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Intraoperative optical coherence tomography (OCT) systems provide high-resolution, real-time visualization and/or guidance of microsurgical procedures. While the use of intraoperative OCT in ophthalmology has significantly improved qualitative visualization of surgical procedures inside the eye, new surgical techniques to deliver therapeutics have highlighted the lack of quantitative information available with current-generation intraoperative systems. Indirect viewing systems used for retinal surgeries introduce distortions into the resulting OCT images, making it particularly challenging to make calibrated quantitative measurements. Using an intraoperative OCT system based in part on the Leica Enfocus surgical microscope interface, we have devised novel measurement procedures, which allowed us to build optical and mathematical models to perform validation of quantitative measurements of intraocular structures for intraoperative OCT. These procedures optimize a complete optical model of the sample arm including the OCT scanner, viewing attachments, and the patient’s eye, thus obtaining the voxel pitch throughout an OCT volume and performing quantitative measurements of the dimensions of imaged objects within the operative field. We performed initial validation by measuring objects of known size in a controlled eye phantom as well as ex vivo porcine eyes. The technique was then extended to measure other objects and structures in ex vivo porcine eyes and in vivo human eyes.

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.

Ophthalmic microsurgery is technically difficult because the scale of required surgical tool manipulations challenge the limits of the surgeon's visual acuity, sensory perception, and physical dexterity. Intraoperative optical coherence tomography (OCT) imaging with micrometer-scale resolution is increasingly being used to monitor and provide enhanced real-time visualization of ophthalmic surgical maneuvers, but surgeons still face physical limitations when manipulating instruments inside the eye. Autonomously controlled robots are one avenue for overcoming these physical limitations. In this article, we demonstrate the feasibility of using learning from demonstration and reinforcement learning with an industrial robot to perform OCT-guided corneal needle insertions in an ex vivo model of deep anterior lamellar keratoplasty (DALK) surgery. Our reinforcement learning agent trained on ex vivo human corneas, then outperformed surgical fellows in reaching a target needle insertion depth in mock corneal surgery trials. This article shows the combination of learning from demonstration and reinforcement learning is a viable option for performing OCT-guided robotic ophthalmic surgery.

OBJECTIVE: To report our ability to capture, grade reliably and analyze bedside macular optical coherence tomography (OCT) images from preterm infants and relate OCT findings to biological factors and retinopathy of prematurity (ROP) status at a single time window in the STudy of Eye imaging in Preterm infantS (BabySTEPS). DESIGN: Prospective observational study PARTICIPANTS: Preterm infants eligible for ROP screening, with parental consent for research and a 36±1 weeks postmenstrual age (PMA) visit. METHODS: We imaged both eyes of preterm infants with an investigational non-contact, handheld swept-source OCT at the time of clinical ROP examinations. Macular OCT features and layer thicknesses for untreated eyes of infants at 36±1 weeks PMA were compared to demographic data and clinical ROP examination performed by experts. Statistical analyses accounted for the use of both eyes of infants. MAIN OUTCOME MEASURES: Macular OCT features and layer thicknesses, gender, race/ethnicity, gestational age, birth weight, ROP stage, and plus disease. RESULTS: We captured macular OCT from 169 eyes (one eye excluded for prior ROP treatment) at 36±1 weeks PMA. The quality of OCT volumes was excellent in 33 eyes (19%), acceptable in 112 (67%), poor in 24 (14%) and unusable in 0 (0%). Macular edema was present in 60% of eyes and bilateral in 82% of infants with edema. At the fovea, retinal thickness and inner nuclear layer (INL) thickness increased with edema severity: 183±36μm and 51±27μm in mild edema (16% of eyes), 308±57μm and 163±53μm in moderate (25%) and 460±76μm and 280±83μm in severe (12%), respectively. With an increase in ROP stage from 0 to 2, the mean (standard deviation) retinal thickness at fovea increased from 227(124) to 297(99)μm, p

Optical coherence tomography (OCT) is a cross-sectional, micrometre-scale imaging modality with widespread clinical application. Typical OCT systems sacrifice lateral resolution to achieve long depths of focus for bulk tissue imaging, and therefore tend to have better axial than lateral resolution. Such anisotropic resolution can obscure fine ultrastructural features. Furthermore, conventional OCT suffers from refraction-induced image distortions. Here, we introduce optical coherence refraction tomography (OCRT), which extends the superior axial resolution to the lateral dimension, synthesizing undistorted cross-sectional image reconstructions from multiple conventional images acquired with angular diversity. In correcting refraction-induced distortions to register the OCT images, OCRT also achieves spatially resolved refractive index imaging. We demonstrate greater than threefold improvement in lateral resolution as well as speckle reduction in imaging the tissue ultrastructure, consistent with histology. With further optimization in optical designs to incorporate angular diversity into clinical instruments, OCRT could be widely applied as an enhancement over conventional OCT. By synthesizing undistorted cross-sectional image reconstructions from multiple conventional images acquired with angular diversity, optical coherence refraction tomography offers greater than threefold improvement in lateral resolution and speckle reduction in imaging tissue ultrastructure, and reconstructs the tissue’s internal refractive index distribution.

