Real-World Treatment Patterns and Clinical Outcomes Among Patients with Metastatic or Unresectable EGFR-Mutated Non-Small Cell Lung Cancer Previously Treated with Osimertinib and Platinum-Based Chemotherapy.

INTRODUCTION: For patients with epidermal growth factor receptor-mutated (EGFRm) locally advanced/metastatic non-small cell lung cancer (mNSCLC) whose disease has progressed on or after osimertinib and platinum-based chemotherapy (PBC), no uniformly accepted standard of care exists. Moreover, limited efficacy of standard treatments indicates an unmet medical need, which is being addressed by ongoing clinical investigations, including the HERTHENA-Lung01 (NCT04619004) study of patritumab deruxtecan (HER3­DXd). However, because limited information is available on real-world clinical outcomes in such patients, early-phase trials of investigational therapies lack sufficient context for comparison. This study describes the real-world clinical characteristics, treatments, and outcomes for patients with EGFRm mNSCLC who initiated a new line of therapy following previous osimertinib and PBC, including a subset matched to the HERTHENA-Lung01 population. METHODS: This retrospective analysis used a US database derived from deidentified electronic health records. The reference cohort included patients with EGFRm mNSCLC who had initiated a new line of therapy between November 13, 2015 and June 30, 2021, following prior osimertinib and PBC. A subset of patients resembling the HERTHENA-Lung01 population was then extracted from the reference cohort; this matched subset was optimized using propensity score (PS) weighting. Endpoints were real-world overall survival (rwOS) and real-world progression-free survival (rwPFS). Confirmed real-world objective response rate (rwORR; partial/complete response confirmed ≥ 28 days later) was calculated for the response-evaluable subgroups of patients (with ≥ 2 response assessments spaced ≥ 28 days apart). RESULTS: In the reference cohort (N = 273), multiple treatment regimens were used, and none was predominant. Median rwPFS and rwOS were 3.3 and 8.6 months, respectively; confirmed rwORR (response evaluable, n = 123) was 13.0%. In the matched subset (n = 126), after PS weighting, median rwPFS and rwOS were 4.2 and 9.1 months, respectively; confirmed rwORR (response evaluable, n = 57) was 14.1%. CONCLUSION: The treatment landscape for this heavily pretreated population of patients with EGFRm mNSCLC is fragmented, with no uniformly accepted standard of care. A high unmet need exists for therapeutic options that provide meaningful improvements in clinical benefit.

In-vivo high-frequency quantitative ultrasound-derived parameters of the anterior sclera correlated with level of myopia and presence of staphyloma.

BACKGROUND: A high-frequency point-of-care (POC) ultrasound instrument was used to evaluate the microstructural and biomechanical properties of the anterior sclera in vivo using parameters computed from quantitative ultrasound (QUS) methods. METHODS: In this cross-sectional study, both eyes of 85 enrolled patients were scanned with the POC instrument and ultrasound data were processed to obtain QUS parameters. Pearson correlation and multi-linear regression were used to identify relationships between QUS parameters and refractive error (RE) or axial length. After categorising eyes based on RE, binary support vector machine (SVM) classifiers were trained using the QUS or ophthalmic parameters (anterior chamber depth, central corneal thickness, corneal power, and intraocular pressure) to classify each eye. Classifier performance was evaluated by computing the area under the receiver-operating characteristic curve (AUC). RESULTS: Individual QUS parameters correlated with RE and axial length (p < 0.05). Multi-linear regression revealed significant correlation between the set of QUS parameters and both RE (R = 0.49, p < 0.001) and axial length (R = 0.46, p = 0.001). Classifiers trained with QUS parameters achieved higher AUC (𝑝 = 0.06) for identifying myopic eyes (AUC = 0.71) compared to classifiers trained with ophthalmic parameters (AUC = 0.63). QUS-based classifiers attained the highest AUC when identifying highly myopic eyes (AUC = 0.77). CONCLUSIONS: QUS parameters correlate with progressing myopia and may be indicative of myopia-induced microstructural and biomechanical changes in the anterior sclera. These methods may provide critical clinical information complementary to standard ophthalmic measurements for predicting myopia progression and risk assessment for posterior staphyloma formation.

Single Intravenous Dose Dalbavancin Pathway for the Treatment of Acute Bacterial Skin and Skin Structure Infections: Considerations for Emergency Department Implementation and Cost Savings.

