Effects of Topical Bimatoprost 0.01% and Timolol 0.5% on Circadian IOP, Blood Pressure and Perfusion Pressure in Patients with Glaucoma or Ocular Hypertension: A Randomized, Double Masked, Placebo-Controlled Clinical Trial.
OBJECTIVE
To compare the 24-hour (24h) effects on intraocular pressure (IOP) and cardiovascular parameters of timolol 0.5% and bimatoprost 0.01% in open angle glaucoma and ocular hypertensive subjects.


METHODS
In this prospective, randomized, double masked, crossover, clinical trial, after washout from previous medications enrolled subjects underwent 24h IOP, blood pressure (BP) and heart rate (HR) measurements and were randomized to either topical bimatoprost 0.01% at night plus placebo in the morning or to timolol 0.5% bid. After 8 weeks of treatment a second 24h assessment of IOP, BP and HR was performed and then subjects switched to the opposite treatment for additional 8 weeks when a third 24h assessment was performed. The primary endpoint was the comparison of the mean 24h IOP after each treatment. Secondary endpoints included the comparisons of IOP at each timepoint of the 24h curve and the comparison of BP, HR, ocular perfusion pressure and tolerability.


RESULTS
Mean untreated 24h IOP was 20.3 mmHg (95%CI 19.0 to 21.6). Mean 24h IOP was significantly lower after 8 weeks of treatment with bimatoprost 0.01% than after 8 weeks of treatment with timolol 0.5% bid (15.7 vs 16.8 mmHg, p = 0.0003). Mean IOP during the day hours was significantly reduced from baseline by both drugs while mean IOP during the night hours was reduced by -2.3 mmHg (p = 0.0002) by bimatoprost 0.01% plus placebo and by -1.1 mmHg by timolol 0.5% bid (p = 0.06). Timolol 0.5% significantly reduced the mean 24h systolic BP from baseline, the diastolic BP during the day hours, the HR during the night hours, and the mean 24h systolic ocular perfusion pressure.


CONCLUSIONS
Both Bimatoprost 0.01% and Timolol 0.5% are effective in reducing the mean 24h IOP from an untreated baseline but Bimatoprost 0.01% is more effective than timolol 0.5% throughout the 24h. Timolol 0.5% effect on IOP is reduced during the night hours and is associated with reduced BP, HR and ocular perfusion pressure.


BACKGROUND
EU Clinical Trial Register and EudraCT# 2010-024272-26.
Clinical and Research Institute of Ophthalmology IRCCS Fondazione G. B. Bietti, Via Livenza 3, 00198, Rome, Italy.
Francesco
F
Oddone
Clinica Oculistica, Dipartimento di Scienze della Salute, University of Milan, San Paolo Hospital, Via Antonio di Rudinì, 8 20142, Milan, Italy.
Luca
L
Rossetti
Clinical and Research Institute of Ophthalmology IRCCS Fondazione G. B. Bietti, Via Livenza 3, 00198, Rome, Italy.
Lucia
L
Tanga
Clinical and Research Institute of Ophthalmology IRCCS Fondazione G. B. Bietti, Via Livenza 3, 00198, Rome, Italy.
Francesca
F
Berardo
Clinical and Research Institute of Ophthalmology IRCCS Fondazione G. B. Bietti, Via Livenza 3, 00198, Rome, Italy.
Manuela
M
Ferrazza
Clinical and Research Institute of Ophthalmology IRCCS Fondazione G. B. Bietti, Via Livenza 3, 00198, Rome, Italy.
Manuele
M
Michelessi
Clinical and Research Institute of Ophthalmology IRCCS Fondazione G. B. Bietti, Via Livenza 3, 00198, Rome, Italy.
Gloria
G
Roberti
Clinical Science and Translational Medicine Department, University of Rome Tor Vergata, Viale Oxford 81, 00133, Rome, Italy.
Gianluca
G
Manni
Clinical and Research Institute of Ophthalmology IRCCS Fondazione G. B. Bietti, Via Livenza 3, 00198, Rome, Italy; Clinical Science and Translational Medicine Department, University of Rome Tor Vergata, Viale Oxford 81, 00133, Rome, Italy.
Marco
M
Centofanti
D000287:Administration, Topical; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000069580:Bimatoprost / Q000008:administration & dosage* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D005901:Glaucoma / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D011446:Prospective Studies; D013999:Timolol / Q000008:administration & dosage* / Q000627:therapeutic use; D014065:Tonometry, Ocular; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D013999:Timolol; D000069580:Bimatoprost