Main Outcome measuresThe Research Articles

Multimodal Deep Learning for Differentiating Bacterial and Fungal Keratitis Using Prospective, Representative Data

ObjectiveThis study develops and evaluates multimodal machine learning models for differentiating bacterial and fungal keratitis using a prospective, representative dataset from South India. DesignMachine learning classifier training and validation study. Participants599 subjects diagnosed with acute infectious keratitis at Aravind Eye Hospital in Madurai, India. MethodsWe developed and compared three prediction models to distinguish bacterial and fungal keratitis using a prospective, consecutively-collected, representative dataset gathered over a full calendar year (the MADURAI dataset). These models included a clinical data model, a computer vision model using the EfficientNet architecture, and a multimodal model combining both imaging and clinical data. We partitioned the MADURAI dataset into 70% train/validation and 30% test sets. Model training was performed with 5-fold cross-validation. We also compared the performance of the MADURAI-trained computer vision model against a model with identical architecture but trained on a pre-existing dataset collated from multiple prior bacterial and fungal keratitis randomized clinical trials (the RCT-trained computer vision model). Main Outcome MeasuresThe primary evaluation metric was the area under the precision-recall curve (AUPRC). Secondary metrics included area under the receiver operating curve (AUROC), accuracy, and F1 score. ResultsThe MADURAI-trained computer vision model outperformed the clinical data model and the RCT-trained computer vision model on the hold-out test set, with an AUPRC 0.94 (95% CI: 0.92-0.96), AUROC 0.81 (0.76-0.85), accuracy 77%, and F1 score 0.85. The multimodal model did not substantially improve performance compared to the computer vision model. ConclusionsThe best-performing machine learning classifier for infectious keratitis was a computer vision model trained using the MADURAI dataset. These findings suggest that image-based deep learning could significantly enhance diagnostic capabilities for infectious keratitis, and emphasize the importance of using prospective, consecutively-collected, representative data for machine learning model training and evaluation.

Analysis of the impact of a rhinologist-assisted endoscopic approach on a single neurosurgeon’s outcomes in transsphenoidal resection of pituitary adenomas

ObjectivesDetermine the improvements in outcomes of transsphenoidal pituitary adenoma resection following addition of a skull base rhinologist to the neurosurgical team. DesignAll patients that underwent transsphenoidal resection of pituitary adenoma were identified. Demographic data, Otolaryngology (ENT) involvement, initial adenoma size, extent of resection, hormonal secretion status, visual field exam, post-operative DI, CSF leak, recurrence, need for nasoseptal flap (NSF), re-operation rate were all collected. A linear-regression model adjusteds for confounders. SettingA single academic institution Participants271 patients who underwent transsphenoidal surgery between 2015 and 2020.Main Outcome MeasuresThe main outcome measures were Extent of Resection and Endocrinologic remission. ResultsOf the 271 patients identified, 228 (84 %) patients had macroadenomas, one-third of patients presented with bitemporal hemianopsia, and 27 % (72) were hormonally active. For these and demographics there were no statistically significant differences between the microscopic or endoscopic approach (EEA) groups. For patients with cavernous sinus invasion of >50 %, EEA was more likely to achieve gross total resection (GTR) (OR 2.6; p<0.001). For patients who had prior sellar surgery, EEA was 2.5x more likely to get a GTR (p=0.05). The EEA approach resulted in an extra hospital day (1–2 vs 2–3 p<0.05) and surgery lasted an additional hour (1.17 vs 2.5, p<0.05), but did not require fat grafts or lumbar drains on a routine basis. ConclusionsWhile the operating time and LOS were longer, the EEA approach performed by two specialized co-surgeons demonstrates superior value for adenomas that have had a prior surgical attempt or with significant cavernous sinus invasion.

