scholarly journals Therapeutic Approaches with Intravitreal Injections in Geographic Atrophy Secondary to Age-Related Macular Degeneration: Current Drugs and Potential Molecules

2019 ◽  
Vol 20 (7) ◽  
pp. 1693 ◽  
Author(s):  
Marcella Nebbioso ◽  
Alessandro Lambiase ◽  
Alberto Cerini ◽  
Paolo Giuseppe Limoli ◽  
Maurizio La Cava ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Ganglion Cells ◽  
Therapeutic Agents ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
New Drugs ◽  
Complement Cascade ◽  
Complement Inhibitors ◽  
Age Related ◽  
Dry Amd

The present review focuses on recent clinical trials that analyze the efficacy of intravitreal therapeutic agents for the treatment of dry age-related macular degeneration (AMD), such as neuroprotective drugs, and complement inhibitors, also called immunomodulatory or anti-inflammatory agents. A systematic literature search was performed to identify randomized controlled trials published prior to January 2019. Patients affected by dry AMD treated with intravitreal therapeutic agents were included. Changes in the correct visual acuity and reduction in geographic atrophy progression were evaluated. Several new drugs have shown promising results, including those targeting the complement cascade and neuroprotective agents. The potential action of the two groups of drugs is to block complement cascade upregulation of immunomodulating agents, and to prevent the degeneration and apoptosis of ganglion cells for the neuroprotectors, respectively. Our analysis indicates that finding treatments for dry AMD will require continued collaboration among researchers to identify additional molecular targets and to fully interrogate the utility of pluripotent stem cells for personalized therapy.

scholarly journals Therapeutic Approaches with Intravitreal Injections in Geographic Atrophy Secondary to Age-Related Macular Degeneration: Current Drugs and Potential Molecules

2019 ◽  
Author(s):  
Marcella Nebbioso ◽  
Alessandro Lambiase ◽  
Alberto Cerini ◽  
Paolo Giuseppe Limoli ◽  
Maurizio La Cava ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Macular Degeneration ◽  
Ganglion Cells ◽  
Therapeutic Agents ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
New Drugs ◽  
Complement Cascade ◽  
Age Related ◽  
Dry Amd

The present review focuses on recent clinical trials that analyze the efficacy of intravitreal therapeutic agents for the treatment of dry age-related macular degeneration (AMD), such as neuroprotective drugs, and complement inhibitors, also called immunomodulatory or anti-inflammatory. A systematic literature search was performed to identify randomized controlled trials published prior to January 2019. Patients affected by dry AMD treated with intravitreal therapeutic agents were included. The changes in the correct visual acuity and the reduction in geographic atrophy progression were evaluated. Several new drugs have shown some promising results, including those targeting the complement cascade and agents called neuroprotective. The action potential of the two groups of drugs is to block the complement cascade model for immunomodulating agents, and prevent the degeneration and apoptosis of ganglion cells for the neuroprotectors, respectively. To the best of knowledge, and after extensive studies on the matter, there are still many investigations to be carried out on dry AMD in collaboration between researchers. They will have to identify truly effective molecules, understand the practical potential of pluripotent stem cells, and refine gene therapies. Only in-depth clinical trials will be able to allow the most appropriate and personalized treatments for each dry AMD patient.

scholarly journals Outer retinal tubulation formation and clinical course of advanced age-related macular degeneration

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alessandro Arrigo ◽  
Emanuela Aragona ◽  
Ottavia Battaglia ◽  
Andrea Saladino ◽  
Alessia Amato ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Müller Cells ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Advanced Age ◽  
Age Related ◽  
Dry Amd ◽  
Foveal Sparing ◽  
Wet Amd

