Timolol 0.5% versus Latanoprost 0.005% as A Single Hypotensive Drug in Glaucoma Patients: A 2-year Follow-up

Gentian Hoxha, Flaka Shoshi, Fëllanza Ismajli Hoxha, Agim Xhafa, Fitore Shoshi

 
For citation: Hoxha G, Shoshi F, Hoxha FI, Xhafa A, Shoshi F. Timolol 0.5% versus Latanoprost 0.005% as A Single Hypotensive Drug in Glaucoma Patients: A 2-year Follow-up. International Journal of Biomedicine. 2024;14(4):626-631. doi:10.21103/Article14(4)_OA15
 
Originally published December 5, 2024
 

Abstract: 

Background: Glaucoma is a progressive optic nerve disease that, despite its treatment, is associated with retinal ganglion cell damage. However, timely treatment hinders the progression of visual field damage and preserves visual function. Our study aimed to evaluate the treatment outcomes and adverse effects in glaucomatous patients of using a single anti-glaucomatous agent, 0.5% timolol maleate, or 0.005% latanoprost, for 24 months.
Methods and Results: This prospective, single-arm, open-label study included 87 patients (47.13% men and 52.87% women) with open-angle glaucoma treated with a single hypotensive agent. The patients were divided into two groups. Group 1 patients (n=43) were treated with 0.5% timolol, and Group 2 patients (n=44) were treated with 0.005% latanoprost. We assessed the intraocular pressure (IOP) in 7 visits for 24 months, the cup-to-disc ratio (CDR), and the drug's side effects.
At baseline (Visit 1), Group 1 showed an IOP(OD) of 26.46±1.99 mmHg and an IOP(OS) of 26.34±2.14 mmHg. Group 2 showed an IOP(OD) of 26.18±1.98 mmHg and an IOP(OS) of 26.18±2.03 mmHg. There were no significant differences between the two treatments at the initial stage. At the second follow-up visit, the mean IOP(OD) and IOP(OS) significantly decreased from baseline in both groups. There was no significant difference between the two treatments at this stage. By the third follow-up visit, IOP continued to decrease effectively in both groups, and no significant difference was observed between the two treatments at this stage. At Visits 4 and 5, in Group 1, the IOP remained without significant dynamics compared to Visit 3. At the same time, in Group 2, the IOP continued to decrease slightly. However, no significant difference was observed between the two treatments at these stages. Latanoprost appears to result in slightly lower IOP levels overall. By the sixth follow-up visit, IOP continued to decrease effectively in both groups. Although latanoprost provided lower IOP values, there was no significant difference between groups. By Visit 7, the difference between the two treatments becomes more noticeable. Group 1 has an IOP(OD) of 16.09±1.26 mmHg and IOP(OS) of 16.00±1.38 mmHg, while Group 2 continued to show lower IOP levels: IOP(OD) of 14.18±1.04 mmHg and IOP(OS) of 14.13±1.09 mmHg. The differences between the groups became significant (P=0.029), indicating that latanoprost was more effective in reducing IOP in the long term.
Changes in the CDR used to assess the optic nerve were assessed before and after 24 months of treatment.  In Group 1, CDR before treatment was 0.451±0.112 and slightly increased by the end of treatment to 0.484±0.123.  In Group 2, CDR before treatment was 0.436±0.138 and slightly increased to 0.452±0.15.
With timolol therapy, side effects were found in 11(25.58%) patients, and with latanoprost therapy only in 7(15.9%) patients. Although the differences were not statistically significant, latanoprost had a slightly more favorable safety profile than timolol.
Conclusion: The consistently lower mean IOP values for latanoprost treatment suggest it may be more effective in reducing IOP than timolol. However, the lack of statistically significant differences indicates that while one may perform slightly better on average, both treatments are generally effective and may be chosen based on individual patient needs and tolerability.

