Understanding network meta-analysis methodology for the ophthalmologist.

PURPOSE OF REVIEW: Over the past decade, the number of studies published using network meta-analyses (NMAs) has rapidly increased, and there have been continued advancements to further advance this analysis approach. Due to the fast moving and changing landscape in the infancy of NMA methodology, there is a lack of consistency and standardization for this approach. This article aims to summarize the crucial components of an NMA for both future readers, and for potential NMA authors. RECENT FINDINGS: Key components of NMAs include, but are not limited to, reporting the proposed analysis methods, assessment of risk of bias within the included studies, reporting the overall quality of the available evidence, and defining the parameters in which the results will be presented. Although NMA allows for a comprehensive evaluation of all available treatment options for a given condition, we believe that there is importance in ensuring clear understanding and appropriate interpretation of results to inform clinical practice. SUMMARY: While many components of NMA mirror those of traditional pairwise meta-analysis, there are many novel methodologies that are specific to this approach. It is imperative that future NMAs follow guidance from key methodology groups, as these provide valuable tools for conducting and reporting NMAs.

An unexpected turn: a case of torsional anomalous retinal correspondence after myectomy of previously anteriorized inferior oblique muscles in a child.

We report a case of torsional diplopia caused by presumed torsional anomalous retinal correspondence after myectomy of previously asymmetrically anteriorized inferior oblique muscles for inferior oblique overaction. Given this patient's experience, it may be prudent to operate with caution on previously anteriorized inferior oblique muscles, especially when anteriorization is performed at a very young age.

Genomewide architecture of adaptation in experimentally evolved Drosophila characterized by widespread pleiotropy.

Dissecting the molecular basis of adaptation remains elusive despite our ability to sequence genomes and transcriptomes. At present, most genomic research on selection focusses on signatures of selective sweeps in patterns of heterozygosity. Other research has studied changes in patterns of gene expression in evolving populations but has not usually identified the genetic changes causing these shifts in expression. Here we attempt to go beyond these approaches by using machine learning tools to explore interactions between the genome, transcriptome, and life-history phenotypes in two groups of 10 experimentally evolved Drosophila populations subjected to selection for opposing life history patterns. Our findings indicate that genomic and transcriptomic data have comparable power for predicting phenotypic characters. Looking at the relationships between the genome and the transcriptome, we find that the expression of individual transcripts is influenced by many sites across the genome that are differentiated between the two types of populations. We find that single-nucleotide polymorphisms (SNPs), transposable elements, and indels are powerful predictors of gene expression. Collectively, our results suggest that the genomic architecture of adaptation is highly polygenic with extensive pleiotropy.

Anti-vascular endothelial growth factor therapy and retinal non-perfusion in diabetic retinopathy: A meta-analysis of randomised trials.

PURPOSE: Retinal non-perfusion (RNP) is fundamental to disease onset and progression in diabetic retinopathy (DR). Whether anti-vascular endothelial growth factor (anti-VEGF) therapy can modify RNP progression is unclear. This investigation quantified the impact of anti-VEGF therapy on RNP progression compared with laser or sham at 12 months. METHODS: A systematic review and meta-analysis of randomised controlled trials (RCTs) were performed; Ovid MEDLINE, EMBASE and CENTRAL were searched from inception to 4th March 2022. The change in any continuous measure of RNP at 12 months and 24 months was the primary and secondary outcomes, respectively. Outcomes were reported utilising standardised mean differences (SMD). The Cochrane Risk of Bias Tool version-2 and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines informed risk of bias and certainty of evidence assessments. RESULTS: Six RCTs (1296 eyes) and three RCTs (1131 eyes) were included at 12 and 24 months, respectively. Meta-analysis demonstrated that RNP progression may be slowed with anti-VEGF therapy compared with laser/sham at 12 months (SMD: -0.17; 95% confidence interval [CI]: -0.29, -0.06; p = 0.003; I2 = 0; GRADE rating: LOW) and 24-months (SMD: -0.21; 95% CI: -0.37, -0.05; p = 0.009; I2 = 28%; GRADE rating: LOW). The certainty of evidence was downgraded due to indirectness and due to imprecision. CONCLUSION: Anti-VEGF treatment may slightly impact the pathophysiologic process of progressive RNP in DR. The dosing regimen and the absence of diabetic macular edema may impact this potential effect. Future trials are needed to increase the precision of the effect and inform the association between RNP progression and clinically important events. PROSPERO REGISTRATION: CRD42022314418.

