Age-related macular degeneration (AMD) is a serious public health threat, leading to central vision loss through either new blood vessel growth (known as wet or neovascular AMD) and/or the breakdown of photoreceptor cells (“dry AMD”, also called geographic atrophy).

Current treatment options for wet AMD include vitamin supplementation and FDA-approved drugs like bevacizumab and aflibercept, which inhibit abnormal blood vessel growth. Other promising therapies may also be in development.

1. Anti-VEGF Drugs

Anti-VEGF drugs have emerged as an indispensable asset in diabetes retinopathy (DR) management, leading to significant improvements in vision restoration for many patients. VEGF is a protein produced by body cells including those in the retina that stimulates new blood vessel formation; in poor diabetes control situations this production increases abnormally and leads to abnormal new blood vessel growth which results in macular edema or choroidal neovascularization (CNV), leading to decreased visual acuity or even blindness.

Anti-VEGF injections work to stop fluid leakage from newly formed blood vessels, thus slowing vision loss and protecting macula integrity. They may be administered using an eyedropper directly into the eye or with a small probe on top of retina surface (cryotherapy).

Frequent injections may lead to complications, including pain and inflammation. Furthermore, regular follow-up visits are necessary. Unfortunately, some patients may not qualify for a treatment pause if they have been using anti-VEGF injections for more than 30 weeks; it is therefore crucial that your eye health be closely monitored by consulting an eye M.D (ophthalmologist).

Faricimab was recently approved by the FDA to treat neovascular age-related macular degeneration and diabetic macular edema, with various clinical trials such as the VIEW 1 and 2 studies providing safety and efficacy data over one year; both showed noninferiority to Aflibercept in terms of mean change in best corrected visual acuity changes – marking it as the first ever monoclonal antibody trial for wet AMD to achieve such high efficacy levels and durability!

Genzyme’s drug molecule has been designed to outlive current standards of care requiring monthly intravitreal injections and may demonstrate long-term durability similar to that seen with gene therapy treatments for monogenic blinding diseases. Genzyme combines anti-VEGF agents with AAV gene delivery technology in its approach.

2. Stem Cell Therapy

At later stages of dry AMD, light-sensing cells called photoreceptors in the macula begin to break down, leading to blurriness especially in low lighting conditions or dim environments. Some individuals may notice an increasing blind spot at the center of their vision as their symptoms worsen – a sure sign that your disease has advanced into Neovascular (Wet) AMD which involves abnormal new blood vessels leaking fluid and blood into your macula and leading to rapid loss of central vision if left untreated.

To treat wet AMD, doctors administer anti-vascular endothelial growth factor (VEGF) drugs into the eye to block abnormal blood vessels from leaking fluid and blood. While these medicines have proven successful at slowing or stopping progression of disease and improving central vision, patients still lose vision over time despite treatment efforts; hence researchers continue to search for therapies to replace lost photoreceptors and defer onset of wet AMD neovascularization.

Dr. Kapil Bharti, Senior Investigator and Principal Investigator for an iPS cell-based experimental therapy of dry AMD at NEI, shared his research utilizing patient’s own induced pluripotent stem cells (iPSCs) to produce RPE cells which can then be used to patch degenerated retinas of those suffering with dry AMD. These RPE cells form synapses with host inner retinal neurons to restore vision circuitry.

One approach for treating wet AMD is targeting the complement system. This key part of defense helps defend healthy tissue against diseased and foreign cells while clearing away debris from the body; however, due to disease or age related dysregulation of this system can result in its breakdown and resulting in compromised defense mechanisms in host.

Ocugen is working towards solving these problems through its innovative gene therapy platform based on nuclear hormone receptors to develop therapies tailored towards satisfying unmet needs for retinal diseases including wet and dry AMD, thus offering greater hope than single gene replacement therapies which only address one mutation at a time. Recently, it held a pre-Investigational New Drug (IND) meeting with FDA on its candidate OCU200 that can treat neovascular age-related macular degeneration as well as diabetic macular edema.

3. Mitochondrial Therapy

Mitochondrial dysfunction has been associated with various diseases and eye conditions. Mitochondrial gene therapy (MGT) attempts to address mitochondrial DNA that contributes to this dysfunction; however, due to technical complications this therapy remains underutilized. Additionally, its application involves transmitting genetic modifications directly through germline therapy; which has created ethical concerns that remain unanswered.

Researchers have made impressive strides toward treating age-related macular degeneration over the past several years by targeting retinal pigment epithelium cells and gene therapy to stop dry AMD from progressing to geographic atrophy and wet macular degeneration. These advances could prevent vision loss by stopping new blood vessel growth that leak and destroy RPE cells.

These new treatments will require additional research and funding. The National Institutes of Health website lists several macular degeneration clinical trials that may be available; however, participants must meet specific eligibility criteria in order to be considered eligible to join one. These studies may focus on various stages of disease or specific geographic locations.

Risuteganib (Luminate, Allegro Ophthalmics LLC) stands out as one of the most promising new treatments for dry macular degeneration. This medication reduces cell damage and inflammation associated with macular degeneration while potentially slowing its progression by blocking VEGF pathways.

Other treatments are being developed, including photoreceptor implants that bypass damaged cells while providing direct stimulation to healthy ones, and gene therapy involving gene delivery that inhibits abnormal blood vessel growth beneath the retina – wet macular degeneration being one form. Studies are underway to improve its effectiveness using other drugs that block VEGF or inhibit cell growth, while imaging technologies should continue being developed that can detect changes early on in its progression.

4. Nanoparticle Therapy

Geographic Atrophy (GA), the advanced stage of dry age-related macular degeneration, currently lacks effective treatments. GA is the most prevalent and severe form of the condition and results in significant vision impairment for its victims; representing an unmet medical need affecting over 196 million people globally.

Kapil Bharti, Senior Investigator of the Ocular and Stem Cell Translational Research Unit at the National Eye Institute, presented on his first-in-human clinical trial utilizing RPE cells derived from induced pluripotent stem cell technology to treat dry AMD. He shared how they are using it as part of their therapy regime to patch RPE degeneration caused by dry AMD.

Cellular therapy involves converting patient’s own blood cells into iPSCs that are then programmed into RPE cells for injection into their eyes to replace degenerating RPE that might otherwise hinder photoreceptor health.

iPSC-derived RPE cells are being utilized to evaluate new therapeutic approaches, such as using folate-decorated triamcinolone acetonide nanoparticles to prevent choroidal neovascularization in neovascular AMD. The nanoparticles contain high concentrations of an antiangiogenic drug which will be released gradually and slowly into your eye to inhibit new blood vessel formation; furthermore, gp91 ds-tat peptide which binds Nox2 receptor and inhibiting new blood vessel formation is also enclosed inside polymer so as to enhance and prolong release of medication.

Muna Naash, professor of ophthalmology at the University of Oklahoma Health Sciences Center recently reported that experimental drug Risuteganib (Luminate; Allegro Ophthalmics) can effectively stabilize mitochondria and improve photopic best corrected visual acuity in dry macular degeneration by stabilizing them.

Researchers are exploring various delivery mechanisms to the retina to treat neovascular and dry macular degeneration, including using chimeric and adeno-associated virus vectors to deliver genetically modified or pharmacologically active compounds to the retina and surrounding tissues.