Treatment Of AMD Research Articles

Identification and Validation of an Aging-Associated circRNA-miRNA-mRNA Network in Neovascular Age-Related Macular Degeneration

Introduction: Neovascular age-related macular degeneration (NVAMD) is a leading cause of severe vision impairment in the elderly. Aging is one of the most pivotal underlying molecular mechanisms of NVAMD. Methods: In this study, we identified the potential aging-related genes involved in NVAMD. Considering that noncoding RNAs are vital regulators of NVAMD progression, we further explored and constructed an aging-originated circRNA-miRNA-mRNA network of NVAMD. Differential expression of 23 aging-associated genes was identified based on sequencing data and the Human Aging Genomic Resources tool at a threshold of p < 0.05, and log₂|fold change| > 1. Results: We screened 12 microRNAs (miRNAs) using public datasets and miRNet database. A total of 13 circRNAs were subsequently mined using the starBase tool. Merging these 13 circRNAs, 12 miRNAs, and 15 genes together, we obtained 281 pairs of circRNA-miRNA and 30 pairs of miRNA-mRNA. Conclusion: We created an aging-related circRNA-miRNA-mRNA network, which could be a promising target for future AMD treatments.

Process development for the extraction of rare earth elements from an acid mine drainage treatment sludge

The study focused on developing a separation approach to recover REEs from AMD treatment sludge. Parametric leaching tests were first conducted, and optimum leaching conditions were determined as a pH value of 0.5 and a leaching time of 8 min. Stage-wise precipitation tests were then applied to illustrate the precipitation behaviors of various groups of elements at different pH regions. Test results indicate that selectively recovering individual REEs by targeting one particular pH region was not feasible. However, impurities, specifically iron and silicon, could be selectively removed from REEs at pH 3.5. Afterward, three different solvent extraction methodologies, including regular solvent extraction with DEHPA, solvent extraction with a phase modifier of TBP, and post-oxidation solvent extraction, were evaluated for enhanced rare earth oxide purity. As a result of the developed process, a mixed rare earth product with a purity of 80% by weight was produced from the AMD treatment sludge.

Prevention Surpasses Treatment: 5-year Follow-Up, Cost-Utility, and Cost-Benefit of Zeaxanthin Therapy for Neovascular Age-Related Macular Degeneration.

Oral administration of zeaxanthin (Zx) 20mg daily in patients with unilateral neovascular age-related macular degeneration (nAMD) treated with triple therapy (photodynamic therapy/intravitreal bevacizumab/intravitreal dexamethasone) reduced fellow-eye 2-year nAMD incidence from 23 to 6% (p = 0.02) in a prior clinical trial. We questioned the long-term benefit and thus analyzed case-control 5-year patient data of trial participants and additional participants with 5-year follow-up, also performing cost-utility and cost-benefit analyses. Consecutive, unilateral nAMD patient outcomes for those taking 20mg Zx supplementation orally for ≥ 5years were compared with the Comparison of AMD Treatments Trials (CATT) 5-year historical controls for fellow-eye nAMD conversion. Eleven-year mean life expectancy, cost-utility and cost-benefit models were undertaken employing a 3% discount rate and 2020 US real dollars. Among 227 consecutive patients with nAMD/Zx-supplementation, 202 (90%) had 5-year follow-up. The fellow-eye nAMD 5-year conversion incidence using a Kaplan-Meier cumulative event estimate was 22% (49/227), versus 48% (167/348) with CATT control data (p < 0.0001). An 11-year cost-utility model with estimates for years 6-11 demonstrated a 0.42 (7.7%) QALY (quality-adjusted life-year) gain, including 3months of life saved per patient due to decreased nAMD fellow-eye conversion. This yielded a direct ophthalmic medical cost perspective, incremental cost-utility ratio (CUR) of -$576/QALY and a societal cost perspective CUR of -$125,071/QALY. Zx supplementation for all 2020 US unilateral nAMD cases would have theoretically saved society, primarily patients, $6.0 billion over 11years, a 1531% return on investment (ROI), or 31.3% annual ROI, on Zx costs. Oral zeaxanthin supplementation for unilateral nAMD patients appears to decrease fellow-eye long-term incidence and is cost-effective and financially rewarding. It is dominant vs. no supplementation in patients presenting with unilateral nAMD. ClinicalTrials.gov identifier, NCT01527435.

