Synthesized Gold Nanoparticles with Moringa Oleifera leaf Extract Induce Mitotic Arrest (G2/M phase) and Apoptosis in Dalton's Lymphoma Cells.

The therapeutic potential of chemically synthesized AuNPs has been demonstrated in various types of cancer. However, gold nanoparticles (AuNPs) synthesized using typical chemical methods have concerns regarding their environmental safety and adverse impact on human well-being. To overcome this issue, we used an environmentally friendly approach in which gold nanoparticles were synthesized using Moringa oleifera leaf extract (MLE). The present research was mainly focused on the biosynthesis and characterization of gold nanoparticles (AuNPs) using Moringa oleifera leaf extract (MLE-AuNPs) and explore its anticancer potential against Dalton's Lymphoma (DL) cells. Characterization of the MLE-AuNPs was conducted using UV-Vis Spectroscopy to confirm the reduction process, FTIR analysis to ascertain the presence of functional groups, and XRD analysis to confirm the crystallinity. SEM and TEM images were used to examine size and morphology. After characterization, MLE-AuNPs were evaluated for their cytotoxic effects on Dalton's lymphoma cells, and the results showed an IC50 value of 75 ± 2.31 µg/mL; however, there was no discernible cytotoxicity towards normal murine thymocytes. Furthermore, flow cytometric analysis revealed G2/M phase cell cycle arrest mediated by the downregulation of cyclin B1 and Cdc2 and upregulation of p21. Additionally, apoptosis induction was evidenced by Annexin V Staining, accompanied by modulation of apoptosis-related genes including decreased Bcl-2 expression and increased expression of Bax, Cyt-c, and Caspase-3 at both the mRNA and protein levels. Collectively, our findings underscore the promising anti-cancer properties of MLE-AuNPs, advocating their potential as a novel therapeutic avenue for Dalton's lymphoma.

Incidence of ocular pathology following bariatric surgery for with morbid obesity across a large United States National Database.

BACKGROUND/OBJECTIVES: Bariatric surgery, as indicated for treatment of morbid obesity, has been studied in association with short term effects on ocular pathology. However, effects of surgery on postoperative disease incidence is largely unknown. SUBJECTS/METHODS: In this retrospective cohort study, the TriNetX United States Collaborative Network national database, was queried for patients with an ICD-10 code for morbid obesity and a procedural code for bariatric surgery. Patients were propensity score matched across baseline demographics at the time of surgery and compared to those presenting with an ICD10 code for morbid obesity with no records of a procedural code for bariatric surgery, identifying 42,408 patients per cohort. New diagnoses or procedural codes found after the surgical index date for diabetic retinopathy, age-related macular degeneration, glaucoma, low vision, and blindness along with pertinent treatment metrics were monitored. RESULTS: Bariatric surgery was found to be associated with reduced future risk of diabetic retinopathy (RR: 0.283; 95% CI: 0.252-0.319), macular edema (RR: 0.224; 95% CI: 0.170-0.297), vitreous hemorrhage (RR: 0.459; 95% CI: 0.323-0.653), ocular hypertension (RR: 0.387; 95% CI: 0.387-0.487), glaucoma (RR: 0.360; 95% CI: 0.326-0.399), use of ocular pressure lowering medications (RR: 0.565; 95% CI: 0.496-0.644), age-related macular degeneration (RR: 0.628; 95% CI: 0.447-0.882), cataract surgery (RR: 0.524; 95% CI: 0.448-0.612), and low vision and blindness (RR: 0.328; 95% CI: 0.294-0.365) compared to patients not surgically managed. CONCLUSIONS: The present analysis comprising a large US cohort of patients suggests that bariatric surgery is associated with a decreased risk of future ocular morbidity and mortality.

Comparing Three-Dimensional Digitally Enabled Intraoperative OCT With Conventional Microscope-Integrated OCT in Vitreoretinal Surgery: A Post Hoc Analysis of the Discover Study.

