Medically Reviewed by Dr. Mayur Jawale (MBBS, MS- Ophthalmology, Fellowship in Phacoemulsification)
Introduction
Age-related macular degeneration (AMD) creates haziness on central vision and is a leading cause of irreversible vision loss in individuals over 50. It affects the macula, the central part of the retina responsible for sharp, detailed vision. AMD is affecting central vision without causing complete blindness. This can make everyday activities such as reading, driving, recognizing faces, and detailed tasks much more challenging. While there is no cure for AMD, recent advancements in medical research have led to groundbreaking treatments that slow disease progression and, in some cases, restore vision. This article explores the latest innovations in AMD therapy, including gene therapy; stem cell treatments, and novel drug delivery systems.
Types of AMD
Age-related macular degeneration (AMD) is classified into two main forms: dry (atrophic) AMD and wet (neovascular) AMD. They differ in progression, symptoms, and treatment approaches.
Dry AMD (Non-Exudative or Atrophic AMD)
Most common type (about 80-90% of AMD cases)
Slow progression over years, leading to gradual central vision loss.
Caused by thinning of the macula and accumulation of drusen (yellow protein deposits) under the retina
Advanced stage: Geographic atrophy (GA), where retinal cells degenerate, causing permanent blind spots
Current treatments: No cure, but AREDS2 supplements may slow progression
Wet AMD (Exudative or Neovascular AMD)
Less common but more severe (10-15% of AMD cases)
Rapid progression, often leading to sudden vision loss
Caused by abnormal blood vessel growth (choroidal neovascularisation) that leak fluid/blood, damaging the macula
Symptoms: Distorted vision (metamorphopsia), dark spots, rapid central vision decline
Treatments: Anti-VEGF injections (e.g., Lucentis, Eylea), laser therapy, and photodynamic therapy
Current Standard Treatments
Before delving into new advancements, it’s essential to understand the existing treatments:
Anti-VEGF Injections – The gold standard for wet AMD, these drugs (e.g., ranibizumab, aflibercept, bevacizumab) block vascular endothelial growth factor (VEGF), preventing abnormal blood vessel growth. No clinically major variation in the effectiveness and safety of different anti-VEGF treatments.
Laser Therapy – Laser photocoagulation is a type of laser therapy Used in certain cases of wet AMD to destroy abnormal blood vessels.
Laser photocoagulation is only used in wet AMD, where irregular blood vessels develop, but it’s not suitable for all patients.”
Vitamin Supplements (AREDS2 Formula): According to the NIH-funded AREDS2 research, taking certain vitamin and mineral supplements reduces the risk of dry AMD progressing to sight-threatening stages by 25 percent.
This formula involve Vitamin C: 500 mg, Vitamin E: 400 IU, Zinc: 80 mg (as zinc oxide), Copper: 2 mg (as cupric oxide), Lutein: 10 mg, Zeaxanthin: 2 mg
While effective, these treatments have limitations, such as frequent injections and incomplete efficacy in dry AMD. Researchers are now developing next-generation therapies to overcome these challenges.
Cutting-Edge Advancements in AMD Treatment
Gene Therapy for AMD
Gene therapy is emerging as a promising approach for treating age-related macular degeneration (AMD), particularly its neovascular (wet) form. Traditional treatments for wet AMD often require frequent intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents to control abnormal blood vessel growth in the retina. Gene therapy aims to provide a more sustainable solution by enabling the eye to produce therapeutic proteins internally, potentially reducing or eliminating the need for repeated injections.
Advancements in Gene Therapy for Wet AMD
RGX-314 (REGENXBIO): This therapy utilizes an adeno-associated virus (AAV) vector to deliver a gene encoding a monoclonal antibody fragment that inhibits VEGF. It is designed for subretinal or suprachoroidal delivery, with the goal of providing long-term suppression of VEGF activity. Clinical trials are ongoing to evaluate its safety and efficacy
Ixo-vec, formerly ADVM-022 (Adverum Biotechnologies): Ixo-vec employs an AAV vector to deliver a gene encoding an anti-VEGF protein. Following favourable results from Phase 1 and Phase 2 trials, Adverum is preparing to initiate Phase 3 clinical trials in the first half of 2025.
Gene Therapy for Dry AMD (Geographic Atrophy)
While much focus has been on wet AMD, gene therapy is also being explored for geographic atrophy (GA), the advanced form of dry AMD.
GT005 (Gyroscope Therapeutics): This investigational gene therapy aims to increase the production of complement factor I, a protein that regulates the complement system implicated in GA. Clinical trials are underway to assess its safety and efficacy.
OCU410 (Ocugen): A Phase 1/2 study is evaluating the safety and efficacy of OCU410 for GA secondary to dry AMD. The study involves randomized, sequential assignment with single masking and aims to enroll 63 patients.
Stem Cell Therapy
Stem cell therapy is emerging as a promising avenue for treating age-related macular degeneration (AMD), particularly its dry form, known as geographic atrophy (GA). Recent advancements have led to several clinical trials aimed at evaluating the safety and efficacy of stem cell-based treatments for AMD. Scientists are focusing on replacing damaged retinal pigment epithelium (RPE) cells, which are crucial for supporting photoreceptors, the cells responsible for detecting light.
Embryonic and Induced Pluripotent Stem Cells (iPSCs) – Researchers are implanting retinal pigment epithelium (RPE) cells derived from stem cells to replace damaged tissue.
Phase I/II Clinical Trials – One notable initiative is a Phase I/IIa clinical trial conducted by the National Eye Institute (NEI), focusing on the transplantation of autologous induced pluripotent stem cell-derived retinal pigment epithelium (iRPE) cells. This trial aims to assess the safety of implanting iRPE patches into areas adjacent to GA in patients with advanced dry AMD.
Complement Inhibitors (For Dry AMD)
Significant advancements have been made in the development of complement inhibitors for the treatment of dry age-related macular degeneration (AMD), particularly in addressing geographic atrophy (GA), an advanced form of dry AMD.
Approved Treatments
Pegcetacoplan (Syfovre): This C3 inhibitor received approval from the U.S. Food and Drug Administration (FDA) in February 2023 for the treatment of GA. Administered via intravitreal injection every 25 to 60 days, pegcetacoplan has demonstrated a reduction in the progression of GA lesions over time.
Avacincaptad Pegol (Izervay): Approved by the FDA in August 2023, this C5 inhibitor is administered through monthly intravitreal injections. Clinical trials have shown that avacincaptad pegol can slow the growth of GA lesions, with its protective effect increasing over
There are multiple clinical trial are going on to investigate new complement inhibitors like NGM621, ANX007, IONIS-FB-LRx (ASO Factor B).
Sustained Drug Delivery Systems
Reducing injection frequency is a major focus.
Port Delivery System (Susvimo, Roche) – A refillable implant that continuously releases ranibizumab, requiring only biannual refills.
Extended-Release Anti-VEGF Formulations – Drugs like KSI-301 (Kodiak Sciences) use antibody biopolymers to prolong therapeutic effects.
Artificial Intelligence (AI) in AMD Diagnosis & Monitoring
AI is revolutionizing early detection and personalized treatment.
Retinal Imaging Analysis – AI algorithms (e.g., IDx-DR, Optos) detect AMD progression earlier than traditional methods.
Predictive Modelling – AI helps predict which patients will progress to advanced AMD, enabling timely intervention
Future Directions
CRISPR Gene Editing – Potential to correct genetic mutations causing AMD.
Bionic Retina Implants – Devices like the PRIMA implant restore partial vision in late-stage AMD.
Conclusion
The landscape of AMD treatment is rapidly evolving, with gene therapy, stem cells, and sustained drug delivery systems offering hope for long-term solutions. While challenges remain, these innovations promise to transform AMD management, reducing treatment burden and improving quality of life for millions. Continued research and clinical trials will be crucial in bringing these therapies to mainstream ophthalmology.
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