Diabetic macular edema (DME) is a common complication of diabetes mellitus and a leading cause of visual impairment worldwide. It is defined as the diabetes-related accumulation of fluid, proteins, and lipids, with retinal thickening, within the macular area. DME affects a significant proportion of individuals with diabetes, with the prevalence increasing with disease duration and severity. It is estimated that approximately 25-30% of diabetic patients will develop DME during their lifetime. Poor glycemic control, hypertension, hyperlipidemia, diabetes duration, and genetic predisposition are recognized as risk factors for the development and progression of DME. Although the exact pathophysiology is still not completely understood, it has been demonstrated that chronic hyperglycemia triggers a cascade of biochemical processes, including increased oxidative stress, inflammation, activation of vascular endothelial growth factor (VEGF), cellular dysfunction, and apoptosis, with breakdown of the blood-retinal barriers and fluid accumulation within the macular area. Early diagnosis and appropriate management of DME are crucial for improving visual outcomes. Although the control of systemic risk factors still remains the most important strategy in DME treatment, intravitreal pharmacotherapy with anti-VEGF molecules or steroids is currently considered the first-line approach in DME patients, whereas macular laser photocoagulation and pars plana vitrectomy may be useful in selected cases. Available intravitreal steroids, including triamcinolone acetonide injections and dexamethasone and fluocinolone acetonide implants, exert their therapeutic effect by reducing inflammation, inhibiting VEGF expression, stabilizing the blood-retinal barrier and thus reducing vascular permeability. They have been demonstrated to be effective in reducing macular edema and improving visual outcomes in DME patients but are associated with a high risk of intraocular pressure elevation and cataract development, so their use requires an accurate patient selection. This manuscript aims to provide a comprehensive overview of the pathology, epidemiology, risk factors, physiopathology, clinical features, treatment mechanisms of actions, treatment options, prognosis, and ongoing clinical studies related to the treatment of DME, with particular consideration of intravitreal steroids therapy.

Delivering medication to the posterior segment of the eye presents a significant challenge. Intravitreal injection has emerged as the preferred method for drug delivery to this area. However, current injectable non-biodegradable implants for fluocinolone acetonide (FA) require surgical removal after prolonged drug release, potentially affecting patient compliance. This study aimed to develop an in-situ forming biodegradable implant (ISFBI) optimal formulation containing PLGA504H and PLGA756S (50:50 w/w%) with the additive NMP solvent. The goal was to achieve slow and controlled release of FA over a two-month period with lower burst release, following a single intravitreal injection. Through morphology, rheology, stability and in-vitro release evaluations, the optimal formulation demonstrated low viscosity (0.12-1.25 Pa. s) and sustained release of FA at a rate of 0.36 µg/day from the third day up to two months. Furthermore, histopathology and in-vivo studies were conducted after intravitreal injection of the optimal formulation in rabbits\' eye. Pharmacokinetic analysis demonstrated mean residence time (MRT) of 20.02 ± 0.6 days, half-life (t1/2) of 18.80 ± 0.4 days, and clearance (Cl) of 0.29 ± 0.03 ml/h for FA in the vitreous humor, indicating sustained and slow absorption of FA by the targeted retinal tissue from vitrea over the two-month period and eliminating through the anterior section of the eye, as revealed by its presence in the aqueous humor. Additionally, FA exhibited no detection in the blood and no evidence of systemic side effects or damage on the retinal layer and other organs. Based on these findings, it can be concluded that in-situ forming injectable biodegradable PLGA implants can show promise as a long-acting and controlled-release system for intraocular drug delivery.

Power-to-Gas (P2G) is considered as a promising energy storage technology in a long-time horizon. The rapid growth in the share of intermittent renewables in the energy mix is driving forward research and development in large-scale energy storage. This paper presents a feasibility analysis of a power-to-gas system in terms of various operating points and capacities. The analysis was performed using a system model, which features a solid oxide electrolyzer (SOE), a CO2 separation unit, and a methanation reactor as the key components. For the purposes of the techno-economic assessment (TEA) of the system, the CAPEX/OPEX estimation was performed and the cost structure defined. The model proposed in the study enables system-level optimization, including technical and economic criteria, considering two nominal scales: 10 kW and 40 GW, which corresponds to the nominal capacity of SOE in each case. According to the study, in an SOE-based P2G system, the cost of synthetic natural gas (SNG) production will fall by 15-21% by 2030 and 29-37% by 2050. SNG production would cost 3.15-3.75 EUR2023/kgSNG in 2030 and 2.6-3.0 EUR2023/kgSNG in 2050 for systems with SOE power >10 MW. Generally, product cost reductions occur as a result of material development and large-scale production, which influences the system\'s CAPEX. According to the research, the technology will break even by 2050. The large-scale power-to-gas system with a total of 40 GW installed capacity delivers a product price of 2.4 EUR2023/kgSNG with the average conversion efficiency of 68%.