Subthreshold Compared with Threshold Macular Photocoagulation for Diabetic Macular Edema: A Systematic Review and Meta-Analysis.

TOPIC: To compare the efficacy and safety of subthreshold macular laser to conventional focal laser photocoagulation for the treatment of vision loss secondary to diabetic macular edema (DME). CLINICAL RELEVANCE: Macular laser remains an important and cost effective treatment option for vision loss secondary to DME. Although anti-VEGF therapy is often first-line, macular laser is of utility in low-resource or remote settings, for patients at risk of loss to follow-up, and for DME not meeting country-specific reimbursement criteria for anti-VEGF therapy. Subthreshold laser is a modality that does not produce clinical or histologic evidence of thermal damage, thereby potentially limiting the common complications of conventional laser. METHODS: Ovid MEDLINE, EMBASE, and CENTRAL databases were searched for randomized controlled trials (RCTs) from inception to September 28, 2022. Meta-analyses were performed using random-effects modeling. Data were collected at 12 and 24 months for best-corrected visual acuity (BCVA), central retinal thickness, diabetic retinopathy severity scale, rate of adverse events, rate of enrolled patients not completing treatment, rate of patients receiving retreatment, and quality-of-life measures. The risk of bias and certainty of evidence were assessed using Cochrane's Risk-of-Bias version 2 and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) frameworks, respectively. Subgroup analysis was performed between subthreshold laser modalities and evaluated with Instrument to assess the Credibility of Effect Modification Analyses tool. RESULTS: Fourteen RCTs comprising 514 eyes receiving conventional laser and 574 eyes receiving subthreshold laser were included. Subthreshold laser likely results in no difference to BCVA (moderate GRADE certainty) compared with conventional laser. Conventional laser demonstrated a small, statistically significant improvement in central retinal thickness (low GRADE certainty); however, the magnitude of this improvement is unlikely to be clinically important. There may not be a difference in the rate of adverse events (low GRADE certainty) at 12 months when comparing subthreshold laser to conventional laser for DME. CONCLUSION: Randomized controlled trial literature to date suggests subthreshold laser to be as effective as conventional laser in the treatment of DME. Increased follow-up duration is needed to observe any long-term safety benefit from reduced retinal damage. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Extreme coronary radiation doses from intravascular brachytherapy.

PURPOSE: To evaluate coronary artery integrity after very high radiation doses from intravascular brachytherapy (IVBT) in the setting of source asymmetry. METHODS: Ten patients treated for right coronary artery (RCA) in-stent restenosis (ISR) between 2017 and 2021 and for whom follow-up angiograms were available were identified from departmental records. Procedural angiograms, taken to document source position, were used to estimate vascular wall doses. The 2.5 mm proximal source marker was used to estimate the distance from source center to the media and adventitia. Distances were converted to dose (Gy) using the manufacturers' dose fall-off table, measured in water. Follow-up films were scrutinized for any sign of late vascular damage. RESULTS: The average minimal distance from catheter center to the adjacent media and the adventitia was 0.9 mm (±0.2) mm and 1.4 mm (±0.2), respectively. The average maximum media and adventitial doses adjacent to the source were 75 Gy (±26) and 39 Gy (±14), respectively. Follow-up angiograms were available from 0.6 years to 3.9 years following IVBT (median: 1.6 years). No IVBT-treated vascular segment showed signs of degeneration, dissection or aneurysm. CONCLUSION: IVBT vascular wall doses are frequently far higher than prescribed. The lack of complications in this unselected group of patients gives a modicum of reassurance that raising the prescription dose is unlikely to lead to a sudden appearance of complications.

