scholarly journals Specific Autoantibodies in Neovascular Age-Related Macular Degeneration: Evaluation of Morphological and Functional Progression over Five Years

2021 ◽  
Vol 11 (11) ◽  
pp. 1207
Author(s):  
Michelle Prasuhn ◽  
Caroline Hillers ◽  
Felix Rommel ◽  
Gabriela Riemekasten ◽  
Harald Heidecke ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Morphological Characteristics ◽  
Age Related Macular Degeneration ◽  
Daily Routine ◽  
Vegf Receptor ◽  
Angiotensin Ii Receptor ◽  
Protease Activated Receptors ◽  
Age Related ◽  
Endothelial Growth Factor

(1) Background: Altered levels of autoantibodies (aab) and their networks have been identified as biomarkers for various diseases. Neovascular age-related macular degeneration (nAMD) is a leading cause for central vision loss worldwide with highly variable inter- and intraindividual disease courses. Certain aab networks could help in daily routine to identify patients with a high disease activity who need to be visited and treated more regularly. (2) Methods: We analyzed levels of aab against Angiotensin II receptor type 1 (AT1-receptor), Protease-activated receptors (PAR1), vascular endothelial growth factor (VEGF) -A, VEGF-B, and VEGF-receptor 2 in sera of 164 nAMD patients. In a follow-up period of five years, we evaluated changes in functional and morphological characteristics. Using correlation analyses, multiple regression models, and receiver operator characteristics, we assessed whether the five aab have a clinical significance as biomarkers that correspond to the clinical properties. (3) Results: Neither the analyzed aab individually nor taken together as a network showed statistically significant results that would allow us to draw conclusions on the clinical five-year course in nAMD patients. (4) Conclusions: The five aab that we analyzed do not correspond to the clinical five-year course of nAMD patients. However, larger, prospective studies should reevaluate different and more aab to gain deeper insights.

Aflibercept as a Treatment for Age-related Macular Degeneration

2013 ◽  
Vol 06 (01) ◽  
pp. 58 ◽  
Author(s):  
Michael W Stewart ◽  
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Retinal Pigment ◽  
Subretinal Fluid ◽  
Age Related Macular Degeneration ◽  
Unit Price ◽  
Vegf Receptor ◽  
Duration Of Action ◽  
Age Related ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) plays a central role in the development of several chorioretinal vascular disorders including exudative age-related macular degeneration (AMD). Detailed understanding of VEGF biochemistry has led to the development of four drugs which specifically inhibit its actions. Bevacizumab and ranibizumab have been the dominant ophthalmic anti-VEGF drugs for seven years and their regular use has significantly decreased vision loss. In late 2011, aflibercept, a high-affinity, fusion protein that acts as a soluble VEGF receptor, was approved for the treatment of exudative AMD. Phase three trials showed that monthly and bimonthly aflibercept maintained vision in 95 % of patients, improved average visual acuity by +8.3 to +9.4 letters, and thinned the macula comparably to monthly ranibizumab. Since its approval, aflibercept has been shown to decrease retinal edema and subretinal fluid, and flatten retinal pigment epithelial detachments in eyes that have responded incompletely to frequent ranibizumab and bevacizumab injections. Aflibercept’s longer duration of action coupled with its comparable unit price (versus ranibizumab) promise to decrease the total cost of treatment.

scholarly journals Introduction to the multi-author review on macular degeneration

2020 ◽  
Vol 77 (5) ◽  
pp. 779-780 ◽  
Author(s):  
Anu Kauppinen
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
The Elderly ◽  
Developed Countries ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Severe Vision Loss ◽  
Author Review ◽  
Dry Amd ◽  
Endothelial Growth Factor

AbstractProlonged life expectancies contribute to the increasing prevalence of age-related macular degeneration (AMD) that is already the leading cause of severe vision loss among the elderly in developed countries. In dry AMD, the disease culminates into vast retinal atrophy, whereas the wet form is characterized by retinal edema and sudden vision loss due to neovascularization originating from the choroid beneath the Bruch’s membrane. There is no treatment for dry AMD and despite intravitreal injections of anti-vascular endothelial growth factor (VEGF) that suppress the neovessel formation, also wet AMD needs new therapies to prevent the disease progression and to serve patients lacking of positive response to current medicines. Knowledge on disease mechanisms is a prerequisite for the drug development, which is hindered by the multifactorial nature of AMD. Numerous distinguished publications have revealed AMD mechanisms at the cellular and molecular level and in this multi-author review, we take a bit broader look at the topic with some novel aspects.