Intensive chemotherapy versus standard chemotherapy among patients with high risk, operable, triple negative breast cancer based on integrated mRNA-lncRNA signature (BCTOP-T-A01): randomised, multicentre, phase 3 trial

ObjectiveTo evaluate the feasibility of using a multigene signature to tailor individualised adjuvant therapy for patients with operable triple negative breast cancer.DesignRandomised, multicentre, open label, phase 3 trial.Setting7 cancer centres...

Deep Learning to Predict the Future Growth of Geographic Atrophy from Fundus Autofluorescence

PurposeThe region of growth (ROG) of geographic atrophy (GA) throughout the macular area has an impact on visual outcomes. Here, we developed multiple deep learning (DL) models to predict the 1-year ROG of GA lesions using fundus autofluorescence (FAF) images. DesignIn this retrospective analysis, 3 types of models were developed using FAF images collected 6 months after baseline to predict the GA lesion area (segmented lesion mask) at 1.5 years, FAF images collected at baseline and 6 months to predict the GA lesion at 1.5 years, and FAF images collected 6 months after baseline to predict the GA lesion at 1 and 1.5 years. The 1-year ROG from the 6-month visit was derived by taking the difference between the GA lesion area (segmented lesion mask) at the 1.5-year and 6-month visits. ParticipantsPatients enrolled in the following lampalizumab clinical trials and prospective observational studies: NCT02247479, NCT02247531, NCT02479386, and NCT02399072. MethodsDatasets of study eyes from 597 patients were split into model training (310), validation (78), and test sets (209), stratified by baseline or initial lesion area, lesion growth rate, foveal involvement, and focality. DL experiments were performed using the 2-dimensional U-Net, whole-lesion and multiclass models were developed. Main Outcome MeasuresThe performance of the models was evaluated by calculating the Dice score, coefficient of determination (R2), and the squared Pearson correlation coefficient (r2) between the true and derived GA lesion 1-year ROG. ResultsThe model using baseline and 6-month FAF images to predict GA lesion enlargement at 1.5 years had the best performance for the derived 1-year ROG. Mean Dice scores were 0.73, 0.68, and 0.70, respectively, in the training, validation, and test sets. The R2 (0.77, 0.53, and 0.79) and r2 (0.83, 0.61, and 0.79) showed similar trends across the 3 sets. ConclusionsThese findings show the potential of using baseline and/or 6-month visit FAF images to predict 1-year GA ROG using a DL approach. This work could potentially help support decision making in clinical trials and more informed treatment decisions in clinical practice.

Substance P- and Insulin-like Growth Factor 1-derived Tetrapeptides for Neurotrophic Keratopathy Related to Leprosy: A Clinical Trial

PurposeNeurotrophic keratopathy is part of the leprosy sequelae and causes progressive deterioration of visual acuity. Although leprosy is bacteriologically curable, there is currently no efficient treatment. Eye drops containing tetrapeptides, Phenylalanine-Glycine-Leucine-Methionine-amide (FGLM-NH2) and Serine-Serine-Serine-Arginine (SSSR), derived from substance P and insulin-like growth factor 1 (IGF-1), are clinically efficacious in the treatment of corneal epithelial disorders caused by neurotrophic keratopathy. To further investigate the effect of this treatment on leprosy sequalae, we evaluated the clinical efficacy of FGLM-NH2+SSSR eye drops for treating neurotrophic keratopathy. DesignClinical trial: Interventional, multicenter, exploratory, single-arm, before and after comparison. ParticipantsThe eyes (12) of 11 patients, aged >60 years, were studied from two leprosy sanatoriums in Japan. MethodsPatients with neurotrophic keratopathy in leprosy sanatorium, specifically those with corneal perception of <40 mm, assessed by the Cochet-Bonnet corneal esthesiometer, and persistent corneal epithelial defects (PEDs) and/or corneal stromal thinning were included in this study. Those treated for infection in the acute phase were excluded from the study. Eye drops containing FGLM-NH2 0.05% and SSSR 5x10-6% were administered four times daily for up to 3 months. Fluorescein staining and optical corneal sections were photographed using a slit-lamp microscope at protocol-set intervals. Where possible, anterior segment optical coherence tomography was performed before and after the intervention. Main outcome measuresThe primary outcome measured was improvement in neurotrophic keratopathy. The patient was judged to have improved when one or more of the following criteria were met: 1) healing epithelial defects or 2) increased thickness in the thin area of the cornea. Secondary endpoints were visual acuity, subjective findings, and time to complete healing for a PED. ResultsNeurotrophic keratopathy on epithelial defects or stromal thickness improved in 83.3% of the patients (90% confidence interval 56.2%–97.0%, P<0.00001). The mean value of corrected visual acuity increased -0.16 by logarithm of the minimum angle of resolution. There were no adverse events reported in association with the treatment. ConclusionsWe confirmed that FGLM-NH2+SSSR eye drops are effective for neurotrophic keratopathy without any adverse reaction in leprosy. These results should be disseminated to any parties who could need this information.

