Skip to main content
NCBI home page
The British Journal of Ophthalmology logoLink to The British Journal of Ophthalmology
. 2001 Aug;85(8):983–990. doi: 10.1136/bjo.85.8.983

Meta-analysis of randomised controlled trials comparing latanoprost with timolol in the treatment of patients with open angle glaucoma or ocular hypertension

W Zhang 1, A Po 1, H Dua 1, A Azuara-Blanco 1
PMCID: PMC1724079  PMID: 11466259

Abstract

AIM—To evaluate the comparative efficacy and tolerance of latanoprost versus timolol through a meta-analysis of randomised controlled trials (RCTs).
METHODS—Systematic retrieval of RCTs of latanoprost versus timolol to allow pooling of results from head to head comparison studies. Quality of trials was assessed based on randomisation, masking, and withdrawal. Sensitivity analyses were used to estimate the effects of quality of study on outcomes. The data sources were Medline, Embase, Scientific Citation Index, Merck Glaucoma, and Pharmacia and Upjohn ophthalmology databases. There were 1256 patients with open angle glaucoma or ocular hypertension reported in 11 trials of latanoprost versus timolol. The main outcome measures were (i) percentage intraocular pressure (IOP) reduction for efficacy; (ii) relative risk, risk difference, and number needed to harm for side effects such as hyperaemia, conjunctivitis, increased pigmentation, hypotension, and bradycardia expressed as dichotomous outcomes; and (iii) reduction in systemic blood pressure and heart rate as side effects.
RESULTS—Both 0.005% latanoprost once daily and 0.5% timolol twice daily reduced IOP. The percentage reductions in IOP from baseline (mean (SE)) produced by latanoprost and timolol were 30.2 (2.3) and 26.9 (3.4) at 3 months. The difference in IOP reduction between the two treatments were 5.0 (95% confidence intervals 2.8, 7.3). However, latanoprost caused iris pigmentation in more patients than timolol (relative risk = 8.01, 95% confidence intervals 1.87, 34.30). The 2 year risk with latanoprost reached 18% (51/277). Hyperaemia was also more often observed with latanoprost (relative risk =2.20, 95% confidence intervals 1.33, 3.64). Timolol caused a significant reduction in heart rate of 4 beats/minute (95% confidence interval 2, 6).
CONCLUSION—This meta-analysis suggests that latanoprost is more effective than timolol in lowering IOP. However, it often causes iris pigmentation. While current evidence suggests that this pigmentation is benign, careful lifetime evaluation of patients is still justified.



