IndraLab
Statements
sparser
"Whilst methods are being developed to image RGCs in vivo noninvasively using adaptive optics (AO), in combination with a scanning laser ophthalmoscopy (SLO), xref optical coherence tomography (OCT) xref , xref , xref or a multimodal system combining both AO‐SLO and AO‐OCT, xref significant challenges remain. xref For example, there are still difficulties in differentiating RGC subtypes from each other and from displaced amacrine cells (AC). xref In addition, studies using such technologies have only been conducted so far on very small samples using specialist equipment not widely available to researchers or clinicians."
sparser
"Combined with infrared or near-infrared (NIR) AF, enhanced with indocyanin green, or in multimodal setups, AO-SLO successfully identified the RPE mosaic in healthy volunteers xref , xref , xref , xref , xref and patients. xref , xref However, AF-based imaging methods generate significantly long-lasting AF reduction at exposures lower than those imposed by safety norms. xref Hence, despite methodologic improvements, RPE visualization remains hindered by safety concerns and relatively long acquisition times. xref "
sparser
"All previously published reports have used 2D evaluation of laminar pore area with AO-SLO, [ xref ] auto-segmentation of the laminar pores with SS-OCT [ xref , xref ], or have used new types of OCT. [ xref ] However, when the disc angle is tilted, accurate evaluation of pore structure in 2D is very difficult."
sparser
"Figure xref (A-J) shows the angiography of retina and choroid through green fluorescing fluorescein and micellar nanoparticle tagged with red fluorescing rhodamine-X. Comprehensively, a combined OCT/SLO system comprises AO-SLO for imaging physiological events of retinal components such as blood flow, microglia cells, capillaries, GFP expression of cone photoreceptor cells and its three-dimensional localization by combining with the widefield OCT/pv-OCT and SLO records."
sparser
"To address this challenge, adaptive optics (AO) has been combined with SLO to correct the optical aberrations, enabling fine cellular structures within the retina to be resolved. xref developed a custom AO-SLO instrument for non-invasive imaging of the mouse retina and generated the first in vivo images of the photoreceptor mosaic in mice."
sparser
"Here, an imaging platform combining multimodal AO-scanning light ophthalmoscopy (AO-SLO) with AO-optical coherence tomography (AO-OCT) is developed to make a side-by-side comparison of the same RPE cells imaged across four modalities: AO-darkfield, AO-enhanced indocyanine green (AO-ICG), AO-infrared autofluorescence (AO-IRAF), and AO-OCT."
sparser
"Using the results from the fine-tuning (Layer 5) method, they calculated four different cone mosaic parameters that were similar to the results found in AO-SLO images, showing the utility of their method. xref Christopher et al . demonstrated that deep learning methodologies have high diagnostic accuracy for identifying fundus photographs with glaucomatous damage to the optic nerve head in a racially and ethnically diverse population."
sparser
"Retinal imaging techniques such as color fundus photography, scanning laser ophthalmoscopy (SLO), and optical coherence tomography (OCT), combined with procedures such as fluorescein angiography (FA), have enabled multidimensional en face and cross-sectional imaging to resolve critical structural information about the retinal vasculature. xref – xref However, clinical biomarkers observed via these modalities are largely limited to qualitative assessments of vascular health and fail to adequately quantify retinal hemodynamics. xref Advanced retinal imaging techniques such as OCT-angiography (OCT-A), adaptive optics-SLO (AO-SLO), and Doppler-OCT have begun to elucidate and quantify the relationships between retinal vascular anatomy and function, but each with its own limitations. xref – xref For example, OCT-A offers high resolution and three-dimensional reconstruction of the retinal microvasculature without the use of exogenous contrast agents, but the limited temporal resolution makes it difficult to evaluate blood flow dynamics in slow flow regions. xref Doppler-OCT is a technique that enables quantitative velocimetry based on OCT, but this method is highly sensitive to the orientation of vessels with respect to the illumination source, complicating its clinical use. xref , xref Moreover, AO-SLO offers unprecedented lateral resolution and may complement OCT-A for resolving the microvasculature, but velocity measurements with AO-SLO are sensitive to vessel orientation and size and are limited to a relatively small field of view (FOV). xref , xref , xref Computational tools have been developed to improve retinal blood flow speed mapping in OCT-A and to automate and hasten velocity determinations with AO-SLO, but limitations in temporal resolution and FOV remain to be addressed. xref , xref Therefore, the development and validation of complementary imaging strategies that can not only detect structural changes to the retina but also quantify physiological variations (i.e., changes in retinal hemodynamics) with high temporal resolution and a wide FOV may critically expand the arsenal of tools for studying and monitoring retinal disease."
