Michael D. Twa

A focused air-pulse system for optical-coherence-tomography-based measurements of tissue elasticity

Accurate non-invasive assessment of tissue elasticity in vivo is required for early diagnostics of many tissue abnormalities. We have developed a focused air-pulse system that produces a low-pressure and short-duration air stream, which can be used to excite transient surface waves (SWs) in soft tissues. System characteristics were studied using a high-resolution analog pressure transducer to describe the excitation pressure. Results indicate that the excitation pressure provided by the air-pulse system can be easily controlled by the air source pressure, the angle of delivery, and the distance between the tissue surface and the port of the air-pulse system. Furthermore, we integrated this focused air-pulse system with phase-sensitive optical coherence tomography (PhS-OCT) to make non-contact measurements of tissue elasticity. The PhS-OCT system is used to assess the group velocity of SW propagation, which can be used to determine Youngs modulus. Pilot experiments were performed on gelatin phantoms with different concentrations (10%, 12% and 14% w/w). The results demonstrate the feasibility of using this focused air-pulse system combined with PhS-OCT to estimate tissue elasticity. This easily controlled non-contact technique is potentially useful to study the biomechanical properties of ocular and other tissues in vivo.

Noncontact measurement of elasticity for the detection of soft-tissue tumors using phase-sensitive optical coherence tomography combined with a focused air-puff system

We report on an optical noncontact method for the detection of soft-tissue tumors based on the measurement of their elasticity. A focused air-puff system is used to excite surface waves (SWs) on soft tissues with transient static pressure. A high-speed phase-sensitive optical coherence tomography system is used to measure the SWs as they propagate from the point of excitation. To evaluate the stiffness of soft tissues, the Youngs modulus is quantified based on the group velocity of SWs. Pilot experiments were performed on ex vivo human myxoma and normal fat. Results demonstrate the feasibility of the proposed method to measure elasticity and differentiate soft-tissue tumors from normal tissues.

CHARACTERISTICS OF CORNEAL ECTASIA AFTER LASIK FOR MYOPIA

Purpose: There are numerous reports of corneal ectasia after laser in situ keratomileusis (LASIK) for myopia without a consistent definition of this condition or a definitive etiology. We conducted a retrospective analysis of published case reports to describe common characteristics of this postoperative event and compared them with findings from a group of successful LASIK patients. Methods: A MEDLINE search for “LASIK” and “ectasia” yielded 21 relevant articles published before May 2003 (n = 86 eyes, 59 patients). A comparison group (n = 103 eyes, 63 patients) was selected from a clinic-based sample of successful LASIK patients with 12 months of follow-up after treatment. Descriptive statistics are reported as median and interquartile range. Comparisons were performed using the Wilcoxon rank sum, Wilcoxon signed rank, and chi-square tests. Results: Time to diagnosis of ectasia after LASIK was 13 months (6 to 20 months). Residual myopia in the ectasia group was −3.69 D (−6.00 to −2.13 D) and was significantly greater than the comparison group, −0.38 D (−0.75 to 0.00 D), P < 0.001. After surgery, eyes with ectasia had increased corneal toricity 2.87 D (2.00 to 4.9 D) with increased oblique astigmatism 1.3 D (0.23 to 2.89 D) relative to eyes in the comparison group 0.00 D (0.00 to 0.08 D), and a loss of 2 lines (−0.5 to −6 lines) of best spectacle-corrected visual acuity (all P < 0.001). Thirty-five percent of reported cases resulted in subsequent corneal transplantation. Conclusions: Preoperative characteristics of corneal ectasia include worse visual acuity, less corneal thickness, greater residual myopia, and greater corneal toricity than nonectatic eyes. Treatment factors associated with corneal ectasia after LASIK are greater stromal ablation and less residual stromal bed thickness. Postoperative characteristics of corneal ectasia are myopic refractive error with increased astigmatism, worse spectacle-corrected visual acuity, increased corneal toricity with topographic abnormality, and progressive corneal thinning.

