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Clinical systems for optical coherence tomography (OCT) are used routinely to diagnose and monitor patients with a range of ocular diseases. They are large tabletop instruments operated by trained staff, and require mechanical stabilization of the head of the patient for positioning and motion reduction. Here we report the development and performance of a robot-mounted OCT scanner for the autonomous contactless imaging, at safe distances, of the eyes of freestanding individuals without the need for operator intervention or head stabilization. The scanner uses robotic positioning to align itself with the eye to be imaged, as well as optical active scanning to locate the pupil and to attenuate physiological eye motion. We show that the scanner enables the acquisition of OCT volumetric datasets, comparable in quality to those of clinical tabletop systems, that resolve key anatomic structures relevant for the management of common eye conditions. Robotic OCT scanners may enable the diagnosis and monitoring of patients with eye conditions in non-specialist clinics.

Optical coherence tomography (OCT) has seen widespread success as an in vivo clinical diagnostic 3D imaging modality, impacting areas including ophthalmology, cardiology, and gastroenterology. Despite its many advantages, such as high sensitivity, speed, and depth penetration, OCT suffers from several shortcomings that ultimately limit its utility as a 3D microscopy tool, such as its pervasive coherent speckle noise and poor lateral resolution required to maintain millimeter-scale imaging depths. Here, we present 3D optical coherence refraction tomography (OCRT), a computational extension of OCT that synthesizes an incoherent contrast mechanism by combining multiple OCT volumes, acquired across two rotation axes, to form a resolution-enhanced, speckle-reduced, refraction-corrected 3D reconstruction. Our label-free computational 3D microscope features a novel optical design incorporating a parabolic mirror to enable the capture of 5D plenoptic datasets, consisting of millimetric 3D fields of view over up to ± 75 ∘ without moving the sample. We demonstrate that 3D OCRT reveals 3D features unobserved by conventional OCT in fruit fly, zebrafish, and mouse samples.

Optical coherence tomography (OCT) has revolutionized diagnostics in ophthalmology. However, OCT requires a trained operator and patient cooperation to carefully align a scanner with the subject’s eye and orient it in such a way that it images a desired region of interest at the retina. With the goal of automating this process of orienting and aligning the scanner, we developed a robot-mounted OCT scanner that automatically aligned with the pupil while matching its optical axis with the target region of interest at the retina. The system used two 3D cameras for face tracking and three high-resolution 2D cameras for pupil and gaze tracking. The tracking software identified 5 degrees of freedom for robot alignment and ray aiming through the ocular pupil: 3 degrees of translation (x, y, z) and 2 degrees of orientation (yaw, pitch). We evaluated the accuracy, precision, and range of our tracking system and demonstrated imaging performance on free-standing human subjects. Our results demonstrate that the system stabilized images and that the addition of gaze tracking and aiming allowed for region-of-interest specific alignment at any gaze orientation within a 28° range.

Point-scanned imaging modalities such as optical coherence tomography (OCT) are subject to frame rate limits governed by the image resolution, sampling rate, and scanner dynamics. For scenes with dynamic features on static backgrounds, adaptive scanning escapes these limits by visiting scan positions only as needed. We implemented adaptive scanning using a probabilistic approach that balanced re-imaging of known dynamic positions with exploration for undiscovered ones. We evaluated our approach in model systems that simulated multitarget tracking and ophthalmic surgery using a swept-source OCT system. We demonstrated frame rate speedups in excess of 5 × without degradation in image quality, a performance that would have otherwise required a significantly faster source.

Optical coherence tomography (OCT) may be useful for guidance of ocular microsurgeries such as deep anterior lamellar keratoplasty (DALK), a form of corneal transplantation that requires delicate insertion of a needle into the stroma to approximately 90% of the corneal thickness. However, visualization of the true shape of the cornea and the surgical tool during surgery is impaired in raw OCT volumes due to both light refraction at the corneal boundaries, as well as geometrical optical path length distortion due to the group velocity of broadband OCT light in tissue. Therefore, uncorrected B-scans or volumes may not provide an accurate visualization suitable for reliable surgical guidance. In this article, we introduce a method to correct for both refraction and optical path length distortion in 3D in order to reconstruct corrected OCT B-scans in both natural corneas and corneas deformed by needle insertion. We delineate the separate roles of phase and group index in OCT image distortion correction, and introduce a method to estimate the phase index from the group index which is readily measured in samples. Using the measured group index and estimated phase index of human corneas at 1060 nm, we demonstrate quantitatively accurate geometric reconstructions of the true cornea and inserted needle shape during simulated DALK surgeries.

