Trends in functional outcome measures in orthopedic oncology.

The purpose of this study was to identify trends in the use of functional outcome measures within orthopedic oncology. The search engine, PubMed, was reviewed for all articles over an 11-year period from 2011 to 2021 from five major journals that publish in the field of orthopedic oncology. The functional outcome measures used in the articles were recorded along with study date, study design, clinical topic/pathology, and level of evidence. Out of 5968 musculoskeletal tumor-focused articles reviewed, 293 (4.9%) included at least one outcome measure. A total of 28 different outcome tools were identified. The most popular were Musculoskeletal Tumor Society (MSTS) score (61.1%) and Toronto Extremity Salvage (TESS) score (14.0%), followed by 36-Item Short Form Survey (SF-36) (4.1%) and Patient-Reported Outcomes Measurement Information System (PROMIS) (3.8%). The use of MSTS scores decreased by 0.7% each year, whereas PROMIS increased by 1.2% each year. Seventy-four articles used more than one outcome measure. Of these 74 articles, 61 had the MSTS as one of the outcome measures. Orthopedic oncology utilizes functional outcome measures less commonly in comparison to other orthopedic subspecialties. However, this may be due in large part to orthopedic oncologists putting more emphasis on outcomes such as local recurrence, implant failure, and mortality. MSTS score is the most widely used functional outcome measure, but the utilization of PROMIS has increased recently, and could be the next step in evaluating outcomes in orthopedic oncology as it is patient-derived rather than physician-derived.

KIBRA repairs synaptic plasticity and promotes resilience to tauopathy-related memory loss.

Synaptic plasticity is obstructed by pathogenic tau in the brain, representing a key mechanism that underlies memory loss in Alzheimer's disease (AD) and related tauopathies. Here, we found that reduced levels of the memory-associated protein KIdney/BRAin (KIBRA) in the brain and increased KIBRA protein levels in cerebrospinal fluid are associated with cognitive impairment and pathological tau levels in disease. We next defined a mechanism for plasticity repair in vulnerable neurons using the C-terminus of the KIBRA protein (CT-KIBRA). We showed that CT-KIBRA restored plasticity and memory in transgenic mice expressing pathogenic human tau; however, CT-KIBRA did not alter tau levels or prevent tau-induced synapse loss. Instead, we found that CT-KIBRA stabilized the protein kinase Mζ (PKMζ) to maintain synaptic plasticity and memory despite tau-mediated pathogenesis. Thus, our results distinguished KIBRA both as a biomarker of synapse dysfunction and as the foundation for a synapse repair mechanism to reverse cognitive impairment in tauopathy.

Global incidence of adverse clinical events in non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is associated with a multitude of adverse outcomes. We aimed to estimate the pooled incidence of NAFLD-related adverse events. METHODS: We performed a systematic review and meta-analysis of cohort studies of adults with NAFLD to evaluate the pooled incidence of adverse events. RESULTS: 19,406 articles were screened, 409 full-text articles reviewed, and 79 eligible studies (1,377,466 persons) were included. Mean age was 51.47 years and body mass index 28.90 kg/m2. Baseline comorbidities included metabolic syndrome (41.73%), cardiovascular disease (CVD) (16.83%), cirrhosis (21.97%), and nonalcoholic steatohepatitis (NASH) (58.85%). Incidence rate per 1,000 person-years for mortality included: all-cause (14.6), CVD-related (4.53), non-liver cancer-related (4.53), and liver-related (3.10). Incidence for liver-related events included overall (24.3), fibrosis progression (49.0), cirrhosis (10.9), liver transplant (12.0), and hepatocellular carcinoma (HCC) (3.39). Incidence for non-liver events included metabolic syndrome (25.4), hypertension (25.8), dyslipidemia (26.4), diabetes (19.0), CVD (24.77), renal impairment (30.3), depression/anxiety (29.1), and non-liver cancer (10.5). Biopsy-proven NASH had higher incidence of HCC (P=0.043) compared to non-NASH. Higher rates of CVD and mortality were observed in North America and Europe, hypertension and non-liver cancer in North America, and HCC in Western Pacific/Southeast Asia (P<0.05). No significant differences were observed by sex. Time-period analyses showed decreasing rates of cardiovascular and non-liver cancer mortality and increasing rates of decompensated cirrhosis (P<0.05). CONCLUSION: People with NAFLD have high incidence of liver and non-liver adverse clinical events, varying by NASH, geographic region, and time-period, but not sex.

