Sir,

Corneal sub-basal nerve plexus morphology, epithelial, and stromal cellular changes in dry eye disease (DED) determined by in vivo confocal microscopy (IVCM) has been well documented. Despite a strong association between these changes to the severity of DED and its clinical relevance, its specific causal role towards DED pathogenesis is yet to be determined. In a recent report, Iaccheri B et al,1 have described favorable changes in cell density of the intermediate epithelium, sub-basal nerve features and keratocytes state by IVCM in DED patients over time who were on topical 0.05% cyclosporine ophthalmic emulsion treatment. These observations were in addition to decrease in DED signs and symptoms.1 The findings are clinically relevant and interesting indeed, especially with the IVCM assessments during follow-ups. However, it is important to point out a few observations regarding the IVCM analysis based on the representative images shown in Figure 2 in the report by Iaccheri B et al. The authors did point out the subtlety involved in IVCM imaging and analysis by referring to the importance of the unusual striking angles of the light rays from the confocal microscope that may influence the reflectivity of the cells and structures. Similarly, the depth and region of central cornea imaged will also greatly influence the analysis.2 Along with varied patterns, the penetration density of the nerve plexus is known to be lower in the area around and inferonasal to the corneal apex.2 Therefore, it is absolutely essential to ensure imaging at the same depth and region of central cornea during the follow-ups for a more accurate analysis. The other factor is with reference to corneal dendritic cell or Langerhans cell (cDC) density that is routinely assessed by IVCM. cDC density been well documented to be increased and associated with the severity of DED, and reduced during resolution of the disease.3, 4 It is rather unique not to observe cDC in the representative images nor in the IVCM findings of DED patients in the report by Iaccheri B et al. Combined corneal sub-basal nerve plexus morphology and cDC density changes are being used effectively in monitoring the resolution of DED.5