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To determine prevalence of probable polypoidal choroidal vasculopathy (PCV) among White patients with neovascular age-related macular degeneration (nAMD) using non-indocyanine green angiography (ICGA) criteria DESIGN: Multicenter, multinational, retrospective, cross-sectional study.A total of 208 treatment-naive eyes from Hispanic and non-Hispanic White individuals diagnosed with nAMD were included. All underwent color fundus photography (CFP), optical coherence tomography (OCT), and fluorescein angiography (FFA). De-identified images of study eyes were sent to 2 groups of graders. Group 1 reviewed CFP, OCT, and FFA to confirm nAMD diagnosis. Group 2 reviewed CFP and OCT to determine highly suggestive features for PCV. Probable PCV diagnosis defined as the presence of ≥2 of 4 highly suggestive features for PCV: notched or fibrovascular pigment epithelial detachment (PED) on CFP, sharply-peaked PED, notched PED, and hyperreflective ring on OCT.Eleven eyes were excluded because of poor image quality (6) or non-nAMD diagnosis (5). Of 197 eligible eyes (197 patients), the mean age (SD) was 78.8 years (8.9), 44.2% were men, 26.4% were Hispanic, and 73.6% were non-Hispanic White individuals; 41.1%, 23.4%, 9.1%, and 2.5% had ≥1, ≥2, ≥3, and 4 highly suggestive features. Results showed that 23.4% (95% CI, 17.6%-29.9%) had probable PCV diagnosis. Predominantly occult CNV was more frequently found in probable PCV than nAMD subgroup (84.8% vs 64.9%, P = .01). Hispanic White individuals had a lower prevalence of probable PCV than non-Hispanic White individuals (9.6% vs 28.2%, P = .006) CONCLUSIONS: These findings suggest that probable PCV occurs between 17.6% and 29.9% in White individuals with nAMD, and more commonly in non-Hispanic than in Hispanic White individuals.

To determine accuracy and relative risk (RR) of posttreatment optical coherence tomography (OCT) features in identifying complete or incomplete polypoidal regression in polypoidal choroidal vasculopathy (PCV).Validity analysis.Treatment-naive PCV eyes undergoing OCT and indocyanine green angiography (ICGA) at baseline and posttreatment were included. Two graders confirmed diagnosis and identified posttreatment complete or incomplete regression on ICGA. Two other graders classified OCT characteristics of pigment epithelial detachment (PED) (polypoidal lesion) based on 5 prespecified features: "A," no PED; "B," PED with internal homogeneous reflectivity with predominant "BUN" (blended retinal pigment epithelium with underlying structure) sign; "C," PED with internal homogeneous reflectivity with minimal "BUN"; "D," heterogeneous PED; and "E," PED with hyporeflectivity.Among 130 polypoidal lesions (65 pretreatment and 65 posttreatment) of 39 PCV eyes (39 patients; 54% female; mean age±SD: 64.6±8.2), all pretreatment lesions showed feature D on OCT. Posttreatment lesions with complete regression (31 lesions) showed OCT features A, B, C, D, and E in 32%, 45%, 13%, 10%, and 0%, respectively. Posttreatment lesions with incomplete regression (34 lesions) showed OCT features A, B, C, D, and E in 0%, 6%, 15%, 79%, and 0%, respectively. Presence of either feature A or B had highest accuracy (86%; 95% confidence interval: 75%-93%); 77% sensitivity; 94% specificity; RR 5.0 (3.5-7.1, P0.001) for complete regression. Presence of feature D had highest accuracy (85%; 95% confidence interval: 74%-92%); 79% sensitivity; 90% specificity; RR 4.6 (3.0-6.9, P0.001) for incomplete regression.Without ICGA, OCT features could provide high accuracy in identifying posttreatment complete or incomplete polypoidal regression in PCV.

