Efficacy and safety of 0.1 % brimonidine as a starting monotherapy and when added to combination therapy of glaucoma

Purpose: to analyze the efficacy and safety of Santabrim® as a starting monotherapy and when added to combination therapy for glaucoma.

Material and methods. The study was conducted on 60 patients (60 eyes), including 21 (35 %) men and 39 (65 %) women, with initial or advanced primary open-angle glaucoma with moderately elevated IOP. The average age of patients was 63.4 years. The first group (30 eyes) consisted of patients who were prescribed Santabrim® 2 times a day as a starting monotherapy. The second group consisted of patients (30 eyes) who had an enhanced regimen using Santabrim® 2 times a day as a third drug. To analyze the hypotensive effect, the data of corneally compensated IOP were compared at the first visit and 1 month after the appointment or enhancement of the local hypotensive regimen. Safety was assessed by comparing the degree of fluorescein staining of the cornea, conjunctival hyperemia, OSDI questionnaire indicators and the level of adherence to treatment at the appropriate time in two groups of patients.

Results. Santabrim® significantly reduces the level of IOP. The use of the drug as monotherapy allows to reduce IOP by 26.3 % of the initial level. Strengthening combination therapy by adding Santabrem® as a third drug allows reducing the level of IOP by an additional 15.9 %. Objective indicators of the condition of the tissues of the anterior surface of the eye have not changed significantly. Based on the results of the assessment of the main signs of dry eye syndrome (OSDI) and the degree of patient adherence to treatment, no significant changes were revealed.

Conclusion. Brimonidine 0.1 % (Santabrim®) can be recommended for the hypotensive treatment of glaucoma both in monotherapy and in combination with other groups of local instillation drugs, and its direct neuroprotective effect additionally contributes to the stabilization of glaucoma opticoneuropathy.

1. Erichev V.P., Onishchenko A.L., Kuroyedov A.V., et al. Ophthalmic risk factors for the development of primary open-angle glaucoma. Clinical ophthalmology. 2019; 19 (2): 81–6 (In Russ.). doi: 10.32364/2311-7729-2019-19-2-81-86

2. Le A, Mukesh BN, McCarty CA, Taylor HR. Risk factors associated with the incidence of open-angle glaucoma: the visual impairment project. Invest Ophthalmol Vis Sci. 2003; 44 (9): 3783–9. doi: 10.1167/iovs.03-0077

3. Chauhan BC, Mikelberg FS, Artes PH, et al. Canadian Glaucoma Study: 3. Impact of risk factors and intraocular pressure reduction on the rates of visual field change. Arch Ophthalmol. 2010; 128 (10): 1249–55. doi: 10.1001/archophthalmol.2010.196

4. Erichev V.P., Antonov A.A., Vitkov A.A., Grigoryan L.A. Static automated perimetry in the diagnosis of glaucoma. Part 1: Basic principles. Vestnik oftal’mologii. 2021; 137 (5–2): 281–8 (In Russ.). doi: 10.17116/oftalma2021137052281

5. Erichev V.P., Antonov A.A., Vitkov A.A., Grigoryan L.A. Static automated perimetry in the diagnosis of glaucoma. Part 2: Research protocol, glaucoma classifications, perimetric defects through the prism of structural-functional correlation. Vestnik oftal’mologii. 2021; 137 (5–2): 289–99 (In Russ.). doi: 10.17116/oftalma2021137052289

6. Petrov S.Yu., Subbot A.M., Gabashvili A.N., Volzhanin A.V., Vitkov A.A. Rat models of glaucomatous optic neuropathy. National Journal glaucoma. 2017; 16 (4): 79–85 (In Russ.).

