Dataset Information

Depth-Dependent Corneal Biomechanical Properties in Normal and Keratoconic Subjects by Optical Coherence Elastography.

ABSTRACT: Purpose:Compare depth-resolved biomechanical properties in normal and keratoconic corneas in live human subjects using optical coherence elastography (OCE). Methods:In a prospective series of normal and keratoconus (KC) eyes, a corneal perturbation was applied by a custom swept-source OCE system using a transparent flat lens coupled to force transducers. Cross-correlation was applied to track frame-by-frame OCT speckle displacement. Regional displacements for the anterior and posterior stroma were plotted in force versus displacement (k) graphs. A spatial biomechanical property ratio (ka/kp ) was defined by dividing the maximum total displacement by the maximum force for the anterior (ka ) and posterior cornea (kp) and was compared between normal and KC groups with the Mann-Whitney U test. Area under the receiver operating characteristics curve (AUROC) for differentiating normal and KC eyes was calculated for ka/kp , kmax, and thinnest point of corneal thickness (TPCT). Results:Thirty-six eyes were analyzed (21 eyes of 12 normal subjects and 15 KC eyes of 12 subjects). The ka/kp for the normal group was 1.135 ± 0.07 (mean ± standard deviation) and 1.02 ± 0.08 for the KC group (P < 0.001), indicating a relative deficit in anterior stromal stiffness in KC eyes. AUROC was 0.91 for ka /kp , 0.95 for kmax, and 1 for TPCT. Conclusions:Significant differences in depth-dependent corneal biomechanical properties were observed between normal and KC subjects. Translational Relevance:OCE was applied for the first time to human KC subjects and revealed alterations in the normal anterior-to-posterior stromal stiffness gradient, a novel and clinically accessible disease biomarker.

SUBMITTER: De Stefano VS

PROVIDER: S-EPMC7414661 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Depth-Dependent Corneal Biomechanical Properties in Normal and Keratoconic Subjects by Optical Coherence Elastography.

De Stefano Vinicius S VS Ford Matthew R MR Seven Ibrahim I Dupps William J WJ

Translational vision science & technology 20200603 7

<h4>Purpose</h4>Compare depth-resolved biomechanical properties in normal and keratoconic corneas in live human subjects using optical coherence elastography (OCE).<h4>Methods</h4>In a prospective series of normal and keratoconus (KC) eyes, a corneal perturbation was applied by a custom swept-source OCE system using a transparent flat lens coupled to force transducers. Cross-correlation was applied to track frame-by-frame OCT speckle displacement. Regional displacements for the anterior and post ...[more]

PMID: 32832211

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Project description:SIGNIFICANCE:Measured corneal biomechanical properties are driven by intraocular pressure, tissue thickness, and inherent material properties. We demonstrate tissue thickness as an important factor in the measurement of corneal biomechanics that can confound short-term effects due to UV riboflavin cross-linking (CXL) treatment. PURPOSE:We isolate the effects of tissue thickness on the measured corneal biomechanical properties using optical coherence elastography by experimentally altering the tissue hydration state and stiffness. METHODS:Dynamic optical coherence elastography was performed using phase-sensitive optical coherence tomography imaging to quantify the tissue deformation dynamics resulting from a spatially discrete, low-force air pulse (150-?m spot size; 0.8-millisecond duration; <10 Pa [<0.08 mmHg]). The time-dependent surface deformation is characterized by a viscoelastic tissue recovery response, quantified by an exponential decay constant-relaxation rate. Ex vivo rabbit globes (n = 10) with fixed intraocular pressure (15 mmHg) were topically instilled every 5 minutes with 0.9% saline for 60 minutes and 20% dextran for another 60 minutes. Measurements were made after every 20 minutes to determine the central corneal thickness (CCT) and the relaxation rates. Cross-linking treatment was performed on another 13 eyes, applying isotonic riboflavin (n = 6) and hypertonic riboflavin (n = 7) every 5 minutes for 30 minutes, followed by UV irradiation (365 nm, 3 mW/cm) for 30 minutes while instilling riboflavin. Central corneal thickness and relaxation rates were obtained before and after CXL treatment. RESULTS:Corneal thickness was positively correlated (R = 0.9) with relaxation rates. In the CXL-treated eyes, isotonic riboflavin did not affect CCT and showed a significant increase in relaxation rates (+10%; P = .01) from 2.29 ms to 2.53 ms. Hypertonic riboflavin showed a significant CCT decrease (-31%; P = .01) from 618 ?m to 429 ?m but showed little change in relaxation rates after CXL treatment. CONCLUSIONS:Corneal thickness and stiffness are correlated positively. A higher relaxation rate implied stiffer material properties after isotonic CXL treatment. Hypertonic CXL treatment results in a stiffness decrease that offsets the stiffness increase with CXL treatment.

