Intravitreal Brimonidine Drug Delivery System (Brimo DDS Generation 1) Enhances Spatial Sweep Visual Evoked Potential (sVEP) in a Non-human Primate Model of Chronic Glaucoma

Abstract

Purpose : Brimonidine tartrate, an alpha-2 adrenergic receptor agonist, has been shown to prevent retinal damage in several animal models. The purpose of this study was to evaluate the effects of brimonidine formulated in a biodegradable drug delivery system on sVEP in eyes with glaucomatous optic neuropathy (GON) induced by chronic ocular hypertension.

Methods : IOP was elevated in OD of 17 cynolmogus monkeys by modified laser trabeculoplasty for periods ranging from 3 – 19 years. Retinal nerve fiber layer (RNFL) thickness was measured with OCT. For sVEP measurements, animals were fitted with permanent electrodes over the occipital cortex and visual stimuli were projected unto the central 15° with a fundus camera stimulator and consisted of vertical sinusoidal gratings at 80% contrast, 200 cd/m² luminance and 7.5 Hz temporal frequency that increased linearly from 3 to 30 cycles per degree (cpd) in 10 secs. Acuity (linear regression fits to zero amplitude of the 2nd harmonic) were made with the PowerDiva system (Norcia, 1999, Smith-Kettlewell Eye Research Institute). The animals were stratified into Brimo DDS (132 ug; n=10) and placebo DDS (n=7) study arms based on baseline sVEP measurements, dosed twice (0, 10 months) and followed up for a total of 11 months.

Results : At baseline, IOPs were 38 ± 3 and 20 ± 1 mm Hg in OD and OS, respectively. RNFL thickness compared to OS was 27 ± 9% in the Brimo DDS group and 25 ± 11% in the placebo DDS group. Neither IOP nor RNFL thickness changed over the course of the study. Baseline acuities (OD/OS%) for Brimo DDS and placebo DDS were 43 ± 9% and 39 ± 11%, respectively. After the 1^st dose, acuities in the Brimo DDS group at ½, 1, 2, 4, 6 and 10 months follow-up were 77 ± 14%, 84 ± 10%, 83 ± 10%, 78 ± 9%, 65 ± 11% and 47 ± 6% respectively; p< 0.05 at 0.5 – 4 months. Acuities in the placebo DDS group were 40 ± 10%, 44 ± 12%, 44 ± 9%, 42 ± 12%, 39 ± 12% and 26 ± 4% respectively. After the 2^nd dose, acuities in the Brimo DDS group at 10.5 and 11 months were 77 ± 12% and 73 ± 13% respectively; p<0.05 at 10.5 and 11 months. Acuities in the placebo DDS group were 26 ± 6% and 26 ± 6%, respectively.

Conclusions : Intravitreal Brimo DDS enhanced spatial acuity in experimental GON.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.