Alkali Burn to the Eye

Cade, Fabiano; Paschalis, Eleftherios I.; Regatieri, Caio; Vavvas, Demetrios G.; Dana, Reza; Dohlman, Claes H.

doi:10.1097/ico.0000000000000071

Cited by 70 publications

(63 citation statements)

References 18 publications

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“…It was not clear from the literature describing systemic use of infliximab in different preclinical models, whether it can bind to mouse TNF-α and therefore enable us to demonstrate efficacy in the EAU model161718. Ocular administration of infliximab has been shown to provide significant retinal and corneal protection in an mouse model of alkali injury19, as well as modulating choroidal neovascularization and endotoxin-induced inflammation in rat and rabbit experimental models respectively2021. In the current study we therefore sought to confirm the binding of infliximab to both murine (Fig.…”

Section: Resultsmentioning

confidence: 99%

An anti-TNF-α antibody mimetic to treat ocular inflammation

Khalili

Lee

Khaw

et al. 2016

Sci Rep

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Infliximab is an antibody that neutralizes TNF-α and is used principally by systemic administration to treat many inflammatory disorders. We prepared the antibody mimetic Fab-PEG-Fab (FpFinfliximab) for direct intravitreal injection to assess whether such formulations have biological activity and potential utility for ocular use. FpFinfliximab was designed to address side effects caused by antibody degradation and the presence of the Fc region. Surface plasmon resonance analysis indicated that infliximab and FpFinfliximab maintained binding affinity for both human and murine recombinant TNF-α. No Fc mediated RPE cellular uptake was observed for FpFinfliximab. Both Infliximab and FpFinfliximab suppressed ocular inflammation by reducing the number of CD45+ infiltrate cells in the EAU mice after a single intravitreal injection at the onset of peak disease. These results offer an opportunity to develop and formulate for ocular use, FpF molecules designed for single and potentially multiple targets using bi-specific FpFs.

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Section: Resultsmentioning

confidence: 99%

An anti-TNF-α antibody mimetic to treat ocular inflammation

Khalili

Lee

Khaw

et al. 2016

Sci Rep

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“…11 In mice, TNF-α is highly upregulated within 24 hours after corneal alkali burn and later mediates neovascularization and scarring. 12 Prompt inhibition with an anti-TNF-α antibody (infliximab) after alkali burn has been shown to protect the cornea and promote healing. 12,13 This effect has also been demonstrated in animals with experimental keratoprosthesis 14 and in other settings.…”

mentioning

confidence: 99%

“…12 Prompt inhibition with an anti-TNF-α antibody (infliximab) after alkali burn has been shown to protect the cornea and promote healing. 12,13 This effect has also been demonstrated in animals with experimental keratoprosthesis 14 and in other settings. 15,16 Clinically, infliximab has been found to very effectively suppress inflammation after keratoprosthesis surgery in autoimmune diseases, 17,18 as well as in corneal ulceration.…”

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confidence: 99%

“…It has been shown in animals that alkali can cause substantial apoptosis of retinal ganglion cells, as well as optic nerve changes, which would be expected to result in glaucoma. 12 The effect of the alkali is not a direct one—the pH of the posterior eye segment remains normal and the alkali seems to be effectively buffered before reaching the retina (data submitted for publication). 12 Rather, the damage to the retina comes from cytokines, which can reach the retina within 24 hours.…”

mentioning

confidence: 99%

“…12 The effect of the alkali is not a direct one—the pH of the posterior eye segment remains normal and the alkali seems to be effectively buffered before reaching the retina (data submitted for publication). 12 Rather, the damage to the retina comes from cytokines, which can reach the retina within 24 hours. Tumor necrosis factor-α is quite likely a main offender and systemically administered TNF-α inhibitor (infliximab, a humanized chimeric monoclonal anti-TNFα antibody [Remicade, Jansen Biotech, NJ, USA]) can prevent retinal ganglion cell apoptosis to a considerable degree.…”

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confidence: 99%

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Sustained Subconjunctival Delivery of Infliximab Protects the Cornea and Retina Following Alkali Burn to the Eye

Zhou

Robert

Kapoulea

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PurposeTumor 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).MethodsThe 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.ResultsAfter 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.ConclusionsThis 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.

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Current Concepts and Management of Severely Traumatized Tissues in the Inner Coatings (The Posterior Segment: The Ciliary Body, the Choroid and the Retina) of the Globe: Nonmechanical Injuries

Ünal¹,

Çakir²

2016

Current Concepts and Management of Eye Injuries

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Alkali Burn to the Eye

Cited by 70 publications

References 18 publications

An anti-TNF-α antibody mimetic to treat ocular inflammation

An anti-TNF-α antibody mimetic to treat ocular inflammation

Sustained Subconjunctival Delivery of Infliximab Protects the Cornea and Retina Following Alkali Burn to the Eye

Current Concepts and Management of Severely Traumatized Tissues in the Inner Coatings (The Posterior Segment: The Ciliary Body, the Choroid and the Retina) of the Globe: Nonmechanical Injuries

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