BACKGROUND: A pathway for the treatment of acute bacterial skin and skin structure infections (ABSSSI) with a single intravenous (IV) dose of dalbavancin was previously shown to reduce hospital admissions and shorten inpatient length of stay (LOS). OBJECTIVES: To describe pathway implementation at the emergency department (ED) and evaluate cost-effectiveness of a single-dose dalbavancin administered to ED patients who would otherwise be hospitalized to receive usual care with multidose IV antibiotics. METHODS: The dalbavancin pathway was previously implemented at 11 U.S. EDs (doi:10.1111/acem.14258). Patients with ABSSSI, without an unstable comorbidity or infection complication requiring complex management, were treated with a single dose of dalbavancin. At the emergency physicians' discretion, patients were either discharged and received outpatient follow-up or were hospitalized for continued management. A decision analytic cost-effectiveness model was developed from the U.S. healthcare's perspective to evaluate costs associated with the dalbavancin pathway compared with inpatient usual care. Costs (2021 USD) were modeled over a 14-day horizon and included ED visits, drug costs, inpatient stay, and physician visits. One-way and probabilistic sensitivity analyses examined input parameter uncertainty. RESULTS: Driven largely by the per diem inpatient cost and LOS for usual care, the dalbavancin pathway was associated with savings of $5133.20 per patient and $1211.57 per hospitalization day avoided, compared with inpatient usual care. The results remained robust in sensitivity and scenario analyses. CONCLUSION: The new single-dose dalbavancin ED pathway for ABSSSI treatment, which was previously implemented at 11 U.S. EDs, offers robust cost savings compared to inpatient usual care.

Comparison of manual and artificial intelligence-automated choroidal thickness segmentation of optical coherence tomography imaging in myopic adults.

BACKGROUND: Myopia affects 1.4 billion individuals worldwide. Notably, there is increasing evidence that choroidal thickness plays an important role in myopia and risk of developing myopia-related conditions. With the advancements in artificial intelligence (AI), choroidal thickness segmentation can now be automated, offering inherent advantages such as better repeatability, reduced grader variability, and less reliance for manpower. Hence, we aimed to evaluate the agreement between AI-automated and manual segmented measurements of subfoveal choroidal thickness (SFCT) using two swept-source optical coherence tomography (OCT) systems. METHODS: Subjects aged ≥ 16 years, with myopia of ≥ 0.50 diopters in both eyes, were recruited from the Prospective Myopia Cohort Study in Singapore (PROMYSE). OCT scans were acquired using Triton DRI-OCT and PLEX Elite 9000. OCT images were segmented both automatically with an established SA-Net architecture and manually using a standard technique with adjudication by two independent graders. SFCT was subsequently determined based on the segmentation. The Bland-Altman plot and intraclass correlation coefficient (ICC) were used to evaluate the agreement. RESULTS: A total of 229 subjects (456 eyes) with mean [± standard deviation (SD)] age of 34.1 (10.4) years were included. The overall SFCT (mean ± SD) based on manual segmentation was 216.9 ± 82.7 µm with Triton DRI-OCT and 239.3 ± 84.3 µm with PLEX Elite 9000. ICC values demonstrated excellent agreement between AI-automated and manual segmented SFCT measurements (PLEX Elite 9000: ICC = 0.937, 95% CI: 0.922 to 0.949, P < 0.001; Triton DRI-OCT: ICC = 0.887, 95% CI: 0.608 to 0.950, P < 0.001). For PLEX Elite 9000, manual segmented measurements were generally thicker when compared to AI-automated segmented measurements, with a fixed bias of 6.3 µm (95% CI: 3.8 to 8.9, P < 0.001) and proportional bias of 0.120 (P < 0.001). On the other hand, manual segmented measurements were comparatively thinner than AI-automated segmented measurements for Triton DRI-OCT, with a fixed bias of - 26.7 µm (95% CI: - 29.7 to - 23.7, P < 0.001) and proportional bias of - 0.090 (P < 0.001). CONCLUSION: We observed an excellent agreement in choroidal segmentation measurements when comparing manual with AI-automated techniques, using images from two SS-OCT systems. Given its edge over manual segmentation, automated segmentation may potentially emerge as the primary method of choroidal thickness measurement in the future.

The Spectrum of Relentless Placoid and Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE): Multimodal Imaging Analysis.