PATHOGENETICALLY DIRECTED METHOD OF PREVENTION AND TREATMENT OF AGE-MACULAR DEGENERATION

Background. Age-related macular degeneration is one of the most common causes of blindness in developed countries, especially in people over 60 years old. The incidence of AMD is projected to increase to 288 million in 2040 compared to 196 million in 2020. Cardiovascular factors, smoking, alcohol consumption, overweight, genetic factors, and metabolic disorders are risk factors for the development of AMD. There are disorders of lipid metabolism, as well as hyperreactivity of platelet purine receptors may be associated with the progression of AMD. The AREDS2 formula is currently used to treat AMD. New therapeutic strategies aimed to correct metabolic disorders are needed to decrease the development of the late stages of AMD.&#x0D; Aim: to investigate the effectiveness of improving pathogenetically directed method of prevention and treatment of age-related macular degeneration.&#x0D; Materials and methods. We observed 40 patients (80 eyes), aged 50-85 years, with AMD of category 3 (intermediate AMD), who were divided into 2 groups. The main group included 20 patients (40 eyes), 14 women and 6 men, who have prescribed a complex drug according to the standard AREDS2 scheme, as well as fenofibrate (200 mg) and clopidogrel bisulfate (75 mg). The control group included 20 patients (40 eyes), 13 women and 7 men. These patients received AREDS2 standard treatment. Progression was evaluated according to the results of OCT of the macular area according to the AREDS classification and control of corrected visual acuity (CVA). The observation period was 2 years.&#x0D; Results. No signs of progression were noted in patients of both observation groups within 6 months from the start of the prescribed therapy. In the patients of the control group, the progression of the disease was recorded after 1 year of observation according to both defined criteria. Changes in OCT were observed in 7,5% of patients in the control group, and a decrease in CVA- in 5%. In the patients of the main group who used the extended therapeutic regimen, after 1 year of follow-up, progression according to OCT signs was noted in 2,5% of cases, but there was no worsening of CVA. After 2 years of observation, signs of progression according to OST were recorded in the main group by 50% less than in the control group. According to CVA, disease progression was detected in 15% of the main group and 30% of the control group.&#x0D; Conclusions. This study complemented already existing therapeutic strategies for the preventive treatment of AMD.

High performance and mechanism of Tl(I) removal from solution by synergetic application of nanowire γ-MnOOH@biochar and free radicals: Implications to AMD treatment

Thallium (Tl) is a rare heavy metal with extreme toxicity, and Tl pollution in water bodies has frequently emerged globally. It is a challenge to effectively remove the predominant monovalent thallium from acid wastewater. In this study, highly efficient Tl(I) removal from aqueous solution was realized through synergetic application of nanowire γ-MnOOH@biochar and free radicals (·OH and SO4−) generated via activating persulfate. This method exhibited an overall robust Tl removal capacity in a wide pH range, even can remove over 97% of Tl at pH = 2, and maintain generally stable in the presence of coexisting ion and organic matter. The Tl removal capacity at low initial pH of the solution was up to 20% higher than that at alkaline conditions and fast adsorption realized in the first 10 min. This study offers a novel alternative of Tl-bearing wastewater treatment with facilely engineered composite that combines advanced oxidation and adsorption techniques, thus potentially serving as a promising method towards Tl removal from challenging acid mine drainage.

An injectable thermosensitive hydrogel encapsulating tetramethylpyrazine nanocrystals alleviates angiogenesis and apoptosis in a choroidal neovascularization mouse model

