Effect of unspecific inhibition of cyclooxygenase by indomethacin on retinal and choroidal blood flow.
OBJECTIVE
Animal studies suggest that retinal and choroidal blood flow decrease after administration of indomethacin, a nonspecific cyclooxygenase inhibitor. Cyclooxygenase is the key enzyme involved in the arachidonic pathway and regulates the production of vasoactive substances such as prostaglandins and thromboxans. The aim of the present study was to investigate the short-term effects of indomethacin on ocular blood flow in healthy humans.


METHODS
A randomized, double-masked, placebo-controlled, two-way crossover study in 12 healthy, male, nonsmoking subjects was performed. Indomethacin was administered as a bolus injection of 0.4 mg/kg followed by continuous infusion of 0.4 mg/kg/h over 120 minutes. Ocular hemodynamic parameters were measured at baseline and up to 3 hours after start of the infusion. Subfoveal choroidal blood flow and fundus pulsation amplitude were measured with laser Doppler flowmetry and laser interferometry, respectively. Retinal vessel diameters were assessed using a retinal vessel analyzer. Retinal blood flow was calculated based on retinal vessel diameters, and red blood cell velocity was measured with laser Doppler velocimetry.


RESULTS
Administration of indomethacin decreased retinal arterial diameters up to -4.3% +/- 3.4% and reduced retinal blood velocity by a maximum of -29% +/- 20% (P < 0.05). Calculated retinal blood flow decreased by -27% +/- 21% (P < 0.05), reaching the maximal decrease 60 minutes after administration. Choroidal blood flow and fundus pulsation amplitude (FPA) also decreased during the infusion of indomethacin with maximum effects of -17% +/- 13% (P < 0.05, vs. placebo) and -7% +/- 4% (P < 0.05, vs. placebo), respectively.


CONCLUSIONS
Results showed a marked decrease in retinal and choroidal blood flow after short-term administration of indomethacin. Whether this decrease can be attributed to a reduced production of prostaglandins or an unknown mechanism has yet to be clarified. Further studies appear to be indicated to investigate whether the long-term intake of indomethacin is associated with an increased risk for vascular eye disease.
Weigert
Günther
G
Department of Clinical Pharmacology, Medical University of Vienna, Austria.
Berisha
Fatmire
F
Resch
Hemma
H
Karl
Katharina
K
Schmetterer
Leopold
L
Garhofer
Gerhard
G
D000328:Adult; D001783:Blood Flow Velocity; D002829:Choroid / Q000098:blood supply*; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D007368:Interferometry; D017078:Laser-Doppler Flowmetry; D008027:Light; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D012039:Regional Blood Flow / Q000502:physiology; D012161:Retinal Artery / Q000502:physiology*
D016861:Cyclooxygenase Inhibitors; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin