(J-384) Monitoring Dry Eye Disease and Ocular Surface Inflammation with Colorimetric Scleral Lens Sensor

In recent years, advancements in wearable technology have led to innovative approaches in healthcare monitoring, including the field of ophthalmology. In recent years, people have achieved in exploring tears as a potential medium for monitoring ocular health, as they contain various biomarkers such as combination of lipids, electrolytes, proteins, peptides, glucose, and amino acids reflecting both ocular and systemic physiological conditions. Overall, tear composition mirrors the body and eyes' physiological condition, encompassing hydration levels and infection serving as indicators for chronic or acute diseases, infections, as well as local trauma or injury which can significantly impact an individual's visual health and overall quality of life. Current pH measurement techniques for tears have used micro-combination glass probes and microelectrodes inserted in the eye, revealing a healthy tear pH range of 6.0 to 7.6. To screen other analytes in tears, three steps of clinical tests are processed involving tear sampling, sample extraction from the medium, and analysis with spectroscopies. In other words, establishing reliable methods for tear collection, processing and analysis is still an open challenge. Here, we introduce our novel colorimetric wearable eye-health monitoring platform based on biocompatible pHEMA-PEG hydrogel and PDMS device. Our platform harnesses the potential of biomarkers in tears by leveraging colorimetric sensors capable of detecting fluctuations in chloride anion concentration (Cl-), pH levels, and ocular surface temperature. The non-invasive nature of this technology enables continuous monitoring, thereby reducing the necessity for frequent visits to clinics, while facilitating long-term and sustained ocular health tracking.

Method and Materials

Bromothymol blue, anion exchange resin, 2-hydroxyethyl methacrylate, polyethylene glycol, benzoyl peroxide and DI water were purchased from Sigma-Aldrich and used without further purification. PDMS (SYLGARD 184) was purchased from Dow Chemical Company. The thermochromic inks obtained from Nano I&C in Korea and was used as received. Silver chloranilate was purchased from Citi chemical.

Synthesis of poly(HEMA)-PEG hydrogels

Poly(HEMA) hydrogels were synthesized by free-radical polymerization of HEMA with 0.5 w/w% BP, as the free-radical initiator, 1 v/v% EGDMA, as the crosslinking agent, 30 w/w% of chromogenic sensor. For example, 40.3 mg BP, 6 mL HEMA, 61 μL EGDMA and 1.9 g of colorimetric dye were added to a vial. This hydrogel precursor mixture was vortexed and sonicated until it is homogeneous. The mixture was then filled into a mold and cross-linked hydrogel was obtained after thermal curing the precursor in an oven at 80 °C for overnight. For synthesizing the thermochromic sensor, used Sylgard 184(PDMS) 20:1 and added 5% of thermochromic inks.

In summary, we have developed a novel scleral contact lens that enables non-invasive monitoring of dry eye disease and ocular surface inflammation. The commercial scleral contact lens integrates chromogenic sensors based on pHEMA-PEG hydrogel and PDMS, allowing for the quantitative measurement of chloride concentration, pH levels, and ocular surface temperature. These measurements serve as indicators of the inflammatory response and overall physiological condition of the ocular surface, all conveniently assessed in point-of-care settings. An essential feature of this platform is the rapid response of the colorimetric sensors, providing readings within approximately 40 seconds upon exposure to tear fluid. This efficiency ensures accurate disease analysis, with the pH sensor detecting µM changes, the Cl- sensor demonstrating mM limit of detection, and the thermochromic sensor exhibiting 0.5 ºC sensitivity. To facilitate data processing, we have integrated a custom algorithm into a smartphone application, creating a handheld ophthalmic readout compatible with both IOS and Android operating systems. Furthermore, we have conducted testing on both canine and human subjects, and the results have shown successful disease monitoring without notable side effects. This success underscores the potential of our technology as a safe and reliable tool for long-term ocular health surveillance.