Response of Diabetic Macular Edema to Anti-VEGF Medications Correlates with Improvement in Macular Vessel Architecture Measured with OCT Angiography.

Purpose: Improvements in best-corrected visual acuity (BCVA) and central subfield thickness (CST) have been well documented after intravitreal injection of anti-VEGF medications in diabetic macular edema (DME); however, their effect on the vasculature of the macula in diabetic retinopathy (DR) remains poorly understood. Our aim was to explore the effect of intravitreal injection of anti-VEGF on parameters of retinal vascular microstructure in DR with OCT angiography (OCTA). Design: Retrospective study of adult patients with DME that were treated with anti-VEGF intravitreal injections at the University of Illinois at Chicago between 2017 and 2022. Participants: Forty-one eyes from 30 patients with nonproliferative or proliferative DR with a mean age of 58.83 ± 11.71 years, mean number of intravitreal injections of 2.8 ± 1.4, and mean follow-up of 6.5 ± 1.7 months. Methods: ImageJ was employed to measure parameters of retinal vascular microstructure in OCTA images, which included perfusion density, vessel-length density (VLD), vessel diameter, and foveal avascular zone (FAZ) characteristics (area, perimeter, and circularity). Student t tests and analysis of variance were used to determine statistical significance. Main Outcome Measures: A primary analysis was performed comparing the mean of each parameter of all patients as a single group at the beginning and end of the study period. A subgroup analysis was then performed after stratifying patients based on visual improvement, change in CST, prior injection history, and number of injections. Results: Eyes demonstrated statistical improvement in BCVA logarithm of the minimum angle of resolution score and CST after anti-VEGF treatment. Primary analysis showed a reduction in the vessel diameter of the superficial and deep retinal vasculature, as well as an increase in the circularity of the FAZ within the superficial retinal vasculature after anti-VEGF treatment. Subgroup analysis revealed that eyes with improvement in BCVA exhibited reduced vessel diameter in the superficial retinal vasculature and that eyes with the largest decrease in CST displayed increased perfusion density and VLD in the deep retinal vasculature. Conclusions: Intravitreal injection of anti-VEGF agents to treat DME improved parameters of retinal vascular microstructure on OCTA over a period of 3 to 9 months, and this effect was most pronounced in eyes that experienced improvement in BCVA and CST. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Validating the Generalizability of Ophthalmic Artificial Intelligence Models on Real-World Clinical Data.

Purpose: This study aims to investigate generalizability of deep learning (DL) models trained on commonly used public fundus images to an instance of real-world data (RWD) for glaucoma diagnosis. Methods: We used Illinois Eye and Ear Infirmary fundus data set as an instance of RWD in addition to six publicly available fundus data sets. We compared the performance of DL-trained models on public data and RWD for glaucoma classification and optic disc (OD) segmentation tasks. For each task, we created models trained on each data set, respectively, and each model was tested on both data sets. We further examined each model's decision-making process and learned embeddings for the glaucoma classification task. Results: Using public data for the test set, public-trained models outperformed RWD-trained models in OD segmentation and glaucoma classification with a mean intersection over union of 96.3% and mean area under the receiver operating characteristic curve of 95.0%, respectively. Using the RWD test set, the performance of public models decreased by 8.0% and 18.4% to 85.6% and 76.6% for OD segmentation and glaucoma classification tasks, respectively. RWD models outperformed public models on RWD test sets by 2.0% and 9.5%, respectively, in OD segmentation and glaucoma classification tasks. Conclusions: DL models trained on commonly used public data have limited ability to generalize to RWD for classifying glaucoma. They perform similarly to RWD models for OD segmentation. Translational Relevance: RWD is a potential solution for improving generalizability of DL models and enabling clinical translations in the care of prevalent blinding ophthalmic conditions, such as glaucoma.

Intravitreal anti-vascular endothelial growth factor for the treatment of chronic central serous retinopathy: a meta-analysis of the literature.

