Recent Developments in Agents for the Treatment of Age-Related Macular Degeneration and Stargardt Disease
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in older individuals living in developed countries. There are two major clinical presentations of AMD: atrophic or “dry” and neovascular or “wet.” Geographic atrophy (GA
- PDF / 571,259 Bytes
- 36 Pages / 439.37 x 666.142 pts Page_size
- 98 Downloads / 182 Views
Recent Developments in Agents for the Treatment of Age-Related Macular Degeneration and Stargardt Disease Konstantin Petrukhin
Contents 1 Introduction 2 Inhibition of Retinal Choroidal Neovascularization (CNV) 2.1 Non-VEGF Therapies 2.2 Anti-VEGF Biologics and RNA-Based Therapeutics 3 Treatment of Geographic Atrophy 3.1 Complement System Modulation 3.2 Visual Retinoid Cycle Modulation for Reducing Lipofuscin and Retinaldehyde Toxicities 3.3 Additional Treatment Approaches 4 Conclusion References
Abstract Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in older individuals living in developed countries. There are two major clinical presentations of AMD: atrophic or “dry” and neovascular or “wet.” Geographic atrophy (GA) is the most severe manifestation of dry AMD which represents the form of the disease characterized by the highest prevalence. A smaller fraction of AMD patients (10–20%) develop choroidal neovascularization (CNV) which represents the key feature of neovascular AMD. Historically, laser photocoagulation, surgery, and photodynamic therapy were the first treatment options for patients with CNV. In recent years, the emergence of anti-VEGF therapeutics has transformed the treatment of patients with neovascular AMD. Current anti-VEGF biologics that represent a standard of care (ranibizumab, bevacizumab, and aflibercept) are very effective in improving or maintaining visual acuity in CNV patients over long periods of time. The work on the new generation of anti-VEGF agents with higher potency and long-lasting efficacy is ongoing with the goal of reducing the frequency of intravitreal injections required for achieving good visual acuity outcomes. Brolucizumab, abicipar pegol, and faricimab exemplify the efforts K. Petrukhin (*) Department of Ophthalmology, Columbia University Medical Center, New York, NY, USA e-mail: [email protected]
K. Petrukhin
toward the development of novel therapeutic agents with lower frequency of intravitreal injections. While neovascular AMD can be effectively managed with current anti-VEGF therapeutics, there are no FDA-approved treatments for the atrophic form of AMD. Similarly, there is no therapy for inherited Stargardt disease, an orphan genetic form of macular dystrophy that shares phenotypic similarities with atrophic AMD. Due to the multigenic and multifactorial nature of AMD, it is believed that a combination of several factors may contribute to pathogenesis of atrophic AMD. This includes a complement system dysregulation in the retina and exposure of retinal cells to toxins produced in the visual retinoid cycle reactions (lipofuscin bisretinoids and retinaldehydes). Several therapeutic agents are currently being evaluated in clinical trials for geographic atrophy related to atrophic AMD or Stargardt disease. This includes pegcetacoplan (C3 inhibitor), avacincaptad pegol (C5 inhibitor), emixustat (RPE65 inhibitor), ALK-001 (deuterated form of vitamin A: C20-D3-retinyl acetate), STG-001 (RBP4 antagonist), and tinlarebant (RBP4 antag
Data Loading...
