Regression patterns of central serous chorioretinopathy using en face optical coherence tomography.

PURPOSE: To study the regression patterns of subretinal fluid (SRF) in central serous chorioretinopathy (CSCR) on sequential en face optical coherence tomography (OCT) and its relationship to leak locations. METHODS: Retrospective study on patients with acute CSCR. Inclusion criteria were (i) availability of data, sequential OCT and OCT angiography (B scan and en face OCT) every 2 weeks until resolution of SRF or 6 months, whichever is earlier; (ii) single active leak. Exclusion criteria were (i) presence of macular neovascularization or atypical CSCR, (ii) diffuse pigment epitheliopathy, (iii) multiple leaks. Serial en face OCT scans were evaluated and the area of SRF was measured using ImageJ software. Correlation coefficient was calculated for the regression rate of SRF area and central retinal thickness (CRT) over the first month of follow-up and the time of complete SRF resolution. RESULTS: Out of the 25 eyes, 20 eyes demonstrated a centripetal regression, and 5 eyes demonstrated a centrifugal regression. In eyes with a leakage point <1000µ from the fovea, 86% resolved in a centripetal fashion, and in eyes with leak site ≥1000µ away from fovea, 70% eyes resolved centripetally. There was a correlation (r=-0.47, p=0.018) of the rate regression of SRF area during the first month and timing of resolution. In contrast, this correlation was absent (r=-0.16, p=0.44) for CRT regression. CONCLUSION: Our en face-based analysis of sequential OCTs of regressing CSCR demonstrated a tendency for the subfoveal SRF to resolve towards the end or a centripetal pattern of regression. Prediction of resolution of SRF at 1 month is better with en face area of SRF in comparison to CRT.

Expedient access to α,ß-difunctionalized azepenes using α-halo eneformamides: application to the one-pot synthesis of 2-benzazepanes.

The regioselective synthesis of α,ß-difunctionalized (alkenyl, aryl, sulfonyl, allyl, or alkynyl) azepenes has been accomplished through α-halo eneformamides. A successful implementation of the vicinal functionalization strategy has led to a one-pot synthesis of 2-benzazepanes whose benzenoid portion is highly functionalized.

Direct access to functionalized benzotropones, azepanes, and piperidines by reductive cross-coupling of α-bromo enones with α-bromo enamides.

The synthesis of functionalized azepenes and piperidines bearing an α-cycloheptenone or benzotropone derivative has been accomplished through direct reductive cross-coupling of α-bromo eneformamides or enecarbamates with highly versatile α-bromo benzotropone derivatives, under cobalt catalysis. The coupling products have been further elaborated to other synthetically useful aza-heterocyclic frameworks.

Batch-balanced focal loss: a hybrid solution to class imbalance in deep learning.

Purpose: To validate the effectiveness of an approach called batch-balanced focal loss (BBFL) in enhancing convolutional neural network (CNN) classification performance on imbalanced datasets. Materials and Methods: BBFL combines two strategies to tackle class imbalance: (1) batch-balancing to equalize model learning of class samples and (2) focal loss to add hard-sample importance to the learning gradient. BBFL was validated on two imbalanced fundus image datasets: a binary retinal nerve fiber layer defect (RNFLD) dataset (n=7,258) and a multiclass glaucoma dataset (n=7,873). BBFL was compared to several imbalanced learning techniques, including random oversampling (ROS), cost-sensitive learning, and thresholding, based on three state-of-the-art CNNs. Accuracy, F1-score, and the area under the receiver operator characteristic curve (AUC) were used as the performance metrics for binary classification. Mean accuracy and mean F1-score were used for multiclass classification. Confusion matrices, t-distributed neighbor embedding plots, and GradCAM were used for the visual assessment of performance. Results: In binary classification of RNFLD, BBFL with InceptionV3 (93.0% accuracy, 84.7% F1, 0.971 AUC) outperformed ROS (92.6% accuracy, 83.7% F1, 0.964 AUC), cost-sensitive learning (92.5% accuracy, 83.8% F1, 0.962 AUC), and thresholding (91.9% accuracy, 83.0% F1, 0.962 AUC) and others. In multiclass classification of glaucoma, BBFL with MobileNetV2 (79.7% accuracy, 69.6% average F1 score) outperformed ROS (76.8% accuracy, 64.7% F1), cost-sensitive learning (78.3% accuracy, 67.8.8% F1), and random undersampling (76.5% accuracy, 66.5% F1). Conclusion: The BBFL-based learning method can improve the performance of a CNN model in both binary and multiclass disease classification when the data are imbalanced.

