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Corine Ghosn, Alexandra Almazan, Sherri Decker, James A Burke; Brimonidine drug delivery system (Brimo DDS Generation 1) slows the growth of retinal pigment epithelial hypofluorescence following regional blue light irradiation in a nonhuman primate (NHP) model of geographic atrophy (GA). Invest. Ophthalmol. Vis. Sci. 2017;58(8):1960. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Age related macular degeneration involves GA of the retinal pigment epithelium (RPE), loss of photoreceptors and visual impairment. The aim of this pilot study was to investigate if Brimo DDS Gen 1 slows the loss of RPE and photoreceptors in a NHP model of GA.
Three 5 mm diameter parafoveal lesions were made in 12 eyes of 6 female Cynomolgus monkeys using a light source with a 470 nm filter. Fundus autofluorescence, optical coherence tomography and multifocal electroretinography (mfERG) were performed at baseline and at 1, 2, 4, 8, 12, 16, and 20 weeks post lesion. RPE loss was measured as hypofluorescence within the lesion automatically by referencing the fovea, (darkest area) and applying a pixel intensity cutoff. Photoreceptor structure and function were evaluated as outer nuclear layer (ONL) thickness and mfERG b-wave amplitude, respectively. Hypofluorescence within the lesion increased over time indicating progression. Five weeks post injury 4 monkeys received intravitreal 132 μg of Brimo DDS Gen 1 unilaterally, while the fellow eye received placebo DDS. Two additional monkeys (control; OU) were not dosed but followed-up at the same time points. A two-way repeated measures ANOVA with multiple comparisons (Tukey) was used to compare the effects of drug and duration.
No significant between group difference was observed in the measures prior to dosing. At 3 weeks post dosing area of hypofluorescence was significantly less in the Brimo DDS eyes (13602 ± 1513) compared to control (18756 ± 1039). At 7 weeks post dosing Brimo DDS (14760 ± 2616) was significantly different from both placebo DDS (22681 ± 758) and control eyes (23782 ± 1587) and remained significantly decreased throughout study duration (20 weeks; p<0.05). mfERG b-wave amplitude showed significantly less reduction in Brimo DDS eyes (33.6 ± 5.3%) compared to placebo (55.5 ± 3.4%) at 12 weeks. Brimo DDS showed decreased ONL thinning from baseline (30.3 ± 2.3%) compared to placebo (38.1 ± 1.0%; p>0.05) and control eyes (43.2 ± 4.6%; p<0.05) at 20 weeks.
Brimo DDS slows the increase of hypofluorescence and reduction of mfERG b-wave amplitude following regional blue light irradiation in NHP indicating that Brimo DDS exhibits protective effects in the RPE and photoreceptors.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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