The impact of Vitreo-Macular interface abnormalities on the response to Anti-VEGF therapy for centre involving diabetic macular oedema.

BACKGROUND: The influence of Vitreomacular Interface Abnormalities (VMIA) such as Epiretinal Membrane (ERM) and/or vitreomacular traction (VMT) on the response of patients with Centre Involving Diabetic Macular Edema (CIDME) to standard of care Anti-VEGF medications is under-researched. The aims of this study were: 1) To determine the incidence of VMIA at baseline and 12 months amongst treatment naive patients commencing anti-VEGF treatment 2) To compare the response to Anti-VEGF medications at 3 monthly intervals for 12 months in a large cohort of patients with and without VMIA on their baseline OCT scan. Response was determined in terms of: number of injections, central macular thickness and visual acuity. METHODS: A retrospective case notes review of treatment naïve patients with newly diagnosed CIDME. Included patients had been commenced on intravitreal Anti-VEGF injections (ranibizumab or aflibercept) at a single centre. Inclusion criteria were: treatment naïve DME patients with a CMT of 400µ or more receiving anti-VEGF treatment with at least 12 months follow up and in whom macular OCT scans and visual acuity (VA) measurements were available within two weeks of baseline, 3, 6, 9 and 12 months. Exclusion criteria included: previous intravitreal therapy, previous vitrectomy, cataract surgery during the follow-up period, concurrent eye conditions affecting vision or CMT. RESULTS: 119 eyes met the inclusion criteria and underwent analysis. Groups were comparable in their baseline demographics. Baseline CMT measurements were comparable at baseline (417µ and 430µ in the No-VMIA and VMIA groups respectively) and improved to approximately 300µ in both groups. From 6 months CMT continued to improve in the no-VMIA while progressively deteriorating in the VMIA group. Change in CMT was statistically different at 12 months between the 2 groups (108µ and 79µ, p= 0.04). There was a mean of 7 injections after 12 months. CONCLUSION: Our study has shown a 46% incidence of VMIA amongst patients newly diagnosed with centre involving DME undergoing treatment with anti-VEGF injections. We have also demonstrated a significant difference in CMT and VA response to anti-VEGF treatment in patients with and without VMIA. Initial response was similar between the 2 groups up until 6 months. From 6 to 12 months significant differences in treatment response emerged. Differences in clinical response between patients with and without VMIA may help guide further prospective controlled studies and optimise treatment strategies.

Interpretation of SD-OCT imaging data in real-life conditions versus standardized reading centre analysis in eyes with diabetic macular oedema or macular oedema secondary to retinal vein occlusion: 24-month follow-up of the ORCA study.

PURPOSE: As part of the prospective, non-interventional OCEAN study, the ORCA module evaluated physicians' spectral domain optical coherence tomography (SD-OCT) image interpretations in the treatment of diabetic macular oedema (DME) or macular oedema (ME) secondary to retinal vein occlusion (RVO). METHODS: Presence of intraretinal fluid (IRF) and/or subretinal fluid (SRF) was evaluated independently by physicians and reading centres (RCs) on 1612 SD-OCT scans of 133 patients diagnosed with either DME or ME secondary to RVO. Agreement between physicians and RCs was calculated for both cohorts individually and as a combined ME cohort. Physicians' treatment decisions were analysed related to the results of the OCT-evaluations. RESULTS: For the combined ME cohort, presence of IRF/SRF was recorded by RCs in 792/1612 (49.1%) visits and by physicians in 852/1612 (52.9%) visits, with an agreement regarding presence or absence of foveal fluid in 70.4% of cases. In 64.4% (510/792) of visits with RC-detected foveal IRF and/or SRF no injection was given. In 30.3% of these visits with foveal fluid no reason was identified for a 'watch and wait' approach indicating possible undertreatment. BCVA deterioration was seen in a quarter of these eyes at the following visit. CONCLUSION: Despite good agreement between physicians and RCs to recognize SRF and IRF, our data indicate that omitting injections despite foveal involvement of fluid is frequent in routine clinical practice. This may put patients at risk of undertreatment, which may negatively impact real-life BCVA outcomes. TRIAL REGISTRATION: www. CLINICALTRIALS: gov , identifier NCT02194803.

