Changes in intraocular pressure associated with topical dorzolamide and oral methazolamide in glaucomatous dogs

Objective To compare the reduction in intraocular pressure (IOP) by topical 2% dorzolamide to oral methazolamide (5 mg/kg) in dogs, and determine if the combination of both drugs would reduce IOP more than either drug administered alone. Animals studied Thirteen glaucomatous beagles. Procedures Measurements, including applanation tonometry, pupil size and heart rate, were obtained at 8 am, 12 noon, and 5 pin on days 1, 3 and 5. The 5-day drug studies included placebo (0.5% methylcellulose); 2% dorzolamide administered in one eye twice daily (8 am and 5 pm), and repeated again in one eye three times (8 am, 12 noon and 5 pm) daily; methazolarnide (5 mg/kg per os administered at 8 am and 5 pm); 2 % dorzolamide instilled twice daily (5 days) combined with oral methazolamide on the last 3 days, and methazolamide (5 days) combined with 2% dorzolamide on the last 3 days and instilled twice daily. Statistical comparisons between drug groups included control (nondrug) eye and treated (placebo/drug) eyes for days 1, day 3 and 5. Results Topical 2% dorzolamide, administered twice and three times daily, significantly decreased IOP (mean +/- SEM) in glaucomatous dogs on the first day (twice daily 7.6 +/- 2.4 mmHg, and three times daily 16.4 +/- 3.6 mmHg) that was even greater by day 5 (twice daily 10.4 +/- 2.0 mmHg, and three times daily 13.9 +/- 2.7). Oral methazolamide also significantly lowered IOP in both eyes. Oral methazolamide (administered from day 1 through to day 5) combined with 2% topical dorzolamide (instilled in the drug eye for day 3 through to day 5) also significantly lowered IOP of both eyes for all days, and for day 5 the mean +/- SEM IOP was decreased by 7.9 +/- 1.7 mmHg (methazolamide plus dorzolamide) and 7.5 +/- 2.6 mmHg (methazolamide only). Topical dorzolamide (instilled in the drag eye for day 1 through to day 5) combined with oral methazolamide (administered from day 3 through to day 5) significantly lowered IOP in the drug eye on day 1 (5 pm: 9.6 +/- 1.9 mmHg), for day 3 (11 am and 5 pm) and for all of day 5 for both eyes (5 pm: control eye 9.5 +/- 1.8 mmHg; drug eye 9.2 +/- 1.9 mmHg). Topical dorzolamide (2%) instilled three times daily produces similar IOP declines compared to the combination of oral methazolamide and 2% dorzolamide administered twice daily. Conclusions Dorzolamide (2%) instilled twice or three times daily causes significant decreases in IOP in glaucomatous dogs. Twice daily instillations caused progressive declines in IOP from day I to day 5. Dorzolamide (2%) combined with oral methazolamide (5 mg/kg per os twice daily) produces similar but not additional declines in IOP.