Spiral scanning improves subject fixation in widefield retinal imaging.

Point scanning retinal imaging modalities, including confocal scanning light ophthalmoscopy (cSLO) and optical coherence tomography, suffer from fixational motion artifacts. Fixation targets, though effective at reducing eye motion, are infeasible in some applications (e.g., handheld devices) due to their bulk and complexity. Here, we report on a cSLO device that scans the retina in a spiral pattern under pseudo-visible illumination, thus collecting image data while simultaneously projecting, into the subject's vision, the image of a bullseye, which acts as a virtual fixation target. An imaging study of 14 young adult volunteers was conducted to compare the fixational performance of this technique to that of raster scanning, with and without a discrete inline fixation target. Image registration was used to quantify subject eye motion; a strip-wise registration method was used for raster scans, and a novel, to the best of our knowledge, ring-based method was used for spiral scans. Results indicate a statistically significant reduction in eye motion by the use of spiral scanning as compared to raster scanning without a fixation target.

RobOCTNet: Robotics and Deep Learning for Referable Posterior Segment Pathology Detection in an Emergency Department Population.

Purpose: To evaluate the diagnostic performance of a robotically aligned optical coherence tomography (RAOCT) system coupled with a deep learning model in detecting referable posterior segment pathology in OCT images of emergency department patients. Methods: A deep learning model, RobOCTNet, was trained and internally tested to classify OCT images as referable versus non-referable for ophthalmology consultation. For external testing, emergency department patients with signs or symptoms warranting evaluation of the posterior segment were imaged with RAOCT. RobOCTNet was used to classify the images. Model performance was evaluated against a reference standard based on clinical diagnosis and retina specialist OCT review. Results: We included 90,250 OCT images for training and 1489 images for internal testing. RobOCTNet achieved an area under the curve (AUC) of 1.00 (95% confidence interval [CI], 0.99-1.00) for detection of referable posterior segment pathology in the internal test set. For external testing, RAOCT was used to image 72 eyes of 38 emergency department patients. In this set, RobOCTNet had an AUC of 0.91 (95% CI, 0.82-0.97), a sensitivity of 95% (95% CI, 87%-100%), and a specificity of 76% (95% CI, 62%-91%). The model's performance was comparable to two human experts' performance. Conclusions: A robotically aligned OCT coupled with a deep learning model demonstrated high diagnostic performance in detecting referable posterior segment pathology in a cohort of emergency department patients. Translational Relevance: Robotically aligned OCT coupled with a deep learning model may have the potential to improve emergency department patient triage for ophthalmology referral.

Shot-noise limited optical hybrid based on fused fiber couplers.

We describe a fiber-based coherent receiver topology which utilizes intrinsic phase shifts from fiber couplers to enable instantaneous quadrature projection with shot-noise limited signal-to-noise ratio (SNR). Fused 3 × 3 fiber couplers generate three phase-shifted signals simultaneously that can be combined with quadrature projection methods to detect magnitude and phase unambiguously. We present a novel, to the best of our knowledge, differential detection topology which utilizes a combination of 3 × 3 and 2 × 2 couplers to enable quadrature projection with fully differential detection. We present a mathematical analysis of this 3 × 3 differential detection topology, extended methods for signal calibration, and SNR analysis. We characterize the SNR advantage of this approach and demonstrate a sample application illustrating simultaneous magnitude and phase imaging of a chrome-on-glass test chart.

A pilot optical coherence tomography angiography classification of retinal neovascularization in retinopathy of prematurity.

Extraretinal neovascularization is a hallmark of treatment-requiring retinopathy of prematurity (ROP). Optical coherence tomography angiography (OCTA) offers vascular flow and depth information not available from indirect ophthalmoscopy and structural OCT, but OCTA is only commercially available as a tabletop device. In this study, we used an investigational handheld OCTA device to study the vascular flow in and around retinal neovascularization in seven preterm infants with treatment-requiring ROP and contrasted them to images of vascular flow in six infants of similar age without neovascular ROP. We showed stages of retinal neovascularization visible in preterm infants from 32 to 47 weeks postmenstrual age: Intraretinal neovascularization did not break through the internal limiting membrane; Subclinical neovascular buds arose from retinal vasculature with active flow through the internal limiting membrane; Flat neovascularization in aggressive ROP assumed a low-lying configuration compared to elevated extraretinal neovascular plaques; Regressed neovascularization following treatment exhibited decreased vascular flow within the preretinal tissue, but flow persisted in segments of retinal vessels elevated from their original intraretinal location. These findings enable a pilot classification of retinal neovascularization in eyes with ROP using OCTA, and may be helpful in detailed monitoring of disease progression, treatment response and predicting reactivation.

Hybrid spiral scanning in a double-clad fiber-based handheld confocal scanning light ophthalmoscope.

High-speed, accessible, and robust in vivo imaging of the human retina is critical for screening of retinal pathologies, such as diabetic retinopathy, age-related macular degeneration, and others. Scanning light ophthalmoscopy (SLO) is a retinal imaging modality that produces digital, en face images of the human retina with superior image gradability rates when compared to the current standard of care in screening for these diseases, namely the flood-illumination handheld fundus camera (HFC). However, current-generation commercial SLO systems are mostly tabletop devices, limiting their accessibility and utility in screening applications. Moreover, most existing SLO systems use raster scan patterns, which are both inefficient and lead to undesired subject gaze drift when used with visible or pseudo-visible illumination. Non-raster scan patterns, especially spiral scanning as described herein, promise advantages in both scan efficiency and reduced subject eye motion. In this work, we introduce a novel "hybrid spiral" scan pattern and the associated hardware design and real-time image reconstruction techniques necessary for its implementation in an SLO system. Building upon this core hybrid spiral scanning SLO (HSS-SLO) technology, we go on to present a complete handheld HSS-SLO system, featuring a fiber-coupled portable patient interface which leverages a dual-clad fiber (DCF) to form a single-path optical topology, thus ensuring mechanically robust co-alignment of illumination and collection apertures, a necessity for a handheld system. The feasibility of HSS-SLO for handheld, in vivo imaging is demonstrated by imaging eight human volunteers.

Erratum: Methods for real-time feature-guided image fusion of intrasurgical volumetric optical coherence tomography with digital microscopy: publisher's note.

[This corrects the article on p. 3308 in vol. 14, PMID: 37497493.].

MACULAR NEUROVASCULAR ABNORMALITIES IN A CHILD WITH INCONTINENTIA PIGMENTI ON HANDHELD OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To report macular neurovascular abnormalities in a child with incontinentia pigmenti using handheld optical coherence tomography (OCT) and OCT angiography (OCT-A). METHODS: An eye of a child with incontinentia pigmenti enrolled in BabySTEPS was imaged using an investigational noncontact, handheld swept-source OCT device during examination under anesthesia. Custom MATLAB scripts were used to generate depth-resolved vascular slabs, B-scans with flow overlay, and retinal thickness maps. RESULTS: Depth-resolved OCT and OCT-A imaging demonstrated focal areas of decreased capillary flow that corresponded to areas of both inner retinal and outer retinal thinning on retinal thickness maps. Atypical diving of superficial retinal vessels occurred as they traversed from thin retina to normal-thickness retina. CONCLUSION: Depth-resolved OCT and OCT-A identified retinal vascular abnormalities that were not evident on fundus photography or fluorescein angiography. This case depicted concurrent, localized abnormalities in retinal thickness and microvasculature in an eye with incontinentia pigmenti.

Methods for real-time feature-guided image fusion of intrasurgical volumetric optical coherence tomography with digital microscopy.

4D-microscope-integrated optical coherence tomography (4D-MIOCT) is an emergent multimodal imaging technology in which live volumetric OCT (4D-OCT) is implemented in tandem with standard stereo color microscopy. 4D-OCT provides ophthalmic surgeons with many useful visual cues not available in standard microscopy; however it is challenging for the surgeon to effectively integrate cues from simultaneous-but-separate imaging in real-time. In this work, we demonstrate progress towards solving this challenge via the fusion of data from each modality guided by segmented 3D features. In this way, a more readily interpretable visualization that combines and registers important cues from both modalities is presented to the surgeon.

Visualization of surgical maneuvers using intraoperative real-time volumetric optical coherence tomography.

Ophthalmic microsurgery is traditionally performed using stereomicroscopes and requires visualization and manipulation of sub-millimeter tissue structures with limited contrast. Optical coherence tomography (OCT) is a non-invasive imaging modality that can provide high-resolution, depth-resolved cross sections, and has become a valuable tool in clinical practice in ophthalmology. While there has been substantial progress in both research and commercialization efforts to bring OCT imaging into live surgery, its use is still somewhat limited due to factors such as low imaging speed, limited scan configurations, and suboptimal data visualization. In this paper we describe, to the best of our knowledge, the translation of the fastest swept-source intraoperative OCT system with real-time volumetric imaging with stereoscopic data visualization provided via a heads-up display into the operating room. Results from a sampling of human anterior segment and retinal surgeries chosen from 93 human surgeries using the system are shown and the benefits that this mode of intrasurgical OCT imaging provides are discussed.

NOVEL METHOD FOR VISUALIZING PERIPHERAL RETINAL STRUCTURES WITH MICROSCOPE-INTEGRATED OPTICAL COHERENCE TOMOGRAPHY.

BACKGROUND/PURPOSE: Visualization of peripheral retinal structures with optical coherence tomography (OCT) can be challenging but can offer valuable clinical information. We describe a method for intraoperative OCT of the peripheral retina. METHODS: An investigational microscope-integrated OCT system with real-time 4D volumetric imaging was used in conjunction with a Goldmann style mirrored contact lens intraoperatively to capture peripheral images in three patients. RESULTS: We identified retinoschisis, a retinal break, and areas of focal retinal detachment using our peripheral OCT method. CONCLUSION: Use of a Goldmann lens in conjunction with intraoperative OCT offers surgeons the ability to resolve peripheral pathology that cannot be easily evaluated with OCT otherwise.

Robotic Optical Coherence Tomography Retinal Imaging for Emergency Department Patients: A Pilot Study for Emergency Physicians' Diagnostic Performance.

STUDY OBJECTIVE: To evaluate the diagnostic performance of emergency physicians' interpretation of robotically acquired retinal optical coherence tomography images for detecting posterior eye abnormalities in patients seen in the emergency department (ED). METHODS: Adult patients presenting to Duke University Hospital emergency department from November 2020 through October 2021 with acute visual changes, headache, or focal neurologic deficit(s) who received an ophthalmology consultation were enrolled in this pilot study. Emergency physicians provided standard clinical care, including direct ophthalmoscopy, at their discretion. Retinal optical coherence tomography images of these patients were obtained with a robotic, semi-autonomous optical coherence tomography system. We compared the detection of abnormalities in optical coherence tomography images by emergency physicians with a reference standard, a combination of ophthalmology consultation diagnosis and retina specialist optical coherence tomography review. RESULTS: Nine emergency physicians reviewed the optical coherence tomography images of 72 eyes from 38 patients. Based on the reference standard, 33 (46%) eyes were normal, 16 (22%) had at least 1 urgent/emergency abnormality, and the remaining 23 (32%) had at least 1 nonurgent abnormality. Emergency physicians' optical coherence tomography interpretation had 69% (95% confidence interval [CI], 49% to 89%) sensitivity for any abnormality, 100% (95% CI, 79% to 100%) sensitivity for urgent/emergency abnormalities, 48% (95% CI, 28% to 68%) sensitivity for nonurgent abnormalities, and 64% (95% CI, 44% to 84%) overall specificity. In contrast, emergency physicians providing standard clinical care did not detect any abnormality with direct ophthalmoscopy. CONCLUSION: Robotic, semi-autonomous optical coherence tomography enabled ocular imaging of emergency department patients with a broad range of posterior eye abnormalities. In addition, emergency provider optical coherence tomography interpretation was more sensitive than direct ophthalmoscopy for any abnormalities, urgent/emergency abnormalities, and nonurgent abnormalities in this pilot study with a small sample of patients and emergency physicians.

Quantitative measurements of intraocular structures and microinjection bleb volumes using intraoperative optical coherence tomography.

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.

Optical coherence tomography refraction and optical path length correction for image-guided corneal surgery.

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.

Video-rate high-precision time-frequency multiplexed 3D coherent ranging.

Frequency-modulated continuous wave (FMCW) light detection and ranging (LiDAR) is an emerging 3D ranging technology that offers high sensitivity and ranging precision. Due to the limited bandwidth of digitizers and the speed limitations of beam steering using mechanical scanners, meter-scale FMCW LiDAR systems typically suffer from a low 3D frame rate, which greatly restricts their applications in real-time imaging of dynamic scenes. In this work, we report a high-speed FMCW based 3D imaging system, combining a grating for beam steering with a compressed time-frequency analysis approach for depth retrieval. We thoroughly investigate the localization accuracy and precision of our system both theoretically and experimentally. Finally, we demonstrate 3D imaging results of multiple static and moving objects, including a flexing human hand. The demonstrated technique achieves submillimeter localization accuracy over a tens-of-centimeter imaging range with an overall depth voxel acquisition rate of 7.6 MHz, enabling densely sampled 3D imaging at video rate.

