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We report an AEC-Q101-qualified 750V, 15 mΩ planar SiC MOSFETs with a long short circuit withstand time (SCWT) of > 9μs at VDS=400V and VGS=15V and a low specific on-resistance (RON,SP) of 2.1 mΩ.cm2 at VGS=15V designed for xEV traction inverter applications. The RDS(on) at VGS=15V increases from 15mΩ at 25 °C to 21 mΩ at 175 °C. A low turn-on (EON) and turn-off (EOFF) switching energy loss of 95.5μJ and 67μJ at IDS=75A, VDS=400V was measured at 25 °C. The gate oxide lifetime at worst case operating fields of 5MV/cm is >> 20 years.

This report presented the longitudinal optical coherence tomography angiography (OCTA) findings in a patient with malignant hypertension choroidopathy. An 87-year-old woman presented with acute unilateral central vision loss in the setting of hypertensive emergency. Spectral domain optical coherence tomography showed massive serous macular detachment. OCTA revealed extensive flow loss in the neuroretina and choriocapillaris. With blood pressure (BP) normalization and without any ocular intervention, visual acuity recovered on subsequent visits. Flow loss in the neuroretinal capillaries persisted, but significant improvement in the perfusion of the choriocapillaris was observed. This case demonstrates extensive choriocapillaris flow loss in the acute phase of malignant hypertension, and a temporal relationship between BP normalization, improvement of choriocapillaris perfusion, and decrease of subretinal fluid, providing additional insight into the pathophysiology of this life- and sight-threatening systemic condition.

Choroidal macrovessel (CM) is a rare anomalous vascular lesion in the choroid. In this case report, we describe a 72-year-old Caucasian man diagnosed with an incidental heavily branching CM in the macula of his right eye based on multimodal imaging, including enhanced depth imaging optical coherence tomography (OCT), swept-source OCT angiography, and indocyanine green angiography. Multimodal imaging is valuable in demonstrating the distinctive appearance of this entity and differentiating it from more vision-threatening differential diagnoses, such as ophthalmomyiasis interna, choroidal neoplasms, retinochoroidal anastomosis, and inflammatory conditions.

To determine global current practice patterns for the management of open globe injuries and identify areas of variation.Cross-sectional survey.An online survey assessed global management paradigms for open globe injuries from August 2020 to January 2021. Responses were collected from experts at eye trauma centers and emergency departments worldwide who manage ≥1 open globe injury per month. The survey assessed the use/selection of antibiotics and steroids, procedural and imaging decisions, and admission practices for open globe injuries.Responses were received from representatives of 36 of 42 institutions (85.7%), of which 33 (78.6%) had sufficient trauma volume to be included. Included responses were distributed across North America (n=12, 36.4%), Asia (n=12, 36.4%), South America (n=4, 12.1%), Africa (n=3, 9.1%), Europe (n=1, 3.0%), and Australia (n=1, 3.0%). Preoperative systemic antibiotics for open globe injuries were administered by 75.8% (n = 25/33) of institutions, while 30.3% (n = 10/33) administered preoperative topical antibiotics. Intraoperative ophthalmic antibiotics for open globe injuries were used by 54.5% (n = 18/33) of experts. Most institutions also administered postoperative systemic antibiotics (n = 23 [69.7%]) and topical steroids (n = 29 [87.9%]), although specific medication choices diverged. At 19 responding centers (61.3% of the 31 that had trainees), residents participated in surgical repairs. Many institutions discharged patients after repair, but 54.5% (n = 18/33) of locations routinely admitted them for observation.Preferred management practices for open globe injuries vary widely. To ensure the highest standard of care for all patients, evidence-based international guidelines for the treatment of these injuries are needed.