Background According to the Committee on STEM Education, K-12 science students need access to learning experiences that promote collaboration and engagement. To fill that void, we need to develop activities that stimulate engaged learning and scaffold effective collaboration. K-12 teacher candidates see value in utilizing games for this purpose. Specifically, tabletop science games can help teachers engage students in science learning and scaffold collaboration. Aim For this study, we designed a collaborative, STEM-themed card game called MOUNTAIN RESCUE and explored its capacity to promote engaged learning and collaboration. Method Four groups of STEM campers (n = 14) in a suburban Mid-Atlantic region played MOUNTAIN RESCUE. All groups had a mix of boys and girls. Play-testers ranged from 10–13 years old. The tabletop game took approximately 30-minutes. During gameplay, players embodied unique STEM roles: physicist, chemist, structural engineer, and electrical engineer. They collaborated to solve challenges related to electricity, physics, chemistry, and engineering design. Discourse was audio-recorded throughout gameplay. Immediately after gameplay, self-report survey data were collected to assess flow and perceptions of collaborative learning. Results Findings demonstrated that the game promoted engagement and collaboration. Specifically, students had a flow-like experience and felt positively about the game's value for collaborative learning. Utterances demonstrating active engagement and constructive thinking became more group-focused over time. Conclusion This study contributes to science education by demonstrating potential benefits of a well-designed, low-tech, science learning environment or—in other words—a tabletop game.

To develop a classification system of visual field (VF) abnormalities in highly myopic eyes with and without glaucoma.Secondary analysis of VF data from a longitudinal cohort study.One thousand eight hundred ninety-three VF tests from 1302 eyes (825 individuals).All participants underwent VF testing (Humphrey 24-2 Swedish interactive threshold algorithm standard program; Carl Zeiss Meditec) and detailed ophthalmic examination. A comprehensive set of VF defect patterns was defined via observation of the 1893 VF reports, literature review, and consensus meetings. The classification system comprised 4 major types of VF patterns, including normal type, glaucoma-like defects (paracentral defect, nasal step, partial arcuate defect, arcuate defect), high myopia-related defects (enlarged blind spot, vertical step, partial peripheral rim, nonspecific defect), and combined defects (nasal step with enlarged blind spot). A subset (n = 1000) of the VFs was used to evaluate the interobserver and intraobserver agreement and weighted κ values of the classification system by 2 trained readers. The prevalence of various VF patterns and their associated factors were determined.The classification of VF in highly myopic eyes and its associated risk factors.We found that normal type, glaucoma-like defects, high myopia-related defects, and combined defects accounted for 74.1%, 10.8%, 15.0%, and 0.1% of all unique VF tests, respectively. The interobserver and intraobserver agreements were89%, and the corresponding κ values were 0.86 or more between readers. Both glaucoma-like and high myopia-related VF defects were associated with older age (odds ratios [ORs], 1.07 [95% confidence interval (CI), 1.04-1.10; P0.001] and 1.06 [95% CI, 1.04-1.10; P0.001]) and longer axial length (ORs, 1.65 [95% CI, 1.32-2.07; P0.001] and 1.37 [95% CI, 1.11-1.68; P = 0.003]). Longer axial length showed a stronger effect on the prevalence of glaucoma-like VF defects than on the prevalence of high myopia-related VF defects (P = 0.036).We propose a new and reproducible classification system of VF abnormalities for nonpathologic high myopia. Applying a comprehensive classification system will facilitate communication and comparison of findings among studies.