sparser
"The application of the aforementioned optical retinal imaging techniques in mice xref is particularly important as rodents serve as a primary animal model for exploring not only fundamental aspects of vision science and ophthalmic research, xref xref – xref including investigations into phototransduction mechanisms, xref , xref but also broader applications in the field of general neuroscience. xref Various groups studied neurovascular coupling in rodents subject to flicker stimulation. xref , xref Inner retinal blood flow has been monitored with LDH in rodents at a temporal resolution of. xref Ultrahigh-resolution images of the mouse retina have been acquired with visible light OCT xref and AO-SLO. xref Zhang et al. xref , xref demonstrated in vivo cellular resolution neuronal and vascular retinal imaging in mice without AO and, more recently, with AO. xref A sensorless AO approach has also provided volumetric cellular imaging of microglia throughout the inner retina. xref "
sparser
"In vivo, the basal and apical parts of the CB are summed along the optical axis with variable contributions, influenced by the light scattering of apical M and neuroretina. xref In addition, outer choroidal melanin contributes to NIR-AF (λ exc 787 nm) signals, as shown in subjects aged 48 to 77 years. xref Nonetheless, high-resolution SW-AF (λ exc 532 nm) and NIR-AF (λ exc 757 nm, 796 nm) images of the RPE by AO-SLO show a hexagonal RPE cell mosaic xref with peripheral signal distribution surrounding putative cell nuclei, xref which could reflect, at least in part, L and ML granule distribution detected in SIM microscopy in SW-AF (λ exc 488 nm) images. xref "
sparser
"This technique further bypasses absorption by macular pigment, thereby improving image quality compared to NIR-FAF. xref With regard to R-AF, subsequent studies by Vienola et al. xref and Lee et al. xref described a custom-built confocal scanning laser ophthalmoscope using adaptive optics (AO-SLO) with λ exc 660, 663, 680, 700, and 720 nm."
sparser
"Similar imaging
technique, adaptive optics scanning laser ophthalmoscopy (AO-SLO),
was used to track the spatiotemporal dynamics of GFP + microglia
in a mouse model of photoreceptor damage, xref but this imaging method is not able to detect NLRP3 inflammasomes
in activated cells."
sparser
"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))."
sparser
"Another potential strategy to improve the accuracy of LSCI-based flow rate measurements would be to derive a standardized scale of speckle contrast relative to flow velocity by comparing speckle intensity to absolute particle velocity within specific vessels as calculated using other advanced imaging modalities such as AO-SLO, which has demonstrated the ability to quantify single cell velocities across the full range of retinal vessels, from capillaries to primary arteries and veins. xref , xref – xref Although automated analysis workflows have simplified the lengthy and laborious process of determining cell velocities with AO-SLO, the limited FOV still requires flow analysis to be performed on a vessel-by-vessel basis. xref A side-by-side comparison of LSCI and AO-SLO would enable LSCI-based measurements of speckle intensity to be related directly to flow velocity (at least within the individual animal) and would allow quantitative measurements of flow in vessels across the whole retina without montaging."
sparser
"To evaluate adaptive optics scanning laser ophthalmoscope (AO-SLO) features and identify their multimodal retinal imaging characteristics using AO-SLO, swept-source optical coherence tomography (SS-OCT), and color fundus photography in patients undergoing surgery for epiretinal membrane (ERM), and to provide valuable insights into the mechanism underlying postoperative ERM progression."
sparser
"Image quality constitutes a potentially significant drawback for the majority of imaging technologies including FA, AO-SLO and OCT-A, since intraocular scattering and absorption have a strong impact on the quality of images. xref Situations affecting image quality may include small pupil, media opacities and poor subject cooperation, which may be common in older subjects."
