Ophthalmology, Hôpital des. Quinze-Vingts, 28 rue de. Charenton, 75012 Paris, ..... Denis Gruber, 34 Place de l´Hotel de Ville, Le Havre;. Pascale Hamard ...
Br J Ophthalmol 2000;84:181–185
181
Comparison of the intraocular pressure lowering eVect of latanoprost and a fixed combination of timolol-pilocarpine eye drops in patients insuYciently controlled with â adrenergic antagonists Jean-Philippe Nordmann, Mats Söderström, Jean-François Rouland, François Malecaze, the French Latanoprost Study Group, and the Swedish Latanoprost Study Group
Department of Ophthalmology, Hôpital des Quinze-Vingts, Paris, France J-P Nordmann Department of Ophthalmology, Huddinge University Hospital, Sweden M Söderström Department of Ophthalmology, Hôpital Huriez, Lille, France J-F Rouland Department of Ophthalmology, Hôpital Purpan, Toulouse, France J-F Rouland Correspondence to: Jean-Philippe Nordmann, MD, PhD, Department of Ophthalmology, Hôpital des Quinze-Vingts, 28 rue de Charenton, 75012 Paris, France Accepted for publication 15 September 1999
Abstract Aims—To compare the eVect on intraocular pressure (IOP) of latanoprost monotherapy and timolol-pilocarpine in patients with glaucoma or ocular hypertension with inadequately controlled IOP on topical â adrenergic antagonists. Methods—This was a multicentre, randomised, observer masked, 6 week study performed in France and Sweden. 23 centres enrolled 237 patients with glaucoma or ocular hypertension and an IOP of at least 22 mm Hg on treatment with topical â adrenergic antagonists, alone or in combination. After a 21 day run in period on timolol 0.5% twice daily, patients were randomised either to latanoprost 0.005% once daily or to a fixed combination of timolol-pilocarpine twice daily. Changes in mean diurnal IOP from the baseline to the 6 week visit were determined with an analysis of covariance. Results—Mean diurnal IOP was statistically significantly decreased from baseline in both groups (p20 cells). At the prestudy visit and at the 6 week visit ophthalmoscopy was performed through dilated pupils. Throughout the study adverse events were carefully monitored. An adverse event was defined as any undesirable event occurring in a subject regardless if it was considered related to the investigational drugs. A serious adverse event was defined as potentially fatal, life threatening, sight threatening, permanently disabling, requiring hospitalisation, or requiring intervention to prevent permanent impairment or damage. An analysis of covariance (ANCOVA) was performed with diurnal IOP change at week 6 from baseline as response variable, baseline diurnal IOP as covariate and group and centre as factors. The diurnal IOP was defined as the mean value of measurements at 8 am, 12 noon, Table 2
Demographic characteristics of the patients
Characteristics Age (years) Mean (SD) Range Sex Female Male Glaucoma diagnosis Primary open angle glaucoma Exfoliation glaucoma Pigmentary glaucoma Ocular hypertension Mixed glaucoma
Latanoprost (n=118)
Timolol-pilocarpine (n=119)
63 (11.9) 28–89
64 (13.2) 25–94
62 56
64 55
62 21 6 26 3
78 16 1 23 1
183
Comparison of the IOP lowering eVect of latanoprost and timolol-pilocarpine Reasons for patient withdrawal from the study
Reasons
Latanoprost (n=5)
Timolol-pilocarpine (n=13)
Blurred vision and/or decreased visual acuity Headache Allergic conjunctivitis Treatment mistake, surgery required Vertigo Poor patient compliance Patient lost to follow up Patient decided to withdraw without specifying reason
0 0 1 1 1* 0 1 1
6 2 2 0 0 1 2 0
*Reported as serious adverse event.
Table 4 IOP (mm Hg), mean (SD) in each group at each measurement Time Baseline 8/9 am* 12 noon 4 pm Week 2 8/9 am* Week 6 8/9 am* 12 noon 4 pm
Latanoprost (n=102)
Timolol-pilocarpine (n=95)
24.7 (4.5) 24.6 (3.9) 23.7 (3.7)
24.8 (3.8) 24.3 (4.1) 23.4 (3.8)
18.9 (3.4)
19.4 (4.0)
19.4 (3.7) 19.3 (3.6) 18.5 (3.1)
19.2 (4.8) 19.7 (4.2) 19.4 (3.5)
*8 am measurement (Sweden), 9 am measurement (France).
and 4 pm (Sweden) or 9 am, 12 noon, and 4 pm (France). If both eyes of a patient were studied, the mean IOP of both eyes was used in the analysis. Results Of the 237 patients included in the study, 118 patients were randomised to the latanoprost treatment group and 119 patients to the timolol-pilocarpine treatment group. The demographic characteristics of the two treatment groups are presented in Table 2. There was no major diVerence between the two treatment groups with respect to age, sex, or diagnosis with the exception that there were six patients with pigmentary glaucoma in the latanoprost group and only one patient with this type of glaucoma in the timolol-pilocarpine group. A comparison of the mean diurnal IOP after 6 weeks of treatment to the mean diurnal IOP at baseline was performed for 197 patients; 102 patients in the latanoprost group and 95 patients in the timolol-pilocarpine group. Five patients in the latanoprost group and 13 patients in the timolol-pilocarpine group were withdrawn before the study termination. The reasons for withdrawal are listed in Table 3. Thirteen patients in the latanoprost group and nine patients from the timolol-pilocarpine group were excluded from the analysis of eYcacy owing to protocol violations; for example, if the eye drops were not taken as stated in the protocol or if there were unacceptable deviations in tonometry times. The mean IOP at each measurement for the two treatment groups is presented in Table 4. In Table 5 the percentage reductions of baseline IOP at 6 weeks are presented. The changes in mean diurnal IOP from the baseline to the 6 week visit, determined with ANCOVA, are presented in Figure 1. Switching from timolol 0.5% twice daily to latanoprost 0.005% once daily caused a statistically significant reduction in mean diurnal IOP of 5.4 (SEM
0.3) mm Hg (p