Health Economic Assessments of Hyaluronic Acid Treatments for Knee Osteoarthritis: A Systematic Review.

INTRODUCTION: Hyaluronic acid (HA) use to treat knee osteoarthritis (OA) has been extensively investigated in the literature. There are also multiple economic assessments comparing intra-articular HAs with oral anti-inflammatory medicines and other conservative measures (NSAIDs), as well as different types and formulations of HA. Owing to the broad landscape of evidence across this area, it is important to further understand the empirical data comparing HA products, as well as the health economic implications that exist between commercially available HAs. This systematic review aims to identify and summarize the available evidence comparing commercially available HA products in the USA, as well as the health economic evidence and socioeconomic outcomes associated with HA use for knee OA. METHODS: A systematic literature review within the OVID Medline, Embase, HealthStar, and Cochrane EBM HTA databases was conducted. Articles were screened for eligibility, and a qualitative summary of the findings was provided based on specific themes: (1) trials comparing the safety and/or efficacy of two or more HA products in knee OA, (2) economic/cost analyses of HA use in knee OA, and (3) studies investigating healthcare resource utilization in patients treated with HA for knee OA. RESULTS: The search strategy identified 398 studies, 27 of which were deemed eligible: 21 health economic analyses with US relevance and six head-to-head trials of HA products available in the USA, cumulatively assessing 5,782,156 patients with knee OA. The evidence demonstrates a clear distinction between high and low molecular weight HAs, as both efficacy and cost analyses provided favorable results for the high molecular weight options. In all but one cost analysis, HA use was a cost-effective option when compared to routine nonoperative care, captured in administrative databases, which typically included NSAID use and/or corticosteroids. HA saw benefits in delaying the need for total knee arthroplasty (TKA), decreasing the use of rescue medication, and limiting the need for additional corticosteroid injection. The included evidence highlights that the treatment's cost-effectiveness is improved when HA is utilized in earlier stages of the disease, as opposed to when HA is reserved for late stages of knee OA. Additionally, among HAs, Bio-HA and Hylan G-F 20 evidence made up the majority of available literature with beneficial efficacy and cost outcomes. Head-to-head evidence between them indicated similar pain outcomes; however, Bio-HA required less rescue with acetaminophen and had fewer joint effusions in this comparison. CONCLUSIONS: The available efficacy and safety data as well as health economic analyses on the use of HA for knee OA management suggest that there are economic benefits of this treatment option. From a healthcare system perspective, the body of HA literature summarizes favorable costs profile, decreased opioid and corticosteroid use as rescue medication, and a delay to the need for TKA in patients who have HA included in their treatment regimen.

Human Heart Failure Alters Mitochondria and Fiber 3D Structure Triggering Metabolic Shifts.

This study, utilizing SBF-SEM, reveals structural alterations in mitochondria and myofibrils in human heart failure (HF). Mitochondria in HF show changes in structure, while myofibrils exhibit increased cross-sectional area and branching. Metabolomic and lipidomic analyses indicate concomitant dysregulation in key pathways. The findings underscore the need for personalized treatments considering individualized structural changes in HF.

3D reconstruction of murine mitochondria reveals changes in structure during aging linked to the MICOS complex.

