What is on the horizon for dry age-related macular degeneration drug treatment?

Abstract

ABSTRACTIntroduction Age-related Macular Degeneration (AMD) is one of the leading causes of irreversible visual acuity reduction among the elderly population. Dry AMD, the most frequent AMD form, is characterized by photoreceptor loss, Retinal Pigmented Epithelium (RPE) dysfunction and retinal degeneration. Although in the last years several clinical trials have been carried out and many therapeutic molecules have been examined to treat dry AMD, currently its treatment remains unsatisfactory.Areas covered In this review we report and analyze the most important molecules and treatment that have been studied and carried out till nowadays, and the future therapies that may be a hope in this complex and serious disease. We have provided a narrative review after having analyzed the literature and we have selected more than 120 papers to deliver this article.Expert opinion Although in 2023 has been carried out the first FDA approved drugs, there is still a long way to go in developing effective therapies for dry-AMD. In the future, a better understanding of its pathogenesis may lead to the development of targeted or genetic therapies that not only have an anatomical effect on the retina but also have a functional impact.KEYWORDS: Age related macular degenerationGeographic atrophydrusencomplement inhibitorsneuroprotectiongenetic therapyintravitreal injectionDisclaimerAs a service to authors and researchers we are providing this version of an accepted manuscript (AM). Copyediting, typesetting, and review of the resulting proofs will be undertaken on this manuscript before final publication of the Version of Record (VoR). During production and pre-press, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal relate to these versions also. Article highlightsIn this review we have summarized the most important molecules and trials that have been carried out till now in the attempt to treat dry-AMD.AREDS nutritional supplementation remains the standard of care for dry-AMD.In 2023 FDA has approved the first proven effect therapies for dry-AMD: Pegcetacoplan, and Avacincaptad Pegol.In the future, a genetic therapy focused on preventing and blocking the development of dry-AMD could be the most effective treatment, but at the present time, its development is at the embryonic stage.Declaration of InterestsR Sacconi has the following disclosures: Allergan Inc, Bayer Shering-Pharma, Medivis, Novartis, Zeiss.G Querques has the following disclosures: Alimera Sciences, Allergan Inc, Amgen, Bayer Shering-Pharma, Heidelberg, KBH, LEH Pharma, Lumithera, Novartis, Sandoz, Sifi, Sooft-Fidea, Zeiss.F Bandello has the following disclosures: Alcon (consultant), Alimera Sciences (consultant), Allergan Inc (consultant), Farmila-Thea (consultant), Bayer Shering-Pharma (consultant), Bausch and Lomb Genentech (consultant), Hoffmann-La-Roche (consultant), Novagali Pharma (consultant), Novartis (consultant), Sanofi-Aventis (consultant), Thrombogenics (consultant), Zeiss (consultant).The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Figure 1: The image shows an intermediate AMD through Multicolor image and OCT. Yellow arrows indicate a group of drusen, blue arrow indicates a drusen shown both on Multicolor and OCT scan.Display full sizeFigure 2: The image shows the typical GA pattern, pointed out by different filters.Display full sizeFigure 3: The image shows a foveal sparing GA through infra-red, multicolor and OCT imagesDisplay full sizeFigure 4: The image shows the main complement inhibitors drugs and their complement cascade corresponding targetDisplay full sizeAdditional informationFundingThis paper was not funded