Dose-dependent neurotoxic chemotherapy and corneal nerve morphological changes

Chemotherapy-induced peripheral neuropathy (CIPN) is a common, serious, long-term complication of neurotoxic chemotherapy that alters nerve fibre morphology, and is one of the most common dose-limiting factors. Detection is challenging and usually occurs after significant symptoms. Thus, early and accurate detection is crucial.

CIPN accounts for the main dose-limiting factor in cancer treatment. Its early detection however is challenging and often occurs only after the development of significant symptoms. In-vivo corneal confocal microscopy may be a potential method of detecting early changes in CIPN. The aim of this study was to determine whether corneal nerve parameters enable early detection of CIPN, to report any dose-dependent effects of treatments used, and to observe longitudinally corneal nerve changes during and after treatment.

Fifteen individuals receiving taxane-based chemotherapy for breast, gynaecological, or prostate cancers were recruited and compared to an oxaliplatin-treated group (n = 18). Corneal nerve measurements were taken at the beginning, middle, and end of treatment, and up to 12 months post-treatment. Central corneal and inferior whorl nerve fibre images were obtained with an in-vivo laser scanning confocal microscope.

A dose-dependent reduction in corneal nerves was observed for every 100 mg/m² of neurotoxic chemotherapy, especially in taxane-treated participants (p = 0.02). The average nerve fibre length, which refers to both the central cornea and inferior whorl, showed significant changes earlier in the treatment course. After treatment, especially in the taxane-treated group, CIPN participants had lower corneal nerve fibre length at the middle and end of treatment compared to those without persistent neuropathy (p = 0.02 and p = 0.006, respectively).

Average nerve fibre length loss may have clinical utility as an early marker of CIPN progression. Imaging a wider area of the sub-basal corneal nerve plexus including the inferior whorl region may be more beneficial for monitoring early neuropathic changes.