Full Text

The Full Text of this article is available as a PDF (198.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aguinaga Ontoso I., Guillen Grima F., Aguinaga Ontoso E., Fernandez Fernandez L. R. Does medical treatment of mild intraocular hypertension prevent glaucoma? Eur J Epidemiol. 1997 Jan;13(1):19–23. doi: 10.1023/a:1007324907818. [DOI] [PubMed] [Google Scholar]
  2. Alm A. Comparative phase III clinical trial of latanoprost and timolol in patients with elevated intraocular pressure. Adv Prostaglandin Thromboxane Leukot Res. 1995;23:527–532. [PubMed] [Google Scholar]
  3. Alm A., Stjernschantz J. Effects on intraocular pressure and side effects of 0.005% latanoprost applied once daily, evening or morning. A comparison with timolol. Scandinavian Latanoprost Study Group. Ophthalmology. 1995 Dec;102(12):1743–1752. doi: 10.1016/s0161-6420(95)30798-1. [DOI] [PubMed] [Google Scholar]
  4. Alm A., Villumsen J., Törnquist P., Mandahl A., Airaksinen J., Tuulonen A., Marsk A., Resul B., Stjernschantz J. Intraocular pressure-reducing effect of PhXA41 in patients with increased eye pressure. A one-month study. Ophthalmology. 1993 Sep;100(9):1312–1317. doi: 10.1016/s0161-6420(93)31482-x. [DOI] [PubMed] [Google Scholar]
  5. Alm A., Widengård I., Kjellgren D., Söderström M., Friström B., Heijl A., Stjerschantz J. Latanoprost administered once daily caused a maintained reduction of intraocular pressure in glaucoma patients treated concomitantly with timolol. Br J Ophthalmol. 1995 Jan;79(1):12–16. doi: 10.1136/bjo.79.1.12. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Alm A., Widengård I., Kjellgren D., Söderström M., Friström B., Heijl A., Stjerschantz J. Latanoprost administered once daily caused a maintained reduction of intraocular pressure in glaucoma patients treated concomitantly with timolol. Br J Ophthalmol. 1995 Jan;79(1):12–16. doi: 10.1136/bjo.79.1.12. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Alm A., Widengård I. Latanoprost: experience of 2-year treatment in Scandinavia. Acta Ophthalmol Scand. 2000 Feb;78(1):71–76. doi: 10.1034/j.1600-0420.2000.078001071.x. [DOI] [PubMed] [Google Scholar]
  8. Alward W. L. Medical management of glaucoma. N Engl J Med. 1998 Oct 29;339(18):1298–1307. doi: 10.1056/NEJM199810293391808. [DOI] [PubMed] [Google Scholar]
  9. Bucci M. G. Intraocular pressure-lowering effects of latanoprost monotherapy versus latanoprost or pilocarpine in combination with timolol: a randomized, observer-masked multicenter study in patients with open-angle glaucoma. Italian Latanoprost Study Group. J Glaucoma. 1999 Feb;8(1):24–30. [PubMed] [Google Scholar]
  10. Calissendorff B., Marén N., Wettrell K., Ostberg A. Timolol versus pilocarpine separately or combined with acetazolamide-effects on intraocular pressure. Acta Ophthalmol (Copenh) 1980 Aug;58(4):624–631. doi: 10.1111/j.1755-3768.1980.tb08304.x. [DOI] [PubMed] [Google Scholar]
  11. Camras C. B., Alm A., Watson P., Stjernschantz J. Latanoprost, a prostaglandin analog, for glaucoma therapy. Efficacy and safety after 1 year of treatment in 198 patients. Latanoprost Study Groups. Ophthalmology. 1996 Nov;103(11):1916–1924. doi: 10.1016/s0161-6420(96)30407-7. [DOI] [PubMed] [Google Scholar]
  12. Camras C. B. Comparison of latanoprost and timolol in patients with ocular hypertension and glaucoma: a six-month masked, multicenter trial in the United States. The United States Latanoprost Study Group. Ophthalmology. 1996 Jan;103(1):138–147. doi: 10.1016/s0161-6420(96)30749-5. [DOI] [PubMed] [Google Scholar]
  13. Camras C. B. Mechanism of the prostaglandin-induced reduction of intraocular pressure in humans. Adv Prostaglandin Thromboxane Leukot Res. 1995;23:519–525. [PubMed] [Google Scholar]
  14. Camras C. B., Wax M. B., Ritch R., Weinreb R., Robin A. L., Higginbotham E. J., Lustgarten J., Stewart W. C., Sherwood M., Krupin T. Latanoprost treatment for glaucoma: effects of treating for 1 year and of switching from timolol. United States Latanoprost Study Group. Am J Ophthalmol. 1998 Sep;126(3):390–399. doi: 10.1016/s0002-9394(98)00094-4. [DOI] [PubMed] [Google Scholar]
  15. Cook R. J., Sackett D. L. The number needed to treat: a clinically useful measure of treatment effect. BMJ. 1995 Feb 18;310(6977):452–454. doi: 10.1136/bmj.310.6977.452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Coyle D., Drummond M. The economic burden of glaucoma in the UK. The need for a far-sighted policy. Pharmacoeconomics. 1995 Jun;7(6):484–489. doi: 10.2165/00019053-199507060-00003. [DOI] [PubMed] [Google Scholar]
