title: Corneal sensation and subbasal nerve alterations in patients with herpes simplex keratitis: an in vivo confocal microscopy study.
abstract: OBJECTIVE
  To study and correlate corneal sensation in patients with herpes simplex keratitis (HSK) with density and morphologic features of subbasal corneal nerves by in vivo confocal microscopy (IVCM).
  
  
  METHODS
  Prospective, cross-sectional, controlled, single-center study.
  
  
  METHODS
  Thirty-one eyes with the diagnosis of acute (n = 7) or chronic (n = 24) 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 Ophthalmlogie, 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 corneal nerve density, total nerve number, main nerve trunks, branching, and tortuosity were evaluated after IVCM and were correlated to corneal sensation, disease duration, and number of recurrences.
  
  
  RESULTS
  Herpes simplex keratitis eyes, as compared with controls, demonstrated significant (P < 0.001) decrease in mean nerve density (448.9 ± 409.3 vs. 2258.4 ± 989.0 μm/frame), total nerve number (5.2 ± 4.5 vs. 13.1 ± 3.8), main nerve trunks (2.3 ± 1.6 vs. 4.7 ± 1.2), and nerve branches (3.2 ± 4.3 vs. 9.8 ± 3.3). In contralateral unaffected eyes, mean nerve density (992.7 ± 465.0 μm/frame), total nerve number (7.8 ± 3.3), and branches (4.5 ± 2.3) were decreased significantly as compared with controls (P < 0.002). Reduced nerve density, total nerve count, and main trunks in HSK eyes were correlated significantly with corneal sensation across all subgroups (P < 0.001). Nerve density decreased within days of infection and was correlated to frequency of episodes in patients with HSK (P < 0.02).
  
  
  CONCLUSIONS
  In vivo confocal microscopy revealed that the loss of corneal sensation in HSK correlates strongly with profound diminishment of the subbasal nerve plexus after herpes simplex virus infection. Surprisingly, the contralateral, clinically unaffected eyes also demonstrated a diminishment of the subbasal nerve plexus as compared with normal subjects, revealing bilateral nerve alteration in an apparently unilateral disease.
authors.affiliation: Massachusetts Eye & Ear Infirmary, Cornea Service & Ocular Surface Imaging Center, Department of Ophthalmology, Harvard Medical School, Boston, Massachusett 02114, USA. pedram_hamrah@meei.harvard.edu
authors.forename: Pedram
authors.initials: P
authors.lastname: Hamrah
authors.forename: Andrea
authors.initials: A
authors.lastname: Cruzat
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Dastjerdi
authors.forename: Lixin
authors.initials: L
authors.lastname: Zheng
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: D000208:Acute Disease; D002908:Chronic Disease; D003315:Cornea / Q000294:innervation* / Q000503:physiopathology*; D003389:Cranial Nerve Diseases / Q000175:diagnosis*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D016849:Keratitis, Herpetic / Q000175:diagnosis*; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009412:Nerve Fibers; D009415:Nerve Net; D009882:Ophthalmic Nerve / Q000473:pathology*; D011446:Prospective Studies; D012677:Sensation / Q000502:physiology*; D016037:Single-Blind Method
references.citation: Cornea. 2001 May;20(4):374-84
references.pmid: 11333324
references.citation: J Exp Med. 2004 Nov 15;200(10):1347-58
references.pmid: 15545358
references.citation: Invest Ophthalmol Vis Sci. 2000 Sep;41(10):2915-21
references.pmid: 10967045
references.citation: Exp Eye Res. 2008 Jun;86(6):879-85
references.pmid: 18436208
references.citation: N Engl J Med. 1973 Mar 29;288(13):648-50
references.pmid: 4347057
references.citation: Invest Ophthalmol Vis Sci. 2000 Feb;41(2):393-7
references.pmid: 10670467
references.citation: J Neurol Sci. 1993 May;116(1):6-11
references.pmid: 8389816
references.citation: Br J Ophthalmol. 2007 Sep;91(9):1165-9
references.pmid: 17389741
references.citation: Ophthalmology. 2003 Mar;110(3):493-6
references.pmid: 12623810
references.citation: Invest Ophthalmol Vis Sci. 2003 Jun;44(6):2545-9
references.pmid: 12766055
references.citation: Invest Ophthalmol Vis Sci. 2007 Feb;48(2):621-6
references.pmid: 17251458
references.citation: Clin Exp Ophthalmol. 2002 Jun;30(3):187-90
references.pmid: 12010212
references.citation: Cornea. 2005 Jul;24(5):608-13
references.pmid: 15968170
references.citation: Invest Ophthalmol Vis Sci. 2004 Sep;45(9):3030-5
references.pmid: 15326117
references.citation: Curr Opin Ophthalmol. 2009 Jul;20(4):276-81
references.pmid: 19537364
references.citation: Arch Ophthalmol. 1989 Aug;107(8):1155-9
references.pmid: 2787981
references.citation: Br J Ophthalmol. 2009 Jul;93(7):853-60
references.pmid: 19019923
references.citation: Science. 1972 Oct 20;178(4058):306-7
references.pmid: 4342752
references.citation: Diabetologia. 2003 May;46(5):683-8
references.pmid: 12739016
references.citation: Eur J Ophthalmol. 2008 Nov-Dec;18(6):994-7
references.pmid: 18988174
references.citation: Invest Ophthalmol Vis Sci. 2004 Nov;45(11):3991-6
references.pmid: 15505047
references.citation: Cornea. 2009 Aug;28(7):735-40
references.pmid: 19574916
references.citation: Cont Lens Anterior Eye. 2005 Dec;28(4):185-92
references.pmid: 16332504
references.citation: Eye (Lond). 2005 Dec;19(12):1276-9
references.pmid: 15550934
references.citation: Invest Ophthalmol Vis Sci. 2006 Apr;47(4):1348-51
references.pmid: 16565367
references.citation: Invest Ophthalmol Vis Sci. 2007 Jan;48(1):173-81
references.pmid: 17197530
references.citation: Cornea. 2001 Jan;20(1):1-13
references.pmid: 11188989
references.citation: Eye (Lond). 2009 Mar;23(3):586-92
references.pmid: 18344958
references.citation: Ger J Ophthalmol. 1996 Nov;5(6):513-7
references.pmid: 9479548
references.citation: Cornea. 2002 Apr;21(3):265-9
references.pmid: 11917174
references.citation: Invest Ophthalmol Vis Sci. 2005 Dec;46(12):4485-8
references.pmid: 16303938
references.citation: Am J Ophthalmol. 2005 Dec;140(6):1059-1064
references.pmid: 16376651
references.citation: Invest Ophthalmol Vis Sci. 1999 Feb;40(2):513-9
references.pmid: 9950612
references.citation: Br J Ophthalmol. 1981 Jun;65(6):385-7
references.pmid: 7260008