UNASSIGNED: The 0.18 mg fluocinolone acetonide implant (FAi) is marketed for up to 36 months for treatment of noninfectious uveitis. An additional short-term corticosteroid burst prior to the 0.18 mg FAi, followed by attempt at long-term inflammation control with the 0.18 mg FAi may be beneficial given the low dose of the implant. We retrospectively reviewed all patients undergoing this treatment approach at our institution to determine its efficacy.
UNASSIGNED: Patients who received a corticosteroid burst followed by the 0.18 mg FAi with at least 6-month follow-up post 0.18 mg FAi were included. The primary outcome, treatment escalation (defined as worsening inflammation requiring escalation of therapy), was modeled using Kaplan-Meier analysis. Secondary outcomes included cystoid macular edema (CME), central macular thickness, retinal vasculitis, visual acuity, anterior chamber and vitreous cell, use of systemic therapy, use of corticosteroid drops, IOP, number of IOP lowering medications, need for glaucoma surgery, need for cataract surgery, and additional local corticosteroids.
UNASSIGNED: 32 eyes were included (mean follow-up: 19.8 months). Prior to corticosteroid burst, 37.5% were on systemic therapy, 53% had CME, and 25% had retinal vasculitis. At FAi visit, CME had decreased to 18.8%. Mean time to treatment escalation after FAi was 20.3 months (95% CI 14.8-25.7 months). No patient discontinued systemic therapy and on average 15.0% of eyes required additional local corticosteroids at each follow-up interval.
UNASSIGNED: This treatment approach demonstrates that the 0.18 mg FAi is a useful adjuvant for the treatment of noninfectious uveitis but may not be adequate as solo therapy.

UNASSIGNED: To assess ocular, visual, and anatomical outcomes following the 0.19-mg fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN®) and incisional intraocular pressure (IOP)-lowering surgery in diabetic macular edema.
UNASSIGNED: From a 36-month, phase 4, open-label, observational study (N = 202 eyes, 159 patients), 8 eyes (7 patients) required IOP-lowering surgery post-FAc; eyes were segregated by FAc-induced (n = 5, 2.47%) versus neovascular glaucoma (NVG)-related (n = 3, 1.49%) IOP elevations and assessed for IOP, best corrected visual acuity (BCVA), central subfield thickness (CST), and cup-to-disc ratio (c/d).
UNASSIGNED: Changes at 36 months were +5.4 letters BCVA (P > 0.05) and +0.09 c/d (P = 0.0217); IOP and CST were unchanged. FAc-induced-group eyes required fewer IOP-lowering medications than NVG-group eyes (2.0 versus 4.0; P < 0.01) but for longer duration (15.2 versus 2.6 months; P < 0.001).
UNASSIGNED: Post-FAc IOP-lowering surgery, regardless of cause, largely did not affect the outcomes measured; these procedures, then, may not meaningfully threaten positive outcomes. [Ophthalmic Surg Lasers Imaging Retina 2024;55:22-29.].