Purpose: To assess the correlation between the change in central subfield thickness (CST) and change in best-corrected visual acuity (BCVA) in eyes with diabetic macular edema (DME) treated with fixed-dosing intravitreal aflibercept injection (IAI). Methods: This post hoc analysis of the VISTA and VIVID randomized controlled clinical trials, in which 862 eyes with central-involved DME were randomly assigned to IAI 2 mg every 4 weeks (2q4; 290 eyes), IAI 2 mg every 8 weeks after 5 initial monthly doses (2q8; 286 eyes), or macular laser (286 eyes) and followed through 100 weeks. Correlations between the change in CST and change in BCVA from baseline to weeks 12, 52, and 100 were assessed using the Pearson correlation. Results: The respective correlations ( r [95% CI]) at weeks 12, 52, and 100 were −0.39 (−0.49 to −0.29), −0.27 (−0.38 to −0.15), and −0.30 (−0.41 to −0.17) in the 2q4 arm and −0.28 (−0.39 to −0.17), −0.29 (−0.41 to −0.17), and −0.33 (−0.44 to −0.20) in the 2q8 arm. Linear regression analysis of the correlation at week 100, adjusted for relevant baseline factors, showed CST changes accounted for 17% of the variance in BCVA changes; every 100-µm decrease in CST was associated with a 1.2-letter increase in BCVA ( P = .001). Conclusions: Correlations between the change in CST and change in BCVA after 2q4 or 2q8 fixed-dosing IAI for DME were modest. Although a change in CST might be important in determining the need for antivascular endothelial growth factor for DME at follow-up, it was not a good surrogate for VA outcomes.

Purpose Assess correlation between change in central subfield thickness (CST) and change in best-corrected visual acuity (BCVA) in eyes with macular edema due to retinal vein occlusion (RVO) that received intravitreal aflibercept injections (IAI). Methods Post hoc analysis of COPERNICUS and GALILEO trials for CRVO and VIBRANT trial for BRVO with relationships determined using Pearson correlation coefficient. Results In COPERNICUS, correlations (r) between change in CST and change in BCVA from baseline at weeks 12, 24, 52, and 100 were −0.36 (95% CI: −0.52, −0.18; P P P P P = 0.003). Similar findings were noted for GALILEO (r, −0.45 to −0.23) and VIBRANT (r, −0.36 to −0.32) trials. Conclusion In eyes treated with IAI for macular edema due to RVO, correlation between change in CST and change in BCVA was weak to moderate. While change in CST may be helpful in determining the need for anti-VEGF therapy, these findings do not support using changes in CST as a surrogate for changes in visual acuity outcomes.

Supplementary Data Methods, Figures S1-S7, and Table S1

Surgery is the only potentially curative treatment for localized soft-tissue sarcomas. However, for sarcomas arising in the retroperitoneum, locoregional recurrence rates are 35% to 59% despite resection. Doxorubicin (DOX) is the standard first-line systemic chemotherapy for advanced soft-tissue sarcoma, yet its intravenous administration yields limited clinical efficacy and results in dose-limiting cardiotoxicity. We report the fabrication and optimization of a novel electrospun poly(caprolactone) (PCL) surgical mesh coated with layers of a hydrophobic polymer (poly(glycerol monostearate-co-caprolactone), PGC-C18), which delivers DOX directly to the operative bed following sarcoma resection. In xenograft models of liposarcoma and chondrosarcoma, DOX-loaded meshes (DoM) increased overall survival 4-fold compared with systemically administered DOX and prevented local recurrence in all but one animal. Importantly, mice implanted with DoMs exhibited preserved cardiac function, whereas mice receiving an equivalent dose systemically displayed a 23% decrease from baseline in both cardiac output and ejection fraction 20 days after administration. Collectively, this work demonstrates a feasible therapeutic approach to simultaneously prevent post-surgical tumor recurrence and minimize cardiotoxicity in soft-tissue sarcoma.Significance:A proof-of-principle study in animal models shows that a novel local drug delivery approach can prevent tumor recurrence as well as drug-related adverse events following surgical resection of soft-tissue sarcomas.