Primary care professionals (PCPs) have a central role in screening for diabetic retinopathy (DR), especially in settings where access to specialty eye care is limited. Data on current DR screening practice patterns in primary care are needed to inform screening strategies.To assess the practice patterns of fundoscopic examination for DR screening in a large primary care network and to evaluate the sensitivity and accuracy of PCP fundoscopy for detecting DR.A retrospective cohort study was performed using random sampling and manual review of electronic health records of PCP fundoscopic examination documentation compared with documentation of an examination performed by an eye care professional (ophthalmologist or optometrist) within 2 years before or after primary care encounters. From a single-institution primary care network of 28 clinics, 7449 adult patients with diabetes seen at least once in the primary care network in 2019 were eligible for this study. Data from 2001 encounters were abstracted from the electronic health record for a random sample of 767 patients. Data analysis was performed from January 2021 to May 2022.Fundoscopic examination by PCPs.The frequency of PCPs performing fundoscopy at least once in the calendar year for patients with diabetes. Univariate and multivariable logistic regression analyses were performed to identify patient, clinician, and clinic factors associated with PCPs performing fundoscopy at least once in the calendar year. The PCP examination results were compared with diagnoses made by eye care professionals to assess the sensitivity and accuracy of the findings from PCP examinations.Among the 767 adult patients with diabetes included in the analysis, 387 (50.5%) were female, and the median age was 64 years (IQR, 54-71 years). Primary care professionals documented a fundoscopic examination for 93 patients (12.1%); all results were documented as normal. When eye care professional examination results were used as the reference standard, the accuracy of PCP fundoscopic examination was 62.7% (95% CI, 50.0%-73.9%) and sensitivity for detecting disease was 0.0% (95% CI, 0.0%-14.9%). No patient demographic or clinical characteristics were associated with PCPs performing fundoscopy. In multivariable logistic regression, the number of PCP years in practice was associated with greater odds of patients receiving fundoscopy at least once in the year (adjusted odds ratio per 10 years in practice, 1.26; 95% CI, 1.01-1.59; P = .04); having nurse practitioner credentials was associated with lower odds of receiving fundoscopy (adjusted odds ratio, 0.23; 95% CI, 0.04-0.79; P = .049; compared with having physician credentials); after adjusting for rural clinic location, clinic location in a primary care shortage area, and documentation of an up-to-date eye care professional examination by a PCP in the study year.In this cohort study, fundoscopic examination was rarely performed and was not sensitive for detecting DR in primary care practice. Because the rate of DR screening by eye care professionals remains low, research to explore and break down barriers to the implementation of effective primary care-based DR screening strategies, such as teleretinal imaging, is needed to prevent vision loss from undiagnosed DR.

The physical distancing requirements necessary to prevent spread of the novel coronavirus, SARS-CoV-2, requires a change in approach for clinical ophthalmic imaging. Conventional optical coherence tomography (OCT) systems require patients to position themselves in chin/forehead rests for stabilization with the system operator in close proximity. We developed a robotically aligning OCT (RAOCT) system that provides volumetric retinal images encompassing both the optic nerve head and fovea. Our RAOCT system self aligned to subjects’ eyes (seated, no contact with restraints), acquired OCT images of both normal and diseased retinas, all with allowing the operator behind a barrier >2 m from the subjects.

Optical coherence tomography (OCT) has revolutionized diagnostics in ophthalmology. Traditionally, OCT requires an operator and patient cooperation to compensate refraction error as well as align the scanner with the subject’s eye. We have developed a robot-mounted OCT scanner that automatically focuses and aligns with the subjects’ eye by compensating motion, gaze, and refraction error. The system utilizes a combination of face and pupil tracking cameras to align while focusing through digital control of a tunable lens. We demonstrate our system by self-aligning with human eyes subject to physiological motion and gaze change as well as correcting defocus of a phantom eye.

