Effects of dorzolamide 2% added to timolol maleate 0.5% on intraocular pressure, retrobulbar blood flow, and the progression of visual field damage in patients with primary open-angle glaucoma: a single-center, 4-year, open-label study.
OBJECTIVE
This study assessed the long-term effects of dorzolamide 2% BID added to timolol maleate 0.5% BID on intraocular pressure (IOP), retrobulbar blood flow, and the progression of visual field damage in patients with primary open-angle glaucoma.


METHODS
This was a prospective, 4-year, open-label intervention study. All consecutive patients with a clinical diagnosis of open-angle glaucoma in both eyes (mean defect greater than -6 dB) who presented for a regular check-up between January and July 2001 at the Instituto Galego de Oftalmoloxía were screened for study eligibility. All participants had been treated with timolol 0.5% BID in both eyes for at least 6 months before the screening visit. Dorzolamide 2% BID was added to timolol 0.5% BID in the eye with the larger visual field defect (study eye), whereas timolol 0.5% BID was continued in the eye with the smaller visual field defect (control eye). Variables evaluated at baseline and every 6 months for 48 months included retrobulbar hemodynamic parameters (using color Doppler imaging), progression of visual field damage, and IOP. Progression of visual field damage was defined according to modified Anderson criteria. Visual field progression-free survival rates for the study and control eyes were plotted using Kaplan-Meier analysis and were compared using a log-rank test.


RESULTS
Forty-five patients met the inclusion criteria, of whom 5 were lost to follow-up. Thus, 80 eyes of 40 patients were included in the analysis. Patients' mean (SD) age was 68.0 (7.1) years; all patients were white and 21 (52.5%) were male. Mean baseline IOP was 19.18 (1.34) and 18.23 (1.64) mm Hg in the study and control eyes, respectively (P=0.006). The combination of dorzolamide and timolol was associated with significant increases from baseline in enddiastolic velocity in the ophthalmic and short posterior ciliary arteries (P<0.001) and significant decreases in the resistivity index in both arteries (P<0.001). Twenty-three of the 80 eyes (28.8%) had progression of visual field damage (7 study eyes and 16 control eyes). On Kaplan-Meier survival analysis, the risk of progression was significantly lower in the eye treated with dorzolamide and timolol compared with the eye treated with timolol alone (hazard ratio=0.41; 95% CI, 0.17 to 0.94; P=0.035). Mean changes in IOP from baseline to month 48 were -1.10 mm Hg in the dorzolamide and timolol group (95% CI, -1.73 to -0.51; P<0.001) and 1.27 mm Hg in the control group (95% CI, -2.74 to 1.72; P=NS).


CONCLUSIONS
In this 4-year, open-label study in patients with primary open-angle glaucoma, dorzolamide 2% BID added to timolol 0.5% BID was associated with a significant reduction in IOP and significant increases in retrobulbar hemodynamic parameters in both the ophthalmic and short posterior ciliary arteries. Dorzolamide added to timolol may be effective in preventing progression of glaucomatous visual field damage.
Martínez
Antonio
A
Instituto Galego de Oftalmoloxía, La Coruña, Spain.
Sánchez
Manuel
M
D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D005902:Glaucoma, Open-Angle / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009883:Ophthalmic Solutions; D009915:Orbit / Q000098:blood supply*; D011446:Prospective Studies; D012039:Regional Blood Flow / Q000187:drug effects* / Q000502:physiology; D013449:Sulfonamides / Q000008:administration & dosage*; D013876:Thiophenes / Q000008:administration & dosage*; D013997:Time Factors; D013999:Timolol / Q000008:administration & dosage*; D016896:Treatment Outcome; D014794:Visual Fields / Q000187:drug effects* / Q000502:physiology
D000959:Antihypertensive Agents; D004338:Drug Combinations; D009883:Ophthalmic Solutions; D013449:Sulfonamides; D013876:Thiophenes; D013999:Timolol; C062765:dorzolamide