Meta-analysis of 24-Hour Intraocular Pressure Studies Evaluating the Efficacy of Glaucoma Medicines

• Published in: Ophthalmology (Rochester, Minn.) Vol. 115; no. 7; pp. 1117 - 1122.e1
• Main Authors: Stewart, William C., MD, Konstas, Anastasios G.P., MD, PhD, Nelson, Lindsay A., BS, Kruft, Bonnie, BS
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.07.2008; Elsevier
• Subjects: Amides - administration & dosage; Antihypertensive Agents - administration & dosage; Bimatoprost; Biological and medical sciences; Circadian Rhythm - drug effects; Circadian Rhythm - physiology; Cloprostenol - administration & dosage; Cloprostenol - analogs & derivatives; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Exfoliation Syndrome - drug therapy; Exfoliation Syndrome - physiopathology; Glaucoma and intraocular pressure; Glaucoma, Open-Angle - drug therapy; Glaucoma, Open-Angle - physiopathology; Humans; Intraocular Pressure - drug effects; Intraocular Pressure - physiology; Medical sciences; Miscellaneous; Ocular Hypertension - drug therapy; Ocular Hypertension - physiopathology; Ophthalmic Solutions - administration & dosage; Ophthalmology; Prostaglandins F, Synthetic - administration & dosage; Randomized Controlled Trials as Topic; Single-Blind Method; Sulfonamides - administration & dosage; Thiophenes - administration & dosage; Timolol - administration & dosage; Tonometry, Ocular; Travoprost; Treatment Outcome; Glaucoma; Medicine; Protozoa; Eye disease; Glaucoma (eye); Ciliata; Ophthalmology; Metaanalysis; Intraocular pressure
• ISSN: 0161-6420; 1549-4713
• DOI: 10.1016/j.ophtha.2007.10.004

Purpose To evaluate efficacy and safety data of currently available ocular hypotensive medicines derived from 24-hour studies, of similar design, in patients with primary open-angle glaucoma (POAG), exfoliative glaucoma, or ocular hypertension (OH). Design Meta-analysis of published articles evaluating patients with POAG, exfoliative glaucoma, or OH. Methods We included articles that were randomized, prospective, single- or double-masked, comparative studies of ocular hypotensive therapies over 24 hours. Each article selected contained an untreated baseline, ≥4-week treatment period, ≥20 patients per treatment arm, and ≥6 time points not spaced >5 hours apart and used Goldmann applanation or Tonopen tonometry (supine measurements) to measure intraocular pressure (IOP). Main Outcome Measure Twenty-four–hour IOP efficacy. Results This analysis included 864 separate 24-hour treatment curves from 386 patients in 28 treatment arms from 11 studies. A statistical difference in the mean diurnal pressure decrease existed between monotherapy treatments for POAG/OH patients, with bimatoprost (29%) and travoprost (27%) showing the greatest 24-hour reduction ( P = 0.026). Timolol 0.5% was less effective than latanoprost (24% vs. 19% reduction) but decreased the pressure at each night time point ( P = 0.0003). Dorzolamide showed a 19% 24-hour pressure reduction and brimonidine 0.2% a 14% one. In exfoliative glaucoma patients, latanoprost and travoprost showed higher baseline and treatment pressures, although the pressure reductions (29% and 31%, respectively) were greater generally than observed with POAG/OH. An evening-dosed latanoprost/timolol fixed combination reduced the pressure 33%, and the dorzolamide/timolol fixed combination (DTFC), 26%. However, the power to detect a difference for this specific comparison was probably low, due to the limited number of patients (n = 20) in the DTFC group. A statistical difference between evening-dosed (24%) and morning-dosed (18%) latanoprost ( P <0.0001) was noted, but not between evening (27%) and morning (26%) travoprost ( P = 0.074). The mean reduction of night time points was statistically lower than day time points for latanoprost ( P = 0.031), timolol ( P = 0.032), and brimonidine ( P = 0.050), but not for dorzolamide. Dorzolamide ( P = 0.60), travoprost ( P = 0.064), and bimatoprost ( P = 0.057) did not demonstrate nighttime pressures lower than daytime ones. The mean reduction of night time points was statistically lower than that of day time points for latanoprost ( P = 0.031), timolol ( P = 0.032), and brimonidine ( P = 0.050), but not for dorzolamide ( P = 0.60), bimatoprost ( P = 0.057), travoprost ( P = 0.064). Conclusions Similar relative efficacies generally exist in various classes of ocular hypotensive agents during night and day hours.