Tracheostomy-related durable medical equipment: Insurance coverage, gaps, and barriers.

PURPOSE: Tracheostomy care is supply- and resource-intensive, and airway-related adverse events in community settings have high rates of readmission and mortality. Devices are often implicated in harm, but little is known about insurance coverage, gaps, and barriers to obtaining tracheostomy-related medically necessary durable medical equipment. We aimed to identify barriers patients may encounter in procuring tracheostomy-related durable medical equipment through insurance plan coverage. MATERIALS AND METHODS: Tracheostomy-related durable medical equipment provisions were evaluated across insurers, extracting data via structured telephone interviews and web-based searches. Each insurance company was contacted four times and queried iteratively regarding the range of coverage and co-pay policies. Outcome measures include call duration, consistency of explanation of benefits, and the number of transfers and disconnects. We also identified six qualitative themes from patient interviews. RESULTS: Tracheostomy-related durable medical equipment coverage was offered in some form by 98.1 % (53/54) of plans across 11 insurers studied. Co-pays or deductibles were required in 42.6 % (23/54). There was significant variability in out-of-pocket expenditures. Fixed co-pays ranged from $0-30, and floating co-pays ranged from 0 to 40 %. During phone interviews, mean call duration was 19 ± 10 min, with an average of 2 ± 1 transfers between agents. Repeated calls revealed high information variability (mean score 2.4 ± 1.5). Insurance sites proved challenging to navigate, scoring poorly on usability, literacy, and information quality. CONCLUSIONS: Several factors may limit access to potentially life-saving durable medical equipment for patients with tracheostomy. Barriers include out-of-pocket expenditures, lack of transparency on coverage, and low-quality information. Further research is necessary to evaluate patient outcomes.

Enhanced Stability of Dimethyl Ether Carbonylation through Pyrazole Tartrate on Tartaric Acid-Complexed Cobalt-Iron-Modified Hydrogen-Type Mordenite.

In this study, pyrazole tartrate (Pya·DL) and tartaric acid (DL) complexed with cobalt-iron bimetallic modified hydrogen-type mordenite (HMOR) were prepared using the ion exchange method. The results demonstrate that the stability of the dimethyl ether (DME) carbonylation reaction to methyl acetate (MA) was significantly improved after the introduction of Pya·DL to HMOR. The Co∙Fe∙DL-Pya·DL-HMOR (0.8) sample exhibited sustainable stability within 400 h DME carbonylation, exhibiting a DME conversion rate of about 70% and MA selectivity of above 99%. Through modification with the DL-complexed cobalt-iron bimetal, the dispersion of cobalt-iron was greatly enhanced, leading to the formation of new metal Lewis acidic sites (LAS) and thus a significant improvement in catalysis activity. Pya·DL effectively eliminated non-framework aluminum in HMOR, enlarged its pore size, and created channels for carbon deposition diffusion, thereby preventing carbon accumulation and pore blockage. Additionally, Pya·DL shielded the Bronsted acid sites (BAS) in the 12 MR channel, effectively suppressing the side reactions of carbon deposition and reducing the formation of hard carbon deposits. These improvements collectively contribute to the enhanced stability of the DME carbonylation reaction.

A new intelligent system based deep learning to detect DME and AMD in OCT images.

Optical Coherence Tomography (OCT) is widely recognized as the leading modality for assessing ocular retinal diseases, playing a crucial role in diagnosing retinopathy while maintaining a non-invasive modality. The increasing volume of OCT images underscores the growing importance of automating image analysis. Age-related diabetic Macular Degeneration (AMD) and Diabetic Macular Edema (DME) are the most common cause of visual impairment. Early detection and timely intervention for diabetes-related conditions are essential for preventing optical complications and reducing the risk of blindness. This study introduces a novel Computer-Aided Diagnosis (CAD) system based on a Convolutional Neural Network (CNN) model, aiming to identify and classify OCT retinal images into AMD, DME, and Normal classes. Leveraging CNN efficiency, including feature learning and classification, various CNN, including pre-trained VGG16, VGG19, Inception_V3, a custom from scratch model, BCNN (VGG16) 2 , BCNN (VGG19) 2 , and BCNN (Inception_V3) 2 , are developed for the classification of AMD, DME, and Normal OCT images. The proposed approach has been evaluated on two datasets, including a DUKE public dataset and a Tunisian private dataset. The combination of the Inception_V3 model and the extracted feature from the proposed custom CNN achieved the highest accuracy value of 99.53% in the DUKE dataset. The obtained results on DUKE public and Tunisian datasets demonstrate the proposed approach as a significant tool for efficient and automatic retinal OCT image classification.