BACKGROUND AND OBJECTIVE: This study compared the surgeon experience between conventional microscope-integrated intraoperative optical coherence tomography (iOCT) and digitally enabled microscope-integrated iOCT in vitreoretinal surgery. PATIENTS AND METHODS: This is a post hoc case-control analysis of the DISCOVER study. Conventional microscope-integrated iOCT (Rescan 700, Zeiss) was compared with digitally enabled iOCT (Artevo 800, Zeiss). Compared variables included surgical field-based visualization (ie, ocular heads-up display in the conventional group; three-dimensional screen-based visualization in the digital iOCT group) and non-surgical field-based visualization (ie, review on the external two-dimensional monitor). RESULTS: A total of 200 patients were included. Surgical field-based visualization of iOCT was significantly higher in the digitally enabled group (P < 0.0001). Required endoillumination level was significantly lower in the digital iOCT group (P < 0.0001). Surgeons reported "significant" back discomfort and headache more frequently when using conventional iOCT (P = 0.003 and P = 0.001, respectively). CONCLUSIONS: Digitally enabled iOCT resulted in greater surgical visualization efficiency, appeared to require a lower illumination level, and may provide advantages for ergonomic-related discomfort. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Associations between lipid abnormalities and diabetic retinopathy across a large United States national database.

BACKGROUND/OBJECTIVES: While dyslipidaemia has been suggested as a potential risk factor for diabetic retinopathy (DR), previous studies have reported conflicting findings. This study aimed to better characterize the relationship between abnormal serum levels of various lipid markers and the risk of the development and progression of DR. SUBJECTS/METHODS: This retrospective cohort study utilized a United States national database of electronic medical records. Adults with a history of type 2 diabetes mellitus without type 1 diabetes mellitus were divided into cohorts based on the presence of abnormal serum levels of various lipid markers. Propensity score matching was performed to match cohorts with abnormal lipid levels to those with normal lipid levels on covariates. The cohorts were then compared to evaluate the hazard ratios (HR) of receiving a new DR diagnosis, pars plana vitrectomy, panretinal photocoagulation, vitreous haemorrhage, proliferative diabetic retinopathy, diabetic macular oedema (DMO), and traction retinal detachment. RESULTS: The database contained 1,126,231 eligible patients (mean age: 60.8 [14.2] years; 46.0% female). Among patients without prior DR, low HDL (HR = 0.94, CI = 0.90-0.98), total cholesterol (HR = 0.88, CI = 0.85-0.91), and high triglyceride (HR = 0.91, CI = 0.86-0.97) levels were associated with a decreased risk of receiving a DR diagnosis. Among patients with preexisting DR, high LDL levels was associated with an increased risk of DMO (HR = 1.42, CI = 1.15-1.75), whereas low HDL levels was associated with a marginally decreased risk (HR = 0.92, CI = 0.85-0.99). CONCLUSIONS: Elevated levels of markers of dyslipidaemia are inversely associated with the risk of receiving a DR diagnosis, but this relationship is blunted after the onset of DR.

Evidence-Based Use of Bevacizumab in the Management of Neovascular Age-Related Macular Degeneration.

Indicated for colorectal cancer for decades, bevacizumab has been widely used off label to treat retinal diseases, and the benefits of its use, specifically in neovascular age-related macular degeneration, have been demonstrated in multiple clinical trials. The intravitreal delivery of bevacizumab requires it to be aseptically repackaged into individual syringes by compounding pharmacies for use in the eye. Although the repackaging process is permitted by the US Food and Drug Administration, the resultant product does not meet the specific standards of products approved for use as ophthalmic injectables nor is the parenteral innovator solution compliant with ophthalmic standards. Studies have also demonstrated variability in the quality and quantity of repackaged bevacizumab. This narrative review summarizes the evidence and discusses the role of off-label bevacizumab in the treatment and management of retinal diseases, its mechanism of action, current challenges and provides a critical appraisal of current evidence, clinical implications, and future directions. [Ophthalmic Surg Lasers Imaging Retina 2024;55:155-162.].

Real-world effects of anti-vascular endothelial growth factor injection frequency on visual outcomes in patients with diabetic macular oedema.

