Influence of static and dynamic ocular aberrations on full-field optical coherence tomography for in vivo high-resolution retinal imaging.

Under spatially incoherent illumination, time-domain full-field optical coherence tomography (FFOCT) offers the possibility to achieve in vivo retinal imaging at cellular resolution over a wide field of view. Such performance is possible, albeit there is the presence of ocular aberrations even without the use of classical adaptive optics. While the effect of aberrations in FFOCT has been debated these past years, mostly on low-order and static aberrations, we present, for the first time to our knowledge, a method enabling a quantitative study of the effect of statistically representative static and dynamic ocular aberrations on FFOCT image metrics, such as SNR, resolution, and image similarity. While we show that ocular aberrations can decrease FFOCT SNR and resolution by up to 14 dB and fivefold, we take advantage of such quantification to discuss different possible compromises between performance gain and adaptive optics complexity and speed, to optimize both sensor-based and sensorless FFOCT high-resolution retinal imaging.

Inpatients' experiences of falls: A qualitative meta-synthesis.

OBJECTIVES: Identify and synthesize published qualitative research reporting inpatient experiences of a fall to determine novel insights and understandings of this longstanding complex problem. RESEARCH DESIGN: Qualitative meta-synthesis. METHODS: Online databases were searched to systematically identify published research reporting inpatient experiences of a fall. The included studies were inductively analysed and interpreted then reported as a meta-synthesis. DATA SOURCES: Databases Ovid MEDLINE, Embase, Ovid Emcare, CINAHL Complete, Scopus and ProQuest Dissertations and Theses Global were searched on 3rd August, 2023. RESULTS: From 10 included publications, four new themes of inpatients' experiences of a fall were constructed. Themes one, two and three related to antecedents of patient falls, and theme four related to consequences. Theme one, 'My foot didn't come with me: Physiological and anatomical changes', encompassed patients' experiences of medical conditions, medication, and anatomical changes. These aspects contributed to alterations in balance and strength, and misconceptions of capability in activities of daily (inpatient) living. Theme two, 'I was in a hurry: Help-seeking', encompassed patients' experiences striving for independence while balancing power and control, minimizing their own needs over care of others', and unavailability of support. Theme three, 'I couldn't find the call light: Environment and equipment', encompassed patients' experiences of not being able to reach or use equipment, and environment changes. Theme four, 'It was my fault too: Blame and confidence', encompassed patients' expressions of blame after their fall, blame directed at both themselves and/or others, and impacts on confidence and fear in mobilizing. CONCLUSIONS: Inpatient falls are embedded in a complexity of individual, relational, and environmental factors, yet there are potential ways forward both informed and led by the patient's voice. Strength-based approaches to address the tenuous balance between independence and support may be one opportunity to explore as a next step in complementing the existing multifaceted interventions. IMPACT: Inpatient falls are a complex and costly health safety and quality problem. Despite global initiatives in the prevention of inpatient falls, they remain intractable. This meta-synthesis provides an in-depth exploration of extant qualitative data on patients' experiences of falls in hospitals. Four themes were constructed expressing the inpatients' experiences: physiological and anatomical changes, help-seeking, environment and equipment, and blame and confidence. Novel considerations for future investigation are offered, drawing from self-determination theory and positive psychological interventions. IMPLICATIONS FOR PATIENT CARE: This meta-synthesis elicits new considerations for future interventions based on people's experiences of their fall in hospital, offering healthcare professionals novel directions in fall prevention. REPORTING METHOD: The review was reported according to the Enhancing transparency in reporting the synthesis of qualitative research statement (ENTREQ; Tong et al., 2012). PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution. REGISTRATION: PROSPERO CRD42023445279.

Adaptive-glasses time-domain FFOCT for wide-field high-resolution retinal imaging with increased SNR.

The highest three-dimensional (3D) resolution possible in in vivo retinal imaging is achieved by combining optical coherence tomography (OCT) and adaptive optics. However, this combination brings important limitations, such as small field-of-view and complex, cumbersome systems, preventing so far the translation of this technology from the research lab to clinics. In this Letter, we mitigate these limitations by combining our compact time-domain full-field OCT (FFOCT) with a multi-actuator adaptive lens positioned just in front of the eye, in a technique we call the adaptive-glasses wavefront sensorless approach. Through this approach, we demonstrate that ocular aberrations can be corrected, increasing the FFOCT signal-to-noise ratio (SNR) and enabling imaging of different retinal layers with a 3D cellular resolution over a 5∘×5∘ field-of-view, without apparent anisoplanatism.

ATTENUATION OUTER RETINAL BANDS ON OPTICAL COHERENCE TOMOGRAPHY FOLLOWING MACULAR EDEMA: A Possible Manifestation of Photoreceptor Misalignment.

PURPOSE: Macular edema is a common retinal disease which may leave important anatomical and functional sequelaes. Directional fundus imaging consists of comparing on- and off-axis images to reveal angle-dependent reflectance properties of fundus structures, which may be related to misaligned photoreceptors. Here, we analyzed directional optical coherence tomography (OCT) and flood-illumination adaptive optics ophthalmoscopy images to detect evidence of misaligned photoreceptors following macular edema. METHODS: Transversal, observational study. Nine patients having recovered a normal macular profile after macular edema due to retinal vein occlusion were included. For each patient, a reference OCT scan (i.e., with the incident beam normal to the fovea) was acquired, and off-axis scans were then acquired by laterally shifting the entry pupil. In addition, in four of these eyes, directional adaptive optics ophthalmoscopy documented the directional variations of cone metrics. RESULTS: Included patients comprised two women and seven men (age range, 19-76 years). Reference OCT scans showed patchy attenuation of the cone outer segment tips and to a lesser extent of the inner segment/outer segment lines in all, but two eyes; these. Increased intensity of the cone outer segment tips and inner segment/outer segment lines could be observed on off-axis scans. Accordingly, fusion images showed 66% average reduction of the length of cone outer segment tips attenuation. In two cases, although reference scans showed continuity of outer bands, focal attenuation was evidenced in off-axis images. Directional adaptive optics ophthalmoscopy imaging showed a strong directional variability of cone counts in these areas, ranging from near absence to roughly two-third of reference values. In each case, directional variations of cone counts paralleled those of the reflectance of outer bands. CONCLUSION: After macular edema, focal attenuations of the inner segment/outer segment and of the cone outer segment tips lines may be present on OCT. These areas may show a strong directional variability by both OCT and adaptive optics ophthalmoscopy, suggesting that misaligned photoreceptor outer segments contribute to such features. The evaluation of outer retinal damage following macular edema should therefore take into account the optical Stiles-Crawford effect to disambiguate missing from misaligned cones.

Higher adaptive optics loop rate enhances axial resolution in nonconfocal ophthalmoscopes.

In this Letter, we propose a way to better understand the impact of dynamic ocular aberrations in the axial resolution of nonconfocal adaptive optics (AO) ophthalmoscopes via a simulation of the 3D PSF in the retina for various AO-loop rates. We then use optical incoherence tomography, a method enabling the generation of tomographic retinal cross sections in incoherent imaging systems, to evaluate the benefits of a fast AO-loop rate on axial resolution and, consequently, on AO-corrected retinal image quality. We used the PARIS AO flood-illumination ophthalmoscope for this study, where retinal images from different focal planes at an AO-loop rate of 10 and 50 Hz were acquired.

High loop rate adaptive optics flood illumination ophthalmoscope with structured illumination capability.

The design and performance of an adaptive optics flood illumination ophthalmoscope (AO-FIO) platform, based on eye motion and dynamic aberrations experimental analysis, are described. The system incorporates a custom-built real-time controller, enabling up to 70 Hz loop rate without jitter, and an AO-corrected illumination capable of projecting high-resolution features in the retina. Wide-field (2.7°×5.4°) and distortionless images from vessel walls, capillaries, and the lamina cribrosa are obtained with an enhanced contrast and signal-to-noise ratio, thanks to careful control of AO parameters. The high spatial and temporal resolution (image acquisition up to 200 Hz) performance achieved by this platform enables the visualization of vessel deformation and blood flow. This system opens up the prospect of a return to favor of flood illumination adaptive optics systems provided that its high pixel rate and structured illumination capabilities are exploited.

Full-field OCT technique for high speed event-based optical flow and particle tracking.

This article introduces a method to extract the speed and density of microparticles in real time at several kHz using an asynchronous event-based camera mounted on a full-field optical coherence tomography (FF-OCT) setup. These cameras detect significant amplitude changes, allowing scene-driven acquisitions. They are composed of an array of autonomously operating pixels. Events are triggered when an illuminance change at the pixel level is significant at 1µs time precision. The event-driven FF-OCT algorithm relies on a time-based optical flow computation to operate directly on incoming events and updates the estimation of velocity, direction and density while reducing both computation and data load. We show that for fast moving microparticles in a range of 0.4 - 6.5mm/s, the method performs faster and more efficiently than existing techniques in real time. The target application of this work is to evaluate erythrocyte dynamics at the microvascular level in vivo with a high temporal resolution.

Pupil motion analysis and tracking in ophthalmic systems equipped with wavefront sensing technology.

Our eyes are constantly in motion, even during "steady" fixation. In ophthalmic systems equipped with wavefront technology, both eye and head motion potentially degrade its performance and/or increase the cost and complexity, as they induce a movement of the entrance optical pupil of the system. Here, we characterize the pupil motion in an aberrometry setting, using a custom, high-speed pupil tracker (478 Hz), and draw conclusions on design considerations of future ophthalmic systems. We also demonstrate the feasibility of tracking such motion directly with a custom-built Hartmann-Shack sensor (236 Hz) using a method that offers certain benefits over previously suggested approaches, thereby paving the way to an efficient and cost-effective approach.

A feasibility study of full-field optical coherence tomography for rapid evaluation of EUS-guided microbiopsy specimens.

BACKGROUND: Rapid on-site evaluation of cytologic specimens is a way of determining the adequacy of fine-needle aspiration (FNA). However, alternatives may be useful when the presence of a cytotechnologist and/or pathologist is not possible. OBJECTIVE: To evaluate the feasibility of using full-field optical coherence tomography (FFOCT) for FNA specimen quality assessment. DESIGN: FFOCT images were acquired on gastric, pancreatic, pelvic, and lymph-node formalin-fixed FNA specimens and were compared with histology of the same samples. SETTING: Pathology suite in a hospital. PATIENTS: Fourteen patients undergoing gastric, pancreatic, pelvic, or lymph-node EUS-guided FNA biopsy. INTERVENTIONS: FFOCT imaging on formalin-fixed samples before histologic procedures. MAIN OUTCOME MEASUREMENTS: FFOCT imaging feasibility and visibility of normal and abnormal features on images. RESULTS: FFOCT imaging was possible. Blood, mucus, muscle, collagen, and digestive mucosa could be identified as well as abnormal architectural features including infiltrative pancreatic ductal carcinoma and a neuroendocrine neoplasm. Lesions at the individual cell level could not be detected. LIMITATIONS: The study was performed on a limited number of cases. CONCLUSION: FFOCT offers rapid, noninvasive, nondestructive imaging of FNA biopsy specimens. In the future, it could be performed in the endoscopy suite to improve detection of satisfactory specimens and obviate the need for rapid on-site evaluation.

Comparison between Two Adaptive Optics Methods for Imaging of Individual Retinal Pigmented Epithelial Cells.

The Retinal Pigment Epithelium (RPE) plays a prominent role in diseases such as age-related macular degeneration, but imaging individual RPE cells is challenging due to their high absorption and low autofluorescence emission. The RPE lies beneath the highly reflective photoreceptor layer (PR) and contains absorptive pigments, preventing direct backscattered light detection when the PR layer is intact. Here, we used near-infrared autofluorescence adaptive optics scanning laser ophthalmoscopy (NIRAF AOSLO) and transscleral flood imaging (TFI) in the same healthy eyes to cross-validate these approaches. Both methods revealed a consistent RPE mosaic pattern and appeared to reflect a distribution of fluorophores consistent with findings from histological studies. Interestingly, even in apparently healthy RPE, we observed dynamic changes over months, suggesting ongoing cellular activity or alterations in fluorophore distribution. These findings emphasize the value of NIRAF AOSLO and TFI in understanding RPE morphology and dynamics.

Label-Free Imaging of Inflammation at the Level of Single Cells in the Living Human Eye.

