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Purpose: Patients with Crohn's disease (CD) and subsequent ocular manifestations may have worse outcomes when compared to matched patients with CD without ocular disease. Methods: In this retrospective cohort study, an aggregated electronic health records research network, TriNetX (Cambridge, MA, USA), was used to identify patients diagnosed with CD stratified by the presence or absence of ocular involvement with at least 1 year of follow-up. Propensity score matching (PSM) was performed to control for baseline demographics and medical comorbidities. Results: Patients with CD with ocular disease showed a greater risk of undergoing bowel resections (RR: 2.06, 95% CI: 1.48–2.85, p < 0.001), developing other CD-related gastrointestinal complications (RR: 1.31, CI: 1.15–1.49, p < 0.001), or acquiring Clostridioides difficile infections (RR: 2.19, CI: 1.89–2.54, p < 0.001). Further, patients with CD with ocular sequelae had a greater risk of developing NASH (RR: 1.43, CI: 1.31–1.56, p < 0.001), CD-related nutrient deficiencies (RR: 1.38, CI: 1.29–1.49, p < 0.001), iron deficiency anemia (RR: 1.41, CI: 1.33–1.50, p < 0.001), CD-related dermatological disease (RR: 1.84, CI: 1.65–2.05, p < 0.001), osteoporosis (RR: 1.49, CI: 1.37–1.64, p < 0.001) and primary sclerosing cholangitis (RR: 1.63, CI: 1.11–2.38, p = 0.011). Among patients with CD with ocular involvement, there was an elevated risk of MI (RR: 1.36, CI: 1.14–1.63, p < 0.001), stroke (RR: 1.42, CI: 1.18–1.70, p < 0.001), VTE (RR: 1.37, CI: 1.22–1.54, p < 0.001), and sepsis (RR: 1.53, CI: 1.37–1.71, p < 0.001). Conclusions: Patients who have CD and subsequent ocular involvement have an increased risk of local intestinal complications, extraintestinal morbidity, and cardiovascular complications when compared to patients with CD without ocular involvement. [ABSTRACT FROM AUTHOR]

Purpose: We examine the rate of and reasons for follow-up in an Artificial Intelligence (AI)-based workflow for diabetic retinopathy (DR) screening relative to two human-based workflows.Patients and Methods: A DR screening program initiated September 2019 between one institution and its affiliated primary care and endocrinology clinics screened 2243 adult patients with type 1 or 2 diabetes without a diagnosis of DR in the previous year in the San Francisco Bay Area. For patients who screened positive for more-than-mild-DR (MTMDR), rates of follow-up were calculated under a store-and-forward human-based DR workflow ("Human Workflow"), an AI-based workflow involving IDx-DR ("AI Workflow"), and a two-step hybrid workflow ("AI–Human Hybrid Workflow"). The AI Workflow provided results within 48 hours, whereas the other workflows took up to 7 days. Patients were surveyed by phone about follow-up decisions.Results: Under the AI Workflow, 279 patients screened positive for MTMDR. Of these, 69.2% followed up with an ophthalmologist within 90 days. Altogether 70.5% (N=48) of patients who followed up chose their location based on primary care referral. Among the subset of patients that were seen in person at the university eye institute under the Human Workflow and AI–Human Hybrid Workflow, 12.0% (N=14/117) and 11.7% (N=12/103) of patients with a referrable screening result followed up compared to 35.5% of patients under the AI Workflow (N=99/279; χ2df=2 = 36.70, p < 0.00000001).Conclusion: Ophthalmology follow-up after a positive DR screening result is approximately three-fold higher under the AI Workflow than either the Human Workflow or AI–Human Hybrid Workflow. Improved follow-up behavior may be due to the decreased time to screening result. [ABSTRACT FROM AUTHOR]

