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Retinoblastoma and uveal melanoma are the most common intraocular malignancies observed in pediatric and adult populations, respectively. For retinoblastoma, intra-arterial chemotherapy has dramatically improved treatment outcomes and eye salvage rates compared with traditional salvage rates of systemic chemotherapy and external beam radiation therapy. Intravitreal injections of chemotherapy have also demonstrated excellent efficacy for vitreous seeds. Uveal melanoma, on the other hand, is treated predominantly with iodine-125 plaque brachytherapy or with proton beam therapy. Major strides in uveal melanoma genomics have been made since the early 2000s, allowing ocular oncologists to better understand the metastatic risks of the tumor on the basis of specific genetic signatures. Loss-of-function mutations of the BAP1 gene are associated with the highest metastatic risk, whereas gain-of-function mutations of SF3B1 and EIF1AX often confer a better prognosis. Expression of a cancer-testis antigen called PRAME (preferentially expressed antigen in melanoma) has been shown to increase metastatic risks in both low-risk and high-risk melanomas. New therapeutic approaches, including molecular therapies and nanoparticle phototherapy, are currently being investigated as alternative treatment modalities for uveal melanoma.

Despite being a common presenting symptom to eye-care clinics, many ophthalmologists have difficulty diagnosing and managing ocular surface pain. The purpose of this review is to discuss potential causes of ocular surface pain, focusing on both nociceptive and neuropathic aetiologies. Specifically, we outline an approach to the diagnosis of ocular surface pain and focus on various management strategies, providing supporting evidence on the efficacy of various treatments.

PurposeTo assess the efficacy of a treat-and-extend strategy with intravitreal ranibizumab for radiation-related macular edema.MethodsForty eyes with radiation-induced macular edema and decreased visual acuity were enrolled in the phase IIb, prospective clinical trial and randomized into 3 cohorts: (A) monthly ranibizumab, (B) monthly ranibizumab with targeted retinal photocoagulation (TRP), or (C) as-needed ranibizumab and TRP. In year 2, all subjects entered a treat-and-extend protocol for ranibizumab. The primary outcome measure was mean change in early treatment diabetic retinopathy study (ETDRS) best-corrected visual acuity (BCVA) from baseline.ResultsThrough year 1, the mean change in ETDRS BCVA was significantly different between the three cohorts (p < 0.001); cohort A saw the largest gain with + 4.0 letters. Significant anatomic improvements were also seen in all cohorts. Comparatively, through year 2, cohorts A, B, and C had a mean change in ETDRS BCVA of − 1.9, − 3.9, and + 1.3 letters, respectively; additionally, no significant differences were found in absolute ETDRS BCVA across time (ANOVA, p = 0.123). Overall, 90% of eyes maintained VA 20/200 or better and 33.3% of subjects gained at least one line of vision. There were no significant differences in mean central macular thickness for any cohort compared to baseline (p = 0.09). The presence of retinal hemorrhage and intraretinal exudates stayed consistent from year 1 to year 2 for all cohorts.ConclusionsAmong eyes with radiation-related macular edema, a treat-and-extend regimen with ranibizumab may not result in as many visual and anatomic improvements as monthly injections. However, treat-and-extend still may prevent serious visual complications compared to historical controls. Trial registrationClinicalTrials.gov Identifier: NCT02222610

PurposeTo evaluate the association between traditional clinical high-risk features of uveal melanoma patients and gene expression profile (GEP).MethodsThis was a retrospective, single-center, case series of patients with uveal melanoma. Eighty-three patients met inclusion criteria for the study. Patients were examined for the following clinical risk factors: drusen/retinal pigment epithelium (RPE) changes, vascularity on B-scan, internal reflectivity on A-scan, subretinal fluid (SRF), orange pigment, apical tumor height/thickness, and largest basal dimensions (LBD). A novel point system was created to grade the high-risk clinical features of each tumor. Further analyses were performed to assess the degree of association between GEP and each individual risk factor, total clinical risk score, vascularity, internal reflectivity, American Joint Committee on Cancer (AJCC) tumor stage classification, apical tumor height/thickness, and LBD.ResultsOf the 83 total patients, 41 were classified as GEP class 1A, 17 as class 1B, and 25 as class 2. The presence of orange pigment, SRF, low internal reflectivity and vascularity on ultrasound, and apical tumor height/thickness ≥ 2 mm were not statistically significantly associated with GEP class. Lack of drusen/RPE changes demonstrated a trend toward statistical association with GEP class 2 compared to class 1A/1B. LBD and advancing AJCC stage was statistically associated with higher GEP class.ConclusionsIn this cohort, AJCC stage classification and LBD were the only clinical features statistically associated with GEP class. Clinicians should use caution when inferring the growth potential of melanocytic lesions solely from traditional funduscopic and ultrasonographic risk factors without GEP data.