Small Cell Cervical Carcinoma in Pregnancy: Therapeutic Options for an Aggressive Cancer Diagnosis.

Neuroendocrine small cell cervical carcinoma is an aggressive cancer which accounts for approximately 1 to 3% of all cervical neoplasms. Therapy must be altered in pregnancy to optimize maternal-fetal outcomes. A 39-year-old woman presented for a routine prenatal visit and was noted to have a grossly abnormal cervix. Cervical biopsies confirmed small cell carcinoma. At 19 weeks' gestation, chemotherapy was initiated. The patient delivered at 34 weeks' gestation to initiate radiation therapy. Six months later, she was diagnosed with metastatic disease and died from cancer complications. In pregnancy, treatment modalities for small cell cervical carcinoma are based on the patient's gestational age at diagnosis. While aggressive early treatment is preferred, platinum-based chemotherapy can be initiated in the second trimester and radiation therapy delayed until delivery. Small cell cervical carcinoma complicating pregnancy requires aggressive treatment. Chemotherapy in the second trimester with planned delayed radiation therapy, may optimize fetal outcomes.

Evaluating spatial dependency of the spectral efficiency in trans-palpebral illumination for widefield fundus photography.

Multi-spectral widefield fundus photography is valuable for the clinical diagnosis and management of ocular conditions that may impact both central and peripheral regions of the retina and choroid. Trans-palpebral illumination has been demonstrated as an alternative to transpupillary illumination for widefield fundus photography without requiring pupil dilation. However, spectral efficiency can be complicated due to the spatial variance of the light property through the palpebra and sclera. This study aims to investigate the effect of light delivery location on spectral efficiency in trans-palpebral illumination. Four narrow-band light sources, covering both visible and near infrared (NIR) wavelengths, were used to evaluate spatial dependency of spectral illumination efficiency. Comparative analysis indicated a significant dependence of visible light efficiency on spatial location, while NIR light efficiency is only slightly affected by the illumination location. This study confirmed the pars plana as the optimal location for delivering visible light to achieve color imaging of the retina. Conversely, spatial location is not critical for NIR light imaging of the choroid.

Color Fusion Effect on Deep Learning Classification of Uveal Melanoma.

Background: Reliable differentiation of uveal melanoma and choroidal nevi is crucial to guide appropriate treatment, preventing unnecessary procedures for benign lesions and ensuring timely treatment for potentially malignant cases. The purpose of this study is to validate deep learning classification of uveal melanoma and choroidal nevi, and to evaluate the effect of color fusion options on the classification performance. Methods: A total of 798 ultra-widefield retinal images of 438 patients were included in this retrospective study, comprising 157 patients diagnosed with UM and 281 patients diagnosed with choroidal nevus. Color fusion options, including early fusion, intermediate fusion and late fusion, were tested for deep learning image classification with a convolutional neural network (CNN). Specificity, sensitivity, F1-score, accuracy, and the area under the curve (AUC) of a receiver operating characteristic (ROC) were used to evaluate the classification performance. The saliency map visualization technique was used to understand the areas in the image that had the most influence on classification decisions of the CNN. Results: Color fusion options were observed to affect the deep learning performance significantly. For single-color learning, the red color image was observed to have superior performance compared to green and blue channels. For multi-color learning, the intermediate fusion is better than early and late fusion options. Conclusion: Deep learning is a promising approach for automated classification of uveal melanoma and choroidal nevi, and color fusion options can significantly affect the classification performance.

