INTRODUCTION: Unilateral herpes zoster ophthalmicus (HZO) results in bilateral corneal denervation in patients with corneal involvement, which correlates with corneal sensation loss. The study aimed to analyze bilateral corneal nerve changes in patients with acute unilateral HZO and no keratitis compared with healthy controls. METHODS: This was a prospective, single-center study. Using in vivo confocal microscopy (IVCM) and an automatized single image analysis software (ACCmetrics, University of Manchester, UK), seven corneal nerve parameters, including corneal nerve fiber density (CNFD
no/mm RESULTS: Forty-six patients with HZO and 49 controls were recruited and compared. In the HZO group, ipsilateral and contralateral eyes presented a significant decrease (p <
0.001) in all seven IVCM parameters compared with controls: CNFD (13.25 ± 5.23 and 15.24 ± 4.70 vs. 23.54 ± 6.54), CNBD (14.67 ± 9.03 and 16.59 ± 7.98 vs. 31.72 ± 17.89), CNFL (8.42 ± 2.83 and 9.06 ± 2.69 vs. 13.08 ± 4.02), CTBD (27.11 ± 13.71 and 23.58 ± 12.69 vs. 46.88 ± 24.90), CNFA (0.0044 ± 0.002 and 0.0042 ± 0.001 vs. 0.0056 ± 0.002), CNFW (0.0213 ± 0.003 and 0.0221 ± 0.003 vs. 0.0222 ± 0.001) and CFracDim (1.39 ± 0.06 and 1.38 ± 0.06 vs. 1.45 ± 0.05). In the ipsilateral HZO eye group, a positive Hutchinson sign or a reduced corneal sensitivity was associated with more extensive corneal denervation. A significant negative correlation was found between patient age and CNFD (rho = - 0.312, p <
0.002), CNFL (rho = - 0.295, p = 0.004), and CFracDim (rho = - 0.284, p = 0.005). CONCLUSIONS: Unilateral HZO in patients without apparent keratitis leads to bilateral subbasal nerve plexus alteration in the early days after disease onset, especially in those with a positive Hutchinson sign. Early follow-up of patients with HZO and bilateral application of preservative-free artificial tears during the initial months of symptom onset may help reduce the risk of developing neurotrophic keratopathy (NTK).