scholarly journals New molecular targets for the treatment of neovascular age-related macular degeneration

2017 ◽  
Vol 1 (3) ◽  
Author(s):  
Gian Marco Tosi ◽  
Marcella Barbarino ◽  
Maurizio Orlandini ◽  
Federico Galvagni
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Current Treatment ◽  
Age Related Macular Degeneration ◽  
Western World ◽  
Treatment Protocols ◽  
Anti Vegf ◽  
Age Related ◽  
Long Term Follow Up ◽  
New Treatments

Age-related macular degeneration (AMD) is a progressive chronic disease that currently represents the leading cause of irreversible vision loss in the western world. Experimental and clinical evidence has demonstrated that vascular endothelial growth factor A (VEGF-A) plays an important role in promoting the choroidal neovascularization that characterizes the wet form of AMD. Intravitreal injection of anti- VEGF-A agents is the current treatment of choice for neovascular AMD (nAMD). These agents have brought about dramatic changes in the treatment of nAMD, but most patients require frequently repeated injections and regular long-term follow-up, with a significant percentage of them showing resistance to anti-VEGF-A drugs. Thus, the identification of additional therapies that could improve the treatment protocols is needed. There are numerous areas of investigation into new treatments, with increasing efforts being made to study drugs that address various targets along the angiogenic signaling cascade, or other pathways related to the onset of nAMD. The aim of the present review is to summarize and discuss promising new therapies and targets that have the potential to improve outcomes and to lengthen treatment durability, especially in patients with recalcitrant or recurrent forms of nAMD.

scholarly journals Mingjing granule, a traditional Chinese medicine in the treatment of neovascular age-related macular degeneration: study protocol for a randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yamin Li ◽  
Lina Liang ◽  
Torkel Snellingen ◽  
Kai Xu ◽  
Yun Gao ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Macular Degeneration ◽  
Vision Loss ◽  
Age Related Macular Degeneration ◽  
Case Report Form ◽  
Link Type ◽  
Anti Vegf ◽  
Age Related ◽  
Function Test

Abstract Background Neovascular age-related macular degeneration (nAMD) is the most common cause of irreversible vision loss and blindness among the older people aged 50 and over. Although anti-vascular endothelial growth factor (anti-VEGF) therapies have resulted in improving patient outcomes, there are limitations associated with these treatments. In China, traditional Chinese medicine (TCM) has been used to treat eye diseases for more than 2000 years. Previous studies have shown that TCM may be beneficial for nAMD patients. However, explicit evidence has not been obtained. The purpose of the present trial is to examine the efficacy and safety of the Mingjing granule, a compound Chinese herbal medicine, for nAMD patients. Methods/design This is a double-blind, placebo-controlled, randomized trial of Mingjing granule as an add-on to intravitreous ranibizumab for nAMD. One hundred eighty nAMD patients from six hospitals in China will be enrolled according to the inclusion and exclusion criteria and randomly allocated into two groups, 90 in each. All participants will receive a 24-week treatment and then be followed up for another 24 weeks. The primary outcome is the mean change of best-corrected visual acuity at week 24 and 48 as compared to the baseline. The secondary outcomes include mean change in central retinal thickness, area of retinal hemorrhage and exudation, and TCM syndrome score, mean number of intravitreal ranibizumab injection, and total cost of the treatment. Indexes of safety include blood regular test, urine regular test, liver function test, renal function test, and electrocardiogram from baseline to weeks 24 and 48. Qualitative control and some standard operating processes will be formed throughout the trial. Any ocular or systemic adverse events will be treated suitably, and related data will be recorded accurately and completely in the case report form. Discussion Based on previous empirical and animal laboratory studies, this study will address the question of whether Mingjing granule could contribute to improving efficacy, safety, and efficiency with need for fewer intravitreal injections of anti-VEGF, improving compliance and visual outcomes in the management of persons with nAMD. Trial registration Chinese Clinical Trial Registry (http://www.chictr.org.cn), ChiCTR2000035990. Registered on 21 August 2020.

