Corneal sensation and subbasal nerve alterations in patients with herpes simplex keratitis: an in vivo confocal microscopy study.

PURPOSE 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). DESIGN Prospective, cross-sectional, controlled, single-center study. PARTICIPANTS 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. MAIN OUTCOME MEASURES 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.

[1]  W. Petroll,et al.  Effect of myopic LASIK on corneal sensitivity and morphology of subbasal nerves. , 2000, Investigative ophthalmology & visual science.

[2]  D. Patel,et al.  Corneal Sensitivity and Slit Scanning In Vivo Confocal Microscopy of the Subbasal Nerve Plexus of the Normal Central and Peripheral Human Cornea , 2009, Cornea.

[3]  C. McGhee,et al.  Laser scanning in vivo confocal microscopy and quantitative aesthesiometry reveal decreased corneal innervation and sensation in keratoconus , 2009, Eye.

[4]  T. Nishida,et al.  Advances in treatment for neurotrophic keratopathy , 2009, Current opinion in ophthalmology.

[5]  I. Messaoudi,et al.  Age-related CD8 T Cell Clonal Expansions Constrict CD8 T Cell Repertoire and Have the Potential to Impair Immune Defense , 2004, The Journal of experimental medicine.

[6]  A. Balestrazzi,et al.  In Vivo Confocal Microscopy in Bilateral Herpetic Keratitis: A Case Report , 2008, European journal of ophthalmology.

[7]  N Efron,et al.  Morphology of Corneal Nerves Using Confocal Microscopy , 2001, Cornea.

[8]  J. García-Sánchez,et al.  An in vivo confocal masked study on corneal epithelium and subbasal nerves in patients with dry eye. , 2004, Investigative ophthalmology & visual science.

[9]  E. Lignitz,et al.  Age distribution of latent herpes simplex virus 1 and varicella-zoster virus genome in human nervous tissue , 1993, Journal of the Neurological Sciences.

[10]  K. Wilhelmus,et al.  Bilateral herpetic keratitis. , 1981, The British journal of ophthalmology.

[11]  M. C. Acosta,et al.  Measurement of corneal sensitivity to mechanical and chemical stimulation with a CO2 esthesiometer. , 1999, Investigative ophthalmology & visual science.

[12]  T. Tervo,et al.  In Vivo Confocal Microscopy After Herpes Keratitis , 2002, Cornea.

[13]  I. Immonen,et al.  Corneal structure and sensitivity in type 1 diabetes mellitus. , 2000, Investigative ophthalmology & visual science.

[14]  L. Melton,et al.  Epidemiology of ocular herpes simplex. Incidence in Rochester, Minn, 1950 through 1982. , 1989, Archives of ophthalmology.

[15]  J. Baringer,et al.  Recovery of herpes-simplex virus from human trigeminal ganglions , 1973 .

[16]  T. Liesegang.  Herpes Simplex Virus Epidemiology and Ocular Importance , 2001, Cornea.

[17]  C. O'donnell,et al.  An evaluation of corneal nerve morphology and function in moderate keratoconus. , 2005, Contact lens & anterior eye : the journal of the British Contact Lens Association.

[18]  Dipika V Patel,et al.  Mapping the corneal sub-basal nerve plexus in keratoconus by in vivo laser scanning confocal microscopy. , 2006, Investigative ophthalmology & visual science.

[19]  M. C. Acosta,et al.  Relation between corneal innervation with confocal microscopy and corneal sensitivity with noncontact esthesiometry in patients with dry eye. , 2007, Investigative Ophthalmology and Visual Science.

[20]  E. Holland,et al.  Bilateral herpetic keratoconjunctivitis. , 2003, Ophthalmology.

[21]  Y. Konttinen,et al.  Corneal innervation and morphology in primary Sjögren's syndrome. , 2003, Investigative ophthalmology & visual science.

[22]  A. Wree,et al.  Epithelial Innervation of Human Cornea: A Three-Dimensional Study Using Confocal Laser Scanning Fluorescence Microscopy , 2005, Cornea.

[23]  C. McGhee,et al.  Corneal innervation and cellular changes after corneal transplantation: an in vivo confocal microscopy study. , 2007, Investigative ophthalmology & visual science.

[24]  Dipika V Patel,et al.  Mapping of the normal human corneal sub-Basal nerve plexus by in vivo laser scanning confocal microscopy. , 2005, Investigative ophthalmology & visual science.

[25]  C. McGhee,et al.  In vivo confocal microscopy of human corneal nerves in health, in ocular and systemic disease, and following corneal surgery: a review , 2008, British Journal of Ophthalmology.

[26]  Y. Konttinen,et al.  Alterations in corneal sensitivity and nerve morphology in patients with primary Sjögren's syndrome. , 2008, Experimental eye research.

[27]  C. McGhee,et al.  Assessing the sub‐basal nerve plexus of the living healthy human cornea by in vivo confocal microscopy , 2002, Clinical & experimental ophthalmology.

[28]  C. Yee,et al.  Herpesvirus hominis: Isolation from Human Trigeminal Ganglion , 1972, Science.

[29]  A. Elhan,et al.  Morphology of corneal nerves and corneal sensation in dry eye: a preliminary study , 2005, Eye.

[30]  C. McGhee,et al.  Age-related differences in the normal human cornea: a laser scanning in vivo confocal microscopy study , 2007, British Journal of Ophthalmology.

[31]  J. McLaren,et al.  Recovery of corneal subbasal nerve density after PRK and LASIK. , 2005, American journal of ophthalmology.

[32]  J. McLaren,et al.  Corneal reinnervation after LASIK: prospective 3-year longitudinal study. , 2004, Investigative ophthalmology & visual science.

[33]  R. A. Malik,et al.  Corneal confocal microscopy: a non-invasive surrogate of nerve fibre damage and repair in diabetic patients , 2003, Diabetologia.

[34]  R. Guthoff,et al.  Corneal reinnervation following penetrating keratoplasty--correlation of esthesiometry and confocal microscopy. , 1996, German journal of ophthalmology.