PURPOSE: To showcase the spectrum between APMPPE and relentless placoid utilizing ultra-widefield imaging findings of a case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) progressing to relentless placoid chorioretinitis (RPC). METHODS: A 23-year-old Caucasian female presented with worsening vision in both eyes. Clinical examination and multimodal imaging modalities including fundus photos, fundus autofluorescence, fluorescein angiography (FA), indocyanine green angiography (ICGA) and spectral-domain optical coherence tomography and angiography were utilized to diagnose APMPPE and clinically follow the patient. RESULTS: Clinical examination of the patient initially revealed posterior lesions consistent with APMPPE but subsequent multimodal images including ultra-widefield FA and ICGA revealed newer, more peripheral lesions more typical of RPC. CONCLUSION: When compared to standard multimodal imaging, ultra-widefield imaging is an effective tool to delineate nuances between APMPPE and RPC through identification of peripheral lesions, which may be of clinical importance when determining management and therapeutics for patients.

The radical scavenging activity of monocaffeoylquinic acids: the role of neighboring hydroxyl groups and pH levels.

Caffeoylquinic acids (CQAs) are well-known antioxidants. However, a key aspect of their radical scavenging activity - the mechanism of action - has not been addressed in detail thus far. Here we report on a computational study of the mechanism of activity of CQAs in scavenging hydroperoxyl radicals. In water at physiological pH, the CQAs demonstrated ≈ 104 times higher HOO˙ antiradical activity than in lipid medium (k(lipid) ≈ 104 M-1 s-1). The activity in the aqueous solution was determined by the hydrogen transfer mechanism of the adjacent hydroxyl group (O6'-H) of the dianion states (Γ = 93.2-95.2%), while the single electron transfer reaction of these species contributed 4.8-6.8% to the total rate constants. The kinetics estimated by the calculations are consistent with experimental findings in water (pH = 7.5), yielding a kcalculated/kexperimental = 2.4, reinforcing the reliability and precision of the computational method and demonstrating its utility for evaluating radical reactions in silico. The results also revealed the pH dependence of the HOO˙ scavenging activity of the CQAs; activity was comparable for all compounds below pH 3, however at higher pH values 5CQA reacted with the HOO˙ with lower activity than 3CQA or 4CQA. It was also found that CQAs are less active than Trolox below pH 4.7, however over pH 5.0 they showed higher activity than the reference. The CQAs had the best HOO˙ antiradical activity at pH values between 5.0 and 8.6. Therefore, in the physiological environment, the hydroperoxyl antiradical capacity of CQAs exhibits similarity to renowned natural antioxidants including resveratrol, ascorbic acid, and Trolox.

Pathologic myopia in highly myopic patients with high axial anisomyopia.

PURPOSE: To determine prevalence of anisomyopia (axial length (AL) difference ≥2.5 mm) among high myopes ((HMs), defined by spherical equivalent of ≤6.0 diopters or AL ≥ 26.5 mm). To characterise the shorter anisomyopic eye (SAE) and evaluate if pathologic myopia (PM) in the longer anisomyopic eye (LAE) was associated with increased risk of PM in the SAE. METHODS: 1168 HMs were recruited from Singapore National Eye Centre clinic for this cross-sectional study. Biometry, fundus photography and swept-source optical coherence tomography were performed. Patients with high axial anisomyopia were identified. Structural characteristics and presence of PM were described. Stepwise multivariate regression explored associations between PM in the LAE and pathology in the SAE, controlling for confounding variables. RESULTS: Prevalence of anisomyopia was 15.8% (184 of 1168 patients). Anisomyopic patients (age 65.8±13.5 years) had mean AL of 30.6±2.0 mm and 26.2±2.3 mm in the LAE and SAE, respectively. 52.7% of SAEs had AL < 26.5 mm. Prevalence of myopic macular degeneration, macula-involving posterior staphyloma (PS), myopic traction maculopathy (MTM) and myopic choroidal neovascularisation (mCNV) in the SAE was 52.2%, 36.5%, 13.0% and 8.2%, respectively. Macular hole in the LAE was associated with increased risk of MTM in the SAE (OR=4.88, p=0.01). mCNV in the LAE was associated with mCNV in the SAE (OR=3.57, p=0.02). PS in the LAE was associated with PS in the SAE (OR=4.03, p<0.001). CONCLUSIONS: Even when controlled for AL, PM complications in the LAE predict similar PM complications in the SAE. Patients with high axial anisometropia with PM in the LAE should be monitored carefully for complications in the SAE.

ULTRA-WIDEFIELD IMAGING DETECTION RATE IN IDENTIFYING PERIPHERAL RETINAL TEARS IN SINGLE VERSUS MONTAGE OF PERIPHERAL STEERING.

PURPOSE: To compare the detection rate of orthogonal, directed peripheral steering, and automontaged images with ultra-widefield imaging and the factors influencing the ability to identify retinal breaks. DESIGN: Retrospective cohort study. METHODS: Three hundred and seventy-six treatment-naive eyes (349 patients) that underwent laser retinopexy for retinal breaks between 2015 and 2021 were included. Pretreatment ultra-widefield orthogonal, peripheral steering, and automontage were cross-referenced to scleral-depressed examination to determine whether images successfully visualized all retinal breaks. Total relative retinal area (RRA) visualized was divided by its optic disk area (pixels) to calculate relative retinal area. Potential associations were assessed by linear regression analysis. RESULTS: One hundred and sixty two eyes (154 patients) met inclusion criteria. Orthogonal, peripheral steering, and automontage images showed detection rates of 47.5%, 90.7%, and 80.0%, respectively. Relative retinal area increased from orthogonal versus montage by 34.7% ± 26.5% (mean ± SD), which increased the detection rate by 90.8% ( P = 0.006). In linear probability models, vertical meridian tears decreased probability of identification in orthogonal, peripheral steering, and automontage by -26.6%, -86.2%, and -68.7%, respectively ( P < 0.001), and horizontal meridian tears increased the probability by 62.2%, 92.9%, and 85.5%, respectively, ( P < 0.001). Tears posterior to the equator in orthogonal images increased the probability (91.4%, P < 0.001). Artifacts such as lids/lashes, reflection, and face guard decreased the probability in directed peripheral steering by -28.6%, -50.0%, and -66.7%, respectively, ( P = 0.020, P = 0.049, and P = 0.016). CONCLUSION: Using directed peripheral steering and automontage increases RRA and detection rate of identifying peripheral retinal breaks. Tears in horizontal meridians or posterior to the equator increase the probability of identification. Common ultra-widefield imaging artifacts can significantly limit the probability of identifying retinal tears.

The Theoretical and Experimental Insights into the Radical Scavenging Activity of Rubiadin.

Rubiadin (RBD), an anthraquinone derivative, is obtained from Rubia cordifolia, a plant species classified under the Rubiaceae family. Rubiadin has proven beneficial properties, such as anticancer, neuroprotective, anti-inflammatory, and antidiabetic activity. The antioxidant activity of this molecule was suggested by some experimental results but has not been clearly established thus far. In this study, we employ DFT calculations to comprehensively assess the mechanism and kinetics of the HO•/HOO• radical scavenging activity of this compound in relation to solvents. RBD showed moderate HO• radical scavenging activity, with rate constants of 2.95 × 108 and 1.82 × 1010 M-1 s-1 in lipid and polar media, respectively. In the aqueous solution, the compound exhibited remarkable superoxide anion radical scavenging activity (k = 4.93 × 108 M-1 s-1) but modest HOO• antiradical activity. RBD also showed promising antiradical activity against a variety of radicals (CCl3O•, CCl3OO•, NO2, SO4•-, and N3•), while experimental and computational results confirmed that RBD has moderate activity in DPPH/ABTS•+ assays. Thus, RBD is predicted to be a good, albeit selective, radical scavenger.

A Comprehensive Study of the Radical Scavenging Activity of Rosmarinic Acid.

Rosmarinic acid (RA) is reported in separate studies to be either an inducer or reliever of oxidative stress, and this contradiction has not been resolved. In this study, we present a comprehensive examination of the radical scavenging activity of RA using density functional theory calculations in comparison with experimental data. In model physiological media, RA exhibited strong HO• radical scavenging activity with overall rate constant values of 2.89 × 1010 and 3.86 × 109 M-1 s-1. RA is anticipated to exhibit excellent scavenging properties for HOO• in an aqueous environment (koverall = 3.18 × 108 M-1 s-1, ≈2446 times of Trolox) following the hydrogen transfer and single electron transfer pathways of the dianion state. The neutral form of the activity is equally noteworthy in a lipid environment (koverall = 3.16 × 104 M-1 s-1) by the formal hydrogen transfer mechanism of the O6(7,15,16)-H bonds. Chelation with RA may prevent Cu(II) from reduction by the ascorbic acid anion (AA-), hence blocking the OIL-1 pathway, suggesting that RA in an aqueous environment also serves as an OIL-1 antioxidant. The computational findings exhibit strong concurrence with the experimental observations, indicating that RA possesses a significant efficacy as a radical scavenger in physiological environments.