Factors that impact second attempt success for neonatal intubation following first attempt failure: a report from the National Emergency Airway Registry for Neonates

ObjectiveTo determine the factors associated with second attempt success and the risk of adverse events following a failed first attempt at neonatal tracheal intubation.DesignRetrospective analysis of prospectively collected data on...

Medication optimization clinic decreases hospitalizations and mortality for patients with heart failure with reduced ejection fraction

Study objectiveTo evaluate the impact of a medication optimization clinic (MOC) on GDMT and outcomes for patients with HFrEF versus usual care. DesignRetrospective evaluation of a multi-site MOC was conducted. SettingLarge health system with academic and community hospitals. ParticipantsPatients with HFrEF referred to MOC by their cardiologist versus usual care. InterventionsGDMT use managed by an advanced practice provider or clinical pharmacist through weekly telemedicine visits. Main outcome measuresThe primary outcome was HF hospitalization. Cardiovascular hospitalization and all-cause mortality were also assessed. Kaplan−Meier Curve, Cumulative Incidence Function, and competing risk analysis with regression models were conducted. Results1419 patients in MOC group were compared to 5116 control patients. GDMT use was significantly higher in MOC: quadruple therapy (49 % vs. 19 %; p < 0.0001), angiotensin-receptor neprilysin inhibitor (62 % vs. 45 %; p < 0.0001), beta blocker (92 % vs. 88 %; p < 0.0001), mineralocorticoid receptor antagonist (69 % vs. 45 %; p < 0.0001), and sodium glucose cotransporter-2 inhibitor (68 % vs. 35 %; p < 0.0001). Competing risk analyses showed that HF and CV hospitalizations were significantly lower at all times points (3, 6, and 12 months) for MOC vs. control (p < 0.001). All-cause mortality was significantly lower at 6 months (p = 0.006) and 12 months (p < 0.001), but did not differ at 3 months (p = 0.35), for MOC vs. control. ConclusionsMOC was associated with improved GDMT and lower risks of hospitalizations due to HF and any cardiovascular cause, and all-cause mortality in patients with HFrEF.

Paternal metformin use and risk of congenital malformations in offspring in Norway and Taiwan: population based, cross national cohort study

ObjectiveTo evaluate the association between paternal metformin use and risk of congenital malformations in offspring.DesignPopulation based, cross national cohort study.SettingNorway and Taiwan.Participants619 389 offspring with paternal data during the period...

ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating Elamipretide in Age-related Macular Degeneration, Geographic Atrophy Growth, Visual Function, and Ellipsoid Zone Preservation

