Brolucizumab in Pretreated Neovascular Age-Related Macular Degeneration: Case Series, Systematic Review, and Meta-Analysis.

BACKGROUND Recalcitrant neovascular age-related macular degeneration (rnAMD) despite intensive intravitreal anti-neovascular endothelial growth factor (VEGF) treatment, can be handled by switching to another anti-VEGF agent. This first systematic review and meta-analysis presents long-term data after switching from another anti-VEGF agent to brolucizumab. METHODS Retrospective case series over two years of patients switched to brolucizumab, and a systematic review and meta-analysis of peer-reviewed studies presenting patients switched to brolucizumab. Weighted mean differences based on the random-effects models were calculated for best-corrected visual acuity (BCVA) and central subfield thickness (CST). RESULTS The systematic review draws on 1200 eyes switched to brolucizumab. The meta-analysis showed a clinically irrelevant decrease in BCVA after one and two months, together with significant decreases in CST for up to one year after the switch but lacking power over 2 years. Of twelve eyes (twelve patients) in our case series, five continued treatment for two years without experiencing significant changes. CONCLUSIONS After switch to brolucizumab, a significant morphological improvement with CST reduction was shown in eyes with rnAMD. The small worsening of BCVA may be owing to the chronically active nature of rnAMD. Brolucizumab thus remains a treatment option in rnAMD despite its potential side effects

Functional Outcomes of Brolucizumab-Induced Intraocular Inflammation Involving the Posterior Segment-A Meta-Analysis and Systematic Review.

Early poor outcomes of intraocular inflammation (IOI) after intravitreal brolucizumab (IVB) have negatively affected the use of brolucizumab in clinical routine. We wished to identify factors related to the treatment details of IOI involving the posterior segment resulting from IVB for neovascular AMD (nAMD), if these were reported in detail. Articles were retrieved from PubMed, Scopus, ClinicalTrials, and CENTRAL using the following search terms: AND AND . The risk of bias was rated using the JBI Critical Appraisal Tool. We included 31 reports (41 patients and 46 eyes). Patients were 75.9 ± 8.5 years, and 58.5% were female. IOI occurred 41.7 ± 37.5 (median 37.0) days after treatment initiation with 2.0 ± 1.3 (1-6) IVB injections. A mean change in visual acuity of -14.6 ± 21.0 (median -6.5) letters was reported. The mean time from first IOI signs to the initiation of any anti-inflammatory treatment was 3.3 ± 6.2 days, with 63% of the patients receiving systemic corticosteroids as standard treatment. Finally, a period effect was observed, with a change in visual acuity of -25.3 ± 27.1 and -2.6 ± 7.3 letters in the chronologically first and last third, respectively, of treated eyes (effect size: r = 0.71; p = 0.006). Functional outcomes markedly improved with increasing experience in managing IOI

Aqueous Humor Apolipoprotein Concentration and Severity of Diabetic Retinopathy in Type 2 Diabetes.

An imbalance of plasma apolipoproteins has been linked to diabetic retinopathy (DR); however, there is scarce information regarding their presence in the aqueous humor (AH) and their role in DR. Here, we aimed at analysing the relationship between apolipoprotein concentrations in human AH and the severity of DR. Concentrations of apolipoproteins were measured retrospectively in patients with type 2 diabetes mellitus (T2DM) without DR (n = 23), with mild to moderate nonproliferative DR (NPDR) (n = 13), and advanced NPDR/proliferative DR (PDR) (n = 14) using a multiplex immunoassay. Compared to the non-apparent DR group, the concentrations of seven apolipoproteins were elevated in advanced NPDR/PDR (Apo AI 5.8-fold, Apo AII 4.5-fold, Apo CI 3.3-fold, Apo CIII 6.8-fold, Apo D 3.3-fold, Apo E 2.4-fold, and Apo H 6.6-fold). No significant differences were observed in apolipoprotein concentrations between patients with non-apparent DR and healthy controls (n = 17). In conclusion, the AH concentrations of apolipoproteins AI, AII, CI, CIII, D, E, and H increased in advancing stages of DR, suggesting their role in the pathogenesis of DR, which deserves further examination

Outer retinal features in OCT predict visual recovery after primary macula-involving retinal detachment repair.

PURPOSE To find predictive markers for the visual potential in optical coherence tomography (OCT) one month after surgical repair of macula-involving rhegmatogenous retinal detachment (miRD) with and without internal limiting membrane (ILM) peeling. METHODS This retrospective single-center, single-surgeon cohort study included 74 patients who underwent pars plana vitrectomy (PPV) for primary miRD between January 2013 and August 2020 with follow-up examinations for at least 6 months. Patients developing recurrent detachments, media opacities, or with an axial length over 27 mm were excluded from the analysis. LogMAR visual (VA) and LogRAD reading acuity (RA) ± standard deviation (SD), and OCT measurements 6 months after surgery were compared to OCT and VA measurements one month after surgery using multiple linear regression analysis for predictions. RESULTS VA increased from 0.34 ± 0.25 at one month to 0.22 ± 0.21 after 6 months [p < 0.001; effect size = -0.662, 95% confidence interval (CI): -(0.99-0.33)]. The continuity of the external limiting membrane (ELM) and ellipsoid zone (EZ) increased between 1 and 6 months. Subfoveal ELM integrity after one month predicted VA [adjusted R2 of 8.0%, F(2, 71) = 4.17, p = 0.018] and RA [adjusted R2 of 29%, F(2, 27) = 6.81, p = 0.002] after 6 months. EZ integrity had a less pronounced predictive effect on VA and RA. ELM integrity after 1 month correlated with better reading acuity after 6 months (p = 0.016). CONCLUSION VA and morphological OCT parameters improve between 1 and 6 months after surgery for miRD. The grade of ELM is a better predictor for RA than for VA, explaining more variance

