Unilateral Herpes Zoster Ophthalmicus Results in Bilateral Corneal Nerve Alteration An In Vivo Confocal Microscopy Study

Purpose: Herpes zoster ophthalmicus (HZO), thought to be a unilateral disease, results in loss of corneal sensation, leading to neurotrophic keratopathy. This study aimed to analyze bilateral corneal nerve changes in patients with HZO by in vivo confocal microscopy (IVCM) and their correlation with corneal sensation as a measure of nerve function. Design: Prospective, cross-sectional, controlled, single-center study. Participants: Twenty-seven eyes with the diagnosis of HZO 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. 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: Eyes with herpes zoster ophthalmicus had a significant (P<0.001) decrease in total nerve length (595.8 +/- 358.1 vs. 2258.4 +/- 989.0 mu m/frame), total number of nerves (5.4 +/- 2.8 vs. 13.1 +/- 3.8), number of main nerve trunks (2.3 +/- 1.1 vs. 4.7 +/- 1.2), and number of nerve branches (3.2 +/- 2.3 vs. 8.4 +/- 3.7) as compared with controls. In the contralateral clinically unaffected eyes, total nerve length (1053.1 +/- 441.4 mu m/frame), total number of nerves (8.3 +/- 2.9), and main nerve trunks (3.1 +/- 1.0) also were decreased significantly as compared with controls (P<0.01). Reduced nerve density, total nerve count, main trunks, and tortuosity was correlated significantly with corneal sensation across all subgroups (P<0.001). Conclusions: Patients with unilateral HZO demonstrated a profound and significant bilateral loss of the corneal nerve plexus as compared with controls, demonstrating bilateral changes in a clinically unilateral disease. Loss of corneal sensation strongly correlated with subbasal nerve plexus alterations as shown by IVCM.