During aging, muscle gradually undergoes sarcopenia, the loss of function associated with loss of mass, strength, endurance, and oxidative capacity. However, the 3D structural alterations of mitochondria associated with aging in skeletal muscle and cardiac tissues are not well described. Although mitochondrial aging is associated with decreased mitochondrial capacity, the genes responsible for the morphological changes in mitochondria during aging are poorly characterized. We measured changes in mitochondrial morphology in aged murine gastrocnemius, soleus, and cardiac tissues using serial block-face scanning electron microscopy and 3D reconstructions. We also used reverse transcriptase-quantitative PCR, transmission electron microscopy quantification, Seahorse analysis, and metabolomics and lipidomics to measure changes in mitochondrial morphology and function after loss of mitochondria contact site and cristae organizing system (MICOS) complex genes, Chchd3, Chchd6, and Mitofilin. We identified significant changes in mitochondrial size in aged murine gastrocnemius, soleus, and cardiac tissues. We found that both age-related loss of the MICOS complex and knockouts of MICOS genes in mice altered mitochondrial morphology. Given the critical role of mitochondria in maintaining cellular metabolism, we characterized the metabolomes and lipidomes of young and aged mouse tissues, which showed profound alterations consistent with changes in membrane integrity, supporting our observations of age-related changes in muscle tissues. We found a relationship between changes in the MICOS complex and aging. Thus, it is important to understand the mechanisms that underlie the tissue-dependent 3D mitochondrial phenotypic changes that occur in aging and the evolutionary conservation of these mechanisms between Drosophila and mammals.

The effect of complement C3 or C5 inhibition on geographic atrophy secondary to age-related macular degeneration: A living systematic review and meta-analysis.

With the introduction of therapies to treat geographic atrophy (GA), GA management in clinical practice is now possible. A living systematic review can provide access to timely and robust evidence synthesis. This review found that complement factor 3 and 5 (C3 and C5) inhibition compared to sham likely reduces change in square root GA area at 12 months and untransformed GA area at 24 months. There is likely little to no difference in the rate of systemic treatment-emergent adverse events compared to sham. C3 and C5 inhibition, however, likely does not improve best-corrected visual acuity (BCVA) at 12 months, and the evidence is uncertain regarding change in BCVA at 24 months. Higher rates of ocular treatment emergent adverse effects with complement inhibition occur at 12 months and likely at 24 months. Complement inhibition likely results in new onset neovascular age-related macular degeneration at 12 months. This living meta-analysis will continuously incorporate new evidence.

Impact of environmental oxygen on nanoparticle formation and agglomeration in aluminum laser ablation plumes.

The role of ambient oxygen gas (O2) on molecular and nanoparticle formation and agglomeration was studied in laser ablation plumes. As a lab-scale surrogate to a high explosion detonation event, nanosecond laser ablation of an aluminum alloy (AA6061) target was performed in atmospheric pressure conditions. Optical emission spectroscopy and two mass spectrometry techniques were used to monitor the early to late stages of plasma generation to track the evolution of atoms, molecules, clusters, nanoparticles, and agglomerates. The experiments were performed under atmospheric pressure air, atmospheric pressure nitrogen, and 20% and 5% O2 (balance N2), the latter specifically with in situ mass spectrometry. Electron microscopy was performed ex situ to identify crystal structure and elemental distributions in individual nanoparticles. We find that the presence of ≈20% O2 leads to strong AlO emission, whereas in a flowing N2 environment (with trace O2), AlN and strong, unreacted Al emissions are present. In situ mass spectrometry reveals that as O2 availability increases, Al oxide cluster size increases. Nanoparticle agglomerates formed in air are found to be larger than those formed under N2 gas. High-resolution transmission electron microscopy demonstrates that Al2O3 and AlN nanoparticle agglomerates are formed in both environments; indicating that the presence of trace O2 can lead to Al2O3 nanoparticle formation. The present results highlight that the availability of O2 in the ambient gas significantly impacts spectral signatures, cluster size, and nanoparticle agglomeration behavior. These results are relevant to understanding debris formation in an explosion event, and interpreting data from forensic investigations.

Cost-effectiveness analysis of the Geriatric Fracture Center (GFC) concept: a prospective multicentre cohort study.

