INTRAOCULAR INFLAMMATION INCIDENCE AFTER INTRAVITREAL BROLUCIZUMAB INJECTION FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: We evaluated the clinical outcomes of intraocular inflammation (IOI) of eyes with neovascular age-related macular degeneration (AMD) injected with brolucizumab in our tertiary referral center. METHODS: A retrospective case series for which clinical records of all eyes that received intravitreal brolucizumab at Bascom Palmer Eye Institute between December 1, 2019, and April 1, 2021, were reviewed. RESULTS: There were 345 eyes of 278 patients who received 801 brolucizumab injections. IOI was detected in 16 eyes of 13 patients (4.6%). In those patients, baseline Logarithm of Minimu Angle of Resolution (logMAR) best-corrected visual acuity was 0.32 0.2 (20/42), while it was 0.58 0.3 (20/76) at IOI presentation. The mean number of injections among eyes experiencing IOI was 2.4, and the interval between the last brolucizumab injection and IOI presentation was 20 days. There was no known case of retinal vasculitis. Management of IOI included topical steroids in seven eyes (54%), topical and systemic steroids in five eyes (38%), and observation in one eye (8%). Best-corrected visual acuity returned to baseline and inflammation resolved in all eyes by the last follow-up examination. CONCLUSION: Intraocular inflammation after brolucizumab injection for neovascular AMD was not uncommon. Inflammation resolved in all eyes by the last follow-up visit.

Ocular and inflammatory markers associated with Gulf War illness symptoms.

To examine the utility of ocular coherence tomography (OCT) metrics, in conjunction with systemic markers of inflammation, in identifying individuals with Gulf War Illness (GWI) symptoms. Prospective case-control study of 108 Gulf War Era veterans, split into 2 groups based on the presence of GWI symptoms, defined by the Kansas criteria. Information on demographics, deployment history, and co-morbidities were captured. 101 individuals underwent OCT imaging and 105 individuals provided a blood sample which was analyzed for inflammatory cytokines using an enzyme-linked immunosorbent assay-based chemiluminescent assay. The main outcome measure was predictors of GWI symptoms, examined with multivariable forward stepwise logistic regression analysis followed by receiver operating characteristic (ROC) analysis. The mean age of the population was 55 ± 4, 90.7% self-identified as male, 53.3% as White, and 54.3% as Hispanic. A multivariable model that considered demographics and co-morbidities found that a lower inferior temporal ganglion cell layer-inner plexiform layer (GCL‒IPL) thickness, higher temporal nerve fiber layer (NFL) thickness, lower interleukin (IL)-1ß levels, higher IL-1α levels, and lower tumor necrosis factor-receptor I levels correlated with GWI symptoms. ROC analysis demonstrated an area under the curve of 0.78 with the best cut-off value for the prediction model having a sensitivity of 83% and specificity of 58%. RNFL and GCL‒IPL measures, namely increased temporal thickness and decreased inferior temporal thickness, respectively, in conjunction with a number of inflammatory cytokines, had a reasonable sensitivity for the diagnosis of GWI symptoms in our population.

Early Mechanisms of Chemoresistance in Retinoblastoma.

Retinoblastoma is the most common eye cancer in children and is fatal if left untreated. Over the past three decades, chemotherapy has become the mainstay of eye-sparing treatment. Nevertheless, chemoresistance continues to represent a major challenge leading to ocular and systemic toxicity, vision loss, and treatment failure. Unfortunately, the mechanisms leading to chemoresistance remain incompletely understood. Here, we engineered low-passage human retinoblastoma cells to study the early molecular mechanisms leading to resistance to carboplatin, one of the most widely used agents for treating retinoblastoma. Using single-cell next-generation RNA sequencing (scRNA-seq) and single-cell barcoding technologies, we found that carboplatin induced rapid transcriptomic reprogramming associated with the upregulation of PI3K-AKT pathway targets, including ABC transporters and metabolic regulators. Several of these targets are amenable to pharmacologic inhibition, which may reduce the emergence of chemoresistance. We provide evidence to support this hypothesis using a third-generation inhibitor of the ABCB1 transporter.

Correlation Between Altmetric Attention Scores and Citations for Articles Published in High-Impact Factor Ophthalmology Journals From 2018 to 2019.