Long-term outcome of neovascular age-related macular degeneration: association between treatment outcome and major risk alleles

2021 ◽  
pp. bjophthalmol-2021-319054
Author(s):  
Brice Nguedia Vofo ◽  
Gala Beykin ◽  
Jaime Levy ◽  
Itay Chowers
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Age Related Macular Degeneration ◽  
Long Term Outcome ◽  
Risk Alleles ◽  
Macular Atrophy ◽  
Anti Vegf ◽  
Age Related

AimsTo evaluate the long-term functional and anatomical outcomes of neovascular age-related macular degeneration (nvAMD) treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) for up to 10 years, and to identify associated risk factors.MethodsClinical and optical coherence tomography findings were retrieved for nvAMD cases treated with intravitreal anti-VEGF compounds using a treat-and-extend protocol. In addition, the major risk alleles for AMD in the CFH (rs1061170), HTRA1 (rs1200638) and C3 (rs2230199) genes were genotyped.ResultsFrom 276 eligible eyes in 206 patients, 80 eyes (29%) in 66 patients (32.0%) had a follow-up period of ≥8 years and were included in this study. Over a 10-year period, 73.3±28.0 (mean±SD) anti-VEGF injections were administered. Best-corrected visual acuity (BCVA; LogMAR) deteriorated from 0.55±0.53 at baseline to 1.00±0.73 at 10 years (p<0.0005). Central subfield thickness (CST) decreased from 415.8±162.1 µm at baseline to 323±113.6 µm (p<0.0005) after three monthly injections and remained lower than baseline throughout the follow-up period. Visual outcome was associated with BCVA and intraretinal fluid (IRF) at baseline, macular atrophy, and macular thinning at follow-up. The decrease in CST was inversely correlated with the number of CFH and/or C3 risk alleles carried by the patient (Pearson’s r: −0.608; p=0.003).ConclusionsPatients with nvAMD who received anti-VEGF therapy for 10 years developed substantial vision loss associated with the presence of IRF at baseline and macular atrophy. Major risk alleles for AMD in two complement genes were associated with a reduced long-term reduction in macular thickness.

scholarly journals Current and upcoming anti-VEGF therapies and dosing strategies for the treatment of neovascular AMD: a comparative review

2019 ◽  
Vol 4 (1) ◽  
pp. e000398 ◽  
Author(s):  
Saira Khanna ◽  
Rahul Komati ◽  
David A Eichenbaum ◽  
Ishani Hariprasad ◽  
Thomas A Ciulla ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Disease Process ◽  
Age Related Macular Degeneration ◽  
Anti Vegf ◽  
Age Related ◽  
Optimal Dosing ◽  
Comparative Review ◽  
Dosing Strategies ◽  
Endothelial Growth Factor

Age-related macular degeneration is the leading cause of vision loss in the developed world, with the expected number of affected elderly individuals reaching 17.8 million. Antivascular endothelial growth factor (anti-VEGF) injection therapy has been instrumental in treating a disease process that was previously thought to be untreatable. Over the past two decades, landmark studies have demonstrated the efficacy of different anti-VEGF medications and investigated the optimal dosing regimen and delivery mechanism to increase overall vision and minimise patient burden. In this review, we outline landmark neovascular age-related macular degeneration clinical trials that have demonstrated level 1 evidence for its usage or have contributed to the understanding of how to dose these agents.

scholarly journals Anti-VEGF therapy of neovascular age-related macular degeneration: from randomized trials to routine clinical practice

2019 ◽  
Vol 12 (2) ◽  
pp. 97-105 ◽  
Author(s):  
R. R. Fayzrakhmanov
Keyword(s):  
Clinical Practice ◽  
Macular Degeneration ◽  
Randomized Clinical Trials ◽  
High Reliability ◽  
Functional Results ◽  
Routine Clinical Practice ◽  
Age Related Macular Degeneration ◽  
Treatment Protocols ◽  
Anti Vegf ◽  
Age Related

