Three-year outcomes of vascular endothelial growth factor inhibitors in naïve branch retinal vein occlusion: Fight Retinal Blindness!

PURPOSE: To evaluate the 3-year outcomes of vascular endothelial growth factor (VEGF) inhibitors in the treatment of cystoid macular oedema (CME) due to branch retinal vein occlusion (BRVO) in an international multicenter cohort of eyes. DESIGN: Multicenter, international, BRVO database study. SUBJECTS: Seven hundred forty-seven patients (760 eyes) undergoing intravitreal therapy for BRVO for 3 years in a multicenter international setting. METHODS: Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution (logMAR) letters, central subfield thickness (CST), treatments, number of injections and visits data was collected using a validated web-based tool. MAIN OUTCOME MEASURES: Visual acuity (VA) gain at 3 years in LogMAR letters. Secondary outcome measures included anatomical results, treatment pattern and percentage of completers. A subgroup analysis by study drug was conducted for clinical outcomes. RESULTS: Mean adjusted VA change was +11 letters (95% CI 9,13), mean adjusted change in CST was -176µm (-193, -159). Median number of injections/visits was 16/24 at 3 years of follow-up. Most eyes received VEGF inhibitors exclusively (89%, n=677) and as a monotherapy in 71% (n=538). Few eyes were switched to steroids (11%, n=83). Suspensions in treatment >180 days occurred in 26% of study eyes. Aflibercept showed greater CST reductions (-147 vs -128 vs -114µm; p< 0.001) and significantly lower switching rates (14% vs 38% vs 33%, p< 0.001) compared with ranibizumab and bevacizumab, respectively. CONCLUSIONS: This international study of 3-year BRVO outcomes after starting treatment with VEGF inhibitors found adequate visual and anatomical results in routine clinical care. Visual outcomes were similar amongst the different initiating VEGF inhibitors, although eyes starting with aflibercept had better anatomical outcomes and a lower switching rate.

Initial response and 12-month outcomes after commencing dexamethasone or vascular endothelial growth factor inhibitors for retinal vein occlusion in the FRB registry.

To compare baseline characteristics, initial response and 12-month efficacy and safety outcomes in eyes with branch and central retinal vein occlusion (BRVO and CRVO) treated with dexamethasone implants (DEX) or anti-vascular endothelial growth factor (anti-VEGF) we performed a multi-centre, retrospective and observational study using Fight Retinal Blindness! Registry. Of 725 eligible eyes, 10% received DEX initially with very frequent adjunctive anti-VEGF (BRVO-DEX 49%, CRVO-DEX 60%). The primary outcome of mean adjusted change in VA at 12 months with DEX and anti-VEGF initiated groups were not statistically significantly different (BRVO: DEX + 6.7, anti-VEGF + 10.6 letters; CRVO: DEX + 2.8, anti-VEGF + 6.8 letters). DEX initiated eyes had fewer injections and visits than anti-VEGF initiated eyes. The BRVO-DEX eyes had greater initial mean changes in VA and central subfield thickness (CST) and achieved inactivity sooner than BRVO-anti-VEGF eyes. The mean CST after the first three months was above 350 µm in all but the BRVO-anti-VEGF group, suggesting undertreatment. In routine care DEX is uncommonly used when available as initial treatment of BRVO and CRVO requiring supplemental anti-VEGF within the first year. The 12-month outcomes were similar, but DEX initiated eyes had fewer injections and visits but more episodes of raised IOP Vs those starting anti-VEGF.

European Unmet Needs in the Management of Neovascular Age-Related Macular Degeneration in Daily Practice: Data from the Fight Retinal Blindness! Registry.

