Latanoprost and brimonidine: therapeutic and physiologic assessment before and after oral nonsteroidal anti-inflammatory therapy.
OBJECTIVE
To assess, before and during oral nonsteroidal anti-inflammatory drug coadministration, latanoprost's and brimonidine's hypotensive action in eyes at risk of glaucomatous progression, assessing the effect of each drug on ocular perfusion and visual function.


METHODS
Twenty consenting adults with open-angle glaucoma or ocular hypertension underwent a double-masked, bilateral, randomized prospective study. Treatment started with either latanoprost 0.005% in the morning and placebo in the evening, or brimonidine 0.2% twice daily in one eye; after 1 week starting the other in the fellow eye. After another week, oral indomethacin 25 mg four times a day, commenced for 2 more weeks. Intraocular pressure, ocular circulation, and visual function were monitored pretreatment, after unilateral monotherapy (day 7), bilateral ocular therapy (day 14), and coadministered oral indomethacin (day 28). Intrasubject differences (interocular and intraocular relative to baseline) were determined by two-tailed paired t test.


RESULTS
A loss of the significance of intraocular pressure reduction with brimonidine was noted after oral indomethacin coadministration (-14%; P =.004 for brimonidine alone versus -11%; P =.3 with indomethacin). Significant intraocular pressure reduction with latanoprost persisted despite indomethacin (-25%; P <.0001 for latanoprost alone versus -30%; P <.0001 with indomethacin). Pulsatile ocular blood flow increased 40% with latanoprost, but was unchanged with brimonidine (interdrug difference, P =.004). Midperipheral retinal microcirculation increased 23% (P =.03) with latanoprost. Humphrey perimetry and contrast sensitivity remained consistently at or above baseline with both latanoprost and brimonidine. Indomethacin had no significant effect on ocular perfusion or visual function measures.


CONCLUSIONS
Circulatory and hydrodynamic findings differed substantially for the two drugs. The loss of significance of intraocular pressure reduction with brimonidine during indomethacin treatment may be clinically important.
Sponsel
William E
WE
South Texas Ocular Imaging Center, University of Texas Health Science Center at San Antonio, Department of Ophthalmology, San Antonio, Texas 78229-3900, USA. sponsel@uthscsa.edu
Paris
Gianmarco
G
Trigo
Yolanda
Y
Pena
Melanie
M
Weber
Anke
A
Sanford
Keith
K
McKinnon
Stuart
S
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001783:Blood Flow Velocity / Q000187:drug effects; D000068438:Brimonidine Tartrate; D015350:Contrast Sensitivity / Q000187:drug effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005902:Glaucoma, Open-Angle / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007213:Indomethacin / Q000627:therapeutic use*; D007429:Intraocular Pressure / Q000187:drug effects* / Q000502:physiology; D017078:Laser-Doppler Flowmetry; D000077338:Latanoprost; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000188:drug therapy / Q000503:physiopathology; D009883:Ophthalmic Solutions; D011446:Prospective Studies; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011810:Quinoxalines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012171:Retinal Vessels / Q000187:drug effects; D014794:Visual Fields / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic; D011810:Quinoxalines; D000068438:Brimonidine Tartrate; D000077338:Latanoprost; D007213:Indomethacin