Antivasoproliferative therapy is a revolutionary trend in the treatment of neovascular age-related macular degeneration (nAMD), as it is aimed at blocking growth factors of the newly formed vessels. Currently, two anti-VEGF drugs are registered for ophthalmological use, and the search for new molecules is only gaining momentum. Studying new approaches to treatment and developing innovative drugs, modern medicine relies on the data from international randomized clinical trials (RCT). The fact that this direction attracts much scientific interest is explained by high reliability of the data obtained with RCTs. However, when analyzing the effectiveness of anti-VEGF therapy in patients with nAMD in routine clinical practice, many ophthalmologists are confronted with discrepancies between the expected morphological and functional results as predicted by RCTs and those obtained in reality. It is thus important to bear in mind that RCTs simply determine how the dynamics of morphofunctional parameters should look like, whilst the ideal result is only achievable through correct implementation of therapeutic strategy in real clinical practice. The results obtained in the practice of any specialist wholly depend on how carefully the prescribed treatment protocols are followed by doctors and patients, how burdensome the treatment is, as well as on the potential of the medication. This literary review offers a comparative analysis of the results achieved by using anti-VEGF drugs (ranibizumab and aflibercept) obtained in key RCTs and in routine clinical treatment of nAMD patients.

scholarly journals Neovascular Age-Related Macular Degeneration: Therapeutic Management and New-Upcoming Approaches

2020 ◽  
Vol 21 (21) ◽  
pp. 8242
Author(s):  
Federico Ricci ◽  
Francesco Bandello ◽  
Pierluigi Navarra ◽  
Giovanni Staurenghi ◽  
Michael Stumpp ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Repeated Administration ◽  
Current Treatment ◽  
Age Related Macular Degeneration ◽  
Significant Advance ◽  
Neovascular Amd ◽  
Significant Treatment ◽  
Anti Vegf ◽  
Age Related ◽  
Ankyrin Repeat Proteins

Age-related macular degeneration (AMD) constitutes a prevalent, chronic, and progressive retinal degenerative disease of the macula that affects elderly people and cause central vision impairment. Despite therapeutic advances in the management of neovascular AMD, none of the currently used treatments cures the disease or reverses its course. Medical treatment of neovascular AMD experienced a significant advance due to the introduction of vascular endothelial growth factor inhibitors (anti-VEGF), which dramatically changed the prognosis of the disease. However, although anti-VEGF therapy has become the standard treatment for neovascular AMD, many patients do not respond adequately to this therapy or experience a slow loss of efficacy of anti-VEGF agents after repeated administration. Additionally, current treatment with intravitreal anti-VEGF agents is associated with a significant treatment burden for patients, caregivers, and physicians. New approaches have been proposed for treating neovascular AMD. Among them, designed ankyrin repeat proteins (DARPins) seem to be as effective as monthly ranibizumab, but with greater durability, which may enhance patient compliance with needed injections.

scholarly journals Sunitinib-Loaded MPEG-PCL Micelles for the Treatment of Age-Related Macular Degeneration

2020 ◽  
Vol 88 (3) ◽  
pp. 30 ◽  
Author(s):  
Jarriaun Streets ◽  
Priyanka Bhatt ◽  
Deepak Bhatia ◽  
Vijaykumar Sutariya
Keyword(s):  
Macular Degeneration ◽  
Polymeric Micelles ◽  
Retinal Pigment Epithelial Cell ◽  
Retinal Pigment ◽  
Current Treatment ◽  
Age Related Macular Degeneration ◽  
Intravitreal Injections ◽  
Epithelial Cell Line ◽  
Anti Vegf ◽  
Age Related

Age-related macular degeneration (AMD) will be responsible for the vision impairment of more than five million late-aged adults in the next 30 years. Current treatment includes frequent intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents. However, there are methods of drug delivery that can decrease the frequency of intravitreal injections by sustaining drug release. MPEG-PCL ((methoxypoly(ethylene glycol) poly(caprolactone)) has been reported as biocompatible and biodegradable. Polymeric micelles of MPEG-PCL can be useful in efficiently delivering anti-VEGF drugs such as sunitinib to the posterior segment of the eye. In this study, the novel micellar formulation exhibited an average dynamic light scattering (DLS) particle size of 134.2 ± 2.3 nm with a zeta potential of −0.159 ± 0.07 mV. TEM imaging further confirmed the nanoscopic size of the micelles. A sunitinib malate (SM)-MPEG-PCL formulation exhibited a sustained release profile for up to seven days with an overall release percentage of 95.56 ± 2.7%. In addition to their miniscule size, the SM-MPEG-PCL formulation showed minimal cytotoxicity onto the ARPE-19 human retinal pigment epithelial cell line, reporting a percent viability of more than 88% for all concentrations tested at time intervals of 24 h. The SM-MPEG-PCL micelles also exhibited exceptional performance during an anti-VEGF ELISA that decreased the overall VEGF protein expression in the cells across a 24–72 h period. Furthermore, it can be concluded that this type of polymeric vehicle is a promising solution to symptoms caused by AMD and improving the management of those suffering from AMD.