We have developed a new technique for micron scale resolution cross-sectional imaging in biological systems called Optical Coherence Tomography (OCT)1,2 In OCT, low-coherence optical interferometry3,4 is used to resolve the position of reflective or optical backscattering sites within a sample. Two-dimensional tomographic images of a thin, optical slice of tissue may be obtained with 10 μm longitudinal and lateral resolution. Narrowband optical heterodyne detection achieves a sensitivity to reflected light as small as 10-10 of the incident optical power. OCT is non-contact, non-invasive, and has superior resolution to conventional clinical ultrasound. Unlike scanning laser ophthalmoscopy and scanning laser tomography, the optical sectioning capability of OCT is not restricted by the pupil-limited numerical aperture of the eye or ocular aberrations. OCT may be implemented in a compact, low-cost, fiber-optic based interferometer that is easily coupled to existing ophthalmic instrumentation. We demonstrate high-speed, in vivo OCT imaging in both the anterior and posterior eye.

Confocal microscopy has become a standard technique for high resolution optical imaging in many fields1,2. Confocal imaging is conventionally limited to relatively transparent specimens, since image contrast is degraded by light scattering in turbid samples. We have developed a new method for coherent confocal microsopy which uses low-coherence interferometry to enhance optical sectioning in highly scattering media. In optical coherence microscopy (OCM), improved confocal imaging is achieved through high detection sensitivity and high contrast rejection of out-of-focus light. OCM is an adaptation of optical coherence tomography (OCT), which has recently been demonstrated for noninvasive, ten-micron-scale resolution imaging in the eye and other biological tissues3-5. The extension of this technique to confocal microscopy offers the potential for micron-resolution imaging deep into highly scattering media such as skin and endoscopically accessible tissues, and may make possible the development of a new form of noninvasive "optical biopsy."

We present a novel spectral-scanning FMCW 3D imaging and velocimetry system that can produce 3D depth maps of 507 X 500 pixels at 33 Hz, with 48° X 68° FOV and 32.8 cm depth range.

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.

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) 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.

Purpose: Subretinal delivery of stem cells and gene therapy vectors hold great promise in clinical care. Delivery techniques are evolving. We investigate the utility of 4-dimensional (volumes over time) microscope-integrated optical coherence tomography (4D-MIOCT) to guide such maneuvers. Methods: This investigational 4D-MIOCT system displayed heads-up cross-sectional and stereoscopic volumetric views through the microscope oculars at 3.3–10 volumes/second. In enucleated porcine eyes, we evaluated novel information available to the surgeon during subretinal: 1) injection of fluid and cell suspensions, 2) retinotomy creation, 3) insertion of membranes with a retinal pigment epithelium (RPE) cell monolayer and 4) subretinal instrument maneuvers, all in postmortem porcine eyes. Results: Interactions between tools, membranes, retina and RPE were often not detectable on the conventional microscope view but were obvious with 4D-MIOCT. 4D-MIOCT visualization was essential to: monitor the extent of induced retinal detachment, guide the cannula tip and instrument maneuvers in the subretinal space, and identify efflux of cells into the vitreous cavity. This allowed adjustment by the surgeon to avoid complications—e.g. scissors scraping RPE. Conclusions: 4D-MIOCT is useful for continuous monitoring of model subretinal surgery and may help avoid technique-related complications. 4D-MIOCT can contribute to the advancement of subretinal delivery of therapies under development.

Super-resolution optical microscopy techniques have enabled the discovery and visualization of numerous phenomena in physics, chemistry and biology(1–3). However, the highest resolution super-resolution techniques depend on nonlinear fluorescence phenomena and are thus inaccessible to the myriad applications that require reflective imaging(4,5). One promising super-resolution technique is optical reassignment(6), which so far has only shown potential for fluorescence imaging at low speeds. Here, we present novel advances in optical reassignment to adapt it for any scanning microscopy, including reflective imaging, and enable an order of magnitude faster image acquisition than previous optical reassignment techniques. We utilized these advances to implement optically reassigned scanning laser ophthalmoscopy, an in vivo super-resolution human retinal imaging device not reliant on confocal gating. Using this instrument, we achieved high-resolution imaging of living human retinal cone photoreceptor cells (determined by minimum foveal eccentricity) without adaptive optics or chemical dilation of the eye(7).