sparser
"The complete elimination of artefacts produced by fast motion occurring for example during saccades has yet to be accomplished, but with reasonable compliance from the test subject, the region of interest selected for high-resolution imaging by AO-OCT can be imaged to a level of practical utility and residual motion is then corrected by multimodal image registration software that uses the recorded SLO and AO-SLO images as reference for registration and alignment of the OCT and AO-OCT images, respectively."
sparser
"Regarding the measurement of total cone density, current AO-FC and AO-SLO systems have two relevant benefits over AO-OCT systems: First, the images are less prone to motion artefacts due to faster en-face acquisition times; second, they often utilize image-averaging algorithms, improving the overall image quality and thus cone depiction [ xref , xref – xref ]."
sparser
"Using different AO-SLO systems, Song et al. reported mean densities between 18.500 to 24.200/mm 2 at ecc 0.9 mm [ xref ], Zhang et al. showed approximately 20 to 25.000 cones/mm 2 at ecc 1mm [ xref ], and Park et al. found densities between 18.600 and 20.200/mm 2 at ecc 1mm [ xref ]."
sparser
"While a lower eccentricity-dependent decline of cone density was described for the horizontal meridians in histology and AO-SLO (referred as “cone streak”), a statistical difference was so far only reported by Park et al. who found the same effect of meridians on cone density as we did (N,T > I, S) at ecc 1.0mm, but not at other eccentricities [ xref – xref ]."
sparser
"Previous analysis of structural characteristics of microaneurysms using AO-SLO xref , xref in different stages of diabetic retinopathy has described intraluminal hyperreflective structures as in our study, and the method has been reported to have a higher sensitivity for the detection of microaneurysms than fundus photography xref ."
sparser
"Retinal microaneurysms have furthermore been examined with electron microscopy and confocal scanning laser microscopy altogether suggesting that their intraluminal content, which we saw as hyperreflective granularities in AO-SLO imaging, may represent aggregates of endothelial cells xref , xref , inflammatory cells, erythrocytes and lipid deposits xref , xref ."
sparser
"Recently, there have been studies investigating the repeatability of cone photoreceptor imaging via adaptive optics scanning laser ophthalmoscopes (AO-SLO) in subjects with no pathology as well as various retinal genetic diseases. xref xref xref xref xref – xref AO-SLO images are created by scanning a small point source of light in a raster fashion; when combined with a pinhole filter, this technique leads to improved axial and lateral resolution compared to flood-illuminated AO."
sparser
"In order to investigate the generalizability of denoiseGAN to AO retinal images captured on different devices and with distinct signal distributions and patterns, we directly applied the trained denoiseGAN to a split detector AO-SLO dataset ( xref ) and quantified the signal enhancement effect through power spectra comparison ( xref ) and BIQI scores ( xref )."
sparser
"It is noteworthy that despite the distinct visual appearance of images captured on split-detector AO-SLO, denoiseGAN consistently enhances the spatial frequency signals associated with cellular structure and overall image quality indices, which validates the generalizability of denoiseGAN."
sparser
"In this Letter, we use the Pittsburgh multi-offset AO-SLO [ xref ], which contains an off-axis detector that can be precisely positioned perpendicularly to the optic axis in eight different positions [ xref ], to demonstrate that while one axis will indeed present an asymmetric light distribution generating high cellular contrast, the perpendicular axis has a symmetric light distribution strongly diminishing cellular contrast for this given direction."
sparser
"Although we recently demonstrated an improved image contrast of in-vivo human retinal ganglion cells using a multi-offset aperture AO-SLO 4(a) [ xref ] compared to the work of Rossi et al. [ xref ], there was still regions where we could not clearly identify the cells because of low contrast."
sparser
"Initially described histologically as rosette-like formations, ORT has gained clinical relevance with the advent of high-resolution imaging modalities such as spectral-domain optical coherence tomography (SD-OCT) and adaptive optics scanning laser ophthalmoscopy (AO-SLO), which enable in vivo visualization of its tubular architecture."
