Treatment Of Ligneous Conjunctivitis Research Articles

Treatment of Ligneous Conjunctivitis with Plasminogen Eyedrops

Ligneous conjunctivitis (LC) is the most frequent manifestation of plasminogen deficiency type 1 (approximately 80% of cases), 1 Schuster V. Seregard S. Ligneous conjunctivitis. Surv Ophthalmol. 2003; 48: 369-388 Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar an ultrarare disease that affects 1.6 per 1 million individuals and is probably underdiagnosed. Ligneous conjunctivitis is characterized by recurrent fibrin-rich, “woody” pseudomembranes on the palpebral (tarsal) conjunctivae. 1 Schuster V. Seregard S. Ligneous conjunctivitis. Surv Ophthalmol. 2003; 48: 369-388 Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar Corneal involvement, reported in 20% to 30% of patients, may lead to visual loss. 1 Schuster V. Seregard S. Ligneous conjunctivitis. Surv Ophthalmol. 2003; 48: 369-388 Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar Several topical treatments have been tried for disease control or prevention without consistent results, and surgical excision of membranes alone provides only short-lived relief. 2 Watts P. Suresh P. Mezer E. et al. Effective treatment of ligneous conjunctivitis with topical plasminogen. Am J Ophthalmol. 2002; 133 (erratum in Am J Ophthalmol. 2002;134(2):310): 451-455 Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar ,3 Shapiro A.D. Nakar C. Parker J.M. et al. Plasminogen replacement therapy for the treatment of children and adults with congenital plasminogen deficiency. Blood. 2018; 131: 1301-1310 Crossref PubMed Scopus (17) Google Scholar Systemic plasminogen replacement (fresh frozen plasma) was found to be effective, but is hampered by the need for repeated infusions. 4 Gürlü V.P. Demir M. Alimgil M.L. Erda S. Systemic and topical fresh-frozen plasma treatment in a newborn with ligneous conjunctivitis. Cornea. 2008; 27: 501-503 Crossref PubMed Scopus (19) Google Scholar ,5 Yurttaser Ocak S. Bas E. Treatment of ligneous conjunctivitis with fresh frozen plasm in twin babies. J AAPOS. 2021; 25: 50-52 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar Topical plasminogen concentrate treatment allows for easy administration and has demonstrated efficacy in several case studies. 2 Watts P. Suresh P. Mezer E. et al. Effective treatment of ligneous conjunctivitis with topical plasminogen. Am J Ophthalmol. 2002; 133 (erratum in Am J Ophthalmol. 2002;134(2):310): 451-455 Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar ,6 Caputo R. Pucci N. Mori F. et al. Long-term efficacy of surgical removal of pseudomembranes in a child with ligneous conjunctivitis treated with plasminogen eyedrops. Thromb Haemost. 2008; 100: 1196-1198 PubMed Google Scholar ,7 Heidemann D.G. Williams G.A. Hartzer M. et al. Treatment of ligneous conjunctivitis with topical plasmin and topical plasminogen. Cornea. 2003; 22: 760-762 Crossref PubMed Scopus (40) Google Scholar

Allogenic Plasma Aliquots in the Treatment of Ligneous Conjunctivitis

Allogenic Plasma Aliquots in the Treatment of Ligneous Conjunctivitis

Retraction: Treatment of Ligneous Conjunctivitis Using Topical Plasminogen Therapy in An 8-Week-Old Female Infant.

Retraction: Treatment of Ligneous Conjunctivitis Using Topical Plasminogen Therapy in An 8-Week-Old Female Infant.

