Abstract
Age-related macular degeneration (AMD) is the leading cause of legal blindness in the industrialized world. AMD is characterized by accumulation of extracellular deposits, namely drusen, along with progressive degeneration of photoreceptors and adjacent tissues. AMD is a multifactorial disease encompassing a complex interplay between ageing, environmental risk factors and genetic susceptibility. Chronic inflammation, lipid deposition, oxidative stress and impaired extracellular matrix maintenance are strongly implicated in AMD pathogenesis. However, the exact interactions of pathophysiological events that culminate in drusen formation and the associated degeneration processes remain to be elucidated. Despite tremendous advances in clinical care and in unravelling pathophysiological mechanisms, the unmet medical need related to AMD remains substantial. Although there have been major breakthroughs in the treatment of exudative AMD, no efficacious treatment is yet available to prevent progressive irreversible photoreceptor degeneration, which leads to central vision loss. Compelling progress in high-resolution retinal imaging has enabled refined phenotyping of AMD in vivo. These insights, in combination with clinicopathological and genetic correlations, have underscored the heterogeneity of AMD. Hence, our current understanding promotes the view that AMD represents a disease spectrum comprising distinct phenotypes with different mechanisms of pathogenesis. Hence, tailoring therapeutics to specific phenotypes and stages may, in the future, be the key to preventing irreversible vision loss.
| Original language | English |
|---|---|
| Article number | 31 |
| Journal | Nature Reviews Disease Primers |
| Volume | 7 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2021 |
Bibliographical note
Funding Information:M.F. and S.S.-V. were in part supported by National Institutes of Health Core Grant (EY014800), and an Unrestricted Grant from Research to Prevent Blindness, New York, NY, to the Department of Ophthalmology & Visual Sciences, University of Utah and the German Research Foundation (DFG) grant FL 658/4-1 and FL 658/4-2.
Funding Information:
M.F. reports grants from Heidelberg Engineering, Genentech/ Roche, Novartis and Optos; and personal fees from Bayer, Heidelberg Engineering, Genentech/Roche and Novartis; and non-financial support from Heidelberg Engineering, Optos and Zeiss Meditech, outside the submitted work. In addition, M.F. has a patent, US20140303013 A1, pending. R.H.G serves on the advisory boards of Apellis, Bayer, Genentech/ Roche and Novartis. U.C. reports personal fees from Apellis, Alimera, Boehringer Ingelheim, Iveric Bio, Novartis, and Roche. S.S.-V. reports grants from Acucela/Kubota Vision, grants and personal fees from Allergan, personal fees from Bayer, non-financial support from Carl Zeiss MediTec, non-financial support from Centervue, personal fees from Gailmedix, personal fees and non-financial support from Heidelberg Engineering, grants from Katairo, grants and personal fees from Novartis, grants and personal fees from Roche, personal fees from Oxurion, grants and personal fees from Bioeq/Formycon, personal fees from Apellis, grants from SparingVision, grants from Pixium, outside the submitted work. E.Y.C., T.D.L.K and W.T.W. are co-inventors on a patent application (‘Methods and systems for predicting rates of progression of age-related macular degeneration’). W.T.W. is a current employee at Janssen Research and Development. C.C.K. declares no competing interests.
Publisher Copyright:
© 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.