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 Nanotechnology for Age-Related Macular Degeneration

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2035
Author(s):  
Bo Yang ◽  
Ge Li ◽  
Jiaxin Liu ◽  
Xiangyu Li ◽  
Shixin Zhang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Gene Therapy ◽  
Macular Degeneration ◽  
Vision Loss ◽  
Cumulative Risk ◽  
Age Related Macular Degeneration ◽  
Delivery Methods ◽  
Age Related ◽  
Therapy Strategies ◽  
Endothelial Growth Factor

Age-related macular degeneration (AMD) is a degenerative eye disease that is the leading cause of irreversible vision loss in people 50 years and older. Today, the most common treatment for AMD involves repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs. However, the existing expensive therapies not only cannot cure this disease, they also produce a variety of side effects. For example, the number of injections increases the cumulative risk of endophthalmitis and other complications. Today, a single intravitreal injection of gene therapy products can greatly reduce the burden of treatment and improve visual effects. In addition, the latest innovations in nanotherapy provide the best drug delivery alternative for the treatment of AMD. In this review, we discuss the development of nano-drug delivery systems and gene therapy strategies for AMD in recent years. In addition, we discuss some novel targeting strategies and the potential application of these delivery methods in the treatment of AMD. Finally, we also propose that the combination of CRISPR/Cas9 technology with a new non-viral delivery system may be promising as a therapeutic strategy for the treatment of AMD.

Pegaptanib for Neovascular Age-Related Macular Degeneration

2020 ◽  
pp. 239-244
Author(s):  
Alan D. Penman ◽  
Kimberly W. Crowder ◽  
William M. Watkins
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Efficacy And Safety ◽  
Neovascular Amd ◽  
Ocular Neovascularization ◽  
Age Related ◽  
Discontinue Therapy ◽  
Endothelial Growth Factor

The VEGF Inhibition Study in Ocular Neovascularization (V.I.S.I.O.N.) study comprised two concurrent randomized, double-masked, sham-controlled clinical trials to evaluate the efficacy and safety of a second year of treatment with pegaptanib sodium (an anti-vascular endothelial growth factor [VEGF] agent) in patients with neovascular age-related macular degeneration (AMD). In combined analyses, 88% of patients were re-randomized at week 54, and 89% were assessed at week 102. At week 54, those initially assigned to pegaptanib were re-randomized to continue or discontinue therapy for 48 more weeks (8 injections). Those initially assigned to sham were re-randomized to continue sham, discontinue sham, or receive 1 of 3 pegaptanib doses. The study showed that in patients with a diverse mix of neovascular AMD presentations, treatment with pegaptanib every 6 weeks for 2 years reduced the risk of vision loss regardless of lesion composition or size; this benefit was maintained during year 2.

scholarly journals Therapeutic Efficacy of a Novel Acetylated Tetrapeptide in Animal Models of Age-Related Macular Degeneration

2021 ◽  
Vol 22 (8) ◽  
pp. 3893
Author(s):  
Hye Cheong Koo ◽  
Yi-Yong Baek ◽  
Jun-Sup Choi ◽  
Young-Myeong Kim ◽  
Bokyung Sung ◽  
...  
Keyword(s):  
Animal Models ◽  
Macular Degeneration ◽  
Choroidal Neovascularization ◽  
Systemic Exposure ◽  
Age Related Macular Degeneration ◽  
Vegf Receptor ◽  
Age Related ◽  
Human Plasminogen ◽  
Endothelial Growth Factor

It has been shown previously that a novel tetrapeptide, Arg-Leu-Tyr-Glu (RLYE), derived from human plasminogen inhibits vascular endothelial growth factor (VEGF)-induced angiogenesis, suppresses choroidal neovascularization in mice by an inhibition of VEGF receptor-2 (VEGFR-2) specific signaling pathway. In this study, we report that a modified tetrapeptide (Ac-RLYE) showed improved anti-choroidal neovascularization (CNV) efficacy in a number of animal models of neovascular age-related macular degeneration (AMD) which include rat, rabbit, and minipig. The preventive and therapeutic in vivo efficacy of Ac-RLYE via following intravitreal administration was determined to be either similar or superior to that of ranibizumab and aflibercept. Assessment of the intraocular pharmacokinetic and toxicokinetic properties of Ac-RLYE in rabbits demonstrated that it rapidly reached the retina with minimal systemic exposure after a single intravitreal dose, and it did not accumulate in plasma during repetitive dosing (bi-weekly for 14 weeks). Our results suggested that Ac-RLYE has a great potential for an alternative therapeutics for neovascular (wet) AMD. Since the amino acids in human VEGFR-2 targeted by Ac-RLYE are conserved among the animals employed in this study, the therapeutic efficacies of Ac-RLYE evaluated in those animals are predicted to be observed in human patients suffering from retinal degenerative diseases.

scholarly journals Review of intravitreal vascular endothelial growth factor inhibitor toxicity and report of collapsing focal and segmental glomerulosclerosis with thrombotic microangiopathy in patient with age-related macular degeneration

