IndraLab

Statements


| 118

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"TRANSLATIONAL RELEVANCE The current work describes the application of cellular-level imaging technique called adaptive optics scanning laser ophthalmoscopy (AO-SLO) to the clinical condition of resolved endophthalmitis."

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"In relating our AO-SLO results to our OCT findings, we note (again) that there was no significant change from normal cone density in our small cohort of preterm subjects."
| PMC

sparser
"AD contributed to AO-SLO instrument and DeMotion image registration software development."

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
"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
"AO-SLO provides exceptionally detailed images of the retina in both human and animal models."

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
"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
"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
"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
"The new system allows either independent or simultaneous data acquisition of AO-SLO and AO-OCT, depending on the requirements of specific scientific experiments."

sparser
"Currently, the most commonly used AO enhanced imaging technologies are AO flood illumination fundus camera (AO-FC) and AO scanning laser ophthalmoscopy (AO-SLO), which have both been applied on healthy eyes and in several retinal pathologies [ xref – xref ]."

sparser
"Similar to AO-SLO, ICCs between graders were excellent and results of density measurements differed in most cases between 1.0% and 3% or roughly 150 to 500 cones/mm 2 ."

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
"Reduced image overlap is an inherent limitation of all AO retinal imaging modalities, including AO flood illumination, AO scanning laser ophthalmoscopy (AO-SLO), and AO-OCT, due to their small field of view."

sparser
"AO-SLO imaging revealed widespread dark cones intermixed with normally reflective cones in all areas imaged during the entire longitudinal study, and the high-resolution images provided by AO-SLO allowed the same dark cones to be tracked longitudinally ( xref , xref )."

sparser
"AO-SLO has the advantage of using a confocal configuration to generate images at different planes and depths in the retina [ xref , xref , xref ]."

sparser
"A further aim of our study was to utilize the “Find Maxima” function in the open-source image platform Fiji as an easy tool for semi-automated counting of cone density, which has been previously applied on AO-SLO images [ xref ]."

sparser
"The study of retinal cell biology at the cellular level is possible using the emerging technology of AO-SLO."

sparser
"AO-SLO may have particular utility for assessing short-term glaucoma-related changes in the retinal nerve fibers."

sparser
"As we will discuss, we have previosuly adapted this algorithm to AO-OCT volumes because their en face projections are distorted similarly to AO-SLO images."

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"During image acquisition, the total power entering the eye from the AO-SLO and the wavefront sensor beacon were respectively 600 µW and 20 µW , which are below the ocular safety limits established by the ANSI."

sparser
"AO-SLO can provide precise localization of intraretinal structures such as hyperreflective dots (HRDs) which represent cellular debris from serous detachment of RPE and decreased retinal metabolic support [ xref ]."

sparser
"The current study showed that the expansion of nerve fiber bundle narrowing over time is distinguishable on AO-SLO."

sparser
"In the current study, AO-SLO images had better resolution and contrast than red-free fundus photography or red-free SLO images, and microstructural changes in the NFL were only detected on AO-SLO images in a proportion of eyes."

sparser
"The above study also have reported the fluorescence images and mapping of the retina in which the AO-SLO images are localized within the distinct axial focal planes and patterns of knocked GFP expressed cells."

sparser
"Integration of multiply scattered light detection xref , xref – xref and single- and multiphoton fluorescence xref , xref , xref – xref of intrinsic and extrinsic fluorophores has greatly expanded the structural and functional properties of cells that the AO-SLO can reach."

sparser
"To report the foveal cone count in eyes with resolved endophthalmitis vis-à-vis normal fellow eyes using an indigenous adaptive optics scanning laser ophthalmoscopy (AO-SLO)."

sparser
"This image is comparable to what can be obtained with two-dimensional imaging methods such as AL-FC or AO-SLO."

sparser
"Moreover, the use of a non-scanning system makes the acquisition process more stable under the effects of eye motion, especially because AO-SLO and AO-OCT require measurement time of several minutes."

sparser
"The Pittsburgh multi-offset AO-SLO was described in details elsewhere [ xref ]."

