In Vivo Monitoring of Corneal Dendritic Cells in the Subbasal Nerve Plexus during Trastuzumab and Paclitaxel Breast Cancer Therapy—A One-Year Follow-Up

Abstract

Paclitaxel and trastuzumab have been associated with adverse effects including chemotherapy-induced peripheral neuropathy (CIPN) or ocular complications. In vivo confocal laser scanning microscopy (CLSM) of the cornea could be suitable for assessing side effects since the cornea is susceptible to, i.e., neurotoxic stimuli. The study represents a one-year follow-up of a breast cancer patient including large-area in vivo CLSM of the subbasal nerve plexus (SNP), nerve function testing, and questionnaires during paclitaxel and trastuzumab therapy. Six monitoring sessions (one baseline, four during, and one after therapy) over 58 weeks were carried out. Large-area mosaics of the SNP were generated, and identical regions within all sessions were assigned. While corneal nerve morphology did not cause alterations, the number of dendritic cells (DCs) showed dynamic changes with a local burst at 11 weeks after baseline. Simultaneously, paclitaxel treatment was terminated due to side effects, which, together with DCs, returned to normal levels as the therapy progressed. Longitudinal in vivo CLSM of the SNP could complement routine examinations and be helpful to generate a comprehensive clinical picture. The applied techniques, with corneal structures acting as biomarkers could represent a diagnostic tool for the objective assessment of the severity of adverse events and the outcome.

Corneal immune cells as a biomarker of inflammation in multiple sclerosis: a longitudinal study

“…Corneal dendritic cell density increased dramatically without corneal nerve alterations in a patient with breast cancer after 11 weeks of treatment with paclitaxel and trastuzumab 52 and then returned to baseline values after cessation of paclitaxel therapy. 53 In the present study, baseline NCF and NCP were higher in patients who switched disease-modifying treatment during follow-up and baseline NCP was higher in patients on interferon. In this context, we hypothesize that higher corneal IC density may reflect reduced treatment effectiveness against underlying inflammation.…”

Taxane-Induced Neuropathy and Its Ocular Effects—A Longitudinal Follow-up Study in Breast Cancer Patients

“…The experimental data confirmed that in vivo confocal microscopy is a helpful, non-invasive tool with promise for the diagnosis of CIPN [20]. However, at the present time, despite a case report [21], no prospective longitudinal studies which monitor breast cancer patients before, during, and after the course of chemotherapy exist for detecting corneal nerves by using advanced biophotonic techniques. In addition, currently, representative selections of CLSM images and valid image analyses are a challenge.…”

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

“…The most commonly used methodology in clinical research settings involves random selection of a set number of images with sufficient quality from a pool of images obtained from a participant's eye prior to analysis 33,34 . Sampling strategy of adequate images has been shown to produce sufficient accuracy, however for longitudinal or clinical monitoring purposes, real-time widefield imaging capabilities may provide more insight into regional changes in the cornea over time or following exposure to various stimuli 77,78 . In fact, a minimum repeatable area of 1.5 mm 2 is shown to have reliable morphological characterisation of the sub-basal nerve plexus 79,80 .…”