Five vascular endothelial growth factor receptor (VEGFR) ligands (VEGF-A, -B, -C, -D, and placental growth factor [PlGF]) constitute the VEGF family. VEGF-A binds VEGF receptors 1 and 2 (VEGFR1/2), whereas VEGF-B and PlGF only bind VEGFR1. Although much research has been conducted on VEGFR2 to elucidate its key role in retinal diseases, recent efforts have shown the importance and involvement of VEGFR1 and its family of ligands in angiogenesis, vascular permeability, and microinflammatory cascades within the retina. Expression of VEGFR1 depends on the microenvironment, is differentially regulated under hypoxic and inflammatory conditions, and it has been detected in retinal and choroidal endothelial cells, pericytes, retinal and choroidal mononuclear phagocytes (including microglia), Müller cells, photoreceptor cells, and the retinal pigment epithelium. Whilst the VEGF-A decoy function of VEGFR1 is well established, consequences of its direct signaling are less clear. VEGFR1 activation can affect vascular permeability and induce macrophage and microglia production of proinflammatory and proangiogenic mediators. However the ability of the VEGFR1 ligands (VEGF-A, PlGF, and VEGF-B) to compete against each other for receptor binding and to heterodimerize complicates our understanding of the relative contribution of VEGFR1 signaling alone toward the pathologic processes seen in diabetic retinopathy, retinal vascular occlusions, retinopathy of prematurity, and age-related macular degeneration. Clinically, anti-VEGF drugs have proven transformational in these pathologies and their impact on modulation of VEGFR1 signaling is still an opportunity-rich field for further research.

Importance: Telemedicine has been shown to have had reduced uptake among historically marginalized populations within multiple medical specialties during the COVID-19 pandemic. An evaluation of health disparities among patients receiving ophthalmic telemedical care during the pandemic is needed. Objective: To evaluate disparities in the delivery of ophthalmic telemedicine at Massachusetts Eye and Ear (MEE) during the COVID-19 pandemic. Design, Setting, and Participants: This retrospective, cross-sectional study analyzed clinical visits at a single tertiary eye care center (MEE) from January 1 to December 31, 2020. Patients who had ophthalmology and optometry clinical visits at the MEE during the study period were included. Exposures: Telemedicine vs in-person clinical encounters. Main Outcomes and Measures: Variables associated with use of ophthalmic telemedicine during the study period. Results: A total of 2262 telemedicine ophthalmic encounters for 1911 patients were included in the analysis. The median age of the patients was 61 (interquartile range, 43-72) years, and 1179 (61.70%) were women. With regard to race and ethnicity, 87 patients (4.55%) identified as Asian; 128 (6.70%), as Black or African American; 23 (1.20%), as Hispanic or Latino; and 1455 (76.14%), as White. On multivariate analysis, factors associated with decreased receipt of telemedical care included male sex (odds ratio [OR], 0.86; 95% CI, 0.77-0.96), Black race (OR, 0.69; 95% CI, 0.56-0.86), not speaking English (OR, 0.63; 95% CI, 0.48-0.81), educational level of high school or less (OR, 0.83; 95% CI, 0.71-0.97), and age (OR per year of age, 0.99; 95% CI, 0.989-0.998). When comparing telephone- and video-based telemedicine visits, decreased participation in video-based visits was associated with age (OR per year of age, 0.96; 95% CI, 0.94-0.98), educational level of high school or less (OR, 0.54; 95% CI, 0.29-0.99), being unemployed (OR, 0.28; 95% CI, 0.12-0.68), being retired (OR, 0.22; 95% CI, 0.10-0.42), or having a disability (OR, 0.09; 95% CI, 0.04-0.23). Conclusions and Relevance: The findings of this cross-sectional study, though limited to retrospective data from a single university-based practice, suggest that historically marginalized populations were less likely to receive ophthalmic telemedical care compared with in-person care during the first year of the COVID-19 pandemic in the US. Understanding the causes of these disparities might help those who need access to virtual care.