Rab11 negatively regulates wingless preventing JNK-mediated apoptosis in Drosophila epithelium during embryonic dorsal closure.

Rab11, a small Ras like GTPase marking the recycling endosomes, plays instrumental roles in Drosophila embryonic epithelial morphogenesis where an array of reports testify its importance in the maintenance of cyto-architectural as well as functional attributes of the concerned cells. Proper Rab11 functions ensure a precise regulation of developmentally active cell signaling pathways which in turn promote the expression of morphogens and other physico-chemical cues which finally forge an embryo out of a single layer of cells. Earlier reports have established that Rab11 functions are vital for fly embryonic development where amorphic mutants such as EP3017 homozygotes show a fair degree of epithelial defects along with incomplete dorsal closure. Here, we present a detailed account of the effects of Rab11 loss of function in the dorso-lateral epithelium which resulted in severe dorsal closure defects along with an elevated JNK-Dpp expression. We further observed that the dorso-lateral epithelial cells undergo epithelial to mesenchymal transition as well as apoptosis in Rab11 mutants with elevated expression levels of MMP1 and Caspase-3, where Caspase-3 contributes to the Rab11 knockout phenotype contrary to the knockdown mutants or hypomorphs. Interestingly, the elevated expressions of the core JNK-Dpp signaling could be rescued with a simultaneous knockdown of wingless in the Rab11 knockout mutants suggesting a genetic interaction of Rab11 with the Wingless pathway during dorsal closure, an ideal model of epithelial wound healing.

Diabetic Macular Edema and Diode Subthreshold Micropulse Laser: A Randomized Double-Masked Noninferiority Clinical Trial.

PURPOSE: To determine clinical effectiveness, safety, and cost-effectiveness of subthreshold micropulse laser (SML), compared with standard laser (SL), for diabetic macular edema (DME) with central retinal thickness (CRT) < 400 µm. DESIGN: Pragmatic, multicenter, allocation-concealed, double-masked, randomized, noninferiority trial. PARTICIPANTS: Adults with center-involved DME < 400 µm and best-corrected visual acuity (BCVA) of > 24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in one/both eyes. METHODS: Randomization 1:1 to 577 nm SML or SL treatment. Retreatments were allowed. Rescue with intravitreal anti-vascular endothelial growth factor therapies or steroids was permitted if 10 or more ETDRS letter loss occurred, CRT increased > 400 µm, or both. MAIN OUTCOME MEASURES: Primary outcome was mean change in BCVA in the study eye at 24 months (noninferiority margin 5 ETDRS letters). Secondary outcomes were mean change from baseline to month 24 in binocular BCVA; CRT and mean deviation of Humphrey 10-2 visual field in the study eye; percentage meeting driving standards; EuroQoL EQ-5D-5L, 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), and Vision and Quality of Life Index (VisQoL) scores; cost per quality-adjusted life-years (QALYs) gained; adverse effects; and number of laser and rescue treatments. RESULTS: The study recruited fully (n = 266); 87% of SML-treated and 86% of SL-treated patients had primary outcome data. Mean ± standard deviation BCVA change from baseline to month 24 was -2.43 ± 8.20 letters and -0.45 ± 6.72 letters in the SML and SL groups, respectively. Subthreshold micropulse laser therapy was deemed not only noninferior but also equivalent to SL therapy because the 95% confidence interval (CI; -3.9 to -0.04 letters) lay wholly within both upper and lower margins of the permitted maximum difference (5 ETDRS letters). No statistically significant difference was found in binocular BCVA (0.32 ETDRS letters; 95% CI, -0.99 to 1.64 ETDRS letters; P = 0.63); CRT (-0.64 µm; 95% CI, -14.25 to 12.98 µm; P = 0.93); mean deviation of the visual field (0.39 decibels (dB); 95% CI, -0.23 to 1.02 dB; P = 0.21); meeting driving standards (percentage point difference, 1.6%; 95% CI, -25.3% to 28.5%; P = 0.91); adverse effects (risk ratio, 0.28; 95% CI, 0.06-1.34; P = 0.11); rescue treatments (percentage point difference, -2.8%; 95% CI, -13.1% to 7.5%; P = 0.59); or EQ-5D, NEI-VFQ-25, or VisQoL scores. Number of laser treatments was higher in the SML group (0.48; 95% CI, 0.18-0.79; P = 0.002). Base-case analysis indicated no differences in costs or QALYs. CONCLUSIONS: Subthreshold micropulse laser therapy was equivalent to SL therapy, requiring slightly higher laser treatments.

