title: Sustained Subconjunctival Delivery of Infliximab Protects the Cornea and Retina Following Alkali Burn to the Eye.
abstract: Tumor necrosis factor (TNF)-α is upregulated in eyes following corneal alkali injury and contributes to corneal and also retinal damage. Prompt TNF-α inhibition by systemic infliximab ameliorates retinal damage and improves corneal wound healing. However, systemic administration of TNF-α inhibitors carries risk of significant complications, whereas topical eye-drop delivery is hindered by poor ocular bioavailability and the need for patient adherence. This study investigates the efficacy of subconjunctival delivery of TNF-α antibodies using a polymer-based drug delivery system (DDS).
  
  
  
  The drug delivery system was prepared using porous polydimethylsiloxane/polyvinyl alcohol composite fabrication and loaded with 85 μg of infliximab. Six Dutch-belted pigmented rabbits received ocular alkali burn with NaOH. Immediately after the burn, subconjunctival implantation of anti-TNF-α DDS was performed in three rabbits while another three received sham DDS (without antibody). Rabbits were followed with photography for 3 months.
  
  
  
  After 3 months, the device was found to be well tolerated by the host and the eyes exhibited less corneal damage as compared to eyes implanted with a sham DDS without drug. The low dose treatment suppressed CD45 and TNF-α expression in the burned cornea and inhibited retinal ganglion cell apoptosis and optic nerve degeneration, as compared to the sham DDS treated eyes. Immunolocalization revealed drug penetration in the conjunctiva, cornea, iris, and choroid, with residual infliximab in the DDS 3 months after implantation.
  
  
  
  This reduced-risk biologic DDS improves corneal wound healing and provides retinal neuroprotection, and may be applicable not only to alkali burns but also to other inflammatory surgical procedures such as penetrating keratoplasty and keratoprosthesis implantation.
authors.affiliation: Boston Keratoprosthesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear and Schepens Eye Research Institute, Boston, Massachusetts, United States 2Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Chengxin
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Ophthalmology, Université de Montreal, Montreal, Quebec, Canada 4Centre Hospitalier de l'Université de Montreal, Hospital Notre-Dame, Montreal, Quebec, Canada.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Robert
authors.affiliation: Boston Keratoprosthesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear and Schepens Eye Research Institute, Boston, Massachusetts, United States 2Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Kapoulea
authors.affiliation: Boston Keratoprosthesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear and Schepens Eye Research Institute, Boston, Massachusetts, United States 2Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Fengyang
authors.initials: F
authors.lastname: Lei
authors.affiliation: Harvard Medical School, Boston, Massachusetts, United States 5David G. Cogan Ophthalmic Pathology Laboratory, Massachusetts Eye and Ear, Boston, Massachusetts, United States.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Stagner
authors.affiliation: Harvard Medical School, Boston, Massachusetts, United States 5David G. Cogan Ophthalmic Pathology Laboratory, Massachusetts Eye and Ear, Boston, Massachusetts, United States.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Jakobiec
authors.affiliation: Boston Keratoprosthesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear and Schepens Eye Research Institute, Boston, Massachusetts, United States 2Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Claes H
authors.initials: CH
authors.lastname: Dohlman
authors.affiliation: Boston Keratoprosthesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear and Schepens Eye Research Institute, Boston, Massachusetts, United States 2Harvard Medical School, Boston, Massachusetts, United States 6Disruptive Technology Laboratory (D.T.L.), Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Eleftherios I
authors.initials: EI
authors.lastname: Paschalis
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage; D002057:Burns, Chemical / Q000175:diagnosis / Q000188:drug therapy*; D003228:Conjunctiva; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D065306:Corneal Injuries / Q000175:diagnosis / Q000188:drug therapy*; D016510:Corneal Neovascularization / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004343:Drug Implants; D005126:Eye Burns / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D000069285:Infliximab / Q000008:administration & dosage*; D011817:Rabbits; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012164:Retinal Diseases / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D018501:Antirheumatic Agents; D003692:Delayed-Action Preparations; D004343:Drug Implants; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab