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.

Outcomes and Complications of Limbal Stem Cell Allograft Transplantation: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature on the safety and outcomes of keratolimbal allograft (KLAL) transplantation and living-related conjunctival limbal allograft (lr-CLAL) transplantation for bilateral severe/total limbal stem cell deficiency (LSCD). METHODS: Literature searches were last conducted in the PubMed database in February 2023 and were limited to the English language. They yielded 523 citations; 76 were reviewed in full text, and 21 met the inclusion criteria. Two studies were rated level II, and the remaining 19 studies were rated level III. There were no level I studies. RESULTS: After KLAL surgery, best-corrected visual acuity (BCVA) improved in 42% to 92% of eyes at final follow-up (range, 12-95 months). The BCVA was unchanged in 17% to 39% of eyes and decreased in 8% to 29% of eyes. Two of 14 studies that evaluated the results of KLAL reported a notable decline in visual acuity over time postoperatively. Survival of KLAL was variable, ranging from 21% to 90% at last follow-up (range, 12-95 months) and decreased over time. For patients undergoing lr-CLAL surgery, BCVA improved in 31% to 100% of eyes at final follow-up (range, 16-49 months). Of the 9 studies evaluating lr-CLAL, 4 reported BCVA unchanged in 30% to 39% of patients, and 3 reported a decline in BCVA in 8% to 10% of patients. The survival rate of lr-CLAL ranged from 50% to 100% at final follow-up (range, 16-49 months). The most common complications were postoperative elevation of intraocular pressure, persistent epithelial defects, and acute allograft immune rejections. CONCLUSIONS: Given limited options for patients with bilateral LSCD, both KLAL and lr-CLAL are viable choices that may provide improvement of vision and ocular surface findings. The studies trend toward a lower rejection rate and graft failure with lr-CLAL. However, the level and duration of immunosuppression vary widely between the studies and may impact allograft rejections and long-term graft survival. Complications related to immunosuppression are minimal. Repeat surgery may be needed to maintain a viable ocular surface. Reasonable long-term success can be achieved with both KLAL and lr-CLAL with appropriate systemic immunosuppression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

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.

Advanced Corneal Imaging in Keratoconus: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature on the diagnostic capabilities of the newest generation of corneal imaging devices for the identification of keratoconus. METHODS: Corneal imaging devices studied included tomographic platforms (Scheimpflug photography, OCT) and functional biomechanical devices (imaging an air impulse on the cornea). A literature search in the PubMed database for English language studies was last conducted in February 2023. The search yielded 469 citations, which were reviewed in abstract form. Of these, 147 were relevant to the assessment objectives and underwent full-text review. Forty-five articles met the criteria for inclusion and were assigned a level of evidence rating by the panel methodologist. Twenty-six articles were rated level II, and 19 articles were rated level III. There were no level I evidence studies of corneal imaging for the diagnosis of keratoconus found in the literature. To provide a common cross-study outcome measure, diagnostic sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were extracted. (A perfect diagnostic test that identifies all cases properly has an AUC of 1.0.) RESULTS: For the detection of keratoconus, sensitivities for all devices and parameters (e.g., anterior or posterior corneal curvature, corneal thickness) ranged from 65% to 100%. The majority of studies and parameters had sensitivities greater than 90%. The AUCs ranged from 0.82 to 1.00, with the majority greater than 0.90. Combined indices that integrated multiple parameters had an AUC in the mid-0.90 range. Keratoconus suspect detection performance was lower with AUCs ranging from 0.66 to 0.99, but most devices and parameters had sensitivities less than 90%. CONCLUSIONS: Modern corneal imaging devices provide improved characterization of the cornea and are accurate in detecting keratoconus with high AUCs ranging from 0.82 to 1.00. The detection of keratoconus suspects is less accurate with AUCs ranging from 0.66 to 0.99. Parameters based on single anatomic locations had a wide range of AUCs. Studies with combined indices using more data and parameters consistently reported high AUCs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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.].

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.

Systematic analysis of levels of evidence supporting American Academy of Ophthalmology Preferred Practice Pattern guidelines, 2012-2021.

BACKGROUND: Despite the increased emphasis on evidence-based medicine, the current state of evidence behind ophthalmology clinical practice guidelines is unknown. The purpose of this systematic analysis was to understand the levels of evidence (LOE) supporting American Academy of Ophthalmology (AAO) Preferred Practice Pattern (PPP) guidelines, assess changes over time, and compare LOE across ophthalmology subspecialties. METHODS: All current PPP guidelines and their immediate predecessors were comprehensively reviewed to identify all recommendations with LOE provided (I [randomized controlled trials], II [case-control or cohort studies], and III [nonanalytic studies]). RESULTS: Twenty-three out of 24 current PPPs had a prior edition. Among the PPPs with a prior edition, the number of recommendations with LOE decreased from 1254 in prior PPPs to 94 in current PPPs. The number of recommendations with LOE I decreased from 114 to 83, LOE II decreased from 147 to 2, and LOE III decreased from 993 to 9. However, the proportion of LOE I recommendations increased from 9 to 88%, driven by a disproportionate decrease in reporting of evidence lower than LOE I. Subgroup analysis by subspecialty showed similar trends (LOE I recommendations in prior PPPs vs current PPPs: retina: 57 [12%] vs 19 [100%]; cornea: 33 [5%] vs 24 [100%]; glaucoma: 9 [23%] vs 17 [100%]; cataract: 13 [17%] vs 18 [100%]). CONCLUSIONS: Trends in LOE reporting in PPP guidelines indicate an increasing emphasis on evidence from randomized controlled trials from 2012 to 2021. The decline in the number of recommendations with LOE reported suggests an area for improvement in future guidelines as the presence of LOE is crucial to facilitate interpretation of clinical practice guidelines.

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.

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.

Practice Patterns of Fundoscopic Examination for Diabetic Retinopathy Screening in Primary Care.

Importance: 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. Objectives: 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. Design, Setting, and Participants: 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. Exposure: Fundoscopic examination by PCPs. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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.

Nonlinear distortion correction for posterior eye segment optical coherence tomography with application to tree shrews.

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.

Ultrawide field, distortion-corrected ocular shape estimation with MHz optical coherence tomography (OCT).

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.

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.

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.

Robotically aligned optical coherence tomography with 5 degree of freedom eye tracking for subject motion and gaze compensation.

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.

QUANTITATIVE TOPOGRAPHIC CURVATURE MAPS OF THE POSTERIOR EYE UTILIZING OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: Deformations of the retina such as staphylomas in myopia or scleral flattening in high intracranial pressure can be challenging to quantify with en face imaging. We describe an optical coherence tomography-based method for the generation of quantitative posterior eye topography maps in normal and pathologic eyes. METHODS: Using "whole eye" optical coherence tomography, we corrected for subjects' optical distortions to generate spatially accurate posterior eye optical coherence tomography volumes and created local curvature (KM, mm-1) topography maps for each consented subject. We imaged nine subjects, three normal, two with myopic degeneration, and four with papilledema including one that was imaged longitudinally. RESULTS: Normal subjects mean temporal KM was 0.0923 mm-1, nasal KM was 0.0927 mm-1, and KM local variability was 0.0162 mm-1. In myopic degeneration, subjects KM local variability was higher at 0.0836 mm-1. In papilledema subjects nasal KM was flatter compared with temporal KM (0.0709 vs. 0.0885 mm-1). Mean intrasession KM repeatability for all subjects was 0.0036 mm-1. CONCLUSION: We have developed an optical coherence tomography based method for quantitative posterior eye topography that offers the ability to analyze local curvature with micron scale resolution and offers the potential to help clinicians and researchers characterize subtle, local retinal deformations earlier in patients and follow their development over time.

Multimodal handheld adaptive optics scanning laser ophthalmoscope.

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.