Keywords: 
glaucoma • intraocular pressure • timolol • latanoprost • cup-to-disc ratio • adverse effects
References: 
  1. Guven Yilmaz S, Degirmenci C, Karakoyun YE, Yusifov E, Ates H. The efficacy and safety of bimatoprost/timolol maleate, latanoprost/timolol maleate, and travoprost/timolol maleate fixed combinations on 24-h IOP. Int Ophthalmol. 2018 Aug;38(4):1425-1431. doi: 10.1007/s10792-017-0601-8. Epub 2017 Jun 14. PMID: 28616797.
  2. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration.The AGIS Investigators. Am J Ophthalmol. 2000 Oct;130(4):429-40. doi: 10.1016/s0002-9394(00)00538-9. PMID: 11024415.
  3. Heijl A, Leske MC, Bengtsson B, Hyman L, Bengtsson B, Hussein M; Early Manifest Glaucoma Trial Group. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002 Oct;120(10):1268-79. doi: 10.1001/archopht.120.10.1268. PMID: 12365904.
  4. Leske MC, Heijl A, Hyman L, Bengtsson B, Komaroff E. Factors for progression and glaucoma treatment: the Early Manifest Glaucoma Trial. Curr Opin Ophthalmol. 2004 Apr;15(2):102-6. doi: 10.1097/00055735-200404000-00008. PMID: 15021220.
  5. Xing Y, Jiang FG, Li T. Fixed combination of latanoprost and timolol vs the individual components for primary open angle glaucoma and ocular hypertension: a systematic review and meta-analysis. Int J Ophthalmol. 2014 Oct 18;7(5):879-90. doi: 10.3980/j.issn.2222-3959.2014.05.26. PMID: 25349811; PMCID: PMC4206899.
  6. Lundberg LU, Thygesen J, Damgaard-Jensen L, Serup L, Kessing SV. Glaukompatienter i behandling hos praktiserende øjenlaeger i Danmark. Estimat af antal patienter samt omfang af synsfeltsdefekter [Glaucoma patients treated by practicing ophthalmologists in Denmark. Estimated number of patients and the extent of visual field defects]. Ugeskr Laeger. 2000 May 22;162(21):3028-33. Danish. PMID: 10850191.
  7. Wang Y, Liao Y, Nie X. Comparative evaluation of Latanoprostene Bunod, Timolol Maleate, and latanoprost Ophthalmic Solutions to assess their safety and efficacy in lowering intraocular pressure for the management of Open-Angle Glaucoma. Clinics (Sao Paulo). 2020 Nov 30;75:e1874. doi: 10.6061/clinics/2020/e1874. PMID: 33263632; PMCID: PMC7688071.
  8. Mishra D, Sinha BP, Kumar MS. Comparing the efficacy of latanoprost (0.005%), bimatoprost (0.03%), travoprost (0.004%), and timolol (0.5%) in the treatment of primary open angle glaucoma. Korean J Ophthalmol. 2014 Oct;28(5):399-407. doi: 10.3341/kjo.2014.28.5.399. Epub 2014 Sep 18. PMID: 25276082; PMCID: PMC4179117.
  9. Schenker HI, Silver LH. Long-term intraocular pressure-lowering efficacy and safety of timolol maleate gel-forming solution 0.5% compared with Timoptic XE 0.5% in a 12-month study. Am J Ophthalmol. 2000 Aug;130(2):145-50. doi: 10.1016/s0002-9394(00)00458-x. PMID: 11004287.
  10. Parrish RK, Palmberg P, Sheu WP; XLT Study Group. A comparison of latanoprost, bimatoprost, and travoprost in patients with elevated intraocular pressure: a 12-week, randomized, masked-evaluator multicenter study. Am J Ophthalmol. 2003 May;135(5):688-703. doi: 10.1016/s0002-9394(03)00098-9. PMID: 12719078.
