Corneal ectasia is a major cause of impaired vision-related quality of life in the United States and a leading indication for corneal transplantation. The lack of clinical tools for resolving biomechanical properties throughout the cornea is a critical barrier to understanding mechanisms of corneal instability and applying potentially transformative bioengineering approaches to risk screening and treatment optimization. The goal of this research program is to develop a robust OCT-based simulation platform for quantifying ectasia risk and predicting individual responses to a broad range of corneal treatments. The objective, which is aided by the sensitive link between corneal shape and visual function, is to identify the key structural predictors of ectatic disease and develop rationl approaches to customized crosslinking therapy through integrated patient- specific biomechanical measurement and modeling. The central hypothesis is that the magnitude and distribution of biomechanical properties in the cornea are key drivers of corneal shape. This hypothesis and the methods for testing it have been developed in part through the applicants'preliminary work in corneal optical coherence elastography (OCE) and in patient-specific finite element (FE) analysis studies that suggest important dependencies between material properties and shape. The hypothesis will be tested through the following specific aims: 1) Characterize the magnitude and distribution of corneal biomechanical properties across normal, surgically altered and pathologic states, 2) determine the accuracy of elastography-driven FE models for predicting outcomes of corneal interventions in donor eyes and patients, and 3) identify the key biomechanical drivers of keratoconus progression, post-refractive surgery ectasia, and crosslinking response using patient-specific simulations.
Under Aim 1, OCE will be used in donor eye and clinical studies to test the hypothesis that the human cornea has intrinsic regional differences in biomechanical properties that are altered in characteristic ways by LASIK, keratoconus and collagen crosslinking. After generating FE models using subject-specific geometry for all pre-intervention eyes in Aim 1, Aim 2 will test the hypothesis that models populated with subject-specific OCE property data better predict outcomes than those with idealized bulk property estimates. Finally, in large-scale, multifactorial FE simulations using al normal and keratoconic patients as modeling substrates, Aim 3 will determine how elastic properties, initial corneal geometry and procedure variables interact to influence ectasia risk and crosslinking responses. Expected outcomes include clinical translation of OCT-based capabilities for mapping corneal biomechanical properties and generating patient-specific computational models capable of predicting treatment responses. Simulation-based optimizations will support novel, customizable calculators for ectasia risk and new algorithms for enhancing the effects of collagen crosslinking in individual eyes. These outcomes directly address gaps identified by the NEI and will enable new simulation-based treatment strategies for existing and emerging corneal procedures.

Public Health Relevance

This research program addresses core challenges in the development and integration of tools for simulation-based surgical planning. Major clinical targets of the proposal include keratoconus and post-LASIK ectasia, corneal diseases in which visual function and emerging treatments all depend explicitly on corneal structural properties. Projected outcomes of the work include development of noninvasive methods for biomechanical property mapping and integration of such measurements into patient-specific computational models that can be used to project disease risk and facilitate rational customization of treatment.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY023381-02
Application #
8664399
Study Section
Special Emphasis Panel (BNVT)
Program Officer
Mckie, George Ann
Project Start
2013-06-01
Project End
2018-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
2
Fiscal Year
2014
Total Cost
$388,325
Indirect Cost
$143,325
Name
Cleveland Clinic Lerner
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
135781701
City
Cleveland
State
OH
Country
United States
Zip Code
44195
Girard, Michaƫl J A; Dupps, William J; Baskaran, Mani et al. (2015) Translating ocular biomechanics into clinical practice: current state and future prospects. Curr Eye Res 40:18-Jan
Hallahan, Katie M; Sinha Roy, Abhijit; Ambrosio Jr, Renato et al. (2014) Discriminant value of custom ocular response analyzer waveform derivatives in keratoconus. Ophthalmology 121:459-68
Roberts, Cynthia J; Dupps Jr, William J (2014) Biomechanics of corneal ectasia and biomechanical treatments. J Cataract Refract Surg 40:991-8
Ford, Matthew R; Sinha Roy, Abhijit; Rollins, Andrew M et al. (2014) Serial biomechanical comparison of edematous, normal, and collagen crosslinked human donor corneas using optical coherence elastography. J Cataract Refract Surg 40:1041-7
Seven, Ibrahim; Sinha Roy, Abhijit; Dupps Jr, William J (2014) Patterned corneal collagen crosslinking for astigmatism: computational modeling study. J Cataract Refract Surg 40:943-53
Hallahan, Katie M; Rocha, Karolinne; Roy, Abhijit S et al. (2014) Effects of corneal cross-linking on ocular response analyzer waveform-derived variables in keratoconus and postrefractive surgery ectasia. Eye Contact Lens 40:339-44
Torricelli, Andre A M; Ford, Matthew R; Singh, Vivek et al. (2014) BAC-EDTA transepithelial riboflavin-UVA crosslinking has greater biomechanical stiffening effect than standard epithelium-off in rabbit corneas. Exp Eye Res 125:114-7
Xu, David; Dupps Jr, William J; Srivastava, Sunil K et al. (2014) Automated volumetric analysis of interface fluid in descemet stripping automated endothelial keratoplasty using intraoperative optical coherence tomography. Invest Ophthalmol Vis Sci 55:5610-5