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The Effect of Latanoprost vs Timolol on Intraocular Pressure in Patients with Glaucoma and Ocular Hypertension

Mario V Aquino, MD, Margarita Lat-Luna, MD
Glaucoma Unit, Department of Ophthalmology, University of the Philippines College of Medicine,
Manila, The Philippines.


Discussion

This study demonstrates that latanoprost 0.005%, given once daily, safely and effectively reduces the IOP during the study period of 12 weeks in patients with open angle glaucoma or ocular hyper-tension. Compared with timolol 0.5% given twice daily, latanoprost once daily was significantly more effective in re-ducing mean diurnal IOP after 6 weeks and at least as effective after 12 weeks. This is in agreement with long-term phase III studies lasting for 3 to 6 months in which latanoprost was found to be more effective than,2,3,5 or at least as effective as,4 timolol in lowering the IOP in patients with similar diagnosis. The IOP reduction in the latanoprost group of 39 to 41% was higher than the 30 to 35% reduction seen in previously reported randomised, double-masked studies;2-5 the IOP reduction of 30 to 32% in the timolol group was also higher,2,3,5 or comparable to,4 these earlier results.

Table 3. Number of ocular and systemic adverse events reported during the study (withdrawn patients included).
Adverse event 

Latanoprost 

Timolol 


OCULAR
Change in refractive   power
Increased intraocular   pressure
Blepharitis/lid swelling
Hypersensitivity/stinging
Blurred vision
Conjunctivitis

n = 12
7

3

2
2
1
0

n = 11 








SYSTEMIC
Increase blood pressure
Dizziness
Upper respiratory tract   infection
Fever/Influenza

n = 2
1
1
0

0

n = 5 




The design of the present study in-cluded IOP measurements at 1, 5 and 9 hours after the last dose of timolol and at 13, 17, and 21 hours after the last dose of latanoprost. There is no noticeable peak or trough effect after each dose of timolol or latanoprost since they both have a long duration. Comparing the effect on mean diurnal IOP thus seems to be a reason-able evaluation of the clinical effect.

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Another way to evaluate the clinical efficacy of different ocular hypotensive drugs is to analyse the number of patients that reached a target IOP. In this study the patients in the latanoprost group were more successful in reaching a specific target IOP compared with the timolol group. A total of 46% of all latanoprost-treated patients succeeded in reaching a mean diurnal IOP of 15 mm Hg or lower, whereas 10% of all timolol-treated patients succeeded in reaching that target. This finding is in agreement with the results from the three 6-month phase III clinical trials2-4 where 27% of the latanoprost-treated patients reached the target IOP of 15 mm Hg or less com-pared with 14% of the timolol-treated patients (Katarina Hedman, unpublished observations).

Most side effects observed were mild and transient and no serious adverse events were reported. Slit-lamp examina-tions were performed regularly to detect any cells or flare in the anterior chamber as a sign of increased permeability of the blood-aqueous barrier. In several clinical studies,9,11-14 no signs of break-down of the blood-aqueous barrier were observed. In the three 6-month phase III clinical studies,2-4 there was no difference between latanoprost and timolol in the incidence of cells or flare. During 1 year of treatment with latanoprost, slight aqueous flare and a few cells have been reported in a small number of patients, however 2 of these patients had cells present at baseline.6 In this 12-week study, no signs of flare or cells in the anterior chamber were found, indicating an intact blood-aqueous barrier in pa-tients receiving latanoprost treatment as well as for those receiving timolol treatment.

Iris pigmentation has been reported following latanoprost treatment.2-4,6,7 After 1 year of treatment this was reported in approximately 16% of patients.15 The increased pigmentation predominantly occurred in patients with mixed coloured iris, ie blue/grey-brown, green-brown or yellow-brown eyes. Between 3 and 17 months of latanoprost treatment preceded the first sign of increased brown pigment in these irides.7,15 Melanogenesis is considered the underlying mechanism of increased iris pigmentation and no signs of a proliferative effect have been found.15 In our study, all participating patients had homogeneously brown iris colour and there were no signs of in-creased iris pigmentation in any of the patients in the 2 treatment groups.

In conclusion, the results of this study show that latanoprost 0.005% admini-stered once daily in the evening is statistically significantly more effective than timolol 0.5% administered twice daily in reducing the mean diurnal IOP after 6 weeks of treatment and at least as effective as timolol after 12 weeks of treatment. Systemic and ocular side effects were mild and transient for both medications. Latanoprost can be con-sidered to be a safe and effective agent for treating ocular hypertension and open angle glaucoma.

 

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