BACKGROUND AND OBJECTIVE: Anti-vascular endothelial growth factor (VEGF) injections are often administered less frequently in real-world treatment of diabetic macular oedema (DMO) than what was studied in clinical trials. This study aims to characterise real-world DMO treatment patterns and the effect of treatment intervals on patient outcomes. STUDY DESIGN/PATIENTS AND METHODS: This was a retrospective study of 291 patients with DMO treated with anti-VEGF therapy. 12- and 24-month best visual acuity (BVA) and central subfield thickness (CST) were compared between injection interval groups, which were determined by averaging the two most recent injection intervals. Multiple linear regressions were performed to identify factors associated with injection interval, BVA, and CST. RESULTS: 48.8% of patients received injections less than or equal to every 8 weeks (≤ q8w), 27.5% between every 8 to 12 weeks (q8-12w), and 23.7% greater than every 12 weeks (> q12w). Baseline CST was similar (p = 0.32), but BVA differed significantly in q8-12w patients (p = 0.0095). BVA and CST at 12 months were similar, but q8-12w patients experienced greater 12-month BVA improvement (7.36 ± 12.4 letters) than > q12w patients (1.26 ± 12.3 letters; p = 0.0056). 24-month BVA and CST changes were similar between groups (p = 0.30 and 0.87). Baseline BVA, HbA1c, and sex were associated with 12-month BVA, and baseline BVA and CST were associated with 12-month CST. CONCLUSION: Many patients experienced improvements in BVA and CST over 12 months of treatment despite receiving less frequent anti-VEGF therapy than recommended in the pivotal trials. The present study showed that extended treatment intervals with bevacizumab were effective in preserving vision of many individuals with high baseline BVA.

Pharmacological Insights: Mitochondrial ROS Generation by FNC (Azvudine) in Dalton's Lymphoma Cells Revealed by Super Resolution Imaging.

Nucleoside analogs are a common form of chemotherapy that disrupts DNA replication and repair, leading to cell cycle arrest and apoptosis. Reactive oxygen species (ROS) production is a significant mechanism through which these drugs exert their anticancer effects. This study investigated a new nucleoside analog called FNC or Azvudine, and its impact on ROS production and cell viability in Dalton's lymphoma (DL) cells. The study found that FNC treatment resulted in a time- and dose-dependent increase in ROS levels in DL cells. After 15 and 30 min of treatment with 2 and 1 mg/ml of FNC, mitochondrial ROS production was observed in DL cells. Furthermore, prolonged exposure to FNC caused structural alterations and DNA damage in DL cells. The results suggest that FNC's ability to impair DL cell viability may be due to its induction of ROS production and indicate a need for further investigation.

The Risk of Optic Neuritis following mRNA Coronavirus Disease 2019 Vaccination Compared to Coronavirus Disease 2019 Infection and Other Vaccinations.

