Raman spectroscopy to investigate early biochemical alterations in human tears caused by contact lenses

Clinical relevance: The interaction between contact lenses and tear film plays a critical role in lens biocompatibility and can influence discomfort during wear. Early detection of biochemical changes is important for improving ocular surface health, preventing complications, and developing advanced lens materials to enhance long-term comfort. Background: The pursuit of biocompatible lens materials requires a thorough understanding of their interaction with tear environment. The aim of this study is to evaluate different approaches to investigate early alterations in tear biomolecular profiles induced by lens wear. Methods: Two participants wore different CLs and underwent ocular analysis before CL insertion (T0), after 2-hour wear (T2), and two hours after removing the CL (T4), evaluating non-invasive tear break-up time (NIBUT), tear meniscus height (TMH), and osmolarity. Forty CLs were used. At the same time points, tears were collected and analysed by Raman spectroscopy. Results: Tear film stability, as measured by NIBUT, decreased post-lens wear (T0 vs T2, p = 0.034 and 0.025 for S1 and S2, respectively) but showed recovery within 2 hours (T0 vs T4, p > 0.05 for both S1 and S2), while TMH and osmolarity remained unchanged (T0 vs T2 vs T4, p > 0.05 for both S1 and S2). Raman spectroscopy highlighted notable changes in the biomolecular profile of tears after lens wear, particularly in the 2700-3200 cm(-1) spectral window related to C-H stretching, which is sensitive to CH, CH2 and CH3 groups, their functional chemistry group, and the surrounding microenvironment. Conclusions: Contact lens wear induces subtle biochemical, subclinical alterations in tears that can be detected early by Raman spectroscopy. The method is promising for analysing the subject-specific responses to lenses, also with possible individual variability in the timing of these changes. In addition, this approach can provide insights for designing biocompatible materials and for the early detection of subclinical biomarkers.