sparser
"Furthermore, SD-OCT failed to show any structural changes in the asymptomatic eye (right eye) while the AO-SLO was able to detect smaller focal areas of cone loss, demonstrating the ability to detect structural changes before manifestation of functional loss noticed by the patient."
sparser
"Applying the principles of spectroscopy and known absorption properties of hemoglobin, Schuman discussed using visible-light OCT to evaluate with very high resolution the oxygen saturation of the various layers of the eye attributable to the known absorption spectrum of hemoglobin. xref Used in conjunction with other technologies, such as OCTA or AO-SLO, structure and function can be evaluated simultaneously with visible-light OCT, providing powerful new insights into the pathology of eye disease. xref , xref "
sparser
"She presented several AO-SLO studies that tracked disease progression by evaluating changes in the cone photoreceptor mosaic and noted that cone spacing and regularity have been correlated with photoreceptor function. xref The subtle, cellular-level data gathered from the addition of AO can provide critical information on changes in retinal disease, ranging from rare retinal dystrophies xref to prevalent conditions, such as age-related macular degeneration. xref Moreover, AO-SLO can be coupled with other techniques, such as microperimetry, to measure both structure and function at the cellular level. xref Austin Roorda, PhD, concluded, “The cellular-level access that we get with AO drives the paradigm shift in how we use ophthalmoscopy to study eye disease."
sparser
"AO-SLO systems enabled direct visualization of RNFL, photoreceptors, microvasculature, and immune cells in vivo , establishing adaptive optics as a powerful framework for high-resolution retinal imaging in rodents. xref , xref , xref , xref More recently, Zhang et al. and Mujat et al. developed a high-speed AO-SLO-OCT platform that significantly reduced wavefront error and improved resolution. xref , xref Consistent with these pioneering studies, our WSAO implementation increased image sharpness by 55% and contrast by 61%."
sparser
"The precision found on human eyes and the artificial eye is equal or better than any reported values in literature (0.0069 degrees on a DPI Gen5.5 with an non-moving artificial eye xref and 0.012 degrees on a human eye xref ; 0.0012 to 0.0045 on the EWET1 prototypes on human eyes xref ) without being affected by lens-wobble artifacts, such as in a DPI or distortion artifacts, such as in an AO-SLO system (no RMS-S2S values found for AO-SLO in literature)."
sparser
"By reducing the effects of wavelength distortions, AO is able to improve the performance of an optical system. xref provides a comparison of the performance of the AO-SLO against commonly used imaging modalities: fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), OCT and fundus autofluorescence (FAF)."
sparser
"A related imaging modality, Adaptive Optics Scanning Laser Ophthalmoscopy (AO-SLO), was recently used to study the spatiotemporal dynamics of GFP + microglia in a mouse model of photoreceptor damage, ( xref ) but this method does not provide key information about the presence or absence of NLRP3 inflammasomes in microglia."
sparser
"Dark-field AO-SLO offers no specific localized signal sensitivity with respect to RPE cells and typically provides the best contrast in the fovea and increasingly poorer images with increasing eccentricity, owing to scattering noise from other targets, particularly rod photoreceptors."
sparser
"Because of the micron-scale depth resolution afforded by the low coherence interferometry approach, AO-OCT volumes can be precisely segmented to visualize retinal layers and sub-layers, making AO-OCT more immune to crosstalk and interference from other structures of interest (e.g., PR signal imprinted on RPE images in dark-field AO-SLO)."
sparser
"In Steven et al.’s report, they describe a fixation channel design utilizing a combination of custom and off-the-shelf optics for AO scanning laser ophthalmoscopy (AO-SLO) imaging to achieve wide field viewing of 32.2° x 32.2°, a working distance of ∼45 mm (see Discussion for details), and a large dioptric correction range of -25 to +20 diopters by mechanically translating an integrated Badal optometer."
sparser
"In fact, a recent study using AO-SLO, which has poor axial resolution, tracked vitreoretinal interface macrophage cells and found that the majority of these cells traveled very short distances, staying within their niche [ xref ], suggestive of microglia properties in the parenchyma."