Ultra-thin ZrO2overcoating on CuO-ZnO-Al2O3catalyst by atomic layer deposition for improved catalytic performance of CO2hydrogenation to dimethyl ether.

An ultra-thin overcoating of zirconium oxide (ZrO2) film on CuO-ZnO-Al2O3(CZA) catalysts by atomic layer deposition (ALD) was proved to enhance the catalytic performance of CZA/HZSM-5 (H form of Zeolite Socony Mobil-5) bifunctional catalysts for hydrogenation of CO2to dimethyl ether (DME). Under optimal reaction conditions (i.e. 240 °C and 2.8 MPa), the yield of product DME increased from 17.22% for the bare CZA/HZSM-5 catalysts, to 18.40% for the CZA catalyst after 5 cycles of ZrO2ALD with HZSM-5 catalyst. All the catalysts modified by ZrO2ALD displayed significantly improved catalytic stability of hydrogenation of CO2to DME reaction, compared to that of CZA/HZSM-5 bifunctional catalysts. The loss of DME yield in 100 h of reaction was greatly mitigated from 6.20% (loss of absolute value) to 3.01% for the CZA catalyst with 20 cycles of ZrO2ALD overcoating. Characterizations including hydrogen temperature programmed reduction, x-ray powder diffraction, and x-ray photoelectron spectroscopy revealed that there was strong interaction between Cu active centers and ZrO2.

New imidazole-2-ones and their 2-thione analogues as anticancer agents and CAIX inhibitors: Synthesis, in silico ADME and molecular modeling studies.

The present study involves the synthesis of a series of new imidazole-2-ones derivatives and their 2-thione analogs using conventional heating and the environmentally friendly benign technique, the microwave technique. Structure of the compounds was well elucidated by considering the data of both elemental and spectral analyses. The obtained data and theoretical values of the synthesized molecules correlated with the proposed molecular structure. Moreover, all the synthesized compounds were evaluated in vitro for antitumor activity against HCT-116 and HeP2 human cancer cell panels and assessed as selective carbonic anhydrase IX isozyme (CA9/CAIX) inhibitors, thereby providing useful preliminary evidence for drug development. In addition, computational techniques were used to investigate the molecular and electronic characteristics of the investigated organic compounds. The 4b compound exhibited the best quantum chemistry features, as the highest occupied molecular orbital, softness, energy gap, and dipole moment, indicating the highest biological activity. This was supported by the experimental findings. Moreover, the in silico evaluation of drug candidates was also investigated. Thereafter, the anticancer activity of the most reactive candidate was studied via molecular docking to determine the types of interactions between this molecule and CAIX. According to the docking experiments, the 4b molecule generates five hydrogen bond interactions with active amino acid residues, Gln 92, Gln 67, and Thr 200.

Vitrectomy with ILM peeling in diabetic macular edema in one eye vs. intravitreal anti-VEGF injections in the second eye: a comparative study.

