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Biomedicines
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WAMD: From Pathophysiology to Therapeutic Approaches Treatment
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WAMD: From Pathophysiology to Therapeutic Approaches Treatment

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 26768

Special Issue Editors

Dr. Enzo Maria Vingolo

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Guest Editor
Department of Medical-Surgical Sciences and Biotechnologies, U.O.C. Ophthalmology, Sapienza University of Rome, Via Firenze 1, 04019 Terracina, Italy
Interests: retinitis pigmentosa; inherited retinal degenerations; retinal electrophysiology; low vision; visual rehabilitation; legal ophthalmology
Special Issues, Collections and Topics in MDPI journals
Dr. Stefano Lupo

E-Mail Website
Guest Editor
Department of Medical-Surgical Sciences and Biotechnologies, U.O.C. Ophthalmology, Sapienza University of Rome, Via Firenze 1, 04019 Terracina, Italy
Interests: medical retina; retinal imaging; macular degeneration; OCT; fluorescein angiography
Special Issues, Collections and Topics in MDPI journals
Dr. Francesca Toja

E-Mail Website
Guest Editor
Department of Medical-Surgical Sciences and Biotechnologies, U.O.C. Ophthalmology, Sapienza University of Rome, Via Firenze 1, 04019 Terracina, Italy
Interests: medical retina; retinal imaging; macular degeneration; OCT; fluorescein angiography
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In this Special Issue on wet age-related macular degeneration (wAMD), we would like to explore new wAMD strategies to achieve better visual acuity and retina structural outcomes. Age-related macular degeneration is one of the main causes of visual impairment in elderly people. While the dry form has no approved treatment, several therapies have been proposed for the wAMD form to try to change the course of the disease and to improve visual acuity. The main treatments for wAMD are based on targeting choroidal neovascular membranes. The anti-VEGF agents have dramatically improved the disease outcome. In this issue, we are especially interested in examining consolidated and new anti-VEGF therapies and also considering the treatment protocols. Potential topics will include:

  • Aflibercept, ranibizumab and brolucizumab treatment regimen
  • Clinical trials for new drugs development
  • Different types of wAMD and related disease outcomes
  • Possible application of telemedicine in wAMD diagnosis and follow-up
  • Nutritional supplements in wAMD

Dr. Enzo Maria Vingolo
Dr. Stefano Lupo
Dr. Francesca Toja
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • anti-VEGF
  • aflibercept
  • ranibizumab
  • brolucizumab
  • telemedicine
  • OCT
  • macular diseases
  • treatment regimen
  • nutritional supplements
  • long term outcomes

Related Special Issue

Published Papers (6 papers)

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Editorial

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4 pages, 203 KiB  
Editorial
WAMD: From Pathophysiology to Therapeutic Treatments
by Feliciana Menna, Alessandro Meduri, Stefano Lupo and Enzo Maria Vingolo
Biomedicines 2022, 10(8), 1996; https://doi.org/10.3390/biomedicines10081996 - 17 Aug 2022
Cited by 1 | Viewed by 1056
Abstract
Age-related macular degeneration (AMD) is referred to as the leading cause of irreversible visual loss in developed countries, with a profound effect on the quality of life [...] Full article
(This article belongs to the Special Issue WAMD: From Pathophysiology to Therapeutic Approaches Treatment)

