We describe an automated algorithm allowing extraction of quantitative corneal transparency parameters with clinical Spectral-Domain Optical Coherence Tomography (SD-OCT). Our algorithm employs a novel pre-processing procedure to standardize SD-OCT image analysis and to numerically correct common instrumental artifacts before extracting mean intensity stromal-depth (z) profiles over a 6-mm-wide corneal area. The z-profiles are analyzed using our previously developed objective method deriving quantitative transparency parameters which are directly related to the physics of light propagation in tissues. Tissular heterogeneity is quantified by the Birge ratio, Br; for homogeneous tissues (i.e., Br~1), the photon mean-free path (ls) may be determined. Images of 83 normal corneas (ages 22–50 years) from a standard SD-OCT device (RTVue-XR Avanti, Optovue Inc.) were processed to establish a normative dataset of transparency values. After confirming stromal homogeneity (Br⪅10), we measured a median ls of 570 μm (interdecile range: 270–2400 μm). Considering corneal thicknesses, this may be translated into a median fraction of transmitted (coherent) light Tcoh(stroma) of 51% (interdecile range: 22–83%). Excluding images with central saturation artifact raised our median Tcoh(stroma) to 73% (inter-decile range: 34–84%). These transparency values are slightly lower than previously reported, which we attribute to the detection configuration of SD-OCT with a relatively small and selective acceptance angle. No statistically significant correlation between transparency and age or thickness was found. Our algorithm provides robust and quantitative measurements of corneal transparency from standard SD-OCT images with sufficient quality and addresses the demand for such an objective means in the clinical setting.
In vivo 3D OCT imaging of live animal generally suffers from motion artifacts due to involuntary tissue movement. Here, we propose a real-time 3D OCT imaging approach using a convolution neural network (CNN)/regression-based algorithm to correct tissue motion in vivo. The system first scans four reference images along the slow axis within millisecond-scale acquisition time before acquiring a C-mode image. The algorithm recognizes the tissue surface by CNN, then uses the segmentation result along with reference images to compensate lateral and axial motion. We evaluated the system performance using a fish eye model.
Significance: Optical coherence tomography (OCT) allows high-resolution volumetric three-dimensional (3D) imaging of biological tissues in vivo. However, 3D-image acquisition can be time-consuming and often suffers from motion artifacts due to involuntary and physiological movements of the tissue, limiting the reproducibility of quantitative measurements.
Aim: To achieve real-time 3D motion compensation for corneal tissue with high accuracy.
Approach: We propose an OCT system for volumetric imaging of the cornea, capable of compensating both axial and lateral motion with micron-scale accuracy and millisecond-scale time consumption based on higher-order regression. Specifically, the system first scans three reference B-mode images along the C-axis before acquiring a standard C-mode image. The difference between the reference and volumetric images is compared using a surface-detection algorithm and higher-order polynomials to deduce 3D motion and remove motion-related artifacts.
Results: System parameters are optimized, and performance is evaluated using both phantom and corneal (ex vivo) samples. An overall motion-artifact error of <4.61 microns and processing time of about 3.40 ms for each B-scan was achieved.
Conclusions: Higher-order regression achieved effective and real-time compensation of 3D motion artifacts during corneal imaging. The approach can be expanded to 3D imaging of other ocular tissues. Implementing such motion-compensation strategies has the potential to improve the reliability of objective and quantitative information that can be extracted from volumetric OCT measurements.
Optical coherence tomography (OCT) has evolved into a powerful imaging technique that allows high-resolution visualization of biological tissues. However, most in vivo OCT systems for real-time volumetric (3D) imaging suffer from image distortion due to motion artifacts induced by involuntary and physiological movements of the living tissue, such as the eye that is constantly in motion.While several methods have been proposed to account for and remove motion artifacts during OCT imaging of the retina, fewer works have focused on motion-compensated OCT-based measurements of the cornea. Here, we propose an OCT system for volumetric imaging of the cornea, capable of compensating both axial and lateral motion with micron-scale accuracy and millisecond-scale time consumption based on higher-order regression. System performance was evaluated during volumetric imaging of corneal phantom and bovine (ex vivo) samples that were positioned in the palm of a hand to simulate involuntary 3D motion. An overall motion-artifact error of less than 4.61 μm and processing time of about 3.40 ms for each B-scan was achieved.