Anterior uveitis is the most common form of intraocular inflammation, and one of its main signs is the presence of white blood cells (WBCs) in the anterior chamber (AC). Clinically, the true composition of cells can currently only be obtained using AC paracentesis, an invasive procedure to obtain AC fluid requiring needle insertion into the AC. We previously developed a spectroscopic optical coherence tomography (SOCT) analysis method to differentiate between populations of RBCs and subtypes of WBCs, including granulocytes, lymphocytes and monocytes, both in vitro and in ACs of excised porcine eyes. We have shown that different types of WBCs have distinct characteristic size distributions, extracted from the backscattered reflectance spectrum of individual cells using Mie theory. Here, we further develop our method to estimate the composition of blood cell mixtures, both in vitro and in vivo. To do so, we estimate the size distribution of unknown cell mixtures by fitting the distribution observed using SOCT with a weighted combination of reference size distributions of each WBC type calculated using kernel density estimation. We validate the accuracy of our estimation in an in vitro study, by comparing our results for a given WBC sample mixture with the cellular concentrations measured by a hemocytometer and SOCT images before mixing. We also conducted a small in vivo quantitative cell mixture validation pilot study which demonstrates congruence between our method and AC paracentesis in two patients with uveitis. The SOCT based method appears promising to provide quantitative diagnostic information of cellular responses in the ACs of patients with uveitis.

Optical coherence tomography (OCT) has revolutionized diagnostics in ophthalmology. However, OCT traditionally requires an operator and patient cooperation to align a scanner with the subject’s eye and image a specific location of the retina. We have developed a robot-mounted OCT scanner that automatically aligns with the subjects’ eye by compensating motion and gaze. In addition to using face and pupil tracking feedback to align the scanner, the system uses gaze feedback to track a retinal region of interest, such as the fovea. We demonstrate our system by tracking the fovea of human eyes subject to physiological motion and gaze change.

Adaptive optics scanning laser ophthalmoscopy (AOSLO) has advanced the study of retinal structure and function by enabling in vivo imaging of individual photoreceptors. Most implementations of AOSLOs are large, complex tabletop systems, thereby preventing high quality photoreceptor imaging of patients who are unable to sit upright and/or fixate for an imaging session. We have previously addressed this limitation in the clinical translation of AOSLO by developing the first confocal handheld AOSLO (HAOSLO) capable of cone photoreceptor visualization in adults and infants. However, confocal AOSLO images suffer from imaging artifacts and the inability to detect remnant cone structure, leading to ambiguous or potentially misleading results. Recently, it has been shown that non-confocal split-detection (SD) AOSLO images, created by the collection of multiply backscattered light, enables more reliable studies of retinal photoreceptors by providing images of the cone inner segment. In this paper, we detail the extension of our HAOSLO probe to enable multi-channel light collection resulting in the first ever multimodal handheld AOSLO (M-HAOSLO). Imaging sessions were conducted on two dilated, healthy human adult volunteers, and M-HAOSLO images taken in handheld operation mode reveal the cone photoreceptor mosaic. Aside from being the first miniaturized and portable implementation of a SD AOSLO system, M-HAOSLO relies on sensorless optimization of the wavefront to correct aberrations. Thus, we also show the first ever SD images collected after correction of the eye’s estimated wavefront.

We propose an empirical distortion correction approach for optical coherence tomography (OCT) devices that use a fan-scanning pattern to image the posterior eye segment. Two types of reference markers were used to empirically estimate the distortion correction approach in tree shrew eyes: retinal curvature from MRI images and implanted glass beads of known diameter. Performance was tested by correcting distorted images of the optic nerve head. In small animal eyes, our purposed method effectively reduced nonlinear distortions compared to a linear scaling method. No commercial posterior segment OCT provides anatomically correct images, which may bias the 3D interpretation of these scans. Our method can effectively reduce such bias.

Keratoconus (KC) is the most common corneal ectatic disorder affecting >300,000 people in the US. KC normally has its onset in adolescence, progressively worsening through the third to fourth decades of life. KC patients report significant impaired vision-related quality of life. Genetic factors play an important role in KC pathogenesis. To identify novel genes in familial KC patients, we performed whole exome and genome sequencing in a four-generation family. We identified potential variants in the PPIP5K2 and PCSK1 genes. Using in vitro cellular model and in vivo gene-trap mouse model, we found critical evidence to support the role of PPIP5K2 in normal corneal function and KC pathogenesis. The gene-trap mouse showed irregular corneal surfaces and pathological corneal thinning resembling KC. For the first time, we have integrated corneal tomography and pachymetry mapping into characterization of mouse corneal phenotypes which could be widely implemented in basic and translational research for KC diagnosis and therapy in the future.