Analyzing an immunization resource website: User browsing trends.

PURPOSE: Access to internet-based resources may help to improve population health awareness and literacy surrounding immunization related topics. The primary aim of this study was to evaluate and analyze trends for a single immunization resource website, the Melbourne Vaccine Education Centre (MVEC). PRINCIPAL RESULTS: Over a four-year period from 2019 to 2022, the website had over 2 million visitors from 236 countries. Users were predominantly female, in the 25 to 44 year age bracket and accessed resources using a mobile device. There was significant interest in specific vaccine related topics, particularly during the COVID-19 pandemic, that corresponded with key vaccine related recommendations and updates from a national level. Usage patterns saw spikes in interest around topics including COVID-19 vaccine administration techniques and adverse events following immunization. MAJOR CONCLUSIONS: Use of online platforms including websites such as MVEC may reflect trends and behaviors towards immunization related information. Analysis of usage patterns have provided user insights into key domains of interest including areas such as vaccine administration, policies and programs, vaccine safety and barriers to vaccine uptake.

Optimizing the OCTA layer fusion option for deep learning classification of diabetic retinopathy.

The purpose of this study is to evaluate layer fusion options for deep learning classification of optical coherence tomography (OCT) angiography (OCTA) images. A convolutional neural network (CNN) end-to-end classifier was utilized to classify OCTA images from healthy control subjects and diabetic patients with no retinopathy (NoDR) and non-proliferative diabetic retinopathy (NPDR). For each eye, three en-face OCTA images were acquired from the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC) layers. The performances of the CNN classifier with individual layer inputs and multi-layer fusion architectures, including early-fusion, intermediate-fusion, and late-fusion, were quantitatively compared. For individual layer inputs, the superficial OCTA was observed to have the best performance, with 87.25% accuracy, 78.26% sensitivity, and 90.10% specificity, to differentiate control, NoDR, and NPDR. For multi-layer fusion options, the best option is the intermediate-fusion architecture, which achieved 92.65% accuracy, 87.01% sensitivity, and 94.37% specificity. To interpret the deep learning performance, the Gradient-weighted Class Activation Mapping (Grad-CAM) was utilized to identify spatial characteristics for OCTA classification. Comparative analysis indicates that the layer data fusion options can affect the performance of deep learning classification, and the intermediate-fusion approach is optimal for OCTA classification of DR.

Recurrent Metastatic Colorectal Adenocarcinoma to the Thyroid Gland Presenting With Vocal Cord Paralysis and Inspiratory Stridor.

The most common sites for metastases of colorectal cancer include the liver, lungs, brain, and regional lymph nodes. However, a limited number of reported cases describe colon cancer metastasis to the thyroid gland. Metastatic colorectal adenocarcinoma to the thyroid gland is rare. The majority of these cases with colon cancer metastases to the thyroid gland are diagnosed years after initial treatment of colon cancer. The discovery is usually made after routine surveillance imaging, and often patients have minimal or absent symptoms. We report a case of a recurrence of metastatic colorectal adenocarcinoma to the thyroid gland presenting with vocal cord paralysis and inspiratory stridor.

KIBRA repairs synaptic plasticity and promotes resilience to tauopathy-related memory loss.

Synaptic plasticity is obstructed by pathogenic tau in the brain, representing a key mechanism that underlies memory loss in Alzheimer's disease (AD) and related tauopathies. Here, we define a mechanism for plasticity repair in vulnerable neurons using the C-terminus of the KIdney/BRAin (KIBRA) protein (CT-KIBRA). We show that CT-KIBRA restores plasticity and memory in transgenic mice expressing pathogenic human tau; however, CT-KIBRA did not alter tau levels or prevent tau-induced synapse loss. Instead, we find that CT-KIBRA binds to and stabilizes protein kinase Mζ (PKMζ) to maintain synaptic plasticity and memory despite tau-mediated pathogenesis. In humans we find that reduced KIBRA in brain and increased KIBRA in cerebrospinal fluid are associated with cognitive impairment and pathological tau levels in disease. Thus, our results distinguish KIBRA both as a novel biomarker of synapse dysfunction in AD and as the foundation for a synapse repair mechanism to reverse cognitive impairment in tauopathy.