2021 ◽  
Author(s):  
Gautam Phadke ◽  
Ramy M Hanna ◽  
Antoney Ferrey ◽  
Everardo Arias Torres ◽  
Anjali Singla ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Macular Degeneration ◽  
Case Reports ◽  
Age Related Macular Degeneration ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Segmental Glomerulosclerosis ◽  
Age Related ◽  
Endothelial Growth Factor

Abstract Intravitreal vascular endothelial growth factor (VEGF) receptor blockade is used for a variety of retinal pathologies. These include age-related macular degeneration (AMD), diabetic macular edema (DME) and central retinal vein obstruction. Reports of absorption of intravitreal agents into systemic circulation have increased in number and confirmation of depletion of VEGF has been confirmed. Increasingly there are studies and case reports showing worsening hypertension, proteinuria, renal dysfunction and glomerular disease. The pathognomonic findings of systemic VEGF blockade, thrombotic microangiopathies (TMAs), are also being increasingly reported. One lesion that occurs in conjunction with TMAs that has been described is collapsing focal segmental glomerulosclerosis (cFSGS). cFSGS has been postulated to occur due to TMA-induced chronic glomerular hypoxia. In this updated review we discuss the mechanistic, pharmacological, epidemiological and clinical evidence of intravitreal VEGF toxicity. We review cases of biopsy-proven toxicity presented by our group and other investigators. We also present the third reported case of cFSGS in the setting of intravitreal VEGF blockade with a chronic TMA component that was crucially found on biopsy. This patient is a 74-year-old nondiabetic male receiving aflibercept for AMD. Of the two prior cases of cFSGS in the setting of VEGF blockade, one had AMD and the other had DME. This case solidifies the finding of cFSGS and its association with chronic TMA as a lesion that may be frequently encountered in patients receiving intravitreal VEGF inhibitors.

Ranibizumab for Neovascular Age-Related Macular Degeneration

2020 ◽  
pp. 245-250
Author(s):  
Alan D. Penman ◽  
Kimberly W. Crowder ◽  
William M. Watkins
Keyword(s):  
Visual Acuity ◽  
Macular Degeneration ◽  
Choroidal Neovascularization ◽  
Vision Loss ◽  
Age Related Macular Degeneration ◽  
Controlled Clinical Trial ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Age Related ◽  
Endothelial Growth Factor

The Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD (MARINA) study was a randomized, double-blind, sham-controlled clinical trial to determine whether intravitreal administration of ranibizumab (an anti-vascular endothelial growth factor [VEGF] agent) prevents vision loss and improves mean visual acuity in patients with minimally classic or occult choroidal neovascularization related to age-related macular degeneration (AMD). Ranibizumab therapy was associated with clinically and statistically significant benefits in visual acuity and the amount of angiographic leakage from choroidal neovascularization during two years of follow-up, with low rates of serious adverse events.

scholarly journals Advances in Age-related Macular Degeneration Understanding and Therapy

2017 ◽  
Vol 10 (02) ◽  
pp. 119 ◽  
Author(s):  
Joan W Miller ◽  
Saghar Bagheri ◽  
Demetrios G Vavvas ◽  
◽  
◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Disease Process ◽  
Age Related Macular Degeneration ◽  
Great Success ◽  
Neovascular Amd ◽  
Clinical Endpoints ◽  
Age Related ◽  
Cell Death Mechanisms ◽  
Endothelial Growth Factor

While the development of anti-vascular endothelial growth factor (anti-VEGF) as a therapy for neovascular age-related macular degeneration (AMD) was a great success, the pathologic processes underlying dry AMD that eventually leads to photoreceptor dysfunction, death, and vision loss remain elusive to date, with a lack of effective therapies and increasing prevalence of the disease. There is an overwhelming need to improve the classification system of AMD, to increase our understanding of cell death mechanisms involved in both neovascular and non-neovascular AMD, and to develop better biomarkers and clinical endpoints to eventually be able to identify better therapeutic targets—especially early in the disease process. There is no doubt that it is a matter of time before progress will be made and better therapies will be developed for non-neovascular AMD.

scholarly journals Non-Response to Anti-VEGF in Patients with Wet-Form (Neovascular) Age-Related Macular Degeneration, Treatment Resistance and Switch of Anti-VEGF Agents

2017 ◽  
pp. 219-228
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Treatment Resistance ◽  
Drug Efficacy ◽  
Age Related Macular Degeneration ◽  
Response To Treatment ◽  
Similar Response ◽  
Anti Vegf ◽  
Age Related ◽  
Endothelial Growth Factor

Age-related macular degeneration (AMD) is a chronic and degenerative disease that causes vision loss. Although anti-vascular endothelial growth factor (Anti-VEGF) drugs are the mainstay of treatment in cases of age-related AMD, there is no similar response to treatment in each patient. In the case of non-response, the treatment approach for the cause must be regulated. Although there is no consensus on the concept of response to treatment, the use of alternative anti-VEGF in cases where drug efficacy is weak is quite common.

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