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
"AO-SLO has been used in the detection and diagnosis of CSCR."

sparser
"Accordingly, AO-SLO has potential utility for monitoring glaucoma over shorter periods than is feasible with other modalities."

sparser
"AO-SLO is an imaging tool that can be used to evaluate retinal layer integrity and changes in visual outcomes before and after resolution of CSCR."

sparser
"Collected data included measurement of the best-corrected visual acuity (BCVA), spectral-domain optical coherence tomography (OCT) imaging and AO-SLO imaging and cone counting at the fovea in both eyes."

sparser
"To circumvent this when detecting photoreceptors—light-sensitive cells that form a 2D mosaic—from AO-OCT images, Heisler et al. [ xref ] took advantage of existing manually labeled AO-SLO datasets."

sparser
"Moreover, in several eyes, this expansion was only detectable on AO-SLO images."

sparser
"Finally, they divided each quasi AO-SLO image into 50 strips and translated the strips based on the quasi-eye movement to simulate the distorted AO-SLO image."

sparser
"For comparison of overall cone densities, integrating AO-OCT signals from the cone layers to a FEF image can be used, with results similar to findings obtained by AO-SLO or AO-FC imaging."

sparser
"However, the slower volume image acquisition rate of AO-OCT (, compared tofor AO-SLO) results in more severe distortions."

sparser
"We observed the expansion of retinal nerve fiber bundle narrowing with AO-SLO."

sparser
"AO-OCT also permits the sensitivity and axial resolution that AO-SLO lacks in imaging the LC with depth, even though AO-SLO can provide very-high-resolution imaging of the LC surface ( xref )."

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
"The inherent inter- and intra-variability of human graders in marking images due to the subjective nature of the task, as has been demonstrated for OCT and AO-SLO images [ xref , xref , xref ], could also contribute to the higher SD values of previous studies."

sparser
"In 3 eyes, changes in the NFL were only detectable on AO-SLO images; in these eyes, no expansion of NFL defects was detectable on color fundus photography, red-free SLO imaging, or SD-OCT ( xref , xref )."

sparser
"In the retina such a method could potentially enable a direct, non-invasive detection of PARP activity in vivo , with single-cell resolution, using techniques such adaptive optics scanning laser ophthalmoscopy (AO-SLO) [ xref – xref ]."

sparser
"The Adaptive Optics technology has been used to analyse the status of photoreceptors after idiopathic macular hole surgery by Ooto xref , Yokota xref , and Hansen xref with AO-SLO, and by Markan using AO-FIO xref ."

sparser
"First (as noted above), the AO-OCT cone counts at the same locations did not recapitulate the AO-SLO results."
| PMC

sparser
"Numerous algorithms have been developed for registering images from adaptive optics scanning laser ophthalmoscopes (AO-SLO) xref xref xref – xref and AO-OCT. xref xref – xref These are based universally on strip-wise registration of two-dimensional (2D) en face images."

sparser
"The AO-SLO is able to detect decrease in cone density and disruption of inner segment/outer segment (IS/OS) or intermediate line on OCT [ xref ]."

sparser
"Currently, technological limitations, with regard to both field of view and image acquisition, hinder the clinical utility of AO-OCT and AO-SLO."

sparser
"The AO-SLO images can be used to facilitate image registration, correcting for eye movement artifacts and allowing cellular-level resolution of photoreceptors and retinal pigment epithelium."

sparser
"The current work describes the application of cellular-level imaging technique called adaptive optics scanning laser ophthalmoscopy (AO-SLO) to the clinical condition of resolved endophthalmitis."

sparser
"AO-SLO is one of the most appropriate imaging biomarkers used in recent times designed exquisitely for the fluorescence and reflectance imaging of the retina of the mouse xref ."

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"Nerve fiber bundle narrowing expanded vertically on AO-SLO images."

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"Bedggood and Metha xref used a strip-wise registration algorithm to register simulated AO-SLO images from high-speed AO flood illumination (200 Hz)."