Importance: The Altmetric attention score (AAS) provides new information to gauge the impact of a research article not found through typical metrics, such as impact factor or citation counts. Objective: To explore the association between AAS and common impact markers among high-impact ophthalmology journals from 2018 to 2019. Design, Setting, and Participants: All articles published in the American Journal of Ophthalmology (AJO), JAMA Ophthalmology (JAMAO), and Ophthalmology (OPH) from January 1, 2018, to December 31, 2019, were collected for this cross-sectional study. Excluded articles were those missing Altmetric data at the time of data collection. The AAS and associated social media impact for each article were collected with the AAS calculator bookmarklet. Spearman rank correlation analyses and analysis of variance tests were conducted to assess differences in various metrics between AJO, JAMAO, and OPH. The study included articles published of all document types (article, conference paper, editorial, erratum, letter, note, retracted, review, and short survey) and access status (open access and not open access). Main Outcomes and Measures: The correlation between citation counts and Altmetric variables including AAS. Results: A total of 2467 articles were published in the study period. There were 351 articles excluded owing to missing Altmetric data. Of the 2116 articles included in the analysis, 1039 (49.1%) were published in 2018, and 1077 (50.9%) were published in 2019; the mean number of citations was 8.8 (95% CI, 7.9-9.6) for AJO, 6.2 (95% CI, 5.3-7.1) for JAMAO, and 15.1 (95% CI, 13.3-17.0) for OPH. The mean AAS was 4.5 (95% CI, 3.3-5.6) for AJO (723 publications), 27.4 (95% CI, 22.1-32.8) for JAMAO (758 publications), and 15.1 (95% CI, 10.9-19.3) for OPH (635 publications). Citation rate was moderately correlated with AAS across the 3 journals (AJO, ρ = 0.39; P < .001; JAMAO, ρ = 0.41; P < .001; OPH, ρ = 0.40; P < .001), as well as minimally or moderately correlated with engagement or mention by Facebook posts (AJO, ρ = 0.38; P < .001; JAMAO, ρ = 0.24; P < .001; OPH, ρ = 0.20; P < .001), news outlet reporting (AJO, ρ = 0.12; P < .001; JAMAO, ρ = 0.38; P < .001; OPH, ρ = 0.19; P < .001), and Twitter posts (AJO, ρ = 0.40; P < .001; JAMAO, ρ = 0.38; P < .001; OPH, ρ = 0.42; P < .001). Conclusions and Relevance: Results of this cross-sectional study suggest that citation rate has a moderate positive correlation with online and social media sharing of research in ophthalmology literature. Peer-reviewed journals may increase their reach and impact by sharing their literature through social media and online platforms.

Predictors of Local Recurrence and Progression-Free Survival in Iodine-125 Brachytherapy-Treated Uveal Melanomas: A Modern Institutional Study.

Introduction: Iodine-125 brachytherapy is an effective eye-sparing treatment for uveal melanoma. Previous work has shown that uveal melanomas cluster into distinct molecular classes based on gene expression profiles - discriminating low-grade from high-grade tumors. Our objective was to identify clinical and molecular predictors of local recurrence (LR) and progression-free survival (PFS). Methods: We constructed a retrospective database of uveal melanoma patients from the University of Miami's electronic medical records that were treated between January 8, 2012, and January 5, 2019, with either COMS-style or Eye Physics plaque. Data on tumor characteristics, pretreatment retinal complications, post-plaque treatments, LR, and PFS were collected. Univariate and multivariate Cox models for cumulative incidence of LR and PFS were conducted using SAS version 9.4. Results: We identified 262 patients, with a median follow-up time of 33.5 months. Nineteen patients (7.3%) had LR, and 56 patients (21.4%) were classified as PFS. We found that ocular melanocytosis (hazard ratio = 5.55, p < 0.001) had the greatest impact on PFS. Genetic expression profile did not predict LR outcomes (hazard ratio = 0.51, p = 0.297). Conclusion: These findings help physicians identify predictors for short-term brachytherapy outcomes, allowing better shared decision making with patients preoperatively when deciding between brachytherapy versus enucleation. Patients stratified to higher risk groups based on preoperative characteristics such as ocular melanocytosis should be monitored more closely. Future studies must validate these findings using a prospective cohort study.

Case-Control Study Examining the Composition of the Gut Microbiome in Individuals With and Without Immune-Mediated Dry Eye.

PURPOSE: Gut microbiome alterations have been associated with various autoimmune diseases. There are limited data, however, on relationships between gut dysbiosis and immune-related dry eye (DE). Our aim was to compare the gut microbiome composition of individuals with early and late markers of Sjögren syndrome (SS) with controls without DE. METHODS: We compared 20 individuals with positive early markers [antisalivary protein 1 (SP1), antiparotid secretory protein (PSP), anticarbonic anhydrase 6 (CA6) IgG, IgA, and IgM, n = 19)], or late markers (anti-Ro/SS-A and anti-La/SS-B, n = 1) of SS with no comorbid autoimmune diagnoses and 20 age-matched and sex-matched controls. Collected stool samples underwent deep RNA sequencing. The main outcomes measured included gut microbiome composition and diversity. RESULTS: A total of 20 cases [Dry Eye Questionnaire-5 15.2 ± 3.4, Ocular Surface Disease Index 55.1 ± 22.8, and Schirmer 7.1 ± 5.2 mm] were compared with 20 controls (Dry Eye Questionnaire-5 4.8 ± 3.8, Ocular Surface Disease Index 14.2 ± 12.3, and Schirmer 20.4 ± 9.2 mm). No differences were observed in α-diversity (P = 0.97) or overall community structure (P = 0.62). Between groups, 32 species were differentially abundant (P < 0.01). Among cases, 27 were relatively more abundant, including 10 Lactobacillus and 4 Bifidobacterium species. A relative depletion of 5 species was found in cases compared with controls, notably Fusobacterium varium and Prevotella stercorea. CONCLUSIONS: Differences in gut microbiome composition were found in individuals with mostly early markers of SS compared with controls. However, their clinical significance to DE manifestations remains unclear. Further studies are needed to elucidate the role of gut dysbiosis on immune dysregulation and disease activity in the various forms of immune-mediated DE.