Background: Eye plaque brachytherapy is currently an optimal therapy for intraocular cancers. Due to the lack of an effective and practical technique to measure the seed radioactivity distribution, current quality assurance (QA) practice according to the American Association of Physicists in Medicine TG129 only stipulates that the plaque assembly be visually inspected. Consequently, uniform seed activity is routinely adopted to avoid possible loading mistakes of differential seed loading. However, modulated dose delivery, which represents a general trend in radiotherapy to provide more personalized treatment for a given tumor and patient, requires differential activities in the loaded seeds. Purpose: In this study, a fast and low‐cost radio‐luminescent imaging and dose calculating system to verify the seed activity distribution for differential loading was developed. Methods: A proof‐of‐concept system consisting of a thin scintillator sheet coupled to a camera/lens system was constructed. A seed‐loaded plaque can be placed directly on the scintillator surface with the radioactive seeds facing the scintillator. The camera system collects the radioluminescent signal generated by the scintillator on its opposite side. The predicted dose distribution in the scintillator's sensitive layer was calculated using a Monte Carlo simulation with the planned plaque loading pattern of I‐125 seeds. Quantitative comparisons of the distribution of relative measured signal intensity and that of the relative predicted dose in the sensitive layer were performed by gamma analysis, similar to intensity‐modulated radiation therapy QA. Results: Data analyses showed high gamma (3%/0.3 mm, global, 20% threshold) passing rates for correct seed loadings and low passing rates with distinguished high gamma value area for incorrect loadings, indicating that possible errors may be detected. The measurement and analysis only required a few extra minutes, significantly shorter than the time to assay the extra verification seeds the physicist already must perform as recommended by TG129. Conclusions: Radio‐luminescent QA can be used to facilitate and assure the implementation of intensity‐modulated, customized plaque loading. [ABSTRACT FROM AUTHOR]

Purpose--To identify temporal and geographic trends in private equity (PE)--backed acquisitions of ophthalmology and optometry practices in the United States from 2012 to 2021. Methods--In this cross-sectional time series, acquisition data from 10/21/2019 to 9/1/2021 and previously published data from 1/1/2012 to 10/20/2019 were analyzed. Acquisition data were compiled from 6 financial databases, 5 industry news outlets, and publicly available press releases. Linear regression models were used to compare rates of acquisition. Outcomes included number of total acquisitions, practice type, locations, provider details, and geographic footprint. Results--A total of 245 practices associated with 614 clinical locations and 948 ophthalmologists or optometrists were acquired by 30 PE-backed platform companies between 10/21/2019 and 9/1/2021. Of 30 platform companies, 18 were new vis-à-vis our prior study. Of these acquisitions, 127 were comprehensive practices, 29 were retina practices, and 89 were optometry practices. From 2012 to 2021, monthly acquisitions increased by 0.947 acquisitions per year (P < 0.001*). Texas, Florida, Michigan, and New Jersey were the states with the greatest number of PE acquisitions, with 55, 48, 29, and 28 clinic acquisitions, respectively. Average monthly PE acquisitions were 5.71 per month from 1/1/2019 to 2/29/2020 (pre-COVID), 5.30 per month from 3/1/2020 to 12/31/2020 (COVID pre-vaccine [P = 0.81]), and 8.78 per month from 1/1/2021 to 9/1/2021 (COVID post-vaccine [P = 0.20]). Conclusions--PE acquisitions increased during the period 2012-2021 as companies continue to utilize regionally focused strategies for acquisitions. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has had a profound effect on the delivery of healthcare in the United States and globally. The aim of this study was to evaluate the impact of COVID-19 on common ophthalmic procedure utilization and normalization to pre-pandemic daily rates. Leveraging a national database, Clinformatics™ DataMart (OptumInsight, Eden Prairie, MN), procedure frequencies and daily averages, defined by Current Procedural Terminology codes, of common elective and non-elective procedures within multiple ophthalmology sub-specialties were calculated. Interrupted time-series analysis with a Poisson regression model and smooth spline functions was used to model trends in pre-COVID-19 (January 1, 2018–February 29, 2020) and COVID-19 (March 1, 2020–June 30, 2020) periods. Of 3,583,231 procedures in the study period, 339,607 occurred during the early COVID-19 time period. Anti-vascular endothelial growth factor injections (44,412 to 39,774, RR 1.01, CI 0.99–1.02; p =.212), retinal detachment repairs (1,290 to 1,086, RR 1.07, CI 0.99–1.15; p =.103), and glaucoma drainage implants/trabeculectomies (706 to 487, RR 0.93, CI 0.83–1.04; p =.200) remained stable. Cataract surgery (61,421 to 33,054, RR 0.77; CI 0.76–0.78; p <.001), laser peripheral iridotomy (1,875 to 890, RR 0.82, CI 0.76–0.88; p <.001), laser trabeculoplasty (2,680 to 1,753, RR 0.79, CI 0.74–0.84; p <.001), and blepharoplasty (1,522 to 797, RR 0.71, CI 0.66–0.77; p <.001) all declined significantly. All procedures except laser iridotomy returned to pre-COVID19 rates by June 2020. Most ophthalmic procedures that significantly declined during the COVID-19 pandemic were elective procedures. Among these, the majority returned to 2019 daily averages by June 2020. [ABSTRACT FROM AUTHOR]