Antiradical Activity of Lignans from Cleistanthus sumatranus: Theoretical Insights into the Mechanism, Kinetics, and Solvent Effects.

Sumatranus lignans (SL) isolated from Cleistanthus sumatranus have demonstrated bioactivities, e.g., they were shown to exhibit immunosuppressive properties in previous research. Their structure suggests potential antioxidant activity that has not attracted any attention thus far. Consistently, a comprehensive analysis of the antioxidant activity of these compounds is highly desirable with the view of prospective medical applications. In this work, the mechanism and kinetics of the antiradical properties of SL against hydroperoxyl radicals were studied by using calculations based on density functional theory (DFT). In the lipid medium, it was discovered that SL reacted with HOO• through the formal hydrogen transfer mechanism with a rate constant of 101-105 M-1 s-1, whereas in aqueous media, the activity primarily occurred through the sequential proton loss electron transfer mechanism with rate constants of 102-108 M-1 s-1. In both lipidic and aqueous environments, the antiradical activity of compounds 6 and 7 exceeds that of resveratrol, ascorbic acid, and Trolox. These substances are therefore predicted to be good radical scavengers in physiological environments.

Ultrasound Assessment of Gaze-induced Posterior Eyewall Deformation in Highly Myopic Eyes.

Purpose: To establish a quantitative metric of posterior eyewall deformability in different directions of gaze in highly myopic eyes with and without posterior staphyloma. Methods: A prospective study was performed on 53 highly myopic patients (106 eyes). Ultrasound scans were acquired in primary, up, downward, nasal, and temporal gazes. A validated intensity-based segmentation algorithm was used to quantify the posterior eyewall geometry on digitalized B-scan images. Posterior eyewall local curvature (K) and distance (L) to the transducer were calculated. The associations between directions of gaze, axial length (AL), and presence of staphyloma with the K and L parameters were assessed. Results: A total of 53 participants (106 eyes) were studied. Multivariate regression analysis demonstrated that, after accounting for longer AL, and presence of staphyloma, eccentric gaze was often independently associated with various K and L parameters. Specifically, downward gaze was associated with increased posterior eyewall concavity as reflected in the maximum of K (KMax) (ß = 0.050, P < 0.001) and absolute value of KMax (ß = 0.041, P = 0.011). Both downward gaze and upgaze were independently associated with increase in the derivative of absolute KMax (which is consistent with more apparent, steeper staphyloma ridges), local KMax (which detects KMax at smaller intervals), and Kstd (which represents likelihood of staphyloma presence) and decrease in maximum of L (which represents movement of the staphyloma apex) with all P < 0.05. The ß coefficients for downward gaze were consistently greater in magnitude compared with those in upgaze. After accounting for AL and presence of staphyloma, horizontal gazes were independently associated only with decrease in the standard deviation of L (which also represents likelihood of staphyloma presence) and maximum of L. Conclusions: Downward gaze results in a significant increase in posterior eyewall concavity in highly myopic eyes after accounting for AL and staphyloma presence. In comparison with downward gaze, upgaze resulted in a lower magnitude, but significant changes in staphyloma ridge steepness and the likelihood of staphyloma presence. Horizontal gazes seemed to be associated with less posterior eyewall geometric parameters. Studies are required to further assess the association between downward gaze during near work on posterior eyewall concavity and possible effects on myopia development and progression.

The alkoxy radical polymerization of N-vinylpyrrolidone in organic solvents: theoretical insight into the mechanism and kinetics.

