High-precision, non-invasive anti-microvascular approach via concurrent ultrasound and laser irradiation

Antivascular therapy represents a proven strategy to treat angiogenesis. By applying synchronized ultrasound bursts and nanosecond laser irradiation, we developed a novel, selective, non-invasive, localized antivascular method, termed photo-mediated ultrasound therapy (PUT). PUT takes advantage of the high native optical contrast among biological tissues and can treat microvessels without causing collateral damage to the surrounding tissue. In a chicken yolk sac membrane model, under the same ultrasound parameters (1 MHz at 0.45 MPa and 10 Hz with 10% duty cycle), PUT with 4 mJ/cm2 and 6 mJ/cm2 laser fluence induced 51% (p = 0.001) and 37% (p = 0.018) vessel diameter reductions respectively. With 8 mJ/cm2 laser fluence, PUT would yield vessel disruption (90%, p < 0.01). Selectivity of PUT was demonstrated by utilizing laser wavelengths at 578 nm or 650 nm, where PUT selectively shrank veins or occluded arteries. In a rabbit ear model, PUT induced a 68.5% reduction in blood perfusion after 7 days (p < 0.001) without damaging the surrounding cells. In vitro experiments in human blood suggested that cavitation may play a role in PUT. In conclusion, PUT holds significant promise as a novel non-invasive antivascular method with the capability to precisely target blood vessels.R01AR060350R01CA1867694K12EY022299-4BL2014089

Smartphone-based, rapid, wide-field fundus photography for diagnosis of pediatric retinal diseases

PurposeAn important, unmet clinical need is for cost-effective, reliable, easy-to-use, and portable retinal photography to evaluate preventable causes of vision loss in children. This study presents the feasibility of a novel smartphone-based retinal imaging device tailored to imaging the pediatric fundus.MethodsSeveral modifications for children were made to our previous device, including a child-friendly 3D printed housing of animals, attention-grabbing targets, enhanced image stitching, and video-recording capabilities. Retinal photographs were obtained in children undergoing routine dilated eye examination. Experienced masked retina-specialist graders determined photograph quality and made diagnoses based on the images, which were compared to the treating clinician's diagnosis.ResultsDilated fundus photographs were acquired in 43 patients with a mean age of 6.7 years. The diagnoses included retinoblastoma, Coats' disease, commotio retinae, and optic nerve hypoplasia, among others. Mean time to acquire five standard photographs totaling 90-degree field of vision was 2.3 ± 1.1 minutes. Patients rated their experience of image acquisition favorably, with a Likert score of 4.6 ± 0.8 out of 5. There was 96% agreement between image-based diagnosis and the treating clinician's diagnosis.ConclusionsWe report a handheld smartphone-based device with modifications tailored for wide-field fundus photography in pediatric patients that can rapidly acquire fundus photos while being well-tolerated.Translational relevanceAdvances in handheld smartphone-based fundus photography devices decrease the technical barrier for image acquisition in children and may potentially increase access to ophthalmic care in communities with limited resources

Photo-Mediated Ultrasound Therapy for the Treatment of Corneal Neovascularization in Rabbit Eyes

Purpose: Corneal neovascularization (CNV) is the invasion of new blood vessels into the avascular cornea, leading to reduced corneal transparency and visual acuity, impaired vision, and even blindness. Current treatment options for CNV are limited. We developed a novel treatment method, termed photo-mediated ultrasound therapy (PUT), that combines laser and ultrasound, and we tested its feasibility for treating CNV in a rabbit model. Methods: A suture-induced CNV model was established in New Zealand White rabbits, which were randomly divided into two groups: PUT and control. For the PUT group, the applied light fluence at the corneal surface was estimated to be 27 mJ/cm2 at 1064-nm wavelength with a pulse duration of 5 ns, and the ultrasound pressure applied on the cornea was 0.43 MPa at 0.5 MHz. The control group received no treatment. Red-free photography and fluorescein angiography were utilized to evaluate the efficiency of PUT. Safety was evaluated by histology and immunohistochemistry. For comparison with the PUT safety results, conventional laser photocoagulation (LP) treatment was performed with standard clinical parameters: 532-nm continuous-wave (CW) laser with 0.1-second pulse duration, 450-mW power, and 75-µm spot size. Results: In the PUT group, only 1.8% ± 0.8% of the CNV remained 30 days after treatment. In contrast, 71.4% ± 7.2% of the CNV remained in the control group after 30 days. Safety evaluations showed that PUT did not cause any damage to the surrounding tissue. Conclusions: These results demonstrate that PUT is capable of removing CNV safely and effectively in this rabbit model. Translational Relevance: PUT can remove CNV safely and effectively

Photo-Mediated Ultrasound Therapy for the Treatment of Corneal Neovascularization in Rabbit Eyes

Purpose: Corneal neovascularization (CNV) is the invasion of new blood vessels into the avascular cornea, leading to reduced corneal transparency and visual acuity, impaired vision, and even blindness. Current treatment options for CNV are limited. We developed a novel treatment method, termed photo-mediated ultrasound therapy (PUT), that combines laser and ultrasound, and we tested its feasibility for treating CNV in a rabbit model. Methods: A suture-induced CNV model was established in New Zealand White rabbits, which were randomly divided into two groups: PUT and control. For the PUT group, the applied light fluence at the corneal surface was estimated to be 27 mJ/cm2 at 1064-nm wavelength with a pulse duration of 5 ns, and the ultrasound pressure applied on the cornea was 0.43 MPa at 0.5 MHz. The control group received no treatment. Red-free photography and fluorescein angiography were utilized to evaluate the efficiency of PUT. Safety was evaluated by histology and immunohistochemistry. For comparison with the PUT safety results, conventional laser photocoagulation (LP) treatment was performed with standard clinical parameters: 532-nm continuous-wave (CW) laser with 0.1-second pulse duration, 450-mW power, and 75-µm spot size. Results: In the PUT group, only 1.8% ± 0.8% of the CNV remained 30 days after treatment. In contrast, 71.4% ± 7.2% of the CNV remained in the control group after 30 days. Safety evaluations showed that PUT did not cause any damage to the surrounding tissue. Conclusions: These results demonstrate that PUT is capable of removing CNV safely and effectively in this rabbit model. Translational Relevance: PUT can remove CNV safely and effectively

A Smartphone-Based Tool for Rapid, Portable, and Automated Wide-Field Retinal Imaging.