PURPOSE: To evaluate the proportion, predictors, and outcomes of patients with neovascular age-related macular degeneration (nAMD) treated with a high burden of VEGF inhibitor intravitreal (IVT) injections after 2 years in routine clinical practice. DESIGN: Retrospective analysis of data from a prospectively designed observational outcomes registry, the Fight Retinal Blindness! Project, of patients treated in European centers. PARTICIPANTS: Treatment-naïve eyes (1 eye per patient) starting VEGF inhibitors for nAMD from January 2017 to March 2020 with 24 months of follow-up. We analyzed the following 3 treatment-burden groups defined by the mean interval of the 3 closest injections to the 24-month visit: (1) those with a high-treatment burden had injection intervals ≤ 42 days, (2) those with a low-treatment burden had injection intervals between 43 and 83 days; and (3) those with tolerable treatment burden had injection intervals between 84 and 365 days. METHODS: Multinomial regression was used to evaluate baseline risk predictors of patients requiring a high-treatment burden. MAIN OUTCOME MEASURES: The proportion of patients that experienced a high-treatment burden at 2 years and its predictors. RESULTS: We identified 2038 eligible patients completing 2 years of treatment (2038/3943 patients [60%]) with a median (quartile 1, quartile 3) of 13 (10, 17) injections. The proportion of patients with a high-treatment burden was 25% (516 patients) at 2 years. Younger patients (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.96-0.99; P < 0.01) were more likely to have high-treatment burden, whereas eyes with type 3 choroidal neovascular lesions at baseline were significantly less likely (OR, 0.26; 95% CI, 0.13-0.52; P < 0.01). Regarding type of fluid, patients with subretinal fluid only at baseline (OR, 3.85; 95% CI, 1.34-11.01; P = 0.01) and persistent active intraretinal (OR, 1.56; 95% CI, 1.18-2.06; P < 0.01) or subretinal fluid only (OR, 2.21; 95% CI, 1.52-3.21; P < 0.01) after the loading phase had a higher risk of high treatment burden at 2 years. CONCLUSIONS: High treatment burden is a common issue in routine clinical practice in Europe, with a quarter of patients requiring injections of conventional VEGF inhibitors every 6 weeks at 2 years and 40% discontinuing treatment within 2 years. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

An inorganic-rich but LiF-free interphase for fast charging and long cycle life lithium metal batteries.

Li metal batteries using Li metal as negative electrode and LiNi1-x-yMnxCoyO2 as positive electrode represent the next generation high-energy batteries. A major challenge facing these batteries is finding electrolytes capable of forming good interphases. Conventionally, electrolyte is fluorinated to generate anion-derived LiF-rich interphases. However, their low ionic conductivities forbid fast-charging. Here, we use CsNO3 as a dual-functional additive to form stable interphases on both electrodes. Such strategy allows the use of 1,2-dimethoxyethane as the single solvent, promising superior ion transport and fast charging. LiNi1-x-yMnxCoyO2 is protected by the nitrate-derived species. On the Li metal side, large Cs+ has weak interactions with the solvent, leading to presence of anions in the solvation sheath and an anion-derived interphase. The interphase is surprisingly dominated by cesium bis(fluorosulfonyl)imide, a component not reported before. Its presence suggests that Cs+ is doing more than just electrostatic shielding as commonly believed. The interphase is free of LiF but still promises high performance as cells with high LiNi0.8Mn0.1Co0.1O2 loading (21 mg/cm2) and low N/P ratio (~2) can be cycled at 2C (~8 mA/cm2) with above 80% capacity retention after 200 cycles. These results suggest the role of LiF and Cs-containing additives need to be revisited.

Morphology Dependent Reactivity of CsOx Nanostructures on Au(111): Binding and Hydrogenation of CO2 to HCOOH.