Ocular deformation may be associated with biomechanical alterations in the structures of the eye, especially the cornea and sclera in conditions such as keratoconus, congenital glaucoma, and pathological myopia. Here, we propose a method to estimate ocular shape using an ultra-wide field MHz swept-source optical coherence tomography (SS-OCT) with a Fourier Domain Mode-Locked (FDML) laser and distortion correction of the images. The ocular biometrics for distortion correction was collected by an IOLMaster 700, and localized Gaussian curvature was proposed to quantify the ocular curvature covering a field-of-view up to 65°×62°. We achieved repeatable curvature shape measurements (intraclass coefficient = 0.88 ± 0.06) and demonstrated its applicability in a pilot study with individuals (N = 11) with various degrees of myopia.

The majority of the eye's refractive power lies in the cornea, and pathological changes in its shape can affect vision. Small animal models offer an unparalleled degree of control over genetic and environmental factors that can help elucidate mechanisms of diseases affecting corneal shape. However, there is not currently a method to characterize the corneal shape of small animal eyes with topography or pachymetry maps, as is done clinically for humans. We bridge this gap by demonstrating methods using optical coherence tomography (OCT) to generate the first topography and pachymetry (thickness) maps of mouse corneas. Radii of curvature acquired using OCT were validated using calibration spheres as well as in vivo mouse corneas with a mouse keratometer. The resulting topography and pachymetry maps are analogous to those used diagnostically in clinic and potentially allow for characterization of genetically modified mice that replicate key features of human corneal disease.

There is potential clinical significance in identifying cellular responses in the anterior chamber (AC) of the eye, which can indicate hyphema (an accumulation of red blood cells [RBCs]) or aberrant intraocular inflammation (an accumulation of white blood cells [WBCs]). In this work, we developed a spectroscopic OCT analysis method to differentiate between populations of RBCs and subtypes of WBCs, including granulocytes, lymphocytes and monocytes, both in vitro and in ACs of porcine eyes. We developed an algorithm to track single cells within OCT data sets, and extracted the backscatter reflectance spectrum of each single cell from the detected interferograms using the short-time Fourier transform (STFT). A look-up table of Mie back-scattering spectra was generated and used to correlate the backscatter spectral features of single cells to their characteristic sizes. The extracted size distributions based on the best Mie spectra fit were significantly different between each cell type. We also studied theoretical backscattering models of single RBCs to further validate our experimental results. The described work is a promising step towards clinically differentiating and quantifying AC blood cell types.

High speed optical coherence tomography (OCT) systems with A-scan rates greater than 100 kHz allow for 4D visualizations in applications such as intraoperative OCT. However, traditional triangle or sawtooth waveforms used to drive galvanometer scanners often have frequency content that exceeds the bandwidth of the scanners, leading to distorted scans. Sinusoidal waveforms used to drive resonant scanners also lead to distorted scans due to the nonlinear scan velocity. Additionally, with raster scan patterns, the scanner needs time to stop and reverse direction in between B-scans, leading to significant acquisition dead time. Continuous scan patterns such as constant frequency spiral scanning or Lissajous scanning no longer have acquisition dead times, but suffer from non-uniform sampling across the imaging plane. We previously introduced constant linear velocity (CLV) spiral scanning as a novel scan pattern to maximize the data acquisition efficiency of high speed OCT systems. While this continuous scan pattern has no acquisition dead time and produces more uniform sampling compared to raster scanning, it required significant processing time. We introduce a processing pipeline implemented using CUDA in C++, which drastically reduces the amount of processing time needed, allowing real time visualization of 4D OCT data. To demonstrate its potential utility, we used CLV scanning with a 100 kHz swept-source OCT system to image retinas of enucleated porcine eyes undergoing mock ophthalmic surgery movements. Additionally, we rendered these volumes in virtual reality (VR) in real time, allowing for interactive manipulation and sectioning.

Imaging the entire human cornea with a conventional OCT system configuration requires trade-offs between resolution and depth-of-focus because the cornea is curved over a depth of approximately 4 mm. These system trade-offs result in image quality variations in the corneal image such as a bright apex surrounded by decreasing intensity as the cornea curves away from the apex. These intensity changes cause non-biological ambiguities in interpreting the image, make it difficult to see anatomy in the dim areas, and make automated surface detection difficult in the periphery. To address this problem, we developed a continuously focusing corneal OCT system coupled with a constant linear velocity (CLV) spiral scan pattern that is able to better maintain focus from the apex to the deeper cornea during a scan. The continuous focusing was implemented by introducing a focusing telescope on a motorized stage into the sample arm and matching the translation of the telescope with the CLV scan as it spiraled from the corneal apex outwards. Orthogonal B-scans prior to volume acquisition were used as a reference to estimate and correct motion that occurred during the subsequent CLV scan. A consented subject was imaged, and the resultant image showed increased intensity in the peripheral and deeper cornea and anterior chamber. Continuous focusing with CLV spiral scanning is a promising design change to OCT systems allowing adequate focus over relatively large depths such as for scanning the human cornea.