Poly(N-vinylpyrrolidone) (PVP) is a polymer with many applications in cosmetic, pharmaceutical, and biomedical formulations due to its minimal toxicity. PVP can be synthesized through radical polymerization in organic solvents; this well-known industrial process is thoroughly characterized experimentally, however, quantum chemical modeling of the process is scarce: the mechanism and kinetics have not been thoroughly investigated yet. In this work, the mechanism and kinetics of the alkoxy radical polymerization of N-vinylpyrrolidone in organic solvents, namely isopropanol (IP) and toluene (TL), were successfully modeled by computational chemistry. The initiator radicals di-tert-butyl peroxide (TBO˙) and dicumyl peroxide (CMO˙) as well as the solvents isopropanol and toluene, were shown to be capable of assisting in the initiation reactions. The rate constant was influenced by the combination of initiators and solvent and the values of the rate constant of propagation were approximately 101-103 M-1 s-1. The radical polymerization of NVP with dicumyl peroxide as an initiator was comparable to that of di-tert-butyl peroxide in all of the examined organic solvents, whereas the solvents had less of an effect.

How Myopia and Glaucoma Influence the Biomechanical Susceptibility of the Optic Nerve Head.

Purpose: The purpose of this study was to assess optic nerve head (ONH) deformations following acute intraocular pressure (IOP) elevations and horizontal eye movements in control eyes, highly myopic (HM) eyes, HM eyes with glaucoma (HMG), and eyes with pathologic myopia (PM) alone or PM with staphyloma (PM + S). Methods: We studied 282 eyes, comprising of 99 controls (between +2.75 and -2.75 diopters), 51 HM (< -5 diopters), 35 HMG, 21 PM, and 75 PM + S eyes. For each eye, we imaged the ONH using spectral-domain optical coherence tomography (OCT) under the following conditions: (1) primary gaze, (2) 20 degrees adduction, (3) 20 degrees abduction, and (4) primary gaze with acute IOP elevation (to ∼35 mm Hg) achieved through ophthalmodynamometry. We then computed IOP- and gaze-induced ONH displacements and effective strains. Effective strains were compared across groups. Results: Under IOP elevation, we found that HM eyes exhibited significantly lower strains (3.9 ± 2.4%) than PM eyes (6.9 ± 5.0%, P < 0.001), HMG eyes (4.7 ± 1.8%, P = 0.04), and PM + S eyes (7.0 ± 5.2%, P < 0.001). Under adduction, we found that HM eyes exhibited significantly lower strains (4.8% ± 2.7%) than PM + S eyes (6.0 ± 3.1%, P = 0.02). We also found that eyes with higher axial length were associated with higher strains. Conclusions: Our study revealed that eyes with HMG experienced significantly greater strains under IOP compared to eyes with HM. Furthermore, eyes with PM + S had the highest strains on the ONH of all groups.

Study of the Mechanism and Kinetics of the Radical Scavenging Activity of 2-Mercaptoimidazole.

2-Mercaptoimidazole (2MI) is related to natural ovothiols that are recognized as powerful radical scavengers. Yet, despite early reports of its potent antioxidant properties, 2MI received little attention. Specifically, its radical scavenging activity against typical free radicals like HO• and HOO• has not yet been studied in terms of its mechanism and kinetics. In this project, density functional theory (DFT) simulations were used to assess the antiradical activity of 2MI. Calculations indicate that 2MI can demonstrate anti-HO• activity in both lipid and aqueous environments (koverall of 1.05 × 1010 and 2.07 × 1010 M-1 s-1, respectively). The calculated kinetics is extremely close to the experimental data in water (pH = 7.0), resulting in a kcalculated/kexperimental ratio of 1.73, validating the accuracy of the computational method and its usefulness for assessing radical scavenging activity in silico. In lipid media, the HOO• radical scavenging activity of 2MI is faster than that of common typical natural scavengers such as ascorbic acid, Trolox, and trans-resveratrol; hence, 2MI is a powerful radical scavenger in nonpolar media.

Posterior scleral birefringence measured by triple-input polarization-sensitive imaging as a biomarker of myopia progression.

In myopic eyes, pathological remodelling of collagen in the posterior sclera has mostly been observed ex vivo. Here we report the development of triple-input polarization-sensitive optical coherence tomography (OCT) for measuring posterior scleral birefringence. In guinea pigs and humans, the technique offers superior imaging sensitivities and accuracies than dual-input polarization-sensitive OCT. In 8-week-long studies with young guinea pigs, scleral birefringence was positively correlated with spherical equivalent refractive errors and predicted the onset of myopia. In a cross-sectional study involving adult individuals, scleral birefringence was associated with myopia status and negatively correlated with refractive errors. Triple-input polarization-sensitive OCT may help establish posterior scleral birefringence as a non-invasive biomarker for assessing the progression of myopia.

