By Leo Semes, OD
Member, Medical Advisory Board, Macular Degeneration Association
The landscape of treatments for wet age-related macular degeneration (AMD) have undergone revolutionary advances over the past two decades. The FDA approval of Visudyne Ó in 2000 displaced laser photocoagulation as primary treatment. The strategy behind this photodynamic therapy was to stabilize fragile new vessel webs and maintain visual performance. This process involved injecting verteporfin into a vein in the arm and activation using a specific light source directed into the eye. Apart from low-vision devices, little improvement is vision could be expected with either treatment.
The introduction of anti-vegetative growth factor (VEGF) medications in 2004 is considered among the most significant therapeutic innovations in eyecare. If you or someone you know suffers from the wet form of AMD, there may be familiarity with these approaches. The impact of intravitreal administration of anti-VEGF agents was transformative. Initial visual-acuity improvement was seen for the first time and was later found to persist for seven years or more. “Every silver lining has a cloud,” however, to paraphrase the Grateful Dead. Injections required closely scheduled follow-ups and frequent retreatment. Beyond those burdens, treatments are a lifetime proposition.
The first generation of anti-VEGF agents including MacugenÓ, AvastinÓ and LucentisÓ had become household words during the first decade of the twenty-first century. The FDA-approval of EyleaÓ and BeovuÓ in the next decade aimed to reduce treatment burden. This meant longer intervals between observations and, with newer protocols, fewer injections. This group targeted what was identified as the primary driver of neovascularization, VEGF. Further research has identified additional pathways that contribute not only to the subretinal neovascularization of AMD but to other aspects of retinal vascular instability (RVI).
Second-generation agents were also aimed at the angiogenic pathway of angiopoetin-2 (ang-2). These combination agents were then applied to treatment for diabetic macular edema (DME) and macular edema following retinal vein occlusion (MDfVO). If you suffer from wet AMD or other causes of RVI, names like VabysmoÓ and SusvimoÓ may sound familiar. Or perhaps direct-to-consumer advertising has caught your eye. These agents are intended to have faster and improved outcomes as well as prolonged efficacy.
Progress is also being made for the treatment of geographic atrophy (GA), the dry form of AMD. Equally visually devasting and more prevalent than the wet form, GA is characterized as relentlessly progressive. Compounds that target the complement system, at the molecular level, have been available for over three years. Both SyfovreÒand IzervayÒ proved to staunch the progression of GA via the intravitreal injection route. While not as dramatic as vision improvements for wet AMD, these intravitreal injections represent a first step in the fight against dry AMD. Novel IVI treatments being evaluated for GA include neuroprotective agents, gene therapy, which may require only a single injection and cell-based therapies.
Challenges up to this point have centered around durability and persistence, as represented by versions of Vabysmo® and Eylea-HD® which are showing promise but still have a ten-year window before regression to baseline visual acuity. Implantable devices containing currently available compounds to extend treatment intervals and improve visual performance and anatomical stability have been introduced and proven to be clinically accepted. A significant hurdle with newer agents is insurance coverage. Your retina specialist may be making recommendations with these restrictions in mind.
On the horizon is a group of third-generation compounds which aim to further reduce treatment burden as well as targeting other contributors to RVI. These include the bi-and tri-specific drugs, tyrosine-kinase inhibitors, fusion proteins as well as an array of gene therapies. These emerging therapies may also employ alternative routes of administration including suprachoroidal (microneedle, microcannula), port delivery, subconjunctival, subretinal and implantable.
Upcoming treatments for both wet and dry AMD are promising. The future is even brighter than two decades ago. Stay tuned but follow the recommendations of your eye care provider.