PURPOSE: To determine the risk of optic neuritis (ON) after mRNA Coronavirus Disease 2019 (COVID-19) vaccine administration. DESIGN: U.S. National aggregate database retrospective cohort study. PARTICIPANTS: Patients were placed into cohorts based on mRNA COVID-19 vaccination status (no vaccine and positive history of COVID-19 infection, 1 vaccine, or 2 vaccines received) from December 2020 to June 2022. Two control cohorts were created with patients vaccinated against influenza or tetanus diphtheria and pertussis (Tdap) from June 2018 to December 2019. Patients with any history of ON or significant risk factors for ON development including infectious, inflammatory, and neoplastic diseases were excluded. METHODS: A large deidentified database was queried for the Common Procedural Technology codes for immunization encounters specific to first dose and second dose of mRNA COVID-19 vaccine, influenza, or Tdap. Cohorts were 1:1 propensity score matched on age, sex, race, and ethnicity. The risk of ON development after vaccination was calculated and compared for all 5 cohorts with 95% confidence intervals (CIs) reported. MAIN OUTCOME MEASURES: Risk ratio (RR) of ON 21 days after vaccination (or COVID-19 infection) and incidence of ON per 100 000 individuals. RESULTS: After matching, the first dose COVID-19 and influenza vaccine cohorts (n = 1 678 598, mean age [standard deviation] at vaccination of 45.5 [23.3] years and 43.2 [25.5] years, 55% female) the RR of developing ON was 0.44 (95% CI, 0.28-0.80). The first dose of COVID-19 and Tdap vaccinations (n = 797 538, mean age 38.9 [20.0] years, 54.2% female) cohort had 10 and 16 patients develop ON (RR, 0.63; 95% CI, 0.28-1.38). Comparison of COVID-19-vaccinated patients (n = 3 698 848, 48.2 [21.5] years, 54.7% female) to unvaccinated and COVID-19-infected patients (n = 3 698 848, 49.6 [22.0] years, 55.2% female) showed 49 and 506 patients developing ON, respectively (RR, 0.09; 95% CI, 0.07-0.12). The incidence per 100 000 for ON was 1 in the first dose COVID-19 vaccine cohort, 2 in the influenza cohort, and 2 in the Tdap cohort, and 14 in the COVID-19-infected and unvaccinated cohorts. CONCLUSIONS: Risk of ON after mRNA COVID-19 vaccination is rare and comparable to Tdap vaccination, decreased compared with influenza vaccination, and decreased compared with COVID-19 infection in the absence of vaccination. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

TENAYA and LUCERNE: Two-Year Results from the Phase 3 Neovascular Age-Related Macular Degeneration Trials of Faricimab with Treat-and-Extend Dosing in Year 2.

PURPOSE: To evaluate 2-year efficacy, durability, and safety of the bispecific antibody faricimab, which inhibits both angiopoietin-2 and VEGF-A. DESIGN: TENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.gov identifier, NCT03823300) were identically designed, randomized, double-masked, active comparator-controlled phase 3 noninferiority trials. PARTICIPANTS: Treatment-naive patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older. METHODS: Patients were randomized (1:1) to intravitreal faricimab 6.0 mg up to every 16 weeks (Q16W) or aflibercept 2.0 mg every 8 weeks (Q8W). Faricimab fixed dosing based on protocol-defined disease activity at weeks 20 and 24 up to week 60, followed up to week 108 by a treat-and-extend personalized treatment interval regimen. MAIN OUTCOME MEASURES: Efficacy analyses included change in best-corrected visual acuity (BCVA) from baseline at 2 years (averaged over weeks 104, 108, and 112) and proportion of patients receiving Q16W, every 12 weeks (Q12W), and Q8W dosing at week 112 in the intention-to-treat population. Safety analyses included ocular adverse events (AEs) in the study eye through study end at week 112. RESULTS: Of 1326 patients treated across TENAYA/LUCERNE, 1113 (83.9%) completed treatment (n = 555 faricimab; n = 558 aflibercept). The BCVA change from baseline at 2 years was comparable between faricimab and aflibercept groups in TENAYA (adjusted mean change, +3.7 letters [95% confidence interval (CI), +2.1 to +5.4] and +3.3 letters [95% CI, +1.7 to +4.9], respectively; mean difference, +0.4 letters [95% CI, -1.9 to +2.8]) and LUCERNE (adjusted mean change, +5.0 letters [95% CI, +3.4 to +6.6] and +5.2 letters [95% CI, +3.6 to +6.8], respectively; mean difference, -0.2 letters [95% CI, -2.4 to +2.1]). At week 112 in TENAYA and LUCERNE, 59.0% and 66.9%, respectively, achieved Q16W faricimab dosing, increasing from year 1, and 74.1% and 81.2%, achieved Q12W or longer dosing. Ocular AEs in the study eye were comparable between faricimab and aflibercept groups in TENAYA (55.0% and 56.5% of patients, respectively) and LUCERNE (52.9% and 47.5% of patients, respectively) through week 112. CONCLUSIONS: Treat-and-extend faricimab treatment based on nAMD disease activity maintained vision gains through year 2, with most patients achieving extended dosing intervals. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Propensity-Matched Analysis of the Risk of Age-Related Macular Degeneration with Systemic Immune-Mediated Inflammatory Disease.

