Corneal Nerve Changes Observed by In Vivo Confocal Microscopy in Patients Receiving Oxaliplatin for Colorectal Cancer: The COCO Study

Abstract

An objective method of early identification of people at risk of chemotherapy-induced peripheral neuropathy is needed to minimize long-term toxicity and maximize dose intensity. The aims of the study were to observe corneal nerve microstructure and corneal sensitivity changes and peripheral neuropathy in patients receiving oxaliplatin, and to determine its association with corneal parameters at different stages of treatment and assess utility as non-invasive markers to detect and monitor peripheral neuropathy. Twenty-three patients scheduled to receive oxaliplatin chemotherapy with intravenous 5-FU for gastro-intestinal cancer were recruited and followed up with for 12 months. Ocular examinations including corneal and retinal evaluations, alongside peripheral neuropathy assessment, were performed. The corneal nerve density did not show significant change after chemotherapy when measured with a widely used semi-automated program or an automated analysis technique. Macula and optic nerve function did not change during or after oxaliplatin chemotherapy. However, the corneal nerve density modestly correlated with clinical peripheral neuropathy after 20 weeks of chemotherapy (r = 0.61, p = 0.01) when peripheral neuropathy is typical most profound, and corneal nerve sensitivity correlated with neuropathy at 12 (r = 0.55, p = 0.01) and 20 weeks (r = 0.64, p = 0.006). In conclusion, corneal changes detected on confocal microscopy show moderate association with peripheral neuropathy, indicating their potential to identify the development of oxaliplatin-induced peripheral neuropathy. However, further studies are required to confirm these findings.

In-vivo corneal confocal microscopy: Imaging analysis, biological insights and future directions

“…While deep learning algorithms continue to evolve and be developed to enhance nerve segmentation and evaluation, most are limited to research settings and require further validation before implementation in clinical practice 19 , 20 . A software using a customised deep learning-based approach known as deepNerve has recently been developed and used for animal and clinical human studies 21 , 22 , demonstrating the promising potential of artificial intelligence in this area.…”

A mechanistic understanding of the relationship between skin innervation and chemotherapy-induced neuropathic pain

“…Diagnostic sensitivity and several associations between the severity of intraepidermal nerve fiber loss, severity of NCS or QST abnormalities in oxaliplatin-treated patients vs. neurpathic pain were studied (8)(9)(10). Regarding CCM, different studies have shown corneal nerve microstructure and corneal sensitivity changes in patients receiving oxaliplatin (15). In addition, imaging of the corneal sub basal nerve plexus was reported as biomarker for nerve regeneration in CIPN (16).…”