We developed a novel combined SD-OCT + TD-FF-OCT device that provides cell-resolution view of TD-FF-OCT without compromising SD-OCT performance. SD-OCT gives global view for eye exploration and FF-OCT shows cell-detail in the central region of the OCT scan. Eye imaging is fast enough to be part of the routine clinical exam (10 min/patient). Four patients with different eye pathologies were imaged. FF-OCT resolved: striae (stromal mechanical folds), guttata, loss of endothelial cells and stromal cuts following the surgery. Additionally, we could access the trabecular meshwork region of the eye and obtain the first images of meshwork fibers at micron resolution.
KEYWORDS: Transparency, Cornea, Optical coherence tomography, Image segmentation, Principal component analysis, Algorithm development, In vivo imaging, Statistical analysis, Signal to noise ratio, Signal processing
We present an automated data analysis procedure for clinical SD-OCT images, capable of correcting hyperreflective artifacts due to the instrument. Quantitative parameters related to corneal transparency are extracted from n=85 normal corneas.
KEYWORDS: Optical coherence tomography, Real time imaging, Tissues, Natural surfaces, Motion analysis, In vivo imaging, Imaging systems, Detection and tracking algorithms, Cornea
Optical Coherence Tomography (OCT) has evolved into a powerful clinical tool, with a wide range of applications in ophthalmology. However, most OCT systems for real-time volumetric (3D) and in vivo imaging suffer from image distortion due to motion artifacts induced by involuntary and physiological movements of the living tissue. Several methods have been proposed to obtain motion-free images, yet they are generally limited in their applicability due to long acquisition times, requiring multiple volumes [1], and/or the need for additional hardware [2]. Here we propose and analyze a motion-compensated 3D-OCT imaging system that uses a higher-order regression analysis and show that it can effectively correct the motion artifacts within 0 to 5 Hz in real time without requiring additional hardware.
Eye movements are commonly seen as an obstacle to high-resolution ophthalmic imaging. In this context we study the natural axial movements of in vivo human eye and show that they can be used to modulate the optical phase and retrieve tomographic images via time-domain full-field optical coherence tomography (TD-FF-OCT). This approach opens a path to a simplified ophthalmic TD-FF-OCT device, operating without the usual piezo motor-camera synchronization. The device demonstrates in vivo human corneal images under different image retrieval schemes (2-phase and 4-phase) and different exposure times (3.5 ms, 10 ms, 20 ms).
Heterogeneities of biological tissues can strongly affect light propagation at large depths by distorting the initial wavefront. Inspired by previous works in acoustics, we have developed a matrix approach to Full-Field Optical Coherence Tomography (FF-OCT) to push back the fundamental limit of aberrations and multiple scattering. An analysis of the correlations of the matrix allows to correct for aberrations and forward multiple scattering over multiple isoplanatic areas (contrary to classic adaptive optics). Here, we report on the application of this approach to the imaging of the monkey cornea and the quantitative measurement of the corneal transparency.
This talk reviews ongoing work towards computational imaging of the living eye, primarily for the purpose of quantifying corneal transparency, for which to date no objective clinical tool exists.
In optical imaging, light propagation is affected by the medium inhomogeneities. Adaptive optics has been employed to compensate for sample-induced aberrations but the field-of-view is often limited to a single isoplanatic patch. Here, we propose a non-invasive approach based on the distortion matrix concept. This matrix basically connects any focusing point with the distorted part of its wave-front in reflection. Its time-reversal and entropy analysis allows to correct for high-order aberrations over multiple isoplanatic areas. We demonstrate a Strehl ratio enhancement up to 2500 and a diffraction-limited resolution until a depth of ten scattering mean free paths through biological tissues.