  17. DerSimonian R., Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986 Sep;7(3):177–188. doi: 10.1016/0197-2456(86)90046-2. [DOI] [PubMed] [Google Scholar]
  18. Diestelhorst M., Almegård B. Comparison of two fixed combinations of latanoprost and timolol in open-angle glaucoma. Graefes Arch Clin Exp Ophthalmol. 1998 Aug;236(8):577–581. doi: 10.1007/s004170050124. [DOI] [PubMed] [Google Scholar]
  19. Diestelhorst M., Roters S., Krieglstein G. K. The effect of latanoprost 0.005% once daily versus 0.0015% twice daily on intraocular pressure and aqueous humour protein concentration in glaucoma patients. A randomized, double-masked comparison with timolol 0.5%. Graefes Arch Clin Exp Ophthalmol. 1997 Jan;235(1):20–26. doi: 10.1007/BF01007833. [DOI] [PubMed] [Google Scholar]
  20. Diggory P., Cassels-Brown A., Vail A., Abbey L. M., Hillman J. S. Avoiding unsuspected respiratory side-effects of topical timolol with cardioselective or sympathomimetic agents. Lancet. 1995 Jun 24;345(8965):1604–1606. doi: 10.1016/s0140-6736(95)90116-7. [DOI] [PubMed] [Google Scholar]
  21. Dinai Y., Sharir M., Naveh N., Halkin H. Bradycardia induced by interaction between quinidine and ophthalmic timolol. Ann Intern Med. 1985 Dec;103(6 ):890–891. doi: 10.7326/0003-4819-103-6-890. [DOI] [PubMed] [Google Scholar]
  22. Drance S. M., Crichton A., Mills R. P. Comparison of the effect of latanoprost 0.005% and timolol 0.5% on the calculated ocular perfusion pressure in patients with normal-tension glaucoma. Am J Ophthalmol. 1998 May;125(5):585–592. doi: 10.1016/s0002-9394(98)00019-1. [DOI] [PubMed] [Google Scholar]
  23. Frishman W. H., Fuksbrumer M. S., Tannenbaum M. Topical ophthalmic beta-adrenergic blockade for the treatment of glaucoma and ocular hypertension. J Clin Pharmacol. 1994 Aug;34(8):795–803. doi: 10.1002/j.1552-4604.1994.tb02042.x. [DOI] [PubMed] [Google Scholar]
  24. Friström B. A 6-month, randomized, double-masked comparison of latanoprost with timolol in patients with open angle glaucoma or ocular hypertension. Acta Ophthalmol Scand. 1996 Apr;74(2):140–144. doi: 10.1111/j.1600-0420.1996.tb00058.x. [DOI] [PubMed] [Google Scholar]
  25. Hattenhauer M. G., Johnson D. H., Ing H. H., Herman D. C., Hodge D. O., Yawn B. P., Butterfield L. C., Gray D. T. The probability of blindness from open-angle glaucoma. Ophthalmology. 1998 Nov;105(11):2099–2104. doi: 10.1016/S0161-6420(98)91133-2. [DOI] [PubMed] [Google Scholar]
  26. Hedner J., Everts B., Möller C. S. Latanoprost and respiratory function in asthmatic patients: randomized, double-masked, placebo-controlled crossover evaluation. Arch Ophthalmol. 1999 Oct;117(10):1305–1309. doi: 10.1001/archopht.117.10.1305. [DOI] [PubMed] [Google Scholar]
  27. Jadad A. R., Moore R. A., Carroll D., Jenkinson C., Reynolds D. J., Gavaghan D. J., McQuay H. J. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996 Feb;17(1):1–12. doi: 10.1016/0197-2456(95)00134-4. [DOI] [PubMed] [Google Scholar]
  28. Jones F. L., Jr, Ekberg N. L. Exacerbation of asthma by timolol. N Engl J Med. 1979 Aug 2;301(5):270–270. [PubMed] [Google Scholar]
  29. Kass M. A. Timolol treatment prevents or delays glaucomatous visual field loss in individuals with ocular hypertension: a five-year, randomized, double-masked, clinical trial. Trans Am Ophthalmol Soc. 1989;87:598–618. [PMC free article] [PubMed] [Google Scholar]
  30. Konstas A. G., Maltezos A. C., Gandi S., Hudgins A. C., Stewart W. C. Comparison of 24-hour intraocular pressure reduction with two dosing regimens of latanoprost and timolol maleate in patients with primary open-angle glaucoma. Am J Ophthalmol. 1999 Jul;128(1):15–20. doi: 10.1016/s0002-9394(99)00073-2. [DOI] [PubMed] [Google Scholar]
  31. Konstas A. G., Maltezos A. C., Gandi S., Hudgins A. C., Stewart W. C. Comparison of 24-hour intraocular pressure reduction with two dosing regimens of latanoprost and timolol maleate in patients with primary open-angle glaucoma. Am J Ophthalmol. 1999 Jul;128(1):15–20. doi: 10.1016/s0002-9394(99)00073-2. [DOI] [PubMed] [Google Scholar]
  32. Leier C. V., Baker N. D., Weber P. A. Cardiovascular effects of ophthalmic timolol. Ann Intern Med. 1986 Feb;104(2):197–199. doi: 10.7326/0003-4819-104-2-197. [DOI] [PubMed] [Google Scholar]