Simple Summary: The diagnosis of primary vitreoretinal lymphoma and central nervous system lymphoma is challenging. Intraocular biopsy and molecular testing are important for the diagnosis of cases with intraocular involvement. Intraocular biopsy does not always result in a tissue diagnosis. There are many new molecular tests that are currently being used to improve the yield of intraocular biopsy. This article will review the available molecular tests for intraocular lymphoma. The diagnosis of primary vitreoretinal lymphoma and central nervous system lymphoma is challenging. In cases with intraocular involvement, vitreous biopsy plays a pivotal role. Several diagnostic tests are employed to confirm a diagnosis and include cytologic evaluation, immunohistochemistry, flow cytometry, and cytokine analysis. The limitations of these conventional diagnostic tests stem from the often paucicellular nature of vitreous biopsy specimens and the fragility of malignant cells ex vivo. Several emerging molecular techniques show promise in improving the diagnostic yield of intraocular biopsy, possibly enabling more accurate and timely diagnoses. This article will review existing diagnostic modalities for intraocular lymphoma, with an emphasis on currently available molecular tests. [ABSTRACT FROM AUTHOR]

While color fundus photos are used in routine clinical practice to diagnose ophthalmic conditions, evidence suggests that ocular imaging contains valuable information regarding the systemic health features of patients. These features can be identified through computer vision techniques including deep learning (DL) artificial intelligence (AI) models. We aim to construct a DL model that can predict systemic features from fundus images and to determine the optimal method of model construction for this task. Data were collected from a cohort of patients undergoing diabetic retinopathy screening between March 2020 and March 2021. Two models were created for each of 12 systemic health features based on the DenseNet201 architecture: one utilizing transfer learning with images from ImageNet and another from 35,126 fundus images. Here, 1277 fundus images were used to train the AI models. Area under the receiver operating characteristics curve (AUROC) scores were used to compare the model performance. Models utilizing the ImageNet transfer learning data were superior to those using retinal images for transfer learning (mean AUROC 0.78 vs. 0.65, p-value < 0.001). Models using ImageNet pretraining were able to predict systemic features including ethnicity (AUROC 0.93), age > 70 (AUROC 0.90), gender (AUROC 0.85), ACE inhibitor (AUROC 0.82), and ARB medication use (AUROC 0.78). We conclude that fundus images contain valuable information about the systemic characteristics of a patient. To optimize DL model performance, we recommend that even domain specific models consider using transfer learning from more generalized image sets to improve accuracy. [ABSTRACT FROM AUTHOR]

Purpose: Clinical trials are often designed to include homogenous, highly specific patient populations with many resources to reduce patient dropout. Results may not translate to real-world settings. We evaluated discontinuation and loss to follow-up (LTFU) rates in clinical trials of anti-vascular endothelial growth factor (anti-VEGF) injections for diabetic macular edema (DME), age-related macular degeneration (AMD), and retinal vein occlusion (RVO). Methods: Retrospective meta-epidemiological study. The authors queried ClinicalTrials.gov for all completed trials of anti-VEGF injections for DME, AMD, or RVO. Of 658 trials identified, 582 were excluded for being non-interventional, <100 patients, terminating early, or missing study results. The remaining 76 trials of 27,823 patients were analyzed for discontinuation and LTFU rates. Results: Mean discontinuation rate was 12.44% (SD 8.12%, range 0–54.12%), with higher rates among control (18.87%) than treatment arms (10.78%, p =.006). Mean LTFU rate was 1.84% (SD 1.78%, range 0–7.76%), with no differences by disease, treatment type, or treatment frequency. Conclusion: Discontinuation rates of major intravitreal anti-VEGF clinical trials were highly variable, suggesting even trials struggle with overall patient retention. Though trial LTFU rates were low, real-world outcomes may differ due to higher reported LTFU rates, which should be considered when extrapolating trial results to clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: To compare the surgical outcomes of macular hole (MH) surgery performed by trainee surgeons using a three-dimensional heads-up display (3D HUD) versus a standard operating microscope (SOM). Materials and methods: A retrospective review of all consecutive medical records patients operated on for MHs by a trainee surgeon between 2017 and 2020 using either 3D HUD or SOM was performed. Minimum hole diameter, maximum hole diameter, total surgical time, and MH closure rates were compared between the two groups. MH retinal detachments, traumatic MHs, and MHs for which inverted internal limiting membrane flaps were used were excluded from the study. Results: Trainee surgeons operated on 51 patients using 3D HUD and 63 patients using SOM. Age at presentation, intraocular pressure (IOP) at diagnosis, maximum hole diameter, minimum hole diameter, surgical time, duration between diagnosis and surgery were comparable between both groups. MH closure rate was significantly (p < 0.004) higher in the 3D HUD group (n = 44, 86.3%) than that of the SOM group (n = 38, 60.3%). There were no postoperative adverse events such as glaucoma or retinal detachment in either group. Other than the viewing technique, there were no significant variables associated with MH closure in the two groups. Conclusion: Surgeries conducted by trainee surgeons using 3D HUD had higher MH closure rates than those using SOM. [ABSTRACT FROM AUTHOR]

