Abstract
Abstract
Background:
The current objective of antiglaucomatous therapy is to reduce intraocular pressure (IOP), and thus to preserve visual function. Many ophthalmologists believe this objective is best achieved by methods that improve ocular blood flow to the optic nerve head. Beta-blockers are effective ocular hypotensive agents, but they can reduce choroidal blood flow. Bimatoprost, a new prostamide analogue, has been shown to have a better IOP-lowering effect compared with the nonselective beta-adrenergic receptor blocker timolol maleate, but little is known about its effects on the vascular bed of the eye.
Objective:
The aim of this study was to compare the effects of bimatoprost and timolol on IOP and choroidal blood flow (as measured using pulsatile ocular blood flow [pOBF]) in patients with primary open-angle glaucoma (POAG).
Methods:
This prospective, open-label, randomized, 2-arm, parallel-group study was conducted at the Glaucoma Research Centre, Department of Ophthalmology, University Hospital of Bari, Bari, Italy. Patients with POAG having well-controlled IOP (<16 mm Hg) on monotherapy with timolol 0.5% ophthalmic solution (2 drops per affected eye BID) for ≥12 months but with a progressive decrease in pOBF during the same time period were randomly allocated to 1 of 2 treatment groups. One group continued monotherapy with timolol, 2 drops per affected eye BID. The other group was switched (without washout) to bimatoprost 0.3% ophthalmic solution (2 drops per affected eye QD [9 pm]). Treatment was given for 180 days. IOP and pOBF were assessed at the diagnostic visit (pre-timolol), baseline (day 0), and treatment days 15, 30, 60, 90, and 180. Primary adverse effects (AEs) (ie, conjunctival hyperemia, conjunctival papillae, stinging, burning, foreign body sensation, and pigmentation of periorbital skin) were monitored throughout the study.
Results:
Thirty-eight patients were enrolled (22 men, 16 women; mean [SD] age, 51.7 [4.8] years; 19 patients per treatment group; 38 eligible eyes). At 180-day follow-up in the timolol group, the IOP and the pOBF remained unchanged compared with baseline. In the bimatoprost group the IOP remained unchanged and the pOBF was decreased by 38.9% compared with baseline (P < 0.01). All AEs were mild to moderate and included conjunctival hyperemia and ocular itching (5 patients [26.3%] in the bimatoprost group) and pigmentation of periorbital skin (2 patients [40.0%] in the bimatoprost group). The incidence of each AE was higher in the bimatoprost group than in the timolol group (P = 0.008).
Conclusions:
In this population of patients with POAG, bimatoprost was associated with increased pOBF, and the reduction in pOBF associated with timolol was corrected after patients were switched to bimatoprost. Bimatoprost was associated with increased choroidal blood flow, beyond the levels recorded before timolol treatment. The decreased IOP level achieved in the timolol group seemed to be improved further by bimatoprost. Considering the potential efficacy of bimatoprost on IOP and pOBF, we suggest that this new drug may represent a clinical advance in the medical treatment of POAG.
Key words: bimatoprost, timolol, pulsatile ocular blood flow, intraocular pressure, primary open-angle glaucoma
Full Text
The Full Text of this article is available as a PDF (410.5 KB).
References
- 1.Akarsu C, Bilgili YK, Taner P. Short-term effect of latanoprost on ocular circulation in ocular hypertension. Clin Experiment Ophthalmol. 2004;32:373–377. doi: 10.1111/j.1442-9071.2004.00840.x. [DOI] [PubMed] [Google Scholar]
- 2.Zeitz O, Matthiessen ET, Wiermann A. Ocular hemodynamics in normal tension glaucoma: Effect of bimatoprost. Klin Monatsbl Augenheilkd. 2004;221:550–554. doi: 10.1055/s-2004-813354. [in German] [DOI] [PubMed] [Google Scholar]
- 3.Agarwal HC, Gupta V, Sihota R. Effect of changing from concomitant timolol pilocarpine to bimatoprost monotherapy on ocular blood flow and IOP in primary chronic angle closure glaucoma. J Ocul Pharmacol Ther. 2003;19:105–112. doi: 10.1089/108076803321637636. [DOI] [PubMed] [Google Scholar]
- 4.Sharif NA, Kelly CR, Williams GW. Bimatoprost (Lumigan) is an agonist at the cloned human ocular FP prostaglandin receptor: Real-time FLIPR-based intracellular Ca(2+) mobilization studies. Prostaglandins Leukot Essent Fatty Acids. 2003;68:27–33. doi: 10.1016/s0952-3278(02)00232-6. [DOI] [PubMed] [Google Scholar]
- 5.Woodward DF, Krauss AH, Chen J. The pharmacology of bimatoprost (Lumigan) Surv Ophthalmol. 2001;45(Suppl 4):S337–S345. doi: 10.1016/s0039-6257(01)00224-7. [published correction appears in Surv Ophthalmol. 2002;47:295] [DOI] [PubMed] [Google Scholar]
- 6.Davies SS, Ju WK, Neufeld AH. Hydrolysis of bimatoprost (Lumigan) to its free acid by ocular tissue in vitro. J Ocul Pharmacol Ther. 2003;19:45–54. doi: 10.1089/108076803762718105. [DOI] [PubMed] [Google Scholar]