OBJECTIVE: The purpose of this study was to evaluate the role of anti-vascular endothelial growth factor (anti-VEGF) treatment on the functional and structural parameters of chronic central serous retinopathy (CSR). METHODS: PubMed was used to systematically review literature published from 1 January 2009 to 1 July 2022. Studies were included if patients in their cohort had symptoms for more than 3 months, anti-VEGF treatment was provided and the following outcomes were reported: best-corrected visual acuity (BCVA), central macular thickness (CMT) and proportion of subretinal fluid (SRF) resolution. RESULTS: 339 eyes met inclusion criteria with a mean patient age of 45.8±4.9 years. The weighted mean baseline BCVA for the 20 studies was 0.39±0.23 logMAR, which improved to 0.28±0.24 after treatment with anti-VEGF injections (p=0.069). The weighted baseline CMT for the 20 studies decreased from 395.2±52.0 µm to 243.0±41.9 µm (p<0.001). The weighted overall percentage of SRF resolution was 68.4%. CONCLUSION: Anti-VEGF treatment demonstrated significantly decreased macular thickness and resolution of SRF in the treatment of chronic CSR without any reported adverse effects. However, BCVA did not significantly improve with pharmacotherapy.

An Association Between Large Optic Cupping and Total and Regional Brain Volume: The Women's Health Initiative.

PURPOSE: To investigate the relationships between optic nerve cupping and total and regional brain volumes. DESIGN: Secondary analysis of randomized clinical trial data. METHODS: Women 65 to 79 years of age without glaucoma with cup-to-disc ratio (CDR) measurements from the Women's Health Initiative (WHI) Sight Examination study and magnetic resonance imaging (MRI)-based total and regional brain volumes from the WHI Memory Study MRI-1 were included. Large CDR was defined as 0.6 or greater in either eye. Generalized estimating equation models were used to account for intra-brain correlations between the right and left sides. The final analysis was adjusted for demographic and clinical characteristics and for total brain volume (for regional analyses). RESULTS: Final analyses included 471 women, with the mean age ± SD was 69.2 ± 3.6 years; 92.8% of the subjects were white. Of 471 women, 34 (7.2%) had large CDR. Controlling for total brain volume and for demographic and clinical characteristics, lateral ventricle volume was 3.01 cc larger for subjects with large CDR compared to those without large CDR (95% CI = 0.02 to 5.99; P = .048). Furthermore, frontal lobe volume was 4.78 cc lower for subjects with large CDR compared to those without (95% CI = -8.71, -0.84; P = 0.02), and occipital lobe volume was 1.86 cc lower for those with large CDR compared to those without (95% CI = -3.39, -0.3; P =.02). CONCLUSIONS: Our analysis suggests that in women aged 65 years or more, large CDR is associated with lower relative total brain volume and absolute regional volume in the frontal and occipital lobes. Enlarged CDR in individuals without glaucoma may represent a sign of optic nerve and brain aging, although more longitudinal data are needed.

Automated Region of Interest Selection Improves Deep Learning-Based Segmentation of Hyper-Reflective Foci in Optical Coherence Tomography Images.

Hyperreflective foci (HRF) have been associated with retinal disease progression and demonstrated as a negative prognostic biomarker for visual function. Automated segmentation of HRF in retinal optical coherence tomography (OCT) scans can be beneficial to identify the formation and movement of the HRF biomarker as a retinal disease progresses and can serve as the first step in understanding the nature and severity of the disease. In this paper, we propose a fully automated deep neural network based HRF segmentation model in OCT images. We enhance the model's performance by using a patch-based strategy that increases the model's compute on the HRF pixels. The patch-based strategy is evaluated against state of the art HRF segmentation pipelines on clinical retinal image data. Our results shows that the patch-based approach demonstrates a high precision score and intersection over union (IOU) using a ResNet34 segmentation model with Binary Cross Entropy loss function. The HRF segmentation pipeline can be used for analyzing HRF biomarkers for different retinopathies.