Cesium oxide (CsOx) nanostructures grown on Au(111) behave as active centers for the CO2 binding and hydrogenation reactions. The morphology and reactivity of these CsOx systems were investigated as a function of alkali coverage using scanning tunneling microscopy (STM), ambient pressure X-ray photoelectron spectroscopy (AP-XPS), and density functional theory (DFT) calculations. STM results show that initially (0.05-0.10 ML) cesium oxide clusters (Cs2O2) grow at the elbow sites of the herringbone of Au(111), subsequently transforming into two-dimensional islands with increasing cesium coverage (>0.15 ML). XPS measurements reveal the presence of suboxidic (CsyO; y ≥ 2) species for the island structures. The higher coverages of cesium oxide nanostructures contain a lower O/Cs ratio, resulting in a stronger binding of CO2. Moreover, the O atoms in the CsyO structure undergo a rearrangement upon the adsorption of CO2 which is a reversible phenomenon. Under CO2 hydrogenation conditions, the small Cs2O2 clusters are hydroxylated, thereby preventing the adsorption of CO2. However, the hydroxylation of the higher coverages of CsyO did not prevent CO2 adsorption, and adsorbed CO2 transformed to HCOO species that eventually yield HCOOH. DFT calculations further confirm that the dissociated H2 attacks the C in the adsorbate to produce formate, which is both thermodynamically and kinetically favored during the CO2 reaction with hydroxylated CsyO. These results demonstrate that cesium oxide by itself is an excellent catalyst for CO2 hydrogenation that could produce formate, an important intermediate for the generation of value-added species. The role of the alkali oxide nanostructures as active centers, not merely as promoters, may have broad implications, wherein the alkali oxides can be considered in the design of materials tuned for specific applications in heterogeneous catalysis.

Elucidating the active phases of CoOx films on Au(111) in the CO oxidation reaction.

Noble metals supported on reducible oxides, like CoOx and TiOx, exhibit superior activity in many chemical reactions, but the origin of the increased activity is not well understood. To answer this question we studied thin films of CoOx supported on an Au(111) single crystal surface as a model for the CO oxidation reaction. We show that three reaction regimes exist in response to chemical and topographic restructuring of the CoOx catalyst as a function of reactant gas phase CO/O2 stoichiometry and temperature. Under oxygen-lean conditions and moderate temperatures (≤150 °C), partially oxidized films (CoOx<1) containing Co0 were found to be efficient catalysts. In contrast, stoichiometric CoO films containing only Co2+ form carbonates in the presence of CO that poison the reaction below 300 °C. Under oxygen-rich conditions a more oxidized catalyst phase (CoOx>1) forms containing Co3+ species that are effective in a wide temperature range. Resonant photoemission spectroscopy (ResPES) revealed the unique role of Co3+ sites in catalyzing the CO oxidation. Density function theory (DFT) calculations provided deeper insights into the pathway and free energy barriers for the reactions on these oxide phases. These findings in this work highlight the versatility of catalysts and their evolution to form different active phases, both topological and chemically, in response to reaction conditions exposing a new paradigm in the catalyst structure during operation.

Exceptionally well-preserved crocodilian coprolites from the Late Eocene of Northern Vietnam: Ichnology and paleoecological significance.

This study examines 55 coprolites from the Na Duong Basin to reconstruct the paleoenvironment. Coproecology sheds light on understanding the complex prey-predator relationships, trophic dynamics, and ecosystem evolution. Through quantitative and multidisciplinary analysis, the putative coprolites were attributed to crocodilian producers, leading to the establishment of a new ichnogenus and species, Crococopros naduongensis igen. et isp. nov., based on distinct characteristics and comparisons. The study provides compelling evidence of an ancient river or lake-like environment dominated by diverse crocodilian fauna, indicating a thriving food chain in the Na Duong Basin. The findings also highlight the remarkable richness of ichnofauna, fauna, flora, and the presence of a favorable climate, confirming the area as a significant fossil Lagerstätte in Southeast Asia. Overall, this study offers a unique snapshot of the past, providing valuable insights into the regional ecosystem and significantly contributing to our understanding of paleoenvironmental conditions and biotic interactions.

Chemical Profiles of the Oxides on Tantalum in State of the Art Superconducting Circuits.