PURPOSE: The aim of this study was to compare the results of vitrectomy performed in patients' worse eyes with diabetic macular edema to the results of continuous anti-VEGF treatment performed in patients' fellow eyes. METHODS: A retrospective interventional study of 14 patients with diabetic macular edema in both eyes. The better eye was always qualified for aflibercept injections (group 1), and the worse eye was scheduled for vitrectomy (group 2). The follow-up lasted 12 months. The following parameters were measured: visual acuity (V), central retinal thickness (CRT), maximum retinal thickness (MRT), central choroidal thickness (CCT), superficial fovea avascular zone (sFAZ) and deep fovea avascular zone (dFAZ), and vessel density at the level of superficial (sVD) and deep (dVD) retinal vessels. RESULTS: None of the analyzed factors differed between groups with statistical significance at any timepoint. The time of recovery of vision was identical in both eyes (F = 0.91, p = 0.449). The final sFAZ was significantly smaller for group 2 (median 196 µm) than for group 1 (median 375 µm; U = 101.0; p = 0.022; r = 0.44). CONCLUSION: Both techniques resulted in similar improvements in visual acuity and decreases in CRT after 1 year. sFAZ decreased in all eyes, with a higher extent after vitrectomy.

Suprachoroidal triamcinolone versus posterior subtenon triamcinolone either alone or formulated in the management of diabetic macular edema.

PURPOSE: This study aims to compare posterior subtenon triamcinolone acetonide injection either formulated or alone versus suprachoroidal triamcinolone in the management of diabetic macular edema. METHODS: This study is a prospective interventional study that included 75 patients, divided into three groups, each group with 25 patients. Group I received a combination of triamcinolone acetonide (TA) (40 mg) and VISCOAT, which is a combination of sodium chondroitin sulfate (20 mg) and sodium hyaluronate (15 mg). The injection was done in the posterior subtenon space using the NAGATA cannula. Group II received TA (40 mg) in the posterior subtenon space. Group III underwent an injection of 4 mg/100µl of TA in the supra choroidal space. RESULTS: We found a statistically significant difference between the three studied groups regarding BCVA (P = 0.001) and CMT at six months postoperative (P = 0.001) with the highest median BCVA and lowest median CMT observed in the formulated TA group. CONCLUSION: We concluded that early treatment of DME by formulated TA is better than TA alone, and suprachoroidal TA in the form of increasing the BCVA and decreasing the CMT without any elevation of IOP. Trial registration number NCT05464953. Date of registration 17/7/2022 (retrospectively registered).

Treatment patterns and persistence rates with anti-vascular endothelial growth factor treatment for diabetic macular oedema in the UK: A real-world study.

INTRODUCTION: Anti-vascular endothelial growth factors (anti-VEGFs) are considered standard of care therapy for diabetic macular oedema (DME). This study examined treatment patterns and outcomes in patients with DME treated with anti-VEGF therapy. METHODS: Using anonymized electronic medical record data collected from three UK sites, this retrospective cohort study assessed rates of anti-VEGF intravitreal injections in adults with treatment-naïve DME who received their first treatment between 1 September 2010 and 31 July 2018. The proportion of patients with at least one interval of at least 12 weeks between injections; the distribution of injection intervals; the discontinuation rates; and the number of anti-VEGF injection-, injection-free- and total visits were assessed during the first and second years of treatment. RESULTS: Overall, 1606 patient eyes with DME were included, with no minimum follow-up. During the first and second year of treatment, 63.2% and 73.1% of eyes had at least one anti-VEGF injection interval of at least 12 weeks, respectively. In the first and second years of treatment, the mean (standard deviation) numbers of injections were 7.7 (1.9) and 5.6 (2.2), with 14.2 (5.7) and 13.4 (6.4) total clinic visits, and 6.6 (5.0) and 7.8 (5.8) injection-free visits, respectively. In total, 27.8% of patient eyes discontinued treatment during the first 2 years. CONCLUSIONS: The high number of clinic visits and high discontinuation rates demonstrate a significant unmet need for a treatment to enable sustainable extended injection intervals, while maintaining visual acuity. This could improve patient adherence and health-related quality of life for patients with DME.

Cost-effectiveness of dexamethasone compared with aflibercept in naïve diabetic macular edema.

