title: Congenital ectropion uvea and mechanisms of glaucoma in neurofibromatosis type 1: new insights.
abstract: OBJECTIVE
  To describe the clinicopathologic features of congenital ectropion uvea associated with glaucoma in neurofibromatosis-1 (NF-1).
  
  
  METHODS
  Retrospective case series.
  
  
  METHODS
  Five cases of NF-1 associated with glaucoma, from which enucleated eyes were available, and 2 eye bank eyes used as controls.
  
  
  METHODS
  The clinical features and courses of these patients were reviewed. Formalin-fixed, paraffin-embedded eyes were examined by light and electron microscopy. Immunohistochemistry using antineurofibromin, anti-glial fibrillary acidic protein, and antivimentin was performed in 3 patients. Gene expression of the mitogen-activated protein kinase (MAPK) signaling pathway was examined in corneal endothelial cells in 1 patient.
  
  
  METHODS
  Cause of glaucoma in patients with ectropion uvea and NF-1.
  
  
  RESULTS
  The age of patients at the time of glaucoma diagnosis ranged from birth to 13 years. Four of the 5 patients had megalocornea and buphthalmos at presentation. Ectropion uvea was noted clinically in 2 patients, but was demonstrated histopathologically in all 5 patients. On histopathologic examination, all patients had varying degrees of angle closure secondary to endothelialization of the anterior chamber angle. Uveal neurofibromas were noted in all patients; anteriorly displaced ciliary processes were noted in 4 of 5 patients who demonstrated ciliary body involvement with neurofibromas. Absence of Schlemm's canal was observed. The endothelial cells lining the closed angle demonstrated positive stain results with the vimentin antibody. Positive antineurofibromin immunolabeling was detected in normal control corneal endothelium, but was absent in corneal endothelium in patients with endothelialization of the angle. Upregulation of genes from the MAPK signaling pathway was demonstrated in the corneal endothelial cells isolated from the NF-1 eyes.
  
  
  CONCLUSIONS
  Ectropion uvea in NF-1 glaucoma is secondary to endothelialization of the anterior chamber angle and is associated commonly with severe pediatric glaucoma in NF-1 patients. The endothelial cell proliferation may be related to overexpression of the Ras (Rat sarcoma)-MAPK genes in these eyes.
authors.affiliation: Department of Ophthalmology, Summa Health System, Akron, Ohio, USA. dedwar39@jhmi.edu
authors.forename: Deepak P
authors.initials: DP
authors.lastname: Edward
authors.forename: Jose
authors.initials: J
authors.lastname: Morales
authors.forename: Rachida A
authors.initials: RA
authors.lastname: Bouhenni
authors.forename: Jayaprakash
authors.initials: J
authors.lastname: Patil
authors.forename: Priya R
authors.initials: PR
authors.lastname: Edward
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Cummings
authors.forename: Imtiaz A
authors.initials: IA
authors.lastname: Chaudhry
authors.forename: Hind
authors.initials: H
authors.lastname: Alkatan
mesh_terms: D000293:Adolescent; D000869:Anterior Eye Segment / Q000378:metabolism / Q000473:pathology*; D004728:Endothelium, Corneal / Q000378:metabolism / Q000473:pathology; D015353:Eye Enucleation; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015812:Glaucoma, Angle-Closure / Q000209:etiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007499:Iris Diseases / Q000151:congenital*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics; D009456:Neurofibromatosis 1 / Q000150:complications*; D025542:Neurofibromin 1 / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D014746:Vimentin / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D025542:Neurofibromin 1; D014746:Vimentin; D020928:Mitogen-Activated Protein Kinases