The Transcaruncular Corridor of the Medial Transorbital Approach to the Frontal Lobe: Technical Nuances and Applications.

BACKGROUND AND IMPORTANCE: Medial orbital access through a transcaruncular corridor has yet to be fully characterized as a potential approach to intradural lesions within the skull base. Transorbital approaches present unique potential in the management of complex neurological pathologies and require subspecialty collaboration across multiple disciplines. CLINICAL PRESENTATION: A 62-year-old man presented with progressive confusion and mild left-sided weakness. He was found to have a right frontal lobe mass with significant vasogenic edema. A comprehensive systemic workup was otherwise unremarkable. A multidisciplinary skull base tumor board conference recommended a medial transorbital approach through transcaruncular corridor, which was performed by neurosurgery and oculoplastics services. Postoperative imaging demonstrated gross total resection of the right frontal lobe mass. Histopathologic evaluation was consistent with amelanotic melanoma with BRAF (V600E) mutation. At his last follow-up visit, 3 months after surgery, the patient did not experience any visual symptoms and had an excellent cosmetic outcome after surgery. CONCLUSION: The transcaruncular corridor through a medial transorbital approach provides a safe and reliable access to the anterior cranial fossa.

An Optical Coherence Tomography-Based Measure as an Independent Estimate of Retinal Function in Retinitis Pigmentosa.

BACKGROUND: With the clinical advances in the field of gene therapy, the development of objective measures of visual function of patients with inherited retinal dystrophies (IRDs) is of utmost importance. Here, we propose one such measure. METHODS: We retrospectively analyzed data from a cohort of 194 eyes of 97 genetically diagnosed patients with retinitis pigmentosa (RP), the most common IRD, followed at the UPMC Vision Institute. The analyzed data included the reflectivity ratio (RR) of the retinal nerve fiber layer (RNFL) to that of the entire retina, visual acuity (VA) and the thickness of the retinal outer nuclear layer (ONL) and the RNFL. RESULTS: There was a strong positive correlation between the RR and VA. Both VA and the RR were negatively correlated with disease duration; VA, but not the RR, was negatively correlated with age. The RR correlated with the ONL but not with the RNFL thickness or the intraocular pressure. Age, RR, disease duration and ONL thickness were found to be independent predictors of VA by multivariate analysis. CONCLUSION: The OCT RR could serve as an independent predictor of visual acuity, and by extension of retinal function, in genetically diagnosed RP patients. Such objective measures can be of great value in patient selection for therapeutic trials.

Machine Learning Identification of Immunotherapy Targets in Low-Grade Glioma Using RNA Sequencing Expression Data.