  33. Lusky M., Ticho U., Glovinsky J., Weinberger D., Nesher R., Yassur Y., Melamed S. A comparative study of two dose regimens of latanoprost in patients with elevated intraocular pressure. Ophthalmology. 1997 Oct;104(10):1720–1724. doi: 10.1016/s0161-6420(97)30074-8. [DOI] [PubMed] [Google Scholar]
  34. Mastropasqua L., Carpineto P., Ciancaglini M., Gallenga P. E. A 12-month, randomized, double-masked study comparing latanoprost with timolol in pigmentary glaucoma. Ophthalmology. 1999 Mar;106(3):550–555. doi: 10.1016/S0161-6420(99)90115-X. [DOI] [PubMed] [Google Scholar]
  35. McMahon C. D., Shaffer R. N., Hoskins H. D., Jr, Hetherington J., Jr Adverse effects experienced by patients taking timolol. Am J Ophthalmol. 1979 Oct;88(4):736–738. doi: 10.1016/0002-9394(79)90674-3. [DOI] [PubMed] [Google Scholar]
  36. Mishima H. K., Masuda K., Kitazawa Y., Azuma I., Araie M. A comparison of latanoprost and timolol in primary open-angle glaucoma and ocular hypertension. A 12-week study. Arch Ophthalmol. 1996 Aug;114(8):929–932. doi: 10.1001/archopht.1996.01100140137004. [DOI] [PubMed] [Google Scholar]
  37. Nelson W. L., Fraunfelder F. T., Sills J. M., Arrowsmith J. B., Kuritsky J. N. Adverse respiratory and cardiovascular events attributed to timolol ophthalmic solution, 1978-1985. Am J Ophthalmol. 1986 Nov 15;102(5):606–611. doi: 10.1016/0002-9394(86)90532-5. [DOI] [PubMed] [Google Scholar]
  38. Nicolela M. T., Buckley A. R., Walman B. E., Drance S. M. A comparative study of the effects of timolol and latanoprost on blood flow velocity of the retrobulbar vessels. Am J Ophthalmol. 1996 Dec;122(6):784–789. doi: 10.1016/s0002-9394(14)70374-5. [DOI] [PubMed] [Google Scholar]
  39. Pringle S. D., MacEwen C. J. Severe bradycardia due to interaction of timolol eye drops and verapamil. Br Med J (Clin Res Ed) 1987 Jan 17;294(6565):155–156. doi: 10.1136/bmj.294.6565.155-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Rulo A. H., Greve E. L., Hoyng P. F. Additive effect of latanoprost, a prostaglandin F2 alpha analogue, and timolol in patients with elevated intraocular pressure. Br J Ophthalmol. 1994 Dec;78(12):899–902. doi: 10.1136/bjo.78.12.899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Rácz P., Ruzsonyi M. R., Nagy Z. T., Gaygi Z., Bito L. Z. Around-the-clock intraocular pressure reduction with once-daily application of latanoprost by itself or in combination with timolol. Arch Ophthalmol. 1996 Mar;114(3):268–273. doi: 10.1001/archopht.1996.01100130264005. [DOI] [PubMed] [Google Scholar]
  42. Thygesen J., Aaen K., Theodorsen F., Kessing S. V., Prause J. U. Short-term effect of latanoprost and timolol eye drops on tear fluid and the ocular surface in patients with primary open-angle glaucoma and ocular hypertension. Acta Ophthalmol Scand. 2000 Feb;78(1):37–44. doi: 10.1034/j.1600-0420.2000.078001037.x. [DOI] [PubMed] [Google Scholar]
  43. Watson P. G. Latanoprost. Two years' experience of its use in the United Kingdom. Latanoprost Study Group. Ophthalmology. 1998 Jan;105(1):82–87. doi: 10.1016/s0161-6420(98)91372-0. [DOI] [PubMed] [Google Scholar]
  44. Watson P., Stjernschantz J. A six-month, randomized, double-masked study comparing latanoprost with timolol in open-angle glaucoma and ocular hypertension. The Latanoprost Study Group. Ophthalmology. 1996 Jan;103(1):126–137. doi: 10.1016/s0161-6420(96)30750-1. [DOI] [PubMed] [Google Scholar]
  45. Whitehead A., Whitehead J. A general parametric approach to the meta-analysis of randomized clinical trials. Stat Med. 1991 Nov;10(11):1665–1677. doi: 10.1002/sim.4780101105. [DOI] [PubMed] [Google Scholar]
  46. Zadok D., Geyer O., Zadok J., Lazar M., Krakowski D., Nemet P. Combined timolol and pilocarpine vs pilocarpine alone and timolol alone in the treatment of glaucoma. Am J Ophthalmol. 1994 Jun 15;117(6):728–731. doi: 10.1016/s0002-9394(14)70315-0. [DOI] [PubMed] [Google Scholar]
  47. Zhang W. Y., Li Wan Po A. Analgesic efficacy of paracetamol and its combination with codeine and caffeine in surgical pain--a meta-analysis. J Clin Pharm Ther. 1996 Aug;21(4):261–282. doi: 10.1111/j.1365-2710.1996.tb01148.x. [DOI] [PubMed] [Google Scholar]

Articles from The British Journal of Ophthalmology are provided here courtesy of BMJ Publishing Group

RESOURCES