Cardiovascular risk in anti-VEGF treatment of neovascular age-related macular degeneration.

OBJECTIVE: Assess 5-year all-cause mortality (ACM), hemorrhagic stroke, ischemic stroke, and myocardial infarction (MI) risks in nAMD patients receiving anti-VEGF injections compared with controls. DESIGN: Population-based retrospective cohort study using a U.S. federated health research network, containing de-identified data of 96 million patients from 1/1/2003 to 3/6/2023. PARTICIPANTS: nAMD Patients with anti-VEGF injections. Controls included nAMD patients without anti-VEGF injections, non-exudative AMD patients, and patients without AMD. METHODS: Patients were identified using nAMD ICD-10 and anti-VEGF CPT codes and matched for age, sex, and comorbidities. Five-year relative risk of ACM (RR1), hemorrhagic stroke (RR2), ischemic stroke (RR3), and MI (RR4) in nAMD patients receiving anti-VEGF injections were calculated. RESULTS: A total of 27,609 nAMD patients (mean diagnosis age [SD], [78.2 (10.3)]) received anti-VEGF injections; 769 nAMD patients without injections (75.8 [12.2]), 27,599 non-exudative AMD patients (78.2 [10.3]), and 21,902 no-AMD patients (76.1 [10.5]) were identified. After matching, nAMD patients receiving injections did not show increased risk versus nAMD patients without injections (RR1, 0.66; 95% CI [0.53, 0.82]), (RR2, 1.00 [0.42, 2.38]), (RR3, 1.70 [0.92,3.13]), (RR4, 0.63 [0.33, 1.18]). No increased risk was found compared to non-exudative AMD patients (RR1, 0.99 [0.95, 1.03]), (RR2, 0.94 [0.83,1.07]), (RR3, 1.04 [0.96, 1.12]), (RR4, 0.99 [0.91, 1.08]). Increased risk for ACM was observed versus no-AMD patients (RR1, 1.21 [1.15, 1.27]), but no other differences were found (RR2, 0.81 [0.70, 0.93]), (RR3, 1.00 [0.92, 1.09]), (RR4, 0.986 [0.90, 1.09]). CONCLUSION: Anti-VEGF injections were not associated with major cardiovascular events in nAMD patients over 5 years.

Sequence-structure-function characterization of the emerging tetracycline destructase family of antibiotic resistance enzymes.

Tetracycline destructases (TDases) are flavin monooxygenases which can confer resistance to all generations of tetracycline antibiotics. The recent increase in the number and diversity of reported TDase sequences enables a deep investigation of the TDase sequence-structure-function landscape. Here, we evaluate the sequence determinants of TDase function through two complementary approaches: (1) constructing profile hidden Markov models to predict new TDases, and (2) using multiple sequence alignments to identify conserved positions important to protein function. Using the HMM-based approach we screened 50 high-scoring candidate sequences in Escherichia coli, leading to the discovery of 13 new TDases. The X-ray crystal structures of two new enzymes from Legionella species were determined, and the ability of anhydrotetracycline to inhibit their tetracycline-inactivating activity was confirmed. Using the MSA-based approach we identified 31 amino acid positions 100% conserved across all known TDase sequences. The roles of these positions were analyzed by alanine-scanning mutagenesis in two TDases, to study the impact on cell and in vitro activity, structure, and stability. These results expand the diversity of TDase sequences and provide valuable insights into the roles of important residues in TDases, and flavin monooxygenases more broadly.

Lack of racial and ethnic diversity in pediatric ophthalmology clinical trials from 2000 to 2022.

PURPOSE: To examine the prevalence of and factors associated with racial and ethnic reporting and trends in such reporting and to assess whether categories of race and ethnicity have been under- or over-represented in pediatric ophthalmology randomized control trials (RCTs) in the United States. METHODS: We systematically searched the literature on pediatric ophthalmology RCTs in high-impact factor ophthalmology journals published between 2000 and 2022. Logistic regression was used to assess parameters linked to race/ethnicity reporting; linear regression, to gauge the relationship between publication year and race/ethnicity reporting. The racial and ethnic composition of RCTs was contrasted with 2010 US census data by calculating percentage difference. RESULTS: Of 170 eligible articles, 89 (52.4%) included race/ethnicity data. Multivariable analysis showed that academic (OR = 12.19; 95% CI, 3.34-44.44) and government (OR = 3.91; 95% CI, 1.20-12.72) funding was linked to data reporting. During the study period, publication year and race/ethnicity reporting had a nonstatistically significant 1.0% annual increase (r = 0.29, P = 0.18). White participants were over-represented, with a percentage difference of 16.7% (95% CI, 11.8%-21.7%), whereas Hispanic individuals were under-represented, with a percentage difference of -7.6% (95% CI, -11.2% to -4.1%) compared to the 2010 US census data. CONCLUSIONS: Our results indicate a gradual rise in reported race and/or ethnicity in published pediatric ophthalmology RCTs, though not statistically significant, both in the United States and globally. Notably, under-representation of Hispanic, over-representation of White, and proportional representation of Black and Asian individuals were observed in US-based studies.