A prospective study analyzing both inflation and deflation preference for commonly available inflatable penile prostheses.

Despite popularity, satisfaction rates of inflatable penile prosthesis (IPP) use can be improved by evaluating the ability to operate devices in the preoperative setting. The purpose of this study was to prospectively analyze the preference of three commonly available IPPs. In total, 125 IPP-naïve men 60 years of age or older were prospectively recruited from an outpatient Urology clinic from June 2019 to January 2020. A questionnaire standardized to all encounters was utilized to collect demographics, selected medical information, and key pinch strength. Participants were then asked to rank three models in terms of preference (from 1 to 3, 1 representing most preferred) for each inflation and deflation in a double-blinded manner. Statistical analysis was performed using ANOVA, a Chi-square test and multivariable logistical regression analysis. The results demonstrated preference for Coloplast Titan (44%) for inflation, and preference for AMS 700 (40%) for deflation. Men who preferred the Coloplast Titan inflation had a lower chance of preferring the AMS 700 MS deflation (OR = 0.29; p = 0.010) and Coloplast Titan Touch deflation (OR = 0.27; p = 0.012). Preference for Coloplast Titan was weakly associated with participant history of coronary artery disease (OR = 5.96, p = 0.006) and osteoarthritis (OR = 3.04, p = 0.044). Neither key pinch strength nor age was associated with preference for a particular model. IPP-naïve men over 60 years favor Coloplast Titan for inflation and AMS 700 for deflation, and men who preferred the Coloplast Titan for inflation were less likely to choose the AMS 700 MS or Coloplast Titan Touch for deflation. Further studies should aim to confirm these findings.

Assessment of Transport of Lipid Metabolites Within Trabecular Meshwork Cells.

Lipids from trabecular meshwork (TM) cells are of particular interest to ophthalmological researchers as a therapeutic target for lowering intraocular pressure (IOP) in glaucomatous eyes. Fluorescence-based lipid transport assays (FBLTA) and immunocytochemistry (ICC) are dynamic fluorescence analysis techniques that allow for quantitative and qualitative comparisons, respectively, between multiple samples. Here we describe methods for FBLTA, ICC, and mass spectroscopy designed to measure the kinetics and localization of lipid metabolites within the trabecular meshwork.

A growing field: The regulation of axonal regeneration by Wnt signaling.

The canonical Wnt/ß-catenin pathway is a highly conserved signaling cascade that plays critical roles during embryogenesis. Wnt ligands regulate axonal extension, growth cone guidance and synaptogenesis throughout the developing central nervous system (CNS). Recently, studies in mammalian and fish model systems have demonstrated that Wnt/ß-catenin signaling also promotes axonal regeneration in the adult optic nerve and spinal cord after injury, raising the possibility that Wnt could be developed as a therapeutic strategy. In this review, we summarize experimental evidence that reveals novel roles for Wnt signaling in the injured CNS, and discuss possible mechanisms by which Wnt ligands could overcome molecular barriers inhibiting axonal growth to promote regeneration. A central challenge in the neuroscience field is developing therapeutic strategies that induce robust axonal regeneration. Although adult axons have the capacity to respond to axonal guidance molecules after injury, there are several major obstacles for axonal growth, including extensive neuronal death, glial scars at the injury site, and lack of axonal guidance signals. Research in rodents demonstrated that activation of Wnt/ß-catenin signaling in retinal neurons and radial glia induced neuronal survival and axonal growth, but that activation within reactive glia at the injury site promoted proliferation and glial scar formation. Studies in zebrafish spinal cord injury models confirm an axonal regenerative role for Wnt/ß-catenin signaling and identified the cell types responsible. Additionally, in vitro and in vivo studies demonstrated that Wnt induces axonal and neurite growth through transcription-dependent effects of its central mediator ß-catenin, potentially by inducing regeneration-promoting genes. Canonical Wnt signaling may also function through transcription-independent interactions of ß-catenin with cytoskeletal elements, which could stabilize growing axons and control growth cone movement. Therefore, these studies suggest that Wnt-induced pathways responsible for regulating axonal growth during embryogenesis could be repurposed to promote axonal growth after injury.