2012; 73 (5): 691–705. doi: 10.1111/j.1365-2125.2012.04167.x

11. Clinical Gidelines “Primary open angle glaucoma” ID 631_2 (16.08.2024) (In Russ.). http://avo-portal.ru/documents/fkr/KR_PZYG_21_05_2020.pdf

12. Clinical Gidelines “Primary open angle glaucoma” ID 96_2 (17.08.2024) (In Russ.). http://avo-portal.ru/documents/fkr/Klinicheskie_rekomendacii_POUG_2022.pdf

13. Clinical Gidelines “Primary open angle glaucoma” ID 843_1 (17.12.2024) (In Russ.). http://avo-portal.ru/doc/fkr/item/545-glaukomyvtorichnye

14. Clinical Gidelines “Primary open angle glaucoma” ID 628_2 (09.08.2024) (In Russ.). http://avo-portal.ru/doc/fkr/item/561-podozreniena-glaukomu

15. European Glaucoma Society. Terminology and guidelines for glaucoma. 5th edition ed: Savona, Italy PubliComm; 2020. 172 p.

16. Friedman DS, Nordstrom B, Mozaffari E, Quigley H.A. Glaucoma management among individuals enrolled in a single comprehensive insurance plan. Ophthalmology. 2005; 112 (9): 1500–4. doi: 10.1016/j.ophtha.2005.02.030

17. Li T, Lindsley K, Rouse B, et al. Comparative Effectiveness of first-line medications for primary open-angle glaucoma: A systematic review and network meta-analysis. Ophthalmology. 2016; 123 (1): 129–40. doi: 10.1016/j.ophtha.2015.09.005

18. Musch DC, Lichter PR, Guire KE, Standardi CL. The Collaborative Initial Glaucoma Treatment Study: study design, methods, and baseline characteristics of enrolled patients. Ophthalmology. 1999; 106 (4): 653–62. doi: 10.1016/s0161-6420(99)90147-1

19. Bourne RR. Worldwide glaucoma through the looking glass. Br J Ophthalmol. 2006; 90 (3): 253–4. doi: 10.1136/bjo.2005.083527

20. Bourne RR, Taylor HR, Flaxman SR, et al. Number of people blind or visually impaired by glaucoma worldwide and in world regions 1990–2010: A meta-analysis. PLoS One. 2016; 11 (10): e0162229. doi: 10.1371/journal.pone.0162229

21. Shaikh Y, Yu F, Coleman AL. Burden of undetected and untreated glaucoma in the United States. Am J Ophthalmol. 2014; 158 (6): 1121–9 e1. doi: 10.1016/j.ajo.2014.08.023

22. Topouzis F, Coleman AL, Harris A, et al. Factors associated with undiagnosed open-angle glaucoma: the Thessaloniki Eye Study. Am J Ophthalmol. 2008; 145 (2): 327–35. doi: 10.1016/j.ajo.2007.09.013

23. Glaucoma Treatment Market. Global Market Insight . 2024 [07.07.2025]. Available at: https://www.gminsights.com/industry-analysis/glaucomatreatment-market

24. Egorov E.A., Kuroedov A.V. Clinical and epidemiological characteristics of glaucoma in CIS and Georgia. Results of multicenter opened retrospective trial (part 1). Russian journal of clinical ophthalmology. 2011; 12 (3): 97–100 (In Russ.).

25. Egorov E.A., Kuroedov A.V. Clinical and epidemiological characteristics of glaucoma in CIS and Georgia. Results of multicenter opened retrospective trial (part 2). Russian journal of clinical ophthalmology. 2012; 13 (1): 19–22 (In Russ.).

26. Abysheva L.D., Alexandrov A.S., Arapiev M.U., et al. Optimization of diagnosis and treatment options in primary open-angle glaucoma patients. Russian journal of glaucoma. 2016; 15 (2): 19–34 (In Russ.).

