Abstract
Purpose:
Herpes zoster ophthalmicus (HZO), a unilateral disease, results in recurrent immune-mediated keratitis and neurotrophic keratopathy. This study aimed to analyze by laser in vivo confocal microscopy (IVCM) bilateral corneal immune cell as correlated to subbasal nerve changes in patients with HZO.
Methods:
A prospective, cross-sectional study was conducted in 24 patients with clinical diagnosis of HZO, their contralateral clinically unaffected eyes, and 24 normal age matched controls. IVCM (HRT3/RCM) and corneal sensation (Cochet-Bonnet) of the central cornea were performed bilaterally in all patients and controls. Confocal images were evaluated by 2 masked observers for the presence of dendritiform immune cells (DC), subbasal nerve density and numbers. For each variable, results for 3 frames were averaged, and analyzed utilizing ANOVA and Pearson’s correlation coefficient.
Results:
The mean DC density was significantly higher in patients with HZO (147.4±33.9cells/mm2;p<0.001) as compared to controls (23.0±3.6). Surprisingly, in the contralateral clinically unaffected eyes, DC density was significantly increased (120.1±21.2;p<0.001). Patients with immune-mediated keratitis at the time of the visit, had a 60% higher DC density than patients with no clinical keratitis. DC in HZO eyes showed a significant increase in number of dendrites (4.1±0.8 dendrites/cell) and were larger in size (232.4±47.4µm2) as compared to controls (2.3±0.5, 57.2±11.7;p<0.001). DC increase was correlated (R=-0.43,p<0.001) with diminishment in total nerve density (9052.6±1151.8, 14959.8±903.2, and 22851.4±661.4µm/mm2 respectively; p< 0.001), total number of nerves (5.8±0.9, 11.9±1.2, and 26.6±1.2n/frame;p<0.001), main trunks (2.4±0.3, 3.8±0.3, and 4.4±0.2;p<0.001), and branches (3.4±0.7, 8.2±1.1, and 22.2±1.2;p<0.001) as compared to controls. Further, reduction in nerves was strongly correlated with corneal sensation (p<0.05).
Conclusions:
Patients with unilateral HZO demonstrate a profound and significant bilateral increase in corneal DC as compared to controls, which is correlated to decrease in corneal subbasal nerve. The results may explain bilateral ocular surface disease observed in patients with HZO and suggest a direct interaction between the immune and nervous system in the cornea and a bilateral nerve and immune alteration in an apparently unilateral disease.
Keywords: 557 inflammation •
550 imaging/image analysis: clinical •
747 varicella zoster virus