ObjectiveThis study evaluated the safety and efficacy of elamipretide in dry age-related macular degeneration (AMD) with non-central geographic atrophy (GA). DesignReCLAIM-2 was a prospective, phase 2, randomized, placebo-controlled, double-masked, multicenter trial (NCT03891875). SubjectsPatients aged ≥55 years with at least one eye with dry AMD with GA were enrolled. MethodsAdministration of daily subcutaneous elamipretide 40 mg was investigated in subjects for 48 weeks followed by a 4-week follow-up period. Main Outcome MeasuresThe primary efficacy endpoints were the mean change from baseline in low-luminance best-corrected visual acuity (LL BCVA) and the change in square root converted GA area from baseline as measured by optical coherence tomography (OCT). Additional predefined endpoints included ellipsoid zone (EZ) integrity preservation assessment and categorical changes in LL BCVA. The primary safety endpoint was the incidence and severity of adverse events. ResultsOf the 176 patients randomized, there were 117 and 59 patients in the elamipretide and placebo groups, respectively. Although elamipretide did not meet statistical significance for the primary endpoints (mean change in LL BCVA and mean change in square root converted GA area), elamipretide produced a 43% reduction in the mean progression from baseline in the macular percentage of total EZ attenuation/loss (i.e., complete loss of EZ band; nominal P=0.003) and 47% reduction in the mean progression of macular percentage of partial EZ attenuation/degradation (i.e., EZ-RPE thickness of 20 microns or less; nominal P=0.004) versus placebo at week 48. Elamipretide treatment was also associated with significantly more patients experiencing a ≥10 letter gain in LL-BCVA versus placebo (14.6% vs 2.1%; nominal P=0.0404). Adverse events were reported in 86% of those receiving elamipretide and 71% of the placebo group with the most common events being injection site reactions (e.g., pruritus, injection site pain, bruising, erythema). ConclusionsWhile the primary endpoints were not met in this phase 2 study, elamipretide treatment was associated with a slowing of progressive EZ degradation/loss, a surrogate for photoreceptor damage. These findings have important clinical relevance since EZ attenuation/photoreceptor loss precedes and predicts the progressive pathological changes associated with vision loss and AMD. The EZ attenuation/loss endpoint will serve as the regulatory-approved primary endpoint in the elamipretide Phase 3 clinical development program.

Disparities Between Clinical Trial Recruitment and Real-World Demographics in Macular Edema Secondary to Retinal Vein Occlusion

PurposeClinical trial cohorts frequently differ demographically from the overall population receiving treatment for the condition under study. Our study describes the racial, ethnic, and gender composition of the cohorts of retinal vein occlusion (RVO) macular edema (ME) clinical trials and compares this to the racial, ethnic, and gender composition of patients undergoing treatment for ME secondary to RVO from the (Intelligent Research in Sight) IRIS® Registry. DesignRetrospective observational case series Subjects: Participants in RVO-ME clinical trials that met the following inclusion criteria: conducted in the United States of America, Phase III completed, data reported between Jan 1, 2000, and Jan 1, 2020, and demographic information reported with results. MethodsThis study identified clinical trials by searching PubMed with the following search terms; “retinal vein occlusion” and “clinical trial” and by searching ClinicalTrials.gov with the search term “retinal vein occlusion”. Main Outcome MeasuresThe primary outcome was the enrollment fraction defined as the number of trial enrollees divided by the reference sample size of RVO patients undergoing treatment for ME from published IRIS® Registry (Intelligent Research in Sight) data. Enrollment fraction was compared between different races, ethnicities, and genders. ResultsEight clinical trials met our inclusion criteria. Compared to the enrollment fraction of 7.69% among Whites, lower enrollment fractions were found in Black patients (4.32%, odds ratio [OR] 0.541, confidence interval [CI] 0.468-0.626, P< 0.001) and Hispanic patients (3.38%, OR 0.420, CI 0.351-0.503, P<0.001), and higher enrollment fraction in Asian patients (10.68%, OR 1.436, CI 1.207-1.708, P<0.001). Men were more likely to enroll in the clinical trials compared to women (enrollment fraction, 7.69% vs 5.77%, respectively, OR 1.364, CI 1.273-1.462, P < 0.001). ConclusionsRVO-ME clinical trials have a higher relative proportion of Asian, White and male subjects when compared to the population undergoing treatment for ME secondary to RVO. Further efforts should encourage clinical trial recruitment that is reflective of the RVO population undergoing treatment for ME to ensure generalizability of clinical trial results.