Neovascular age-related macular degeneration (nAMD) is a leading global cause of blindness characterized by vascular endothelial growth factor (VEGF)-mediated choroidal neovascularization (CNV), in which aberrant pathological angiogenesis extends from the choriocapillaris into the subretinal region. However, the lifelong regime of intraocular anti-VEGF agents, as the front-line treatment for excessive angiogenesis, is not effective for all patients and can induce devastating ocular complications. Thus, it is crucial to develop an available, durable, and affordable drug system capable of overcoming ocular obstacles and enabling the sustained release of a drug to target CNV. Owing to its multitarget properties, tetramethylpyrazine (TMP) has been widely used in clinics for its anti-angiogenic, anti-inflammatory, antioxidant, and anti-fibrotic effects. Yet, its potential clinical use in ocular disorders has been hindered by its lipophilic properties and poor absorption. Herein, we developed and optimized an injectable thermosensitive polymeric hydrogel using the solvent evaporation drying method and the “cold” approach in turn for the controlled release and high drug-loading of TMP nanoparticles, facilitating the sustained release of TMP both in vitro and in vivo. The hydrogel-encapsulated TMP nanocrystals (NCs) were synthesized and characterized by zeta potential, dynamic light scattering, scanning and transmission electron microscopy, and rheometer. The payload of the hydrophobic drug TMP to the symmetrical poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) hydrogel (TMP-NCs-gel) had a porous structure (pore size, 10–200 mm), and the transparent in situ hydrogel system immediately transitioned from the liquid to gel phase when the phase transition temperature was reached. We also demonstrated that the TMP-NCs-gel ameliorated abnormal angiogenesis and repressed photoreceptor apoptosis in vivo without inducing toxicity. Furthermore, the TMP-NCs-gel were observed to accumulate in CNV lesions in vivo, confirming their targeting characterization. Overall, this advanced formulation, combining TMP and an in situ gel system, is promising for AMD treatment and may represent an effective therapeutic strategy for patients with CNV.

Screening for biomarkers in age-related macular degeneration

ObjectiveAge-related macular degeneration (AMD) is a significant cause of blindness, initially characterized by the accumulation of sub-Retinal pigment epithelium (RPE) deposits, leading to progressive retinal degeneration and, eventually, irreversible vision loss. This study aimed to elucidate the differential expression of transcriptomic information in AMD and normal human RPE choroidal donor eyes and to investigate whether it could be used as a biomarker for AMD. MethodsRPE choroidal tissue samples (46 Normal samples, 38 AMD samples) were obtained from the GEO (GSE29801) database and screened for differentially expressed genes in normal and AMD patients using GEO2R and R to compare the degree of enrichment of differentially expressed genes in the GO, KEGG pathway. Firstly, we used machine learning models (LASSO, SVM algorithm) to screen disease signature genes and compare the differences between these signature genes in GSVA and immune cell infiltration. Secondly, we also performed a cluster analysis to classify AMD patients. We selected the best classification by weighted gene co-expression network analysis (WGCNA) to screen the key modules and modular genes with the strongest association with AMD. Based on the module genes, four machine models, RF, SVM, XGB, and GLM, were constructed to screen the predictive genes and further construct the AMD clinical prediction model. The accuracy of the column line graphs was evaluated using decision and calibration curves. ResultsFirstly, we identified 15 disease signature genes by lasso and SVM algorithms, which were associated with abnormal glucose metabolism and immune cell infiltration. Secondly, we identified 52 modular signature genes by WGCNA analysis. We found that SVM was the optimal machine learning model for AMD and constructed a clinical prediction model for AMD consisting of 5 predictive genes. ConclusionWe constructed a disease signature genome model and an AMD clinical prediction model by LASSO, WGCNA, and four machine models. The disease signature genes are of great reference significance for AMD etiology research. At the same time, the AMD clinical prediction model provides a reference for early clinical detection of AMD and even becomes a future census tool. In conclusion, our discovery of disease signature genes and AMD clinical prediction models may become promising new targets for the targeted treatment of AMD.

The Efficacy, Safety, and Efficiency of the Off-Label Use of Bevacizumab in Patients Diagnosed With Age-Related Macular Degeneration: Protocol for a Systematic Review and Meta-Analysis