Computational 3D microscopy with optical coherence refraction tomography.

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 which 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.

Depth-Resolved Visualization of Perifoveal Retinal Vasculature in Preterm Infants Using Handheld Optical Coherence Tomography Angiography.

Purpose: To establish methods to visualize depth-resolved perifoveal retinal vasculature in preterm infants using handheld optical coherence tomography angiography (OCT-A). Methods: In this exploratory study, eyes of preterm infants were imaged using an investigational noncontact, handheld swept-source OCT-A device as part of the prospective BabySTEPS infant retinal imaging study. We selected high-quality OCT-A volumes at two developmental stages for analysis. Customized MATLAB scripts were used to segment retinal layers, test offset parameters, and generate depth-resolved OCT-A slabs. The superficial (SCP), intermediate (ICP), and deep (DCP) capillary plexuses were visualized and qualitatively assessed by three image graders. Results: Six eyes from six preterm infants were included in this analysis. A three-layered perifoveal retinal vasculature was successfully visualized in all three eyes (three infants) in the 40 weeks postmenstrual age (PMA) group (one of three eyes with treated type 1 retinopathy of prematurity [ROP]). No obvious ICP or DCP was found in good-quality scans of the three eyes (three infants) in the 35 weeks PMA group (three of three eyes developed type 1 ROP). Conclusions: Custom segmentation parameters are useful to visualize perifoveal retinal vasculature in preterm infants. At term age, a three-layered capillary structure is visible in most eyes, while prior to detectable flow within the ICP and DCP, the perifoveal vasculature may be better visualized in two layers. Translational Relevance: Development of segmentation parameters for depth-resolved OCT-A of perifoveal retinal vasculature in preterm infants facilitates the study of human retinal vascular development and vascular pathologies of ROP.

Contactless optical coherence tomography of the eyes of freestanding individuals with a robotic scanner.

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.

Microscope-Integrated OCT-Guided Volumetric Measurements of Subretinal Blebs Created by a Suprachoroidal Approach.

Purpose: To investigate the use of imaging modalities in the volumetric measurement of the subretinal space and examine the volume of subretinal blebs created by a subretinal drug delivery device utilizing microscope-integrated optical coherence tomography (MIOCT). Methods: An MIOCT image-based volume measurement method was developed and assessed for accuracy and reproducibility by imaging ceramic spheres of known size that were surgically implanted into ex vivo porcine eyes. This method was then used to measure subretinal blebs created in 10 porcine eyes by injection of balanced salt solution utilizing a subretinal delivery device via a suprachoroidal cannula. Bleb volumes obtained from MIOCT were compared to the intended injection volume. Results: Validation of image-based volume measurements of ceramic spheres showed accuracy to ±0.029 µL (5.6%) for objects imaged over the posterior pole and ±0.025 µL (4.8%) over peripheral retina. The mean expected injection volume from extraocular tests of the suprachoroidal cannula was 66.44 µL (σ = 2.4 µL). The mean injection volume as measured by the MIOCT imaging method was 54.8 µL (σ = 12.3 µL), or 82.48% of expected injection volume. Conclusions: MIOCT can measure the volume of subretinal blebs with accuracy and precision. The novel suprachoroidal approach using a subretinal delivery device was able to deliver greater than 80% of expected injection volume into the subretinal space, as assessed by MIOCT. Translational Relevance: MIOCT provides a method for visualization, and analysis of images enables surgeons to quantify and evaluate the success of subretinal drug delivery via a suprachoroidal approach.

In vivo quantitative analysis of anterior chamber white blood cell mixture composition using spectroscopic optical coherence tomography.

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.

COMBINED INTERNAL LIMITING MEMBRANE FLAP AND AUTOLOGOUS PLASMA CONCENTRATE TO CLOSE A LARGE TRAUMATIC MACULAR HOLE IN A PEDIATRIC PATIENT.

PURPOSE: To describe a case of a large, traumatic macular hole in a pediatric patient closed using an internal limiting membrane flap in combination with autologous plasma concentrate (APC). METHODS: Description of a surgical technique as performed in one patient. RESULTS: Successful macular hole closure and improvement in postoperative visual acuity were achieved in the patient in whom the technique was performed. CONCLUSION: The combined use of APC with the internal limiting membrane flap is advantageous because the APC acts to hold the internal limiting membrane in proper position and promotes the proliferation of glial cells through the presence of growth factors. This technique may be particularly advantageous in chronic or recalcitrant holes particularly in the setting of trauma.