Identifying Content for an Item Bank to Measure the Quality-of-Life Impact of Myopia Refractive Interventions.

Purpose: To report on the content generation and item refinement phases for a myopia refractive intervention-specific quality-of-life (QoL) item bank that will be operationalized using computerized adaptive testing. Methods: Myopia refractive intervention-specific QoL domains and items were generated from (1) a literature search of existing refractive-intervention QoL questionnaires; (2) semistructured interviews with myopic patients corrected using spectacles, contact lenses and/or refractive surgery (n = 32); (3) and myopia experts (n = 9) recruited from the Singapore National Eye Centre. After a thematic analysis, items were systematically refined and tested using cognitive interviews with 24 additional patients with corrected myopia. Results: Of the 32 participants with myopia interviewed (mean ± standard deviation age, 35.6 ± 9.0 years; 71.9% female; 78.1% Chinese), 12 (37.5%) wore spectacles, 7 (21.9%) used contact lenses, and 20 (62.5%) had undergone laser refractive surgery. Initially, 912 items within 7 independent QoL domains were identified. After refinement, 204 items were retained, including those relating to mobility challenges and work-related difficulties that are not well-represented in current refractive intervention-specific questionnaires. Conclusions: Through a rigorous item generation and selection process, we have developed a 204-item and 7-domain myopia refractive intervention-specific item bank that will now undergo rigorous psychometric testing to generate item calibrations for the validation of a novel computerized adaptive testing instrument designed for use in research and routine clinical practice. Translational Relevance: Once psychometrically validated and operationalized using computerized adaptive testing, this myopia refractive intervention-specific instrument will enable researchers and clinicians to quickly and comprehensively assess the impact of myopic refractive interventions across seven QoL domains.

Place of care and costs associated with acute episodes and remission in schizophrenia.

BACKGROUND: Schizophrenia imposes significant economic burden on patients, families, caregivers, and society. To our knowledge, place of care and associated costs of acute schizophrenia episodes have not been well characterized. OBJECTIVE: To describe the care settings and costs associated with likely acute episodes and untreated remission periods among patients with schizophrenia. METHODS: Adults with schizophrenia were identified using the IBM MarketScan Commercial and Medicare Supplemental databases (2009-2018); claims for capitated benefits plans were excluded. Acute episode index date was defined as at least 1 inpatient schizophrenia claim or outpatient schizophrenia claim (frequency of claim dependent on visit type, such as hospitalization, emergency department, private practice, clinic, urgent care, or laboratory). Mental health-related medical costs (health plan+patient) associated with acute episodes were collected over a 2-month follow-up period and stratified by setting (inpatient vs outpatient); acute episode data were reported in subgroups of patients without or with prior clozapine use, as an indication of disease severity. Remission index date was defined as at least 1 outpatient claim with a schizophrenia diagnosis with no acute episode and no oral or injectable antipsychotic therapy. Remission costs were assessed over a 3-month period. All data were analyzed descriptively. RESULTS: A total of 14,824 patients with schizophrenia met criteria for an acute episode (12,896 [87.0%] without prior clozapine use; 1,427 [9.6%] with prior clozapine use). Most acute episodes were treated in an outpatient setting (all patients, 76.3%; without prior clozapine use, 74.5%; with prior clozapine use, 87.1%). When treated inpatient, mean (SD) episode medical costs were $17,045 ($28,101) for all patients, $16,060 ($22,786) for those without prior clozapine use, and $22,827 ($55,860) for those with prior clozapine use. When treated outpatient, mean (SD) medical costs for acute episodes were $2,478 ($6,961) for all patients, $2,609 ($7,068) for those without prior clozapine use, and $1,770 ($6,560) for those with prior clozapine use. For all patients with acute episodes, regardless of clozapine use, patient-incurred out-of-pocket costs were approximately 30% of total medical costs. For an untreated period of remission, 6,950 patients with schizophrenia met criteria. Total medical costs were $2,399 for these patients over a 3-month period. CONCLUSIONS: The majority of acute schizophrenia episodes were treated in the outpatient setting. For episodes that required inpatient care, inpatient episodes were approximately 7 times more costly than episodes treated in outpatient-only settings. For acute episodes and remission periods, health plans covered most costs; however, there were additional patient-incurred out-of-pocket costs. DISCLOSURES: All authors met the International Committee of Medical Journal Editors authorship criteria. Neither honoraria nor payments were made for authorship. Dr McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC) and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, AbbVie, Atai Life Sciences. Dr McIntyre is a CEO of Braxia Scientific Corp. Mr Doan, Dr Amari, and Mr Mercer are employees of Genesis Research, which was funded to perform the study. Ms Higa, Dr Gillard, and Dr Harrington were employees of AbbVie at the time of the study and may hold stock. This study was sponsored by AbbVie.