Value of cardiac enzyme spectrum for the risk assessment of mortality in critically ill children: a single-centre retrospective study

ObjectivesIdentifying high-risk paediatric patients with a poor prognosis and providing timely and adequate treatment are critical. This study aimed to evaluate the effects of different types of cardiac enzyme spectrum...

Excessive Gestational Weight Gain, Independent of Body Mass Index, Is Associated With Child Fat Mass Index at Age 2 Years in the Growing life, Optimizing Wellness Study

BackgroundExcessive gestational weight gain (eGWG) increases risk for pregnancy complications and future obesity for pregnant persons and children. Yet, it is unclear whether eGWG leads to higher child adiposity at 2 years, independent of the pregnant person’s body mass index (BMI) while considering important covariates. Moreover, understanding the characteristics of pregnant persons experiencing eGWG will help design future targeted interventions. ObjectiveThe objectives of the analyses were to assess the association between eGWG and childhood adiposity at age 2 years, while controlling for pregnant persons’ BMI and other important covariates and to describe the characteristics of pregnant persons who experience eGWG during their second pregnancy. DesignThis is a secondary analysis of 221 pregnant persons and their children aged 2 years who were enrolled in the Growing Life, Optimizing Wellness longitudinal observational study. Participants/settingParticipants were recruited between 2011 and 2014 in central Arkansas. Participants were secundigravida persons with BMI 18.5 to 35, older than age 20 years, and who conceived without assistance. Main outcome measuresThe main outcome measure was fat mass index of children aged 2 years measured by quantitative nuclear magnetic resonance imaging. Secondary outcomes included first pregnancy GWG, dietary and physical activity characteristics between pregnancies, second pregnancy nausea levels, and motivation level to adhere to the GWG guidelines. Statistical analysis performedMultivariable regression analyses were used to examine the associations between GWG and childhood fat mass index at age 2 years. Pearson correlations and Wilcoxon rank sum tests were used to identify the characteristics of pregnant persons who experienced eGWG. ResultsPregnant persons’ eGWG (β = .503; P = .03) was positively associated with child adiposity at age 2 years independent of maternal BMI (P = 0.3). Pregnant persons who experienced eGWG during their second pregnancy had greater odds of eGWG during first pregnancies (odds ratio 7.5; P < .001), dieting behavior (odds ratio 14.3; P = .02), and low motivation to adhere to the GWG guidelines (odds ratio 11.2; P = .009). Fewer participants had eGWG during their second pregnancy (52.5%) compared with their first pregnancy (66.8%), which was different by BMI groups (BMI 18.5 to 24.9: 23.6% decrease in participants who gained eGWG, BMI 25 to 29.9: 20.0% decrease, and BMI ≥ 30: 37.9% decrease). ConclusionseGWG among pregnant persons is associated with child adiposity at age 2 years. Pregnant persons who experienced eGWG during their second pregnancy reported low motivation to gain weight within guidelines, eGWG in first pregnancy, and reported prior dieting behavior. Future research focusing on patients with these characteristics may increase success of interventions designed to limit eGWG.

Prevalence of hazardous alcohol consumption and associated factors among HIV-positive pregnant women attending public hospitals in Northwest Ethiopia: a multicentred cross-sectional study

BackgroundAlcohol is a major public health problem in pregnant women due to its harmful effects on pregnancy and adverse birth outcomes. Therefore, assessing the prevalence and the factors associated with...