Metastatic Seeding of Abdominal Wall After Drainage of Perforated Colorectal Cancer in a Presumed Complicated Diverticular Disease.

A 37-year-old male presented multiple times for abdominal pain with a persistent diverticular abscess on imaging that was managed previously with antibiotics and percutaneous drainages. Due to unrelenting abdominal pain and multiple presentations of unresolved acute complicated diverticulitis, the patient underwent an exploratory laparotomy. A colonic mass was discovered, and the patient had a colonic resection. Pathology revealed invasive transverse colonic adenocarcinoma with perforation and involvement of the stomach. Imaging showed no distant metastatic disease and chemotherapy was started. Months after treatment, the patient developed skin lesions and a palpable mass at the previous drain site. Biopsy showed metastatic adenocarcinoma consistent with colonic origin. Colonic adenocarcinoma with metastasis to the abdominal wall after drainage of presumed diverticular abscess is rare. Clinicians should consider malignancy when a patient has a recurrent diverticular abscess that has failed medical management and multiple drainages. Clinicians should remain vigilant of the risk of seeding colonic adenocarcinoma to the abdominal wall when repeated drainage is performed.

Spontaneous urinary bladder regeneration after subtotal cystectomy increases YAP/WWTR1 signaling and downstream BDNF expression: Implications for smooth muscle injury responses.

Rodents have the capacity for spontaneous bladder regeneration and bladder smooth muscle cell (BSMC) migration following a subtotal cystectomy (STC). YAP/WWTR1 and BDNF (Brain-derived neurotrophic factor) play crucial roles in development and regeneration. During partial bladder outlet obstruction (PBO), excessive YAP/WWTR1 signaling and BDNF expression increases BSMC hypertrophy and dysfunction. YAP/WWTR1 and expression of BDNF and CYR61 were examined in models of regeneration and wound repair. Live cell microscopy was utilized in an ex vivo model of STC to visualize cell movement and division. In Sprague-Dawley female rats, STC was performed by resection of the bladder dome sparing the trigone, followed by closure of the bladder. Smooth muscle migration and downstream effects on signaling and expression were also examined after scratch wound of BSMC with inhibitors of YAP and BDNF signaling. Sham, PBO and incision (cystotomy) were comparators for the STC model. Scratch wound in vitro increased SMC migration and expression of BDNF, CTGF and CYR61 in a YAP/WWTR1-dependent manner. Inhibition of YAP/WWTR1 and BDNF signaling reduced scratch-induced migration. BDNF and CYR61 expression was elevated during STC and PBO. STC induces discrete genes associated with endogenous de novo cell regeneration downstream of YAP/WWTR1 activation.

Deep learning for artery-vein classification in optical coherence tomography angiography.

Major retinopathies can differentially impact the arteries and veins. Traditional fundus photography provides limited resolution for visualizing retinal vascular details. Optical coherence tomography (OCT) can provide improved resolution for retinal imaging. However, it cannot discern capillary-level structures due to the limited image contrast. As a functional extension of OCT modality, optical coherence tomography angiography (OCTA) is a non-invasive, label-free method for enhanced contrast visualization of retinal vasculatures at the capillary level. Recently differential artery-vein (AV) analysis in OCTA has been demonstrated to improve the sensitivity for staging of retinopathies. Therefore, AV classification is an essential step for disease detection and diagnosis. However, current methods for AV classification in OCTA have employed multiple imagers, that is, fundus photography and OCT, and complex algorithms, thereby making it difficult for clinical deployment. On the contrary, deep learning (DL) algorithms may be able to reduce computational complexity and automate AV classification. In this article, we summarize traditional AV classification methods, recent DL methods for AV classification in OCTA, and discuss methods for interpretability in DL models.

