Cargando…

Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects

Geographic atrophy (GA) of the retinal pigment epithelium (RPE) is a devastating complication of age-related macular degeneration (AMD). GA may be classified as drusen-related (drusen-associated GA) or neovascularization-related (neovascular-associated GA). Drusen-related GA remains a large public h...

Descripción completa

Detalles Bibliográficos
Autores principales: Danis, Ronald P, Lavine, Jeremy A, Domalpally, Amitha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4662367/
https://www.ncbi.nlm.nih.gov/pubmed/26640366
http://dx.doi.org/10.2147/OPTH.S92359
_version_ 1782403152762372096
author Danis, Ronald P
Lavine, Jeremy A
Domalpally, Amitha
author_facet Danis, Ronald P
Lavine, Jeremy A
Domalpally, Amitha
author_sort Danis, Ronald P
collection PubMed
description Geographic atrophy (GA) of the retinal pigment epithelium (RPE) is a devastating complication of age-related macular degeneration (AMD). GA may be classified as drusen-related (drusen-associated GA) or neovascularization-related (neovascular-associated GA). Drusen-related GA remains a large public health concern due to the burden of blindness it produces, but pathophysiology of the condition is obscure and there are no proven treatment options. Genotyping, cell biology, and clinical imaging point to upregulation of parainflammatory pathways, oxidative stress, and choroidal sclerosis as contributors, among other factors. Onset and monitoring of progression is accomplished through clinical imaging instrumentation such as optical coherence tomography, photography, and autofluorescence, which are the tools most helpful in determining end points for clinical trials at present. A number of treatment approaches with diverse targets are in development at this time, some of which are in human clinical trials. Neovascular-associated GA is a consequence of RPE loss after development of neovascular AMD. The neovascular process leads to a plethora of cellular stresses such as ischemia, inflammation, and dramatic changes in cell environment that further taxes RPE cells already dysfunctional from drusen-associated changes. GA may therefore develop secondary to the neovascular process de novo or preexisting drusen-associated GA may continue to worsen with the development of neovascular AMD. Neovascular-associated GA is a prominent cause of continued vision loss in patients with otherwise successfully treated neovascular AMD. Clearly, treatment with vascular endothelial growth factor (VEGF) inhibitors early in the course of the neovascular disease is of great clinical benefit. However, there is a rationale and some suggestive evidence that anti-VEGF agents themselves could be toxic to RPE and enhance neovascular-associated GA. The increasing prevalence of legal blindness from this condition due to the aging of the general population lends urgency to the search for a therapy to ameliorate GA.
format Online
Article
Text
id pubmed-4662367
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Dove Medical Press
record_format MEDLINE/PubMed
spelling pubmed-46623672015-12-04 Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects Danis, Ronald P Lavine, Jeremy A Domalpally, Amitha Clin Ophthalmol Review Geographic atrophy (GA) of the retinal pigment epithelium (RPE) is a devastating complication of age-related macular degeneration (AMD). GA may be classified as drusen-related (drusen-associated GA) or neovascularization-related (neovascular-associated GA). Drusen-related GA remains a large public health concern due to the burden of blindness it produces, but pathophysiology of the condition is obscure and there are no proven treatment options. Genotyping, cell biology, and clinical imaging point to upregulation of parainflammatory pathways, oxidative stress, and choroidal sclerosis as contributors, among other factors. Onset and monitoring of progression is accomplished through clinical imaging instrumentation such as optical coherence tomography, photography, and autofluorescence, which are the tools most helpful in determining end points for clinical trials at present. A number of treatment approaches with diverse targets are in development at this time, some of which are in human clinical trials. Neovascular-associated GA is a consequence of RPE loss after development of neovascular AMD. The neovascular process leads to a plethora of cellular stresses such as ischemia, inflammation, and dramatic changes in cell environment that further taxes RPE cells already dysfunctional from drusen-associated changes. GA may therefore develop secondary to the neovascular process de novo or preexisting drusen-associated GA may continue to worsen with the development of neovascular AMD. Neovascular-associated GA is a prominent cause of continued vision loss in patients with otherwise successfully treated neovascular AMD. Clearly, treatment with vascular endothelial growth factor (VEGF) inhibitors early in the course of the neovascular disease is of great clinical benefit. However, there is a rationale and some suggestive evidence that anti-VEGF agents themselves could be toxic to RPE and enhance neovascular-associated GA. The increasing prevalence of legal blindness from this condition due to the aging of the general population lends urgency to the search for a therapy to ameliorate GA. Dove Medical Press 2015-11-20 /pmc/articles/PMC4662367/ /pubmed/26640366 http://dx.doi.org/10.2147/OPTH.S92359 Text en © 2015 Danis et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Review
Danis, Ronald P
Lavine, Jeremy A
Domalpally, Amitha
Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects
title Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects
title_full Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects
title_fullStr Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects
title_full_unstemmed Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects
title_short Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects
title_sort geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4662367/
https://www.ncbi.nlm.nih.gov/pubmed/26640366
http://dx.doi.org/10.2147/OPTH.S92359
work_keys_str_mv AT danisronaldp geographicatrophyinpatientswithadvanceddryagerelatedmaculardegenerationcurrentchallengesandfutureprospects
AT lavinejeremya geographicatrophyinpatientswithadvanceddryagerelatedmaculardegenerationcurrentchallengesandfutureprospects
AT domalpallyamitha geographicatrophyinpatientswithadvanceddryagerelatedmaculardegenerationcurrentchallengesandfutureprospects