Project description:ObjectiveTo map the corneal epithelial thickness with Fourier-domain optical coherence tomography (OCT) and to develop epithelial thickness-based variables for keratoconus detection.DesignCross-sectional observational study.ParticipantsOne hundred forty-five eyes from 76 normal subjects and 35 keratoconic eyes from 22 patients.MethodsA 26,000-Hz Fourier-domain OCT system with 5-μm axial resolution was used. The cornea was imaged with a Pachymetry + Cpwr scan pattern (6-mm scan diameter, 8 radials, 1024 axial-scans each, repeated 5 times) centered on the pupil. Three scans were obtained at a single visit in a prospective study. A computer algorithm was developed to map the corneal epithelial thickness automatically. Zonal epithelial thicknesses and 5 diagnostic variables, including minimum, superior-inferior (S-I), minimum-maximum (MIN-MAX), map standard deviation (MSD), and pattern standard deviation (PSD), were calculated. Repeatability of the measurements was assessed by the pooled standard deviation. The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy.Main outcome measuresDescriptive statistics, repeatability, and AUC of the zonal epithelial thickness and diagnostic variables.ResultsThe central, superior, and inferior epithelial thickness averages were 52.3 ± 3.6 μm, 49.6 ± 3.5 μm, and 51.2 ± 3.4 μm in normal eyes and 51.9 ± 5.3 μm, 51.2 ± 4.2 μm, and 49.1 ± 4.3 μm in keratoconic eyes. Compared with normal eyes, keratoconic eyes had significantly lower inferior (P = 0.03) and minimum (P<0.0001) corneal epithelial thickness, greater S-I (P = 0.013), more negative MIN-MAX (P<0.0001), greater MSD (P<0.0001), and larger PSD (P<0.0001). The repeatability of the zonal average, minimum, S-I, and MIN-MAX epithelial thickness variables were between 0.7 and 1.9 μm. The repeatability of MSD was better than 0.4 μm. The repeatability of PSD was 0.02 or better. Among all epithelial thickness-based variables investigated, PSD provided the best diagnostic power (AUC = 1.00). Using an PSD cutoff value of 0.057 alone gave 100% specificity and 100% sensitivity.ConclusionsHigh-resolution Fourier-domain OCT mapped corneal epithelial thickness with good repeatability in both normal and keratoconic eyes. Keratoconus was characterized by apical epithelial thinning. The resulting deviation from the normal epithelial pattern could be detected with very high accuracy using the PSD variable.Financial disclosure(s)Proprietary or commercial disclosure may be found after the references.

Project description:PurposeTo assess depth-dependent corneal displacements in live normal subjects using optical coherence elastography (OCE).MethodsA corneal elastography method based on swept-source optical coherence tomography (OCT) was implemented in a clinical prototype. Low amplitude corneal deformation was produced during OCT imaging with a linear actuator-driven lens coupled to force transducers. A cross-correlation algorithm was applied to track frame-by-frame speckle displacement across horizontal meridian scans. Intra-measurement force and displacement data series were plotted against each other to produce local axial stiffness approximations, k, defined by the slope of a linear fit to the force/displacement data (ignoring non-axial contributions from corneal bending). Elastographic maps displaying local k values across the cornea were generated, and the ratio of mean axial stiffness approximations for adjacent anterior and posterior stromal regions, ka/kp, was calculated. Intraclass correlation coefficients (ICC) were used to estimate repeatability.ResultsSeventeen eyes (ten subjects) were included in this prospective first-in-humans translational study. The ICC was 0.84. Graphs of force vs. displacement demonstrated that, for simultaneously acquired measurements involving the same applied force, anterior stromal displacements were lower (suggesting stiffer behavior) than posterior stromal displacements. Mean ka was 0.016±0.004 g/mm and mean kp was 0.014±0.004 g/mm, giving a mean ka/kp ratio of 1.123±0.062.ConclusionOCE is a clinically feasible, non-invasive corneal biomechanical characterization method capable of resolving depth-dependent differences in corneal deformation behavior. The anterior stroma demonstrated responses consistent with stiffer properties in compression than the posterior stroma, but to a degree that varied across normal eyes. The clinical capability to measure these differences has implications for assessing the biomechanical impact of corneal refractive surgeries and for ectasia risk screening applications.

Dataset Information

Depth-Dependent Corneal Biomechanical Properties in Normal and Keratoconic Subjects by Optical Coherence Elastography.

Publications

Depth-Dependent Corneal Biomechanical Properties in Normal and Keratoconic Subjects by Optical Coherence Elastography.

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