Characterization of the gut microbiome in an osteosarcoma mouse model.

Compelling evidence has mounted surrounding the relationship between the gut microbiome and many intestinal and extraintestinal cancers. Few studies exist investigating the relationship between the gut microbiome and sarcoma. We hypothesize that the presence of distant osteosarcoma induces change to the profile of flora within the mouse. Twelve mice were used for this experiment: six were sedated and received an injection of human osteosarcoma cells into the flank, while six served as controls. Baseline stool and weight were collected. Tumor size and mouse weight were recorded weekly, and stool samples were collected and stored. Fecal microbiomes of the mice were profiled by 16S rRNA gene sequencing and analyzed for alpha diversity, relative abundances of microbial taxa, and abundance of specific bacteria at different time points. Alpha diversity was increased in the osteosarcoma group compared with the control group. The family Lachnospiraceae had the second strongest negative net average change in relative abundance over time in the osteosarcoma group whereas it had a positive net average change in the control group. An increased Firmicutes/Bacteroidota (F/B) ratio was observed in the osteosarcoma group relative to the control mice. These differences suggest that there may be an interplay between the gut microbiome and osteosarcoma. Clinical significance: Due to the paucity of literature available, our work can support novel research on this relationship and the development of new, personalized treatments for osteosarcoma.

Medical Literature Writing With ChatGPT: A Rare Case of Choriocarcinoma Syndrome With Hemorrhagic Brain Metastases Due to Burned Out Metastatic Mixed Testicular Cancer.

Testicular tumors are one of the most commonly observed malignancies among men. An aggressive and rare subtype of the disease, testicular choriocarcinoma, has a worse prognosis due to the tendency of early hematogenous spread to multiple organs and advanced symptoms at presentation time. Characteristic features of choriocarcinoma include elevated beta human chorionic gonadotropin (ß-hCG) in a young male with testicular mass. However, when the primary testicular tumor overutilizes its blood supply and spontaneously regresses, it is presumed to have been "burnt out" with remnants evident by metastatic retroperitoneal lymphadenopathy, scarred tissue, and calcifications. Treatment of advanced testicular cancer may be complicated by a rare entity known as choriocarcinoma syndrome, distinguished by rapid and fatal hemorrhaging of metastatic tumor sites. Prior described cases of choriocarcinoma syndrome involve pulmonary and gastrointestinal hemorrhages. We present an uncommon case of a 34-year-old male with a "burnt out" metastatic mixed testicular cancer who presented with choriocarcinoma syndrome (CS) treated with chemotherapy but developed deadly hemorrhaging of brain metastases. In addition, with the assistance of ChatGPT, we report our experience with this OpenAI tool and its potential uses in medical literature writing.

An open-source deep learning network AVA-Net for arterial-venous area segmentation in optical coherence tomography angiography.

