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G. J. McLellan, T.-L. Lin, S. Hildreth, C. Petersen, A. Leon, J. K. Jens, N. M. Ellinwood; Diurnal Intraocular Pressure and Response to Topically Administered 1% Brinzolamide in a Spontaneous Feline Model of Primary Congenital Glaucoma. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4059.
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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.
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
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.
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.
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