title: Pathology of Internal Limiting Membrane Specimens Following Intravitreal Injection of Ocriplasmin.
abstract: OBJECTIVE
  To describe ultrastructure and immunocytochemistry of internal limiting membrane peelings after unsuccessful treatment with ocriplasmin, to compare with untreated eyes, and to correlate with clinical imaging data.
  
  
  METHODS
  Interventional comparative case series.
  
  
  METHODS
  Internal limiting membrane specimens were removed from 10 eyes with small macular holes and vitreomacular traction during vitrectomy after intravitreal ocriplasmin injection without release of traction or closure of macular holes during follow-up. Based on optical coherence tomography analysis, specimens from 10 other eyes without ocriplasmin treatment served as controls. All specimens were processed as flat mounts for phase-contrast microscopy followed by immunolabeling for fluorescence microscopy and embedding in epoxy resin with serial sectioning for transmission electron microscopy.
  
  
  RESULTS
  Despite the absence of contractive epiretinal membranes on optical coherence tomography, we found epiretinal cells and vitreous collagen fibrils on the internal limiting membrane in specimens removed from eyes with and without previous pharmacologic vitreolysis. Immunolabeling revealed glial cells and hyalocytes in macular holes, whereas myofibroblasts were predominant in vitreomacular traction. There was no apparent damage of the vitreoretinal interface after unsuccessful pharmacologic vitreolysis compared to untreated controls.
  
  
  CONCLUSIONS
  Epiretinal cell proliferation and vitreous collagen fibrils with close adhesions to the internal limiting membrane are not always detectable by optical coherence tomography or may not have been recognized. Since they are associated with unsuccessful ocriplasmin treatment, presence and topography of epiretinal cells and vitreous collagen remnants on the internal limiting membrane should be further elucidated in order to refine criteria and indications for case selection in pharmacologic vitreolysis.
authors.affiliation: Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany. Electronic address: ricarda.schumann@med.uni-muenchen.de.
authors.forename: Ricarda G
authors.initials: RG
authors.lastname: Schumann
authors.affiliation: Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Wolf
authors.affiliation: Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Wolfgang J
authors.initials: WJ
authors.lastname: Mayer
authors.affiliation: Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Compera
authors.affiliation: Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Hagenau
authors.affiliation: Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Jean
authors.initials: J
authors.lastname: Ziada
authors.affiliation: Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Anselm
authors.initials: A
authors.lastname: Kampik
authors.affiliation: Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Christos
authors.initials: C
authors.lastname: Haritoglou
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001485:Basement Membrane / Q000648:ultrastructure; D015415:Biomarkers / Q000378:metabolism; D019773:Epiretinal Membrane / Q000378:metabolism / Q000473:pathology*; D005128:Eye Diseases / Q000188:drug therapy* / Q000601:surgery; D005260:Female; D005341:Fibrinolysin / Q000008:administration & dosage*; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage*; D012164:Retinal Diseases / Q000188:drug therapy* / Q000601:surgery; D012167:Retinal Perforations / Q000188:drug therapy* / Q000601:surgery; D041623:Tomography, Optical Coherence; D014821:Vitrectomy; D014822:Vitreous Body / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D005343:Fibrinolytic Agents; D010446:Peptide Fragments; C054561:microplasmin; D005341:Fibrinolysin