Volume 37, July 2025, Pages 105-114Author links open overlay panelAnsa Anam a, Mingyi Yu b, Chang Liu b, Isabelle Xin Yu Lee b, Juanita Yang b, A.V. Shanmathi b, Ching-Yu Cheng c d e, Yu-Chi Liu b d f gShow moreHighlights•

Smoking reduces corneal nerve density, length, area, and fractal dimension.

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Longer smoking duration was significantly associated with worse corneal nerve status.

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Smokers had more swollen nerves and larger neuromas compared to non-smokers.

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Smokers had higher dendritic cell (DC) density and higher DC maturity than non-smokers.

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Smoking led to reduced tear break-up time and increased ocular surface staining.

AbstractPurpose

To evaluate the effects of smoking on ocular surface through comprehensive analysis of corneal nerves, corneal epithelium, dendritic cells (DCs), and clinical assessments.

Methods

This cross-sectional study included 250 healthy smokers and 272 healthy non-smokers. Patients’ smoking status and duration were recorded. In vivo confocal microscopy was performed to assess 7 quantitative corneal nerves parameters, 3 corneal neuroma parameters, 3 DCs parameters, and 3 epithelial parameters. Ocular surface evaluations included tear break-up time (TBUT), ocular surface and corneal staining, corneal sensitivity, and Schirmer test. Ocular Surface Disease Index questionnaire was used for symptom assessment.

Results

Compared to non-smokers, smokers exhibited significantly lower corneal nerve fiber density (CNFD), nerve branch density, nerve fiber length, nerve total branch density, corneal nerve fiber area (CNFA), and corneal nerve fractal dimension (CFracDim; all p < 0.001). Smokers also presented with a significantly swollen corneal nerve fiber (p < 0.001). Longer smoking duration was significantly associated with lower CNFD (β = −0.04, P = 0.010), lower CNFA (β = −0.00002, P = 0.033), and lower CFracDim (β = −0.0008, P = 0.016). Additionally, a significantly larger neuroma total area (p = 0.040), size (p < 0.001) and perimeter (p < 0.001), as well as a significantly higher DCs density (p < 0.001), DCs count (p = 0.003), and lower DCs elongation which suggested higher DCs maturity (p < 0.001), were observed in the smoking group. Smokers demonstrated significantly higher ocular surface staining scores (p < 0.001) and reduced TBUT (p = 0.001). Corneal epithelial circularity was borderline higher in the smoking subjects (p = 0.059).

Conclusions

Smoking is associated with significant alterations in corneal nerve morphology and quantity, increased immunological cells, and compromised ocular surface integrity.

Previous article in issueNext article in issueKeywords

Smoking

Cornea

Corneal nerves

Ocular surface

In vivo confocal microscopy

Neuroma

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© 2025 The Author(s). Published by Elsevier Inc.