Reliability and Construct Validity of Three Self-report Questionnaires Assessing Dual-Task Difficulties in People With Multiple Sclerosis: An International Study

ObjectiveTo evaluate the reliability and validity of the dual-tasking questionnaire (DTQ), dual-task screening list (DTSL), and dual-task impact on daily life activities questionnaire (DIDA-Q). DesignMulticenter, cross-sectional study SettingPersons with multiple sclerosis (pwMS) were recruited from 7 multiple sclerosis centers across 6 countries (Belgium, Chile, Italy, Israel, Spain, and Turkey). ParticipantsA total of 356 pwMS (mean age 47.5±11.5y, expanded disability status scale, 3.79±1.83) were enrolled. InterventionsNot applicable Main Outcome MeasuresThe reliability (internal consistency, test-retest, and measurement error) and construct validity (structural and convergent) were assessed. ResultsThe DTQ, DTSL, and DIDA-Q demonstrated excellent test-retest reliability (intraclass correlation coefficients [95% CI], 0.84 [0.80-0.87] to 0.90 [0.87-0.92]) and internal consistency (Cronbach α: 0.86-0.96). As hypothesized, the 3 questionnaires showed a strong correlation with each other, moderate-to-strong correlations with other self-report questionnaires (perceived walking difficulties, fatigue, and fear of falling), and low-to-moderate correlations with cognitive information processing speed, manual dexterity, and dual-task walking performance (walking with word list generation task), showing convergent validity. The DIDA-Q exhibited systematically superior properties. These results were also verified in subsets from 6 different countries. In the structural validity analysis, all questionnaires displayed 2 main factors, allocated as “motor-driven” and “cognitive-driven” subscales. ConclusionsThe DTQ, DTSL, and DIDA-Q have good-to-excellent measurement properties, with the highest properties observed in DIDA-Q. The use of these self-reported questionnaires can be used in research and clinical practice to assess the effect of dual-task difficulties on the daily life of ambulatory pwMS.

Real-world safety profile of zanubrutinib: a disproportionality analysis based on the FAERS database

ObjectiveZanubrutinib is a second-generation Bruton’s tyrosine kinase inhibitor that has been approved for the treatment of several B cell malignancies. The aim of this study was to evaluate adverse events...

Association of Calf Circumference, Hand Grip Strength, and Physical Performance With Serious Adverse Events in Individuals With Subacute Stroke Hospitalized for Rehabilitation: An Observational Study

ObjectiveTo determine whether calf circumference, hand grip strength, and physical performance are linked to the incidence of serious adverse events (SAEs) in patients with subacute stroke. DesignRetrospective cohort study. SettingSingle rehabilitation hospital. ParticipantsPatients with stroke admitted for rehabilitation hospital. InterventionNot applicable. Main Outcome MeasuresThe incidence of SAEs, such as death, cardiovascular events including recurrent stroke, and conditions requiring transfer to another hospital for specialized care or immediate treatment for an acute illness during hospitalization. ResultsA total of 341 patients (median age: 74y) participated in this study, with 232 patients (68%) exhibiting low-physical performance. In the adjusted model, low-physical performance was significantly associated with SAEs (hazard ratio [HR], 3.01; 95% confidence interval [CI], 1.04-8.68; P=.042). However, low calf circumference (HR, 1.60; 95% CI, 0.76-3.38; P=.219) and low hand grip strength (HR, 0.98; 95% CI, 0.39-2.42; P=.960) did not show an independent association. ConclusionsLow-physical performance was independently associated with the occurrence of SAEs during hospitalization for rehabilitation in patients with subacute stroke.

Individualized Versus General Exercise Therapy in People With Subacromial Pain Syndrome: A Randomized Controlled Trial