PurposeTo 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.MethodsConsecutive 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.ResultsThree 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).ConclusionsIn 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.

A search for beyond the Standard Model particles that are heavy, long-lived, and charged in protonproton collisions at center-of-mass energy √ s = 13 TeV is presented. The datasets used are recorded by the Compact Muon Solenoid detector in 2017 and 2018, triggered with missing transverse energy in the events and corresponding to an integrated luminosity of 101 fb−1. The particles are required to have large energy deposited per path length (dE/dx) in the silicon pixel detector and in the silicon strip detector. The ABCD method utilizes the independence of the dE/dx discriminators in the two detectors to predict the number of background events in data. No significant excess of events over the predicted number of background events is observed. The results of this signature driven search are interpreted in the context of signal hypotheses, specifically for two models of the pair-produced supersymmetric gluino R-hadrons. The gluino R-hadron cloud interaction model is excluded at the 95% confidence level with a mass up to 2.182 TeV (compared to an expected limit of 2.089 TeV), and the gluino R-hadron charge suppressed model is excluded at the 95% confidence level with a mass up to 2.160 TeV (compared to an expected limit of 2.077 TeV). These observed limits are the best to date for detector-stable gluino R-hadron models.

Background: The treatment of chronic ankle sprains has largely focused on lateral ankle instability in the literature. There is a scarcity of data regarding the diagnosis and management of chronic medial ankle instability secondary to deltoid ligament injury. Methods: A literature search was performed using the National Center for Biotechnology Information (NCBI) database for studies evaluating chronic ankle instability (CAI) involving deltoid ligament pathology. Studies were evaluated for workup including clinical presentation, imaging, treatment algorithm and operative techniques. Descriptive statistical analysis was conducted across the pooled data set. Results: Nine studies representing 516 patients with CAI were included in our analysis. Plain radiographs assessed talar-tilt angle in 440 patients (85%) and anterior displacement in 296 patients (57%). A total of 465 patients underwent magnetic resonance imaging, with deltoid injuries identified in 289 (62%) of patients. Of these 289 patients, superficial deltoid involvement was specified in 61 patients and deep deltoid in 146 patients. Surgical treatment most commonly included arthroscopy in 255 patients with open deltoid ligament repair in 199 patients. Repair method included suture anchors in 173 patients (87%), bone tunnels in 23 patients (12%), and unspecified technique in 3 patients (1.5%). Thirteen patients (6.5%) had suture anchor repairs augmented with an internal brace. Three patients underwent deltoid reconstruction with plantaris tendon autograft. Conclusion: Deltoid ligament injuries are common in patients with CAI. These data improve our understanding of chronic deltoid injuries and can help patients and surgeons better comprehend the pathoanatomy of chronic ankle instability. Level of Evidence: Level III, retrospective cohort study.

The differential diagnosis of a pigmented choroidal lesion includes choroidal nevus, choroidal melanoma, congenital hypertrophy of the retinal pigment epithelium (CHRPE), melanocytoma, extramacular disciform lesion, and other rarer entities. Given that a missed uveal melanoma diagnosis can be life-threatening, both general ophthalmologists and retinal specialists should be well versed in distinguishing these lesions from each other.

Separating structure and electrons in VO2Above 341 kelvin—not far from room temperature—bulk vanadium dioxide (VO2) is a metal. But as soon as the material is cooled below 341 kelvin, VO2 turns into an insulator and, at the same time, changes its crystal structure from rutile to monoclinic. Lee et al. studied the peculiar behavior of a heterostructure consisting of a layer of VO2 placed underneath a layer of the same material that has a bit less oxygen. In the VO2 layer, the structural transition occurred at a higher temperature than the metal-insulator transition. In between those two temperatures, VO2 was a metal with a monoclinic structure—a combination that does not occur in the absence of the adjoining oxygen-poor layer.Science, this issue p. 1037The metal-insulator transition in correlated materials is usually coupled to a symmetry-lowering structural phase transition. This coupling not only complicates the understanding of the basic mechanism of this phenomenon but also limits the speed and endurance of prospective electronic devices. We demonstrate an isostructural, purely electronically driven metal-insulator transition in epitaxial heterostructures of an archetypal correlated material, vanadium dioxide. A combination of thin-film synthesis, structural and electrical characterizations, and theoretical modeling reveals that an interface interaction suppresses the electronic correlations without changing the crystal structure in this otherwise correlated insulator. This interaction stabilizes a nonequilibrium metallic phase and leads to an isostructural metal-insulator transition. This discovery will provide insights into phase transitions of correlated materials and may aid the design of device functionalities.