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K.H. Greiner, C. Murphy, F. Willermain, L. Duncan, L. Kuffova, J. Plskova, I. Tomida, G. Hale, J.V. Forrester, A. Dick; Anti-TNFalpha Therapy in Patients with Posterior Segment Intraocular Inflammation Refractory to Conventional Immunosuppressants . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2010.
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Purpose: Clinically, non-infectious posterior segment intraocular inflammation (PSII) represents Th1 cell mediated disorders where experimental correlates show that the immunomodulatory effect of neutralising TNF alpha activity profoundly suppresses target organ damage. This study investigated the efficacy and possible immunomodulatory effects of anti-TNFalpha therapy in PSII. Methods: Sixteen patients with PSII refractory to previous immunosuppressive therapy were enrolled. A single i.v. infusion of a recombinant protein (TNFr-Ig) generated by fusing the p55 TNF receptor with human IgG1 was administered. During 20 treatment periods clinical outcome measures (visual acuity, BIO score, occurrence and extent of macular oedema) were monitored at 0, 2, 4, 8 and 12 weeks. Reduction of other immunosuppressive agents was recorded as a secondary outcome measure. Flow cytometric assessment of CD69 and CD62L expression on CD4+ T cells was performed to determine surrogate markers of treatment effectivity. Expression levels of CD69 and CD62L were compared to a population of normal controls. Results: All clinical outcome measures (visual acuity, BIO score, macular oedema) significantly improved 2 and 4 weeks after treatment with TNFr-Ig (p<0.01). Recurrences of PSII typically occurred after 8-12 weeks. A repeat infusion led to clinical improvement in these patients. No serious side effects of TNFr-Ig were observed. Treatment reduced extent of CD69 expression (p<0.05) and level of CD62L expression (MFI) after 2 weeks as compared to pretreatment (p<0.05) and normal (p<0.01) controls. Conclusions: Neutralising TNF alpha activity in PSII results in a marked and rapid resolution of inflammation and recovery of visual function, which lasts for 4-6 weeks, and is accompanied by down-regulation of peripheral CD4+ T cell activation.
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