Association between cognitive function and large optic nerve cupping, accounting for cup-disc-ratio genetic risk score.

PURPOSE: To investigate if accounting for a cup-to-disc ratio (CDR) genetic risk score (GRS) modified the association between large CDR and cognitive function among women. DESIGN: This was a retrospective study using data from the Women's Health Initiative. METHODS: Patients with glaucoma or ocular hypertension were excluded. Large CDR was defined as ≥ 0.6 in either eye. Cognitive function was measured by the Modified Mini-Mental State Examination (3MSE). We used the combined effects from 13 single nucleotide polymorphisms (SNPs) to formulate the GRS for CDR. We used logistic regression to investigate associations between weighted GRS and large CDR, then a linear regression to assess the association between weighted GRS and 3MSE scores, and between weighted GRS, CDR, and 3MSE scores, adjusted for demographic and clinical characteristics. RESULTS: Final analyses included 1,196 White women with mean age of 69.60 ± 3.62 years and 7.27% with large CDR. Mean GRS in women with and without large CDR was 1.51 ± 0.31 vs. 1.41 ± 0.36, respectively (p = 0.004). The odds of large CDR for a one unit increase in GRS was 2.30 (95% CI: (1.22, 4.36), p = 0.011). Adding the CDR GRS in the model with CDR and 3MSE, women with large CDR still had statistically significantly lower 3MSE scores than those without large CDR, yielding a predicted mean difference in 3MSE scores of 0.84 (p = 0.007). CONCLUSIONS: Independent of the CDR GRS, women with large CDR had a lower cognitive function.

Outcomes and Patterns of Care in Elderly Patients with Glioblastoma Multiforme.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults, with an increased incidence among the elderly. However, the optimal treatment strategy in elderly patients remains unclear. This study seeks to investigate the effect of patient selection and treatment strategies on survival trends in these patients. METHODS: Patients with diagnosis codes specific for GBM were queried from the National Cancer Database during 2004-2016. Univariate and multivariate Cox regression analysis was performed to investigate outcomes. Survival curves and 5-year survival were also generated based on patient-specific factors. RESULTS: Among 104,456 patients with GBM identified, elderly patients were less likely to receive radiotherapy (61.3% vs. 77.8%; P < 0.001) or chemotherapy (47.2% vs. 62.9%; P < 0.001) or to undergo surgical resection (68.3% vs. 81.8; P < 0.001). Mean overall survival was 9.1 months (standard deviation, 10.0) and 5-year survival was 5.3%. Multivariate analysis showed age 75-84 years (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.12-1.73; P = 0.003) and lower Karnofsky Performance Status (50-70: HR, 1.68, 95% CI, 1.35-2.08, P < 0.001; ≤40: HR, 1.79, 95% CI 1.18-2.72, P = 0.006) were associated with decreased overall survival, whereas surgical resection (subtotal resection: HR, 0.52, 95% CI, 0.38-0.71, P < 0.001; gross total resection: HR, 0.29, 95% CI, 0.21-0.41, P < 0.001), radiotherapy (HR, 0.65; 95% CI, 0.47-0.91; P = 0.012), and chemotherapy (HR, 0.65; 95% CI, 0.48-0.88; P = 0.006) were associated with increased overall survival in elderly patients. CONCLUSIONS: In an analysis of 104,456 patients with GBM, all treatment modalities were found to be used less frequently in elderly patients. Increasing age and poor performance status were associated with worsened survival. Gross total resection was associated with the greatest survival benefit, and chemotherapy and radiotherapy also improved survival outcomes. These treatment options improved outcomes regardless of performance status. Although maximal treatment strategies may improve survival in elderly patients with GBM, these treatment strategies must be balanced against patient-specific factors and quality-of-life concerns.

Comprehensive validation of halcyon 2.0 plans and the implementation of patient specific QA with multiple detector platforms.