BACKGROUND: Neurotrophic keratopathy (NK) is a relatively uncommon, underdiagnosed degenerative corneal disease that is caused by damage to the ophthalmic branch of the trigeminal nerve by conditions such as herpes simplex or zoster keratitis, intracranial space-occupying lesions, diabetes, or neurosurgical procedures. Over time, epithelial breakdown, corneal ulceration, corneal melting (thinning), perforation, and loss of vision may occur. The best opportunity to reverse ocular surface damage is in the earliest stage of NK. However, patients typically experience few symptoms and diagnosis is often delayed. Increased awareness of the causes of NK, consensus on when and how to screen for NK, and recommendations for how to treat NK are needed. METHODS: An 11-member expert panel used a validated methodology (a RAND/UCLA modified Delphi panel) to develop consensus on when to screen for and how best to diagnose and treat NK. Clinicians reviewed literature on the diagnosis and management of NK then rated a detailed set of 735 scenarios. In 646 scenarios, panelists rated whether a test of corneal sensitivity was warranted; in 20 scenarios, they considered the adequacy of specific tests and examinations to diagnose and stage NK; and in 69 scenarios, they rated the appropriateness of treatments for NK. Panelist ratings were used to develop clinical recommendations. RESULTS: There was agreement on 94% of scenarios. Based on this consensus, we present distinct circumstances when we strongly recommend or may consider a test for corneal sensitivity. We also present recommendations on the diagnostic tests to be performed in patients in whom NK is suspected and treatment options for NK. CONCLUSIONS: These expert recommendations should be validated with clinical data. The recommendations represent the consensus of experts, are informed by published literature and experience, and may improve outcomes by helping improve diagnosis and treatment of patients with NK.

The advent of optical coherence tomography (OCT) revolutionized both clinical assessment and research of vitreoretinal conditions. Since then, extraordinary advances have been made in this imaging technology, including the relatively recent development of swept-source OCT (SS-OCT). SS-OCT enables a fast scan rate and utilizes a tunable swept laser, thus enabling the incorporation of longer wavelengths than conventional spectral-domain devices. These features enable imaging of larger areas with reduced motion artifact, and a better visualization of the choroidal vasculature, respectively. Building on the principles of OCT, swept-source OCT has also been applied to OCT angiography (SS-OCTA), thus enabling a non-invasive in depth-resolved imaging of the retinal and choroidal microvasculature. Despite their advantages, the widespread use of SS-OCT and SS-OCTA remains relatively limited. In this review, we summarize the technical details, advantages and limitations of SS-OCT and SS-OCTA, with a particular emphasis on their relevance for the study of retinal conditions. Additionally, we comprehensively review relevant studies performed to date to the study of retinal health and disease, and highlight current gaps in knowledge and opportunities to take advantage of swept source technology to improve our current understanding of many medical and surgical chorioretinal conditions. We anticipate that SS-OCT and SS-OCTA will continue to evolve rapidly, contributing to a paradigm shift to more widespread adoption of new imaging technology to clinical practice.

