Abstract
Purpose: :
To establish diurnal intraocular pressure (IOP) curves and determine the effect of the topical carbonic anhydrase inhibitor, 1% brinzolamide, on IOP in a recessively inherited feline model of primary congenital glaucoma.
Methods: :
The study consisted of 3 phases: 1) acclimation to frequent tonometry and application of drug vehicle in both eyes three times daily (4 days); 2) treatment phase (4 days); 3) post-treatment measurements (1 day). Treatment consisted of 1 drop of 1% brinzolamide (Azopt, Alcon Laboratories, Inc) applied to one randomly assigned eye of each cat, every 8 hours (7am, 3pm, 11pm). The contralateral eye was treated with vehicle only and served as a control. IOP measurements were obtained in lightly restrained cats by applanation tonometry (Tonopen XL, Mentor) following application of topical anesthetic. Tonometry was carried out at 6 hour intervals (8am, 2pm, 8pm, 2am) by a consistent, masked observer for the duration of the study. Five adult cats with primary congenital glaucoma and 4 normal adult domestic short-haired cats were studied. Cats were housed under standard laboratory conditions with a consistent 12 hour light / dark cycle. All dark phase measurements were obtained in dim red light. Mixed effect models were used to analyze the data using SAS 9.1.3
Results: :
Mean IOP in affected cats (24.9 +/-0.83mmHg) was significantly higher than in normal cats (15.9 +/- 0.93mmHg) (p=0.0002). Both glaucomatous and normal cats exhibited diurnal fluctuations in IOP (mean diurnal fluctuation, 17.7+/-1.76 and 5.1+/-1.97 mmHg respectively), but these fluctuations were of significantly greater magnitude in cats with glaucoma (p=0.0021). Peak IOP (mean 34.6 +/-1.81 and 18.6 +/- 2.02 mmHg, in glaucomatous and normal cats respectively) consistently occurred in the evening, about 2 hours after the onset of the dark cycle. Application of 1% brinzolamide led to a significant reduction in mean IOP (-3.1 +/-0.38mmHg; p<0.0001) and mean diurnal IOP fluctuation (-2.2 +/-0.84 mmHg; p=0.0305) in treated relative to control eyes in glaucomatous cats. A significant reduction in IOP or in diurnal fluctuation was not observed in normal cats.
Conclusions: :
In this inherited feline model of glaucoma, IOP is significantly elevated, and demonstrates accentuated diurnal fluctuation compared to normal cats. Application of brinzolamide 1% significantly decreases IOP, and reduces the magnitude of diurnal IOP fluctuations in cats with primary glaucoma.
Keywords: intraocular pressure • genetics