INTRODUCTION: Geriatric Fracture Centers (GFCs) are dedicated treatment units where care is tailored towards elderly patients who have suffered fragility fractures. The primary objective of this economic analysis was to determine the cost-utility of GFCs compared with usual care centres. METHODS: The primary analysis was a cost-utility analysis that measured the cost per incremental quality-adjusted life-year gained from treatment of hip fracture in GFCs compared with treatment in usual care centres from the societal perspective over a 1-year time horizon. The secondary analysis was a cost-utility analysis from a societal perspective over a lifetime time horizon. We evaluated these outcomes using a cost-utility analysis using data from a large multicentre prospective cohort study comparing GFCs versus usual care centres that took place in Austria, Spain, the USA, the Netherlands, Thailand and Singapore. RESULTS: GFCs may be cost-effective in the long term, while providing a more comprehensive care plan. Patients in usual care centre group were slightly older and had fewer comorbidities. For the 1-year analysis, the costs per patient were slightly lower in the GFC group (-$646.42), while the quality-adjusted life-years were higher in the usual care centre group (+0.034). The incremental cost-effectiveness ratio was $18 863.34 (US$/quality-adjusted life-year). The lifetime horizon analysis found that the costs per patient were lower in the GFC group (-$7210.35), while the quality-adjusted life-years were higher in the usual care centre group (+0.02). The incremental cost-effectiveness ratio was $320 678.77 (US$/quality-adjusted life-year). CONCLUSIONS: This analysis found that GFCs were associated with lower costs compared with usual care centres. The cost-savings were greater when the lifetime time horizon was considered. This comprehensive cost-effectiveness analysis, using data from an international prospective cohort study, found that GFC may be cost-effective in the long term, while providing a more comprehensive care plan. A greater number of major adverse events were reported at GFC, nevertheless a lower mortality rate associated with these adverse events at GFC. Due to the minor utility benefits, which may be a result of greater adverse event detection within the GFC group and much greater costs of usual care centres, the GFC may be cost-effective due to the large cost-savings it demonstrated over the lifetime time horizon, while potentially identifying and treating adverse events more effectively. These findings suggest that the GFC may be a cost-effective option over the lifetime of a geriatric patient with hip fracture, although future research is needed to further validate these findings. LEVEL OF EVIDENCE: Economic, level 2. TRIAL REGISTRATION NUMBER: NCT02297581.

H2O and temperature measurements in propagating hydrogen/oxygen flames using a broadband swept-wavelength ECQCL.

We present experimental results using a swept-wavelength external cavity quantum cascade laser (swept-ECQCL) diagnostic to measure broadband absorption spectra over a range of 920-1180c m -1 (8.47-10.87 µm) with 2 ms temporal resolution in premixed hydrogen/oxygen flames propagating inside an enclosed chamber. Broadband spectral fits are used to determine time-resolved temperatures and column densities of H 2 O produced during combustion. Modeling of the flowfield within the test chamber under both equilibrium conditions and using a 1D freely propagating flame model is compared with the experiment in terms of temporal dynamics, temperatures, and H 2 O column density. Outputs from the numerical models were used to simulate radiative transport through an inhomogeneous combustion region and evaluate the performance of the spectral fitting model. Simulations show that probing hot-band H 2 O transitions in the high-temperature combustion regions minimizes errors due to spatial inhomogeneity. Good agreement is found between the experimental and modeling results considering experimental uncertainties and model assumptions.

Nebulized Recombinant Tissue Plasminogen Activator (rt-PA) for Acute COVID-19-Induced Respiratory Failure: An Exploratory Proof-of-Concept Trial.