Visual acuity changes in the preoperative period in patients undergoing cataract surgery.

OBJECTIVE: This study quantifies change in best visual acuity (BVA) over the preoperative period and assesses factors associated with postoperative outcomes. DESIGN: Retrospective chart review conducted at a single institution. PARTICIPANTS: A total of 691 patients underwent cataract surgery and had a preoperative assessment 0-30 days prior to surgery following their surgical evaluation. METHODS: Baseline demographics and past medical and clinical data were collected through electronic medical record query. BVA was noted at initial surgical evaluation, preoperative assessment, and nearest postoperative assessment. RESULTS: A total of 691 patients (911 eyes) were included with mean BVAs at the initial evaluation, preoperative assessment, and postoperative assessment of 68.3 ± 16.8, 64.6 ± 18.5, and 81.1 ± 12.0 ETDRS letters, respectively. Mean BVA was significantly higher postoperatively compared with the preoperative assessment and initial evaluation (p < 0.0001). There was a mean of 53.8 days between initial surgical evaluation and surgery date and a mean of 49.9 days between the preoperative assessment and initial surgical evaluation. The mean interval between the preoperative assessment and surgery was 11.7 days. In the preoperative period, 9.1% of eyes experienced worsening of BVA by >3 eyes and 0.9% experienced improvement of BVA by >3 lines. Time to surgery was significantly associated with change in postoperative BVA (effect size, -0.03 ETDRS letters; p = 0.015) but was not significant on multiple linear regression. BVA at initial evaluation, glaucoma, and glaucoma surgery were all significantly associated with postoperative outcomes. CONCLUSION: Most eyes experienced stable vision in the preoperative period for cataract surgery. On average, patients with high BVAs at the time of initial surgical evaluation may be able to defer surgery without the risk of poorer surgical outcomes.

Outcomes for maximal bilateral lateral rectus recession in large-angle exotropia.

BACKGROUND: Surgical treatment for large-angle exotropia can be challenging. The aim of this study was to evaluate short-term surgical outcomes of patients with large-angle exotropia (≥50Δ) undergoing maximal bilateral lateral rectus muscle recession of 10 mm. METHODS: This was a retrospective study of consecutive patients at our institution who underwent maximal bilateral lateral rectus muscle recession for exodeviation ≥50Δ from January 1, 2008, to July 22, 2022. We subdivided the cohort into large-angle exotropia (largest amount of exodeviation at near and/or distance ≥50Δ and <65Δ) and very large-angle exotropia (largest exodeviation ≥65Δ). Patients with a history of prior eye muscle surgery, neurologic deficits, and three- or four-muscle surgery were excluded. RESULTS: A total of 22 patients were included. Mean preoperative exodeviation at distance was 51.9Δ in the large-angle group and 67.5Δ in the very-large-angle group (P = 0.001). Outcomes for the large-angle and very-large angle groups were, respectively, as follows: mean follow-up, 31.1 weeks and 11.8 weeks (P = 0.97); success, 75.0% and 16.7% (P = 0.02); undercorrection rates, 18.7% and 83.3% (P = 0.01); and mean postoperative exodeviation at distance, 3.7Δ ± 6.3Δ and 28.0Δ ± 13.5Δ (P = 0.001). CONCLUSIONS: Our study identified good surgical outcomes (75%) with maximal bilateral lateral rectus muscle recession of 10 mm in treating patients with large-angle exotropia between 50Δ and <65Δ. Other surgical techniques such as recession-resection and three- or four-muscle surgery may result in better outcomes when treating patients with exotropia ≥65Δ.