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EFFICACY
SAFETY AND EFFICACY

A Randomized Trial Comparing the

Dorzolamide–Timolol Combination Given

Twice Daily to Monotherapy with Timolol

and Dorzolamide

3
2
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1
Janet E. Boyle, BA, Kalyan Ghosh, PhD, David K. Gieser, MD, Ingrid A. Adamsons, MD, MPH, the
Dorzolamide–Timolol Study Group*
Objective: To compare the efficacy and safety of a fixed combination of 2.0% dorzolamide and 0.5% timolol
administered twice daily with each of the individual components administered in their usual monotherapy dose
regimens in patients who had washed out all ocular hypotensive medications.
Design: A 3-month, parallel, randomized, double-masked, active-controlled, multicenter clinical trial.
Participants: A total of 335 patients with bilateral ocular hypertension or open-angle glaucoma participated.
Intervention: After completing a washout of ocular hypotensive medications, patients were randomized to
receive either the dorzolamide–timolol combination twice daily plus placebo once daily, 0.5% timolol twice daily
plus placebo once daily, or 2.0% dorzolamide three times daily.
Main Outcome Measures: Intraocular pressure (IOP) was measured at morning trough (hour 0) and peak (2
hours postdose) on day 1, week 2, and months 1, 2, and 3. Ocular and systemic safety were evaluated at each
study visit.
Results: Intraocular pressure reduction was greater on average in the combination group than in the dorzolamide
and timolol groups. At morning trough (month 3, hour 0), the mean reduction in IOP from baseline was 27.4% ( 7.7
mmHg) for the combination, 15.5% ( 4.6 mmHg) for dorzolamide, and 22.2% ( 6.4 mmHg) for timolol. At morning
peak (month 3, hour 2), the mean IOP reduction from baseline was 32.7% ( 9.0 mmHg), 19.8% ( 5.4 mmHg), and
22.6% ( 6.3 mmHg) for the combination, dorzolamide, and timolol, respectively. Overall, the incidence of clinical
adverse experiences was comparable between the combination and each of its components. The proportion of
patients who discontinued from the study because of clinical adverse experiences was also comparable between the
combination and dorzolamide, although it was significantly greater in the combination group than in the timolol group
(7% vs. 1%, P 0.035). Similarly, comparable numbers of patients in the combination and dorzolamide groups
reported ocular symptoms; however, when compared to the timolol group, more patients receiving the combination
reported blurred vision, burning eye, stinging eye, and tearing eye.
Conclusions: After a washout of ocular hypotensive therapy, the IOP-lowering effect of the dorzolamide–
timolol combination was greater than that of either of its components administered as monotherapy. The
combination is generally well-tolerated and provides a convenient alternative to concomitant therapy with its
individual components. Ophthalmology 1998;105:1945–1951

Open-angle glaucoma is a chronic disease characterized by
Originally received: November 11, 1997. the painless elevation of intraocular pressure (IOP), progres-
Revision accepted: May 19, 1998. Manuscript no. 97779.
1 Department of Clinical Research, Merck Research Laboratories, West sive optic nerve damage, and visual field loss leading to
Point, Pennsylvania. blindness. Currently, lowering IOP is the only established
2 Department of Statistics, Merck Research Laboratories, West Point, medical treatment for open-angle glaucoma. There is in-
Pennsylvania. creasing evidence that reducing IOP as much as possible
3 Wheaton Eye Clinic, Wheaton, Illinois. improves the likelihood of delaying or halting progression
1
Ms. Boyle, Dr. Ghosh, and Dr. Adamsons were employees of Merck & of optic nerve damage and visual field loss. The most
Co., Inc, the manufacturer of timolol and dorzolamide, at the time this common first-line therapy for the treatment of glaucoma is
study was conducted. COSOPT and TRUSOPT are trademark products of topical beta-blockers, specifically timolol maleate. Because
Merck & Co., Inc, Whitehouse Station, New Jersey. The other authors have glaucoma is a chronic progressive disease, however, the
no proprietary interest in timolol, dorzolamide, or Merck. majority of patients eventually require more than one med-
* Members of the Dorzolamide–Timolol Study Group are listed in the ication to control their IOP. Dorzolamide hydrochloride
Appendix at the end of this article. (TRUSOPT, Merck & Co., Inc, Whitehouse Station, NJ) is
Address correspondence and reprint requests to Ingrid A. Adamsons, MD, a topical carbonic anhydrase inhibitor that is frequently
MPH, Clinical Research/Ophthalmology, Merck & Co., Inc, 10 Sentry
Parkway, BL1-3, Blue Bell, PA 19422. prescribed as adjunctive therapy to timolol to achieve ad-

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