1 Targeted proteomic signatures differentiate molecular classes of uveal melanoma: a The vitreous contains native vitreous proteins, systemic protein biomarkers, and tumor biomarkers that can be sampled through proteomic analysis. Our research has demonstrated that retinal proteins leak into the vitreous, and that proteomic analysis of vitreous biopsies can detect molecular changes in the adjacent retina, uncover biomarkers, and identify protein targets for adjuvant therapy [[6]]. Keywords: Proteomics; Vitreous; Liquid biopsy; Uveal melanoma; Cancer; Biomarker; SCFR; HGFR; STAT3 EN Proteomics Vitreous Liquid biopsy Uveal melanoma Cancer Biomarker SCFR HGFR STAT3 1 5 5 03/02/21 20210224 NES 210224 Supplementary Information The online version contains supplementary material available at https://doi.org/10.1186/s12943-021-01336-4. [Extracted from the article]

Purpose: Wet (neovascular) age‐related macular degeneration (AMD) is the leading cause of blindness in the United States. The mainstay treatment requires monthly intravitreal injection of anti‐vascular endothelial growth factor (anti‐VEGF) drugs, associated with multiple visits, high cost, and the risk of procedural injury and infection. Anti‐VEGF drugs inhibit the formation of neovasculature but do not directly attack it. Radiotherapy can destroy neovasculature and potentially also inhibit wet‐AMD associated inflammation and fibrosis not addressed by VEGF inhibitors. However, the current collimation‐based radiotherapy device uses fixed 4 mm beams, which are prone to overtreat or undertreat the choroidal neovascularization (CNV) lesions because of their various sizes and shapes. This simulation study evaluates personalized conformal treatment with focused kV radiation using cutting‐edge polycapillary x‐ray optics. Methods: Simulation of the polycapillary optics was achieved via Monte Carlo (MC)‐based three‐dimensional (3D) geometric ray tracing. Phase‐space files modeling the focused photons were generated. The method was previously verified by phantom measurements. The ultrasmall ~0.2 mm beam focal spot perpendicular to the beam direction enables spatially fractionated grid therapy, which has been shown to preferentially damage abnormal neovascular blood vessels vs normal ones. Geant4‐based MC simulations of scanning while rotating beam delivery were performed to conformally treat three clinical cases of large, medium, and small CNV lesions with regular and grid deliveries. Dose delivery uncertainties due to positioning errors were analyzed, including ±0.75 mm displacement in the three orthogonal directions and ±5° vertical/horizontal rotation of the eyeball. Results: The simulated CNV treatments by 60‐kVp focused x‐ray beams show highly conformal delivery of dose to the lesion plus margin (0.75 mm) with sharp dose fall‐offs and controllable spatial modulation patterns. The 90%–10% isodose penumbra is <0.5 mm. With a prescription dose of 16 Gy to the lesions, the critical structure doses are well below the tolerance. The average CNV dose varies within 10% (mostly within 4%) due to 0.75‐mm linear displacements and 5‐degree gaze angle rotation of the eyeball. Conclusion: Focused kV technique allows personalized treatment of CNV lesions and reduces unwanted radiation to adjacent healthy tissue. The simulated dose distribution is superior to currently available techniques. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the relationship between surgical approach for intraocular tumor biopsy of uveal melanoma and tumor morphologic features such as size and intraocular location and the effect of these variables on diagnostic yield and biopsy outcome. Methods: Consecutive patients from nine Ocular Oncology centers with uveal melanoma (UM) undergoing tumor biopsy immediately preceding I125 plaque brachytherapy with tissue sent for gene expression profiling (GEP) testing were reviewed retrospectively. Results: Three hundred sixty patients were included (50% men, mean age 60.2 years). Overall biopsy yield was 99% and 83% for GEP and cytopathology, respectively. Surgeon choice of biopsy approach (trans-vitreal vs. trans-scleral) was found to associate with both tumor location and tumor thickness. A trans-scleral rather than trans-vitreal approach was used more commonly for anteriorly located tumors (92% vs. 38% of posterior tumors, p < 0.001) and thicker tumors (86% vs. 55% of thin tumors, p < 0.001). When performing trans-vitreal biopsies, ocular oncologists with previous vitreoretinal surgery fellowship training were more likely to use wide-field surgical viewing systems, compared with indirect ophthalmoscopy (82.6% vs. 20.6%, p < 0.001). Surgical complications were rare and occurred more frequently with trans-vitreal biopsies (3.6% vs. 0.46%, p = 0.046). Conclusions: In this multi-center analysis of UM tumor biopsy, surgical yield was high for obtaining tumor tissue for GEP and cytopathology analysis with both trans-scleral and trans-vitreal techniques. Fellowship-trained ocular oncologists' preferred intraocular biopsy techniques associated strongly with tumor location, tumor thickness, and fellowship training of the surgeon. Short-term complication rates were low. [ABSTRACT FROM AUTHOR]

