Self-monitoring of tear glucose: the development of a tear based glucose sensor as an alternative to self-monitoring of blood glucose.

Tear glucose sensing for diabetes management has long been sought as an alternative to more invasive self-monitoring of blood glucose (SMBG). However, tear glucose sensors were known to have limitations, including correlation issues with blood glucose due to low sample volume, low concentration of glucose in the tear fluid, and evaporation of the tear sample. An engineering design approach to solve these problems led to the development of an integrated device capable of collecting the tear sample from the ocular surface with little to no stress on the eye, with an extremely low limit of detection, broad dynamic range, and rapid detection and analysis of sample. Here we present the development of a prototypical self-monitoring of tear glucose (SMTG) sensor, summarizing bench studies on the enzymes and their specificity, the development of the fluid capture device and its manufacture and performance and results of system testing in an animal study where safety, lag time and tear glucose to blood glucose correlation were assessed.

A Disposable Tear Glucose Biosensor-Part 4: Preliminary Animal Model Study Assessing Efficacy, Safety, and Feasibility.

OBJECTIVE: A prototype tear glucose (TG) sensor was tested in New Zealand white rabbits to assess eye irritation, blood glucose (BG) and TG lag time, and correlation with BG. METHODS: A total of 4 animals were used. Eye irritation was monitored by Lissamine green dye and analyzed using image analysis software. Lag time was correlated with an oral glucose load while recording TG and BG readings. Correlation between TG and BG were plotted against one another to form a correlation diagram, using a Yellow Springs Instrument (YSI) and self-monitoring of blood glucose as the reference measurements. Finally, TG levels were calculated using analytically derived expressions. RESULTS: From repeated testing carried over the course of 12 months, little to no eye irritation was detected. TG fluctuations over time visually appeared to trace the same pattern as BG with an average lag times of 13 minutes. TG levels calculated from the device current measurements ranged from 4 to 20 mg/dL and correlated linearly with BG levels of 75-160 mg/dL (TG = 0.1723 BG = 7.9448 mg/dL; R2 = .7544). CONCLUSION: The first steps were taken toward preliminary development of a sensor for self-monitoring of tear glucose (SMTG). No conjunctival irritation in any of the animals was noted. Lag time between TG and BG was found to be noticeable, but a quantitative modeling to correlate lag time in this study is unnecessary. Measured currents from the sensors and the calculated TG showed promising correlation to BG levels. Previous analytical bench marking showed BG and TG levels consistent with other literature.