scholarly journals Modulated anti-VEGF therapy under the influence of lipid metabolizing proteins in Age related macular degeneration: a pilot study

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Kaushal Sharma ◽  
Priya Battu ◽  
Ramandeep Singh ◽  
Suresh Kumar Sharma ◽  
Akshay Anand
Keyword(s):  
Visual Acuity ◽  
Macular Degeneration ◽  
Vision Loss ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Clinical Images ◽  
Anti Vegf ◽  
Age Related ◽  
Wet Amd ◽  
Group 1

AbstractAge-related macular degeneration (AMD) is a devastating retinal disease that results in irreversible vision loss in the aged population. The complex genetic nature and degree of genetic penetrance require a redefinition of the current therapeutic strategy for AMD. We aimed to investigate the role of modifiers for current anti-VEGF therapy especially for non-responder AMD patients. We recruited 78 wet AMD cases (out of 278 AMD patients) with their socio-demographic and treatment regimen. Serum protein levels were estimated by ELISA in AMD patients. Data pertaining to the number of anti-VEGF injections given (in 1 year) along with clinical images (FFA and OCT) of AMD patients were also included. Visual acuity data (logMAR) for 46 wet AMD cases out of a total of 78 patients were also retrieved to examine the response of anti-VEGF injections in wet AMD cases. Lipid metabolizing genes (LIPC and APOE) have been identified as chief biomarkers for anti-VEGF response in AMD patients. Both genotypes ‘CC’ and ‘GC’ of LIPC have found to be associated with a number of anti-VEGF injections in AMD patients which could influence the expression of B3GALTL,HTRA1, IER3, LIPC and SLC16A8 proteins in patients bearing both genotypes as compared to reference genotype. Elevated levels of APOE were also observed in group 2 wet AMD patients as compared to group 1 suggesting the significance of APOE levels in anti-VEGF response. The genotype of B3GALTL has also been shown to have a significant association with the number of anti-VEGF injections. Moreover, visual acuity of group 1 (≤ 4 anti-VEGF injections/year) AMD patients was found significantly improved after 3 doses of anti-VEGF injections and maintained longitudinally as compared to groups 2 and 3. Lipid metabolising genes may impact the outcome of anti-VEGF AMD treatment.

scholarly journals Systemic complement levels in patients with age-related macular degeneration carrying rare or low frequency variants in the CFH gene

2021 ◽  
Author(s):  
Sarah de Jong ◽  
Anita de Breuk ◽  
Elena B Volokhina ◽  
Bjorn Bakker ◽  
Alejandro Garanto ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Rare Variants ◽  
Low Frequency ◽  
Missense Variant ◽  
Factor H ◽  
Age Related Macular Degeneration ◽  
Western World ◽  
Complement Factor ◽  
Age Related

Abstract Age-related macular degeneration (AMD) is a major cause of vision loss among the elderly in the Western world. Genetic variants in the complement factor H (CFH) gene are associated with AMD, but the functional consequences of many of these variants are currently unknown. In this study we aimed to determine the effect of 64 rare and low frequency variants in the CFH gene on systemic levels of factor H (FH) and complement activation marker C3bBbP using plasma samples of 252 carriers and 159 non-carriers. Individuals carrying a heterozygous nonsense, frameshift or missense variant in CFH presented with significantly decreased FH levels, and significantly increased C3bBbP levels in plasma compared to non-carrier controls. FH and C3bBbP plasma levels were relatively stable over time in samples collected during follow-up visits. Decreased FH and increased C3bBbP concentrations were observed in carriers compared to non-carriers of CFH variants among different AMD stages, with the exception of C3bBbP levels in advanced AMD stages, which were equally high in carriers and non-carriers. In AMD families, FH levels were decreased in carriers compared to non-carriers, but C3bBbP levels did not differ. Rare variants in the CFH gene can lead to reduced FH levels or reduced FH function as measured by increased C3bBbP levels. The effects of individual variants in the CFH gene reported in this study will improve the interpretation of rare and low frequency variants observed in AMD patients in clinical practice.

