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 mu m/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 mu m/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.