Safety & Efficacy of Human Plasma Derived Plasminogen Ophthalmic Drops for Treatment of Ligneous Conjunctivitis: Report of Phase 2/3 Clinical Trial

INTRODUCTIONPlasminogen deficiency is a rare autosomal recessive disorder with variable penetrance with multisystem manifestations that may result in significant morbidity. Most commonly, type-1 (quantitative defect) is associated with characteristic fibrin rich pseudomembranes in mucosal surfaces, the most common site being the eye, called Ligneous Conjunctivitis (LC). Two-thirds of patients have bilateral eye lesions and 1/3 have corneal involvement. Initially, patients present with non-specific conjunctivitis with epiphora, followed by white-red woody lesions replacing normal membranes and resulting in visual impairment/loss. LC may be triggered/exacerbated by infection, inflammation, or trauma. Although some non-specific modalities have been reported to result in lesion improvement/resolution, only FFP and topical/systemic plasminogen are consistently effective. Surgical intervention without effective replacement therapy results in lesion regrowth. Currently, local or systemic plasminogen replacement therapy is unavailable. Therefore, development of locally administered plasminogen concentrate represents an important advance in therapeutic options for LC.OBJECTIVESA phase 2/3 study is being conducted to evaluate the safety and efficacy of Kedrion plasma derived (pd) plasminogen ophthalmologic drops for treatment of LC associated with type I plasminogen deficiency.METHODSAn ongoing open-label, multicenter, historically-controlled trial divided into 3 segments began on 5/22/2012. Three sites (1 US, 2 Italy) enrolled subjects. Segment 1 is 4 week treatment to evaluate clinical safety/efficacy followed by surgical excision of residual pseudomembranous, if required; segment 2 includes 8 weeks post-operative treatment/monitoring; segment 3 is a continuation phase with long-term safety monitoring until product licensure. Treatment regimens range from 2 drops/eye 4-12 times daily based on symptoms, study group and segment. The investigational medical product is a sterile human pd plasminogen, solvent/detergent treatment, nanofiltrated virally inactivated. During processing, the plasma pool is supplemented with bovine aprotinin to prevent plasminogen conversion to plasmin.RESULTSSegments 1 and 2 are complete; segment 3 is ongoing. The interim analysis is according to study protocol. Eleven subjects were enrolled (plasminogen activity range 5.1-34.26%; median 17.08%); age ranged between 1-44 yrs (median 4 yrs) including 4 males and 7 females; 7 had unilateral and 4 had bilateral lesions at enrolment. Three subjects did not require surgical intervention, and 8 required one excision of residual lesions after 4 weeks of therapy. In all compliant subjects, full regression and/or absence of recurrence post-excision were reported. One adult male subject, with bilateral involvement and severe visual impairment, was withdrawn due to noncompliance in study segment 2 after excision with subsequent lesion recurrence. Two subjects (1 during segment 1-2 and 1 during segment 3) developed plasma anti-plasminogen antibodies which are being further characterized as to specificity; these two subjects continue to respond to local therapy and remain symptom-free (Table 1). No viral seroconversion was detected.CONCLUSIONLC in type 1 plasminogen deficiency can result in significant morbidity without an available effective local therapy. Kedrion human pd plasminogen ophthalmologic drops were found to be effective and well tolerated and represent an important advance in the treatment of this unusual manifestation of a rare disease, plasminogen deficiency.Table 1Study Data SummarySubject #Age (Yrs)SexEye LesionsSurgery RequiredTherapeutic ResponsePlasminogen AbWithdrawal (Reason)LeftRight12MXNoFNegativeNo244FXYesPNegativeNo332MXXYesRNegativeYes (poor compliance)41FXNoFNegativeNo54MXXYesPPositiveNo61FXNoFNegativeNo71FXYesPNegativeNo83MXXYesPNegativeNo94FXYesPNegativeNo108FXXYesPPositiveNo117FXYesPNegativeNoTotal968 procedures2115 symptomatic FFull regression of lesions by end segment 1; no surgery required, no recurrence in segment 3 PPartial regression by the end of segment 1 with surgery required for residual lesion(s). No recurrence post-operatively or in segment 3. RRecurrence DisclosuresNakar:Kedrion: Research Funding. Caputo:Kedrion: Research Funding. Price:Kedrion: Research Funding; Alphaeon, Calhoun Vision Inc., Interactive Medical Publishing, Inc., ReVital Vision, TearLab,Valeant Pharmaceuticals/Bausch and Lomb: Equity Ownership; Cornea Research Foundation of America: Membership on an entity's Board of Directors or advisory committees; STAAR Surgical: Consultancy. Sartori:Kedrion: Research Funding. Suffredini:Kedrion SpA: Employment. Thukral:Kedrion: Research Funding. Secci:Kedrion: Research Funding. Jeng:Kedrion: Consultancy. Shapiro:Baxalta, Novo Nordisk, Biogen, ProMetic Life Sciences, and Kedrion Biopharma: Consultancy; Baxalta, Novo Nordisk, Biogen,: Membership on an entity's Board of Directors or advisory committees; Biogen: Speakers Bureau; Bayer Healthcare, Baxalta, Biogen, CSL Behring, Daiichi Sankyo, Kedrion Biopharma, Octapharma, OPKO, ProMetic Life Sciences, PTC Therapeutics, and Selexys: Research Funding.