AbstractOuter retinal tubulations (ORT) are a relatively new finding characterizing outer retinal atrophy. The main aim of the present study was to describe ORT development in advanced age-related macular degeneration (AMD) and to assess its relationship with disease’s severity. Patients with advanced AMD characterized either by macular neovascularization or geographic atrophy, showing signs of outer retinal disruption or retinal pigment epithelium atrophy on structural optical coherence tomography (OCT) at the inclusion examination were prospectively recruited. All the patients underwent complete ophthalmologic evaluation, structural OCT scans and fundus autofluorescence imaging. The planned follow-up was of 3-years. Main outcome measures were ORT prevalence, mechanism of ORT formation, mean time needed for complete ORT formation, best-corrected visual acuity (BCVA), definitely decreased autofluorescence (DDAF) area, questionably decreased autofluorescence (QDAF) area, retinal layer thickness, foveal sparing, number of intravitreal injections. We also assessed the possible role of external limiting membrane (ELM) and Müller cells in ORT pathogenesis. Seventy eyes (70 patients) were included; 43 showed dry AMD evolving to geographic atrophy, while 27 displayed the features of wet AMD. Baseline BCVA was 0.5 ± 0.5 LogMAR, decreasing to 0.9 ± 0.5 LogMAR at the 3-year follow-up (p < 0.01). We detected completely formed ORT in 26/70 eyes (37%), subdivided as follows: 20 eyes (77%) wet AMD and 6 eyes (23%) dry AMD (p < 0.01). ORT took 18 ± 8 months (range 3–35 months) to develop fully. We described the steps leading to ORT development, characterized by progressive involvement of, and damage to the photoreceptors, the ELM and the RPE. Eyes displaying ORT were associated with a smaller QDAF area, less retinal layers damage and lower rate of foveal sparing than eyes free of ORT (p < 0.01). We also described pigment accumulations simulating ORT, which were detected in 16/70 eyes (23%), associated with a greater loss of foveal sparing, increased DDAF area and smaller QDAF area at the 3-year follow-up (p < 0.01). In conclusion, this study provided a description of the steps leading to ORT development in AMD. ELM and Müller cells showed a role in ORT pathogenesis. Furthermore, we described a subtype of pigment hypertrophy mimicking ORT, evaluating its clinical utility.

Non-Nutritional Medical Treatments in Dry-Form (Non-Neovascular) Age-Related Macular Degeneration

2017 ◽  
pp. 145-148
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
The Elderly ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Medical Treatments ◽  
Age Related ◽  
Dry Amd ◽  
Disease Study ◽  
Developed World

Age-related macular degeneration (AMD) is the major cause of blindness for the elderly population in the developed world. Although vision loss is mainly due to the neovascular form, dry AMD remains a challenge for ophthalmologists because of the lack of effective therapies. The Age-Related Eye Disease Study (AREDS) demonstrated the protective effect of dietary supplementation of antioxidants to slow down the progression of dry AMD. On the other hand, there has been no proven drug treatment for dry AMD to date. This review is aimed to discuss recent non-nutritional treatments for dry AMD and geographic atrophy.

scholarly journals Complement Inhibitors in Age-Related Macular Degeneration: A Potential Therapeutic Option

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Shuqi Qin ◽  
Ning Dong ◽  
Ming Yang ◽  
Jialin Wang ◽  
Xue Feng ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Macular Degeneration ◽  
Complement System ◽  
Vision Loss ◽  
Age Related Macular Degeneration ◽  
Phase Iii ◽  
Complement Inhibitors ◽  
Age Related ◽  
Dry Amd ◽  
The Complement System

Age-related macular degeneration (AMD) is a multifactorial disease, which can culminate in irreversible vision loss and blindness in elderly. Nowadays, there is a big gap between dry AMD and wet AMD on treatment. Accounting for nearly 90% of AMD, dry AMD still lacks effective treatment. Numerous genetic and molecular researches have confirmed the significant role of the complement system in the pathogenesis of AMD, leading to a deeper exploration of complement inhibitors in the treatment of AMD. To date, at least 14 different complement inhibitors have been or are being explored in AMD in almost 40 clinical trials. While most complement inhibitors fail to treat AMD successfully, two of them are effective in inhibiting the rate of GA progression in phase II clinical trials, and both of them successfully entered phase III trials. Furthermore, recently emerging complement gene therapy and combination therapy also offer new opportunities to treat AMD in the future. In this review, we aim to introduce genetic and molecular associations between the complement system and AMD, provide the updated progress in complement inhibitors in AMD on clinical trials, and discuss the challenges and prospects of complement therapeutic strategies in AMD.

Age-related macular degeneration treatment: current view (literature review)

2014 ◽  
Vol 21 (1) ◽  
pp. 43-50
Author(s):  
Monika Kalesinskaitė ◽  
Diana Uljanionok ◽  
Rasa Liutkevičienė
Keyword(s):  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Treatment Options ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Current View ◽  
Neovascular Amd ◽  
Age Related ◽  
Dry Amd

