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Chengxin Zhou, Vassiliki Kapoulea, James Chodosh, Claes H Dohlman, Eleftherios I Paschalis; Evaluation of a sustained drug delivery system for anti-VEGF antibody after alkali burns to the eye. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2579.
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Ocular burns cause corneal neovascularization (CNV), inflammation, and scarring. We previously showed that sustained delivery of anti-tumor necrosis factor alpha (anti-TNF-α), using a novel drug delivery system (DDS), improves corneal wound healing and reduces ocular inflammation. In this study, we assessed the therapeutic effect of the DDS for sustained delivery of anti-vascular endothelial growth factor (anti-VEGF) in corneal alkali burns.
An established rabbit ocular alkali burn model was used to assess the efficacy of the anti-VEGF DDS in terms of reduction of corneal CNV, opacity, and improvement in corneal re-epithelialization. DDS was prepared using porous PDMS/PVA composite fabrication and loaded with 3mg bevacizumab. Evaluation was performed in 6 Dutch-belted pigmented rabbits which received ocular alkali burn with 2N NaOH, followed by subconjunctival implantation of either anti-VEGF DDS (n=3) or sham DDS (n=3) in the lower eyelid immediately after the burn. Rabbits were followed with photography for 3 months and analyzed for CNV, opacity and re-epithelialization. Corneal inflammation was assessed by immunofluorescent staining against CD45 in tissue cryosections, and epithelial defects by fluorescein staining.
Rabbits treated with anti-VEGF DDS exhibited initial retardation in corneal re-epithelialization during the first 24 days followed by subsequent acceleration thereafter, with almost total corneal re-epithelialization 58 days post burn. Sham DDS group had persistent epithelial defects (9~12% of cornea area) until the end of the study (90 days after the burn). CNV progressed significantly slower (p<0.01) in the anti-VEGF DDS group with a 70% decrease in mean CNV area at 1 month (p<0.05), as compared to sham group. CD45+ immune cell infiltration was also significantly reduced in the anti-VEGF DDS group (mean= 1332 cells/ cornea) as compared to the sham DDS (mean= 14282 cells/ cornea, p<0.05). Antibody (bevacizumab) was still detectable in the DDS 3 months after implantation, as evident by anti-human IgG immunolocalization.
Sustained, low-dose, subconjunctival delivery of anti-VEGF suppresses corneal inflammation and CNV, and improves re-epithelialization after ocular alkali burns. No adverse effects from the DDS were observed. This treatment modality may also be feasible for other ocular surface diseases amenable to anti-VEGF therapy.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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