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
"The expansion of nerve fiber bundle narrowing was detected on AO-SLO images in 8 eyes (57.1%) over an observation period of 1.44 ± 0.42 years (range, 1.0–2.2 years)."

sparser
"One in-vivo autofluorescence AO-SLO study provided a RPE cell density of 5890 cells/mm 2 (168 μm 2 area) and 5630 cells/mm 2 (195 μm 2 area) at 5° and 6.25° respectively (2 subjects) xref ."

sparser
"Further studies are necessary to evaluate the sensitivity and specificity of AO-SLO for detecting microstructural changes in glaucoma."

sparser
"These results are similar to histology and two-dimensional AO-FC and AO-SLO imaging."

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
"Adaptive optics scanning light ophthalmoscope (AO-SLO) can directly image the cone photoreceptor mosaic in the living human retina, which offers a potentially great tool to detect cone-related ocular pathologies by quantifying the changes in the cone mosaic."

sparser
"However, the AO-SLO study included many patients with myopia, and the study population overall had significantly elongated axial length, which could have caused the laminar pores to have a larger area."

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
"Recently, Guevara-Torres et al. [ xref ] proposed a geometric optical model for offset aperture in AO-SLO."

sparser
"Vogel et al. xref utilized a map-seeking circuit algorithm to register images from AO-SLO."

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"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
"In this study, we investigated longitudinal changes in retinal nerve fiber bundles using AO-SLO in eyes of patients with primary open angle glaucoma (POAG)."

sparser
"Arichika et al. reported that the HbA1c was positively correlated with the retinal artery wall thickness in diabetic patients without retinopathy using AO-SLO, suggesting the AO imaging can evaluate the microvascular damage in early phase."

sparser
"In recent works, optical methods to observe the neuroretina and the RPE cells were proposed using AO-SLO with offset aperture xref – xref , split detector xref , xref , darkfield xref , autofluorescence xref , or AO-OCT xref , xref ."

sparser
"Combined with microglia-specific fluorescent reporter mice, AO-SLO and AO-TPEFM imaging will be useful tools to examine in vivo longitudinal changes in microglia in retinal diseases."

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
"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
"This further illustrates the localization and visualization of the morphological structures and cells in 3D by combining the AO-SLO data with wide field OCT/phase variance OCT and SLO data."

sparser
"Recently, Palochak et al. reported that the blood flow in eyes with DM without DR determined by AO-SLO was significantly higher than controls which contrasted with the significantly decrease in blood flow in eyes with NPDR xref ."

sparser
"These dark cones can be readily identified by examining the co-registered confocal reflectance and non-confocal split detection AO-SLO images, which reveal the cone outer segment reflectivity and cone inner segment structure, respectively ( xref )."

sparser
"A general method was developed using the pv-OCT and AO-SLO system for the localization and characterizing the retinal microvasculature."

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
"Although the number of included eyes is similar to histologic studies and reports using AO-SLO/FC [ xref , xref , xref , xref ], Park et al. were able to assess the density in 192 eyes using AO-SLO [ xref ]."

sparser
"In the field of AO-SLO imaging, any static distortions are expected to be less obvious than modelled here (e.g. worst case in xref )."

sparser
"Azimipour et al. xref used a strip-wise registration algorithm to register AO-SLO and AO-OCT images and estimate the motion within a reference image."

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
"On the contrary, for cellular-resolution imaging, AO-SLO and AO-OCT would be more difficult to implement in clinical setting."

sparser
"Different implementations of such off-axis detection methods on both AO-SLO and AO-FIO, as offset aperture, split detection, dark-field, and multi-offset contributed to directly image red blood cells, blood vessel walls, photoreceptor inner segment and ganglion cells in-vivo ."

sparser
"AO-SLO — based on raster scanning a focused spot of light across the retina — has been the most extensively used ophthalmoscope for cellular-level scientific and clinical studies of the retina."

sparser
"Amongst them are FA, ICGA, adaptive optics-scanning laser ophthalmoscopy (AO-SLO), optical coherence tomography (OCT; swept source (SS) and spectral domain (SD)), and optical coherence tomography angiography (OCTA) [ xref ]."