7. Vitkov A.A., Kuroyedov A.V., Makarova A.S., et al. Repeat glaucoma surgery: modern view of the problem. National Journal glaucoma. 2023; 22 (4): 80–8 (In Russ.). doi: 10.53432/2078-4104-2023-22-4-80-88

8. Antonov A.A., Vostrukhin S.V., Volzhanin A.V. Influence of prostaglandin analogues on intraocular pressure fluctuations in body position change. Russian Clinical ophthalmology. 2022; 22 (2): 103–7 (In Russ.). doi: 10.32364/2311-7729-2022-22-2-103-107

9. Christiansen GA, Nau CB, McLaren JW, Johnson DH. Mechanism of ocular hypotensive action of bimatoprost (Lumigan) in patients with ocular hypertension or glaucoma. Ophthalmology. 2004; 111 (9): 1658–62. doi: 10.1016/j.ophtha.2004.02.006

10. Antonov A.A., Agadzhanyan T.M., Vitkov А.А. Hypotensive efficacy of bimatoprost in the treatment of primary open-angle glaucoma. National Journal glaucoma. 2019; 18 (1): 95–104 (In Russ.). doi: 10.25700/NJG.2019.01.11

11. Antonov A.A., Vitkov A.A., Agadzhanyan T.M. The efficacy and safety of the domestic travoprost generic in various modes of therapy for primary open-angle glaucoma. National Journal glaucoma. 2021; 20 (4): 50–6 (In Russ.). doi: 10.53432/2078-4104-2021-20-4-50-56

12. Hu J, Vu JT, Hong B, Gottlieb C. Uveitis and cystoid macular oedema secondary to topical prostaglandin analogue use in ocular hypertension and open angle glaucoma. Br J Ophthalmol. 2020; 104 (8): 1040–4. doi:10.1136/bjophthalmol-2019-315280

13. Lopilly Park HY, Kim JH, Lee KM, Park CK. Effect of prostaglandin analogues on tear proteomics and expression of cytokines and matrix metalloproteinases in the conjunctiva and cornea. Exp Eye Res. 2012; 94 (1): 13–21. doi: 10.1016/j.exer.2011.10.017

14. Horsley MB, Chen TC. The use of prostaglandin analogs in the uveitic patient. Semin Ophthalmol. 2011; 26 (4–5): 285–9. doi: 10.3109/08820538.2011.588650

15. Erichev V.P., Petrov S.Yu., Volzhanin A.V. Alpha-adrenergic receptor agonists in terms of modern views on glaucoma monitoring and treatment. Clinical ophthalmology. 2019; 19 (2): 87–91 (In Russ.).

16. Derick RJ, Robin AL, Walters TR, et al. Brimonidine tartrate: a one-month dose response study. Ophthalmology. 1997; 104 (1): 131–6. doi:10.1016/s0161-6420(97)30349-2

17. Antonov A.A., Kozlova I.V., Vitkov A.A. Maximum medical therapy for glaucoma — what is in our arsenal? National Journal glaucoma. 2020;19 (2): 51–8 (In Russ.). doi: 10.25700/NJG.2020.02.06

18. Petrov S.Yu., Zinina V.S., Volzhanin A.V. The role of fixed dose combinations in the treatment of primary open-angle glaucoma. Vestnik oftal’mologii. 2018; 134 (4): 100–7 (In Russ.). https://doi.org/10.17116/oftalma2018134041100

19. Adkins JC, Balfour JA. Brimonidine. A review of its pharmacological properties and clinical potential in the management of open-angle glaucoma and ocular hypertension. Drugs Aging. 1998; 12 (3): 225–41. doi:10.2165/00002512-199812030-00005

20. Stjernschantz J, Selen G, Astin M, Resul B. Microvascular effects of selective prostaglandin analogues in the eye with special reference to latanoprost and glaucoma treatment. Prog Retin Eye Res. 2000; 19 (4): 459–96. doi:10.1016/s1350-9462(00)00003-3

21. Kurysheva N.I. Selective α2-agonists in the treatment of glaucoma: pharmacology, efficacy and safety. Vestnik oftal’mologii. 2019; 135 (2): 144–50 (In Russ.). doi: 10.17116/oftalma2019135021144

22. Lambert WS, Ruiz L, Crish SD, Wheeler LA, Calkins DJ. Brimonidine prevents axonal and somatic degeneration of retinal ganglion cell neurons. Mol Neurodegener. 2011; 6 (1): 4. doi: 10.1186/1750-1326-6-4

23. Dong CJ., Guo Y, Agey P, Wheeler L, Hare WA. Alpha2 adrenergic modulation of NMDA receptor function as a major mechanism of RGC protection in experimental glaucoma and retinal excitotoxicity. Invest Ophthalmol Vis Sci. 2008; 49 (10): 4515–22. doi: 10.1167/iovs.08-2078

