September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Evaluation of a therapeutic anti-TNF-α drug delivery system for ocular alkali burns
Author Affiliations & Notes
  • Chengxin Zhou
    Department of Ophthalmology, Schepens Eye Research Institute-Massachusetts Eye and Ear, Boston, Massachusetts, United States
    Harvard Medical School, Boston, Massachusetts, United States
  • Marie-Claude Robert
    Department of Ophthalmology, Universite de Montreal, Montreal, Quebec, Canada
    Centre Hospitalier de l'Universite de Montreal , Hopital Notre-Dame, Montreal, Quebec, Canada
  • Fengyang Lei
    Department of Ophthalmology, Schepens Eye Research Institute-Massachusetts Eye and Ear, Boston, Massachusetts, United States
    Harvard Medical School, Boston, Massachusetts, United States
  • Vassiliki Kapoulea
    Department of Ophthalmology, Schepens Eye Research Institute-Massachusetts Eye and Ear, Boston, Massachusetts, United States
    Harvard Medical School, Boston, Massachusetts, United States
  • James Chodosh
    Massachusetts Eye and Ear, Boston, Massachusetts, United States
    Harvard Medical School, Boston, Massachusetts, United States
  • Claes H Dohlman
    Massachusetts Eye and Ear, Boston, Massachusetts, United States
    Harvard Medical School, Boston, Massachusetts, United States
  • Eleftherios I Paschalis
    Department of Ophthalmology, Schepens Eye Research Institute-Massachusetts Eye and Ear, Boston, Massachusetts, United States
    Harvard Medical School, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Chengxin Zhou, None; Marie-Claude Robert, None; Fengyang Lei, None; Vassiliki Kapoulea, None; James Chodosh, None; Claes Dohlman, None; Eleftherios Paschalis, None
  • Footnotes
    Support  Boston Keratoprosthesis Research Fund, Massachusetts Eye and Ear, Boston, MA
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 1271. doi:
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      Chengxin Zhou, Marie-Claude Robert, Fengyang Lei, Vassiliki Kapoulea, James Chodosh, Claes H Dohlman, Eleftherios I Paschalis; Evaluation of a therapeutic anti-TNF-α drug delivery system for ocular alkali burns. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1271.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Ocular burns cause corneal inflammation, neovascularization (CNV) and scarring. We have shown that tumor necrosis factor alpha (TNF-α) is upregulated after burn and that prompt TNF-α inhibition improves corneal wound healing. However, systemic administration of TNF-α inhibitors can cause significant adverse events, while topical administration is limited by poor corneal bioavailability and the need for frequent drug application. This study was designed to test a novel drug delivery system (DDS) for sustained-release of TNF-α inhibitor to the ocular surface. We used a rabbit ocular alkali burn model to assess the efficacy of the DDS in terms of reduction of corneal CNV, opacity and improvement of corneal wound healing.

Methods : DDS was prepared using porous PDMS/PVA composite fabrication that was loaded with 80μg infliximab. Evaluation was performed in 6 Dutch-belted pigmented rabbits that received ocular alkali burn with 2N NaOH. Three rabbits received subconjunctival implantation of anti-TNF-α DDS and 3 sham DDS immediately after the burn. Rabbits were followed with photography for 3 months and analyzed for CNV, opacity and re-epithelialization. Inflammation was assessed using CD45 antibody in tissue sections.

Results : Rabbits treated with anti-TNF-α DDS achieved complete corneal re-epithelialization within 63.6 ± 7.5 days of burn, reduced CNV (0.13 ± 0.05 % of cornea area) and corneal opacity (central score = 2.17 ± 0.85; peripheral score = 0.33 ± 0.41 in a 0-4 scale), while sham DDS treated rabbits exhibited persistent epithelial defect until the end of the study (92 days), increased CNV (0.31 ± 0.14 % of cornea area, p<0.05) and corneal opacity (central score = 3.5 ± 0.57, p>0.05; peripheral score = 2.44 ± 1.41, p<0.05). Anti-TNF-α DDS was well tolerated. The number of CD45+ cells in anti-TNF-α DDS treated eyes was significantly lower (mean=4322 cells/ cornea) compared to sham DDS eyes (mean=17049 cells/ cornea, p<0.05). Infliximab was still present in the DDS 3 months after implantation, evident by anti-human IgG immunolocalization.

Conclusions : Sustained topical delivery of anti-TNF-α for the treatment of ocular alkali burn is feasible using the described DDS. Local anti-TNF-α therapy suppresses corneal inflammation and CNV, and improves wound healing. The described DDS may be beneficial to a variety of ocular surface diseases amenable to biologic therapy.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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