Response of the posterior corneal surface to laser in situ keratomileusis for myopia

Purpose: To describe the response of the posterior corneal surface in laser in situ keratomileusis (LASIK) and determine whether residual stromal bed thickness or treatment magnitude is predictive of the posterior corneal surface elevation after uneventful LASIK. Setting: A private hospital‐based refractive surgery practice, Hong Kong SAR, China. Methods: Orbscan I (Bausch & Lomb) videokeratography examinations were performed on 1124 patients before and 6 months after LASIK for myopia (mean −6.81 diopters [D] ± 2.52 [SD]; range −0.88 to −14.50 D). The best‐fit sphere (BFS) over the central 9.0 mm region of the posterior corneal surface before and after treatment was compared. The location and magnitude of the 1.0 mm diameter region of highest elevation above the BFS for the central 4.0 mm diameter zone were calculated before and after treatment and compared using a paired t test. Stepwise regression was used to model the best predictors of the posterior radius of the BFS and the central elevation of the corneal surface above the BFS before and after treatment. Results: The mean radius of curvature of the posterior surface BFS decreased 0.10 mm after LASIK, from 6.31 to 6.21 mm (P<.001). Elevation above this BFS was increased 10 μm within a 1.00 mm diameter region of interest, and this was correlated with postoperative corneal thickness, inferotemporal decentration of the highest point, residual myopia, and steeper central posterior radius of curvature. Conclusions: No eye was diagnosed with corneal ectasia at the time of the 6‐month postoperative visit. After LASIK, there was a decreased radius of curvature for the BFS of the posterior corneal surface, with the highest elevation point located paracentrally. These findings are similar to the anterior corneal surface changes observed in corneal ectasia after LASIK but smaller in magnitude.

CLMI The Cone Location and Magnitude Index

Purpose: To develop an index for the detection of keratoconic patterns in corneal topography maps from multiple devices. Methods: For development, an existing Keratron (EyeQuip) topographic dataset, consisting of 78 scans from the right eyes of 78 healthy subjects and 25 scans from the right eyes of 25 subjects with clinically diagnosed keratoconus, was retrospectively analyzed. The Cone Location and Magnitude Index (CLMI) was calculated on the available axial and tangential curvature data. Stepwise logistic regression analysis was performed to determine the best predictor(s) for the detection of keratoconus. A sensitivity and specificity analysis was performed by using the best predictor of keratoconus. Percent probability of keratoconus was defined as the optimal probability threshold for the detection of disease. For validation, CLMI was calculated retrospectively on a second distinct dataset, acquired on a different topographer, the TMS-1. The validation dataset consisted of 2 scans from 24 eyes of 12 healthy subjects with no ocular history and 4 scans from 21 eyes of 14 subjects with clinically diagnosed keratoconus. Probability of keratoconus was calculated for the validation set from the equation determined from the development dataset. Results: The strongest significant sole predictor in the stepwise logistic regression was aCLMI, which is CLMI calculated from axial data. Sensitivity and specificity for aCLMI on the development dataset were 92% and 100%, respectively. A complete separation of normals and keratoconics with 100% specificity and 100% sensitivity was achieved by using the validation set. Conclusions: CLMI provides a robust index that can detect the presence or absence of a keratoconic pattern in corneal topography maps from 2 devices.

Automated decision tree classification of corneal shape

Purpose. The volume and complexity of data produced during videokeratography examinations present a challenge of interpretation. As a consequence, results are often analyzed qualitatively by subjective pattern recognition or reduced to comparisons of summary indices. We describe the application of decision tree induction, an automated machine learning classification method, to discriminate between normal and keratoconic corneal shapes in an objective and quantitative way. We then compared this method with other known classification methods. Methods. The corneal surface was modeled with a seventh-order Zernike polynomial for 132 normal eyes of 92 subjects and 112 eyes of 71 subjects diagnosed with keratoconus. A decision tree classifier was induced using the C4.5 algorithm, and its classification performance was compared with the modified Rabinowitz–McDonnell index, Schwiegerling’s Z3 index (Z3), Keratoconus Prediction Index (KPI), KISA%, and Cone Location and Magnitude Index using recommended classification thresholds for each method. We also evaluated the area under the receiver operator characteristic (ROC) curve for each classification method. Results. Our decision tree classifier performed equal to or better than the other classifiers tested: accuracy was 92% and the area under the ROC curve was 0.97. Our decision tree classifier reduced the information needed to distinguish between normal and keratoconus eyes using four of 36 Zernike polynomial coefficients. The four surface features selected as classification attributes by the decision tree method were inferior elevation, greater sagittal depth, oblique toricity, and trefoil. Conclusion. Automated decision tree classification of corneal shape through Zernike polynomials is an accurate quantitative method of classification that is interpretable and can be generated from any instrument platform capable of raw elevation data output. This method of pattern classification is extendable to other classification problems.

