CLINICAL SCIENCE Combined Use of Rituximab and Intravenous Immunoglobulin for Severe Autoimmune Cicatricial Conjunctivitis—An Interventional Case Series Bernhard Steger, MD,*† Savitha Madhusudan, FRCOphth,* Stephen B. Kaye, MD, FRCOphth,*‡ Amira Stylianides, FRCOphth,* Vito Romano, MD,* Sundas E. Maqsood, MBBS,* Janice Harper, FRCP,§ and Sajjad Ahmad, FRCOphth, PhD*‡ Purpose: Despite the availability of systemic immunosuppressants, cicatricial conjunctivitis (CC) remains a potentially blinding ocular surface disease. We aim to describe the combined use of rituximab (RTX) and intravenous immunoglobulin (IVIg) for severe recalcitrant autoimmune CC. Methods: In this single-center retrospective interventional case series with follow-up between 32 and 65 months, 3 cases with mucous membrane pemphigoid (patients 1–3) and 1 case with linear IgA disease (patient 4) were included. Initial conventional immunosup- pressive therapy regimens included systemic steroids, dapsone, and mycophenolate. At the time of initiation of RTX and IVIg, all patients had only one eye with good visual acuity or good visual potential. Treatment included 1 to 2 cycles of RTX (1000 mg twice at an interval of 2 weeks apart), and 2 to 9 monthly courses of IVIg (2 g/kg over 3 days). Outcome measures were blindness, as defined by best spectacle- corrected visual acuity ,0.05 on a decimal scale, and clinical staging of cicatricial disease (Rowsey and Foster staging). Results: In 4 presented cases, progression of cicatricial disease was stopped as assessed by the Foster grading scale and visual acuity was stabilized in all patients. Conjunctival scarring was stabilized in 2 cases and continued to progress in 2 cases. One patient developed septicemia 6 weeks after RTX infusion, which was successfully treated. Conclusions: Combination therapy of RTX and IVIg is a potent treatment regimen for recalcitrant autoimmune CC. Further pro- spective controlled studies on efficacy and safety are warranted before widespread clinical application. Key Words: cicatricial conjunctivitis, mucous membrane pemphi- goid, linear IgA disease, rituximab, intravenous immunoglobulin (Cornea 2016;35:1611–1614) C icatricial conjunctivitis (CC) is a potentially severe sight- threatening disease for which appropriate immune sup- pression treatment is essential. The cause of CC in the majority of cases is mucous membrane pemphigoid (MMP), although there are less frequent causes such as linear IgA disease (LAD). MMP is a systemic autoimmune disease resulting from autoantibodies against structural glycoproteins of the epithe- lial basement membrane complex. It is characterized by chronic inflammation and submucosal blistering with exces- sive scar formation. Ocular involvement of MMP has been defined by a consensus conference as a high-risk subgroup of MMP requiring more aggressive systemic immunosuppres- sive therapy to prevent devastating irreversible blindness. 1 Epidemiologic reports indicate that ocular MMP occurs in 70% of cases of MMP 2 ; the incidence is 1.16 per million population per year, and blindness occurs in 27% of affected individuals. 3 LAD is a bullous disease of the skin and mucous membranes, characterized by linear deposition of IgA along the basement membrane zone with consecutive subepidermal blistering. It is currently recognized as a form of MMP. The ocular signs in LAD may be identical to those observed in patients with MMP, although the majority of patients with LAD present with milder symptoms initially. In addition, although direct immunofluorescence for IgG, IgA, and complement is characteristic of MMP, identical biopsy findings are also found in LAD. 1 In contrast to MMP, the disease may be caused by drugs such as vancomycin. Ocular involvement occurs in 50% of cases of LAD. Circulating autoantibodies against various epidermal basement membrane antigens have been found. 4 It commonly affects a younger population than MMP. 5 The therapeutic management of MMP and LAD is of critical importance in preventing blindness. The main goals of treatment are to control inflammation and subsequent fibrosis. Control of these prevents sight- and eye-threatening primary corneal complications or secondary complications as a result Received for publication April 30, 2016; revision received July 22, 2016; accepted July 23, 2016. Published online ahead of print September 21, 2016. From the *Department of Corneal and External Eye Diseases, St. Paul’s Eye Unit, Royal Liverpool University Hospital, Liverpool, United Kingdom; †Department of Ophthalmology, Medical University of Innsbruck, Inns- bruck, Austria; ‡Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom; and §Department of Nephrology, Royal Liverpool University Hospital, Liverpool, United Kingdom. The authors have no funding or conflicts of interest to disclose. Reprints: Bernhard Steger, MD, Department of Ophthalmology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria (e-mail: bernhard.steger@i-med.ac.at). Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Cornea  Volume 35, Number 12, December 2016 www.corneajrnl.com | 1611 Copyright Ó 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.