Neutralizing tumor necrosis factor activity leads to remission in patients with refractory noninfectious posterior uveitis

被引:46
作者
Murphy, CC
Greiner, K
Plskova, J
Duncan, L
Frost, A
Isaacs, JD
Rebello, P
Waldmann, H
Hale, G
Forrester, JV
Dick, AD
机构
[1] Univ Bristol, Div Ophthalmol, Bristol BS1 2LX, Avon, England
[2] Univ Aberdeen, Dept Ophthalmol, Aberdeen, Scotland
[3] Univ Newcastle, Sch Clin Med Sci, Newcastle Upon Tyne, Tyne & Wear, England
[4] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England
关键词
D O I
10.1001/archopht.122.6.845
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Objective: To evaluate the efficacy and safety of tumor necrosis factor (TNF) inhibition with the p55 TNF receptor fusion protein (TNFr-Ig) for severe sight-threatening noninfectious posterior segment intraocular inflammation. Methods: Seventeen patients with refractory noninfectious posterior segment intraocular inflammation received TNFr-Ig by intravenous infusion in this nonrandomized, open-label, pilot study. The primary outcome measure was logMAR visual acuity. Secondary outcome measures were binocular indirect ophthalmoscopy score, cystoid macular edema, adverse effects, and vision-related (visual core module 1) and health-related (36-Item Short-Form Health Survey) quality of life. Results: Within 1 month of TNFr-Ig therapy, 9 patients (53%) achieved at least a 2-line improvement in visual acuity, 8 (57%) of 14 patients with vitreous haze before treatment achieved an improvement in binocular indirect ophthalmoscopy score to 0, and macular edema resolved in 5 (56%) of 9 affected patients. Twelve (71%) of the patients achieved complete cessation of intraocular inflammation following TNFr-Ig therapy. A reduction in concomitant immunosuppression was possible for 11 patients (65%) following TNFr-Ig therapy. However, all but 1 patient required continuing adjuvant therapy during the response to TNFr-Ig, which had a median duration of 3 months. Adverse effects included mild infusion reactions in 3 patients and transient lymphocytopenia in 2 patients. Conclusion: Therapy with TNFr-Ig was safe and effective for treating patients with sight-threatening noninfectious posterior segment intraocular inflammation resistant to conventional immunotherapy, but adjuvant immunosuppression and repeat infusions would be required to maintain long-term remission.
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收藏
页码:845 / 851
页数:7
相关论文
共 43 条
[1]  
BenEzra D., 1991, Uveitis scoring system
[2]  
Brandt J, 2000, ARTHRITIS RHEUM-US, V43, P1346, DOI 10.1002/1529-0131(200006)43:6<1346::AID-ANR18>3.0.CO
[3]  
2-E
[4]   T cell mechanisms in experimental autoimmune uveoretinitis: Susceptibility is a function of the cytokine response profile [J].
Caspi, RR ;
Sun, B ;
Agarwal, RK ;
Silver, PB ;
Rizzo, LV ;
Chan, CC ;
Wiggert, B ;
Wilder, RL .
EYE, 1997, 11 :209-212
[5]   THE LENS OPACITIES CLASSIFICATION SYSTEM-III [J].
CHYLACK, LT ;
WOLFE, JK ;
SINGER, DM ;
LESKE, MC ;
BULLIMORE, MA ;
BAILEY, IL ;
FRIEND, J ;
MCCARTHY, D ;
WU, SY .
ARCHIVES OF OPHTHALMOLOGY, 1993, 111 (06) :831-836
[6]   A SIMPLE METHOD FOR MEASURING PATIENT ANTI-GLOBULIN RESPONSES AGAINST ISOTYPIC OR IDIOTYPIC DETERMINANTS [J].
COBBOLD, SP ;
REBELLO, PRUB ;
DAVIES, HFS ;
FRIEND, PJ ;
CLARK, MR .
JOURNAL OF IMMUNOLOGICAL METHODS, 1990, 127 (01) :19-24
[7]   Neutralizing TNF-alpha activity modulates T-cell phenotype and function in experimental autoimmune uveoretinitis [J].
Dick, AD ;
Duncan, L ;
Hale, G ;
Waldmann, H ;
Isaacs, J .
JOURNAL OF AUTOIMMUNITY, 1998, 11 (03) :255-264
[8]   Immunosuppressive therapy for chronic uveitis: optimising therapy with steroids and cyclosporin A [J].
Dick, AD ;
Azim, M ;
Forrester, JV .
BRITISH JOURNAL OF OPHTHALMOLOGY, 1997, 81 (12) :1107-1112
[9]   Campath-1H therapy in refractory ocular inflammatory disease [J].
Dick, AD ;
Meyer, P ;
James, T ;
Forrester, JV ;
Hale, G ;
Waldmann, H ;
Isaacs, JD .
BRITISH JOURNAL OF OPHTHALMOLOGY, 2000, 84 (01) :107-109
[10]   Inhibition of tumor necrosis factor activity minimizes target organ damage in experimental autoimmune uveoretinitis despite quantitatively normal activated T cell traffic to the retina [J].
Dick, AD ;
McMenamin, PG ;
Korner, H ;
Scallon, BJ ;
Ghrayeb, J ;
Forrester, JV ;
Sedgwick, JD .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1996, 26 (05) :1018-1025