  11. Chauhan BC, Mikelberg FS, Balaszi AG, LeBlanc RP, Lesk MR, Trope GE; Canadian Glaucoma Study Group. Canadian Glaucoma Study: 2. risk factors for the progression of open-angle glaucoma. Arch Ophthalmol. 2008 Aug;126(8):1030-6. doi: 10.1001/archopht.126.8.1030. Erratum in: Arch Ophthalmol. 2008 Oct;126(10):1364. PMID: 18695095.
  12. Heijl A, Leske MC, Bengtsson B, Hyman L, Bengtsson B, Hussein M; Early Manifest Glaucoma Trial Group. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002 Oct;120(10):1268-79. doi: 10.1001/archopht.120.10.1268. PMID: 12365904.
  13. Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, Parrish RK 2nd, Wilson MR, Gordon MO. 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 Jun;120(6):701-13; discussion 829-30. doi: 10.1001/archopht.120.6.701. PMID: 12049574.
  14. Covert D, Robin AL. Adjunctive glaucoma therapy use associated with travoprost, bimatoprost, and latanoprost. Curr Med Res Opin. 2006 May;22(5):971-6. doi: 10.1185/030079906x104777. PMID: 16709319.
  15. Tsai JC. A comprehensive perspective on patient adherence to topical glaucoma therapy. 14Ophthalmology. 2009 Nov;116(11 Suppl):S30-6. doi: 10.1016/j.ophtha.2009.06.024. PMID: 19837258.
  16. Robin AL, Covert D. Does adjunctive glaucoma therapy affect adherence to the initial primary therapy? Ophthalmology. 2005 May;112(5):863-8. doi: 10.1016/j.ophtha.2004.12.026. PMID: 15878067.
  17. Carkeet A. A Review of the Use of Confidence Intervals for Bland-Altman Limits of Agreement in Optometry and Vision Science. Optom Vis Sci. 2020 Jan;97(1):3-8. doi: 10.1097/OPX.0000000000001465. PMID: 31895271.
  18. Heo JH, Rascati KL, Wilson JP, Lawson KA, Richards KM, Nair R. Comparison of Prostaglandin Analog Treatment Patterns in Glaucoma and Ocular Hypertension. J Manag Care Spec Pharm. 2019 Sep;25(9):1001-1010. doi: 10.18553/jmcp.2019.25.9.1001. PMID: 31456491; PMCID: PMC10398081.
  19. Guo X, Zhang J, Liu X, Lu Y, Shi Y, Li X, Wang S, Huang J, Liu H, Zhou H, Li Q, Luo L, You J. Antioxidant nanoemulsion loaded with latanoprost enables highly effective glaucoma treatment. J Control Release. 2023 Sep;361:534-546. doi: 10.1016/j.jconrel.2023.08.004. Epub 2023 Aug 15. PMID: 37567509.
  20. Varma R, Hwang LJ, Grunden JW, Bean GW, Sultan MB. Assessing the efficacy of latanoprost vs timolol using an alternate efficacy parameter: the intervisit intraocular pressure range. Am J Ophthalmol. 2009 Aug;148(2):221-6. doi: 10.1016/j.ajo.2009.02.035. Epub 2009 May 9. PMID: 19427617.
  21. Konstas AG, Nakos E, Tersis I, Lallos NA, Leech JN, Stewart WC. A comparison of once-daily morning vs evening dosing of concomitant latanoprost/timolol. Am J Ophthalmol. 2002 Jun;133(6):753-7. doi: 10.1016/s0002-9394(02)01460-5. PMID: 12036665.
  22. Bacharach J, Brubaker JW, Evans DG, Lu F, Odani-Kawabata N, Yamabe T, Wirta DL. Omidenepag Isopropyl Versus Timolol in Patients With Glaucoma or Ocular Hypertension: Two Randomized Phase 3 Trials (SPECTRUM 4 and 3). Am J Ophthalmol. 2024 Jul;263:23-34. doi: 10.1016/j.ajo.2024.02.010. Epub 2024 Feb 21. PMID: 38395329.

Download Article
Received October 20, 2024.
Accepted December 2, 2024.
©2024 International Medical Research and Development Corporation.