Background: Wide-field imaging plays an increasingly important role in ocular oncology clinics. The purpose of this review is to describe the commonly used wide-field imaging devices and review conditions seen in ocular oncology clinic that underwent wide-field imaging as part of the multimodal evaluation. Summary of review: Wide-field or wide-angle imaging is defined as greater than 50° field of view. Modern devices can reach far beyond this reporting fields of view up to 267°, when utilizing montage features, with increasingly impressive resolution. Wide-field imaging modalities include fundus photography, fluorescein angiography (FA), fundus autofluorescence (FAF), indocyanine angiography (ICG), spectral domain optical coherence tomography (SD-OCT), and recently wide-field OCT Angiography (OCTA). These imaging modalities are increasingly prevalent in practice. The wide-field systems include laser, optical, and lens based systems that are contact or non-contact lens systems each with its own benefits and drawbacks. The purpose of this review is to discuss commonly used wide-field imaging modalities for retinal and choroidal tumors and demonstrate the use of various widefield imaging modalities in select ocular oncology cases. Conclusions: Clinical examination remains the gold standard for the evaluation of choroidal and retinal tumors. Wide-field imaging plays an important role in ocular oncology for initial documentation, surgical planning, determining the relationship of the tumor to adjacent ocular structures, following tumor size after treatment, and monitoring for recurrence. [ABSTRACT FROM AUTHOR]

Background/aims To assess peripheral retinal lesions and the posterior pole in single widefield optical coherence tomography (OCT) volumes. Methods A wide field of view (FOV) swept-source OCT (WFOV SSOCT) system was developed using a commercial swept-source laser and a custom sample arm consisting of two indirect ophthalmic lenses. Twentyseven subjects with peripheral lesions (choroidal melanomas, choroidal naevi, sclerochoroidal calcification, retinitis pigmentosa, diabetic retinopathy, retinoschisis and uveitis) were imaged with the WFOV SSOCT. Volumes were taken in primary gaze. Using the optic nerve to fovea distance as a reference measurement, comparisons were made between the lateral FOV of the WFOV SSOCT, current generation spectral-domain OCT (SDOCT) and widefield scanning laser ophthalmoscopy (SLO) of the same eyes. Results Peripheral pathologies were captured with WFOV SSOCT in 26 of the 27 subjects. The one not captured was in the far nasal periphery and was not seen in the primary gaze volume. Posterior pole associated pathologies were captured in all subjects. Current generation SDOCT had a mean lateral FOV of 2.08±0.21 optic nerve to fovea distance units, WFOV SSOCT had an FOV of 4.62±0.62 units and SLO had an FOV of 9.35±1.02 units. Conclusions WFOV OCT can be used to examine both peripheral retinal pathology and the posterior pole within a single volume acquisition. SLO had the greatest FOV, but does not provide depth information. Future studies using widefield OCT systems will help further delineate the role of WFOV OCT to quantitatively assess and monitor peripheral retinal disease in three dimensions. [ABSTRACT FROM AUTHOR]