Age-related macular degeneration (AMD) – is a damage of the macula, accompanied by a significant and irreversible loss of central vision. It is a major cause of blindness and visual impairment in older adults (>60 years). Damage of the retina always includes both eyes, though the intensity can vary. Early AMD is defined as the presence of drusen and retinal pigmentary abnormalities (RPE); late AMD includes dry AMD (geographic atrophy of the RPE in the absence of neovascular AMD) or neovascular AMD  (detachment of the retinal pigment epithelium, hemorrhages, and/or scars). Unfortunately, the etiology and pathogenesis of AMD aren’t fully understood up to now, so treatment options are limited and not always effective. This article briefly reviews the options of initial and late forms of AMD treatment

scholarly journals Complement cascade inhibition in geographic atrophy: a review

Eye ◽  
2022 ◽  
Author(s):  
Dhaval Desai ◽  
Pravin U. Dugel
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Serum Proteins ◽  
Geographic Atrophy ◽  
Innate Immune ◽  
Age Related Macular Degeneration ◽  
Complement Cascade ◽  
Complement Factors ◽  
Age Related ◽  
Dry Amd

AbstractThe pathophysiology of dry age-related macular degeneration (AMD) and specifically geographic atrophy (GA) has been linked to the complement cascade. This cascade is part of the innate immune system and is made up of the classical, alternative, and lectin pathways. The pathways comprise a system of plasma and membrane-associated serum proteins that are activated with identification of a nonself entity. A number of these proteins have been implicated in the development and progression of dry AMD. The three pathways converge at C3 and cascade down through C5, making both of these proteins viable targets for the treatment of dry AMD. In addition, there are a number of complement factors, CFB, CFD, CFH, and CFI, which are potential therapeutic targets as well. Several different complement-directed therapeutics are being studied for the treatment of dry AMD with the hope that one of these approaches will emerge as the first approved treatment for GA.

Nanotherapies for the Treatment of Age-Related Macular Degeneration (AMD) Disease: Recent Advancements and Challenges

2020 ◽  
Vol 13 (4) ◽  
pp. 283-290 ◽  
Author(s):  
Vamshi Krishna Rapalli ◽  
Srividya Gorantla ◽  
Tejashree Waghule ◽  
Arisha Mahmood ◽  
Prem Prakash Singh ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Targeted Delivery ◽  
Large Population ◽  
Posterior Part ◽  
Therapeutic Agents ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Disease Site ◽  
Therapeutic Molecules ◽  
Invasive Techniques

Age-related Macular Degeneration (AMD) is one of the common diseases affecting the posterior part of the eye, of a large population above 45 years old. Anti-Vascular Endothelial Growth Factor- A (Anti-VEGF-A) agents have been considered and approved as therapeutic agents for the treatment of AMD. Due to the large molecular weight and poor permeability through various eye membranes, VEGF-A inhibitors are given through an intravitreal injection, even though the delivery of small therapeutic molecules by topical application to the posterior part of the eye exhibits challenges in the treatment. To overcome these limitations, nanocarrier based delivery systems have been utilized to a large extent for the delivery of therapeutics. Nanocarriers system offers prodigious benefits for the delivery of therapeutics to the posterior part of the eye in both invasive and non-invasive techniques. The nano size can improve the permeation of therapeutic agent across the biological membranes. They provide protection from enzymes present at the site, targeted delivery or binding with the disease site and extend the release of therapeutic agents with prolonged retention. This leads to improved therapeutic efficacy, patient compliance, and cost effectiveness of therapy with minimum dose associated side-effects. This review has summarized various nanocarriers explored for the treatment of AMD and challenges in translation.

scholarly journals A Review of Completed and Ongoing Complement Inhibitor Trials for Geographic Atrophy Secondary to Age-Related Macular Degeneration

2021 ◽  
Vol 10 (12) ◽  
pp. 2580
Author(s):  
Omar A. Halawa ◽  
Jonathan B. Lin ◽  
Joan W. Miller ◽  
Demetrios G. Vavvas
Keyword(s):  
Macular Degeneration ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Western World ◽  
Complement Factor ◽  
Complement Protein ◽  
Pivotal Phase ◽  
Complement Inhibition ◽  
Exudative Amd ◽  
Age Related

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness among older adults in the Western world. While therapies exist for patients with exudative AMD, there are currently no approved therapies for non-exudative AMD and its advanced form of geographic atrophy (GA). The discovery of genetic variants in complement protein loci with increased susceptibility to AMD has led to the investigation of the role of complement inhibition in AMD with a focus on GA. Here, we review completed and ongoing clinical trials evaluating the safety and efficacy of these studies. Overall, complement inhibition in GA has yielded mixed results. The inhibition of complement factor D has failed pivotal phase 3 trials. Studies of C3 and C5 inhibition meeting their primary endpoint are limited by high rates of discontinuation and withdrawal in the treatment arm and higher risks of conversion to exudative AMD. Studies evaluating other complement members (CFB, CFH, CFI and inhibitors of membrane attack complex—CD59) are ongoing and could offer other viable strategies.

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