A Cross-Sectional Study of Sub-Basal Corneal Nerve Reduction Following Neurotoxic Chemotherapy

Jeremy Chung Bo Chiang*, David Goldstein, Terry Trinh, Kimberley Au, David Mizrahi, Mark Muhlmann, Philip Crowe, Siobhan O’Neill, Katie Edwards, Susanna B. Park, Arun V. Krishnan, Maria Markoulli

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Purpose: Sub-basal corneal nerves have been shown to change during neuro-toxic chemotherapy treatment. This cross-sectional study investigated corneal nerve morphology in patients who have completed neurotoxic chemotherapy well after treatment cessation and its association with peripheral nerve function. Methods: Central corneal nerve fiber length (CNFL) and inferior whorl length (IWL), average nerve fiber length (ANFL), corneal nerve fiber density (CNFD) and corneal nerve branch density (CNBD), and nerve fiber area (CNFA) were examined using in vivo corneal confocal microscopy in patients with cancer who had completed treatment with either paclitaxel or oxaliplatin between 3 and 24 months prior to assessment in comparison with 2 separate groups of healthy controls. Neurological assessments were conducted including clinician-and patient-reported outcomes, and neurological grading scales. Results: Both paclitaxel-(n = 40) and oxaliplatin-treated (n = 30) groups had reduced IWL and ANFL compared to the respective healthy control groups (n = 15 in each group) (paclitaxel: IWL = P = 0.02, ANFL = P = 0.009; and oxaliplatin: IWL = P = 0.008, ANFL P = 0.02). CNFL and CNFD reduction were observed only in the paclitaxel-treated group compared with healthy controls (P = 0.008 and P = 0.02, respectively), whereas CNFA was reduced in the oxaliplatin-treated group (P = 0.04). IWL reduction correlated with worse fine hand dexterity in chemotherapy-treated patients (r =−0.33, P = 0.007). Conclusions: There is evidence of corneal nerve loss in patients with cancer who have been treated with paclitaxel and oxaliplatin well after treatment cessation associated with worse upper limb function. Translational Relevance: Sub-basal corneal nerve reduction is evident even after cessation of neurotoxic treatment. In vivo corneal confocal microscopy may be useful in the monitoring of nerve function in patients receiving chemotherapy.

Original languageEnglish
Article number24
Number of pages11
JournalTranslational Vision Science and Technology
Issue number1
Publication statusPublished - 12 Jan 2021

Bibliographical note

Copyright © 2021, The Authors. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License [https://creativecommons.org/licenses/by-nc-nd/4.0/]

Funding Information:
Supported by an Australian Government Research Training Program (RTP) Scholarship awarded by UNSW Sydney to JCB Chiang. This study was supported by a Cancer Institute NSW Program Grant (14/TPG/1-05) and a National Health and Medical Research Council of Australia (NHMRC) Project Grant (1080521). S.B. Park is supported by an NHMRC Career Development Fellowship (1148595).


  • Chemotherapy-induced peripheral neuropathy
  • Corneal nerves
  • In-vivo corneal confocal microscopy
  • Inferior whorl
  • Neurotoxic chemotherapy


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