Air-pulse OCE for assessment of age-related changes in mouse cornea in vivo

We demonstrate the use of phase-stabilized swept source optical coherence elastography (PhS-SSOCE) to assess the relaxation rate of deformation created by a focused air-pulse in tissue-mimicking gelatin phantoms of various concentrations and mouse corneas of different ages in vivo. The results show that the relaxation rate can be quantified and is different for gels with varying concentrations of gelatin and mouse corneas of different ages. The results indicate that gel phantoms with higher concentrations of gelatin as well as older mouse corneas have faster relaxation rates indicating stiffer material. This non-contact and non-invasive measurement technique utilizes low surface displacement amplitude (in µm scale) for tissue excitation and, therefore, can be potentially used to study the biomechanical properties of ocular and other sensitive tissues.

Spatial characterization of corneal biomechanical properties with optical coherence elastography after UV cross-linking

Corneal collagen cross-linking (CXL) is a clinical treatment for keratoconus that structurally reinforces degenerating ocular tissue, thereby limiting disease progression. Clinical outcomes would benefit from noninvasive methods to assess tissue material properties in affected individuals. Regional variations in tissue properties were quantified before and after CXL in rabbit eyes using optical coherence elastography (OCE) imaging. Low-amplitude (<1µm) elastic waves were generated using micro air-pulse stimulation and the resulting wave amplitude and speed were measured using phase-stabilized swept-source OCE. OCE imaging following CXL treatment demonstrates increased corneal stiffness through faster elastic wave propagation speeds and lower wave amplitudes.

Estimation of pupil size by digital photography

Purpose: To evaluate a digital photography method of pupil size estimation over a broad range of illumination conditions and to compare this method with common clinical techniques. Setting: College of Optometry, Ohio State University, Columbus, Ohio, USA. Methods: Two examiners measured the pupil diameter in 45 right eyes at 3 illumination levels: <0.63 lux (dark), 5 lux (dim), and 1000 lux (bright). Estimation by infrared video recording, the reference standard, was compared with measurements by digital photography, ruler, semicircular templates, and the Colvard pupillometer. Masked graders measured pupil size from infrared video recordings and digital photographs. Results: The repeatability of the measurement method determined by the mean intraclass correlation coefficients was highest for video recording across conditions (0.86–0.97), followed by digital photography (0.76–0.94), Colvard pupillometry (0.63–0.82), ruler (0.71–0.85), and templates (0.70–0.83). An analysis of variance showed a significant difference in pupil size by method (P<.001). All methods except digital photography estimated smaller pupil sizes under dark and dim illumination than infrared video measurements (all P<.01). Under bright illumination, the ruler measurements were significantly smaller (–0.15 mm) and the Colvard pupillometer measurements were greater (+0.30 mm) than the reference (P<.01). The 95% limits of agreement (LoA) between examiners were smallest for video measurements at all light levels. The remaining measures ranked from best to worst by 95% LoA were digital photography, Colvard pupillometry, ruler, and templates. Conclusions: Estimation of pupil size by digital photography was more repeatable and accurate than estimates by common clinical techniques over a wide range of illumination. Although not as quick as other methods, digital photography is relatively inexpensive, permits lasting documentation, and allows independent grading suitable for clinical research purposes.

Dynamic optical coherence tomography measurements of elastic wave propagation in tissue-mimicking phantoms and mouse cornea in vivo

Abstract. We demonstrate the use of phase-stabilized swept-source optical coherence tomography to assess the propagation of low-amplitude (micron-level) waves induced by a focused air-pulse system in tissue-mimicking phantoms, a contact lens, a silicone eye model, and the mouse cornea in vivo. The results show that the wave velocity can be quantified from the analysis of wave propagation, thereby enabling the estimation of the sample elasticity using the model of surface wave propagation for the tissue-mimicking phantoms. This noninvasive, noncontact measurement technique involves low-force methods of tissue excitation that can be potentially used to assess the biomechanical properties of ocular and other delicate tissues in vivo.