BACKGROUND: To assess the cost-effectiveness of the delayed-release device of dexamethasone compared with aflibercept in the treatment of patients with naïve diabetic macular edema (DME) from a societal perspective in the healthcare sector Zaragoza III in Spain. METHODS: A Markov model with five states defined by visual acuity (VA) in the better-seeing eye (Snellen scale) and an additional death state were constructed. Two cohorts of patients were distributed along the VA states and treated during a year with either dexamethasone or aflibercept. One-year follow-up on each group was performed. Medical costs related to the DME treatment and follow-up, medical costs related to the DME comorbidities, and non-medical-related costs were taken into account. Costs (2020 €), health outcomes (Quality-Adjusted Life Years-QALYs), both discounted at a 3.5% annual rate, and incremental cost-effectiveness ratios (ICER: €/QALY) were determined for a lifetime horizon in the base case analysis. RESULTS: Patients treated with dexamethasone were €77,349 more costly and provided 2.667 additional QALYs (€29,002/QALY) than those treated with aflibercept. The variable efficiency per patient was calculated dividing the improvement in quality of life (on the VFQ-25 scale) by the cost of the treatment. With the obtained results it can be concluded that the efficiency of treating the patients with dexamethasone is significantly superior than the efficiency of treating them with aflibercept. CONCLUSIONS: The cost per QALY gained with the delayed-release device of dexamethasone compared with the one obtained by aflibercept in the naïve DME population is just below the €30,000 threshold, below which, new drugs are sometimes regarded as cost-effective strategies in Spain. In this model, the key variables with greater impact on the cost-effectiveness results were the selected time horizon, the chosen extrapolation method and the number of aflibercept and dexamethasone injections.

Efficacy and safety of single-dose dexamethasone implantation for patients with persistent diabetic macular edema: a systematic review and meta-analysis.

PURPOSE: This meta-analysis was conducted to evaluate the efficacy and safety of single-dose dexamethasone implantation for treating persistent DME (diabetic macular edema) refractory to anti-VEGF (anti-vascular endothelial growth factor) drugs over a period of 6 months. METHODS: All related clinical trials were reviewed by searching electronic databases of PubMed, Medline, Web of Science, Cochrane Library, and EMBASE. The primary outcome parameters were best-corrected visual acuity (BCVA) and central macular thickness (CMT). We performed this meta-analysis by using Stata15.0. RESULTS: Ten clinical trials involving 362 eyes from 328 patients were eligible in the final analysis. After single-dose dexamethasone implantation, there was a significant improvement in BCVA from baseline to 1, 3, and 6 months with an average increase of - 0.15 logMAR (p < 0.001), - 0.14 logMAR (p < 0.001), and - 0.07 logMAR (p = 0.004), respectively. Further, mean CMT decreased significantly with an average reduction of 249.18 µm (p < 0.001), 217.66 µm (p < 0.001), and 91.56 µm (p < 0.001) at months 1, 3, and 6, respectively. CONCLUSIONS: Our results indicate that switching to a dexamethasone implant could achieve significant anatomical and functional improvement among patients with refractory DME. Clinicians should be aware of this treatment option in refractory DME.

High remnant cholesterol level is relevant to diabetic retinopathy in type 2 diabetes mellitus.

BACKGROUND: Diabetic retinopathy (DR) is the primary oculopathy causing blindness in diabetic patients. Currently, there is increasing interest in the role of lipids in the development of diabetic retinopathy, but it remains controversial. Remnant cholesterol (RC) is an inexpensive and easily measurable lipid parameter; however, the relationship between RC and DR in type 2 diabetes mellitus (T2DM) has not been elucidated. This research investigates the relevance between RC levels and DR severity while building a risk prediction model about DR. METHODS: In this single-centre retrospective cross-sectional study. Each hospitalised T2DM patient had no oral lipid-lowering drugs in the past three months, and coronary angiography showed epicardial coronary artery stenosis of less than 50% and completed seven-field stereo photographs, fluorescein fundus angiography, and optical coherence tomography detection. The RC value is calculated according to the internationally recognised formula. Binary logistic regression was used to correct confounding factors, and the receiver operating characteristic (ROC) analysis was used to identify risk factors and assess the nomogram's diagnostic efficiency. RESULTS: A total of 456 T2DM patients were included in the study. The RC levels in the DR team was higher [0.74 (0.60-1.12) mmo/l vs 0.54 (0.31-0.83) mmol/l P < 0.001] in the non-DR team. After adjusting for confounding elements, RC levels are still associated with DR risk (OR = 5.623 95%CI: 2.996-10.556 P < 0.001). The ratio of DR in every stage (except mild non-proliferative diabetic retinopathy) and DME in the high RC level team were further increased compared to the low-level team (all P < 0.001). After ROC analysis, the overall risk of DR was predicted by a nomogram constructed for RC, diabetes duration, and the neutrophil-lymphocyte ratio as 0.758 (95%CI 0.714-0.802 P < 0.001). CONCLUSIONS: High RC levels may be a potential risk factor for diabetic retinopathy, and the nomogram does better predict DR. Despite these essential findings, the limitation of this study is that it is single-centred and small sample size analysis.

