Abstract
Purpose :
There is a growing subset of age-related macular degeneration patients that do not successfully respond to a monthly monotherapy treatment of anti-vascular endothelial growth factor (VEGF). Recent studies suggest that this subset may respond to a combination therapy of corticosteroid and anti-VEGF. The current combination therapy is administered in separate injections where anti-VEGF injections are repeated monthly/bimonthly. Recently, we developed a single drug delivery system that can release dexamethasone (DEX) and aflibercept (AFL) simultaneously. This study was to determine the treatment efficacy of DEX and AFL released from a single drug delivery system (DDS) in a choroidal neovascularization (CNV) rodent model.
Methods :
AFL and DEX were encapsulated into poly(lactic-co-glycolic acid) particles that were embedded into a single thermoresponsive hydrogel DDS. CNV lesions were created by laser photocoagulation (50um, 0.5W) in Long-Evans rats. Animals were randomly assigned into: control (no treatment), blank-DDS (5ul, no drugs), bolus AFL intravitreal (IVT) injections (5ul, 10ug, bimonthly), AFL-DDS (5ul, 1.5ug), AFL+DEX-DDS (5ul, 1.5ug, 20ug, respectively), and DEX-DDS (5ul, 20ug). At week 0 (14 days after the laser induction), treatment was administered. Fluorescein angiography (FA) was obtained at weeks 0, 2, 6, 10, 14, 18 and 22. Multi-Otsu Thresholding was used to quantify lesion area to determine treatment efficacy.
Results :
Before the treatment, FA confirmed that CNV lesions were fully developed. At week 14, increases in lesion size were seen in control(10±8%), while slight decreases were seen in blank-DDS(-1±8%), bolus AFL injections(-3±7%), and DEX-DDS(-5±5%), and larger decreases were seen in AFL-DDS(-21±5%), and AFL+DEX-DDS(-33±5%). At week 22, decreases were seen in bolus AFL injections(-11±7%), DEX-DDS(-12±7%), AFL-DDS(-33±4%), and AFL+DEX-DDS (-30±7%), and increases were seen in control(2±8%) and blank DDS(4±10%).
Conclusions :
The combination treatment of AFL and DEX released from a single DDS delivered a lower amount of overall aflibercept compared to bolus injection, with improved treatment efficacy. [MOU1] The study suggests that a combination treatment may be a viable alternative for non-responsive patients.
This is a 2021 ARVO Annual Meeting abstract.