# Determining the Efficacy of Corneal Cross-Linking Protocols using Brillouin Microscopy

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2022 · $402,582

## Abstract

ABSTRACT:
Keratoconus and related corneal ectatic diseases cause significantly decreased quality of life, are the leading
cause for full thickness corneal transplant in the US, and are significantly more prevalent than previously thought.
Corneal cross-linking (CXL) has emerged as a clinical technique to halt keratoconus progression by stiffening
the corneal stroma. Despite being used clinically for more than a decade, it is currently impossible to assess
CXL protocol efficacy or predict the long-term stability and because we lack quantitative biomechanical measures
to inform predictive models. Currently available metrics to characterize CXL responses are morphologic and
have not proven predictive of clinical outcomes. The major gap is the lack of measurement techniques that can
accurately and non-perturbatively characterize corneal mechanics with three-dimensional (3-D) resolution in
vivo. To address this need, in the past decade we have pioneered Brillouin microscopy, a high-resolution optical
technology that can measure corneal longitudinal modulus in situ in 3-D without contacting or perturbing the eye.
Brillouin microscopy has provided the first and only direct mechanical evidence of decreased modulus in
keratoconus corneas in vivo and the only 3-D maps of CXL-induced corneal stiffening. The overall goal of this
research program is to combine 3-D Brillouin corneal maps and finite element (FE) modeling to quantitatively
predict corneal shape outcomes after CXL protocols. In strong preliminary data, we demonstrated that, by
accounting for tissue hydration, we can establish the quantitative relationship between Brillouin-measured
longitudinal modulus and Young’s modulus. Thus, our central hypothesis is that spatial maps of corneal Young’s
modulus derived from quantitative Brillouin microscopy will enable accurate prediction of corneal shape behavior
via FE modeling. The development of this noninvasive measure of corneal stiffness also enables us to use a
rabbit model to evaluate, for the first time, both morphologic and mechanical evolution in longitudinal studies in
vivo, validated by direct mechanical analysis using experimental protocols that cannot be performed in human
subjects. We will test our central hypothesis through the three specific aims: 1) Validate in vivo Brillouin
mechanical measurements after CXL; 2) Quantify the in vivo mechanical outcomes of novel CXL protocols; and
3) Link CXL biomechanical impact to morphologic outcome with Brillouin imaging and FE modeling. This
research is significant because accurate nondestructive, nonperturbative elasticity-based metrics will drive a
paradigm shift in how CXL protocols are evaluated, developed, and performed clinically as well as ultimately
allow us to develop individualized CXL treatment protocols.

## Key facts

- **NIH application ID:** 10443488
- **Project number:** 1R01EY032537-01A1
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** William Joseph Dupps
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $402,582
- **Award type:** 1
- **Project period:** 2022-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10443488

## Citation

> US National Institutes of Health, RePORTER application 10443488, Determining the Efficacy of Corneal Cross-Linking Protocols using Brillouin Microscopy (1R01EY032537-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10443488. Licensed CC0.

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