Purpose:High-quality, wide-field retinal imaging is a valuable method for screening preventable, vision-threatening diseases of the retina. Smartphone-based retinal cameras hold promise for increasing access to retinal imaging, but variable image quality and restricted field of view can limit their utility. We developed and clinically tested a smartphone-based system that addresses these challenges with automation-assisted imaging. Methods:The system was designed to improve smartphone retinal imaging by combining automated fixation guidance, photomontage, and multicolored illumination with optimized optics, user-tested ergonomics, and touch-screen interface. System performance was evaluated from images of ophthalmic patients taken by nonophthalmic personnel. Two masked ophthalmologists evaluated images for abnormalities and disease severity. Results:The system automatically generated 100° retinal photomontages from five overlapping images in under 1 minute at full resolution (52.3 pixels per retinal degree) fully on-phone, revealing numerous retinal abnormalities. Feasibility of the system for diabetic retinopathy (DR) screening using the retinal photomontages was performed in 71 diabetics by masked graders. DR grade matched perfectly with dilated clinical examination in 55.1% of eyes and within 1 severity level for 85.2% of eyes. For referral-warranted DR, average sensitivity was 93.3% and specificity 56.8%. Conclusions:Automation-assisted imaging produced high-quality, wide-field retinal images that demonstrate the potential of smartphone-based retinal cameras to be used for retinal disease screening. Translational Relevance:Enhancement of smartphone-based retinal imaging through automation and software intelligence holds great promise for increasing the accessibility of retinal screening

Reproducibility in the absence of selective reporting: An illustration from large‐scale brain asymmetry research

The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p‐hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left–right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta‐analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an “ideal publishing environment,” that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically‐used sample sizes

Preretinal hemorrhages following chiropractor neck manipulation

Purpose: To report a case of a new complication following complementary and alternative medicine chiropractor neck manipulation with multiple preretinal hemorrhages. Observations: A 59-year-old Caucasian female presented with the acute, painless constant appearance of 3 spots in her vision immediately after a chiropractor performed cervical spinal manipulation using the high-velocity, low-amplitude technique. Examination multiple unilateral preretinal hemorrhages with no retinal tears. The preretinal hemorrhages were self-limited and resolved by 2 months later. Conclusions: Chiropractor neck manipulation has previously been reported leading to complications related to the carotid artery and arterial plaques. This presents the first case of multiple unilateral preretinal hemorrhages immediately following chiropractic neck manipulation. This suggests that chiropractor spinal adjustment can not only affect the carotid artery, but also could lead to preretinal hemorrhages. Keywords: Chiropractor, Neck manipulation, Preretinal hemorrhage, Complementary and alternative medicine, CA

Photoacoustic Ophthalmoscopy: Principle, Application, and Future Directions

Photoacoustic ophthalmoscopy (PAOM) is a novel, hybrid, non-ionizing, and non-invasive imaging technology that has been used to assess the retina. PAOM can provide both anatomic and functional retinal characterizations with high resolution, high sensitivity, high contrast, and a high depth of penetration. Thus, ocular diseases can be precisely detected and visualized at earlier stages, resulting in an improved understanding of pathophysiology, improved management, and the improved monitoring of retinal treatment to prevent vision loss. To better visualize ocular components such as retinal vessels, choroidal vessels, choroidal neovascularization, retinal neovascularization, and the retinal pigment epithelium, an advanced multimodal ocular imaging platform has been developed by a combination of PAOM with other optical imaging techniques such as optical coherence tomography (OCT), scanning laser ophthalmoscopy (SLO), and fluorescence microscopy. The multimodal images can be acquired from a single imaging system and co-registered on the same image plane, enabling an improved evaluation of disease. In this review, the potential application of photoacoustic ophthalmoscopy in both research and clinical diagnosis are discussed as a medical screening technique for the visualization of various ocular diseases. The basic principle and requirements of photoacoustic ocular imaging are introduced. Then, various photoacoustic microscopy imaging systems of the retina in animals are presented. Finally, the future development of PAOM and multimodal imaging is discussed

Advances in Retinal Optical Imaging

Retinal imaging has undergone a revolution in the past 50 years to allow for better understanding of the eye in health and disease. Significant improvements have occurred both in hardware such as lasers and optics in addition to software image analysis. Optical imaging modalities include optical coherence tomography (OCT), OCT angiography (OCTA), photoacoustic microscopy (PAM), scanning laser ophthalmoscopy (SLO), adaptive optics (AO), fundus autofluorescence (FAF), and molecular imaging (MI). These imaging modalities have enabled improved visualization of retinal pathophysiology and have had a substantial impact on basic and translational medical research. These improvements in technology have translated into early disease detection, more accurate diagnosis, and improved management of numerous chorioretinal diseases. This article summarizes recent advances and applications of retinal optical imaging techniques, discusses current clinical challenges, and predicts future directions in retinal optical imaging