Light scattering in biological tissues can be reduced by using optical clearing agents. Various physical methods in conjunction with agents have been studied to enhance the optical clearing efficacy of skin for diagnostic and therapeutic applications. In this study, we propose a new physical method to enhance the optical clearing potential of topically applied glycerol. A microneedle roller is used to easily create numerous transdermal microchannels prior to glycerol application. The optical clearing efficacy of skin is quantitatively evaluated with the use of a modulation transfer function target placed underneath ex vivo porcine skin samples. From cross-polarized images acquired at various time points after glycerol application, we find that samples treated with the microneedle roller resulted in an approximately two-fold increase in contrast compared to control samples 30 min after glycerol application. In conclusion, our data suggest that the microneedle roller can be a good physical method to enhance transdermal delivery of optical clearing agents, and hence their optical clearing potential over large regions of skin.

Blood flow changes are highly related to neural activities in the retina. It has been reported that neural activity increases when flickering light stimulation of the retina is used. It is known that blood flow changes with flickering light stimulation can be altered in patients with vascular disease and that measurement of flicker-induced vasodilatation is an easily applied tool for monitoring functional microvascular alterations. However, details of distortions in retinal neurovascular coupling associated with major eye diseases are not well understood due to the limitation of existing techniques. In this study, flickering light stimulation was applied to mouse retinas to investigate stimulus evoked hemodynamic responses in individual retinal layers. A spectral domain optical coherence tomography (OCT) angiography imaging system was developed to provide dynamic mapping of hemodynamic responses in the ganglion cell layer, inner plexiform layer, outer plexiform layer and choroid layer before, during and after flickering light stimulation. Experimental results showed hemodynamic responses with different magnitudes and time courses in individual retinal layers. We anticipate that the dynamic OCT angiography of stimulus evoked hemodynamic responses can greatly foster the study of neurovascular coupling mechanisms in the retina, promising new biomarkers for retinal disease detection and diagnosis.

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Quantitative evaluation of retinal neurovascular coupling is essential for a better understanding of visual function and early detection of eye diseases. However, there is no established method to monitor coherent interactions between stimulus-evoked neural activity and hemodynamic responses at high resolution. Here, we report a multimodal functional optical coherence tomography (OCT) imaging methodology to enable concurrent intrinsic optical signal (IOS) imaging of stimulus-evoked neural activity and hemodynamic responses at capillary resolution. OCT angiography guided IOS analysis was used to separate neural-IOS and hemodynamic-IOS changes in the same retinal image sequence. Frequency flicker stimuli evoked neural-IOS changes in the outer retina; that is, photoreceptor layer, first and then in the inner retina, including outer plexus layer (OPL), inner plexiform layer (IPL), and ganglion cell layer (GCL), which were followed by hemodynamic-IOS changes primarily in the inner retina; that is, OPL, IPL, and GCL. Different time courses and signal magnitudes of hemodynamic-IOS responses were observed in blood vessels with various diameters.

This study is to demonstrate deep learning for automated artery-vein (AV) classification in optical coherence tomography angiography (OCTA). The AV-Net, a fully convolutional network (FCN) based on modified U-shaped CNN architecture, incorporates enface OCT and OCTA to differentiate arteries and veins. For the multi-modal training process, the enface OCT works as a near infrared fundus image to provide vessel intensity profiles, and the OCTA contains blood flow strength and vessel geometry features. A transfer learning process is also integrated to compensate for the limitation of available dataset size of OCTA, which is a relatively new imaging modality. By providing an average accuracy of 86.75%, the AV-Net promises a fully automated platform to foster clinical deployment of differential AV analysis in OCTA.

Background and Objectives Various physical methods, such as microneedling, laser ablation, sonophoresis, and sandpaper, have been widely studied to enhance the transdermal delivery of tissue optical clearing (TOC) agents. A previous study demonstrated that the microneedling method could effectively enhance the permeability of a TOC agent through the skin barrier. Study Design/Materials and Methods In this study, we introduce a new physical combination method which utilizes both microneedling and sonophoresis to further enhance the transdermal delivery of a TOC agent, glycerol. Porcine skin samples were divided into a control group treated only with the microneedle roller and a test group treated with both the microneedle roller and sonophoresis. Glycerol was applied topically after microneedling. The optimal concentration and transdermal delivery efficacy of glycerol were quantitatively evaluated. Results A 70% glycerol solution was determined to be the optimal concentration for the combination method. The combination method resulted in approximately a 2.3-fold higher transdermal diffusion rate of glycerol when compared to the microneedling method alone. Conclusion The combination method and optimal glycerol concentration effectively enhanced transdermal delivery of glycerol by accelerating the diffusion rate through the skin barrier.

This study is to test the feasibility of using trans-pars-planar illumination for ultrawide field pediatric fundus photography. Fundus examination of the peripheral retina is essential for clinical management of pediatric eye diseases. However, current pediatric fundus cameras with traditional trans-pupillary illumination provide a limited field of view (FOV), making it difficult to access the peripheral retina adequately for a comprehensive assessment of eye conditions. Here, we report the first demonstration of trans-pars-planar illumination in ultra-wide field pediatric fundus photography. For proof-of-concept validation, all off-the-shelf optical components were selected to construct a lab prototype pediatric camera (PedCam). By freeing the entire pupil for imaging purpose only, the trans-pars-planar illumination enables a 200 o FOV in a snapshot fundus image, allowing easy visualization of both the central and peripheral retina up to the ora serrata. A low-cost, easy-to-use ultra-wide field PedCam provides a unique opportunity to foster affordable telemedicine in rural and underserved areas.

PurposeTo conduct longitudinal optical coherence tomography angiography (OCTA) to characterize dynamic changes of trilaminar vascular plexuses in wild-type (WT) and retinal degeneration 10 (rd10) mouse retinas.MethodsLongitudinal in vivo OCT/OCTA measurements of WT and rd10 mouse retinas were conducted at postnatal day 14 (P14), P17, P21, P24, and P28. OCT images were used to quantify retinal thickness changes, while OCTA images were used to investigate vascular dynamics within the trilaminar vascular plexuses, that is, superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Blood vessel densities of all three plexus layers were quantitatively evaluated separately. The caliber of first-order blood vessel branches in the SVP layer was also measured.ResultsVascular densities in all three plexuses continuously decreased with aging in both WT and rd10. However, abnormal density reduction in rd10 occurred at P17 in both ICP (P < 0.001) and DCP (P < 0.001). While the ICP of rd10 showed density recovery at P24, the DCP of rd10 showed significantly low density. Remarkable vascular narrowing in rd10 was also observed in the SVP, especially at P28.ConclusionsThe most severe vascular impairment happened in the DCP, while the ICP showed the transient recovery of vascular density after the onset of retinal degeneration. The SVP was most resistant to the retinal degeneration, but the first-order blood vessel branches within the SVP showed progressive narrowing.Translational RelevanceBetter understanding of the vascular changes correlated with retinal development, and retinal degeneration can provide insights in advanced development of treatment protocols of retinal degenerative diseases.