Lack of corneal transparency is a major cause of blindness worldwide. However, means to assess corneal transparency are limited and in current clinical and eye-bank practice usually involve a subjective and qualitative observation of opacities, sometimes with comparison against an arbitrary grading scale, by means of slit-lamp biomicroscopy. To address this unmet need, we have developed a method for corneal transparency assessment based on a new optical data analysis-based approach. Our method allows the objective extraction of quantitative parameters (including the scattering mean-free path, ls, a major indicator of scattering extent and thus of transparency of a medium) based on a physical model of corneal transparency and has been validated by laboratory experiments, using high-resolution, ex-vivo “fullfield” optical coherence tomography (FF-OCT). Here, we apply our algorithm to depth-resolved spectral domain OCT (SD-OCT) images of in-vivo corneas and demonstrate the feasibility of our approach by means of four representative clinical cases. Specifically, we illustrate its potential in discriminating between the four clinical cases and, if applicable, deriving the scattering mean-free path as a quantitative measure of corneal transparency from objective analysis of stromal light backscattering (attenuation of the coherent mean) with SD-OCT. This measure may be related to, or expressed as, Strehl ratio reduction and thus retinal PSF broadening. As such, our approach not only has the potential to supply the demand for an objective means to quantify corneal transparency in the clinical setting, but also to create an association with visual function.
Despite obvious improvements in visualization of the in vivo cornea through the faster imaging speeds and higher axial resolutions, cellular imaging stays unresolvable task for OCT, as en face viewing with a high lateral resolution is required. The latter is possible with FFOCT, a method that relies on a camera, moderate numerical aperture (NA) objectives and an incoherent light source to provide en face images with a micrometer-level resolution. Recently, we for the first time demonstrated the ability of FFOCT to capture images from the in vivo human cornea1. In the current paper we present an extensive study of appearance of healthy in vivo human corneas under FFOCT examination. En face corneal images with a micrometer-level resolution were obtained from the three healthy subjects. For each subject it was possible to acquire images through the entire corneal depth and visualize the epithelium structures, Bowman’s layer, sub-basal nerve plexus (SNP) fibers, anterior, middle and posterior stroma, endothelial cells with nuclei. Dimensions and densities of the structures visible with FFOCT, are in agreement with those seen by other cornea imaging methods. Cellular-level details in the images obtained together with the relatively large field-of-view (FOV) and contactless way of imaging make this device a promising candidate for becoming a new tool in ophthalmological diagnostics.
We present an optical coherence tomography (OCT) imaging system that effectively compensates unwanted axial motion with micron-scale accuracy. The OCT system is based on a swept-source (SS) engine (1060-nm center wavelength, 100-nm full-width sweeping bandwidth, and 100-kHz repetition rate), with axial and lateral resolutions of about 4.5 and 8.5 microns respectively. The SS-OCT system incorporates a distance sensing method utilizing an envelope-based surface detection algorithm. The algorithm locates the target surface from the B-scans, taking into account not just the first or highest peak but the entire signature of sequential A-scans. Subsequently, a Kalman filter is applied as predictor to make up for system latencies, before sending the calculated position information to control a linear motor, adjusting and maintaining a fixed system-target distance. To test system performance, the motioncorrection algorithm was compared to earlier, more basic peak-based surface detection methods and to performing no motion compensation. Results demonstrate increased robustness and reproducibility, particularly noticeable in multilayered tissues, while utilizing the novel technique. Implementing such motion compensation into clinical OCT systems may thus improve the reliability of objective and quantitative information that can be extracted from OCT measurements.
According to the World Health Organization (WHO), corneal diseases alongside with cataract and retinal diseases are major causes of blindness worldwide. For the 95.5% of corneal blindness cases, prevention or rehabilitation could have been possible without negative consequences for vision, provided that disease is diagnosed early. However, diagnostics at the early stage requires cellular-level resolution, which is not achieved with routinely used Slit-lamp and OCT instruments. Confocal microscopy allows examination of the cornea at a resolution approaching histological detail, however requires contact with a patient’s eye. The recently developed full-field OCT technique, in which 2D en face tangential optical slices are directly recorded on a camera, was successfully applied for ex vivo eye imaging. However, in vivo human eye imaging has not been demonstrated yet. Here we present a novel non-contact full-field OCT system, which is capable of imaging in air and, therefore, shows potential for in vivo cornea imaging in patients. The first cellular-level resolution ex vivo images of cornea, obtained in a completely non-contact way, were demonstrated. We were able to scan through the entire cornea (400 µm) and resolve epithelium, Bowman’s layer, stroma and endothelium. FFOCT images of the human cornea in vivo were obtained for the first time. The epithelium structures and stromal keratocyte cells were distinguishable. Both ex vivo and in vivo images were acquired with a large (1.26 mm x 1.26 mm) field of view. Cellular details in obtained images make this device a promising candidate for realization of high-resolution in vivo cornea imaging.