Background To investigate the relationship between intraretinal hyperreflective foci (HRF) and visual function in intermediate age-related macular degeneration (iAMD). Methods Retrospective, cross-sectional study. iAMD patients underwent spectral domain optical coherence tomography (SD-OCT) imaging and vision function testing: normal luminance best corrected visual acuity (VA), low luminance VA (LLVA), quantitative contrast sensitivity function (qCSF), low luminance qCSF (LLqCSF), and mesopic microperimetry. Each OCT volume was graded for the presence and number of HRF. Each HRF was graded for: separation from the retinal pigment epithelium (RPE), above drusen, and shadowing. Central drusen volume was calculated by the built-in functionality of the commercial OCT software after manual segmentation of the RPE and Bruch’s membrane. Results HRF group: 11 eyes; 9 patients; mean age 75.7 years. No-HRF group: 11 eyes; 10 patients; mean age 74.8 years. In linear mixed effect model adjusting for cube-root transformed drusen volume, HRF group showed statistically significant worse VA, LLVA, LLqCSF, and microperimetry. HRF group showed worse cone function, as measured by our pre-defined multicomponent endpoint, incorporating LLVA, LLqCSF and microperimetry (p = 0.018). For eyes with HRF, # of HRF did not correlate with any functional measures; however, % of HRF separated from RPE and # of HRF that created shadowing were statistically associated with low luminance deficit (LLD). Conclusions The association between the presence of HRF and worse cone visual function supports the hypothesis that eyes with HRF have more advanced disease.

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Supplementary Table 2 from HIF Induces Human Embryonic Stem Cell Markers in Cancer Cells

Supplementary Table 5 from HIF Induces Human Embryonic Stem Cell Markers in Cancer Cells

Supplementary Methods, Figures 1-11, Table Legends 1-7 from HIF Induces Human Embryonic Stem Cell Markers in Cancer Cells

Supplementary Table 3 from HIF Induces Human Embryonic Stem Cell Markers in Cancer Cells

Supplementary Table 1 from HIF Induces Human Embryonic Stem Cell Markers in Cancer Cells

Supplementary Table 7 from HIF Induces Human Embryonic Stem Cell Markers in Cancer Cells

Supplementary Table 6 from HIF Induces Human Embryonic Stem Cell Markers in Cancer Cells

Sarah C Miller,1 Prajna Meeralakshmi,2 Michael J Fliotsos,3 Grant A Justin,4 Yoshihiro Yonekawa,5 Ariel Chen,1 Annette K Hoskin,6,7 Richard J Blanch,8– 10 Kara M Cavuoto,11 Rebecca Low,12 Ximin Li,1,13 Matthew Gardiner,14 TY Alvin Liu,1 Ankoor S Shah,14 James D Auran,15 Rupesh Agrawal,12,16– 18 Fasika A Woreta1 On behalf of The International Globe and Adnexal Trauma Epidemiology Study (IGATES)1Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Aravind Eye Hospital, Madurai, India; 3Department of Ophthalmology, Yale New Haven Hospital, New Haven, CT, USA; 4Vitreoretinal Surgery Service, Duke Eye Center, Durham, NC, USA; 5Wills Eye Hospital, Mid Atlantic Retina, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA; 6Save Sight Institute, University of Sydney, Sydney, Australia; 7Lions Eye Institute, University of Western Australia, Perth, Australia; 8Academic Department of Military Surgery and Trauma, Royal Centre for Defence Medicine, Birmingham, England; 9University Hospitals Birmingham, NHS Foundation Trust, Birmingham, England; 10Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, England; 11Bascom Palmer Eye Institute, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA; 12Department of Ophthalmology, Tan Tock Seng Hospital, Singapore, Singapore; 13Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; 14Massachusetts Eye and Ear Infirmary, Boston, MA, USA; 15Columbia University Irving Medical Center, New York City, NY, USA; 16Singapore Eye Research Institute, Singapore; 17Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; 18Duke NUS Medical School, SingaporeCorrespondence: Fasika A Woreta, The Wilmer Eye Institute, Johns Hopkins School of Medicine, 600 North Wolfe Street, Baltimore, MD, 21205, USA, Tel +410-961-2868, Fax +410-614-9632, Email fworeta1@jhmi.edu Rupesh Agrawal, Department of Ophthalmology, Tan Tock Seng Hospital, Singapore Eye Research Institute, Lee Kong Chian School of Medicine, Nanyang Technological University, Duke NUS Medical School, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore, Tel +6563571000, Email Rupesh_agrawal@ttsh.com.sgPurpose: Hyphema is a sequela of ocular trauma and can be associated with significant morbidity. Management of this condition is variable and can depend on individual institutional guidelines. We aimed to summarize current practices in hyphema management across ophthalmological institutions worldwide.Methods: A cross-sectional online survey was conducted across North America, Asia, South America, Africa, Europe, and Australia from August 2020 to January 2021. The survey assessed the existing practices in the management of hyphema at each institution.Results: For layered hyphema, topical steroids were routinely administered by 34 (of 36 respondents, 94.4%) institutions, of which prednisolone was the preferred choice (n = 32, 88.9%). Topical cycloplegics were used at 34 (94.4%) institutions. No institution reported routine use of antifibrinolytics. Head elevation was the most deployed procedure to promote hyphema reabsorption (n = 31, 86.3%), followed by partial bed rest (n = 21, 58.3%). The majority of institutions (n = 25, 69.4%) did not routinely pursue admission for hyphema patients, although 75.0% of institutions (n = 27) scheduled follow-up visits within 48 hours of presentation. Additionally, few institutions performed routine sickle cell trait testing for patients presenting with hyphema (n = 6, 16.7%). The decision to perform anterior chamber washout varied and was often based on intraocular pressure and the speed of hyphema resolution.Conclusion: Unanimity of international institutions on hyphema management is lacking. As it stands, many current interventions have unconvincing evidence supporting their use. Evidence-based guidelines would be beneficial in guiding decision-making on hyphema management. Additionally, areas of consensus can be used as foundations for future standard of care investigations.Keywords: current practices, hyphema, trauma, sickle cell, anterior segment

