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Enrolling by invitation NCT04598932

Corneal Biomechanical Analysis Using Brillouin Microscopy

— Observational Keratoconus Keratoconus, Unstable Keratoconus, Stable

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Brillouin microscopy.
Who it may be relevant to
Registry conditions: Keratoconus, Keratoconus, Unstable, Keratoconus, Stable. Basic parameters: 18 years — 60 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Overview

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.

Interventions

  • Device Brillouin microscopy
    The Brillouin clinical instrument is comprised of three parts: a human interface, a laser-scanning confocal microscope, and an etalon-based spectrometer. The human interface is a modified ophthalmic slit-lamp instrument with chin support and headrest. The light source is a single longitudinal mode CW laser at 780 nm. A polarizing beam splitter and quarter-wave plate assembly sends the laser beam to the human interface. To focus light into the eye, a long-working distance microscope objective is

Primary outcome measures

  • Change in Brillouin Metrics [Time frame: Difference between baseline and 3 months after intervention]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model
Case-control

Study locations

United States · 1 center
  • Cleveland Clinic Cole Eye Institute — Cleveland

Publications

  • Zhang H, Roozbahani M, Piccinini AL, Golan O, Hafezi F, Scarcelli G, Randleman JB. Depth-Dependent Reduction of Biomechanical Efficacy of Contact Lens-Assisted Corneal Cross-linking Analyzed by Brillouin Microscopy. J Refract Surg. 2019 Nov 1;35(11):721-728. doi: 10.3928/1081597X-20191004-01. PMID 31710374
  • Webb JN, Langille E, Hafezi F, Randleman JB, Scarcelli G. Biomechanical Impact of Localized Corneal Cross-linking Beyond the Irradiated Treatment Area. J Refract Surg. 2019 Apr 1;35(4):253-260. doi: 10.3928/1081597X-20190304-01. PMID 30984983
  • Randleman JB, Su JP, Scarcelli G. Biomechanical Changes After LASIK Flap Creation Combined With Rapid Cross-Linking Measured With Brillouin Microscopy. J Refract Surg. 2017 Jun 1;33(6):408-414. doi: 10.3928/1081597X-20170421-01. PMID 28586502
  • Scarcelli G, Pineda R, Yun SH. Brillouin optical microscopy for corneal biomechanics. Invest Ophthalmol Vis Sci. 2012 Jan 20;53(1):185-90. doi: 10.1167/iovs.11-8281. PMID 22159012
  • Scarcelli G, Kling S, Quijano E, Pineda R, Marcos S, Yun SH. Brillouin microscopy of collagen crosslinking: noncontact depth-dependent analysis of corneal elastic modulus. Invest Ophthalmol Vis Sci. 2013 Feb 19;54(2):1418-25. doi: 10.1167/iovs.12-11387. PMID 23361513
  • Scarcelli G, Besner S, Pineda R, Yun SH. Biomechanical characterization of keratoconus corneas ex vivo with Brillouin microscopy. Invest Ophthalmol Vis Sci. 2014 Jun 17;55(7):4490-5. doi: 10.1167/iovs.14-14450. PMID 24938517
  • Scarcelli G, Besner S, Pineda R, Kalout P, Yun SH. In vivo biomechanical mapping of normal and keratoconus corneas. JAMA Ophthalmol. 2015 Apr;133(4):480-2. doi: 10.1001/jamaophthalmol.2014.5641. No abstract available. PMID 25611213

Identifiers

NCT: NCT04598932 · 20-355

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