OBJECTIVE: Immunotherapy has revolutionized cancer treatment in the past decade, but significant hurdles remain. Human studies with immune checkpoint inhibitors targeting programmed cell death protein have demonstrated suboptimal efficacy in the setting of low-grade gliomas (LGGs). Identification of mechanisms leading to inadequate anti-tumor immunity is paramount. The current study evaluates and validates barriers to immunotherapy using a novel machine learning algorithm. METHODS: We utilized The Cancer Genome Atlas (TCGA) to generate expression levels of 28 immune genes related to known immunotherapeutic targets or lymphocyte cytolytic activity. We created training and testing groups and 3 machine learning models to determine the genes most highly correlated to cytolytic activity (CYT). The 3 models were run through multiple regression by exhaustive selection, LASSO, and random forest. We validated computational results by comparing expression of pertinent genes in patient-derived glioma samples. RESULTS: Our models demonstrated linearity, a low mean-squared error, and consistent results with respect to the most important variables. Expression of ICOS, IDO1, and CD40 were the most important variables in all models and demonstrated positive correlation with CYT. Other variables included TIGIT and CD137. Genetic analysis from 3 IDH-mutants (IDHm) and 3 IDH-wild type (IDHwt) patient-derived glioma samples validated TCGA data and demonstrated lower levels of CYT in IDHm gliomas compared with IDHwt. CONCLUSIONS: This novel methodology has elucidated 3 potential targets for immunotherapy development in LGGs. We also demonstrated a novel method of analyzing data using advanced statistical techniques that can be further used in developing treatments for other diseases as well.

A Novel Approach to Teaching Fundoscopy Using a Virtual Format.

Introduction: Ophthalmology education has been underemphasized in medical school curricula despite the fact that patient eye-related complaints are commonplace across primary care specialties. Although previous curricula used direct ophthalmoscopy to teach medical students the fundamentals of ophthalmic examination, there has been a growing call to teach these fundamentals through reading fundus photos due to the increasing prevalence and decreased costs of fundus cameras in primary care settings. We developed a virtual workshop to teach ophthalmoscopy to medical students using fundus photography. Methods: First-year medical students were enrolled in a 2-hour, synchronous, virtual ophthalmoscopy workshop as part of an advanced physical exam curriculum at the University of Pittsburgh School of Medicine. Students participated in a pretest, introductory lecture, interactive small-group session, and posttest. Breakout groups were led by senior medical students or residents. We compared pre- and posttest results for improved understanding of concepts covered in the workshop. Results: Of 147 students, the average scores on the pretest and posttest were 39% and 75%, respectively (p < .01). Students were significantly more confident in their ability to identify various pathologies on fundus photography. After the workshop, the student preceptors indicated increased comfort in a teaching role and greater interest in medical education. The preceptors were also more confident in their own ability to interpret fundus photography and in their understanding of various ocular pathologies. Discussion: Our virtual, interactive workshop is effective in teaching medical students a systematic approach to the interpretation of fundus photographs.

Clinical Features and Multimodal Imaging in Atypical Posterior Uveitis Secondary to Bartonella Henselae Infection.

PURPOSE: To characterize an unusual presentation of infectious posterior uveitis using multimodal imaging, and discuss the clinical decision-making involved in diagnosis and treatment. METHODS: Wide-field fundus photography, swept-source optical coherence tomography (OCT), swept-source OCT angiography, fluorescein angiography, and indocyanine green angiography. RESULTS: This patient presented with cyclical fevers and blurry vision. Fundus examination revealed bilateral optic disc edema, macular intraretinal white spots and many scattered yellow-white chorioretinal lesions. Multimodal imaging characteristics suggested that many of these lesions represent choroidal granulomas. Extensive systemic workup was only notable for borderline elevated Bartonella henselae IgG titers (1:128), however convalescent IgG titers were elevated at 38 days (1:512) supporting the diagnosis of Bartonella chorioretinitis. CONCLUSION: Ocular manifestations of Bartonella henselae infection are varied and may include choroidal granulomas. Multimodal imaging characteristics may help identify etiologies of infectious uveitis. Convalescent titers are important when evaluating patients with suspected Bartonellosis, especially patients with atypical presentations.

En Face Choroidal Vascularity in Both Eyes of Patients with Unilateral Central Serous Chorioretinopathy.