sparser
"Over the course of 25 years of progress in the field, there has been a proliferation of high-resolution AO retinal imaging modalities, including AO flood illuminated fundus photography [ xref ], AO-scanning laser ophthalmoscopy (AO-SLO) [ xref ], and AO-optical coherence tomography (AO-OCT) [ xref , xref ]."
sparser
"Moreover, the offset between our predicted retinal location (19.5°) and that seen in the Spectralis SLO image ( xref ) is consistent with mapping distortions reported by Huang et al. [ xref ], who found errors up to ∼0.8° at 10° eccentricity between the Spectralis and their AO-SLO system."
sparser
"Ophthalmic imaging technologies such as Fundus Photography [ xref – xref , xref ], Doppler Holography [ xref , xref ], AO-SLO [ xref , xref , xref ] and AO-OCT [ xref , xref ] have been used in the past to measure changes in the lateral BVD in response to visual stimulation from en face images."
sparser
"This technology has been extensively applied in assessing structural changes in various retinal pathologies, xref such as diabetic retinopathy, xref age-related macular degeneration xref and resolved central serous chorioretinopathy. xref Therefore, our study aimed to investigate photoreceptor morphology using AO scanning laser ophthalmoscopy (AO-SLO) and examine its relationships with retinal sensitivity (RS), retinal vessel densities (VDs), subretinal thickness and choroid thickness."
sparser
"More recently, non-confocal detection [ xref ], which captures multiply scattered light, has been applied to AO-SLO imaging, showing enhanced contrast and visualization of retinal structures such as cone inner segments [ xref ], retinal pigment epithelium [ xref ], retinal vessels and capillaries [ xref , xref ] and retinal ganglion cells [ xref , xref ]."
sparser
"The optical design is greatly simplified, compared to other confocal and split aperture configurations, as the lens-based system keeps the system aberrations low [ xref ] and removes the need for off-axis configurations [ xref – xref ] typically required in AO-SLO and AO-OCT systems when using spherical mirrors [ xref , xref ]."
sparser
"Here, we expand upon this earlier report by longitudinally characterizing persistent, widespread dark cones observed within and near the macula using multimodal AO scanning light ophthalmoscopy (AO-SLO) and AO optical coherence tomography (AO-OCT), alongside detailed analysis of retinal function in a patient with OT ( xref )."
sparser
"This DCP-specific hypoperfusion shares similarities with diabetic retinopathy, where capillary dropout precedes neuronal damage but diverges in selectively sparing the SCP, a hallmark of HM’s unique vascular pathology. xref Critically, AO-SLO imaging revealed HM’s dual-pathology mechanism: cone loss results not only from mechanical stretching but also from compromised blood perfusion, potentially leading to ‘starved’ photoreceptors deprived of oxygen and nutrients. xref This discovery challenges the traditional view of HM as a purely biomechanical disorder, redefining it as a dual-mechanism disease. xref "
sparser
"Spatially and temporally co-registered AO-SLO imaging confirmed that the dark cones surrounded by reflective rods (e.g., blue arrows in xref ) seen in confocal reflectance did indeed contain intact inner segments, with a small population of cones that remained normally reflective."
sparser
"Investigators in this area have used digital micromirror devices or rolling shutters to create patterns in illumination and/or detection, effectively creating arrays of confocal pinholes in the system. xref – xref This approach has the potential to marry the high speeds achievable with AO fundus imaging (which can exceed 1 kHz with modern scientific CMOS cameras) with the confocality of AO-SLO imaging."
sparser
"The work presented in this paper is concluded with AO imaging experiments representing two important ophthalmic imaging modalities, AO-OCT and adaptive optics-scanning laser ophthalmoscopy (AO-SLO), including the associated contrast and resolution calculations from these images."
sparser
"We also note two unique effects specific to this AO-SLO imaging setup in xref : (1) the horizontal pixel size varies slightly across the image, stretching from left to right; (2) the two arrays on the left side of the image (A4 and A4.5) have a much more distorted appearance than their AO-OCT image counterparts."
sparser
"In our case study with three phantoms and our laboratory multimodal AO system, with theoretical diffraction-limited confocal lateral resolution of 1.7 and 1.8 µm for AO-SLO and AO-OCT [ xref ], respectively, we estimate respective resolution values of 2.62 ± 0.04 and 2.83 ± 0.07 µm."