ObjectiveTo evaluate the effect of individualized exercises based on movement fault (MF) control on pain intensity and disability in subjects with chronic subacromial pain syndrome (SAPS). DesignRandomized Controlled Trial (IRCT20221126056621N1) SettingRehabilitation clinics ParticipantsThirty-eight participants with chronic SAPS (aged 52.23(8.47), 60 %woman). InterventionsThe participants were randomly allocated to one of the intervention groups (individualized exercises based on MFs control test designed to target specific movement faults) or the control group (commonly prescribed general scapular stabilization exercises). Both groups received exercise sessions twice a week for four weeks. Main Outcome MeasuresThe primary outcome measures were pain intensity at rest (PR) and during arm raising (PAR) using a visual analog scale. Disability was assessed as a key secondary outcome, including the disabilities of the arm, shoulder, and hand (DASH) questionnaire and the Shoulder Pain and Disability Index (SPADI). ResultsFollowing completion of all exercise sessions, PAR was significantly lower in the intervention group compared to the control group (mean [CI]: 9.17 [0.31 to 18.03], p=0.04), with a large effect size [0.68]. The reduction of PAR remained significantly lower in the intervention group than in the control group after four months of follow-up (mean [CI]: 18.29 [9.09 to 27.48], p=0.00) with a large effect size [1.27]. Disability significantly decreased at two month (mean=14.58, p=0.002 on SPADI index; mean=10.26, p=0.006 on DASH index) and four month (mean=19.85, p=0.00 on SPADI index; mean=12.09, p=0.001 on DASH index) follow ups in the intervention group compared to the control group. ConclusionIndividualized exercises based on MFs control of the shoulder region was accompanied by decreased PAR and disability in subjects with SAPS.

Relationships between Frailty and the Risk of Glaucoma in Middle-aged and Older Adults

PurposeIncreased frailty in older individuals increases health risks, but its relationship with glaucoma, the leading cause of irreversible blindness in middle-aged and older adults, is unclear. We investigated the association between frailty and glaucoma in a large-scale representative sample and explored possible causal relationships. DesignCombined cross-sectional and Mendelian randomization (MR) study. ParticipantsIn the cross-sectional analysis, we included 5744 participants of the US National Health and Nutrition Examination Surveys 2005–2008 aged ≥40. For the MR analysis, frailty genome-wide association study (GWAS) data were sourced from a UK Biobank and TwinGen meta-analysis, and GWAS data on glaucoma subtypes were derived from FinnGen. MethodsAccording to the 49-item frailty index, we classified participants into nonfrail (≤0.10), prefrail (0.10−0.21), and frail (>0.21) groups. Using survey-weighted logistic regression models adjusted for multiple covariates, we explored the association between frailty and glaucoma. We further assessed causation using MR. Main Outcome MeasuresThe associations between different levels of frailty (nonfrail, prefrail, and frail) and glaucoma, as well as causal relationships between genetically predicted frailty and various subtypes of glaucoma (primary open-angle glaucoma, primary angle-closure glaucoma, normotensive glaucoma, exfoliation glaucoma, and suspected glaucoma). ResultsAfter adjusting for covariates, higher frailty levels were significantly associated with glaucoma in frail individuals (odds ratio [OR]=1.83, 95% confidence interval [CI]=1.05–3.19, P=0.036) but not prefrail (OR=1.90, 95% CI=0.99–3.64, P=0.052). The association was significantly stronger among male participants (P interaction=0.042). The variation in the association between frailty and glaucoma did not reach statistical significance across age groups (P interaction=0.575) or race groups (P interaction=0.092). MR revealed that genetically predicted frailty was linked to greater risks for primary open-angle glaucoma (OR=1.67, 95% CI=1.24–2.25, P=0.001), primary angle-closure glaucoma (OR=2.78, 95% CI=1.48–5.20, P=0.001), exfoliation glaucoma (OR=1.70, 95% CI=1.18–2.43, P=0.004), and suspected glaucoma (OR=1.74, 95% CI=1.30–2.34, P<0.001), but not for normotensive glaucoma (OR=1.01, 95% CI=0.61–1.68, P=0.956). ConclusionsOur study revealed an association between frailty and increased glaucoma risk and emphasized the significance of glaucoma screening in frail individuals. Targeted healthcare strategies can help prevent or delay irreversible blindness among middle-aged and older adults.