Background Age-related macular degeneration (AMD) is recognized as the leading cause of vision loss in older people. Considering the phenomenon of aging societies worldwide, the prevalence of AMD is expected to increase gradually in the future. AMD can be divided into early, intermediate, and late stages, with the early and intermediate stages being mainly asymptomatic, and the late stage being classified as geographic atrophy, neovascular AMD, or both. Current pharmacological treatments for neovascular AMD include anti–vascular endothelial growth factor agents, such as ranibizumab, pegaptanib, and aflibercept. Additionally, it has been reported that the off-label use of intravitreally administered bevacizumab is effective. It is also lower cost than other agents, which makes it an interesting pharmacological approach. Objective This review aims to evaluate the efficacy, safety, and efficiency of bevacizumab for the treatment of neovascular AMD. Methods This review will only consider randomized controlled clinical trials that compare the use of bevacizumab with another pharmacological agent or a placebo in patients aged 50 years and older who are diagnosed with vascular AMD. It will exclude studies that include participants diagnosed with polypoidal choroidal vasculopathy or retinal angiomatous proliferation. To identify and select relevant articles, we will develop a highly sensitive search strategy and apply it in MEDLINE via the PubMed platform. Upon selection of the studies and analysis of the titles, abstracts, and full texts, the results will be presented according to the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The analysis and extraction of the data will be performed by 2 independent reviewers. Risk of bias will be evaluated with the Critical Appraisal Skills Programme (CASP) checklist. Finally, the same reviewers will also perform a quality assessment of the included studies with the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool. Results The search strategy, after the application of the inclusion and exclusion criteria, identified 15 randomized clinical trials, which are currently being analyzed. This project has no funding and it has been developed by a multidisciplinary research team of pharmacologists and orthoptists. The study was initiated in May 2021 and it is expected to conclude by the end of 2023. Conclusions This review will provide a synthesis of current information and underlying evidence about the off-label use of bevacizumab in neovascular AMD. It will provide a clearer vision of a possible new pharmacological approach, as well as the most suitable treatment designs, for the treatment of neovascular AMD. Trial Registration PROSPERO CRD42021244931; https://tinyurl.com/p6m5ycpk International Registered Report Identifier (IRRID) DERR1-10.2196/38658

The Clinical Outcome of Brolucizumab in the Treatment of Neovascular Age-Related Macular Degeneration – A Prospective Observational Study

Background: Neovascular age-related macular degeneration (nAMD), also known as wet AMD, is a chronic eye disease that affects the macula, which is the central part of the retina responsible for sharp, central vision. Brolucizumab is a type of anti-vascular endothelial growth factor (VEGF) drug, which works by blocking the activity of a protein called VEGF that promotes the growth of abnormal blood vessels under the macula in neovascular AMD. The aim of this study was to evaluate the clinical outcome of brolucizumab in the treatment of neovascular age-related macular degeneration. Material &amp; Methods: This prospective observational study was conducted in Department of Ophthalmology, Bangladesh Eye Hospital &amp; Institute Ltd, Dhaka, Bangladesh, during the period from February 2022 to February 2023. Total 60 patients with neovascular AMD were included in this study who were treated with brolucizumab. Results: The mean age of the patients was 74.3 (SD±9.8) years. Majority of the study subjects were (51.7%) female patients in the study. In our study, majority (38.3%) of the patients had only their right eye affected. In optical coherence tomography (OCT) findings, we found that a high percentage of patients had subretinal fluid (85%), intraretinal fluid (61.7%), and sub-RPE fluid (83.3%). The BCVA showed a significant change after 12 weeks of treatment, as indicated by the P-value of 0.0007. Here improvement of vision was seen in patients with AMD with active Choroidal neovascularization (CNV). But in case of AMD with macular scar, no improvement of vision was seen. In addition, the SRT, FCP, and CMT parameters also showed a statistically significant (P&lt;0.001) improvement after brolucizumab treatment. In our study, 4 patients (6.7%) experienced intraocular inflammation, which is inflammation within the eye, 2 patients (3.3%) reported cloudy vision, and 3 patients (5%) experienced eye redness as a complication of the treatment. The majority of the patients, 51 (85%) did not experience any complications from the treatment. After treatment, improved vision was seen in most of the study patients (70%) and 30% had no improvement. Conclusion: From the findings of our study, it can be concluded that brolucizumab may be an effective treatment for neovascular AMD, as it can improve the best-corrected visual acuity and structural outcomes of the retina such as subfoveal retinal thickness, foveal center point, and central macular thickness. There was also a tolerable complication rate after treatment.

