Franceschetti Hereditary Recurrent Corneal Erosion WALTER LISCH, ANTHONY J. BRON, FRANCIS L. MUNIER, DANIEL F. SCHORDERET, LEILA TIAB, CLEMENS LANGE, PARYKSHIT SAIKIA, THOMAS REINHARD, JAYNE S. WEISS, ENKEN GUNDLACH, UWE PLEYER, CHRISTINA LISCH, AND CLAUDIA AUW-HAEDRICH ● PURPOSE: To describe new affected individuals of France- schetti’s original pedigree of hereditary recurrent erosion and to classify a unique entity called Franceschetti corneal dystro- phy. ● DESIGN: Observational case series. ● METHODS: Slit-lamp examination of 10 affected indi- viduals was conducted. Biomicroscopic examinations were supplemented by peripheral corneal biopsy in 1 affected patient with corneal haze. Tissue was processed for light and electron microscopy and immunohistochem- istry was performed. DNA analysis was carried out in 12 affected and 3 nonaffected family members. ● RESULTS: All affected individuals suffered from severe ocular pain in the first decade of life, attributable to recurrent corneal erosions. Six adult patients developed bilateral diffuse subepithelial opacifications in the central and paracentral cor- nea. The remaining 4 affected individuals had clear corneas in the pain-free stage of the disorder. Histologic and immunohis- tochemical examination of the peripheral cornea in a single patient showed a subepithelial, avascular pannus. There was negative staining with Congo red. DNA analysis excluded mutations in the transforming growth factor beta–induced (TGFBI) gene and in the tumor-associated calcium signal transducer 2 (TACSTD2) gene. ● CONCLUSION: We have extended the pedigree of France- schetti corneal dystrophy and elaborated its natural history on the basis of clinical examinations. A distinctive feature is the appearance of subepithelial opacities in adult life, accompanied by a decreased frequency of recurrent erosion attacks. Its clinical features appear to distinguish it from most other forms of dominantly inherited recurrent corneal erosion reported in the literature. (Am J Ophthalmol 2012;153:1073–1081. © 2012 by Elsevier Inc. All rights reserved.) R ECURRENT CORNEAL EROSION IS A CONDITION OF repeated, acute, severe eye pain attributable to defective epithelial adherence and recurrent cor- neal epithelial separation. 1 The severity of the pain reflects that the cornea has one of the richest sensory innervations of the body. 2 The condition is most commonly post- traumatic, following a glancing injury to the cornea, in which case attacks are unilateral and confined to the original site of corneal damage. In most instances, in the absence of infection, each attack recovers without signif- icant subepithelial corneal scarring. Less commonly, the condition is bilateral and occurs either spontaneously or in response to negligible trauma. In this instance a “dystro- phic” basis may be considered, although evidence of a family history is often lacking. In recent decades, in older subjects this presentation has been recognized as a mani- festation of epithelial basement membrane dystrophy, wherein characteristic bilateral biomicroscopic features such as map/dot/fingerprint disorder and superficial bleb, net, and mare’s tail changes are accompanied by recurrent erosion attacks in 1 or both eyes. 3,4 At least some of these are genetically determined by a mutation affecting the transforming growth factor beta–induced (TGFBI) gene. 5 Attacks of recurrent erosion are a well-recognized feature of the phenotypically distinct, major TGFBI corneal dys- trophies, as well as in Fuchs dystrophy; 4,6 additionally, there have been a relatively small number of reports of inherited recurrent corneal erosion occurring as a dystro- phy in its own right. 7–18 All of the recurrent erosion disorders, whether traumatic or dystrophic, are presumed to be attributable to a defect in the epithelial adhesion complex, which normally ensures a tight adhesion between the basal cells of the corneal epithelium and the underly- ing basal lamina and Bowman layer. These attachment structures consist of the hemidesmosomes, the anchoring fibrils of type VII collagen, and the basal lamina contain- ing collagens type IV and VII, laminin, and fibronectin. 19 The International Committee for Classification of Cor- neal Dystrophies (IC3D) published a new classification in 2008 20 that placed each of 25 known corneal dystrophies into 1 of 4 categories based on the quality of evidence for their existence. Supportive clinical, structural, and genetic information was incorporated into a standard template for each corneal dystrophy. One template, headed “Ep- ithelial recurrent erosion dystrophy (ERED),” included the report of Franceschetti’s “Hereditary recurrent ero- sion of the cornea” 7 and the so-called “dystrophia Supplemental Material available at AJO.com. Accepted for publication Dec 19, 2011. From the Department of Ophthalmology, Johannes Gutenberg Uni- versity Mainz, Mainz, Germany (W.L.); Clinical Research Unit, Nuffield Laboratory of Ophthalmology, Oxford, United Kingdom (A.J.B.); Jules Gonin Eye Hospital, Department of Ophthalmology, University of Lausanne, Lausanne, Switzerland (F.L.M.); Institut de Recherche en Ophtalmologie Sion, Sion, the University of Lausanne, and the École polytechnique fédérale de Lausanne, Lausanne, Switzerland (F.L.M., D.F.S., L.T.); University Eye Hospital Freiburg, Freiburg, Germany (C.L., T.R., E.G., C.A.-H.); Private Ophthalmological Office Hanau, Hanau, Germany (P.S., Ch.L.); Department of Ophthalmology, Louisiana State University Health Science Center New Orleans, New Orleans, Louisiana (J.S.W.); and Department of Ophthalmology, Campus Virchow-Klini- kum, Charité Universitaetsmedizin Berlin, Berlin, Germany (U.P.). Inquiries to Walter Lisch, Kurt-Blaum-Platz 8, 63450 Hanau, Ger- many; e-mail: prof.dr.lisch@augenklinik-hanau.de © 2012 BY ELSEVIER INC.ALL RIGHTS RESERVED. 0002-9394/$36.00 1073 doi:10.1016/j.ajo.2011.12.011