Research

Jump to: Editorial, Review

18 pages, 558 KiB  
Article
Association between Polymorphisms in CFH, ARMS2, CFI, and C3 Genes and Response to Anti-VEGF Treatment in Neovascular Age-Related Macular Degeneration
by Oyuna S. Kozhevnikova, Anzhella Zh. Fursova, Anna S. Derbeneva, Ida F. Nikulich, Mikhail S. Tarasov, Vasiliy A. Devyatkin, Yulia V. Rumyantseva, Darya V. Telegina and Nataliya G. Kolosova
Biomedicines 2022, 10(7), 1658; https://doi.org/10.3390/biomedicines10071658 - 10 Jul 2022
Cited by 8 | Viewed by 2608
Abstract
Neovascular age-related macular degeneration (nAMD) is the leading cause of vision loss in the elderly. The gold standard of nAMD treatment is intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors. Genetic factors may influence the response to anti-VEGF therapy and result in [...] Read more.
Neovascular age-related macular degeneration (nAMD) is the leading cause of vision loss in the elderly. The gold standard of nAMD treatment is intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors. Genetic factors may influence the response to anti-VEGF therapy and result in a high degree of response variability. The aim of the study was to evaluate the association of the polymorphisms in genes related to the complement system (rs2285714-CFI, rs10490924-ARMS2, rs2230199-C3, rs800292-CFH, and rs6677604-CFH) with nAMD its clinical features and optical coherent tomography (OCT) biomarkers of treatment response to anti-VEGF therapy. Genotyping by allele-specific PCR was performed in 193 AMD patients and 147 age-matched controls. A prospective study of the dynamics of changes in OCT biomarkers during aflibercept treatment included 110 treatment-naive patients. Allele T rs10490924 was associated with the increased risk of nAMD. For both rs800292 and rs6677604, carriage of the A allele was protective and decreased the nAMD risk. Associations of rs2230199 with central retinal thickness (CRT) and intraretinal cysts were revealed. The height of pigment epithelium detachment and the height of neuroretinal detachment were significantly higher in carriers of the minor allele of rs2285714, both at baseline and during treatment. The reduction of CRT was associated with higher CRT at baseline and the presence of the T allele of rs2285714. By the end of one-year follow-up the patients homozygous for the minor allele rs2285714 had significantly higher odds of the presence of anastomoses and loops and active neovascular membrane. Furthermore, minor allele carriers had decreased levels of complement factor I level in aqueous humor but not in the plasma, which may be due to the influence of rs2285714 on tissue-specific splicing. Our results suggest that the severity of AMD macular lesions is associated with rs2285714 and rs2230199 polymorphisms, which could be explained by their high regulatory potential. Patients with the minor allele of rs2285714 respond worse to antiangiogenic therapy. Full article
(This article belongs to the Special Issue WAMD: From Pathophysiology to Therapeutic Approaches Treatment)
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14 pages, 4739 KiB  
Article
Vascular Analysis of Type 1, 2, and 3 Macular Neovascularization in Age-Related Macular Degeneration Using Swept-Source Optical Coherence Tomography Angiography Shows New Insights into Differences of Pathologic Vasculature and May Lead to a More Personalized Understanding
by Henrik Faatz, Kai Rothaus, Martin Ziegler, Marius Book, Britta Heimes-Bussmann, Daniel Pauleikhoff and Albrecht Lommatzsch
Biomedicines 2022, 10(3), 694; https://doi.org/10.3390/biomedicines10030694 - 17 Mar 2022
Cited by 8 | Viewed by 2769
Abstract
Background: The clinical appearance of macular neovascularization (MNV) in age-related macular degeneration (nAMD) varies widely, but so far, this has had no relevance in terms of therapeutic approaches or prognosis. Therefore, our purpose was to investigate if and which differences exist in the [...] Read more.
Background: The clinical appearance of macular neovascularization (MNV) in age-related macular degeneration (nAMD) varies widely, but so far, this has had no relevance in terms of therapeutic approaches or prognosis. Therefore, our purpose was to investigate if and which differences exist in the vascular architecture of MNV and to quantify them. Methods: In 90 patients with newly diagnosed nAMD, MNV was identified by means of optical coherence tomography angiography (OCTA), and automated quantitative vascular analysis was carried out. The analyzed vascular parameters were area, flow, fractal dimension (FD), total vascular length (sumL), number of vascular nodes (numN), flow, and average vessel caliber (avgW). The current classification of MNVs divides them according to their localization into type 1 (grown from the choroid below the RPE), type 2 (grown from the choroid through RPE), and type 3 (grown from the retina toward the RPE). We compared the analyzed vascular parameters of each of the three MNV types. Kruskal–Wallis test was applied, Dunn test was performed for post hoc analysis, and for pairwise comparison, p-values were adjusted using Bonferroni comparison. Results: Regarding the MNV area, there was no significant difference between types 1 and 2, but type 3 was significantly smaller than types 1 and 2 (p < 0.00001). For FD, types 1 and 2 did not differ significantly, but again, type 3 was lower than type 1 and 2 (p < 0.00001). The numN were significantly higher in types 1 and 3 than in 2 (p < 0.005), but not between types 1 and 3. No significant differences were found between MNV types for flow. As for sumL, types 1 and 2 did not differ significantly, but type 3 was significantly lower than types 1 and 2 (p < 0.00001). For avgW, there was no significant difference between types 1 and 2 or between types 2 and 3, but type 3 was significantly larger than type 1 (p < 0.05). Conclusions OCTA yields detailed information on the vascular morphology of MNV in patients with nAMD and is able to show differences among types 1, 2, and 3. Especially comparing types 1 and 2 with type 3 reveals significant differences in area, FD, sumL, and numN. One explanation could be the similar pathogenesis of types 1 and 2 with their origin in the choroid and their growth towards the retinal pigment epithelium (RPE), whereas type 3 originates in the deep capillary plexus. Between types 1 and 2, however, only the numN differ significantly, which could be due to the fact that type 1 spreads horizontally below the RPE and, thus, display more vascular branching, while type 2 grows more vertically through the RPE and under the neurosensory retina. Detailed information about the pathologic vasculature is important for proper monitoring of the disease and to assess the efficacy of medication, especially with regard to new substances. This should be taken into consideration in future studies. Full article
(This article belongs to the Special Issue WAMD: From Pathophysiology to Therapeutic Approaches Treatment)
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11 pages, 2146 KiB  
Article
Biomarkers in Early Response to Brolucizumab on Pigment Epithelium Detachment Associated with Exudative Age-Related Macular Degeneration
by Marco Rispoli, Chiara M. Eandi, Luca Di Antonio, Raphael Kilian, Andrea Montesel and Maria C. Savastano
Biomedicines 2021, 9(6), 668; https://doi.org/10.3390/biomedicines9060668 - 10 Jun 2021
Cited by 15 | Viewed by 3659
Abstract
Background: The purpose of this study was to describe early changes in the morphology of pigment epithelium detachments (PED) after an intravitreal injection of Brolucizumab into eyes with macular neovascularization secondary to exudative age-related macular degeneration (e-AMD). Method: We included twelve eyes of [...] Read more.
Background: The purpose of this study was to describe early changes in the morphology of pigment epithelium detachments (PED) after an intravitreal injection of Brolucizumab into eyes with macular neovascularization secondary to exudative age-related macular degeneration (e-AMD). Method: We included twelve eyes of 12 patients with PED secondary to e-AMD which were not responding to prior anti-VEGF treatments. An ophthalmic examination and an assessment of PED-horizontal maximal diameter (PED-HMD), PED-maximum high (PED-MH) and macular neovascularization (MNV) flow area (MNV-FA) by the means of structural optical coherence tomography (OCT) and OCT Angiography (OCT-A) were performed at baseline, as well as 1, 7, 14 and 30 days after the injection. Results: The mean age of the population of study was 78.4 (SD ± 4.8). The mean number of previous Ranibizumab or Aflibercept injections was 13 (SD ± 8). At the last follow-up visit, the PED-HMD did not significantly change (p = 0.16; F(DF:1.94, 20,85) = 1.9), the PED-MH showed a significant reduction [p = 0.01; F(DF:1.31, 14.13) = 6.84.] and the MNV-FA did not significantly differ (p = 0.1; F(1.97, 21.67) = 2.54) from baseline. No signs of ocular inflammation were observed during follow-up. Conclusions: A single Brolucizumab injection was able to determine the short-term effects on PEDs’ anatomical features of eyes with an unresponsive e-AMD. Full article
(This article belongs to the Special Issue WAMD: From Pathophysiology to Therapeutic Approaches Treatment)
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Review