Results of anti-VEGF treatment for neovascular AMD in eyes with different baseline visual acuity in Turkish population-based on real life data-Bosphorus retina study group

BackgroundTo investigate the anatomical and visual outcomes of the patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (anti-VEGF), according to the baseline best-corrected visual acuity (BCVA) based on the multicenter real-life data. MethodsFive-hundred-ninety patients who had taken the Pro Re Nata (PRN) treatment regimen with three loading doses and at least one year of follow-up were included. The patients were divided into three groups according to the baseline BCVA: Group 1 (BCVA ≥ 1.3 Logmar), Group 2 (1.3 Logmar > BCVA ≥ 0.3 Logmar), and Group 3 (BCVA ≤ 0.2 Logmar). BCVA, central macular thickness (CMT), and the number of injections and visits were evaluated. ResultsThere were 175, 322, and 93 patients in Group 1, Group 2, and Group 3, respectively. The number of visits and injections in the 1st year was not different between the groups (p = 0.58 and p = 0.08) and was 7.09 and 4.41 (Group 1), 6.59 and 5.58 (Group 2), 6.77 and 4.08 (Group 3). There was a significant difference in CMT between the baseline and 12th month in Group 1 and Group 2 (p < 0.001, p < 0.001, respectively) but not in Group 3 (p = 0.84). BCVA was significantly better in the 12th month in Group 1 (p < 0.001), slightly worse in Group 2 (p = 0.79), and significantly worse in Group 3 (p < 0.001). ConclusionThis study provides evidence that an inadequate number of injections cannot protect vision. Moreover, it can cause vision loss, especially in the eyes with good vision.

Сравнительный анализ эффективности препаратов ранибизумаб и афлиберцепт

Summary. Intravitreal administration of anti-VEGF drugs is currently the main method of treatment for all types of exudative form of age-related macular degeneration (eAMD). However, most studies did not divide patients. Currently, there are two drugs with a long clinical history of use in Russia for the treatment of neovascular AMD, these are ranibizumab and aflibercept. Data regarding the binding affinity of ranibizumab and aflibercept to VEGF have been inconsistent in in vitro studies. To analyze the effectiveness of aflibercept and ranibizumab in real clinical practice over a three-year follow-up period. Material and methods. The clinical material of the study was the data of examination and treatment of 344 patients (344 eyes) aged 50 to 87 years with a diagnosis of exudative form of age-related macular degeneration on the basis of the Federal State Budget Scientific Institution “NIIGB. Results. During the first treatment, the difference between groups in BCVA (0.51 ± 0.25 for both groups) and CRT (403.3 ± 115.9 for ranibizumab and 364.2 ± 119.6 for aflibercept) during the first year was not noted (p &gt; 0.05). During the third year of observation and treatment in both groups, the same number of IVIs was produced – 3.5. BCVA in the aflibercept group was 0.53 ± 0.30, in the ranibizumab group it was 0.41 ± 0.30 (p &lt; 0.05). In our opinion, the main factor in the stabilization of visual functions in the aflibercept group is more thorough “disease control», while in the ranibizumab group, with a comparable number of injections, visual acuity was lower by the end of the 3rd year of observation, which we attribute to the negative effect of persistent edema, leading to to death of retinal cells. Keywords: age related macular degeneration, anti-VEGF therapy, aflibercept, ranibizumab

Establishment of specific age-related macular degeneration relevant gene expression panels using porcine retinal pigment epithelium for assessing fucoidan bioactivity