scholarly journals New Qualitative Methods for Assessing the “Fluid” in the Retina in Age-Related Macular Degeneration

2021 ◽  
Vol 18 (2) ◽  
pp. 222-227
Author(s):  
M. V. Budzinskaya ◽  
A. A. Plyukhova
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Retinal Thickness ◽  
Antiangiogenic Therapy ◽  
Functional Results ◽  
Age Related Macular Degeneration ◽  
Modern World ◽  
Time Interval ◽  
Anti Vegf ◽  
Age Related

Age-related macular degeneration (AMD) is a chronic disease of the central retina and one of the main causes of blindness in patients over 60 years of age in industrialized countries. Currently, anti-vascular endothelial growth factor therapy (anti-VEGF therapy) has become the standard of neovascular AMD treatment, leading to the prevention of progressive vision loss in more than 90 % of treated patients during a two-year follow-up period. In the modern world there are transition from quantitative assessment of “fluid” according to optical coherence tomography (OCT) — the thickness of the central retinal zone, to qualitative — the presence of IRF, SRF, fluid under RPE. The data obtained by Zinkernagel have shown that, despite good functional results (an increase in visual acuity), the administration of the drug once every 2 months leads not only to fluctuations in IRF and SRF, but also to serous PED [4]. The existing qualitative and quantitative analysis is not perfect. Fluctuation is a new qualitative marker of the study of disease activity, it is defined as the sum of all types of fluid (IRF + SRF + fluid under RPE) in a certain time interval (with monthly measurement of the indicator). The fluctuation index was determined from the cumulative change in the thickness of the retina in the fovea over time [6]. Thus, the fluid is considered as a key morphological criterion for the activity of nVMD and an indication for (initiation or continuation) of antiangiogenic therapy. At the same time, there is evidence that a lower level of each type of fluid (IRF, SRF, fluid under RPE) is associated with better BCVA results against the background of anti-VEGF therapy [17]. The stability of retinal thickness during anti-VEGF therapy is no less important parameter than the statement of fluid resolution at a certain time, and it appears that better control of the central retinal thickness was associated with higher overall NEI VFQ-25 scores and individual scales reflecting important daily activities of the patient [16]. 

scholarly journals Principles of anti-VEGF dosing in the treatment of neovascular age-related macular degeneration

2019 ◽  
Vol 12 (3) ◽  
pp. 102-112
Author(s):  
I. E. Ioshin ◽  
T. Anoprieva
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Evidence Base ◽  
Age Related Macular Degeneration ◽  
Neovascular Amd ◽  
Anti Vegf ◽  
Age Related ◽  
Optimal Dosing ◽  
Increased Risk ◽  
Dosing Regimens

Age-related macular degeneration (AMD) is a chronic progressive disease regarded as a leading cause of vision impairment in elderly people in industrial countries. Neovascular AMD is characterized by an increased risk of severe vision loss. Intravitreal injections of anti-VEGF medication has become a standard of treatment of neovascular AMD. Clinical trials demonstrate that the use of anti-VEGF helps stabilize the vision in at least 90 % of patients, while 30 to 40 % gain three or more lines of vision (15 ETDRS letters). However, observational studies suggest that there are barriers diminishing the efficacy of anti-VEGF treatment in routine clinical practice. Finding an optimal dosing regimen for anti-VEGF therapy that could maintain treatment efficacy with a lower number of injections and fewer monitoring visits could be a solution. The review discusses the evidence base regarding anti-VEGF dosing principles and analyzes current dosing regimens with regard to their benefits and limitations.

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