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23 pages, 2406 KiB  
Review
Biomarkers as Predictive Factors of Anti-VEGF Response
by Miriam Bobadilla, Ana Pariente, Ana I. Oca, Rafael Peláez, Álvaro Pérez-Sala and Ignacio M. Larráyoz
Biomedicines 2022, 10(5), 1003; https://doi.org/10.3390/biomedicines10051003 - 26 Apr 2022
Cited by 12 | Viewed by 4942
Abstract
Age-related macular degeneration is the main cause of irreversible vision in developed countries, and intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are the current gold standard treatment today. Although anti-VEGF treatment results in important improvements in the course of this disease, there is [...] Read more.
Age-related macular degeneration is the main cause of irreversible vision in developed countries, and intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are the current gold standard treatment today. Although anti-VEGF treatment results in important improvements in the course of this disease, there is a considerable number of patients not responding to the standardized protocols. The knowledge of how a patient will respond or how frequently retreatment might be required would be vital in planning treatment schedules, saving both resource utilization and financial costs, but today, there is not an ideal biomarker to use as a predictive response to ranibizumab therapy. Whole blood and blood mononuclear cells are the samples most studied; however, few reports are available on other important biofluid samples for studying this disease, such as aqueous humor. Moreover, the great majority of studies carried out to date were focused on the search for SNPs in genes related to AMD risk factors, but miRNAs, proteomic and metabolomics studies have rarely been conducted in anti-VEGF-treated samples. Here, we propose that genomic, proteomic and/or metabolomic markers could be used not alone but in combination with other methods, such as specific clinic characteristics, to identify patients with a poor response to anti-VEGF treatment to establish patient-specific treatment plans. Full article
(This article belongs to the Special Issue WAMD: From Pathophysiology to Therapeutic Approaches Treatment)
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23 pages, 857 KiB  
Review
Visual Side Effects Linked to Sildenafil Consumption: An Update
by Eva Ausó, Violeta Gómez-Vicente and Gema Esquiva
Biomedicines 2021, 9(3), 291; https://doi.org/10.3390/biomedicines9030291 - 12 Mar 2021
Cited by 12 | Viewed by 9761
Abstract
Phosphodiesterase type 5 (PDE5) inhibitors such as Viagra® (sildenafil citrate) have demonstrated efficacy in the treatment of erectile dysfunction (ED) by inducing cyclic guanosine monophosphate (cGMP) elevation followed by vasodilation and increased blood flow. It also exerts minor inhibitory action against PDE6, [...] Read more.
Phosphodiesterase type 5 (PDE5) inhibitors such as Viagra® (sildenafil citrate) have demonstrated efficacy in the treatment of erectile dysfunction (ED) by inducing cyclic guanosine monophosphate (cGMP) elevation followed by vasodilation and increased blood flow. It also exerts minor inhibitory action against PDE6, which is present exclusively in rod and cone photoreceptors. The effects of sildenafil on the visual system have been investigated in a wide variety of clinical and preclinical studies due to the fact that a high dose of sildenafil may cause mild and transient visual symptoms in some patients. A literature review was performed using PubMed, Cochrane Library and Clinical Trials databases from 1990 up to 2020, focusing on the pathophysiology of visual disorders induced by sildenafil. The aim of this review was not only to gather and summarize the information available on sildenafil clinical trials (CTs), but also to spot subpopulations with increased risk of developing undesirable visual side effects. This PDE inhibitor has been associated with transient and reversible ocular side effects, including changes in color vision and light perception, blurred vision, photophobia, conjunctival hyperemia and keratitis, and alterations in the electroretinogram (ERG). Sildenafil may induce a reversible increase in intraocular pressure (IOP) and a few case reports suggest it is involved in the development of nonarteritic ischemic optic neuropathy (NAION). Reversible idiopathic serous macular detachment, central serous retinopathy and ERG disturbances have been related to the significant impact of sildenafil on retinal perfusion. So far, sildenafil does not seem to cause permanent toxic effects on chorioretinal tissue and photoreceptors as long as the therapeutic dose is not exceeded and is taken under a physician’s direction to treat a medical condition. However, the recreational use of sildenafil can lead to harmful side effects, including vision changes. Full article
(This article belongs to the Special Issue WAMD: From Pathophysiology to Therapeutic Approaches Treatment)
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