Acute lung injury in COVID-19 results in diffuse alveolar damage with disruption of the alveolar-capillary barrier, coagulation activation, alveolar fibrin deposition and pulmonary capillary thrombi. Nebulized recombinant tissue plasminogen activator (rt-PA) has the potential to facilitate localized thrombolysis in the alveolar compartment and improve oxygenation. In this proof-of-concept safety study, adults with COVID-19-induced respiratory failure and a <300 mmHg PaO2/FiO2 (P/F) ratio requiring invasive mechanical ventilation (IMV) or non-invasive respiratory support (NIRS) received nebulized rt-PA in two cohorts (C1 and C2), alongside standard of care, between 23 April-30 July 2020 and 21 January-19 February 2021, respectively. Matched historical controls (MHC; n = 18) were used in C1 to explore efficacy. Safety co-primary endpoints were treatment-related bleeds and <1.0-1.5 g/L fibrinogen reduction. A variable dosing strategy with clinical efficacy endpoint and minimal safety concerns was determined in C1 for use in C2; patients were stratified by ventilation type to receive 40-60 mg rt-PA daily for ≤14 days. Nine patients in C1 (IMV, 6/9; NIRS, 3/9) and 26 in C2 (IMV, 12/26; NIRS, 14/26) received nebulized rt-PA for a mean (SD) of 6.7 (4.6) and 9.1(4.6) days, respectively. Four bleeds (one severe, three mild) in three patients were considered treatment related. There were no significant fibrinogen reductions. Greater improvements in mean P/F ratio from baseline to study end were observed in C1 compared with MHC (C1; 154 to 299 vs. MHC; 154 to 212). In C2, there was no difference in the baseline P/F ratio of NIRS and IMV patients. However, a larger improvement in the P/F ratio occurred in NIRS patients (NIRS; 126 to 240 vs. IMV; 120 to 188) and fewer treatment days were required (NIRS; 7.86 vs. IMV; 10.5). Nebulized rt-PA appears to be well-tolerated, with a trend towards improved oxygenation, particularly in the NIRS group. Randomized clinical trials are required to demonstrate the clinical effect significance and magnitude.

Improved safety and quality in intravascular brachytherapy: A multi-institutional study using failure modes and effects analysis.

PURPOSE: Highlight safety considerations in intravascular brachytherapy (IVBT) programs, provide relevant quality assurance (QA) and safety measures, and establish their effectiveness. METHODS AND MATERIALS: Radiation oncologists, medical physicists, and cardiologists from three institutions performed a failure modes and effects analysis (FMEA) on the radiation delivery portion of IVBT. We identified 40 failure modes and rated the severity, occurrence, and detectability before and after consideration of safety practices. Risk priority numbers (RPN) and relative risk rankings were determined, and a sample QA safety checklist was developed. RESULTS: We developed a process map based on multi-institutional consensus. Highest-RPN failure modes were due to incorrect source train length, incorrect vessel diameter, and missing prior radiation history. Based on these, we proposed QA and safety measures: ten of which were not previously recommended. These measures improved occurrence and detectability: reducing the average RPN from 116 to 58 and median from 84 to 40. Importantly, the average RPN of the top 10% of failure modes reduced from 311 to 172. With QA considered, the highest risk failure modes were from contamination and incorrect source train length. CONCLUSIONS: We identified several high-risk failure modes in IVBT procedures and practical safety and QA measures to address them.

Three-dimensional mitochondria reconstructions of murine cardiac muscle changes in size across aging.

With sparse treatment options, cardiac disease remains a significant cause of death among humans. As a person ages, mitochondria breakdown and the heart becomes less efficient. Heart failure is linked to many mitochondria-associated processes, including endoplasmic reticulum stress, mitochondrial bioenergetics, insulin signaling, autophagy, and oxidative stress. The roles of key mitochondrial complexes that dictate the ultrastructure, such as the mitochondrial contact site and cristae organizing system (MICOS), in aging cardiac muscle are poorly understood. To better understand the cause of age-related alteration in mitochondrial structure in cardiac muscle, we used transmission electron microscopy (TEM) and serial block facing-scanning electron microscopy (SBF-SEM) to quantitatively analyze the three-dimensional (3-D) networks in cardiac muscle samples of male mice at aging intervals of 3 mo, 1 yr, and 2 yr. Here, we present the loss of cristae morphology, the inner folds of the mitochondria, across age. In conjunction with this, the three-dimensional (3-D) volume of mitochondria decreased. These findings mimicked observed phenotypes in murine cardiac fibroblasts with CRISPR/Cas9 knockout of Mitofilin, Chchd3, Chchd6 (some members of the MICOS complex), and Opa1, which showed poorer oxidative consumption rate and mitochondria with decreased mitochondrial length and volume. In combination, these data show the need to explore if loss of the MICOS complex in the heart may be involved in age-associated mitochondrial and cristae structural changes.NEW & NOTEWORTHY This article shows how mitochondria in murine cardiac changes, importantly elucidating age-related changes. It also is the first to show that the MICOS complex may play a role in outer membrane mitochondrial structure.

