Purchase this article with an account.
J.A. Burke, T. Lin, K.–M. Zhang, W. Orilla, C. Spada, M. Escobar, C. Ghosn, R. Tzekov, L. Wheeler, S.M. Whitcup; Extended Effect of a Dexamethasone Posterior Segment Drug Delivery System (DexDDS) on VEGF–Induced Retinopathy . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4491.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of retinal disorders, and when administered intravitreally in animals induces retinal changes seen in diabetic retinopathy. DexDDS, a polymer–based biodegradable system administered with a 22–gauge applicator, releases the potent corticosteroid dexamethasone, in a slow, controlled–fashion. This study examined the effect of DexDDS (700 ug) on transient retinopathy following episodic administration of intravitreal VEGF in the sub–human primate eye.
Six cynomolgus monkeys weighing 3–4.5 kg were were anesthetized for dosing and measurement procedures. Animals were divided into 2 groups of 3 each and dosed unilaterally (OD) with either DexDDS or a 22–gauge sham injection. VEGF (hr165), 1.25 ug in 50 ul was delivered 1–2 mm anterior to the fovea using a 29 gauge needle at 1, 7 and 15 weeks following DexDDS or sham treatment. Assessments were made at prior to and 7 days after each VEGF injection and included measurement of anterior chamber flare (0–4 scale w/ slit lamp), retinal vascular leak and dilation (0–3 scale w/ fluorescein angiograms), foveal thickness (w/ OCT), optic nerve cup volume (w/ HRT) and ERGs (w/ Espion electrophysiology system).
DexDDS inhibited the development of VEGF–induced retinopathy throughout the 16 week experiment. Signs of disease including anterior chamber flare, vascular dilation and leakage were consistently observed in the sham–treated group at the 2, 8 and 16 weeks timepoints but were absent in the DexDDS treated animals. Optic nerve head swelling in the sham group caused a decrease in cup volume to ∼ 15 – 18% of the control eye; the cup volumes in the Dex DDS group at 2, 8 and 16 weeks were better preserved: 64 ± 15%, 75 ± 4% and 96 ± 12%, respectively. The VEGF–induced foveal thickness was consistently greater in the sham group: 150 ± 9 um, 462 ± 181 um, 968 ± 270 um at the 2, 8 and 16 week timepoints, respectively. Foveal thickness remained unchanged over time in the DexDDS group: 133 – 137 um out to 4 months. VEGF reduced ERG amplitude over the course of the study in both groups; however, the reductions were 2 to 5–fold less in the DexDDS animals. In the sham group, % of OS responses for b–wave at 1 cd.s/m2 was 52 ± 5%, 32 ± 15% and 10 ± 10% at the 2, 8 and 16 weeks timepoints, respectively. In the DexDDS group, the corresponding values were 103 ± 3%, 87 ± 13% and 51 ± 10%.
DexDDS demonstrates prolonged efficacy at inhibiting episodic VEGF–induced retinopathy.
This PDF is available to Subscribers Only