PurposeAge-related macular degeneration (AMD) is the leading cause of severe vision loss in industrialized nations. Important factors in pathogenesis are oxidative stress, inflammation, and, in the wet form of AMD, angiogenesis. Fucoidans, sulfated polysaccharides from brown algae, may have antioxidant, anti-inflammatory, and antiangiogenic effects. In this study, we established specific gene expression panels for inflammation, oxidative stress and angiogenesis in porcine retinal pigment epithelium (RPE), and investigated the effect of fucoidans on gene expression under different noxious agents. MethodsPrimary porcine RPE cells cultured for at least 14 days were used. Using viability assays with tetrazolium bromide and real-time polymerase chain reaction of marker genes, positive controls were established for appropriate concentrations and exposure times of selected noxious agents (lipopolysaccharide (LPS), H2O2, CoCl2). Three different AMD relevant gene panels specific for porcine RPE for inflammation, oxidative stress, and angiogenesis were established, and the influence of fucoidans (mainly Fucus vesiculosus; FV) on gene expression was investigated. ResultsThe following was shown by gene expression analyses:(1) Inflammation panel: Expression of 18 genes was affected under LPS (three days). Among them, LPS increased genes for interleukin 1 receptor 2, interleukin 8, cyclooxygenase-2 and vascular cell adhesion protein 1 expression which were diminished when FV was present.(2) Oxidative stress panel: Under stimulation of H2O2 (one day) and LPS (one day), expression of a total of 15 genes was affected. LPS induced increase in genes for superoxide dismutase-1, C-X-C motif chemokine 10, and CC chemokine ligand-5 expression was not detected when FV was present.(3) Angiogenesis panel: Under stimulation with CoCl2 (three days) expression of six genes was affected, with the increase of genes for angiopoietin 2, vascular endothelial growth factor receptor-1, and follistatin being diminished when FV was present. ConclusionThree specific gene expression panels for porcine RPE that map genes for three of the major pathological factors of AMD, inflammation, oxidative stress, and angiogenesis, were established. Further, we demonstrated that fucoidans can reduce stress related gene activation in all of these three major pathogenic pathways. This study is another indication that fucoidans can act on different pathomechanisms of AMD simultaneously, which provides further evidence for fucoidans as a possible drug for treatment and prevention of AMD.

Тактика ведения пациентов с экссудативной формой возрастной макулярной дегенерации при резистентности к одному из анти-VEGF препаратов

The exudative form of AMD can develop suddenly, leading within a few weeks or months to the death of photoreceptors, a sharp decrease in BCVA and persistent central scotoma. Despite significant progress in the treatment of neovascular AMD associated with the introduction of anti-VEGF drugs into clinical practice, a number of patients have an insufficient response or its absence with standard administration regimens, and sometimes a decrease in the therapeutic effect after repeated intravitreal injections [1, 2]. Purpose. To development management tactics for patients resistant to one of the anti-VEGF drugs. Material and мethod. This study included 25 patients with a diagnosis of exudative AMD who received Aflibercept in the treat &amp; extend regimen for a year, without a significant effect (persistence of intraretinal, subretinal and/or fluid under RP). Patients were switched to brolucizumab. The mean maximum correctable visual acuity in patients treated with aflibercept before switching drugs was 0.41 ± 0.11. The mean number of injections during the first year in the aflibercept group was 7.1 and 6.8 after switching to brolucizumab. The maximum correctable visual acuity at the end of 1 year of treatment with brolucizumab was 0.47 ± 0.1. Before the start of treatment with aflibercept, the mean CRT was 435.2 ± 119.8, at the end of the first year of treatment 403.3 ± 115.9, before 1 intravitreal injection of brolucizumab 407.2 ± 119.3 and 1 year after the start of therapy 357.6 ± 111.4 (p = 0.042). A statistical difference was found between the preparations and the height of the detachment of the retinal pigment epithelium at the end of the first year of treatment. Changes in the height of detachment of the retinal pigment epithelium in 3 eyes (12 %) were not observed when changing the drug. A positive response to drug switching should be noted, although it cannot be overlooked that there are patients who are resistant to anti-VEGF therapy per se. Keywords: the exudative form of AMD, anti-VEGF drugs, neovascular AMD.

Study protocol on prevalence of non-exudative macular neovascularisation and its contribution to prediction of exudation in fellow eyes with unilateral exudative AMD (EYE-NEON)

PurposeFellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD) are at risk of developing macular neovascularisation (MNV). These eyes may first develop subclinical non-exudative MNV (neMNV) before they leak to form exudative MNV (eMNV). The EYE NEON study is a 2-year study aimed at estimating the prevalence and incidence of neMNV and evaluating its role as a predictor for conversion to neovascular AMD.MethodsEYE NEON is a multicentre study that will run in retinal clinics across 25 National Health Service with the aim to recruit 800 patients with new onset nAMD in the first eye. The fellow-eye with no evidence of nAMD at baseline will be the study eye. All study eyes will have OCT and OCTA done at first and second year following first anti-VEGF treatment to the first eye (non-study eye), with new onset nAMD. We will estimate the prevalence and incidence of neMNV over 2 years, rate of conversion from neMNV to eMNV and numbers initiated on treatment for neovascular AMD in the study eye will be reported. Predictive models of conversion including neMNV with other demographic and imaging parameters will be developed.ConclusionThe study design with proposed target sample size is sufficient to evaluate the retinal imaging characteristics of the study eyes with and without neMNV and develop predictive models to inform risk of conversion to nAMD.