PURPOSE: To perform a comprehensive validation of plans generated on a preconfigured Halcyon 2.0 with preloaded beam model, including evaluations of new features and implementing the patient specific quality assurance (PSQA) process with multiple detectors. METHODS: A total of 56 plans were generated in Eclipse V15.6 (Varian Medical System) with a preconfigured Halcyon treatment machine. Ten plans were developed via the AAPM TG-119 test suite with both IMRT and VMAT techniques. 34 clinically treated plans using C-arm LINAC from 24 patients were replanned on Halcyon using IMRT or VMAT techniques for a variety of sites including: brain, head and neck, lung, breast, abdomen, and pelvis. Six of those plans were breast VMAT plans utilizing the extended treatment field technique available with Halcyon 2.0. The dynamically flattened beam (DFB), another new feature on Halcyon 2.0, was also used for an AP/PA spine and four field box pelvis, as well as ten 3D breast plans. All 56 plans were measured with an ion chamber (IC), film, portal dosimetry (PD), ArcCHECK, and Delta4. Tolerance and action limits were calculated and compared to the recommendations of TG-218. RESULTS: TG-119 IC and film confidence limits met those set by the task group, except for IMRT target point dose. Forty-four of 46 clinical plans were within 3% for IC measurements. Average gamma passing rates with 3% dose difference and 2mm distance-to-agreement for IMRT/VMAT plans were: Film - 96.8%, PD - 99.9%, ArcCHECK - 99.1%, and Delta4 - 99.2%. Calculated action limits were: Film - 86.3%, PD - 98.4%, ArcCHECK - 96.1%, and Delta4 - 95.7%. Extended treatment field technique was fully validated and 3D plans with DFB had similar results to IMRT/VMAT plans. CONCLUSION: Halcyon plan deliveries were verified with multiple measurement devices. New features of Halcyon 2.0 were also validated. Traditional PSQA techniques and process specific tolerance and action limits were successfully implemented.

Magnetic Resonance Imaging-Guided Focused Ultrasound-Based Delivery of Radiolabeled Copper Nanoclusters to Diffuse Intrinsic Pontine Glioma.

Diffuse intrinsic pontine glioma (DIPG) is an invasive pediatric brainstem malignancy exclusively in children without effective treatment due to the often-intact blood-brain tumor barrier (BBTB), an impediment to the delivery of therapeutics. Herein, we used focused ultrasound (FUS) to transiently open BBTB and delivered radiolabeled nanoclusters (64Cu-CuNCs) to tumors for positron emission tomography (PET) imaging and quantification in a mouse DIPG model. First, we optimized FUS acoustic pressure to open the blood-brain barrier (BBB) for effective delivery of 64Cu-CuNCs to pons in wildtype mice. Then the optimized FUS pressure was used to deliver radiolabeled agents in DIPG mouse. Magnetic resonance imaging (MRI)-guided FUS-induced BBTB opening was demonstrated using a low molecular weight, short-lived 68Ga-DOTA-ECL1i radiotracer and PET/CT before and after treatment. We then compared the delivery efficiency of 64Cu-CuNCs to DIPG tumor with and without FUS treatment and demonstrated the FUS-enhanced delivery and time-dependent diffusion of 64Cu-CuNCs within the tumor.

Extensive Cerebrovascular and Visceral Artery Dissection and Pseudoaneurysm with Underlying Segmental Arterial Mediolysis.

Segmental arterial mediolysis (SAM) is a nonatherosclerotic, nonhereditary vasculopathy that most commonly involves abdominal aortic branches and predominantly affects middle-age and elderly populations. Lysis of the outer arterial media results in separation of the media from the adventitia leading to dissecting aneurysms and/or pseudoaneurysms. We report a unique case of a 47-year-old man who presented with bilateral internal carotid artery dissection followed by dissections and aneurysms involving multiple visceral arteries. This case highlights the dramatic manifestation of SAM and discusses the complexity of decision-making related to this disease including differential diagnoses and management.