Choriocapillaris insufficiency may play a role in centripetal retinitis pigmentosa (RP) progression involving the fovea. However, the relationship between choriocapillaris integrity and foveal damage in RP is unclear. We examined the relationship between choriocapillaris flow and the presence of foveal photoreceptor involvement in RP. We categorized the severity of central involvement in RP by the occurrence of foveal ellipsoid zone (EZ) disruption: present (severe RP) or absent (mild RP). Using optical coherence tomography angiography (OCTA, AngioVue, Optovue) in cases and unaffected age-matched controls, we compared vessel density (VD) between the groups using the generalized linear mixed model, controlling for age, gender, and scan quality. Fifty-seven eyes (20 severe RP, 18 mild RP, and 19 controls) were included. Foveal and parafoveal mean outer retinal thickness (µm) were lower in severe RP (fovea: 101.3 ± 14.5; parafovea: 68.4 ± 11.7) than controls (fovea: 161.2 ± 8.9; parafovea: 142.1 ± 11.8; p ≤ 0.001) and mild RP (fovea: 162.0 ± 14.7; parafovea: 116.8 ± 29.4; p ≤ 0.0001). Foveal choriocapillaris VD (%) was lower in severe RP (56.7 ± 6.8) than controls (69.9 ± 4.6; p = 0.008) and mild RP (65.3 ± 5.3; p = 0.01). The parafoveal choriocapillaris VD was lower in severe RP than controls (64.4 ± 5.9 vs. 68.3 ± 4.1; p = 0.04) but no different than in mild RP (p = 0.4). Choriocapillaris flow loss was associated with fovea-involving photoreceptor damage in RP. Further research is warranted to validate this putative association and clarify causation. Choriocapillaris imaging using OCTA may provide information to supplement structural OCT findings when evaluating subjects with RP in neuroprotective or regenerative clinical trials.