sparser
"In vivo visualization of human RPE cells has been demonstrated with dark-field AO-SLO [ xref , xref ], AO-SLO autofluorescence [ xref – xref ] and intravenously injected indocyanine-green (ICG) fluorescence imaging [ xref – xref ], transscleral optical phase imaging (TOPI) with AO [ xref , xref ], and AO-OCT [ xref , xref , xref – xref ]."
sparser
"In particular, combining cSLO with adaptive optics (AO-SLO) has expanded its utility to include three-dimensional and time-resolved imaging. xref , xref While 2PM intrinsically enables three-dimensional imaging deep within the tissue, xref three-dimensional AO-SLO requires coregistration with OCT for focal depth calibration. xref , xref Adaptive optics may provide higher spatial resolution because they continuously correct system-inherent and tissue-inherent wavefront distortions, but their application requires more technical know-how and accordingly seems more challenging than the approach presented in this study."
sparser
"Adaptive optics-scanning laser ophthalmoscopy (AO-SLO) resolves images of the retina at the cellular level[ xref , xref ] and in fact, is capable of revealing subtle alterations including decreased cone density and increased spacing in areas of otherwise normal photoreceptor layer thickness.[ xref , xref , xref ] Numerous technical hurdles specific to AO-SLO—the requirement of stable fixation, complexity of instrument operation, high costs and limited availability—limit its practical utility and makes OCT a more suitable endpoint modality for ABCA4 disease, at least in the near future.[ xref ]"
sparser
"When combining AO with these imaging techniques, the higher transverse resolution offers better visualisation of a small features including individual cells. xref To put this into context, adaptive optics scanning laser ophthalmoscopy (AO‐SLO; Figure xref ) provides up to 2.5 μm transverse resolution compared to a resolution of only 20 μm for a conventional fundus camera. xref , xref When applying AO to OCT (adaptive optics OCT or AO‐OCT), it is possible to achieve isotropic resolution with 2 μm resolution in all dimensions. xref "
sparser
"In future work, introduction of cell-type-specific fluorescent optogenetic reporters into other relevant cell types, including rods, Müller glia, and bipolar cells, will enable detection of individual cell–cell interactions in vivo with AO-SLO, while refined analysis with AO-OCT may reveal the fate of individual rods and other cells ( xref )."
sparser
"High resolution AO-SLO imaging showed in vivo observation of micro-changes of capillary such as occlusion, recanalization, dilatation, resolution of local retinal hemorrhage, capillary hairpin formation, capillary bend formation, or microaneurysm formation in the macula area of DR patients [ xref ]."
sparser
"AO technologies have also been combined with optical coherence tomography (AO-OCT), fundus photography and scanning-laser ophthalmoscopy (AO-SLO), that increased the sensitivity and resolution and thus provided new insights into the effects of retinal degenerations ( xref – xref , xref – xref )."
sparser
"Interestingly, AO-OCT with volume averaging produced images of GCs with unprecedented clarity, allowing reliable mapping of morphometry of retinal neuron somas across the living human retina. xref There have been many reports of imaging inner retinal neurons in the mouse retina labeled by extrinsic fluorescent proteins or dyes and detected by fluorescence emission SLO. xref There have also been reports of imaging retinal neuron somas using AO-SLO with split detection like in human studies. xref However, there have been no reports on the visualization of inner retinal neurons based on volume averaging of OCT or AO-OCT data from the mouse eye."
sparser
"The field has grown rapidly with advances in in vivo imaging technologies which enable us to noninvasively assess vasodilatory response to flicker light stimulation [ xref ], such as laser Doppler velocimetry (LDV) [ xref ], laser Doppler flowmetry (LDF) [ xref ], retinal vessel analyzer (RVA) [ xref ], adaptive optics (AO) flood-illumination ophthalmoscope [ xref ], AO scanning laser ophthalmoscope (AO-SLO) [ xref ], laser speckle flowgraphy (LSFG) [ xref ], Doppler optical coherence tomography (OCT) [ xref , xref ] and OCT angiography (OCTA) [ xref , xref ]."