Over the past decades, superconducting qubits have emerged as one of the leading hardware platforms for realizing a quantum processor. Consequently, researchers have made significant effort to understand the loss channels that limit the coherence times of superconducting qubits. A major source of loss has been attributed to two level systems that are present at the material interfaces. It is recently shown that replacing the metal in the capacitor of a transmon with tantalum yields record relaxation and coherence times for superconducting qubits, motivating a detailed study of the tantalum surface. In this work, the chemical profile of the surface of tantalum films grown on c-plane sapphire using variable energy X-ray photoelectron spectroscopy (VEXPS) is studied. The different oxidation states of tantalum that are present in the native oxide resulting from exposure to air are identified, and their distribution through the depth of the film is measured. Furthermore, it is shown how the volume and depth distribution of these tantalum oxidation states can be altered by various chemical treatments. Correlating these measurements with detailed measurements of quantum devices may elucidate the underlying microscopic sources of loss.

Fast Surface Oxygen Release Kinetics Accelerate Nanoparticle Exsolution in Perovskite Oxides.

Exsolution is a recent advancement for fabricating oxide-supported metal nanoparticle catalysts via phase precipitation out of a host oxide. A fundamental understanding and control of the exsolution kinetics are needed to engineer exsolved nanoparticles to obtain higher catalytic activity toward clean energy and fuel conversion. Since oxygen release via oxygen vacancy formation in the host oxide is behind oxide reduction and metal exsolution, we hypothesize that the kinetics of metal exsolution should depend on the kinetics of oxygen release, in addition to the kinetics of metal cation diffusion. Here, we probe the surface exsolution kinetics both experimentally and theoretically using thin-film perovskite SrTi0.65Fe0.35O3 (STF) as a model system. We quantitatively demonstrated that in this system the surface oxygen release governs the metal nanoparticle exsolution kinetics. As a result, by increasing the oxygen release rate in STF, either by reducing the sample thickness or by increasing the surface reactivity, one can effectively accelerate the Fe0 exsolution kinetics. Fast oxygen release kinetics in STF not only shortened the prereduction time prior to the exsolution onset, but also increased the total quantity of exsolved Fe0 over time, which agrees well with the predictions from our analytical kinetic modeling. The consistency between the results obtained from in situ experiments and analytical modeling provides a predictive capability for tailoring exsolution, and highlights the importance of engineering host oxide surface oxygen release kinetics in designing exsolved nanocatalysts.

Central Retinal Vein Occlusion 36-Month Outcomes with Anti-VEGF: The Fight Retinal Blindness! Registry.

PURPOSE: To analyze the 3-year outcomes in a broad population of patients starting VEGF inhibitors for central retinal vein occlusion (CRVO) in routine clinical practice. DESIGN: Observational database study. PARTICIPANTS: Overall, 527 treatment-naïve CRVO eyes that commenced VEGF inhibitors between December 1, 2010 and 2018 were tracked in the Fight Retinal Blindness! registry. METHODS: Longitudinal models were used to plot changes in visual acuity (VA) and central subfield thickness (CST). MAIN OUTCOME MEASURES: Mean change in VA from baseline to 36 months, injections, visits, completion, switching, and suspensions of therapy > 180 days at the final review. RESULTS: Overall (527 eyes) mean VA change (95% confidence interval [CI]) was + 10 (7, 12) letters, 37% had final VA ≥ 70 and 30% ≤ 35 letters, mean CST changed -306 µm. Completers (257/527, 49%) had mean 36-month changes in VA and CST of + 12 letters and -324 µm with a median of 18 injections at 26 visits. The adjusted mean VA change was similar to each VEGF inhibitor (mean, + 11.4 letters) despite a greater reduction in CST with aflibercept (-310 µm) versus ranibizumab (-258 µm) versus bevacizumab (-216 µm; P < 0.001). Eyes with baseline VA that was trial-eligible (19-73 letters; 356/527, 68%) gained 7 letters, very poor (< 19 letters; 129/527, 24%) gained 22 letters, or very good (> 73 letters; 42/527, 8%) lost 7 letters. Switching (160/527, 30%) was most often to aflibercept (79 eyes). By using suspensions and discontinuation reasons, we identified similar proportions had ceased therapy (154/527, 29%) and were still receiving it at 36 months (165/527, 31%). Only 62/527 eyes (12%) had resolution of macular edema without treatment for > 6 months. CONCLUSIONS: Patients with CRVO that commenced VEGF inhibitors in routine care for whom follow-up was available had VA improvements of around 12 letters at 3 years, but with > 50% lost to follow-up, the VA outcome for the entire group was likely worse. The choice of VEGF inhibitor influenced CST but not VA outcomes. We estimated that around half of the eyes were still receiving injections after 36 months. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Hemiretinal vein occlusion 12-month outcomes are unique with vascular endothelial growth factor inhibitors: data from the Fight Retinal Blindness! Registry.