27. Hoevenaars JG, Schouten JS, van den Borne B, Beckers HJ, Webers CA. Will improvement of knowledge lead to improvement of compliance with glaucoma medication? Acta Ophthalmol. 2008; 86 (8): 849–55. doi: 10.1111/j.1755-3768.2007.01161.x

28. Schwartz GF, Quigley HA. Adherence and persistence with glaucoma therapy. Surv Ophthalmol. 2008; 53 Suppl1 (S57-68). doi: 10.1016/j.survophthal.2008.08.002

29. Moore SG, Richter G, Modjtahedi BS. Factors affecting glaucoma medication adherence and interventions to improve adherence: A narrative review. Ophthalmol Ther. 2023; 12 (6): 2863–80. doi: 10.1007/s40123-023-00797-8

30. Neroyev V.V., Zolotarev A.V., Karlova E.V., et al. Influence of treatment adherence on the progression of primary openangle glaucoma in clinical setting. Vestnik oftal’mologii. 2019; 135 (6): 42–51 (In Russ.). doi: 10.17116/oftalma201913506142

31. Stryker JE, Beck AD, Primo SA, et al. An exploratory study of factors influencing glaucoma treatment adherence. J Glaucoma. 2010; 19 (1): 66–72. doi: 10.1097/IJG.0b013e31819c4679

32. Malewicz K, Pender A, Chabowski M, Jankowska-Polanska B. Impact of sociodemographic and psychological factors on adherence to glaucoma treatment — A cross-sectional study. Clin Ophthalmol. 2024; 18: 2503–20. doi: 10.2147/OPTH.S475812

33. Korneeva A.V., Kuroyedov A.V., Zavadski P.Ch., et al. Adherence to glaucoma hypotensive therapy: patients' opinions on key factors of low compliance. Analytical multi-central study results. National journal of glaucoma. 2020; 19 (3): 12–21 (In Russ.). doi: 10.25700/NJG.2020.03.02

34. Barnebey HS, Robin AL. Adherence to fixed-combination versus unfixed Travoprost 0.004%/Timolol 0.5% for glaucoma or ocular hypertension: A randomized trial. Am J Ophthalmol. 2017; 176: 61–9. doi: 10.1016/j.ajo.2016.12.002

35. Poleon S, Twa M, Schoenberger-Godwin YM, Fifolt M, Racette L. A taxonomy of behavior change techniques for improving medication adherence in primary open-angle glaucoma. J Ophthalmol. 2025; 2025: 9917724. doi: 10.1155/joph/9917724

36. Babic N. Fixed combinations of glaucoma medications. Srp Arh Celok Lek. 2015; 143 (9–10): 626-31. doi: 10.2298/sarh1510626b

37. Wang T, Cao L, Jiang Q, Zhang T. Topical medication therapy for glaucoma and ocular hypertension. Front Pharmacol. 2021; 12:749858. doi: 10.3389/fphar.2021.749858

38. Konstas AG, Schmetterer L, Costa VP, et al. Current and emerging fixed combination therapies in glaucoma: a safety and tolerability review. Expert Opin Drug Saf. 2020; 19 (11): 1445–60. doi: 10.1080/14740338.2020.1826928

39. Patel SC, Spaeth GL. Compliance in patients prescribed eyedrops for glaucoma. Ophthalmic Surg. 1995; 26 (3): 233–6. PMID: 7651690.

40. Sleath B, Robin AL, Covert D, et al. Patient-reported behavior and problems in using glaucoma medications. Ophthalmology. 2006; 113 (3): 431–6. doi: 10.1016/j.ophtha.2005.10.034

41. Tsai JC. Medication adherence in glaucoma: approaches for optimizing patient compliance. Curr Opin Ophthalmol. 2006; 17 (2): 190–5. doi: 10.1097/01.icu.0000193078.47616.aa

42. Higginbotham EJ. Ocular Hypertension Treatment Study. Arch Ophthalmol. 2009; 127 (2): 213–5. doi: 10.1001/archophthalmol.2008.599

43. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002; 120 (6): 701–13; discussion 829–30. doi: 10.1001/archopht.120.6.701

44. Lichter PR, Musch DC, Gillespie BW, et al. Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery. Ophthalmology. 2001; 108 (11): 1943–53. doi: 10.1016/s0161-6420(01)00873-9

45. DuBiner HB, Mroz M, Shapiro AM, Dirks MS, Brimonidine vs. Latanoprost Study G. A comparison of the efficacy and tolerability of brimonidine and latanoprost in adults with open-angle glaucoma or ocular hypertension: a threemonth, multicenter, randomized, double-masked, parallel-group trial. Clin Ther. 2001; 23 (12): 1969–83. doi: 10.1016/s0149-2918(01)80150-8

46. Emmerich KH. Comparison of latanoprost monotherapy to dorzolamide combined with timolol in patients with glaucoma and ocular hypertension.A 3-month randomised study. Graefes Arch Clin Exp Ophthalmol. 2000; 238 (1): 19–23. doi: 10.1007/s004170050003

47. Jampel HD, Bacharach J, Sheu WP, et al. Randomized clinical trial of latanoprost and unoprostone in patients with elevated intraocular pressure. Am J Ophthalmol. 2002; 134 (6): 863–71. doi: 10.1016/s0002-9394(02)01820-2

48. Kampik A, Arias-Puente A, O'Brart DP, Vuori ML, European Latanoprost Study G. Intraocular pressure-lowering effects of latanoprost and brimonidine therapy in patients with open-angle glaucoma or ocular hypertension: a randomized observer-masked multicenter study. J Glaucoma. 2002; 11 (2): 90–6. doi: 10.1097/00061198-200204000-00003

49. Stewart WC, Day DG, Stewart JA, Schuhr J, Latham KE. The efficacy and safety of latanoprost 0.005% once daily versus brimonidine 0.2% twice daily in open-angle glaucoma or ocular hypertension. Am J Ophthalmol. 2001; 131 (5): 631–5. doi: 10.1016/s0002-9394(00)00902-8

50. Alm A, Grunden JW, Kwok KK. Five-year, multicenter safety study of fixed-combination latanoprost/timolol (Xalacom) for open-angle glaucoma and ocular hypertension. J Glaucoma. 2011; 20 (4): 215–22. doi: 10.1097/IJG.0b013e3181e08121

51. Lou H, Wang H, Zong Y, Cheng JW, Wei RL. Efficacy and tolerability of prostaglandin-timolol fixed combinations: an updated systematic review and meta-analysis. Curr Med Res Opin. 2015; 31 (6): 1139–47. doi: 10.1185/03007995.2015.1039504

52. Rigollet JP, Ondategui JA, Pasto A, Lop L. Randomized trial comparing three fixed combinations of prostaglandins/prostamide with timolol maleate. Clin Ophthalmol. 2011; 5: 187–91. doi: 10.2147/OPTH.S16666

53. Feldman RM. An evaluation of the fixed-combination of latanoprost and timolol for use in open-angle glaucoma and ocular hypertension. Expert Opin Pharmacother. 2004; 5 (4): 909–21. doi: 10.1517/14656566.5.4.909

54. Higginbotham EJ, Feldman R, Stiles M, Dubiner H, Fixed Combination Investigative G. Latanoprost and timolol combination therapy vs monotherapy: one-year randomized trial. Arch Ophthalmol. 2002; 120 (7): 915–22. doi: 10.1001/archopht.120.7.915

55. Inoue K, Fujimoto T, Higa R, et al. Efficacy and safety of a switch to latanoprost 0.005% + timolol maleate 0.5% fixed combination eyedrops from latanoprost 0.005% monotherapy. Clin Ophthalmol. 2012; 6: 771–5. doi: 10.2147/OPTH.S31085

56. Cheng JW, Cai JP, Li Y, Wei RL. A meta-analysis of topical prostaglandin analogs in the treatment of chronic angle-closure glaucoma. J Glaucoma. 2009; 18 (9): 652–7. doi: 10.1097/IJG.0b013e31819c49d4

