Discussion

A combination of 2 or more drugs is common in the treatment of glaucoma. As a rule, a drug that increases uveoscleral outflow such as latanoprost or pilocarpine may be combined with a drug that reduces inflow, such as -adrenergic antagonists or carbonic anhydrase inhibitors. However, polytherapy may be inconvenient for patients and can result in poor compliance. Therefore, it is preferable to consider the option of switching a patient from 1 monotherapy to another monotherapy when the IOP is inadequately controlled rather than adding another drug to the first treatment.

In the present study, newly diagnosed patients with POAG or OH with inadequately controlled IOP with topical therapy, either alone or in combination, were switched to treatment with latanoprost once daily. The results of the study demonstrate that latanoprost 0.005% administered once daily reduces IOP in patients with POAG or OH. Latanoprost was administered once daily throughout the treatment period and significantly reduced the IOP. The mean baseline IOP of 27.1 ± 6.0 mm Hg was reduced to 18.0 ± 3.7 mm Hg at the end of 12 weeks of therapy with latanoprost 0.005% once daily (p < 0.05). A consistent reduc-tion in IOP was observed throughout the study. The mean absolute reduction in IOP at 12 weeks compared with baseline was 9.1 ± 3.9 mm Hg (33.6%) (Figure 1) The final IOPs are shown in (Figure 2).

Mishima et al conducted a 12-week comparison study of latanoprost and timolol in POAG and OH.4 In this study, latanoprost reduced IOP at the end of 12 weeks by
6.2 ± 2.7 mm Hg (26.8%), while timolol reduced IOP by 4.4 ± 2.3 mm Hg (19.9%).

Camras et al conducted a 6-month comparative study of latanoprost and timolol in patients with OH and glaucoma.6 In this study, latanoprost reduced the IOP by
6.7 ± 3.4 mm Hg (27%), while timolol reduced the IOP by 4.9 ± 2.9 mm Hg (20%).

O' Donoghue et al conducted a 3-month comparative study of latanoprost and dorzolamide in patients with glaucoma and ocular hypertension.8 In this study latanoprost reduced IOP by 8.5 ± 3.3 mm Hg (32%), while dorzolamide reduced IOP by 5.6 ± 2.6 mm Hg (23%).

Alm et al conducted a 6-month com-parative study of latanoprost and timolol in patients with glaucoma and OH.9 In this study, latanoprost administered in the evening showed a superior reduction in IOP from 24.8 mm Hg to 16.2 mm Hg (35%) to latanoprost applied in the morning from 25.5 mm Hg to 17.7 mm Hg (31% while timolol reduced the IOP from 24.6 to 17.9 mm Hg (27%). This study seems to indicate a slight advantage of evening administration of latanoprost with regard to IOP reduction.

Figure 1. Absolute reduction in mean intraocular pressure (IOP) after 12 weeks of
treatment with latanoprost (n = 109).

Figure 2. Number of patients who achieved specific intraocular pressure (n = 109).

Twenty adverse events were reported, including mild congestion, itching, dryness of the eye, mild discharge and watering, eye pain, swelling of the lid, eyelash growth, episcleritis, and iris pigmentation. Systemic events included headache and diarrhoea. While 17 patients were withdrawn from the study, no patient was withdrawn due to adverse events.

Latanoprost offers several potential advantages over currently available medications for glaucoma therapy. Unlike -blockers, carbonic anhydrase inhibitors, and 2 - agonists, latanoprost acts on uveoscleral outflow rather than formation of aqueous humor. Virtually all glaucoma results from impaired outflow, but not excessive formation of aqueous humor. Avascular ocular structures depend on aqueous flow for metabolic exchanges, therefore chronic excessive reduction of aqueous humor formation may have deleterious effects. Unlike -adrenergic blockers, which do not further reduce aqueous flow at night beyond the decrease already achieved during sleep, latanoprost reduces IOP equally as well at night as during the day. This represents a potential advantage because glaucomatous damage may occur during sleep when the ocular perfusion pressure may be reduced because of low systemic blood pressure. Furthermore, since latanoprost increases uveoscleral outflow, it can theoretically reduce IOP below the episcleral venous pressure, unlike drugs that act by either reducing aqueous humor production or increasing outflow facility. The evening administration that has been shown to be superior to morning administration 9 has been chosen for this study to block an early morning diurnal IOP spike.

The present study demonstrates that 0.005% latanoprost administered once daily reduces IOP for 3 months for Indian patients with POAG or OH. These results confirm the efficacy and safety of latanoprost similar to those studies performed in Japanese, North American, and European patients.5,6,8,9 Latanoprost has a good safety profile, both in terms of ocular and systemic side effects, compared with other currently available ocular medications. Throughout this study, there was a consistent decrease in IOP, which appeared to improve with longer administration. This is probably related to biochemical changes that take place in the uveoscleral outflow.

Acknowledgements

Our grateful thanks to Dr Sutinder Bindra, Regional Medical Director, Pharmacia Asia-Pacific, for his guidance and technical support throughout the entire project, and Dr Anil Shinde, Manager, Medical Services, and Ms Ekta Garg, Clinical Research Associate, Pharmacia India Pvt Ltd, for their help and efforts in the conduct and monitoring of the study, and in the preparation of the manuscript. Pharmacia India Pvt Ltd supported this study.

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