Understanding the Learning Curve of Carpal Tunnel Release With Ultrasound Guidance: A Review.

Carpal tunnel syndrome (CTS) is the most common compressive neuropathy and can be treated through carpal tunnel release (CTR) if nonoperative treatments fail. CTR can be performed through a variety of techniques, including traditional open, mini-open, endoscopic, and CTR with ultrasound guidance (CTR-US). The evidence on endoscopic CTR is mixed, due to a higher potential for nerve injury with endoscopic CTR compared to traditional open CTR. CTR-US offers the potential advantage of allowing the visualization of all key anatomical structures, combined with a very small incision and minimal soft tissue insult. As with any ultrasonographic technique or procedure, the learning curve needs to be considered for any provider considering adopting CTR-US. However, literature on ultrasound use around the wrist, including early evidence on the learning curve of CTR-US specifically, demonstrates this skill can be learned relatively quickly by providers with a wide range of prior experience in ultrasound and CTR. Overall, there is a need for high-quality studies comparing different CTR techniques, particularly CTR-US, as it offers the potential for considerable cost savings.

Patient-Reported Outcome Measure Use in Guidelines Published by the American Academy of Ophthalmology: A Review.

TOPIC: We reviewed the use of patient-reported outcome measures (PROMs) in the treatment of ophthalmologic conditions as recommended by the Clinical Practice Guidelines (CPGs) published by the American Academy of Ophthalmology (AAO). CLINICAL RELEVANCE: Patient-reported outcome measures are standardized instruments that provide information regarding a patient's health status or health-related quality of life. Patient-reported outcome measures are increasingly used to inform study end points in ophthalmology studies. However, the extent to which PROMs are ultimately informing patient management recommendations in ophthalmology as part of CPGs remains an area of evidence gap. METHODS: We included all CPGs published by the AAO from inception to June 2022. We also included all primary studies and systematic reviews cited in the treatment sections of the CPGs evaluating treatment of an ophthalmic condition. The primary outcome was the frequency of PROMs discussed in CPGs and in cited studies evaluating treatment. Secondary outcomes included frequency of minimal important difference (MID) use to contextualize PROM results and percentage of strong and discretionary recommendations supported by PROMs. We published a study protocol a priori on PROSPERO (CRD42022307427). Reporting followed the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. We assessed risk of bias using the Appraisal of Guidelines, Research and Evaluation II (AGREE II) instrument. RESULTS: We identified 24 eligible CPGs, providing 2458 cited studies (2191 primary, 267 secondary) evaluating treatment of eye conditions. Ten CPGs (41.7%) reported consideration of PROMs. Of these, 31 of 94 (33%) recommendations were informed by studies evaluating a PROM as an outcome. Across all studies cited in the development of CPGs, 221 (9.0%) used PROMs as a primary or secondary outcome, of which 4 PROM results (1.8%) were interpreted using an empirically determined MID. Overall, the risk of bias was low for all CPGs. CONCLUSIONS: Overall, outcomes of PROMs are seldom used in ophthalmology CPGs published by the AAO and in cited primary and secondary research on treatments. When PROMs were considered, their interpretation was seldom based on an MID. To improve patient care, guideline developers may consider incorporating PROMs and applicable MIDs to inform key outcomes when formulating treatment recommendations. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Asian Americans in STEM are not a monolith.

Despite tremendous diversity, Asian Americans in STEM are grouped and viewed as a homogeneous monolith, facing stereotypes and disparities. We propose solutions that include disaggregating the Asian American grouping and recognizing the diverse individual ethnic subgroups that comprise Americans of Asian ancestry to implement change within the STEM field.