Aggravation of retinal hard exudates after intravitreal anti-vascular endothelial growth factor therapy for cystoid macular edema and the risk factors: a retrospective study.

BACKGROUND/AIMS: To evaluate retinal hard exudates (HEs) progression in patients with cystoid macular edema (CME) secondary to diabetic retinopathy (DR) or branch retinal vascular occlusion (BRVO) after intravitreal injections of ranibizumab (IVR) treatment and identify the risk factors for the deterioration of HEs. METHODS: This retrospective study enrolled 288 eyes with center-involving CME secondary to DR or BRVO from 288 patients (one eye per patient). All patients were treated with three loading doses of ranibizumab intravitreally at a monthly interval. The morphologic features of HEs were observed, and the HEs areas were quantified using a semi-automatic method at baseline, 1 month after the first dose of IVR and 1 month after the third dose of IVR therapy. HEs progression was defined as having a > =2-grade increase in the HEs severity scale. The best-corrected vision acuity (BCVA) and alterations in HEs areas were compared between DR and BRVO groups. And logistic regression analyses were used to identify the risk factors for HEs exacerbation. RESULTS: Morphological changes of retinal HEs occurred in all eyes after IVR therapy, although HEs area was not significantly changed in some eyes. DR group has a higher percentage of eyes with progressed HEs area than the BRVO groups (34.9% vs. 21.8%, P = 0.019) 1 month after the first dose of IVR. Both DR and BRVO groups had a decreased percentage of enlarged HEs 1 month after the third injection, but the DR group is still higher than the BRVO group (17.1% vs. 8.4%, P = 0.027). At baseline, there was no correlation between VA and HEs areas. After the first and third doses of IVR, there still was no consistent correlation between HEs severity and change in VA over time. Furthermore, CME with subretinal fluid (SRF) is associated with a higher risk of HEs progression (P = 0.001). Long CME duration and high serum low-density lipoprotein cholesterol (LDL-C) level were identified as risk factors for HEs progression following IVR treatment in both univariable and multivariable regression analyses (Odds ratio (OR) = 1.88, P = 0.012 and OR = 1.14, P = 0.021, respectively). CONCLUSIONS: Alterations in the area of retinal HEs are widely observed after IVR treatment for CME. The eyes with CME secondary to DR have a higher percentage of progressed HEs than the BRVO eyes. DME with SRF, extended duration of CME, and high LDL-C level are potential risk factors of deteriorated HEs after IVR treatment.

Assessing the Suitability of DME for Powering SI Engines by Analyzing In-Cylinder Pressure Change.

This article discusses an analysis of in-cylinder pressure change during combustion of LPG-DME fuel in IC engines. The aim of the study is to present a method for assessing the possibility of using DME as a combustion activator, and to establish its impact on the process. The study proposes a method for assessing the shift of the maximum value of cylinder pressure as a parameter which enables the impact of DME on the combustion process to be evaluated. The method was developed on the basis of bench tests carried out on an SI engine with a capacity of 1.6 dm3.

The Role of Intravitreal Corticosteroids in the Treatment of DME: Predictive OCT Biomarkers.