Contemporary anterior segment and retinal optical coherence tomography (OCT) systems only image their particular designated region of the eye and cannot image both areas of the eye at once. This separation is due to the differences in optical system design needed to properly image the front or back of the eye and also due to limitations in the imaging depth of current commercial OCT systems. More recently, research and commercial OCT systems capable of "whole-eye" imaging have been described. These whole-eye OCT systems enable applications such as ocular biometry for cataract surgery, ocular shape analysis for myopia, and others. Further, these whole-eye OCT systems allow us to image the eye as an integrated whole rather than as separate, independent divisions.

Current conventional clinical OCT systems image either only the anterior or the posterior eye during a single acquisition. This localized imaging limits conventional OCT’s use for characterizing global ocular morphometry and biometry, which requires knowledge of spatial relationships across the entire eye. We developed a “whole eye” optical coherence tomography system that simultaneously acquires volumes with a wide field-of-view for both the anterior chamber (14 x 14 mm) and retina (55°) using a single source and detector. This system was used to measure retinal curvature in a pilot population and compared against curvature of the same eyes measured with magnetic resonance imaging.

IMPACT: Despite its importance in systemic diseases such as diabetes, the eye is notably difficult to examine for non-specialists; this study introduces a fully automated approach for eye disease screening, coupling a deep learning algorithm with a robotically-aligned optical coherence tomography system to improve eye care in non-ophthalmology settings. OBJECTIVES/GOALS: This study aims to develop and test a deep learning (DL) method to classify images acquired from a robotically-aligned optical coherence tomography (OCT) system as normal vs. abnormal. The long-term goal of our study is to integrate artificial intelligence and robotic eye imaging to fully automate eye disease screening in diverse clinical settings. METHODS/STUDY POPULATION: Between August and October 2020, patients seen at the Duke Eye Center and healthy volunteers (age ≥18) were imaged with a custom, robotically-aligned OCT (RAOCT) system following routine eye exam. Using transfer learning, we adapted a preexisting convolutional neural network to train a DL algorithm to classify OCT images as normal vs. abnormal. The model was trained and validated on two publicly available OCT datasets and two of our own RAOCT volumes. For external testing, the top-performing model based on validation was applied to a representative averaged B-scan from each of the remaining RAOCT volumes. The model’s performance was evaluated against a reference standard of clinical diagnoses by retina specialists. Saliency maps were created to visualize the areas contributing most to the model predictions. RESULTS/ANTICIPATED RESULTS: The training and validation datasets included 87,697 OCT images, of which 59,743 were abnormal. The top-performing DL model had a training accuracy of 96% and a validation accuracy of 99%. For external testing, 43 eyes of 27 subjects were imaged with the robotically-aligned OCT system. Compared to clinical diagnoses, the model correctly labeled 18 out of 22 normal averaged B-scans and 18 out of 21 abnormal averaged B-scans. Overall, in the testing set, the model had an AUC for the detection of pathology of 0.92, an accuracy of 84%, a sensitivity of 86%, and a specificity of 82%. For the correctly predicted scans, saliency maps identified the areas contributing most to the DL algorithm’s predictions, which matched the regions of greatest clinical importance. DISCUSSION/SIGNIFICANCE OF FINDINGS: This is the first study to develop and apply a DL model to images acquired from a self-aligning OCT system, demonstrating the potential of integrating DL and robotic eye imaging to automate eye disease screening. We are working to translate this technology for use in emergency departments and primary care, where it will have the greatest impact.