Purpose: This work evaluated the use and type of dietary supplements and home monitoring for nonneovascular age-related macular degeneration (AMD), as well as the prevalence of genetic testing among patients with AMD. Methods: A cross-sectional study was conducted of 129 participants older than 50 years who completed self-administered questionnaires regarding usage and type of dietary supplements and home monitoring, as well as the participants’ use of genetic testing for AMD. Results: Of 91 participants with AMD, 83 (91.2%) took vitamins, including 55 (60.4%) who used an Age-Related Eye Disease Study (AREDS) or AREDS2 formulation. Of 38 without AMD, 31 (81.6%) took vitamins (difference from participants with AMD = 9.6% [95% CI, 0%-23.2%]), including 2 on an AREDS formulation. Among 82 participants with AMD who were AREDS candidates (intermediate or advanced AMD in 1 or both eyes), 51 (62.2%; 95% CI, 51.7%-72.7%) took an AREDS or AREDS2 formulation, and 31 (37.8%) did not (5 were unsure). Additionally, 50 (61.0%; 95% CI, 50.4%-71.6%) AREDS candidates did some type of home monitoring. Only 1 (1.2%; 95% CI, 0%-3.6%) underwent genetic testing for AMD. Among 9 with AMD who were not AREDS candidates, 4 (44.4%) used an AREDS formulation, 4 (44.4%) did not, and 1 (11.1%) was unsure; only 1 (11.1%) of these 9 performed home monitoring. Conclusions: Despite similar results from past surveys and AREDS2 data supporting supplement use in 2013 and home monitoring in 2014, these findings suggest about one-third of AREDS candidates do not do so, providing further support for improving education regarding appropriate supplement and home monitoring usage. Genetic testing for AMD also appears infrequent.

Medical specialties with access to a large amount of imaging data, such as ophthalmology, have been at the forefront of the artificial intelligence (AI) revolution in medicine, driven by deep learning (DL) and big data. With the rise of AI and big data, there has also been increasing concern on the issues of bias and privacy, which can be partially addressed by low-shot learning, generative DL, federated learning and a “model-to-data” approach, as demonstrated by various groups of investigators in ophthalmology. However, to adequately tackle the ethical and societal challenges associated with the rise of AI in ophthalmology, a more comprehensive approach is preferable. Specifically, AI should be viewed as sociotechnical, meaning this technology shapes, and is shaped by social phenomena.

Purpose. The goal of this work is to create an active shape model segmentation method based on the statistical shape model of five regions of the globe on computed tomography (CT) scans and to use the method to categorize normal globe from globe injury. Methods. A set of 78 normal globes imaged with CT scans were manually segmented (vitreous cavity, lens, sclera, anterior chamber, and cornea) by two graders. A statistical shape model was created from the regions. An active shape model was trained using the manual segmentations and the statistical shape model and was assessed using leave-one-out cross validations. The active shape model was then applied to a set of globes with open globe injures, and the segmentations were compared to those of normal globes, in terms of the standard deviations away from normal. Results. The active shape model (ASM) segmentation compared well to ground truth, based on Dice similarity coefficient score in a leave-one-out experiment: 90.2% ± 2.1% for the cornea, 92.5% ± 3.5% for the sclera, 87.4% ± 3.7% for the vitreous cavity, 83.5% ± 2.3% for the anterior chamber, and 91.2% ± 2.4% for the lens. A preliminary set of CT scans of patients with open globe injury were segmented using the ASM and the shape of each region was quantified. The sclera and vitreous cavity were statistically different in shape from the normal. The Zone 1 and Zone 2 globes were statistically different than normal from the cornea and anterior chamber. Both results are consistent with the definition of the zonal injuries in OGI. Conclusion. The ASM results were found to be reproducible and accurately correlated with manual segmentations. The quantitative metrics derived from ASM of globes with OGI are consistent with existing medical knowledge in terms of structural deformation.

Purpose of review To review four recent controversial topics arising from deep learning applications in ophthalmology. Recent findings The controversies of four recent topics surrounding deep learning applications in ophthalmology are discussed, including the following: lack of explainability, limited generalizability, potential biases and protection of patient confidentiality in large-scale data transfer. Summary These controversial issues spanning the domains of clinical medicine, public health, computer science, ethics and legal issues, are complex and likely will benefit from an interdisciplinary approach if artificial intelligence in ophthalmology is to succeed over the next decade.

Attempts to replicate in cultivation the natural lithophytic growth habit of many Mexican Pinguicula seem to have taken off in popularity in recent years. Herein I describe my own experience with this technique and the approaches that I have found to be successful in the long-term.