A Modified Intravitreal Methotrexate Protocol for the Prevention of Proliferative Vitreoretinopathy after Silicone Oil Removal

ObjectiveTo utilize a modified intravitreal (IVT) methotrexate (MTX) protocol for the prevention of proliferative vitreoretinopathy (PVR) after silicone oil (SO) removal (SOR). DesignSingle-center nonrandomized retrospective comparative case series. SubjectsEyes with grade C PVR who underwent retinal detachment repair and SO placement between 2019-2022 with at least 6 months of follow-up after SOR. A control group of age- and sex-matched eyes was included. MethodsEyes were treated with one of two MTX protocols. Eyes in Group 1 received 6 IVT MTX injections following SO placement, and another 6 IVT MTX injections following SOR. Eyes in Group 2 received 6 IVT MTX following SO placement only. Each series of 6 IVT MTX injections (400 μg/0.1 mL) consisted of 3 injections every 2 weeks followed by 3 injections every 4 weeks. Main Outcome MeasuresThe primary outcome was the retinal attachment rate at 6 months post-SOR without re-detachment or re-operation. Secondary outcomes included change in visual acuity (VA) and rates of complications after SOR. ResultsFifty-two eyes of 52 patients (13 Group 1, 13 Group 2, 26 control) (mean age 59.8 years, 80.8% male) were included with a mean follow-up of 31.0 months. In aggregate, Group 1 and Group 2 eyes received a median (IQR) of 6 (5.25, 7) IVT MTX injections pre-SOR; eyes in Group 1 received a median (IQR) of 5 (3, 6) IVT MTX injections post-SOR. Twelve (92.3%) Group 1 eyes, 11 (84.6%) Group 2 eyes, and 21 (80.8%) control eyes had primary retinal attachment at 6 months post-SOR (P > 0.05). VA outcomes did not significantly differ between groups (P > 0.05). Rates of epiretinal membrane (ERM) and cystoid macular edema (CME) were significantly lower in Group 1 eyes (7.7% and 15.4%) compared to Group 2 (53.8% and 92.3%) and control (44.3% and 65.4%) eyes, respectively (P < 0.05). ConclusionsThe use of IVT MTX injections in eyes with PVR undergoing RD repair was associated with a high rate of primary retinal attachment after SOR. Eyes that received IVT MTX injections after SOR had significantly lower rates of ERM and CME than eyes that did not.

The Association between Glaucoma Severity and Hip Fractures in California Medicare Beneficiaries

PurposeTo examine the association between glaucoma severity and hip fractures in older adults. DesignRetrospective cross-sectional study. Subjects2019 California Medicare beneficiaries with Parts A & B coverage. MethodsMultivariable logistic regression was used to analyze the association between glaucoma severity (mild, moderate, and severe vs. no glaucoma) and hip fracture, after adjusting for age, sex, race and ethnicity, and Charlson Comorbidity Index score. A subgroup analysis was performed only in individuals with glaucoma to examine the odds of hip fracture for those with moderate and severe glaucoma compared to those with mild glaucoma. Main Outcome MeasuresThe variations in the odds of hip fractures for patients with and without glaucoma and for patients with moderate and severe glaucoma compared to those with mild glaucoma. ResultsOf the 2,717,346 beneficiaries in the study population, 220,662 (8.1%) had glaucoma. In multivariate regression analysis, those with mild (odds ratio [OR]: 0.83, 95% confidence interval [CI]: 0.78-0.88) and moderate glaucoma (OR: 0.88, 95% CI: 0.84-0.92) had reduced odds of hip fracture compared to those with no glaucoma. There was no statistically significant association between severe versus no glaucoma and hip fracture (OR: 0.96, 95% CI: 0.91-1.02). Among individuals with glaucoma, the odds of hip fracture were higher for those with moderate (OR: 1.07; 95% CI: 0.99-1.15) and severe glaucoma (OR: 1.17; 95% CI: 1.08-1.27), compared to those with mild glaucoma. ConclusionsIn the California Medicare population, the presence of glaucoma was associated with decreased likelihood of hip fracture. However, in those with glaucoma, increased glaucoma severity was associated with an increased likelihood of hip fracture. Potential mediating mechanisms requiring further study include fear of falls and physical inactivity in patients with glaucoma.