The aim of this study was to evaluate the choroidal vascularity analyzing en face optical coherence tomography (OCT) images in patients with unilateral central serous chorioretinopathy (CSC). We retrospectively evaluated 40 eyes of 20 CSC patients and 20 eyes of 10 gender- and age-matched healthy individuals. The sample consisted of: (1) CSC affected eyes; (2) unaffected fellow eyes; (3) healthy eyes. Multiple cross-sectional enhanced depth imaging OCT scans were obtained to create a volume scan. En face scans of the whole choroid were obtained at 5µm intervals and were binarized to calculate the choroidal vascularity index (CVI). The latter, defined as the proportion of the luminal area to the total choroidal area, was calculated at the level of choriocapillaris, superficial, medium and deep layers. No significant differences between choriocapillaris, superficial, medium and deep CVI were found in both eyes of CSC patients, whereas a significant different trend of changes was found in healthy eyes. Nevertheless, the en face CVI shows no difference between affected fellow and healthy eyes. In conclusion, CSC-affected eyes and fellow eyes showed a similar vascular architecture, with no statistical difference between all choroidal layers.

Choroidal Vascularity Map in Unilateral Central Serous Chorioretinopathy: A Comparison with Fellow and Healthy Eyes.

BACKGROUND: To map the choroidal vascularity index and compare two eyes in patients with unilateral central serous chorioretinopathy (CSCR). METHODS: This was a retrospective, observational study performed in patients with unilateral CSCR. Choroidal thickness (CT) and Choroidal vascularity index (CVI) were measured and mapped in various zones according to the early treatment diabetic retinopathy (ETDRS) grid. RESULTS: A total of 20 CSCR patients (20 study and 20 fellow eyes) were included in the study. Outer nasal region CT was seen to be significantly lower than central CT (p = 0.042) and inner nasal CT (p = 0.007); outer ring CT was significantly less than central (p = 0.04) and inner ring (p = 0.01) CT in CSCR eyes. On potting all the CVI values against the corresponding CT values, a positive correlation was seen in CSCR eyes (r = 0.54, p < 0.01), which was slightly weaker in fellow eyes (r = 0.3, p < 0.01) and a negative correlation was seen in healthy eyes (r = -0.262, p < 0.01). CONCLUSIONS: Correlation between CVI and CT was altered in CSCR eyes as compared to fellow and normal eyes with increasing CVI towards the center of the macula and superiorly in CSCR eyes.

Correlation of sectoral choroidal vascularity with angiographic leakage in central serous chorioretinopathy.

PURPOSE: To correlate sectoral choroidal vascularity with angiographic leakage in eyes with central serous chorioretinopathy (CSCR). METHODS: This was a retrospective, cross-sectional study including patients with active CSCR. Multimodal imaging including fundus fluorescein angiography (FFA) and optical coherence tomography (OCT) were performed to identify leakage site and obtain choroidal measurements, respectively. An automated algorithm was used to perform shadow compensation, choroidal boundary localization and binarization, three (3-D) dimensional mapping, and early treatment of diabetic retinopathy study (ETDRS) grid based choroidal quantification that is, choroidal thickness (CT) and choroidal vascularity index (CVI). Nested analysis of variance (ANOVA) was performed to compare CT and CVI in different sectors. RESULTS: Thirty-two eyes with active CSCR were analyzed. CT values varied significantly among the sectors (range, 450.27-482.63 µm; p = 0.005) and rings (range, 459.71-480.45 µm; p < 0.001), however, CVI failed to show significant variation among various segments (sectors, rings, and quadrants; range, 0.53-0.54; all p values > 0.05). Among 25 leaking spots in 25 different sectors, 12 (48%) had an increased CT compared to the overall CT whereas only 24% had increased CVI compared to overall CVI. Mean CT and CVI of the sectors with leakage (427.1 ± 81.1 µm; 0.51 ± 0.05) and remaining sectors without leakage (411.3 ± 73.9 µm; 0.53 ± 0.04) were not statistically different (p = 0.48; p = 0.12, respectively). CONCLUSION: Though CT varied in different segments and increased CT corresponded to leakage points on FFA in 48% of eyes, CVI changes were more diffusely spread and local changes in CVI were not predictive of leakage location in eyes with active CSCR.