While validating our newly developed vision screener based on a double-pass retinal scanning system, we noticed that in all patients the signals from the retina were significantly higher when measurements were performed within a certain time interval referenced to the initial moment when the lights were dimmed and the test subject was asked to fixate on a target. This appeared to be most likely attributable to pupil size dynamics and triggered the present study, whose aim was to assess the pupillary “lights-off” response while fixating on a target in the presence of an accommodative effort. We found that pupil size increases in the first 60 to 70 s after turning off the room lights, and then it decreases toward the baseline in an exponential decay. Our results suggest that there is an optimal time window during which pupil size is expected to be maximal, that is during the second minute after dimming the room lights. During this time, window retinal diagnostic instruments based on double-pass measurement technology should deliver an optimal signal-to-noise ratio. We also propose a mathematical model that can be used to approximate the behavior of the normalized pupil size.
Amblyopia (“lazy eye”) is a major public health problem, caused by misalignment of the eyes (strabismus) or defocus. If detected early in childhood, there is an excellent response to therapy, yet most children are detected too late to be treated effectively. Commercially available vision screening devices that test for amblyopia’s primary causes can detect strabismus only indirectly and inaccurately via assessment of the positions of external light reflections from the cornea, but they cannot detect the anatomical feature of the eyes where fixation actually occurs (the fovea). Our laboratory has been developing technology to detect true foveal fixation, by exploiting the birefringence of the uniquely arranged Henle fibers delineating the fovea using retinal birefringence scanning (RBS), and we recently described a polarization-modulated approach to RBS that enables entirely direct and reliable detection of true foveal fixation, with greatly enhanced signal-to-noise ratio and essentially independent of corneal birefringence (a confounding variable with all polarization-sensitive ophthalmic technology). Here, we describe the design and operation of a new pediatric vision screener that employs polarization-modulated, RBS-based strabismus detection and bull’s eye focus detection with an improved target system, and demonstrate the feasibility of this new approach.
Corneal birefringence is a well-known confounding factor with all polarization-sensitive technology used for retinal scanning and other intraocular assessment. It has been studied extensively in adults, but little is known regarding age-related differences. Specifically, no information is available concerning corneal birefringence in children. For applications that are geared towards children, such as retinal birefringence scanning for strabismus screening purposes, it is important to know the expected range of both corneal retardance and azimuth in pediatric populations. This study investigated central corneal birefringence in children (ages three and above), by means of scanning laser polarimetry (GDx-VCC™, Carl Zeiss Meditec, Inc.). Children's measures of corneal retardance and azimuth were compared with those obtained in adults. As with previous studies in adults, corneal birefringence was found to vary widely in children, with corneal retardance ranging from 10 to 77 nm, and azimuth (slow axis) ranging from −11° to 71° (measured nasally downward). No significant differences in central corneal birefringence were found between children and adults, nor were significant age-related differences found in general. In conclusion, establishing knowledge of the polarization properties of the central cornea in children allows better understanding, exploitation, or bypassing of these effects in new polarization-sensitive pediatric ophthalmic applications.
To enhance foveal fixation detection while bypassing the deleterious effects of corneal birefringence in retinal
birefringence scanning (RBS), we developed a new RBS design introducing a double-pass spinning half wave plate
(HWP) and a fixed double-pass retarder into the optical system. Utilizing the measured corneal birefringence from a data
set of 300 human eyes, an algorithm and a related computer program, based on Mueller-Stokes matrix calculus, were
developed in MATLAB for optimizing the properties of both wave plates. Foveal fixation detection was optimized with
the HWP spun 9/16 as fast as the circular scan, with the fixed retarder having a retardance of 45° and fast axis at 90°.
With this new RBS design, a significant statistical improvement of 7.3 times in signal strength, i.e. FFT power, was
achieved for the available data set compared with the previous RBS design. The computer-model-optimized RBS design
has the potential not only for eye alignment screening, but also for remote fixation sensing and eye tracking applications.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.