- 7.Sharif NA, Williams GW, Kelly CR. Bimatoprost and its free acid are prostaglandin FP receptor agonists. Eur J Pharmacol. 2001;432:211–213. doi: 10.1016/s0014-2999(01)01486-8. [DOI] [PubMed] [Google Scholar]
- 8.Brubaker RF. Mechanism of action of bimatoprost (Lumigan) Surv Ophthalmol. 2001;45(Suppl 4):S347–S351. doi: 10.1016/s0039-6257(01)00213-2. [DOI] [PubMed] [Google Scholar]
- 9.Brubaker RF, Schoff EO, Nau CB. Effects of AGN 192024, a new ocular hypotensive agent, on aqueous dynamics. Am J Ophthalmol. 2001;131:19–24. doi: 10.1016/s0002-9394(00)00843-6. [DOI] [PubMed] [Google Scholar]
- 10.Herndon LW, Williams RD, Wand M, Asrani S. Increased periocular pigmentation with ocular hypotensive lipid use in African Americans. Am J Ophthalmol. 2003;135:713–715. doi: 10.1016/s0002-9394(02)02146-3. [DOI] [PubMed] [Google Scholar]
- 11.Wand M, Gaudio AR. Cystoid macular edema associated with ocular hypotensive lipids. Am J Ophthalmol. 2002;133:403–405. doi: 10.1016/s0002-9394(01)01411-8. [DOI] [PubMed] [Google Scholar]
- 12.Stewart WC, Stewart JA, Jenkins JN, Jackson AL. Corneal punctate staining with latanoprost, bimatoprost, and travoprost in healthy subjects. J Glaucoma. 2003;12:475–479. doi: 10.1097/00061198-200312000-00006. [DOI] [PubMed] [Google Scholar]
- 13.Sherwood M, Brandt J, for the Bimatoprost Study Groups 1 & 2 Six-month comparison of bimatoprost once-daily and twice-daily with timolol twice-daily in patients with elevated intraocular pressure. Surv Ophthalmol. 2001;45(Suppl 4):S361–S368. doi: 10.1016/s0039-6257(01)00219-3. [DOI] [PubMed] [Google Scholar]
- 14.Yamazaki S, Baba H, Tokoro T. Effects of timolol and carteolol on ocular pulsatile blood flow. Nippon Ganka Gakkai Zasshi. 1992;96:973–977. [in Japanese] [PubMed] [Google Scholar]
- 15.Easthope SE, Perry CM. Topical bimatoprost: A review of its use in open-angle glaucoma and ocular hypertension. Drugs Aging. 2002;19:231–248. doi: 10.2165/00002512-200219030-00008. [DOI] [PubMed] [Google Scholar]
- 16.Brogliatti B, Rigault R, Palanza L. Intraocular pressure and progression of visual field damage. Acta Ophthalmol Scand Suppl. 2002;236:26–27. doi: 10.1034/j.1600-0420.80.s236.15.x. [DOI] [PubMed] [Google Scholar]
- 17.Flammer J, Gasser P, Prunte CH. The probable involvement of factors other than intraocular pressure in the pathogenesis of glaucoma. In: Drance SM, Van Buskirk EM, Neufeld AH, editors. Pharmacology of Glaucoma. Williams & Wilkins; Baltimore: 1992. pp. 273–283. [Google Scholar]
- 18.Hayreh SS. Optic nerve head and blood supply in health and disease. In: Lambrou GN, Greve EL, editors. Ocular Blood Flow in Glaucoma: Means, Methods and Measurements. Kuger & Ghedini; Baltimore: 1989. pp. 3–49. (European Glaucoma Society Meeting; September 9–10, 1988). [Google Scholar]
- 19.Pillunat LE, Stodtmeister R. Effect of different antiglaucomatous drugs on ocular perfusion pressures. J Ocul Pharmacol. 1988;4:231–242. doi: 10.1089/jop.1988.4.231. [DOI] [PubMed] [Google Scholar]
- 20.Bill A, Sperber GO. Control of retinal and choroidal blood flow. Eye. 1990;4:319–325. doi: 10.1038/eye.1990.43. [DOI] [PubMed] [Google Scholar]
- 21.Buchi ER. The blood supply to the optic nerve head. In: Kaiser HJ, Flammer J, Hendrickson P, editors. Ocular Blood Flow: New Insights into the Pathogenesis of Ocular Disease. Karger; Paris, France: 1996. pp. 1–8. (Glaucoma Meeting; March 24–25, 1995; Basel, Switzerland). [Google Scholar]
- 22.Langham ME. The influence of timolol, clonidine and aminoclonidine on ocular blood flow in the rabbit and human subjects. Invest Ophthalmol Vis Sci. 1990;31:378. [Google Scholar]
- 23.Trew DR, Smith SE. Postural studies in pulsatile ocular blood flow: II. Chronic open angle glaucoma. Br J Ophthalmol. 1991;75:71–75. doi: 10.1136/bjo.75.2.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Hjortdal JO, Hjortdal VE, Hansen ES. Effect of acute intraocular pressure reduction on regional ocular blood flow. Doc Ophthalmol. 1991;77:145. [Google Scholar]
- 25.Sharif NA, Kelly CR, Crider JY. Human trabecular meshwork cell responses induced by bimatoprost, travoprost, unoprostone, and other FP prostaglandin receptor agonist analogues. Invest Ophthalmol Vis Sci. 2003;44:715–721. doi: 10.1167/iovs.02-0323. [DOI] [PubMed] [Google Scholar]
- 26.Schilder P. Ocular blood flow changes with increased vascular resistance external and internal to the eye. Acta Ophthalmol Suppl. 1989;91:19–23. doi: 10.1111/j.1755-3768.1989.tb07082.x. [DOI] [PubMed] [Google Scholar]
- 27.Pillunat LE, Stodtmeister R, Wilmanns I, Christ T. Autoregulation of ocular blood flow during changes in intraocular pressure: Preliminary results. Graefes Arch Clin Exp Ophthalmol. 1985;223:219–223. doi: 10.1007/BF02174065. [DOI] [PubMed] [Google Scholar]