Nanofiber-coated implants: Development and safety after intravitreal application in rabbits

Intravitreal injections are the preferred choice for drug administration to the posterior segment of the eye. However, the required frequent injections may cause complications to the patient and low adherence to the treatment. Intravitreal implants are able to maintain therapeutic levels for a long period. Biodegradable nanofibers can modulate drug release and allow the incorporation of fragile bioactive drugs. Age-related macular degeneration is one of the world major causes of blindness and irreversible vision loss. It involves the interaction between VEGF and inflammatory cells. In this work we developed nanofiber-coated intravitreal implants containing dexamethasone and bevacizumab for simultaneously delivery of these drugs. The implant was successfully prepared and the efficiency of the coating process was confirmed by scanning electron microscopy. Around 68% of dexamethasone was released in 35 days and 88% of bevacizumab in 48hs. The formulation presented activity in the reduction of vessels and was safe to the retina. It was not observed any clinical or histopathological change, neither alteration in retina function or thickness by electroretinogram and optical coherence tomography during 28 days. The nanofiber-coated implants of dexamethasone and bevacizumab may be considered as a new delivery system that can be effective for the treatment of AMD.

Effects of Initial pH and Carbonate Rock Dosage on Bio-Oxidation and Secondary Iron Mineral Synthesis.

The effect of pH is a key factor in biomineralization mediated by Acidithiobacillus ferrooxidans to promote the transformation of Fe into secondary iron minerals. This study aimed to investigate the effects of initial pH and carbonate rock dosage on bio-oxidation and secondary iron mineral synthesis. Variations in pH and the concentrations of Ca2+, Fe2+, and total Fe (TFe) in the growth medium of A. ferrooxidans were examined in the laboratory to determine how they affect the bio-oxidation process and secondary iron mineral synthesis. The results showed that in systems with an initial pH of 1.8, 2.3, and 2.8, the optimum dosages of carbonate rock were 30, 10, and 10 g, respectively, which significantly improved the removal rate of TFe and the amount of sediments. At an initial pH of 1.8 and a carbonate rock dosage of 30 g, the final removal rate of TFe reached 67.37%, which was 28.03% higher than that of the system without the addition of carbonate rock, and 36.9 g·L-1 of sediments were generated, which was higher than that of the system without the addition of carbonate rock (6.6 g·L-1). Meanwhile, the number of sediments generated by adding carbonate rock were significantly higher than those without the addition of carbonate rock. The secondary minerals were characterized by a progressive transition from low crystalline assemblages composed of calcium sulfate and subordinated jarosite, to well crystal-line assemblages composed of jarosite, calcium sulfate, and goethite. These results have important implications for comprehensively understanding the dosage of carbonate rock in mineral formation under different pH conditions. The findings help reveal the growth of secondary minerals during the treatment of AMD using carbonate rocks under low-pH conditions, which offers valuable information for combining the carbonate rocks with secondary minerals to treat AMD.

Qihuang Granule protects the retinal pigment epithelium from oxidative stress via regulation of the alternative complement pathway