Objective To assess ‘time in range’ as a novel measure of treatment response in diabetic macular oedema (DMO). Methods This post hoc analysis of the Protocol T randomised clinical trial included 660 individuals with centre-involved DMO and best-corrected visual acuity (BCVA) letter score ≤78–≥24 (approximate Snellen equivalent 20/32–20/320). Study participants received intravitreal aflibercept 2.0 mg, repackaged (compounded) bevacizumab 1.25 mg, or ranibizumab 0.3 mg given up to every 4 weeks using defined retreatment criteria. Mean time in range was calculated using a BCVA letter score threshold of ≥69 (20/40 or better; minimum driving requirement in many regions), with sensitivity analyses using BCVA thresholds from 100 to 0 (20/10 to 20/800) in 1-letter increments. Results Time in range was defined as either the absolute or relative duration above a predefined BCVA threshold, measured in weeks or as a percentage of time, respectively. Using a BCVA letter score threshold of ≥69 (20/40 or better), the least squares mean time in range (adjusted for baseline BCVA) in Year 1 was 41.2 weeks with intravitreal aflibercept, 4.0 weeks longer (95% CI: 1.7, 6.3; p = 0.002) than bevacizumab and 3.6 weeks longer (1.3, 5.9; p = 0.004) than ranibizumab. Overall, mean time in range was numerically longer for intravitreal aflibercept for all BCVA letter score thresholds between 92 and 30 (20/20 to 20/250). In the Day 365–728 analysis, time in range was 3.9 (1.3, 6.5) and 2.4 (0.0, 4.9) weeks longer with intravitreal aflibercept vs bevacizumab and vs ranibizumab (p = 0.011 and 0.106), respectively. Conclusion BCVA time in range may represent another way to describe visual outcomes and potential impact on vision-related functions over time for patients with DMO and provide a better understanding, for physicians and patients, of the consistency of treatment efficacy.

Background/AimsTo provide longer-term data on efficacy, safety, immunogenicity and pharmacokinetics (PK) of ranibizumab biosimilar SB11 compared with the reference ranibizumab (RBZ) in patients with neovascular age-related macular degeneration (nAMD).MethodsSetting: Multicentre.Design: Randomised, double-masked, parallel-group, phase III equivalence study.Patient population: ≥50 years old participants with nAMD (n=705), one ‘study eye’. Intervention: 1:1 randomisation to monthly intravitreal injection of 0.5 mg SB11 or RBZ.Main outcome measures: Visual efficacy endpoints, safety, immunogenicity and PK up to 52 weeks.ResultsBaseline and disease characteristics were comparable between treatment groups. Of 705 randomised participants (SB11: n=351; RBZ: n=354), 634 participants (89.9%; SB11: n=307; RBZ: n=327) completed the study until week 52. Previously reported equivalence in primary efficacy remained stable up to week 52 and were comparable between SB11 and RBZ. The adjusted treatment difference between SB11 and RBZ in full analysis set at week 52 of change from baseline in best-corrected visual acuity was −0.6 letters (90% CI −2.1 to 0.9) and of change from baseline in central subfield thickness was −14.9 µm (95% CI –25.3 to –4.5). The incidence of ocular treatment-emergent adverse events (TEAEs) (SB11: 32.0% vs RBZ: 29.7%) and serious ocular TEAE (SB11: 2.9% vs RBZ: 2.3%) appeared comparable between treatment groups, and no new safety concerns were observed. The PK and immunogenicity profiles were comparable, with a 4.2% and 5.5% cumulative incidence of antidrug antibodies up to week 52 for SB11 and RBZ, respectively.ConclusionsLonger-term results of this study further support the biosimilarity established between SB11 and RBZ.

PURPOSE: Since eyes with center-involved diabetic macular edema (CI-DME) and good baseline visual acuity (VA) showed no difference in VA loss when managed initially with observation, laser, or aflibercept, understanding the estimated costs of these strategies to the US population is relevant for health care planning. METHODS, SETTING, AND PARTICIPANTS: Total costs for managing participants with CI-DME and good baseline VA assigned to aflibercept (n= 236), laser (n=240), or observation (n = 236) during the 2-year trial were calculated. Using epidemiological data and extrapolating costs, 10-year costs for caring for persons with CI-DME and good baseline VA throughout the US was estimated. INTERVENTIONS: Observation or laser groups initiated aflibercept if VA decreased. Aflibercept group received injections up to every 4 weeks. MAIN OUTCOMES AND MEASURES: Estimated 10-year U.S. population costs to manage CI-DME with good VA. RESULTS: Assuming all patients in the US with CI-DME and good baseline VA received aflibercept initially, 10-year costs were projected to be $28.80 billion compared with $14.42 billion if initially receiving laser treatment or $15.70 billion if initially observed, with aflibercept added if VA worsened in the laser or observation arms. CONCLUSIONS AND RELEVANCE: Similar VA outcomes on average are obtained by initially managing CI-DME and good baseline VA with laser or observation strategies instead of immediately using aflibercept. While any one of these three strategies might be warranted depending on an individual’s specific circumstances, on a societal level, cost savings might be achieved with these first two approaches. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01909791