57. Cheng JW, Cai JP, Wei RL. Meta-analysis of medical intervention for normal tension glaucoma. Ophthalmology. 2009; 116 (7): 1243–9. doi: 10.1016/j.ophtha.2009.01.036

58. Tabet R, Stewart WC, Feldman R, Konstas AG. A review of additivity to prostaglandin analogs: fixed and unfixed combinations. Surv Ophthalmol. 2008; 53 Suppl1: S85-92. doi: 10.1016/j.survophthal.2008.08.011

59. Quaranta L, Biagioli E, Riva I, et al. Prostaglandin analogs and timolol-fixed versus unfixed combinations or monotherapy for open-angle glaucoma: a systematic review and meta-analysis. J Ocul Pharmacol Ther. 2013; 29 (4): 382–9. doi: 10.1089/jop.2012.0186

60. Webers CA, Beckers HJ, Zeegers MP, et al. The intraocular pressure-lowering effect of prostaglandin analogs combined with topical beta-blocker therapy: a systematic review and meta-analysis. Ophthalmology. 2010; 117 (11): 2067-74 e1-6. doi: 10.1016/j.ophtha.2010.03.024

61. Hamacher T, Schinzel M, Scholzel-Klatt A, et al. Short term efficacy and safety in glaucoma patients changed to the latanoprost 0.005%/timolol maleate 0.5% fixed combination from monotherapies and adjunctive therapies. Br J Ophthalmol. 2004; 88 (10): 1295–8. doi: 10.1136/bjo.2004.043232

62. Stewart WC, Stewart JA, Day D, Sharpe ED. Efficacy and safety of timolol maleate/latanoprost fixed combination versus timolol maleate and brimonidine given twice daily. Acta Ophthalmol Scand. 2003; 81 (3): 242–6. doi: 10.1034/j.1600-0420.2003.00065.x

63. Magacho L, Reis R, Shetty RK, Santos LC, Avila MP. Efficacy of latanoprost or fixed-combination latanoprost-timolol in patients switched from a combination of timolol and a nonprostaglandin medication. Ophthalmology. 2006; 113 (3): 442–5. doi: 10.1016/j.ophtha.2005.11.011

64. Apostolova A.S. A comparative study of Xalatan and Xalacom (Pfizer, USA) efficacy in the treatment of pseudoexfoliative glaucoma. Ophthalmology reports. 2013; 6 (3): 71–4 (In Russ.).

65. Makogon S.I., Onishchenko A.L., Yatsenko L.L., Karmanova O.A. The efficacy of first-choice therapy in the treatment of newly diagnosed primary glaucoma. Russian journal of glaucoma. 2018; 17 (2): 28–37 (In Russ.).

66. Weinreb R.N., Libermann J. Drug treatment of glaucoma. The 7th Consensus of the World Glaucomatous Association. SPb.: Publishing House of NL; 2014 (In Russ.).

67. Makogon S.I., Makogon A.S. Primary and recurrent glaucoma-induced disability in senior working-age population in the Altai territory. Russian ophthalmological journal. 2017; 10 (3): 42–8 (In Russ.). doi: 10.21516/2072-0076-2017-10-3-42-48

68. Onishchenko A.I., Isakov I.N., Kolbasko A.V., Makogon S.I. Initial combination therapy for primary openangle glaucoma Vestnik oftal’mologii. 2019; 135 (2): 32–8 (In Russ.). doi: 10.17116/oftalma201913502132


Review

For citations:


Petrov S.Yu., Markelova O.I. Feasibility of a prostaglandin-timolol fixed combination first-line treatment of primary glaucoma. Russian Ophthalmological Journal. 2025;18(4):190-195. (In Russ.) https://doi.org/10.21516/2072-0076-2025-18-4-190-195

Views: 18


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2072-0076 (Print)
ISSN 2587-5760 (Online)