PURPOSE: The pathogenesis of age-related macular degeneration (AMD) involves aberrant complement activation and is a leading cause of vision loss worldwide. Complement aberrations are also implicated in many systemic immune-mediated inflammatory diseases (IMIDs), but the relationship between AMD and these conditions remains undescribed. The aim of this study is to first assess the association between AMD and IMIDs, and then assess the risk of AMD in patients with specific IMIDs associated with AMD. DESIGN: Cross-sectional study and cohort study. SUBJECTS AND CONTROLS: Patients with AMD were compared with control patients with cataracts and no AMD to ensure evaluation by an ophthalmologist. Patients with IMIDs were compared with patients without IMIDs but with cataracts. METHODS: This study used deidentified data from a national database (2006-2023), using International Classification of Diseases 10 codes to select for IMIDs. Propensity score matching was based on patients on age, sex, race, ethnicity, and smoking. Odds ratios were generated for IMIDs and compared between AMD and control patients. For IMIDs associated with AMD, the risk of AMD in patients with the IMID versus patients without IMIDs was determined utilizing a cohort study design. MAIN OUTCOME MEASURES: Odds ratio of IMID, risk ratios (RRs), and 95% confidence intervals (CIs) of AMD diagnosis, given an IMID. RESULTS: After propensity score matching, AMD and control cohorts (n = 217 197 each) had a mean ± standard deviation age of 74.7 ± 10.4 years, were 56% female, and 9% of patients smoked. Age-related macular degeneration showed associations with systemic lupus erythematosus (SLE), Crohn's disease, ulcerative colitis, rheumatoid arthritis (RA), psoriasis, sarcoidosis, scleroderma, giant cell arteritis, and vasculitis. Cohorts for each positively associated IMID were created and matched to control cohorts with no IMID history. Patients with RA (RR, 1.40; 95% CI, 1.30-1.49), SLE (RR, 1.73; 95% CI, 1.37-2.18), Crohn's disease (RR, 1.42; 95% CI, 1.20-1.71), ulcerative colitis (RR, 1.45; 95% CI, 1.29-1.63), psoriasis (RR, 1.48; 95% CI, 1.37-1.60), vasculitis (RR, 1.48; 95% CI, 1.33-1.64), scleroderma (RR, 1.65; 95% CI, 1.35-2.02), and sarcoidosis (RR, 1.42; 95% CI, 1.24-1.62) showed a higher risk of developing AMD compared with controls. CONCLUSIONS: The results suggest that there is an increased risk of developing AMD in patients with RA, SLE, Crohn's disease, ulcerative colitis, psoriasis, vasculitis, scleroderma, and sarcoidosis compared with patients with no IMIDs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Characterizing the Journey of Geographic Atrophy Patients in Routine Ophthalmic Practice.

BACKGROUND AND OBJECTIVE: Geographic atrophy (GA) is a form of late-stage age-related macular degeneration (AMD). This study aims to characterize the journey of patients with GA in real-world ophthalmology practice. PATIENTS AND METHODS: This is a retrospective cohort study of 100 patients with GA and 100 with intermediate AMD (iAMD). RESULTS: Approximately one-third of GA patients' eyes had GA at the time of their initial AMD diagnosis, and nearly half of the iAMD patients' eyes had iAMD at that time. When holding confounders constant, GA patients experienced significantly worse visual acuity outcomes, and a significantly higher proportion required referrals for low vision evaluation, needed assistance for activities of daily living, failed to meet driving standards, and met criteria for legal blindness when compared to iAMD controls. CONCLUSIONS: Many patients have already progressed to GA by the time they receive an AMD diagnosis, emphasizing the importance of providing early detection and intervention, especially considering novel treatment options. [Ophthalmic Surg Lasers Imaging Retina 2024;55:204-210.].

Long-Term Visual Outcomes in Patients With Idiopathic Epiretinal Membrane Surgery.