ImportanceSB11 and reference ranibizumab (RBZ) are monoclonal anti–vascular endothelial growth factor (VEGF)–A antibodies approved for the treatment of neovascular age-related macular degeneration (nAMD) and other retinal diseases. The association of ranibizumab immunogenicity and treatment outcomes in patients with nAMD is unclear but relevant regarding concerns about immunogenicity of anti-VEGF biological products.ObjectiveTo examine the association of immunogenicity to ranibizumab products (SB11 and RBZ) with efficacy, safety, and pharmacokinetics.Design, Setting, and ParticipantsThis was a post hoc analysis of a randomized, double-masked, parallel-group phase 3 equivalence study with participants from 75 centers in 9 countries conducted from March 14, 2018, to December 9, 2019. Included were participants 50 years or older with nAMD and active subfoveal choroidal neovascularization lesions.InterventionsIntravitreal injection of SB11 or RBZ, 0.5 mg, every 4 weeks through week 48.Main Outcomes and MeasuresSerum antidrug antibodies (ADAs) were analyzed during the study period until week 52 to measure immunogenicity. Analyses were performed on immunogenicity (overall ADA positivity) with best-corrected visual acuity (BCVA) and central subfield thickness (CST). Adverse events associated with intraocular inflammation (IOI) and serum ranibizumab levels were compared between overall ADA-positive and ADA-negative participants.ResultsA total of 705 participants (mean [SD] age, 74.1 [8.5] years; 403 female individuals [57.2%]) were included in the study. The overall incidence of ADA-positivity was 32 of 657 (4.9%) at week 52. The least-squares mean (SE) differences between overall ADA-positive and ADA-negative participants up to week 52 for BCVA and CST, respectively, were 1.6 (2.2) letters (95% CI, −2.7 to 5.8; P = .46) and 3 (13) μm (95% CI, −23 to 29; P = .83). IOI-related events occurred in 1 of 32 overall ADA-positive participants (3.1%) and 4 of 620 overall ADA-negative participants (0.6%). Mean (SD) serum ranibizumab concentrations over time were slightly lower in overall ADA-positive participants compared with those of ADA-negative participants, with a maximum value of 1389.3 (875.4) pg/mL at week 16 vs 1665.4 (1124.0) pg/mL at week 36, respectively.Conclusions and RelevanceResults of this post hoc analysis of an equivalence trial suggest that immunogenicity was not associated with efficacy and safety of SB11 and RBZ in participants with nAMD. With a low overall ADA incidence, no clear association was identified between overall ADA positivity and pharmacokinetics. These findings support the biosimilarity of SB11 and RBZ, with no safety concern identified for SB11 vs RBZ associated with immunogenicity.Trial RegistrationClinicalTrials.gov Identifier: NCT03150589

Purpose of review The use of intravitreous antivascular endothelial growth factor to prevent center-involved diabetic macular edema (CI-DME) with vision loss and proliferative diabetic retinopathy (PDR) has been investigated and recently reported in two randomized clinical trials. Although both trials showed substantial superiority of aflibercept at preventing the development of vision-threatening complications (VTCs) of CI-DME or PDR compared with sham at 1 or 2 years, without a concomitant benefit in visual acuity outcomes, the interpretation of the results and its application to clinical practice resulted in two disparate opinions. In this review, we discuss these two trials including their similarities and differences, other relevant studies, and considerations regarding the interpretation and the application of these results into clinical practice. Recent findings The Diabetic Retinopathy Clinical Research Retina Network Protocol W and the PANORAMA study demonstrated significantly lower probabilities of developing CI-DME or PDR at 2 years with intravitreous aflibercept compared with sham in eyes with moderate (Protocol W) or moderately severe (PANORAMA) to severe non-PDR (NPDR). However, visual acuity outcomes were not different. Summary Although intravitreous aflibercept injections reduce the risk of VTCs in eyes with moderate-to-severe NPDR, the absence of visual acuity benefits supports the need for four-year results.

