High-resolution corneal hydration mapping using brillouin microscopy

The National Eye Institute, part of the Department of Health and Human Services National Institutes of Health, awarded The General Hospital Corporation (doing business as Massachusetts General Hospital) $643,357 on June 15, 2026, under the Vision Research program (CFDA 93.867) to develop a Brillouin microscopy-based imaging method for direct, high-resolution measurement of corneal hydration.

The project aims to create a combined Brillouin–optical coherence tomography system to map corneal water content and apply this system to measure hydration patterns in human subjects with various corneal conditions, including Fuchs' dystrophy, corneal guttata, glaucoma, dry eye, keratoconus, and post-LASIK corneas. The technology is intended to enable direct assessment of corneal hydration for disease diagnosis, surgical planning, postoperative monitoring, and routine ophthalmic screening, addressing an unmet clinical need where corneal hydration is currently inferred from corneal thickness rather than directly measured.

Work is performed in Cambridge, Massachusetts through March 31, 2030. Massachusetts Eye and Ear Infirmary, a Harvard Medical School–affiliated nonprofit hospital, serves as a sub-recipient responsible for human subject recruitment and collection of conventional corneal measurements and ophthalmic examinations. Under the direction of Dr. Roberto Pineda II, Massachusetts Eye and Ear Infirmary will enroll 190 human subjects over five years: 70 healthy volunteers aged 20–79 and 120 patients distributed across six disease-specific cohorts of 20 subjects each. All participants will undergo corneal topography, intraocular pressure measurement, and comprehensive eye examinations; selected patient groups will receive specular microscopy to assess endothelial cell status.

Abstract

Proper hydration of the corneal stroma is essential for maintaining corneal transparency and normal visual function. This hydration homeostasis is disrupted in a range of corneal conditions, including refractive surgeries, endothelial dysfunction, epithelial injury, and degenerative disorders. Despite its broad clinical significance, corneal hydration is not directly measured in current practice due to a lack of suitable technology. Instead, IT is inferred from corneal thickness, which is highly variable across individuals and often unreliable. To address this unmet clinical need, this project aims to develop a brillouin-based imaging method for direct, accurate, and morphology-independent measurement of corneal water content. Brillouin light scattering microscopy provides frequency shifts that-while traditionally associated with stiffness-are now understood to correlate more strongly with tissue hydration, particularly in the corneal stroma. Leveraging the high sensitivity of brillouin shifts to the solid-to-water ratio, this project can enable high-resolution mapping of corneal hydration with unprecedented precision. Aim 1 focuses on the development of a combined brillouin- optical coherence tomography system to achieve integrated functional and structural analysis of corneal hydration. Aim 2 applies this system to measure hydration maps in human subjects with various corneal conditions, including fuchs' dystrophy, corneal guttata, glaucoma, dry eye, keratoconus, and post-lasik corneas. The goal is to identify condition-specific hydration patterns and explore their diagnostic relevance. If successful, this technology will offer a transformative clinical tool for direct assessment of corneal hydration, with potential applications in disease diagnosis, surgical planning, postoperative monitoring, and routine ophthalmic screening.