In vivo imaging permits longitudinal study of ocular disease processes in the same animal over time. Two different in vivo optical imaging modalities – optical coherence tomography (OCT) and fluorescence – provide important structural and cellular data respectively about disease processes. In this Methods in Eye Research article, we describe and demonstrate the combination of these two modalities producing a truly simultaneous OCT and fluorescence imaging system for imaging of fluorescently labeled animal models. This system uses only a single light source to illuminate both modalities, and both share the same field of view. This allows simultaneous acquisition of OCT and fluorescence images, and the benefits of both techniques are realized without incurring increased costs in variability, light exposure, time, and post-processing effort as would occur when the modalities are used separately. We then utilized this system to demonstrate multi-modal imaging in a progression of samples exhibiting both fluorescence and OCT scattering beginning with resolution targets, ex vivo thy1-YFP labeled neurons in mouse eyes, and finally an in vivo longitudinal time course of GFP labeled myeloid cells in a mouse model of ocular allergy.

Non-confocal adaptive optics scanning laser ophthalmoscopy (AOSLO) has enhanced the study of human retinal photoreceptors by providing complementary information to standard confocal AOSLO images. Previously we developed the first confocal handheld AOSLO (HAOSLO) capable of in vivo cone photoreceptor imaging in supine and non-cooperative patients. Here, we introduce the first multimodal (M-)HAOSLO for confocal and non-confocal split-detection (SD) imaging to allow for more comprehensive patient data collection. Aside from its unprecedented miniature size and weight, M-HAOSLO is also the first system to perform sensorless wavefront-corrected SD imaging of cone photoreceptors.

Ultrahigh speed optical coherence tomography (OCT) systems with >100 kHz A-scan rates can generate volumes rapidly with minimal motion artifacts and are well suited for 4D imaging (volumes through time) applications such as intra-operative imaging. In such systems, high OCT data acquisition efficiency (defined as the fraction of usable A-scans generated during the total acquisition time) is desired to maximize the volumetric frame rate and sampling pitch. However, current methods for beam scanning using non-resonant and resonant mirror scanners can result in severe scan distortion and transverse oversampling as well as require acquisition dead times, which limit the acquisition efficiency and performance of ultrahigh speed 4D OCT. We introduce constant linear velocity spiral scanning (CLV-SC) as a novel beam scanning method to maximize the data acquisition efficiency of ultrahigh speed 4D OCT systems. We demonstrate that CLV-SC does not require acquisition dead times and achieves more uniform transverse sampling compared to raster scanning. To assess its clinical utility, we implement CLV-SC with a 400 kHz OCT system and image the anterior eye and retina of healthy adults at up to 10 volumes per second with isotropic transverse sampling, allowing B-scans with equal sampling pitch to be extracted from arbitrary locations within a single volume. The feasibility of CLV-SC for intra-operative imaging is also demonstrated using a 800 kHz OCT system to image simulated retinal surgery at 15 volumes per second with isotropic transverse sampling, resulting in high quality volume renders that enable clear visualization of surgical instruments and manipulation of tissue.

Elevated intracranial pressure (ICP) can result from a variety of etiologies including severe head trauma, brain tumors and inflammations, or spontaneously (idiopathic). Sustained elevated ICP can be damaging to the central nervous system and potentially fatal depending on the magnitude and rate of pressure elevation. A classic ophthalmic sign of elevated ICP is optic disc edema or papilledema. A previous study has shown that magnetic resonance imaging (MRI) can visualize posterior eye flattening in the presence of increased ICP. In contrast to MRI, optical coherence tomography (OCT) is a more commonly used and available ocular imaging technique that can readily show swelling of the optic nerve head relative to the surrounding retinal surface. However, the ability to recover an accurate estimate of retinal radius of curvature (Rc) requires several other parameters such as the ocular axial length and distance from the imaging system. To address this need, we developed a custom whole eye OCT system (centered at 1050nm; 100kHz A-scan rate) providing simultaneous wide field of views of the anterior and posterior ocular segments. A subject was seen in the Duke neuro-ophthalmology clinic with papilledema from idiopathic intracranial hypertension (IIH). They were imaged with MRI as part of their clinical workup. Retinal Rc as measured by both OCT and MRI were comparable and indicated posterior flattening of the globe compared to normal.

