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

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.

Precision, agreement and utility of a contemporary non-contact corneal aesthesiometer.

BACKGROUND: The measurement of corneal sensitivity threshold is important for several ocular surface diseases. The current study assesses the precision, agreement and utility of corneal sensitivity threshold measurement using a new, purpose-built non-contact corneal aesthesiometer. METHODS: A new instrument and an established non-contact corneal aesthesiometer device was used to measure the corneal sensitivity threshold on the right eye of 40 healthy human participants. Exclusion criteria included: corneal pathology, previous ocular surgery, ocular trauma, contact lens wear, diabetes or peripheral neuropathy. A forced-response, double-staircase method was used to obtain corneal sensitivity threshold from the mean of three readings per participant, for each non-contact corneal aesthesiometer. Screen demarcations relative to the corneal limbus facilitated alignment with the new device. Repeatability of the new instrument was tested three consecutive times on the same day. Intra-observer and inter-observer reproducibility and agreement were determined using one-way analysis of variance or analysis of variance and Bland-Altman analysis, respectively. RESULTS: Forty eyes of 40 participants were assessed (15:25 M:F, 30.5 ± 11.4 years). The new instrument demonstrated good repeatability (p = 0.47). There was no difference in the mean corneal sensitivity threshold between the new (0.60 ± 0.36 mbar) and established (0.60 ± 0.34 mbar) aesthesiometers (p = 0.92). Utilising the new instrument, inter-observer reproducibility (on a different subset of 10 participants) yielded thresholds of 0.41 ± 0.16 mbar and 0.42 ± 0.13 mbar (p = 0.88) for the two observers. Bland-Altman analysis confirmed good intra and inter-observer agreement. Screen demarcations relative to the limbus, enabled easier corneal alignment. CONCLUSION: The new non-contact corneal aesthesiometer confirmed very good repeatability and reproducibility, as well as good agreement with the long-established instrument. Overall, this contemporary approach enables accurate and precise assessment of corneal sensitivity and thus, corneal nerve function, in normal and diseased cornea.