sparser
"Moreover, in this study, retinal areas within the hyperautofluorescence in FAF image indicated normal outer retinal structures, whereas the AO-FIO images displayed increased spacing in the cone mosaic, as previously found with, AO-SLO imaging ( xref ) and in descriptive analysis ( xref )."
sparser
"The application of AO to SLO and OCT technologies has greatly facilitated the ability to achieve cellular resolution imaging of these cells in both animals and humans ( xref ). ( xref , xref , xref – xref ) Several existing papers summarize the related studies on photoreceptors and limitations of AO-SLO ( xref , xref , xref – xref ) and AO-OCT ( xref , xref , xref ) imaging."
sparser
"AO-SLO has been used in a large number of studies xref , xref – xref , xref – xref covering fundamental cell morphology and cell populations, clinical studies of retinal disease, vision restoration, therapeutics, phototoxicity, visual function of cell types, developmental processes, and neurovascular coupling and microvascular perfusion."
sparser
"The literature already contains an abundance of recent excellent reviews on high-resolution retinal imaging, mostly on the combination of AO and SLO (AO-SLO), including two in this journal ( xref , xref , xref , xref , xref , xref , xref , xref , xref ), and on the combination of AO and OCT (AO-OCT) ( xref , xref , xref ), the subject of this review."
sparser
"Adaptive optics–scanning laser ophthalmoscopy (AO-SLO) resolves images of the retina at the cellular level xref , xref and, in fact, is capable of revealing subtle alterations, including decreased cone density and increased spacing in areas of otherwise normal photoreceptor layer thickness. xref , xref , xref Numerous technical hurdles specific to AO-SLO—the requirement of stable fixation, complexity of instrument operation, high costs, and limited availability—limit its practical utility and make OCT a more suitable endpoint modality for ABCA4 disease, at least in the near future. xref "
sparser
"While these developments have been captured in prior reviews, they are often framed by what AO-OCT can achieve after all of its technological problems are overcome—capturing pristine 3D views of the cellular retina that are not possible using other imaging modalities such as AO-SLO and AO fundus ophthalmoscopy."
sparser
"It is possible to compensate for these aberrations by using imaging systems that incorporate adaptive optics (AO), consisting of a wavefront sensor that measures aberrations in ocular optics and a deformable mirror or spatial light modulator to compensate for aberrations in living eyes. xref We previously demonstrated that AO-SLO captures images of individual retinal nerve fiber bundles in normal eyes and eyes of patients with glaucoma xref , xref and showed that nerve fiber bundle width changed in proportion to NFL thickness in eyes of patients with glaucoma compared to control eyes. xref Yet, it remains unclear whether AO-SLO is useful for detecting microstructural changes in retinal nerve fibers over time."
sparser
"AO-SLO revealed that nerve fiber bundles were narrowed but present in many areas in which NFL defects were observed on fundus photography and red-free SLO imaging. xref For this reason, we refer to abnormalities on AO-SLO images as “nerve fiber bundle narrowing” and those on red-free fundus photograph and red-free SLO imaging as “NFL defects.”"
sparser
"By pairing adaptive optics (AO) technology with scanning laser ophthalmoscopy (AO-SLO) and OCT (AO-OCT), it is now possible to obtain three-dimensional, cellular-level structural images of the optic nerve head and retina to study glaucoma. xref – xref Newly demonstrated AO-OCT methods can reliably quantify GCL soma morphology and density xref – xref and can distinguish retinal capillaries xref at significantly higher resolution than commercially available OCT-A, enabling analysis at multiple eccentricities from the fovea within the macula."
sparser
"Other imaging techniques, such as laser speckle contrast imaging, allow for reproducible, dynamic blood flow analysis, but is limited to bulk flow data, measured in arbitrary units, and unable to determine retinal capillary flowrates. xref Adaptive optics-scanning laser ophthalmoscopy (AO-SLO) has the highest resolution of current technologies and is able to determine absolute erythrocyte velocities and image capillaries precisely, but has a limited field of view and has not yet been used to assess plexus-specific capillary velocities. xref – xref "
sparser
"Various methods have been developed for observing the retinal nerve fiber layer (RNFL) and nerve fiber layer defects (NFLDs): regular fundus photography, red-free fundus photography [ xref ], scanning laser ophthalmoscopy (SLO) [ xref ], adaptive optics SLO (AO-SLO) [ xref ], scanning laser polarimetry (GDx) [ xref ], Heidelberg Retinal Tomography (HRT) [ xref ], and optical coherence tomography (OCT)."
