Abstract
Purpose :
The anti-vascular endothelial growth factor therapy is effective for wet age-related macular degeneration, but in order to be effective, repeated injection is needed. To reduce the frequency of injections, we developed a degradable aflibercept-loaded microsphere-hydrogel drug delivery system (DDS). The purpose of this study was to evaluate in vivo efficacy of our aflibercept-DDS in a laser-induced choroidal neovascularization (CNV) rat model.
Methods :
Laser photocoagulation (four to five laser spots per eye) was performed on twelve Long-Evans male rats. Two weeks after CNV induction, the animals were randomly separated into four experimental groups: (1) control group (no treatment); (2) a single injection of blank DDS (5µl, no active drug) group; (3) bimonthly bolus aflibercept injections (5µl, 200µg) group; (4) a single injection of aflibercept-loaded DDS (5µl, 1µg) group. Fluorescein angiography (FA, 10% iv) was performed before and after the treatment at weeks 2, 6, 10. Multi-Otsu Thresholding analysis based on late-phase FA images were used to quantify and monitor lesion area changes to determine treatment efficacy.
Results :
108 CNV lesions were formed and included in the study. The average lesion areas for four treatment groups at week 0 (before treatment) were: (1) 7906±737µm2 for control (n=25); (2) 6876±1229µm2 for blank DDS (n=26); (3) 11002±2131µm2 for bolus injection (n=28); (4) 14743±2637µm2 for aflibercept-loaded DDS (n=29). No statistically significant differences in lesion area change at week 2 among the 4 groups. At week 6, the aflibercept bolus injection group and the aflibercept-DDS group had a reduction of 10.7±6.4% and 32.3±7.3%, respectively, compared to the control group. At week 10, the aflibercept bolus injection group and the aflibercept-DDS group had a reduction of 15.7±11.0% and 36.1±10.6%, respectively. No significant differences in CNV lesion area changes were found when comparing the bolus aflibercept injection group to the aflibercept-DDS group.
Conclusions :
The aflibercept-DDS delivered a lower overall dose of drug than the bolus injection group. The current results indicate that the aflibercept-DDS is as effective as the bimonthly aflibercept bolus injection in treatment of CNV. This study suggests that our DDS is advantageous over current bolus injections by reducing frequency of intravitreal injections.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.