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
"The simulated AO-SLO images were generated as follows: First, they computed the translational shifts between AO flood illumination images and upsampledto generate quasi-eye movements (from 200 to 1000 Hz)."

sparser
"AO-SLO allows for high transverse resolution, short scanning times, and direct measurements of back-reflected light intensity."

sparser
"Moreover, future investigation with AO-SLO for subtle photoreceptor changes at the margins of EZ loss would be valuable to investigate the hypothesis and anatomic correlates of “photoreceptors at risk” in MacTel."

sparser
"These morphological variations of the microglia from highly branched to amoeboid shape along the axis through the retinal layers can also be visualized by using the AO-SLO system."

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
"Nerve fiber bundle narrowing expanded significantly on AO-SLO images (272 ± 33.0 μm at 1st examination and 325 ± 33.6 μm at final examination; P  < 0.0001, analysis of variance with repeated measurements)."

sparser
"Stevenson and Roorda xref first developed a 2D strip-wise registration algorithm to register images from AO-SLO to a synthetic global reference."

sparser
"Miller et al. demonstrated that AO-SLO can be used to quantify the 3D distribution, morphology and dynamism of microglia within individual layers of the Cx3cr1 GFP mouse retina ( xref )."

sparser
"Foveal cone count reduction in resolved endophthalmitis: an adaptive optics scanning laser ophthalmoscopy (AO-SLO)-based prospective pilot study."

sparser
"However, this limitation affects most AO-SLO and AO-FC systems [ xref , xref , xref , xref , xref , xref , xref , xref ]."

sparser
"In a previous AO-SLO study of five single-gene dichromats, xref cone density and cone mosaic arrangement were found unaltered relative to those in color normals, thus supporting hypothesis 3."

sparser
"Previous studies using AO-SLO xref and AO camera xref also showed that the blood pressure was strongly correlated with the WLR which is in keeping with our results."

sparser
"Although AO-SLO imaging discussed earlier shows localization of intraretinal HRDs, quantification methods have not been established."

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
"On the other hand, AO-SLO findings suggest that pore area is significantly larger in glaucoma than normal subjects."

sparser
"Fourteen eyes from 12 patients with POAG and NFL defects on fundus photography were imaged with AO-SLO."

sparser
"AO–fundus camera imaging provides a large field of view, unlike limited AO-OCT and AO-SLO, although AO-OCT provides the depth information that enriches what is seen on AO–fundus camera images ( xref )."

sparser
"The images were combined with the OCT retinal vasculature data, followed by the localization of fluorescent cells and retinal microvasculature events in higher resolution in AO-SLO imaging xref ."

sparser
"AIM To report the foveal cone count in eyes with resolved endophthalmitis vis-à-vis normal fellow eyes using an indigenous adaptive optics scanning laser ophthalmoscopy (AO-SLO)."

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
"The different findings in dark holes between our study and prior studies may be attributed to the different imaging modalities used: AO flood illumination, xref , xref AO-SLO, xref and AO-OCT (this study)."

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
"So far, cone density values for healthy individuals have been reported in histologic examinations and studies using AO-FC and AO-SLO."

sparser
"AO-OCT allows for high axial resolution, which is limited in AO-SLO."

sparser
"When combined with SLO, AO-SLO enables microglia within distinct retinal layers to be resolved in vivo ( xref )."

sparser
"Historically, AO-OCT — based on low-coherence interferometry and typically raster scanning a focused spot of light across the retina — has been a less mature technology than AO flood illumination and AO-SLO."

sparser
"Second, they temporally downsampled AO flood illumination images (from 200 to 20 Hz) to generate quasi AO-SLO images."

sparser
"The other in vivo diameter measurement study by Rossi et al. [ xref ] measured soma diameters from AO-SLO images, which are different from AO-OCT images in terms of image quality."

sparser
"Here, we present our work integrating OCT into an existing mouse retinal AO-SLO system, resulting in a multi-modal AO-enhanced imaging system of the living mouse eye."