The intraocular pressure-lowering effect of prostaglandin analogs combined with topical β-blocker therapy: a systematic review and meta-analysis.
OBJECTIVE
To estimate the intraocular pressure (IOP)-lowering effect of prostaglandin analogs (PGAs) when added to topical β-blocker (BB) therapy.


METHODS
Systematic review and meta-analyses of randomized clinical trials.


METHODS
Twenty-nine articles reporting on 33 study arms and 3 control arms.


METHODS
Articles published between January 1, 1990, and August 18, 2009, were identified in relevant databases. The pooled IOP-lowering effects at the 1- to 3-month follow-ups were calculated by performing random effects meta-analyses.


METHODS
Absolute and relative change in IOP for mean diurnal curve and highest and lowest IOP decrease on the diurnal IOP curve.


RESULTS
Adding 0.005% latanoprost in the evening to 0.5% timolol twice daily resulted in a pooled change of -6.3 mmHg (95% CI, -7.1 to -5.5 mmHg, mean IOP curve); switching to the fixed combination of 0.5% timolol and 0.005% latanoprost in the morning resulted in a pooled change of -2.8 mmHg (95% CI, -3.3 to -2.3 mmHg, mean IOP curve). Starting with any fixed combination of 0.5% timolol and a PGA in the morning resulted in a pooled change of -8.4 mmHg (95% CI, -9.1 to -7.6 mmHg, mean IOP curve) and varied between -9.1 mmHg (95% CI, -9.9 to -8.2 mmHg, highest) and -7.9 mmHg (95% CI, -8.5 to -7.2 mmHg, lowest); starting with any fixed combination of 0.5% timolol and a PGA in the evening resulted in a pooled change of -8.6 (95% CI, -9.2 to -8.0 mmHg, mean IOP curve) and varied between -10.1 mmHg (95% CI, -11.0 to -9.2 mmHg, highest) and -7.3 mmHg (95% CI, -8.1 to -6.4 mmHg, lowest).


CONCLUSIONS
The concomitant use of latanoprost and timolol leads to a larger additional IOP reduction when compared with the fixed combination. There is no difference in mean IOP-lowering effect between evening and morning dosing of a fixed combination of timolol and a PGA, although the largest IOP decreases are seen with evening dosing. These findings are explained by differences in study design. When time points of IOP measurements close to the peak or trough moment of a drug are included, the IOP-lowering effect will be overestimated or underestimated, respectively.


BACKGROUND
Proprietary or commercial disclosure may be found after the references.
Webers
Carroll A B
CA
Department of Ophthalmology, Maastricht University Hospital, Maastricht, The Netherlands. c.webers@mumc.nl
Beckers
Henny J M
HJ
Zeegers
Maurice P
MP
Nuijts
Rudy M M A
RM
Hendrikse
Fred
F
Schouten
Jan S A G
JS
D000287:Administration, Topical; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005902:Glaucoma, Open-Angle / Q000188:drug therapy*; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D011461:Prostaglandins F, Synthetic