BACKGROUND/AIMS: To describe baseline characteristics and 12-month outcomes with vascular endothelial growth factor (VEGF) inhibitors of treatment-naïve hemiretinal vein occlusion (HRVO) compared with branch (BRVO) and central (CRVO) variants in routine clinical care. METHODS: A database observational study recruited 79 HRVO eyes, 590 BRVO eyes and 344 CRVO eyes that initiated therapy over 10 years. The primary outcome was mean change in visual acuity (VA-letters read on a logarithm of minimal angle of resolution chart) at 12 months. Secondary outcomes included mean change in central subfield thickness (CST), injections and visits. RESULTS: At baseline, mean VA in HRVO (53.8) was similar to CRVO (51.9; p=0.40) but lower than BRVO (59.4; p=0.009). HRVO eyes improved to match BRVO eyes from soon after treatment started through 12 months. Mean change in VA was greater in HRVO (+16.4) than both BRVO (+11.4; p=0.006) and CRVO (+8.5; p<0.001). Mean change in CST in HRVO (-231 µm) was similar to CRVO (-259 µm; p=0.33) but greater than BRVO eyes (-151 µm; p=0.003). The groups had similar median burdens of eight injections and nine visits. CONCLUSIONS: HRVO generally experienced the greatest mean change in VA of the three types of RVO when treated with VEGF inhibitors, ending with similar 12-month VA and CST to BRVO despite starting closer to CRVO. Inclusion of HRVO in BRVO or CRVO cohorts of clinical trials would be expected to proportionally inflate and skew the visual and anatomic outcomes.

Changes in 12-month outcomes over time for age-related macular degeneration, diabetic macular oedema and retinal vein occlusion.

OBJECTIVES: To identify whether the outcomes of neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DMO) and retinal vein occlusion (RVO) in routine clinical practice have changed over time. METHODS: We analysed 12-month outcomes in treatment-naïve eyes that started aflibercept or ranibizumab for nAMD (3802 eyes), DMO (975 eyes), Branch RVO (BRVO, 357 eyes), Central RVO (CRVO, 371 eyes) and Hemi-RVO (HRVO, 54 eyes) from 2015 and 2019 tracked in the prospectively designed observational Fight Retinal Blindness! Registry. RESULTS: The mean VA change at 12-month for each year between 2015 and 2019 remained stable or otherwise showed no discernible trends over time in eyes with nAMD (+3.3 to +6 letters), DMO (+3.6 to +6.7 letters) and RVO (+10.3 to +11.7 letters for BRVO, +5.9 to +17.7 letters for CRVO and 10.2 to 20.7 letters for HRVO). The median number of VEGF-inhibitor injections in eyes that completed 12-month follow-up also remained stable at 8-9 for nAMD, 6-7 for DMO, 7-9 for RVO. Fewer eyes (

Structure Matters: Asymmetric CO Oxidation at Rh Steps with Different Atomic Packing.

