Tear glucose analysis for the noninvasive detection and monitoring of diabetes mellitus

One approach to the noninvasive monitoring of blood glucose concentration is to monitor glucose concentrations in tear fluid. While several methods for sensing glucose in tear fluid have been proposed, controversy remains as to the precise concentrations of tear glucose in normal and diabetic subjects and as to whether tear fluid glucose concentrations correlate with blood glucose concentrations. This review covers the present understanding of the physiology of glucose transport in tears, the regulation of the aqueous tear fraction, and studies of tear glucose concentration over the last 80 years. The various tear collection methods employed greatly influence the measured tear glucose concentrations. Studies that involve mechanical irritation of the conjunctiva during sampling measure the highest tear glucose concentrations, while studies that avoid tear stimulation measure the lowest concentrations. Attempts to monitor tear glucose concentration in situ by using contact lens-based sensing devices are discussed, and new observations are presented of tear glucose concentration obtained by a method designed to avoid tear stimulation. These studies indicate the importance of the sampling method in determining tear glucose concentrations. On the basis of these results, we discuss the future of in vivo tear glucose sensing and outline the studies needed to resolve the remaining questions about the relationship between tear and blood glucose concentrations.