There is great clinical importance in identifying cellular responses in the anterior chamber (AC) which can indicate signs of hyphema (an accumulation of red blood cells (RBCs)) or aberrant intraocular inflammation (an accumulation of white blood cells (WBCs)). These responses are difficult to diagnose and require specialized equipment such as ophthalmic microscopes and specialists trained in examining the eye. In this work, we applied spectroscopic OCT to differentiate between RBCs and subtypes of WBCs, including neutrophils, lymphocytes and monocytes, both in vitro and in ACs of porcine eyes. We located and tracked single cells in OCT volumetric images, and extracted the spectroscopic data of each cell from the detected interferograms using short-time Fourier Transform (STFT). A look-up table of Mie spectra was generated and used to correlate the spectroscopic data of single cells to their characteristic sizes. The accuracy of the method was first validated on 10um polystyrene microspheres. For RBCs and subtypes of WBCs, the extracted size distributions based on the best Mie spectra fit were significantly different between each cell type by using the Wilcoxon rank-sum test. A similar size distribution of neutrophils was also acquired in the measurements of cells introduced into the ACs of porcine eyes, further supporting spectroscopic OCT for potentially differentiating and quantifying blood cell types in the AC in vivo.

Purpose To determine the ability of motion-corrected optical coherence tomography (OCT) to measure the corneal refractive power change due to LASIK. Design Evaluation of a diagnostic test or technology in a cohort. Subjects A total of 70 eyes from 37 subjects undergoing LASIK were measured preoperatively. A total of 39 eyes from 22 subjects were measured postoperatively and completed the study. Methods Consecutive patients undergoing LASIK at the Duke Eye Center who consented to participate were imaged with Placido-ring topography, Scheimpflug photography, and OCT on the day of their surgery. Patients were then reimaged with the same imaging systems at the postoperative month 3 visit. Change in preoperative to postoperative corneal refractive power as measured by each of the imaging modalities was compared with the preoperative to postoperative change in manifest refraction (MRx) using the t test with generalized estimating equations. Main Outcome Measures Corneal refractive power change due to LASIK as measured by Placido-ring topography, Scheimpflug photography, and OCT compared with the MRx change vertexed to the corneal plane. The change in MRx should correspond to the change in the corneal refractive power from LASIK and was considered the reference measurement. Results In 22 individuals (39 eyes) returning after LASIK, we found no significant difference between the clinically measured pre- to post-LASIK change in MRx and both Scheimpflug photography ( P = 0.714) and OCT ( P = 0.216). In contrast, keratometry values from Placido-ring topography were found to be significantly different from the measured refractive change ( P Conclusions Motion-corrected OCT more accurately measures the change in corneal refractive power due to laser refractive surgery than other currently available clinical devices. By offering accurate corneal refractive power measurements in normal and surgically modified subjects, OCT offers a compelling alternative to current clinical devices for determining corneal refractive power.

Optical coherence tomography (OCT) has revolutionized clinical observation of the eye and is an indispensable part of the modern ophthalmic practice. Unlike many other ophthalmic imaging techniques, OCT provides three-dimensional information about the imaged eye. However, conventional clinical OCT systems image only the anterior or the posterior eye during a single acquisition. Newer OCT systems have begun to image both during the same acquisition but with compromises such as limited field of view in the posterior eye or requiring rapid switching between the anterior and posterior eye during the scan. We describe here the development and demonstration of an OCT system with truly simultaneous imaging of both the anterior and posterior eye capable of imaging the full anterior chamber width and 50° on the retina (macula, optic nerve, and arcades). The whole eye OCT system was developed using custom optics and optomechanics. Polarization was utilized to separate the imaging channels. We utilized a 200kHz swept-source laser (Axsun Technologies) centered at 1040±50nm of bandwidth. The clock signal generated by the laser was interpolated 4x to generate 5504 samples per laser sweep. With the whole eye OCT system, we simultaneously acquired anterior and posterior segments with repeated B-scans as well as three-dimensional volumes from seven healthy volunteers (other than refractive error). On three of these volunteers, whole eye OCT and partial coherence interferometry (LenStar PCI, Haag-Streit) were used to measure axial eye length. We measured a mean repeatability of ±47µm with whole eye OCT and a mean difference from PCI of -68µm.

Patient motion artifacts are an important source of data irregularities in OCT imaging. With longer duration OCT scans – as is needed for large wide field of view scans or increased scan density – motion artifacts become increasingly problematic. Strategies to mitigate these motion artifacts are then necessary to ensure OCT data integrity. A popular strategy for reducing motion artifacts in OCT images is to capture two orthogonally oriented volumetric scans containing uncorrelated motion and subsequently reconstructing a motion-free volume by combining information from both datasets. While many different variations of this registration approach have been proposed, even the most recent methods might not be suitable for wide FOV OCT scans which can be lacking in features away from the optic nerve head or arcades. To address this problem, we propose a two-stage motion correction algorithm for wide FOV OCT volumes. In the first step, X and Y axes motion is corrected by registering OCT summed voxel projections (SVPs). To achieve this, we introduce a method based on a custom variation of the dense optical flow technique which is aware of the motion free orientation of the scan. Secondly, a depth (Z axis) correction approach based on the segmentation of the retinal layer boundaries in each B-scan using graph-theory and dynamic programming is applied. This motion correction method was applied to wide field retinal OCT volumes (approximately 80° FOV) of 3 subjects with substantial reduction in motion artifacts.