Curved crystals are a simple but powerful approach to bridge the gap between single crystal surfaces and nanoparticle catalysts, by allowing a rational assessment of the role of active step sites in gas-surface reactions. Using a curved Rh(111) crystal, here, we investigate the effect of A-type (square geometry) and B-type (triangular geometry) atomic packing of steps on the catalytic CO oxidation on Rh at millibar pressures. Imaging the crystal during reaction ignition with laser-induced CO2 fluorescence demonstrates a two-step process, where B-steps ignite at lower temperature than A-steps. Such fundamental dissimilarity is explained in ambient pressure X-ray photoemission (AP-XPS) experiments, which reveal partial CO desorption and oxygen buildup only at B-steps. AP-XPS also proves that A-B step asymmetries extend to the active stage: at A-steps, low-active O-Rh-O trilayers buildup immediately after ignition, while highly active chemisorbed O is the dominant species on B-type steps. We conclude that B-steps are more efficient than A-steps for the CO oxidation.

The Interaction of K and O2 on Au(111): Multiple Growth Modes of Potassium Oxide and Their Catalytic Activity for CO Oxidation.

In industrial catalysis, alkali cations are frequently used to promote activity or selectivity. Scanning tunneling microscopy, ambient-pressure X-ray photoelectron spectroscopy, and density-functional calculations were used to study the structure and reactivity of potassium oxides in contact with the Au(111) surface. Three different types of oxides (K2 O2 , K2 O and KOy with y<0.5) were observed on top of the gold substrate at 300-525 K. Initially, small aggregates of K2 O2 /K2 O (1-2 nm in size) were seen at the elbows of the herringbone structure. After increasing the K coverage (>0.15 ML), large islands of the oxide (20-40 nm in size) appeared. These islands contained a mixture of K2 O and KOy (y<0.5). A key correlation was found involving the structure, oxidation state, and chemical activity of the alkali oxide. The small aggregates of potassium oxide had a very high catalytic activity for the oxidation of CO, being much more than plain promoters.

One-year real-world outcomes of bevacizumab for the treatment of macular oedema secondary to retinal vein occlusion.

BACKGROUND: Bevacizumab is the only agent that many people can afford, yet there are only limited data on whether it improves macular oedema (MO) secondary to retinal vein occlusion (RVO) in real-world clinical practice. Here we studied 12-month real-world treatment outcomes of bevacizumab for RVO-related MO. METHODS: This was a multicentre, observational study analysing 12-month data from the Fight Retinal Blindness! (FRB) database. We studied treatment-naïve eyes with MO secondary to RVO commencing bevacizumab therapy between June 2009 and June 2019. Visual acuity (VA) and central subfield thickness (CST) were measured at baseline, 6 and 12 months. The primary outcome was a change in VA from baseline to 12 months. RESULTS: Two hundred and twenty treatment naive eyes were analyzed. The baseline VA for BRVO was better than CRVO (55.8 vs. 42.6 LogMAR letters) and this gap widened over the 12-month period, with a 12-month VA change of +14.0 (95% CI 11.1, 16.8) letters for BRVO and + 11.9 (95% CI 6.4, 17.4) for CRVO. The mean CST at baseline was 511 µm for BRVO and 627 µm for CRVO, falling at 12 months by -155 µm (-190, -121) in BRVO and -198 µm (-252, -145) in CRVO. The median number of injections for BRVO and CRVO completers was 7 (5, 9). CONCLUSIONS: Bevacizumab can be an effective treatment of RVO-MO in a real-world setting with outcomes approaching those reported by the seminal clinical trials. The functional and anatomical outcomes of intravitreal therapy were better for BRVO than CRVO.

Beyond the Present-Fault Paradigm: Expanding Mens rea Definitions in the General Part.

