Foveolar Drusen Decrease Fixation Stability in Pre-Symptomatic AMD.

Purpose: This study aims at linking subtle changes of fixational eye movements (FEM) in controls and in patients with foveal drusen using adaptive optics retinal imaging in order to find anatomo-functional markers for pre-symptomatic age-related macular degeneration (AMD).

Methods: We recruited 7 young controls, 4 older controls, and 16 patients with presymptomatic AMD with foveal drusen from the Silversight Cohort. A high-speed research-grade adaptive optics flood illumination ophthalmoscope (AO-FIO) was used for monocular retinal tracking of fixational eye movements.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Change in Cone Structure Over 24 Months in USH2A-Related Retinal Degeneration.

Purpose: To describe cone structure changes using adaptive optics scanning laser ophthalmoscopy (AOSLO) in the Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) study.

Design: Multicenter, longitudinal natural history study.

Methods: AOSLO images were acquired at 4 centers, twice at baseline and annually for 24 months in this natural history study.

Full-field Optical Coherence Microscopy for Histology-like Analysis of Stromal Features in Corneal Grafts.

The quality of donor corneal stroma, which makes up about 90% of total corneal thickness, is likely to be one of the main, if not the major, limiting factor(s) for success of deep anterior lamellar and penetrating keratoplasty. These are surgical procedures that involve replacing part or all of the diseased corneal layers, respectively, by donated tissue, the graft, taken from a recently deceased individual. However, means to evaluate stromal quality of corneal grafts in eye banks are limited and lack the capability of high-resolution quantitative assessment of disease indicators.

Characterization and Analysis of Retinal Axial Motion at High Spatiotemporal Resolution and Its Implication for Real-Time Correction in Human Retinal Imaging.

High-resolution ophthalmic imaging devices including spectral-domain and full-field optical coherence tomography (SDOCT and FFOCT) are adversely affected by the presence of continuous involuntary retinal axial motion. Here, we thoroughly quantify and characterize retinal axial motion with both high temporal resolution (200,000 A-scans/s) and high axial resolution (4.5 μm), recorded over a typical data acquisition duration of 3 s with an SDOCT device over 14 subjects.

Long Term Time-Lapse Imaging of Geographic Atrophy: A Pilot Study.

Unlabelled: Geographic atrophy (GA), the late stage of age-related macular degeneration, is a major cause of visual disability whose pathophysiology remains largely unknown. Modern fundus imaging and histology revealed the complexity of the cellular changes that accompanies atrophy. Documenting the activity of the disease in the margins of atrophy, where the transition from health to disease occurs, would contribute to a better understanding of the progression of GA.

Dynamic full-field optical coherence tomography allows live imaging of retinal pigment epithelium stress model.

Retinal degenerative diseases lead to the blindness of millions of people around the world. In case of age-related macular degeneration (AMD), the atrophy of retinal pigment epithelium (RPE) precedes neural dystrophy. But as crucial as understanding both healthy and pathological RPE cell physiology is for those diseases, no current technique allows subcellular in vivo or in vitro live observation of this critical cell layer.

Multi-modal and multi-scale clinical retinal imaging system with pupil and retinal tracking.

We present a compact multi-modal and multi-scale retinal imaging instrument with an angiographic functional extension for clinical use. The system integrates scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT) and OCT angiography (OCTA) imaging modalities and provides multi-scale fields of view. For high resolution, and high lateral resolution in particular, cellular imaging correction of aberrations by adaptive optics (AO) is employed.

Optical phase modulation by natural eye movements: application to time-domain FF-OCT image retrieval.

Eye movements are commonly seen as an obstacle to high-resolution ophthalmic imaging. In this context we study the natural axial movements of the in vivo human eye and show that they can be used to modulate the optical phase and retrieve tomographic images via time-domain full-field optical coherence tomography (TD-FF-OCT). This approach opens a path to a simplified ophthalmic TD-FF-OCT device, operating without the usual piezo motor-camera synchronization.

Design of a radial multi-offset detection pattern for phase contrast imaging of the inner retina in humans.

Previous work has shown that multi-offset detection in adaptive optics scanning laser ophthalmoscopy (AOSLO) can be used to image transparent cells such as retinal ganglion cells (RGCs) in monkeys and humans. Though imaging in anesthetized monkeys with high light levels produced high contrast images of RGCs, images from humans failed to reach the same contrast due to several drawbacks in the previous dual-wavelength multi-offset approach. Our aim here was to design and build a multi-offset detection pattern for humans at safe light levels that could reveal transparent cells in the retinal ganglion cell layer with a contrast and acquisition time approaching results only previously obtained in monkeys.

A New Method for Visualizing Drusen and Their Progression in Flood-Illumination Adaptive Optics Ophthalmoscopy.

Purpose: Drusen are dynamic sub-RPE deposits that are risk factors for late-stage age-related macular degeneration (AMD). Here we show a new imaging method using flood-illumination adaptive optics (FIAO) that reveal drusen with high contrast and resolution.

Methods: A fovea-centered 4° × 4° FIAO image and eight surrounding images with gaze displaced by ±2° vertically and horizontally were acquired.