24. Dong CJ, Guo Y, Wheeler L, Hare WA. Alpha2 adrenergic receptor-mediated modulation of cytosolic Ca++ signals at the inner plexiform layer of the rat retina. Invest Ophthalmol Vis Sci. 2007; 48 (3): 1410–5. doi:10.1167/iovs.06-0890

25. Hondeghem K, Augustinus B, De Smet MD. Bilateral granulomatous uveitis as a side effect of topical brimonidine: two case reports. Bull Soc Belge Ophtalmol. 2009; (311): 51–2. PMID: 19621555

26. Nguyen EV, Azar D, Papalkar D, McCluskey P. Brimonidine-induced anterior uveitis and conjunctivitis: clinical and histologic features. J Glaucoma. 2008; 17 (1): 40–4. doi: 10.1097/IJG.0b013e3181132188

27. Velasque L, Ducousso F, Pernod L, Vignal R, Deral V. Anterior uveitis and topical brimonidine: a case report. J Fr Ophtalmol. 2004; 27 (10): 1150–2. doi: 10.1016/s0181-5512(04)96285-7

28. Carrasco MA, Schlaen BA, Zarate JO. Brimonidine-timolol fixed combination induced granulomatous inflammation of the eye. Int Ophthalmol. 2013; 33 (5): 557–60. doi: 10.1007/s10792-012-9688-0

29. Fudemberg SJ, Batiste C, Katz LJ. Efficacy, safety, and current applications of brimonidine. Expert Opin Drug Saf. 2008; 7 (6): 795–9. doi:10.1517/17425250802457609

30. Walters TR. Development and use of brimonidine in treating acute and chronic elevations of intraocular pressure: a review of safety, efficacy, dose response, and dosing studies. Surv Ophthalmol. 1996; 41 Suppl 1: S19-26. doi: 10.1016/s0039-6257(96)82028-5

31. Katz LJ. Twelve-month evaluation of brimonidine-purite versus brimonidine in patients with glaucoma or ocular hypertension. J Glaucoma. 2002; 11 (2): 119–26. doi: 10.1097/00061198-200204000-00007

32. Nitta K, Shimamoto S, Wajima R, et al. The effect of Brimonidine 0.1 % on disc hemorrhage in primary open-angle glaucoma patients. Clin Ophthalmol. 2020; 14: 213–9. doi: 10.2147/OPTH.S237969

33. Cantor LB, Safyan E, Liu CC, Batoosingh AL. Brimonidine-purite 0.1 % versus brimonidine-purite 0.15 % twice daily in glaucoma or ocular hypertension: a 12-month randomized trial. Curr Med Res Opin. 2008; 24 (7): 2035–43. doi: 10.1185/03007990802199287

34. Erichev V.P., Vitkov A.A. Topical beta-blockers: interactions and adverse events (analytical review). XVIII All-Russian School of Ophthalmology: collection of scientific works. 2019; 37–45 (In Russ.). doi: 10.30808/978-5-6040782-2019-1-1-37-44

35. Erichev V.P., Vitkov A.A. Clinical evaluation of a fixed combination of prostaglandin analogues and beta-blockers. National Journal glaucoma. 2020; 19 (2): 59–65 (In Russ.). https://doi.org/10.25700/NJG.2020.02.07

36. Antonov A.A., Kozlova I.V., Vitkov A.A., Agadzhanyan T.M. A new algorithm of treatment choice in primary open-angle glaucoma. Russian ophthalmological journal. 2021; 14 (4): 7–17 (In Russ.). doi: 10.21516/2072-0076-2021-14-4-7-17

37. Bron AJ, Evans VE, Smith JAJC. Grading of corneal and conjunctival staining in the context of other dry eye tests. Cornea. 2003 Oct; 22 (7): 640–50. doi: 10.1097/00003226-200310000-00008

38. Cantor LB. Brimonidine in the treatment of glaucoma and ocular hypertension. Ther Clin Risk Manag. 2006 Dec; 2 (4): 337–46. doi: 10.2147/tcrm.2006.2.4.337