Drugs administered in the ocular region need to overcome ocular barriers without permanently damaging the ocular tissues. Moreover, ocular disorders of the posterior segment are more difficult to treat due to invasive procedures required to reach the posterior segment. Hence, to treat posterior disorders of the eye an attempt was made to develop nanofiber (NF) scaffolds for effective management of chronic posterior uveitis. Nanofibers (NFs) were formulated using the electrospinning technique.
NF scaffolds were formulated using the electrospinning technique. The effect of different concentrations of chitosan on NF production was studied by considering different ratios of chitosan (CS) and polyvinyl alcohol (PVA). Physicochemical characterization of NFs was performed to evaluate developed NFs.
The optimized NF scaffold had a diameter of 129 ± 3 nm. NF scaffolds were found to have a tensile strength of 0.2882 ± 0.078 N/m2, thickness of 0.16 ± 0.05 mm, and drug entrapment of 95 ± 2.0%. The bioadhesive strength of the NF was found to be 257.3 ± 0.04 g/cm2 indicating high bioadhesion of NFs to the ocular tissues. The in-vitro, ex-vivo corneal and ex-vivo scleral drug release after 12 h was found to be 78.4 ± 1.0%, 65.33 ± 0.2% and 78.41 ± 1.0%, respectively. Ex-vivo whole eye model experiment indicated a concentration of about 40 ± 1.75% of drug permeated from corneal layer to the vitreous humor after 12 h. The Hen\'s egg test-chorioallantoic membrane study (HET-CAM) study and in-vitro cytotoxicity study on Statens Seruminstitut Rabbit Cornea (SIRC) cell lines indicated that the developed drug-loaded NF scaffolds were found to be non-toxic as compared to pure drug, thus suggesting cytocompatibility.
Results of HET-CAM, sterility and ex-vivo studies indicate that the developed formulation is non-toxic, sterile, and effective for the ocular delivery of fluocinolone acetonide to the posterior segment of eye.

UNASSIGNED: To examine the long-term efficacy and safety of the intravitreal 0.2-μg/day fluocinolone acetonide implant (FAi) to treat noninfectious uveitis (NIU) of the posterior segment (PS).
UNASSIGNED: Three-year, phase III, multicenter, randomized, double-masked, controlled, prospective study (clinicaltrials.gov, NCT02746991).
UNASSIGNED: Overall, 153 patients in India with NIU-PS in ≥ 1 eye (with or without anterior uveitis) for ≥ 1 year who had ≥ 2 separate recurrences of uveitis requiring ocular injections or systemic therapy in the prior 12 months.
UNASSIGNED: Patients were randomized 2:1 for baseline FAi or sham injection and monitored for main outcome measures.
UNASSIGNED: Incidence and timing of uveitis recurrence, use of adjunctive therapy, best-corrected visual acuity, central foveal thickness, and monitoring of intraocular pressure (IOP)- and cataract-related events over 36 months.
UNASSIGNED: Overall, 153 patients (FAi, n = 101; treated sham, n = 52) were enrolled. Fluocinolone acetonide implant-treated eyes had significantly reduced uveitis recurrence rates versus treated sham (46.5% vs. 75.0%, respectively; P = 0.001) and a longer median time to recurrence (1116.0 [95% confidence interval, 847.00 to not evaluable] vs. 190.5 [95% confidence interval, 100.0-395.0] days for treated sham). Systemic adjunctive treatments were similar between groups, but fewer FAi-treated eyes required adjunctive injections (8.9% vs. 51.9% for treated sham). Visual outcomes were similar between groups, and residual macular edema was more common at 36 months in treated sham versus FAi-treated eyes (46.2% vs. 24.2%, respectively). The FAi-treated group had a lower central foveal thickness from month 12 onward. Intraocular pressure-lowering surgeries were stable in both groups, but, as expected, rates of IOP elevations were more frequent in the FAi-treated group than in the treated sham (IOP > 25 mmHg: 23.8% vs. 3.8%; IOP > 30 mmHg: 16.8% vs. 1.9%, respectively), and FAi-treated eyes had a higher incidence of cataract surgery than the treated sham (70.5% vs. 26.5%, respectively).
UNASSIGNED: In patients with NIU-PS, the 0.2-μg/day FAi is associated with reduced-uveitis recurrence and increased time to first recurrence while controlling macular edema, maintaining stable IOP levels, and providing an expected safety profile, including a higher occurrence of cataract formation over 36 months.
UNASSIGNED: The authors have no proprietary or commercial interest in any materials discussed in this article.