The universal variability of the stellar initial mass function probed by the TIMER survey

The debate about the universality of the stellar initial mass function (IMF) revolves around two competing lines of evidence. While measurements in the Milky Way, an archetypal spiral galaxy, seem to support an invariant IMF, the observed properties of massive early-type galaxies (ETGs) favor an IMF somehow sensitive to the local star-formation conditions. However, the fundamental methodological and physical differences between the two approaches have hampered a comprehensive understanding of IMF variations. Here, we describe an improved modeling scheme that, for the first time, allows consistent IMF measurements across stellar populations with different ages and complex star-formation histories (SFHs). Making use of the exquisite MUSE optical data from the TIMER survey and powered by the MILES stellar population models, we show the age, metallicity, [Mg/Fe], and IMF slope maps of the inner regions of NGC 3351, a spiral galaxy with a mass similar to that of the Milky Way. The measured IMF values in NGC 3351 follow the expectations from a Milky Way-like IMF, although they simultaneously show systematic and spatially coherent variations, particularly for low-mass stars. In addition, our stellar population analysis reveals the presence of metal-poor and Mg-enhanced star-forming regions that appear to be predominantly enriched by the stellar ejecta of core-collapse supernovae. Our findings therefore showcase the potential of detailed studies of young stellar populations to provide the means to better understand the early stages of galaxy evolution and, in particular, the origin of the observed IMF variations beyond and within the Milky Way

Impacts of Bar-driven Shear and Shocks on Star Formation

Bars drive gas inflow. As the gas flows inward, shocks and shear occur along the bar dust lanes. Such shocks and shear can affect the star formation (SF) and change the gas properties. For four barred galaxies, we present Hα velocity gradient maps that highlight bar-driven shocks and shear using data from the PHANGS-MUSE and PHANGS-ALMA surveys, which allow us to study bar kinematics in unprecedented detail. Velocity gradients are enhanced along the bar dust lanes, where shocks and shear are shown to occur in numerical simulations. Velocity gradient maps also efficiently pick up H ii regions that are expanding or moving relative to the surroundings. We put pseudo-slits on the regions where velocity gradients are enhanced and find that Hα and CO velocities jump up to ∼170 km s−1, even after removing the effects of circular motions due to the galaxy rotation. Enhanced velocity gradients either coincide with the peak of CO intensity along the bar dust lanes or are slightly offset from CO intensity peaks, depending on the objects. Using the Baldwin–Philips–Terlevich BPT diagnostic, we identify the source of ionization on each spaxel and find that SF is inhibited in the high-velocity gradient regions of the bar, and the majority of those regions are classified as a low-ionization nuclear emission-line region (LINER) or composite. This implies that SF is inhibited where bar-driven shear and shocks are strong. Our results are consistent with the results from the numerical simulations that show SF is inhibited in the bar where the shear force is strong

Inside-out formation of nuclear discs and the absence of old central spheroids in barred galaxies of the TIMER survey

The centres of disc galaxies host a variety of structures built via both internal and external processes. In this study, we constrain the formation and evolution of these central structures, in particular, nuclear rings and nuclear discs, by deriving maps of mean stellar ages, metallicities, and [α/Fe] abundances. We use observations obtained with the MUSE integral-field spectrograph for the TIMER sample of 21 massive barred galaxies. Our results indicate that nuclear discs and nuclear rings are part of the same physical component, with nuclear rings constituting the outer edge of nuclear discs. All nuclear discs in the sample are clearly distinguished based on their stellar population properties. As expected in the picture of bar-driven secular evolution, nuclear discs are younger, more metal-rich, and exhibit lower [α/Fe] enhancements, as compared to their immediate surroundings. Moreover, nuclear discs exhibit well-defined radial gradients, with ages and metallicities decreasing, and [α/Fe] abundances increasing with radius out to the nuclear ring. Often, these gradients show no breaks from the edge of the nuclear disc up through the centre, suggesting that these structures extend to the very centres of galaxies. We argue that continuous (stellar) nuclear discs may form from a series of bar-built (initially gas-rich) nuclear rings that expand in their radius as the bar evolves. In this picture, nuclear rings are simply the (often) star-forming outer edge of nuclear discs. Finally, by combining our results with those taken from a accompanying kinematic study, we do not find evidence for the presence of large, dispersion-dominated components in the centres of these galaxies. This could be a result of quiet merger histories, despite the large galaxy masses, or, perhaps, due to high angular momentum and strong feedback processes preventing the formation of these kinematically hot components