BACKGROUND: Differential artery-vein (AV) analysis in optical coherence tomography angiography (OCTA) holds promise for the early detection of eye diseases. However, currently available methods for AV analysis are limited for binary processing of retinal vasculature in OCTA, without quantitative information of vascular perfusion intensity. This study is to develop and validate a method for quantitative AV analysis of vascular perfusion intensity. METHOD: A deep learning network AVA-Net has been developed for automated AV area (AVA) segmentation in OCTA. Seven new OCTA features, including arterial area (AA), venous area (VA), AVA ratio (AVAR), total perfusion intensity density (T-PID), arterial PID (A-PID), venous PID (V-PID), and arterial-venous PID ratio (AV-PIDR), were extracted and tested for early detection of diabetic retinopathy (DR). Each of these seven features was evaluated for quantitative evaluation of OCTA images from healthy controls, diabetic patients without DR (NoDR), and mild DR. RESULTS: It was observed that the area features, i.e., AA, VA and AVAR, can reveal significant differences between the control and mild DR. Vascular perfusion parameters, including T-PID and A-PID, can differentiate mild DR from control group. AV-PIDR can disclose significant differences among all three groups, i.e., control, NoDR, and mild DR. According to Bonferroni correction, the combination of A-PID and AV-PIDR can reveal significant differences in all three groups. CONCLUSIONS: AVA-Net, which is available on GitHub for open access, enables quantitative AV analysis of AV area and vascular perfusion intensity. Comparative analysis revealed AV-PIDR as the most sensitive feature for OCTA detection of early DR. Ensemble AV feature analysis, e.g., the combination of A-PID and AV-PIDR, can further improve the performance for early DR assessment.

Some people with diabetes develop diabetic retinopathy, in which the blood flow through the eye changes, resulting in damage to the back of the eye, called the retina. Changes in blood flow can be measured by imaging the eye using a method called optical coherence tomography angiography (OCTA). The authors developed a computer program named AVA-Net that determines changes in blood flow through the eye from OCTA images. The program was tested on images from people with healthy eyes, people with diabetes but no eye disease, and people with mild diabetic retinopathy. Their program found differences between these groups and so could be used to improve diagnosis of people with diabetic retinopathy.

An open-source framework for synthetic post-dive Doppler ultrasound audio generation.

Doppler ultrasound (DU) measurements are used to detect and evaluate venous gas emboli (VGE) formed after decompression. Automated methodologies for assessing VGE presence using signal processing have been developed on varying real-world datasets of limited size and without ground truth values preventing objective evaluation. We develop and report a method to generate synthetic post-dive data using DU signals collected in both precordium and subclavian vein with varying degrees of bubbling matching field-standard grading metrics. This method is adaptable, modifiable, and reproducible, allowing for researchers to tune the produced dataset for their desired purpose. We provide the baseline Doppler recordings and code required to generate synthetic data for researchers to reproduce our work and improve upon it. We also provide a set of pre-made synthetic post-dive DU data spanning six scenarios representing the Spencer and Kisman-Masurel (KM) grading scales as well as precordial and subclavian DU recordings. By providing a method for synthetic post-dive DU data generation, we aim to improve and accelerate the development of signal processing techniques for VGE analysis in Doppler ultrasound.

Global incidence of non-alcoholic fatty liver disease: A systematic review and meta-analysis of 63 studies and 1,201,807 persons.

BACKGROUND & AIMS: The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing. We aimed to estimate the pooled global NAFLD incidence. METHODS: We performed a systematic review and meta-analysis of cohort studies of adults without NAFLD at baseline to evaluate the global incidence of ultrasound-diagnosed NAFLD. RESULTS: A total of 63 eligible studies (1,201,807 persons) were analyzed. Studies were from Mainland China/Hong Kong (n = 26), South Korea (n = 22), Japan (n = 14), other (n = 2, Sri Lanka, Israel); 63.8% were clinical center studies; median study year 2000 to 2016; 87% were good quality. Among the 1,201,807 persons at risk, 242,568 persons developed NAFLD, with an incidence rate of 4,612.8 (95% CI 3,931.5-5,294.2) per 100,000 person-years and no statistically significant differences by study sample size (p = 0.90) or study setting (p = 0.055). Males had higher incidence vs. females (5,943.8 vs. 3,671.7, p = 0.0013). Both the obese (vs. non-obese) and the overweight/obese groups (vs. normal weight) were about threefold more likely to develop NAFLD (8,669.6 vs. 2,963.9 and 8,416.6 vs. 3,358.2, respectively) (both p <0.0001). Smokers had higher incidence than non-smokers (8,043.2 vs. 4,689.7, p = 0.046). By meta-regression, adjusting for study year, study setting, and study location, study period of 2010 or after and study setting were associated with increased incidence (p = 0.010 and p = 0.055, respectively). By country, China had a higher NAFLD incidence compared to non-China regions (p = 0.012) and Japan a lower incidence compared to non-Japan regions (p = 0.005). CONCLUSIONS: NAFLD incidence is increasing with a current estimate of 4,613 new cases per 100,000 person-years. Males and overweight/obese individuals had significantly higher incidence rates compared to females and those of normal weight. Public health interventions for prevention of NAFLD are needed with a special emphasis on males, overweight/obese individuals, and higher risk regions. IMPACT AND IMPLICATIONS: Non-alcoholic fatty liver disease (NAFLD) affects approximately 30% of people worldwide and appears to be increasing, but data to estimate the incidence rate are limited. In this meta-analytic study of over 1.2 million people, we estimated an incidence rate of NAFLD of 46.13 per 1,000 person-years with significant differences by sex, BMI, geography, and time-period. As treatment options for NAFLD remain limited, prevention of NAFLD should remain the focus of public health strategies. Studies such as these can help policy makers in determining which and whether their interventions are impactful.