Treatment of ligneous conjunctivitis with amniotic membrane transplantation and topical cyclosporine

Ligneous conjunctivitis (LC) is a rare form of bilateral chronic recurrent disease in which thick membranes form on the palpebral conjunctiva and other mucosal sites. We report the clinical features and describe the management of two cases. Case 1 was an 8-month-old patient with bilateral membranous conjunctivitis. Case 2 was a 5-year-old patient with unilateral membranous conjunctivitis, esotropia, mechanical ptosis and complicated cataract, and had been treated with a number of medications. Histological investigation of the membrane in both cases showed LC. Treatments with amniotic membrane transplantation and institution of topical cyclosporine have shown good response. There has been complete resolution of the membranes with no recurrence at the end of 40- and 28-month follow-ups, respectively. No treatment related side effects were seen. Thus, it appears that amniotic membrane transplantation and topical cyclosporine are effective alternatives for the treatment of LC.

Treatment of Ligneous Conjunctivitis with Topical Plasmin and Topical Plasminogen

To describe treatment of a child with recalcitrant ligneous conjunctivitis secondary to a systemic plasminogen deficiency. Interventional case report. A seven-year-old boy developed severe unilateral membranous conjunctivitis recalcitrant to surgical debridement and treatment with topical prednisone, topical cyclosporine, and oral prednisone. Systemic evaluation revealed a severe plasminogen deficiency. Treatment with surgical debridement and topical plasmin was ineffective and resulted in prompt recurrence of dense conjunctival membranes. Treatment with topical plasminogen resulted in dramatic improvement and complete resolution of the membranes. Ligneous conjunctivitis is secondary to a systemic plasminogen deficiency. Treatment with topical plasminogen resulted in prompt resolution of the membranes. Treatment with topical plasmin was ineffective.

Topical Heparin in the Treatment of Ligneous Conjunctivitis

Ligneous conjunctivitis is a rare acute or subacute membranous conjunctivitis of unknown etiology for which no generally accepted form of treatment is available. Between 1972 and 1993, 17 patients with ligneous conjunctivitis were treated with excision biopsy, meticulous hemostasis, and immediate, intensive topical treatment with heparin, steroids, and, in 12 patients, alpha-chymotrypsin until all signs of conjunctival inflammation had subsided. On histologic examination, the lesions consisted of subepithelial deposits of fibrin in all patients. Eight patients had no recurrence (mean follow-up, 33.1 months) and in four patients the conjunctivitis was controlled after one repeat excision and topical treatment (mean follow-up, 40.3 months). One patient had three recurrences before responding to treatment (follow-up, 24 months). In four patients, treatment was unsuccessful, although lesion-free intervals were longer than usually seen in this condition (mean, 7.8 months). These results suggest that intensive and early use of topical heparin may improve therapy results in ligneous conjunctivitis.

Treatment of Ligneous Conjunctivitis

Treatment of Ligneous Conjunctivitis