Copyright © 2016 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. Unauthorized reproduction of this article is prohibited. Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2016 e1 Abstract: Ligneous conjunctivitis is a rare, autosomal recessive, membranous conjunctivitis characterized by a deficiency in type 1 plasminogen. The absence of normal plasmin activity results in the formation of fibrin-rich, membranous material that typically manifests on the palpebral conjunctiva. Surgical treatment often causes irritation of the conjunctiva and accelerated recurrence of pseudomembranes. In this interventional case report, the authors document the results of treatment with topical plasminogen following conjunctival pseudomembrane excision in a 32-year-old woman. The patient underwent pseudomembrane excision in the OS followed immediately by hourly topical application of plasminogen eye drops. The plasminogen was prepared from pooled human plasma purchased under Food and Drug Administration approval from DiaPharma. Follow-up evaluation at 1 week, 1 month, and 5 months showed no evidence of recurrent pseudomembranous change. Adjunctive topical plasminogen application appears to be an effective and safe method of controlling pseudomembrane recurrence in patients with ligneous conjunctivitis. L igneous conjunctivitis is a rare, autosomal recessive, mem- branous conjunctivitis characterized by a deficiency in type 1 plasminogen, an important enzyme in the fibrinolytic system. 1–3 The absence of plasmin activity results in the formation of fibrin-rich pseudomembranes, typically presenting on the upper palpebral conjunctiva. 4–6 Over the past 50 years, only about 150 cases have been reported worldwide and treatment proves to be difficult. The membranes are believed to form in response to ocular irritants, such as dust, foreign bodies, infection, or previous surgery. 1,2 Thus, while surgical resection provides a temporary solution, surgical irritation to the conjunctiva actu- ally accelerates recurrence of pseudomembranes. 7,8 Previously reported therapies including corticosteroids, cyclosporine, hep- arin, alpha-chymotrypsin, fresh-frozen plasma, and antivirals have yielded varying degrees of success. 2,7–12 Recently, there has been a movement toward more targeted treatment of the disease via the administration of intravenous or topical plasminogen with good outcomes. 1,13,14 In this Health Insurance Portability and Accountability Act compliant, interventional case report, the authors share their experience of a 32-year-old Caucasian woman who first presented in 2003 with bilateral ligneous conjunctivitis. Since initial presentation, the patient underwent 4 excisions, 5 biop- sies, 2 grafts, and 7 conjunctivoplasties. In February 2011, the patient underwent pseudomembrane excision followed immedi- ately by topical application of plasminogen eye drops. No other systemic or topical therapies were utilized. An investigational new drug for a single patient was issued by the Food and Drug Administration (#111153) for this purpose. The plasminogen was prepared from pooled human plasma, Technoclone Glu- Plasminogen 1 mg, purchased from DiaPharma (West Chester, OH, U.S.A.). The product was subsequently reconstituted with 1 ml of 0.9% normal saline, filtered, and placed in sterile eye dropper vials for single-day use, then frozen. Once thawed in the refrigerator, the product expired after 24 hours. Following excision of a recurrent ligneous membrane on the left superi- omedial tarsal conjunctiva, a topical regimen of plasminogen was adopted consisting of hourly drops while awake for the first week, gradually tapered over the following 6 weeks. Follow-up evaluations at 1 week, 1 month, and 5 months showed no evi- dence of recurrent pseudomembranous change in the surgically treated area. No other adverse reactions were noted. Currently, plasminogen for the treatment of ligneous con- junctivitis may be administered by 2 routes: systemically via intravenous infusion or topically via eye drops. Mingers et al. 15 were the first to infuse lys-plasminogen intravenously to treat ligneous conjunctivitis. Unfortunately, clinical symptoms did not improve significantly in this initial subset of patients. 15 In addition, long-term intravenous therapy is inherently more inva- sive, requiring placement of a central line for daily infusion. Other drawbacks to lys-plasminogen are short half-life and high cost. 2 Watts et al. 1 first described the use of topical plasmino- gen in patients with ligneous conjunctivitis and reported great success. All 3 patients who underwent surgical resection and topical plasminogen administration maintained complete reso- lution at 12 months. 1 Thus, topical plasminogen drops seems to be more advantageous both in controlling pseudomembrane formation and in decreasing potential complications (Fig. A, B). Given the rarity of this particular disease, it is not surprising that Topical Plasminogen as Adjunctive Treatment in Recurrent Ligneous Conjunctivitis Michael J. Ang, M.D., Konstantinos I. Papageorgiou, M.D., Shu-Hong Chang, M.D., Jocelyn Kohn, M.D., Helen Chokron Garneau, M.P.H., and Robert A. Goldberg, M.D. DOI: 10.1097/IOP.0000000000000694 Jules Stein Eye Institute, Division of Orbital and Oculoplastic Surgery, University of California, Los Angeles, California, U.S.A. Accepted for publication February 24, 2016. Previously presented at the American Society of Ophthalmic Plastic and Reconstructive Surgery 42nd Annual Fall Scientific Symposium, Orlando, FL, October 21–22, 2011. The authors have no financial or conflict of interest to disclose. Address correspondence and reprint requests to Robert A. Goldberg, M.D., Division of Orbital and Ophthalmic Plastic Surgery, Jules Stein Eye Institute, University of California-Los Angeles, 100 Stein Plaza 2-267, Los Angeles, CA 90049. E-mail: Goldberg@jsei.ucla.edu Preoperative (A) and postoperative (B) photographs demonstrate successful resection of a pseudomembrane on the palpebral conjunctiva with no evidence of recurrence at 5 months. CASE REPORTS