We report on a design-based research study that was conducted over three iterations. It chronicles the design, development, and implementation of School Scene Investigators, a forensic science game series for middle school students that utilizes mobile augmented reality. Played on mobile devices while exploring the school environment, School Scene Investigators embeds scientific practices in a real-world context. Students work collaboratively playing unique, interdependent roles as they collect and analyze scientific data in order to solve a mystery. School Scene Investigators aims to (1) engage students through the experience of flow, a positive psychological state often experienced during well-designed games and (2) trigger science interest. In order to better understand how to design mobile game environments that engage students in flow and trigger their interest in science, we analyzed students’ self-reports of flow and interest after playing the game. Previous research demonstrated that each iteration of School Scene Investigators engaged students in a substantive flow-like experience. In this study, since engagement does not guarantee interest, we tested whether such engagement, measured as flow, was predictably related to triggered science interest. Data were pooled from all three iterations into a Bayesian multilevel model. Findings demonstrated that students with higher flow had a higher probability of triggered interest. Implications for the findings are discussed.

Purpose: This work evaluated the use and type of dietary supplements and home monitoring for nonneovascular age-related macular degeneration (AMD), as well as the prevalence of genetic testing among patients with AMD. Methods: A cross-sectional study was conducted of 129 participants older than 50 years who completed self-administered questionnaires regarding usage and type of dietary supplements and home monitoring, as well as the participants’ use of genetic testing for AMD. Results: Of 91 participants with AMD, 83 (91.2%) took vitamins, including 55 (60.4%) who used an Age-Related Eye Disease Study (AREDS) or AREDS2 formulation. Of 38 without AMD, 31 (81.6%) took vitamins (difference from participants with AMD = 9.6% [95% CI, 0%-23.2%]), including 2 on an AREDS formulation. Among 82 participants with AMD who were AREDS candidates (intermediate or advanced AMD in 1 or both eyes), 51 (62.2%; 95% CI, 51.7%-72.7%) took an AREDS or AREDS2 formulation, and 31 (37.8%) did not (5 were unsure). Additionally, 50 (61.0%; 95% CI, 50.4%-71.6%) AREDS candidates did some type of home monitoring. Only 1 (1.2%; 95% CI, 0%-3.6%) underwent genetic testing for AMD. Among 9 with AMD who were not AREDS candidates, 4 (44.4%) used an AREDS formulation, 4 (44.4%) did not, and 1 (11.1%) was unsure; only 1 (11.1%) of these 9 performed home monitoring. Conclusions: Despite similar results from past surveys and AREDS2 data supporting supplement use in 2013 and home monitoring in 2014, these findings suggest about one-third of AREDS candidates do not do so, providing further support for improving education regarding appropriate supplement and home monitoring usage. Genetic testing for AMD also appears infrequent.

Society's serious problems require creative thinkers. Developing an effective workforce relies on cultivating our children's creativity. Unfortunately, we are suffering a creativity crisis, particularly with young children. Since 1990, early elementary students have suffered the largest decrease in creative thinking capacity. Rather than learning through play, young children are taught by rote and tested extensively. Play is indispensable for early learners; without play, students are missing an essential element of early learning that stimulates creative thinking. To promote play, elementary teachers should be trained in maker-centered teaching, a playful approach to learning that embodies the essential elements of STEM education. To truly integrate maker-centered learning, there is a critical need for effective maker-centered professional development. Maker-centered teaching provides playful learning where young children can experience STEM and learn to think more creatively. With maker-centered teaching, we can make the next generation of innovators.