Purpose: Putative microglia were recently detected using adaptive optics ophthalmoscopy in healthy eyes. Here we evaluate the use of nonconfocal adaptive optics scanning light ophthalmoscopy (AOSLO) for quantifying the morphology and motility of presumed microglia and other immune cells in eyes with retinal inflammation from uveitis and healthy eyes. Design: Observational exploratory study. Participants: Twelve participants were imaged, including 8 healthy participants and 4 posterior uveitis patients recruited from the clinic of 1 of the authors (M.H.E.). Methods: The Pittsburgh AOSLO imaging system was used with a custom-designed 7-fiber optical fiber bundle for simultaneous confocal and nonconfocal multioffset detection. The inner retina was imaged at several locations at multiple timepoints in healthy participants and uveitis patients to generate time-lapse images. Main Outcome Measures: Microglia and macrophages were manually segmented from nonconfocal AOSLO images, and their morphological characteristics quantified (including soma size, diameter, and circularity). Cell soma motion was quantified across time for periods of up to 30 minutes and their speeds were calculated by measuring their displacement over time. Results: A spectrum of cell morphologies was detected in healthy eyes from circular amoeboid cells to elongated cells with visible processes, resembling activated and ramified microglia, respectively. Average soma diameter was 16.1 ± 0.9 µm. Cell movement was slow in healthy eyes (0.02 µm/sec on average), but macrophage-like cells moved rapidly in some uveitis patients (up to 3 µm/sec). In an eye with infectious uveitis, many macrophage-like cells were detected; during treatment their quantity and motility decreased as vision improved. Conclusions: In vivo adaptive optics ophthalmoscopy offers promise as a potentially powerful tool for detecting and monitoring inflammation and response to treatment at a cellular level in the living eye. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Detection of capillary abnormalities in early diabetic retinopathy using scanning laser ophthalmoscopy and optical coherence tomography combined with adaptive optics.

This study tested if a high-resolution, multi-modal, multi-scale retinal imaging instrument can provide novel information about structural abnormalities in vivo. The study examined 11 patients with very mild to moderate non-proliferative diabetic retinopathy (NPDR) and 10 healthy subjects using fundus photography, optical coherence tomography (OCT), OCT angiography (OCTA), adaptive optics scanning laser ophthalmoscopy (AO-SLO), adaptive optics OCT and OCTA (AO-OCT(A)). Of 21 eyes of 11 patients, 11 had very mild NPDR, 8 had mild NPDR, 2 had moderate NPDR, and 1 had no retinopathy. Using AO-SLO, capillary looping, inflections and dilations were detected in 8 patients with very mild or mild NPDR, and microaneurysms containing hyperreflective granular elements were visible in 9 patients with mild or moderate NPDR. Most of the abnormalities were seen to be perfused in the corresponding OCTA scans while a few capillary loops appeared to be occluded or perfused at a non-detectable flow rate, possibly because of hypoperfusion. In one patient with moderate NPDR, non-perfused capillaries, also called ghost vessels, were identified by alignment of corresponding en face AO-OCT and AO-OCTA images. The combination of multiple non-invasive imaging methods could identify prominent microscopic abnormalities in diabetic retinopathy earlier and more detailed than conventional fundus imaging devices.

Dynamic optical coherence tomography for cell analysis [Invited].

Label-free live optical imaging of dynamic cellular and subcellular features has been made possible in recent years thanks to the advances made in optical imaging techniques, including dynamic optical coherence tomography (D-OCT) methods. These techniques analyze the temporal fluctuations of an optical signal associated with the active movements of intracellular organelles to obtain an ensemble metric recapitulating the motility and metabolic state of cells. They hence enable visualization of cells within compact, static environments and evaluate their physiology. These emerging microscopies show promise, in particular for the three-dimensional evaluation of live tissue samples such as freshly excised biopsies and 3D cell cultures. In this review, we compare the various techniques used for dynamic OCT. We give an overview of the range of applications currently being explored and discuss the future outlook and opportunities for the field.

Twenty-five years of clinical applications using adaptive optics ophthalmoscopy [Invited].

Twenty-five years ago, adaptive optics (AO) was combined with fundus photography, thereby initiating a new era in the field of ophthalmic imaging. Since that time, clinical applications of AO ophthalmoscopy to investigate visual system structure and function in both health and disease abound. To date, AO ophthalmoscopy has enabled visualization of most cell types in the retina, offered insight into retinal and systemic disease pathogenesis, and been integrated into clinical trials. This article reviews clinical applications of AO ophthalmoscopy and addresses remaining challenges for AO ophthalmoscopy to become fully integrated into standard ophthalmic care.

Introduction to the Feature Issue on Adaptive Optics for Biomedical Applications.

The guest editors introduce a feature issue commemorating the 25th anniversary of adaptive optics in biomedical research.

Interface self-referenced dynamic full-field optical coherence tomography.

