Corneal Nerve Alterations and Sensory Deficits in Unilateral Noninfectious Anterior Uveitis: A Cross-Sectional Study

Highlight

• Unilateral noninfectious anterior uveitis (AU) leads to significant reduction in corneal sensitivity in affected eyes assessed via non-contact and Cochet-Bonnet aesthesiometers.
• In vivo confocal microscopy revealed substantial corneal subbasal nerve plexus abnormalities in affected eyes, including decreased nerve fiber length and density.
• Contralateral clinically unaffected eyes also exhibited subtle but measurable corneal nerve alterations and higher nerve sensitivity thresholds compared to healthy controls.

Study Background

Anterior uveitis (AU) is an inflammatory condition primarily affecting the anterior chamber of the eye, often causing ocular pain, redness, and photophobia. While the pathogenesis is largely immune-mediated and noninfectious in many cases, its impact on the corneal nerve anatomy and sensory function has been under-investigated. Corneal nerves play a crucial role in maintaining corneal health, sensation, and reflex tearing. Abnormalities in this plexus can contribute to ocular surface disease and persistent symptoms. Understanding nerve alterations in AU can elucidate disease mechanisms and potentially guide therapeutic approaches.

Study Design

This cross-sectional investigation enrolled 82 patients with unilateral noninfectious anterior uveitis. Three groups were defined: affected eyes, clinically unaffected contralateral eyes of these patients, and eyes from 25 healthy control subjects. Corneal sensitivity was quantified first by a non-contact corneal aesthesiometer (NCCA) and then by the Cochet-Bonnet aesthesiometer (CBA), two complementary methods assessing tactile sensitivity thresholds.

Corneal subbasal nerve plexus morphology was assessed using in vivo confocal microscopy (IVCM), employing ACCMetrics software for objective quantification of parameters such as corneal nerve fiber length (CNFL), nerve fiber density (CNFD), and fractal dimension (CFracDim). A masked observer evaluated inflammatory cell density within the central cornea and counted microneuromas, which serve as markers for nerve injury or regeneration. Patients were further subclassified based on anterior chamber cell grade and treatment status for exploratory subgroup analyses.

Key Findings

The study demonstrated that eyes affected by AU had significantly elevated threshold values on the NCCA indicating reduced corneal sensitivity compared with both contralateral unaffected eyes and healthy controls (β = 0.97 and 0.48 respectively, adjusted p < 0.001). Similarly, CBA confirmed diminished corneal touch thresholds in AU-affected eyes.

In vivo confocal microscopy showed marked decreases in corneal nerve parameters, most notably CNFL which dropped by an adjusted β of -6.09 compared to controls (95% CI -7.44 to -4.74, p < 0.001), indicating substantial nerve fiber loss or damage. CNFD and fractal dimension were also reduced, reflecting a simplification and loss of nerve network complexity.

Inflammatory cell density and microneuroma counts, indicative of neuroinflammation and reparative nerve changes, were significantly increased in affected eyes relative to controls. Critically, the contralateral clinically unaffected eyes also exhibited intermediate changes: raised NCCA thresholds, decreased CNFL, CNFD, and fractal dimension, and elevated microneuroma counts compared to healthy eyes, albeit less pronounced than affected eyes.

These findings suggest that unilateral AU is associated not only with overt clinical inflammation and nerve damage in one eye but also with bilaterally detectable subclinical corneal nerve alterations.

Expert Commentary

This study robustly extends previous evidence on ocular surface nerve changes in inflammatory eye diseases by combining objective nerve morphology quantification with corneal sensitivity testing. The use of both non-contact and contact aesthesiometers strengthens the functional assessment.

The bilateral involvement—even in clinically unaffected eyes—raises important questions about systemic or contralateral effects of unilateral AU, possibly mediated by immune mechanisms or neural crosstalk. It also suggests that clinician evaluation of presumed unaffected eyes in AU patients may warrant detailed ocular surface assessment, especially in persistent or recurrent cases.

Limitations include the cross-sectional design, which precludes causal inference, and lack of longitudinal follow-up to determine nerve recovery after inflammation resolution. Additionally, stratification by treatment status was exploratory, and larger cohorts are needed for definitive subgroup analyses.

Future research should explore the mechanistic basis of these contralateral changes, their clinical implications for symptomatology and management, and the potential for nerve-targeted therapies in uveitis-related ocular surface complications.

Conclusion

Unilateral noninfectious anterior uveitis leads to significant corneal nerve dysfunction and morphological abnormalities detectable by confocal microscopy and sensitivity testing. Importantly, subclinical alterations also affect the contralateral eye, underscoring possible systemic neural or immune interactions. These insights enhance understanding of uveitis pathophysiology and highlight the need for comprehensive ocular surface evaluation in affected patients.

Funding and Clinical Trials

This study did not report specific funding sources or clinical trial registration information.

References

• Zhou Y, Lin L, Dai M, et al. Corneal sensitivity changes and nerve plexus abnormalities in noninfectious anterior uveitis. Am J Ophthalmol. 2026 Jul 1; PMID: 42385927.
• Benitez-Del-Castillo JM, Acosta MC, Iradier T, et al. Corneal subbasal nerve alterations in anterior uveitis assessed by in vivo confocal microscopy. Invest Ophthalmol Vis Sci. 2019;60(3):918-923.
• Labbe A, Liang H, Wang Z, et al. Corneal nerve plexus alterations in ocular surface diseases. J Ophthalmol. 2017;2017:6928371.
• Keratitis and corneal sensitivity changes in autoimmune eye diseases: a review and clinical implications. Clin Exp Ophthalmol. 2022;50(4):408-419.