This article explores the use of mens rea terms in the criminal general part. We contend the current law fails properly to conceptualise mens rea for a large category of offences, namely bespoke/substantive inchoate offences, attempt, conspiracy, assisting and encouraging, and the general offence of complicity. These offences involve two conduct events: one in the present and one in future. However, current mens rea terms are defined as if applied to the more conventional category of criminal offence which only involves present conduct-a practice which we term the 'present-fault paradigm'. We explore the limits of current mens rea terms, defined for present-conduct targets (circumstances and results), when applied to future-conduct ulterior targets within inchoate and complicity offences. We contend that current mens rea definitions and analysis within the general part are inappropriate for targeting elements related to future conduct/offending, and we suggest more appropriate bases for conceptualising such mens rea.

Characterization of Poor Visual Outcomes of Diabetic Macular Edema: The Fight Retinal Blindness! Project.

PURPOSE: To investigate the incidence, characteristics, and baseline predictors of poor visual outcomes in eyes with diabetic macular edema (DME) receiving intravitreal therapy in routine clinical practice. DESIGN: Observational study. PARTICIPANTS: Treatment-naïve eyes starting intravitreal therapy for DME between 2014 and 2018 tracked in the Fight Retinal Blindness! registry. We examined 2 groups with poor visual outcomes: (1) those with sustained vision loss of > 10 letters from baseline without recovery of visual acuity (VA); and (2) those with a VA of < 55 letters at 2 years. Respective controls were eyes that did not experience poor visual outcomes. METHODS: Kaplan-Meier curves analyzed the proportion of eyes that experienced poor outcomes. Cox proportional hazards models evaluated the potential baseline predictors of poor outcomes. MAIN OUTCOME MEASURES: The proportion of eyes that experienced poor visual outcomes within 2 years of treatment initiation and its baseline predictors. RESULTS: The proportion of eyes with sustained VA of ≥ 10 letter loss was 14% at 2 years; 16% of eyes had VA of ≤ 55 letters 2 years after starting intravitreal therapy. Initial treatment with intravitreal corticosteroid was independently associated with a higher incidence of ≥ 10 letter loss (hazard ratio [HR], 3.21; 95% confidence interval [CI], 1.60-6.44; P < 0.01). No improvement in the VA at 3 months after starting treatment was associated with ≥ 10 letter loss (HR, 6.81; 95% CI, 4.11-11.27; P < 0.01) and VA of ≤ 55 letters at 2 years (HR, 4.28; 95% CI, 2.66-6.89; P < 0.01). The other factors related to higher risk of VA of ≤ 55 letters were older age (HR, 1.02 per year; 95% CI, 1-1.04; P = 0.04) and poor baseline VA (HR, 0.68 per 5 letters; 95% CI, 0.65-0.72, P < 0.001). CONCLUSIONS: Fourteen percent of eyes managed with intravitreal therapy in routine clinical care experienced ≥ 10 letter loss and 16% had VA of ≤55 letters 2 years after starting the treatment for DME. The identification of the incidence and predictors of poor outcomes provides a more accurate assessment of the potential benefit from intravitreal therapy.

Water Formation Reaction under Interfacial Confinement: Al0.25Si0.75O2 on O-Ru(0001).

Confined nanosized spaces at the interface between a metal and a seemingly inert material, such as a silicate, have recently been shown to influence the chemistry at the metal surface. In prior work, we observed that a bilayer (BL) silica on Ru(0001) can change the reaction pathway of the water formation reaction (WFR) near room temperature when compared to the bare metal. In this work, we looked at the effect of doping the silicate with Al, resulting in a stoichiometry of Al0.25Si0.75O2. We investigated the kinetics of WFR at elevated H2 pressures and various temperatures under interfacial confinement using ambient pressure X-ray photoelectron spectroscopy. The apparent activation energy was lower than that on bare Ru(0001) but higher than that on the BL-silica/Ru(0001). The apparent reaction order with respect to H2 was also determined. The increased residence time of water at the surface, resulting from the presence of the BL-aluminosilicate (and its subsequent electrostatic stabilization), favors the so-called disproportionation reaction pathway (*H2O + *O ↔ 2 *OH), but with a higher energy barrier than for pure BL-silica.