This work aims to summarize predictive biomarkers to guide treatment choice in DME. Intravitreal anti-VEGF is considered the gold standard treatment for centers involving DME, while intravitreal steroid treatment has been established as a second-line treatment in DME. However, more than 1/3 of the patients do not adequately respond to anti-VEGF treatment despite up to 4-weekly injections. Not surprisingly, insufficient response to anti-VEGF therapy has been linked to low-normal VEGF levels in the serum and aqueous humor. These patients may well benefit from an early switch to intravitreal steroid treatment. In these patients, morphological biomarkers visible in OCT may predict treatment response and guide treatment decisions. Namely, the presence of a large amount of retinal and choroidal hyperreflective foci, disruption of the outer retinal layers and other signs of chronicity such as intraretinal cysts extending into the outer retina and a lower choroidal vascular index are all signs suggestive of a favorable treatment response of steroids compared to anti-VEGF. This paper summarizes predictive biomarkers in DME in order to assist individual treatment decisions in DME. These markers will help to identify DME patients who may benefit from primary dexamethasone treatment or an early switch.

Aflibercept versus Faricimab in the Treatment of Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: A Review.

Diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) are common retinal vascular diseases responsible for most blindness in the working-age and older population in developed countries. Currently, anti-VEGF agents that block VEGF family ligands, including ranibizumab, bevacizumab (off-label use), brolucizumab, and aflibercept, are the first-line treatment for nAMD and DME. However, due to the complex pathophysiological background of nAMD and DME, non-response, resistance during anti-VEGF therapy, and relapses of the disease are still observed. Moreover, frequent injections are a psychological and economic burden for patients, leading to inadequate adhesion to therapy and a higher risk of complications. Therefore, therapeutic methods are strongly needed to develop and improve, allowing for more satisfactory disease management and lower treatment burden. Currently, the Ang/Tie-2 pathway is a promising therapeutic target for retinal vascular diseases. Faricimab is the first bispecific monoclonal antibody for intravitreal use that can neutralize VEGF and Ang-2. Due to the prolonged activity, faricimab allows extending the interval between successive injections up to three or four months in nAMD and DME patients, which can be a significant benefit for patients and an alternative to implanted drug delivery systems.

Changes of Estimated Glomerular Filtration Rate and Glycated Hemoglobin A1c in Diabetic Macular Edema Patients Treated by Ranibizumab and Aflibercept in the Tertiary Referral Hospital.

Background and Objectives: Intravitreal injections (IVI) of vascular endothelial growth factor (VEGF) inhibitors are guideline-indicated treatments for diabetic macular edema (DME). However, some recent data have suggested that IVI VEGF inhibitors might, through systemic absorption, lead to a reduction in renal function. Our study aims to compare changes in glycated hemoglobin A1c (HbA1c) and estimated glomerular filtration rate (eGFR) between patients who received IVI ranibizumab and aflibercept treatment and patients who have not received IVI treatments. Materials and Methods: There were 17,165 DME patients with documented ophthalmology visits in the China Medical University Hospital-Clinical Research Data Repository. Those with a history of ESRD or bevacizumab treatment history, and those with missing information on HbA1c or eGFR, were excluded. After matching by age (±2 years), gender, and the year of clinical visit, 154 patients with medical treatment (including ranibizumab and aflibercept) and 154 patients without medical treatment were included in the study. The difference between HbA1c and eGFR at baseline and 3 and 12 months after the index date between the two groups was assessed. Results: Mean HbA1c and eGFR decreased between baseline and 12 months after the index date in both groups (p < 0.05). Compared with the non-treatment group, the treatment group had significantly lower HbA1c 3 and 12 months after the index date. There was no significant difference in eGFR between the two groups. In the generalized estimating equations (GEE) model, HbA1c in the treatment group was lower than the non-treatment group (−0.44%, 95% CI = −0.75, −0.14), but eGFR was similar after adjusting for age, gender, and index-year. HbA1c and eGFR decreased with the time in the adjusted GEE model (p < 0.0001) in both groups. Conclusions: This study showed that eGFR decreased with age and time and was not related to IVI anti-VEGF treatments in our tertiary referral hospital. IVI anti-VEGF therapy was also associated with better HbA1c control. It is suggested that DME patients can receive intravitreal VEGF inhibitors without inducing more renal impairment.