BACKGROUND AND OBJECTIVE: Our aim was to assess long-term outcomes following surgical repair of idiopathic epiretinal membrane (ERM) with pars plana vitrectomy (PPV) and membrane peel (MP). PATIENTS AND METHODS: A retrospective study evaluated patients with idiopathic ERM who underwent surgical repair at a single academic tertiary center with five to nine years of postoperative follow-up, assessing preoperative characteristics, surgical techniques, best visual acuity (BVA), and optical coherence tomography biomarkers at various time points. RESULTS: The study involved 67 patients (72 eyes) with an average postoperative follow-up of 82.8 ± 18.8 months. Patients with cone outer segment tips integrity at initial presentation and 1-year follow-up and patients with external limiting membrane and ellipsoid zone integrity at 1-year follow-up were noted to have significantly better long-term visual acuity than those without. More than 85% of patients achieved a BVA > 70 seven years after surgical repair. CONCLUSIONS: Vitreoretinal surgery for idiopathic ERM resulted in improved anatomical recovery and sustained visual acuity gain over long-term follow-up. [Ophthalmic Surg Lasers Imaging Retina 2024;55:70-77.].

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.

Changes in Prevalence of Idiopathic Intracranial Hypertension in the United States Between 2015 and 2022, Stratified by Sex, Race, and Ethnicity.

BACKGROUND AND OBJECTIVES: With the obesity epidemic within the United States, the prevalence of idiopathic intracranial hypertension (IIH) is predicted to rise. IIH prevalence and racial disparities have rarely been reported in the United States. The purpose of this study was to evaluate the prevalence of IIH in a large national database while stratifying by sex, age, race, and ethnicity. METHODS: This was a cross-sectional epidemiologic evaluation conducted in the TriNetX US Collaborative network using data from 2015 to 2022. Patients with an International Classification of Diseases code of IIH and papilledema or unspecified papilledema were included in the study. Any secondary cause of intracranial hypertension including cerebral neoplasms and hydrocephalus were excluded from the study. IIH trends were later compared with TriNetX cohort obesity trends. Prevalence and prevalence odds ratios (ORs) were calculated in Microsoft Excel and R Studio. RESULTS: Among 85 million patients in this database, a 1.35 times increase in the prevalence of IIH occurred between 2015 and 2022 from 7.3 (95% CI 6.9-7.7) individuals per 100,000 to 9.9 (95% CI 9.5-10.3) individuals per 100,000 in 2022. In 2022, Black female individuals had the highest prevalence of IIH with 22.7 individuals per 100,000 compared with the 13.7 White female individuals per 100,000. Patients aged 11-17 years showed the largest growth of IIH prevalence with female individuals increasing by 10 individuals per 100,000 by 2022. Overall, Black and Hispanic patients had the largest prevalence OR of IIH at 1.66 (95% CI 1.49-1.85) and 1.33 (95% CI 1.14-1.56), respectively, compared with White female patients. DISCUSSION: IIH is a rapidly increasing health care concern for the US population, particularly among adolescent patients. Black and Hispanic female individuals are most predominately affected by this incapacitating disorder.

Deep learning-based algorithm for the detection of idiopathic full thickness macular holes in spectral domain optical coherence tomography.