sparser
"This stands in contrast to our previous AO-SLO observations of the cones at greater eccentricities, although it is in agreement with AO-OCT cone counts at the same locations. xref Also in disagreement with our more eccentric AO-SLO data, we did not find greater irregularity in cone packing, as measured by the standard deviation in the number of sides or in intercone distances."
| PMC
sparser
"Zhong et. al. and Guevara-Torres et. al. demonstrated the measurement of absolute blood velocity distribution with AO-SLO in a custom line-scan mode by resolving densely packed red blood cells (RBCs) in medium or large vessels and as a single file flow within capillaries [ xref , xref ]."
sparser
"This could be further substantiated with non-confocal AO-SLO imaging of the inner segment. xref Alternatively, cone loss could be causally related to dichromacy in which the dark holes are a consequence of incomplete replacement of lost cones with cones of another type during retinal development, as suggested in hypothesis 1."
sparser
"AO overcomes this limitation by actively compensating for these aberrations using a deformable mirror, enabling cellular-resolution in vivo imaging. xref , xref Combined AO-SLO and AO-OCT systems are capable of imaging individual photoreceptors with up to two to three times higher transverse resolution than conventional SLO and OCT. xref xref xref – xref When combined with hardware- and software-based retinal-tracking technologies, xref AO systems can be used to quantify retinal photoreceptor distributions across large FOVs and study cellular changes associated with retinal disease progression ( xref ). xref , xref xref xref xref xref xref xref xref xref xref xref xref xref xref xref xref xref xref xref xref xref xref xref xref xref xref xref xref xref xref – xref In addition to structural imaging, AO systems have also demonstrated benefits for functional imaging, including visualizing perfusion in the retinal microvasculature and phase dynamics from photoreceptor photostimulation. xref xref – xref "
sparser
"This follow up study concluded that, while the average cell densities originally reported in Ref. xref are slightly higher than those measured by AO-SLO, especially within 300 µm of the fovea, the overall pattern of cell densities were highly concordant between the two studies xref ."
sparser
"Although Zhong et al. demonstrated that the vessel diameter can be extracted from the AO-SLO line-scan frame from the dark bands surrounding the streak region [ xref ], average AO-OCT volumes produced much more reliable vessel diameter measurements, allowed for more vessel wall metrics (WLR, wall diameter, etc.) to be extracted, and avoided any ambiguity in terms of the axial position of the scan by leveraging the excellent depth sectioning capabilities of OCT."
sparser
"A study of AO‐SLO compared with conventional OCT in NPDR showed improved visualisation of various retinal features including retinal vessels in the inner retinal layers, extensive capillary remodelling despite mild or moderate NPDR, clinically undetected intraretinal vessel remodelling and varying blood flow patterns, and regions of bright cones and dark regions in the photoreceptor layer with dark regions corresponding to areas of overlying vascular remodelling. xref Compared with healthy controls, perifoveal capillary diameters were larger ( p < 0.01) and small arteriolar walls were thicker ( p < 0.05). xref "
sparser
"In a study using AO-scanning laser ophthalmoscopy (SLO), “microfolds” (multiple thin, straight, hyporeflective lines in the photoreceptor layer) were identified in patients with ERM. xref However, the 3-dimensional association between ERM and cone photoreceptors cannot be observed because AO-SLO allows observation in a plane parallel to the retina."
sparser
"It could be performed at the hardware level using the Shack-Hartmann wavefront sensor and a digital deformable micromirror array in real-time, xref or at the computational level where the wavefront aberration sensing and correction are conducted offline. xref Cone photoreceptor cells have been imaged via their intrinsic reflectance using adaptive optics confocal scanning laser ophthalmoscope (AO-SLO), but RGCs have proven more challenging to image due to their near transparency. xref "