Society needs creative problem solvers to work towards solutions of complex global issues such as climate change. Design thinking is a way to solve problems creatively. Unfortunately, in-service teachers are largely unfamiliar with design thinking and their students rarely engage in design thinking during class. To familiarize teachers with design thinking, this study provided three teacher cohorts with a game design experience. Utilizing a predefined game design document, participants designed an educational game. To experience a thorough design cycle, teachers worked through two iterations of their design. Using a pre- and post-survey, this exploratory study empirically examined whether teachers gained an understanding of design thinking. Results indicated that the game design experience worked well to improve overall design perceptions; the results showed a consistent, positive trend. Specifically, two of the three cohorts had statistically significant differences (p

We characterized common exposures reported by a convenience sample of 202 US patients with coronavirus disease during January–April 2020 and identified factors associated with presumed household transmission. The most commonly reported settings of known exposure were households and healthcare facilities; among case-patients who had known contact with a confirmed case-patient compared with those who did not, healthcare occupations were more common. Among case-patients without known contact, use of public transportation was more common. Within the household, presumed transmission was highest from older (>65 years) index case-patients and from children to parents, independent of index case-patient age. These findings may inform guidance for limiting transmission and emphasize the value of testing to identify community-acquired infections.

The purpose of this study was to identify the underlying cognitive attributes used during the design and development of science-based serious educational games. Study methods rely on a modification of cognitive diagnostics, item response theory, and Bayesian estimation with traditional statistical techniques such as factor analysis and model fit analysis to examine the data and model structure. A computational model of the cognitive processing using an artificial neural network (ANN) allowed for examination of underlying mechanisms of cognition from a server-side data set and a 21st century skills assessment. ANN results indicate that the model correctly predicts successful completion of science-based serious educational game (SEG) design tasks related to 21st century skills 86% of the time and correctly predicts failure to complete SEG design tasks related to 21st century skills 78% of the time. The model also reveals the relative importance of each particular cognitive attribute within the 21st century skills framework.

Purpose of review To review four recent controversial topics arising from deep learning applications in ophthalmology. Recent findings The controversies of four recent topics surrounding deep learning applications in ophthalmology are discussed, including the following: lack of explainability, limited generalizability, potential biases and protection of patient confidentiality in large-scale data transfer. Summary These controversial issues spanning the domains of clinical medicine, public health, computer science, ethics and legal issues, are complex and likely will benefit from an interdisciplinary approach if artificial intelligence in ophthalmology is to succeed over the next decade.

To investigate whether anti-vascular endothelial growth factor (anti-VEGF) for diabetic macular edema or proliferative diabetic retinopathy (PDR) increases the risk of traction retinal detachment (TRD) among eyes with PDR.Pooled analysis of PDR eyes from Protocols I, J, N, S, or T with Early Treatment Diabetic Retinopathy Study level ≥61 (prompt vitrectomy was not planned) randomly assigned to the control group (laser photocoagulation, sham, or intravitreal saline; 396 eyes) or anti-VEGF (487 eyes). The primary outcome was investigator-identified TRD within 1 year of randomization.The 1-year cumulative probability of TRD was 6.8% (95% confidence interval: 4.6%-9.9%, 25 events) in control-group eyes and 4.8% (95% confidence interval: 3.2%-7.3%, 22 events) in anti-VEGF group eyes (hazard ratio = 0.95 [95% confidence interval: 0.54-1.66, P = 0.86]). The cumulative probability of vitrectomy for TRD was 4.4% (16 events) in control-group eyes and 2.2% (9 events) in anti-VEGF group eyes (P = 0.19). Percentage with TRD and vitrectomy for TRD were similar within strata of diabetic retinopathy severity.These findings do not support the hypothesis that anti-VEGF therapy for diabetic macular edema or PDR increases the risk of TRD among eyes with PDR similar to those enrolled in five DRCR Retina Network protocols for which prompt vitrectomy was not planned.