BackgroundAge-related macular degeneration (AMD) is a leading cause of vision loss in elderly people, and dry AMD is the most common type of AMD. Oxidative stress and alternative complement pathway activation may play essential roles in the pathogenesis of dry AMD. There are no available drugs for dry AMD. Qihuang Granule (QHG) is an herbal formula for the treatment of dry AMD, and it achieves a good clinical effect in our hospital. However, its potential mechanism is unclear. Our study investigated the effects of QHG on oxidative stress-associated retinal damage to reveal its underlying mechanism.MethodsOxidative stress models were established using H2O2 and NaIO3 in ARPE-19 cells and C57BL/6 mice. Cell apoptosis and viability were assessed using phase contrast microscopy and flow cytometry, respectively. Alterations in the mouse retinal structure were evaluated using Masson staining and transmission electron microscopy (TEM). The expression of complement factor H (CFH), complement component 3a (C3a) and complement component 5a (C5a) in retinal pigment epithelium (RPE) cells and mice was measured using RT‒PCR, Western blot analysis and ELISA.ResultsPretreatment with QHG significantly prevented cell apoptosis and disorder of the RPE and inner segment/outer segment (IS/OS) in H2O2-treated RPE cells and NaIO3-injected mice. QHG alleviated mitochondrial damage in mouse RPE cells, as shown by TEM. QHG also promoted CFH expression and inhibited the expression of C3a and C5a.ConclusionsThe results suggest that QHG protects the retinal pigment epithelium from oxidative stress, likely by regulating the alternative complement pathway.

Heavy Metal Analysis and Health Risk Assessment of Potato (Solanum tuberosum L.) Cultivars irrigated with Fly Ash-Treated Acid Mine Drainage

In water-scant regions, the reuse of (un)treated acid mine drainage effluent (AMD) water for crop irrigation has turned into a prerequisite. The study assesses the levels of heavy metals, and health risk assessment in two potato crop cultivars, namely, Fianna and Lady rosetta (both determinate and indeterminate) when exposed to irrigation with different fly ash: acid mine drainage amelioration ratios. The study investigates the health risk assessment in the potato tissues namely, stem, tubers, new and old leaves of the potato cultivars. The treatments constituted a control, 50% FA: AMD, 75% FA: AMD ratio, and 100% AMD (untreated AMD). The results showed that the heavy metals of plants irrigated with AMD mixed with FA was significantly affected differently at harvest. In summary, the concentration of Cd was over the WHO acceptable standards in untreated acid mine drainage water. Fianna recorded 1.34 mg/kg while a notably decrease was observed in Lady rosetta with (1.01 mg/kg). In any case, FA was proven to significantly lessen the Cd particles in both FA-AMD ratios: Cd content was 0.98 mg/kg and 0.84 mg/kg in 50% FA: AMD treatment for Fianna and Lady rosetta separately, while the recommended maximum limit is 0.1 mg/kg. With the readings recorded, they are slightly high according to the CODEX general standard for food contaminants and toxins in food and feed (CODEX STAN 193-1995). Then again, in 75% FA: AMD ratio, the Cd concentration was 0.04 mg/kg and 0.03 mg/kg for Fianna and Lady rosetta exclusively. It is in this way obvious that FA adsorbed the Cd ions, and the two cultivars fulfill the CODEX guideline, nonetheless the potato crop irrigated with a 75% FA: AMD ratio can be consumed by humans without causing any detrimental effects.

Dynamic experiment on remediation of acid mine drainage by iron–carbon microelectrolysis enhancing sulfate-reducing bacteria

This study combined IC-ME technology with SRB to strengthen biological activity and to achieve the simultaneous removal of heavy metal ions and sulfate to provide new methods for realizing low-cost, efficient and stable treatment of AMD.

Schoenoplectus californicus as Potential Remover of Metal Elements from Mine Effluents: A Laboratory Assessment

AbstractAcid mine drainage (AMD) is one of the most significant environmental challenges facing the mining industry worldwide. For this reason, many methods for AMD treatment are developed, being wetlands a good option for metal elements removal from these mining effluents. The efficiency of Peruvian native plants such as Schoenoplectus californicus (S. californicus) to remove metal elements in effluents through artificial wetlands is studied. Batch removal tests are carried out with different effluents containing copper, zinc, lead, and iron. For iron‐metal binary effluents, copper, zinc, and lead are removed by 82%, 75%, and 88%; while in the effluent containing all metals, the removal rate is 90% and 92% for copper and lead, respectively. According to the preliminary results, it is concluded that iron interferes more in the removal of zinc and lead than in copper from binary effluents. The use of S. californicus turns out to be an efficient, attractive, and economical alternative for the treatment of effluents contaminated with copper, zinc, lead, and iron.