Importance: Uncorrected refractive error in school-aged children may affect learning. Objective: To assess the effect of a school-based vision program on academic achievement among students in grades 3 to 7. Design, Setting, and Participants: This cluster randomized clinical trial was conducted in Baltimore City Public Schools during school years from 2016 to 2019 among 2304 students in grades 3 to 7 who received eye examinations and eyeglasses. Intervention: Participating schools were randomized 1:1:1 to receive eye examinations and eyeglasses during 1 of 3 school years (2016-2017, 2017-2018, and 2018-2019). Main Outcomes and Measures: The primary outcome was 1-year intervention impact, measured by effect size (ES), defined as the difference in score on an academic test (i-Ready or Partnership for Assessment of Readiness for College and Careers tests on reading and mathematics) between intervention and control groups measured in SD units, comparing cohort 1 (intervention) with cohorts 2 and 3 (control) at the end of program year 1 and comparing cohort 2 (intervention) with cohort 3 (control) at the end of program year 2. The secondary outcome was 2-year intervention impact, comparing ES in cohort 1 (intervention) with cohort 3 (control) at the end of program year 2. Hierarchical linear modeling was used to assess the impact of the intervention. Analysis was performed on an intention-to-treat basis. Results: Among the 2304 students included in the study, 1260 (54.7%) were girls, with a mean (SD) age of 9.4 (1.4) years. The analysis included 964 students (41 schools) in cohort 1, 775 students (41 schools) in cohort 2, and 565 students (38 schools) in cohort 3. There were 1789 Black students (77.6%), 388 Latinx students (16.8%), and 406 students in special education (17.6%). There was an overall 1-year positive impact (ES, 0.09; P = .02) as assessed by the i-Ready reading test during school year 2016-2017. Positive impact was also observed among female students (ES, 0.15; P < .001), those in special education (ES, 0.25; P < .001), and students who performed in the lowest quartile at baseline (ES, 0.28; P < .001) on i-Ready reading and among students in elementary grades on i-Ready mathematics (ES, 0.03; P < .001) during school year 2016-2017. The intervention did not show a sustained impact at 2 years or on Partnership for Assessment of Readiness for College and Careers testing. Conclusions and Relevance: Students in grades 3 to 7 who received eyeglasses through a school-based vision program achieved better reading scores. Students had improved academic achievement over 1 year; however, a sustained impact was not observed after 2 years. Trial Registration: The Registry of Efficacy and Effectiveness Studies Identifier: 1573.1v1.

The prevalence and reward-value of targets have an influence on visual search. The strength of the effect of an item's reward-value on attentional selection varies substantially between individuals and is potentially sensitive to aging. We investigated individual and age differences in a hybrid foraging task, in which the prevalence and value of multiple target types was varied. Using optimal foraging theory measures, foraging was more efficient overall in younger than older observers. However, the influence of prevalence and value on target selections was similar across age groups, suggesting that the underlying cognitive mechanisms are preserved in older age. When prevalence was varied but target value was balanced, younger and older observers preferably selected the most frequent target type and were biased to select another instance of the previously selected target type. When value was varied, younger and older observers showed a tendency to select high-value targets, but preferences were more diverse between individuals. When value and prevalence were inversely related, some observers showed particularly strong preferences for high-valued target types, while others showed a preference for high-prevalent, albeit low-value, target types. In younger adults, individual differences in the selection choices correlated with a personality index, suggesting that avoiding selections of low-value targets may be related to reward-seeking behaviour.

The analysis of nuclear morphology plays an important role in glioma diagnosis and grading. We previously described intranuclear rods (rods) labeled with the SDL.3D10 monoclonal antibody against class III beta-tubulin (TUBB3) in human ependymomas. In a cohort of adult diffuse gliomas, we identified nuclear rods in 71.1% of IDH mutant lower-grade gliomas and 13.7% of IDH wild-type glioblastomas (GBMs). The presence of nuclear rods was associated with significantly longer postoperative survival in younger (≤65) GBM patients. Consistent with this, nuclear rods were mutually exclusive with Ki67 staining and their prevalence in cell nuclei inversely correlated with the Ki67 proliferation index. In addition, rod-containing nuclei showed a relative depletion of lamin B1, suggesting a possible association with senescence. To gain insight into their functional significance, we addressed their antigenic properties. Using a TUBB3-null mouse model, we demonstrate that the SDL.3D10 antibody does not bind TUBB3 in rods but recognizes an unknown antigen. In the present study, we show that rods show immunoreactivity for the nucleotide synthesizing enzymes inosine monophosphate dehydrogenase (IMPDH) and cytidine triphosphate synthetase. By analogy with the IMPDH filaments that have been described previously, we postulate that rods regulate the activity of nucleotide-synthesizing enzymes in the nucleus by sequestration, with important implications for glioma behavior.