title: The Pathogenesis of floppy eyelid syndrome: involvement of matrix metalloproteinases in elastic fiber degradation.
abstract: OBJECTIVE
  To investigate histopathologic alterations of eyelid biopsy specimens from patients with floppy eyelid syndrome (FES) with special regard to elastic fiber content and ultrastructure as well as to the expression of elastin-degrading enzymes to elucidate the pathogenesis of this disorder.
  
  
  METHODS
  Retrospective, interventional case series.
  
  
  METHODS
  Eleven consecutive patients with FES and 10 age-matched control patients with basal cell carcinoma of the eyelid.
  
  
  METHODS
  Horizontal pentagonal eyelid resections of 16 upper lids were performed in 11 patients with FES. Full-thickness eyelid biopsy specimens from study and control patients were examined by light and transmission electron microscopy, semiquantitative morphometry, and immunohistochemistry using antibodies against matrix metalloproteinase (MMP)-2, MMP-7, MMP-9, and MMP-12 and neutrophil elastase.
  
  
  RESULTS
  All patients treated with surgical horizontal eyelid shortening were asymptomatic at follow-up. Histopathologic analysis of the surgical specimens showed, apart from unspecific signs of chronic inflammation, a significant decrease in the amount of elastin within the tarsal plate and eyelid skin as compared with controls. Residual elastic fibers revealed an abnormal ultrastructure with a diminished elastin core. Immunohistochemistry demonstrated an increased immunoreactivity for elastolytic proteases, particularly MMP-7 and MMP-9, in areas of elastin depletion in FES specimens as compared with controls.
  
  
  CONCLUSIONS
  The findings indicate that upregulation of elastolytic enzymes, most probably induced by repeated mechanical stress, participates in elastic fiber degradation and subsequent tarsal laxity and eyelash ptosis in FES.
authors.affiliation: Department of Ophthalmology, University of Erlangen-Nürnberg, Erlangen, Germany. ursula.schloetzer@augen.imed.uni-erlangen.de
authors.forename: Ursula
authors.initials: U
authors.lastname: Schlötzer-Schrehardt
authors.forename: Milenko
authors.initials: M
authors.lastname: Stojkovic
authors.forename: Carmen
authors.initials: C
authors.lastname: Hofmann-Rummelt
authors.forename: Claus
authors.initials: C
authors.lastname: Cursiefen
authors.forename: Friedrich E
authors.initials: FE
authors.lastname: Kruse
authors.forename: Leonard M
authors.initials: LM
authors.lastname: Holbach
mesh_terms: D000368:Aged; D001706:Biopsy; D002280:Basal Cell Carcinoma; D004547:Elastic Tissue / Q000201:enzymology / Q000648:ultrastructure; D004549:Elastin / Q000378:metabolism; D005141:Eyelid Diseases / Q000201:enzymology* / Q000473:pathology; D005142:Eyelid Neoplasms; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D053508:Matrix Metalloproteinase 12; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism; D008875:Middle Aged; D012189:Retrospective Studies; D013577:Syndrome
chemical_list: D004549:Elastin; D020782:Matrix Metalloproteinases; D008666:Metalloendopeptidases; D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12