Dynamic full-field optical coherence tomography (D-FFOCT) has recently emerged as an invaluable live label-free and non-invasive imaging modality able to image subcellular biological structures and their metabolic activity within complex 3D samples. However, D-FFOCT suffers from fringe artefacts when imaging near reflective surfaces and is highly sensitive to vibrations. Here, we present interface Self-Referenced (iSR) D-FFOCT, an alternative configuration to D-FFOCT that takes advantage of the presence of the sample coverslip in between the sample and the objective by using it as a defocused reference arm, thus avoiding the aforementioned artefacts. We demonstrate the ability of iSR D-FFOCT to image 2D fibroblast cell cultures, which are among the flattest mammalian cells.

30 Years of Optical Coherence Tomography: introduction to the feature issue.

The guest editors introduce a feature issue commemorating the 30th anniversary of Optical Coherence Tomography.

Adaptive Optics Flood Illumination Ophthalmoscopy in Nonhuman Primates: Findings in Normal and Short-term Induced Detached Retinae.

Objective: To describe adaptive optics flood illumination ophthalmoscopy (AO-FIO) of the photoreceptor layer in normal nonhuman primates (NHPs) and in the case of a short-term induced retinal detachment (RD). Design: Longitudinal fundamental research study. Subjects: Four NHPs were used to image normal retinae with AO-FIO (in comparison with 4 healthy humans); 2 NHPs were used to assess the effects of RD. Intervention: The photoreceptor layer (cone mosaic metrics, including cone density, cone spacing, and cone regularity) was followed with AO-FIO imaging (rtx1, Imagine Eyes) during a surgically induced RD in 2 NHPs using a vehicle solution containing dimethyl sulfoxide, classically used as a chemical solvent. We also performed functional testing of the retina (full-field and multifocal electroretinogram [ERG]). Main Outcome Measures: Correlation of cone mosaic metrics (cone density, spacing, and regularity) between normal retinae of NHPs and humans, and cone metrics, power spectrum, and ERG wave amplitudes after RD. Results: Imaging features were very similar in terms of cone reflectivity, cell density, regularity, and spacing values, showing strong positive correlations between NHPs and humans. After RD, AO-FIO revealed several alterations of the cone mosaic slowly recovering during the 3 months after the reattachment, which were not detected functionally by ERG. Conclusions: These results demonstrate by in vivo AO-FIO imaging the transient structural changes of photoreceptors after an RD in the primate retina. They also provide an interesting illustration of the AO-FIO potential for investigating photoreceptor toxicity during preclinical studies in NHPs with a high translatability to human studies. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Dynamic full-field optical coherence tomography module adapted to commercial microscopes allows longitudinal in vitro cell culture study.

Dynamic full-field optical coherence tomography (D-FFOCT) has recently emerged as a label-free imaging tool, capable of resolving cell types and organelles within 3D live samples, whilst monitoring their activity at tens of milliseconds resolution. Here, a D-FFOCT module design is presented which can be coupled to a commercial microscope with a stage top incubator, allowing non-invasive label-free longitudinal imaging over periods of minutes to weeks on the same sample. Long term volumetric imaging on human induced pluripotent stem cell-derived retinal organoids is demonstrated, highlighting tissue and cell organization processes such as rosette formation and mitosis as well as cell shape and motility. Imaging on retinal explants highlights single 3D cone and rod structures. An optimal workflow for data acquisition, postprocessing and saving is demonstrated, resulting in a time gain factor of 10 compared to prior state of the art. Finally, a method to increase D-FFOCT signal-to-noise ratio is demonstrated, allowing rapid organoid screening.

Automatic diagnosis and classification of breast surgical samples with dynamic full-field OCT and machine learning.

Purpose: The adoption of emerging imaging technologies in the medical community is often hampered when they provide a new unfamiliar contrast that requires experience to be interpreted. Dynamic full-field optical coherence tomography (D-FF-OCT) microscopy is such an emerging technique. It provides fast, high-resolution images of excised tissues with a contrast comparable to H&E histology but without any tissue preparation and alteration. Approach: We designed and compared two machine learning approaches to support interpretation of D-FF-OCT images of breast surgical specimens and thus provide tools to facilitate medical adoption. We conducted a pilot study on 51 breast lumpectomy and mastectomy surgical specimens and more than 1000 individual 1.3×1.3 mm2 images and compared with standard H&E histology diagnosis. Results: Using our automatic diagnosis algorithms, we obtained an accuracy above 88% at the image level (1.3×1.3 mm2) and above 96% at the specimen level (above cm2). Conclusions: Altogether, these results demonstrate the high potential of D-FF-OCT coupled to machine learning to provide a rapid, automatic, and accurate histopathology diagnosis with minimal sample alteration.