Purpose We advance studies of subretinal treatments by developing a microscope-integrated optical coherence tomography (MIOCT) image-based method for measuring the volume of therapeutics delivered into the subretinal space. Methods A MIOCT image-based volume measurement method was developed and assessed for accuracy and reproducibility by imaging an object of known size in model eyes. This method then was applied to subretinal blebs created by injection of diluted triamcinolone. Bleb volumes obtained from MIOCT were compared to the intended injection volume and the surgeon's estimation of leakage. Results Validation of the image-based volume measurement method showed accuracy to ±1.0 μL (6.0% of measured volume) with no statistically significant variation under different imaging settings. When this method was applied to subretinal blebs, four of 11 blebs without surgeon-observed leakage yielded a mean volume of 32 ± 12.5 μL, in contrast to the intended 50 μL volume injected from the delivery device. This constituted a mean difference of −18 μL (mean percent error, 36 ± 25%). For all 11 blebs, the surgeon's estimations of leakage were significantly different from and showed no correlation with the volume loss based on image-based volume measurements (P < 0.001, paired t-test; intraclass correlation = 0). Conclusions We validated an accurate and reproducible method for measuring subretinal volumes using MIOCT. Use of this method revealed that the intended volume might not be delivered into the subretinal space. MIOCT can allow for accurate assessment of subretinal dose delivered, which may have therapeutic implications in evaluating the efficacy and toxicity of subretinal therapies. Translational Relevance Use of MIOCT can provide feedback on the accuracy of subretinal injection volumes delivered.

Clinically, gonioscopy is used to provide en face views of the ocular angle. The angle has been imaged with optical coherence tomography (OCT) through the corneoscleral limbus but is currently unable to image the angle from within the ocular anterior chamber. We developed a novel gonioscopic OCT system that images the angle circumferentially from inside the eye through a custom, radially symmetric, gonioscopic contact lens. We present, to our knowledge, the first 360° circumferential volumes (two normal subjects, two subjects with pathology) of peripheral iris and iridocorneal angle structures obtained via an internal approach not typically available in the clinic.

Age-related macular degeneration (AMD) is a major cause of vision loss in the elderly. To better study the pathobiology of AMD, postmortem eyes offer an excellent opportunity to correlate optical coherence tomography (OCT) imaging characteristics with histopathology. However, postmortem eyes from autopsy present challenges to standard OCT imaging including opaque anterior segment structures and standard of care autopsy processing resulting in oblique views to the macula. To overcome these challenges, we report a custom periscope attached by a standard mount to an OCT sample arm and demonstrate high quality macular OCT acquisitions in autopsy-processed eyes.

The ocular iridocorneal angle is generally an optically inaccessible area when viewed directly through the cornea due to the high angle of incidence required and the large index of refraction difference between air and cornea ( n air = 1.000 and n cornea = 1.376) resulting in total internal reflection. Gonioscopy allows for viewing of the angle by removing the aircornea interface through the use of a special contact lens on the eye. Gonioscopy is used clinically to visualize the angle directly but only en face. Optical coherence tomography (OCT) has been used to image the angle and deeper structures via an external approach. Typically, this imaging technique is performed by utilizing a conventional anterior segment OCT scanning system. However, instead of imaging the apex of the cornea, either the scanner or the subject is tilted such that the corneoscleral limbus is orthogonal to the optical axis of the scanner requiring multiple volumes to obtain complete circumferential coverage of the ocular angle. We developed a novel gonioscopic OCT (GOCT) system that images the entire ocular angle within a single volume via an “internal” approach through the use of a custom radially symmetric gonioscopic contact lens. We present, to our knowledge, the first complete 360° circumferential volumes of the iridocorneal angle from a direct, internal approach.

OCT volumetric acquisition is often subject to motion artifacts. Ocular pupil tracking is a simple and robust method to track patient movement. Real-time tracking of the ocular pupil mitigates lateral motion artifacts in OCT volumes.