Background Deep learning (DL) has demonstrated human expert levels of performance for medical image classification in a wide array of medical fields, including ophthalmology. In this article, we present the results of our DL system designed to determine optic disc laterality, right eye vs left eye, in the presence of both normal and abnormal optic discs. Methods Using transfer learning, we modified the ResNet-152 deep convolutional neural network (DCNN), pretrained on ImageNet, to determine the optic disc laterality. After a 5-fold cross-validation, we generated receiver operating characteristic curves and corresponding area under the curve (AUC) values to evaluate performance. The data set consisted of 576 color fundus photographs (51% right and 49% left). Both 30° photographs centered on the optic disc (63%) and photographs with varying degree of optic disc centration and/or wider field of view (37%) were included. Both normal (27%) and abnormal (73%) optic discs were included. Various neuro-ophthalmological diseases were represented, such as, but not limited to, atrophy, anterior ischemic optic neuropathy, hypoplasia, and papilledema. Results Using 5-fold cross-validation (70% training; 10% validation; 20% testing), our DCNN for classifying right vs left optic disc achieved an average AUC of 0.999 (±0.002) with optimal threshold values, yielding an average accuracy of 98.78% (±1.52%), sensitivity of 98.60% (±1.72%), and specificity of 98.97% (±1.38%). When tested against a separate data set for external validation, our 5-fold cross-validation model achieved the following average performance: AUC 0.996 (±0.005), accuracy 97.2% (±2.0%), sensitivity 96.4% (±4.3%), and specificity 98.0% (±2.2%). Conclusions Small data sets can be used to develop high-performing DL systems for semantic labeling of neuro-ophthalmology images, specifically in distinguishing between right and left optic discs, even in the presence of neuro-ophthalmological pathologies. Although this may seem like an elementary task, this study demonstrates the power of transfer learning and provides an example of a DCNN that can help curate large medical image databases for machine-learning purposes and facilitate ophthalmologist workflow by automatically labeling images according to laterality.

To demonstrate that deep learning (DL) methods can produce robust prediction of gene expression profile (GEP) in uveal melanoma (UM) based on digital cytopathology images.Evaluation of a diagnostic test or technology.Deidentified smeared cytology slides stained with hematoxylin and eosin obtained from a fine needle aspirated from UM.Digital whole-slide images were generated by fine-needle aspiration biopsies of UM tumors that underwent GEP testing. A multistage DL system was developed with automatic region-of-interest (ROI) extraction from digital cytopathology images, an attention-based neural network, ROI feature aggregation, and slide-level data augmentation.The ability of our DL system in predicting GEP on a slide (patient) level. Data were partitioned at the patient level (73% training; 27% testing).In total, our study included 89 whole-slide images from 82 patients and 121 388 unique ROIs. The testing set included 24 slides from 24 patients (12 class 1 tumors; 12 class 2 tumors; 1 slide per patient). Our DL system for GEP prediction achieved an area under the receiver operating characteristic curve of 0.944, an accuracy of 91.7%, a sensitivity of 91.7%, and a specificity of 91.7% on a slide-level analysis. The incorporation of slide-level feature aggregation and data augmentation produced a more predictive DL model (Our current work established a complete pipeline for GEP prediction in UM tumors: from automatic ROI extraction from digital cytopathology whole-slide images to slide-level predictions. Our DL system demonstrated robust performance and, if validated prospectively, could serve as an image-based alternative to GEP testing.

The first ever insurance reimbursement for an artificial intelligence (AI) system, which expedites triage of acute stroke, occurred in 2020 when the Centers for Medicare and Medicaid Services (CMS) granted approval for a New Technology Add-on Payment (NTAP). Key aspects of the AI system that led to its approval by the CMS included its unique mechanism of action, use of robotic process automation, and clear linkage of the system’s output to clinical outcomes. The specific strategies employed encompass a first-case scenario of proving reimbursable value for improved stroke outcomes using AI. Given the rapid change in utilization of AI technology in stroke care, we describe the economic drivers of stroke AI systems in healthcare, focusing on concepts of reimbursement for value added by AI to the stroke care system. This report reviews (1) the successful approach used by the first NTAP-approved AI system, (2) economic variables in insurance reimbursement for AI, and (3) resultant strategies that may be utilized to facilitate qualification for NTAP reimbursement, which may be adopted by other AI systems used in stroke care.