OBJECTIVE: Persistent diabetic macular edema (DME) remains a problem in clinical practice, with many patients having a suboptimal response to the standard of care (SOC). Evidence supports the long-term efficacy of intravitreal fluocinolone acetonide (FAc) implant (ILUVIEN®) in patients that have responded sub-optimally, although there is still scarce data from real-world Portuguese practices. We aimed to monitor the current SOC in selected Portuguese practices prior to FAc implantation and then assess the long-term effectiveness and safety of the FAc implant.
METHODS: The study included patient data from five Portuguese public hospitals.
METHODS: This was a non-interventional, multicenter audit of data collected from Retina.pt registry from patients with persistent or recurrent DME despite treatment.
METHODS: Outcome measures included changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP). Results were compared at regular times over 36 months.
RESULTS: This study included 222 eyes from 152 patients. A significant decrease in BCVA (P < 0.001) and a significant increase in CMT (P = 0.013) were observed prior to FAc. A significant increase in BCVA was registered at 6 months after FAc implant administration (P < 0.001), which was maintained during follow-up. No relevant changes in IOP were observed. Treatment burden was reduced as a result of treatment with FAc (P < 0.001 for anti-VEGF, corticosteroids, or both treatments) in the full population.
CONCLUSIONS: In Portuguese practice, data showed that pre-FAc implantation, some patients did not respond to SOC treatment and/or they were undertreated. Following FAc implant administration, there were rapid, sustained, long-term visual and anatomical improvements, and a marked reduction in treatment burden.

Background and Objectives: The ineffective combination of corticosteroids and antibiotics in treating some atopic dermatitis (AD) cases has been concerning. The skin barrier defects in AD ease the colonization of Staphylococcus aureus (S. aureus), which results in a rise in interleukin-31 (IL-31). Lumbricus rubellus (L. rubellus) has shown antimicrobial and antiallergic effects but has not been studied yet to decrease the growth of S. aureus and IL-31 levels in AD patients. This study aimed to analyze the effect of L. rubellus extract in reducing S. aureus colonization, the IL-31 level, and the severity of AD. Materials and Methods: A randomized controlled trial (RCT) (international registration number TCTR20231025004) was conducted on 40 AD patients attending Dermatology and Venereology Polyclinic, Mother and Child Hospital (RSIA), Aceh, Indonesia, from October 2021 to March 2022. AD patients aged 8-16 who had a Scoring Atopic Dermatitis (SCORAD) index > 25, with total IgE serum level > 100 IU/mL, and had healthy weight were randomly assigned into two groups: one received fluocinolone acetonide 0.025% and placebo (control group) and one received fluocinolone acetonide 0.025% combined with L. rubellus extract (Vermint®) (intervention group). The S. aureus colony was identified using a catalase test, coagulase test, and MSA media. The serum IL-31 levels were measured using ELISA assay, while the SCORAD index was used to assess the severity of and improvement in AD. Mean scores for measured variables were compared between the two groups using an unpaired t-test and Mann-Whitney U test. Results: A significant decline in S. aureus colonization (p = 0.001) and IL-31 (p = 0.013) in patients receiving L. rubellus extract was found in this study. Moreover, fourteen AD patients in the intervention group showed an improvement in the SCORAD index of more than 35% (p = 0.057). Conclusions: L. rubellus extract significantly decreases S. aureus colonization and the IL-31 level in AD patients, suggesting its potential as an adjuvant therapy for children with AD.

Purpose: To assess the impact of retinal thickness variability (RTV) control on visual and treatment burden outcomes in patients with diabetic macular edema (DME) who received the 0.19 mg fluocinolone acetonide (FAc) intravitreal implant (Iluvien, Alimera Sciences). Methods: This post hoc analysis examined the outcomes of a 3-year, phase 4, nonrandomized, open-label observational study. Retinal thickness was measured as central subfield thickness (CST). RTV was quantified by CST area under the curve (CST-AUC), retinal thickness amplitude (RTA), and retinal thickness standard deviation (RTSD). Visual outcomes were measured as best-corrected visual acuity (BCVA), and treatment burden was measured as the number of yearly supplemental DME treatments. Results: The percentage of eyes with a CST ≤300 µm fluctuated throughout the study but was significantly increased relative to baseline at 36 months (baseline: 32.9% vs 36 months: 46.8%; P < .05). FAc significantly reduced RTV in all measures more than 36 months (P < .0001). When divided into quartiles, eyes with the best RTV control post FAc had the greatest BCVA gains and improved disease control (ie, reduced need for supplemental therapy). The last-observed BCVA letter score exhibited linear correlations with CST-AUC (R2 = -0.100), RTA (R2 = -0.125), and RTSD (R2 = -0.162). A multivariate linear regression with baseline BCVA as a covariate displayed improved correlations with the last-observed BCVA, CST-AUC (R2 = -0.448), RTA (R2 = -0.432), and RTSD (R2 = -0.436). Conclusions: The sustained corticosteroid release of the 0.19 mg FAc implant reduced RTV in patients with DME, which directly correlated with significantly improved vision and a reduced supplemental treatment burden.