title: Cellular changes of the corneal epithelium and stroma in herpes simplex keratitis: an in vivo confocal microscopy study.
abstract: OBJECTIVE
  To analyze the morphologic features of corneal epithelial cells and keratocytes by in vivo confocal microscopy in patients with herpes simplex keratitis (HSK) as associated with corneal innervation.
  
  
  METHODS
  Prospective, cross-sectional, controlled, single-center study.
  
  
  METHODS
  Thirty-one eyes with the diagnosis HSK and their contralateral clinically unaffected eyes were studied and compared with normal controls (n = 15).
  
  
  METHODS
  In vivo confocal microscopy (Confoscan 4; Nidek Technologies, Gamagori, Japan) and corneal esthesiometry (Cochet-Bonnet; Luneau Ophthalmologie, Chartres, France) of the central cornea were performed bilaterally in all patients and controls. Patients were grouped into normal (>5.5 cm), mild (>2.5-5.5 cm), and severe (<2.5 cm) loss of sensation.
  
  
  METHODS
  Changes in morphologic features and density of the superficial and basal epithelial cells, as well as stromal keratocytes, were assessed by 2 masked observers. Changes were correlated to corneal sensation, number of nerves, and total length of nerves.
  
  
  RESULTS
  There was a significant and gradual decrease in the density of superficial epithelial cells in HSK eyes, with 852.50 ± 24.4 cells/mm(2) in eyes with severe sensation loss and 2435.23 ± 224.3 cells/mm(2) in control eyes (P = 0.008). Superficial epithelial cell size was 2.5-fold larger in HSK eyes (835.3 μm(2)) compared with contralateral or normal eyes (407.4 μm(2); P = 0.003). A significant number of hyperreflective desquamating superficial epithelial cells were present in HSK eyes with normal (6.4%), mild (29.1%), and severe (52.2%) loss of sensation, but were absent in controls. The density of basal epithelial cells, anterior keratocytes, and posterior keratocytes did not show statistical significance between patients and controls. Changes in superficial epithelial cell density and morphologic features correlated strongly with total nerve length, number, and corneal sensation. Scans of contralateral eyes did not show any significant epithelial or stromal changes compared with controls.
  
  
  CONCLUSIONS
  In vivo confocal microscopy reveals profound HSK-induced changes in the superficial epithelium, as demonstrated by increase in cell size, decrease in cell density, and squamous metaplasia. This study demonstrated that these changes correlate strongly with changes in corneal innervation.
authors.affiliation: Ocular Surface Imaging Center, Cornea Service, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA. pedram_hamrah@meei.harvard.edu
authors.forename: Pedram
authors.initials: P
authors.lastname: Hamrah
authors.forename: Afsun
authors.initials: A
authors.lastname: Sahin
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Dastjerdi
authors.forename: Bashar M
authors.initials: BM
authors.lastname: Shahatit
authors.forename: Hasan A
authors.initials: HA
authors.lastname: Bayhan
authors.forename: Reza
authors.initials: R
authors.lastname: Dana
authors.forename: Deborah
authors.initials: D
authors.lastname: Pavan-Langston
mesh_terms: D002452:Cell Count; D048429:Cell Size; D003315:Cornea / Q000294:innervation; D060527:Corneal Keratocytes / Q000473:pathology*; D003319:Corneal Stroma / Q000473:pathology*; D003389:Cranial Nerve Diseases / Q000473:pathology; D003430:Cross-Sectional Studies; D019573:Epithelium, Corneal / Q000473:pathology*; D005260:Female; D006801:Humans; D016849:Keratitis, Herpetic / Q000473:pathology*; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009882:Ophthalmic Nerve / Q000473:pathology; D011446:Prospective Studies