Corneal Biomechanical Analysis Using Brillouin Microscopy

• Conditions: Keratoconus; Keratoconus, Unstable; Keratoconus, Stable

• Registration Number: NCT04598932
• Lead Sponsor: The Cleveland Clinic

Brief Summary

The objective of this study is to measure the Brillouin biomechanical properties in keratoconic corneas and characterize biomechanical alterations that occur after corneal procedures that inherently strengthen or weaken the cornea by evaluating the change in Brillouin metrics before and after treatments.

Detailed Description

Surgical correction of myopia and keratoconus identification/management are separate but tightly intertwined issues of major significance. For both, there is an unmet need for direct measurements to evaluate corneal stiffness (i.e. its resistance to deformation). The prevalence of myopia is expected to double, affecting more than 50% of the US population, by 2050. Laser in situ keratomileusis (LASIK) is one of the most popular and successful surgeries in the world and compares favorably to long-term contact lens wear use for myopia correction. However, only \~10% of eligible patients undergo LASIK currently; the others cite safety concerns as a major factor in their decision. The primary risk for poor refractive surgery outcomes is biomechanical failure due to unidentified (subclinical) ectasia (i.e. keratoconus). Patients presenting for LASIK evaluation with atypical, suspicious corneal curvature but with undetermined true risk represent the leading reason for surgery screening failures. This results in good candidates being denied surgery, while up to 10% of truly poor candidates are still missed using current screening algorithms.

Keratoconus is up to 10 times more prevalent than the previously reported 1/2000 figure. Corneal cross-linking (CXL) is now FDA approved in the US for keratoconus treatment and is effective at stiffening the cornea and halting ectasia progression. Early identification of keratoconus is critical, but current tests in the clinic are morphological, not biomechanical, and therefore do not allow a definitive diagnosis at the earliest stages resulting in vision loss before CXL treatment is initiated. Thus, the need for accurate identification of subclinical ectasia has never been greater.

In the past years, newly developed technology, Brillouin microscopy, has emerged as the most promising tool to address this clinical need. This study will systemically address the critical gap in current knowledge by linking Brillouin mapping of corneal biomechanical alterations to abnormal morphological behavior and testing the findings in conditions where corneal biomechanics are abruptly altered, by: 1) weakening with refractive surgery procedures, and 2) strengthening through corneal cross-linking.

It is anticipated that a clinical tool assessing the mechanical state of the cornea will improve early diagnosis and management of keratoconus as well as refractive surgery planning. Ultimately, this will lead to predictive models where Brillouin measurements could be an accurate predictor of postoperative outcomes and thus aid in developing individualized surgical parameters.

Study Timeline

• Study First Submitted: 2020-05-19
• Study First Submitted QC: 2020-10-21
• Study First Posted: 2020-10-22
• Study Start: 2021-06-01
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-11
• Last Update Posted: 2025-02-13
• Primary Completion: 2025-07
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

• patients aged 18-60 with keratoconus
• patients aged 18-60 with normal corneas,
• patients aged 18-60 undergoing refractive surgery (LASIK, PRK, SMILE)
• patients aged 18-60 with keratoconus undergoing CXL

Exclusion Criteria

• outside age range
• history of previous ocular surgeries
• unable to cooperate for the Brillouin microscopic examination
• unable to provide informed consent

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change in Brillouin Metrics	Difference between baseline and 3 months after intervention	Brillouin metrics to be evaluated include localized Mean Brillouin modulus measure across the cornea and at each depth of the corneal stroma

Trial Locations

Locations (1)

Cleveland Clinic Cole Eye Institute; 🇺🇸 Cleveland, Ohio, United States