Normalized Blood Flow Index in Optical Coherence Tomography Angiography Provides a Sensitive Biomarker of Early Diabetic Retinopathy.

Purpose: To evaluate the sensitivity of normalized blood flow index (NBFI) for detecting early diabetic retinopathy (DR). Methods: Optical coherence tomography angiography (OCTA) images of healthy controls, diabetic patients without DR (NoDR), and patients with mild nonproliferative DR (NPDR) were analyzed in this study. The OCTA images were centered on the fovea and covered a 6 mm × 6 mm area. Enface projections of the superficial vascular plexus (SVP) and the deep capillary plexus (DCP) were obtained for the quantitative OCTA feature analysis. Three quantitative OCTA features were examined: blood vessel density (BVD), blood flow flux (BFF), and NBFI. Each feature was calculated from both the SVP and DCP and their sensitivities to distinguish the three cohorts of the study were evaluated. Results: The only quantitative feature capable of distinguishing all three cohorts was NBFI in the DCP image. Comparative study revealed that both BVD and BFF were able to distinguish the controls and NoDR from mild NPDR. However, neither BVD nor BFF was sensitive enough to separate NoDR from the healthy controls. Conclusions: The NBFI has been demonstrated as a sensitive biomarker of early DR, revealing retinal blood flow abnormality better than traditional BVD and BFF. The NBFI in the DCP was verified as the most sensitive biomarker, supporting that diabetes affects the DCP earlier than SVP in DR. Translational Relevance: NBFI provides a robust biomarker for quantitative analysis of DR-caused blood flow abnormalities, promising early detection and objective classification of DR.

Portable widefield fundus camera with high dynamic range imaging capability.

Fundus photography is indispensable for the clinical detection and management of eye diseases. Low image contrast and small field of view (FOV) are common limitations of conventional fundus photography, making it difficult to detect subtle abnormalities at the early stages of eye diseases. Further improvements in image contrast and FOV coverage are important for early disease detection and reliable treatment assessment. We report here a portable, wide FOV fundus camera with high dynamic range (HDR) imaging capability. Miniaturized indirect ophthalmoscopy illumination was employed to achieve the portable design for nonmydriatic, widefield fundus photography. Orthogonal polarization control was used to eliminate illumination reflectance artifacts. With independent power controls, three fundus images were sequentially acquired and fused to achieve HDR function for local image contrast enhancement. A 101° eye-angle (67° visual-angle) snapshot FOV was achieved for nonmydriatic fundus photography. The effective FOV was readily expanded up to 190° eye-angle (134° visual-angle) with the aid of a fixation target without the need for pharmacologic pupillary dilation. The effectiveness of HDR imaging was validated with both normal healthy and pathologic eyes, compared to a conventional fundus camera.