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Updated: Mar 2, 2026

In Vivo Confocal Microscopy in the Diagnosis and Management of Dry Eye: A Focus on Imaging Protocols and Interpretation
Published on: November 11, 2025
Correlation between corneal innervation and inflammation evaluated with confocal microscopy and symptomatology in
Tudor C Tepelus1,2, Gloria B Chiu3, Jianyan Huang1,2
1Doheny Image Reading Center, Doheny Eye Institute, 1355 San Pablo Street, DVRC 211, Los Angeles, CA, 90033, USA.
Purpose:
To evaluate corneal innervation and inflammatory cell infiltration using in vivo confocal microscopy (IVCM) and to correlate these findings with subjective symptoms of dry eye, as measured by the Ocular Surface Disease Index (OSDI) in patients with non-Sjögren's (NSDE) and Sjögren's syndrome dry eyes (SSDE).
Methods:
Central corneal images were prospectively captured from 10 age-matched healthy control eyes, 24 eyes with clinically diagnosed NSDE and 44 eyes with clinically diagnosed SSDE, using IVCM (HRT III RCM). Density, tortuosity and reflectivity of corneal nerves, presence of inflammatory dendritic cells (DCs) and OSDI scores were evaluated.
Results:
Images obtained by IVCM from 78 eyes were analyzed. The density of nerve fibers was 1562 ± 996 μm/frame in the SSDE group, 2150 ± 1015 μm/frame in the NSDE group and 2725 ± 687 μm/frame in the control group (P < 0.05, ANOVA). In comparison to the control group, the density of nerve fibers was decreased in the SSDE (P < 0.001) and the NSDE groups (P = 0.06), with increased nerve tortuosity and decreased reflectivity in both groups (both P < 0.05). The density of DCs was 71.65 ± 72.54 cells/mm2 in the SSDE group, 40.33 ± 31.63 cells/mm2 in the NSDE group and 27.53 ± 5.58 cells/mm2 in the control group (P < 0.05, ANOVA). In comparison to the control group, the density of DCs was increased in the SSDE (P < 0.001) and the NSDE groups (P = 0.07). Significant correlations were found between the nerve density and DC density (r = -0.57, P < 0.001), between the nerve density and OSDI scores (r = -0.91, P < 0.001) and between the nerve reflectivity and OSDI scores (r = -0.75, P < 0.001).
Conclusions:
The corneas of eyes affected with NSDE and SSDE are characterized by alterations in corneal innervation and infiltration of inflammatory DCs. Corneal nerve density and reflectivity are correlated with severity of subjective dry eye symptoms, as measured by OSDI score.
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