High-frequency ultrasound point-of-care device to quantify myopia-induced microstructural changes in the anterior sclera.

PURPOSE: To develop a point-of-care (POC) device using high-frequency ultrasound (US) for evaluating microstructural changes in the anterior sclera associated with myopia. METHODS: The proposed POC device must satisfy four primary requirements for effective clinical use: the measurement component is handheld; the software must be simple and provide real-time feedback; patient safety and health data security requirements set forth by relevant governing bodies must be satisfied and the measurement data must have sufficient signal-to-noise ratio (SNR) and repeatability. Radiofrequency (RF) echo data acquired by the POC device will be processed using our quantitative US methods to characterise tissue microstructure and biomechanical properties. RESULTS: All stated requirements have been met in the developed POC device. The high-frequency transducer is housed in a custom, 3D-printed, pen-like holder that allows for easy measurements of the anterior sclera. Custom software provides a simple interface for data acquisition, real-time data display and secure data storage. Exposimetry measurements of the US pressure field indicate device compliance with United States Food and Drug Administration limits for ophthalmic US. In vivo measurements on a volunteer suggest the RF data SNR and acquisition consistency are suitable for quantitative analysis. CONCLUSIONS: A fully functioning POC device using high-frequency US has been created for evaluating the microstructure of the anterior sclera. Planned studies using the POC device to scan the eyes of myopia patients will help clarify how the anterior sclera microstructure may be affected by myopia. If effective, this portable, inexpensive and user-friendly system could be an important part of routine eye examinations.

Quadrant Asymmetry in Optical Coherence Tomography Angiography Metrics in Ischemic Versus Non-Ischemic Central Retinal Vein Occlusion Eyes.

Purpose: To determine whether quadrant asymmetry (QA) of optical coherence tomography angiography (OCTA) metrics differs between non-ischemic versus ischemic central retinal vein occlusion (CRVO). Methods: Fifty-eight eyes (21 non-ischemic, 10 ischemic CRVO, and 27 contralateral control eyes) underwent 3 × 3 mm spectral-domain OCTA scans with quantification of the superficial retinal layer vessel length density (VLD) and perfusion density (PD). QA, defined as the maximum-minus-minimum value among four parafoveal Early Treatment Diabetic Retinopathy Study (ETDRS) quadrants, was compared by linear regression including fixed effects for each eye. Results: Mean age was 73.6 ± 11.4 (range 39-88), 73.8 ± 12.4 (range 39-91) and 77.2 ± 9.83, (range 60-88); and QA was 3.46 ± 1.76, 3.14 ± 1.57, and 4.88 ± 2.42 for VLD and 0.072 ± 0.038, 0.062 ± 0.036, and 0.11 ± 0.056 for PD for control, non-ischemic, and ischemic, respectively. QA was significantly higher in ischemic (0.109 ± 0.056) than non-ischemic CRVO eyes (0.062 ± 0.036; P = 0.02) and control eyes for PD (0.072 ± 0.038; P = 0.03). QA was also greater in ischemic (4.875 ± 2.418) than non-ischemic CRVO (3.141 ± 1.572) for VLD (P = 0.04). In terms of identifying which particular quadrant is most affected by ischemia, multivariate regression analysis comparing intra-quadrant effect on the presence of ischemia versus non-ischemia showed no quadrant was significantly affected (P > 0.05 for all quadrants). Conclusions: Ischemic CRVO increases intraeye QA of OCTA metrics when compared to non-ischemic CRVO and control eyes. No specific ETDRS quadrant appears to be more affected. Translational Relevance: This work uses an intraeye method to delineate between ischemic and non-ischemic CRVO by OCTA imaging, overcoming inter-eye variables encountered in clinical care.