BACKGROUND: Automated identification of spectral domain optical coherence tomography (SD-OCT) features can improve retina clinic workflow efficiency as they are able to detect pathologic findings. The purpose of this study was to test a deep learning (DL)-based algorithm for the identification of Idiopathic Full Thickness Macular Hole (IFTMH) features and stages of severity in SD-OCT B-scans. METHODS: In this cross-sectional study, subjects solely diagnosed with either IFTMH or Posterior Vitreous Detachment (PVD) were identified excluding secondary causes of macular holes, any concurrent maculopathies, or incomplete records. SD-OCT scans (512 × 128) from all subjects were acquired with CIRRUS™ HD-OCT (ZEISS, Dublin, CA) and reviewed for quality. In order to establish a ground truth classification, each SD-OCT B-scan was labeled by two trained graders and adjudicated by a retina specialist when applicable. Two test sets were built based on different gold-standard classification methods. The sensitivity, specificity and accuracy of the algorithm to identify IFTMH features in SD-OCT B-scans were determined. Spearman's correlation was run to examine if the algorithm's probability score was associated with the severity stages of IFTMH. RESULTS: Six hundred and one SD-OCT cube scans from 601 subjects (299 with IFTMH and 302 with PVD) were used. A total of 76,928 individual SD-OCT B-scans were labeled gradable by the algorithm and yielded an accuracy of 88.5% (test set 1, 33,024 B-scans) and 91.4% (test set 2, 43,904 B-scans) in identifying SD-OCT features of IFTMHs. A Spearman's correlation coefficient of 0.15 was achieved between the algorithm's probability score and the stages of the 299 (47 [15.7%] stage 2, 56 [18.7%] stage 3 and 196 [65.6%] stage 4) IFTMHs cubes studied. CONCLUSIONS: The DL-based algorithm was able to accurately detect IFTMHs features on individual SD-OCT B-scans in both test sets. However, there was a low correlation between the algorithm's probability score and IFTMH severity stages. The algorithm may serve as a clinical decision support tool that assists with the identification of IFTMHs. Further training is necessary for the algorithm to identify stages of IFTMHs.

Mitochondrial-mediated apoptosis as a therapeutic target for FNC (2'-deoxy-2'-b-fluoro-4'-azidocytidine)-induced inhibition of Dalton's lymphoma growth and proliferation.

PURPOSE: T-cell lymphomas, refer to a diverse set of lymphomas that originate from T-cells, a type of white blood cell, with limited treatment options. This investigation aimed to assess the efficacy and mechanism of a novel fluorinated nucleoside analogue (FNA), 2'-deoxy-2'-ß-fluoro-4'-azidocytidine (FNC), against T-cell lymphoma using Dalton's lymphoma (DL)-bearing mice as a model. METHODS: Balb/c mice transplanted with the DL tumor model received FNC treatment to study therapeutic efficacy against T-cell lymphoma. Behavioral monitoring, physiological measurements, and various analyses were conducted to evaluate treatment effects for mechanistic investigations. RESULTS: The results of study indicated that FNC prevented DL-altered behavior parameters, weight gain and alteration in organ structure, hematological parameters, and liver enzyme levels. Moreover, FNC treatment restored organ structures, attenuated angiogenesis, reduced DL cell viability and proliferation through apoptosis. The mechanism investigation revealed FNC diminished MMP levels, induced apoptosis through ROS induction, and activated mitochondrial-mediated pathways leading to increase in mean survival time of DL mice. These findings suggest that FNC has potential therapeutic effects in mitigating DL-induced adverse effects. CONCLUSION: FNC represents an efficient and targeted treatment strategy against T-cell lymphoma. FNC's proficient ability to induce apoptosis through ROS generation and MMP reduction makes it a promising candidate for developing newer and more effective anticancer therapies. Continued research could unveil FNC's potential role in designing a better therapeutic approach against NHL.

FNC (4'-azido-2'-deoxy-2'-fluoro(arbino)cytidine) as an Effective Therapeutic Agent for NHL: ROS Generation, Cell Cycle Arrest, and Mitochondrial-Mediated Apoptosis.

Cytotoxic nucleoside analogs (NAs) hold great promise in cancer therapeutics by mimicking endogenous nucleosides and interfering with crucial cellular processes. Here, we investigate the potential of the novel cytidine analog, 4'-azido-2'-deoxy-2'-fluoro(arbino)cytidine (FNC), as a therapeutic agent for Non-Hodgkin lymphoma (NHL) using Dalton's lymphoma (DL) as a T-cell lymphoma model. FNC demonstrated dose- and time-dependent inhibition of DL cell growth and proliferation. IC-50 values of FNC were measured at 1 µM, 0.5 µM, and 0.1 µM after 24, 48, and 72 h, respectively. Further elucidation of FNC's mechanism of action uncovers its role in inducing apoptosis in DL cells. Notable DNA fragmentation and nuclear condensation point to activated apoptotic pathways. FNC-induced apoptosis was concomitant with changes in cellular membranes, characterized by membrane rupture and altered morphology. The robust anticancer effects of FNC are linked to its capacity to induce reactive oxygen species (ROS) production, prompting oxidative stress-mediated apoptosis. Additionally, FNC disrupted mitochondrial membrane potential (MMP), leading to mitochondrial dysfunction, further promoting apoptosis. Dysregulation of apoptotic genes, with upregulation of Bax and downregulation of Bcl-2 and Bcl-xl, implicates the mitochondrial-mediated apoptosis pathway. Furthermore, FNC-induced G2/M phase cell cycle arrest was mediated through modulation of the cell cycle inhibitor p21. Overall, this study highlights the potential of FNC as a promising therapeutic agent for NHL.

