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J. A. Burke, K.-M. Zhang, T. Lin, C. Spada, P. Hughes, B. Kuppermann, L. Wheeler, S. Whitcup; Intravitreal Brimonidine Drug Delivery System Enhances Sweep Visual Evoked Potential. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6240.
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Brimonidine tartrate, an alpha-2 adrenergic receptor agonist, has been shown to prevent retinal damage in a number of animal models. The purpose of this study was to evaluate the effects of brimonidine formulated in a biodegradable drug delivery system on sweep visual evoked potential (sVEP) in normal eyes.
Dutch-Belted (pigmented) rabbits were randomly assigned to receive brimonidine DDS into the left eye at a dose of 66 ug (N=10), 200 ug (N=10), 600 ug (N=10). Placebo DDS implants were placed into the right eye of each animal. Fundus photography and sVEP measurements in dilated, unanesthetized animals were performed at baseline and 2, 4, 8, 12, and 16 weeks after implantation in animals fitted 1 - 6 months earlier with permanent electrodes over the occipital cortex. Visual stimuli were projected unto the central 50° with a high resolution fundus camera stimulator and consisted of vertical sinusoidal gratings at 80% contrast, 600 cd/m2 luminance and 7.5 Hz temporal frequency that increased linearly from 0.1 to 5 cycles per degree (cpd) in 10 secs. Acuity (linear regression fits to zero amplitude of the 2nd harmonic) from 5 - 20 trials were made with the PowerDiva system (Norcia, 1999, Smith-Kettlewell Eye Research Institute) using a signal-to-noise ratio ≥ 1.5:1 and a constant phase as acceptance criteria. Data are presented as mean ± standard error of the mean. A paired Student’s ‘t’ test compared brimonidine-treated with placebo eyes. Retinal histology was performed on eyes from animals receiving 600 ug of brimonidine DDS at 6 months (n=3) and at 12 months (n=2).
Baseline sVEP acuities for the 66 ug group were 1.94 ± 0.09 cpd and 1.95 ± 0.09 cpd for OD and OS, respectively (p>0.05), at 2 weeks 1.67 ± 0.12 cpd and 2.48 ± 0.11 (p=0.0008), and at 4 weeks 1.93 ± 0.11 cpd and 2.20 ± 0.11 cpd (p=0.045). Baseline acuities for the 200 ug group were 2.48 ± 0.12 cpd and 2.47 ± 0.1 cpd, respectively (p>0.05), at 2 weeks 2.12 ± 0.19 cpd and 2.59 ± 0.18 cpd (p=0.02), and at 4 weeks 1.73 ± 0.13 cpd and 2.02 ± 0.15 cpd (p=0.006). Baseline acuities for the 600 ug group were 2.01 ± 0.11 cpd and 1.98 ± 0.15 cpd, respectively (p>0.05), at 2 weeks 2.16 ± 0.15 cpd and 2.68 ± 0.22 cpd (p=0.0034), and at 4 weeks 1.72 ± 0.13 cpd and 2.16 ± 0.1 cpd (p=0.0031). There were no statistically significant differences between OD and OS at later time points, nor were there any abnormalities noted on color fundus photography. Retinal histology showed no difference between brimonidine DDS and placebo DDS eyes.
Intravitreal brimonidine in a sustained drug delivery system enhances sVEP recordings in animal eyes in the absence of funduscopic or histologic changes.
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