Characterization of pentosan polysulfate patients for development of an alert and screening system for ophthalmic monitoring.

OBJECTIVE: Pentosan polysulfate (PPS; ELMIRON, Janssen Pharmaceuticals, Titusville, NJ) is a U.S. Food and Drug Administration-approved oral medication for interstitial cystitis. Numerous reports have been published detailing retinal toxicity with the use of PPS. Studies characterizing this condition are primarily retrospective, and consequently, alert and screening systems need to be developed to actively screen for this disease. The goal of this study was to characterize ophthalmic monitoring trends of a PPS-using patient sample to construct an alert and screening system for monitoring this condition. METHODS: A single-institution retrospective chart review was conducted between January 2005 and November 2020 to characterize PPS use. An electronic medical record (EMR) alert was constructed to trigger based on new PPS prescriptions and renewals offering ophthalmology referral. RESULTS: A total of 1407 PPS users over 15 years was available for characterization, with 1220 (86.7%) being female, the average duration of exposure being 71.2 ± 62.6 months, and the average medication cumulative exposure being 669.7 ± 569.2 g. A total of 151 patients (10.7%) had a recorded visit with an ophthalmologist, with 71 patients (5.0%) having optical coherence tomography imaging. The EMR alert fired for 88 patients over 1 year, with 34 patients (38.6%) either already being screened by an ophthalmologist or having been referred for screening. CONCLUSIONS: An EMR support tool can improve referral rates of PPS maculopathy screening with an ophthalmologist and may serve as an efficient method for longitudinal screening of this condition with the added benefit of informing pentosan polysulfate prescribers about this condition. Effective screening and detection may help determine which patients are at high risk for this condition.

Anti-VEGF and steroid combination therapy relative to anti-VEGF mono therapy for the treatment of refractory DME: A systematic review of efficacy and meta-analysis of safety.

The aim of the study was to determine the efficacy and safety of combined anti-VEGF and steroid therapy in treatment refractory DME patients. We conducted a systematic review and meta-analysis of peer-reviewed articles reporting on visual, anatomical and adverse outcomes to compare the efficacy and safety of combined intravitreal anti-VEGF/steroids versus anti-VEGF monotherapy for refractory DME. Seven studies (4 RCTs and 3 observational studies) reporting on 452 eyes were included. Our systematic review showed that combination therapy is significantly more effective for anatomical outcomes in the treatment of resistant DME compared to anti-VEGF monotherapy in six studies. Two studies found that addition of intravitreal steroids promoted faster visual improvement, but not significantly better final visual outcomes compared to anti-VEGF monotherapy. Combination therapy was associated with a higher incidence of IOP-related adverse events (RR = 0.10, 95% CI = [0.02, 0.42], p = 0.002) and cataract-related adverse events (RR = 0.10, 95% CI = [0.01, 0.71], p = 0.02). Our systematic review and meta-analysis of seven studies and 452 eyes revealed that combination therapy of anti-VEGF and steroid intravitreal drugs in the management of treatment refractory DME resulted in superior anatomical outcomes in all but one study. Combination therapy led to superior short-term visual outcomes in two studies, while others reported no difference between treatment groups. Meta-analysis revealed that combination therapy was associated with more adverse events. Future research should provide guidance on the standard definitions for treatment resistance and therapeutic alternatives for DME patients with sub-optimal response to anti-VEGF treatment.