Retina specialists Eleonora M. Lad, MD, Nancy M. Holekamp and Jaynath R. Sridhar discuss the clinical burden associated with geographic atrophy as well as ways to monitor its progression with new tools.

Regeneron recently reported nonclinical data for Ixo-vec (ixoberogene soroparvovec), their wet AMD treatment, showing that vision gains could be maintained with reduced injections. Pharmacy Times provides more details of this news.

What is neovascular AMD?

Age-related macular degeneration (AMD) is a serious eye disease, leading to central vision loss among the elderly population in developed nations. The condition results from atrophy of retinal pigment epithelium cells and formation of choroidal neovascular membranes under the macula that leak fluid and blood into retina, eventually creating disciform scars in its path resulting in irreversible blindness in adults over 55 in Western nations. Although medical advances have improved visual outcomes significantly for this condition, AMD remains one of the primary causes of irreversible blindness irreversibly blinding adults over 55 in Western nations.

Geographic atrophy (GA) and Neovascular AMD or Wet AMD account for most severe cases of advanced AMD. Wet AMD is caused by abnormal blood vessels forming underneath Bruch’s membrane, leading to choroidal neovascularization and leakage of fluid into the retina causing rapid vision loss. While GA does not yet have FDA-approved treatments available, Neovascular AMD can be treated using anti-VEGF agents.

These medications may slow the progression of neovascular AMD and in some instances provide temporary improvement in visual acuity; however, they cannot reverse its progression and may eventually lose efficacy over time. Furthermore, frequent dosage and cost can make these treatments costly both to individuals as well as healthcare systems.

As such, there has been considerable interest in finding new therapies to treat wet AMD. Pharmaceutical companies are actively exploring various approaches in order to maximize visual outcomes while simultaneously minimizing treatment burden and increasing long-term adherence.

Faricimab-svoa (Vabysmo) was recently introduced to the US market as an innovative treatment option for AMD, diabetic macular edema, and wet AMD. This medication targets and inhibits two disease pathways responsible for these conditions, providing superior two-year results compared to other similar drugs for these conditions. Furthermore, this study underscored the significance of accurate diagnosis when dealing with patient populations with fluid which may not show neovascular activity; proper evaluation using optical coherence tomography angiography or fluorescein angiography may help direct treatment decisions accordingly.

What are the current treatment options for neovascular AMD?

AMD is one of the primary causes of blindness among those over 60, compromising central vision by damaging the macula. Over time, this progressive condition eventually results in legal blindness, making tasks that rely on central vision (such as reading or driving) difficult or impossible.

Anti-VEGF therapy is the primary approach for treating neovascular AMD, and two of the most frequently prescribed drugs are ranibizumab and aflibercept – both have shown to significantly slow progression of neovascular AMD in clinical trials and were FDA-approved as treatment options for both neovascular AMD and diabetic macular edema (DME).

But these drugs have their limitations: their duration of effectiveness is limited and side effects such as cataracts and vitreomacular adhesions may occur; additionally they do not address the underlying pathology of neovascular AMD; new anti-VEGF agents like faricimab are being developed specifically to meet this need.

Adverum Biotechnologies recently presented nonclinical data from their YOSEMITE and RHINE phase 3 clinical studies of faricimab at ARVO 2023 in New Orleans. Their drug SB15 was well tolerated and produced comparable efficacy with Aflibercept through week 56 of their trials, enabling physicians to extend treatment intervals without impacting visual or anatomic outcomes.

These data support a “treat and extend” strategy in managing neovascular AMD, where patients may benefit from receiving frequent doses of Aflibercept for preventative maintenance while still enjoying good anatomic outcomes and no new macular hemorrhages on ocular coherence tomography angiography angiography scans. This approach may prove especially valuable in treating dry AMD cases which do not respond well to anti-VEGF therapy.

Pegaptanib was recently approved by the FDA as an effective treatment for DME among those with AMD and DME. This novel agent targets multiple angiogenesis pathways and its long-acting nature may allow it to be administered more easily than current therapies; its long-acting nature may allow fewer injections than current ones, and may have better safety profile than VEGF inhibitors because it doesn’t promote retinal artery narrowing and has no systemic risks.

What are the risks of neovascular AMD?

Recent research found that taking vasodilators (i.e. blood vessel dilation medications), increases risk of early-stage AMD by 72 percent. As a result, clinicians should avoid prescribing these drugs to those at high risk for AMD.

This study used data from the Eye Disease Case-Control Study, which evaluated health histories of people diagnosed with neovascular AMD as well as those without it, as part of its analysis. It discovered a variety of factors influenced development of neovascular AMD including age, gender and severity of drusen in one eye as well as smoking cigarettes, increased levels of carotenoids in blood, horizontal cup-to-disc ratio in macula and postmenopausal exogenous estrogen use by women. It also discovered that fellow eyes influenced its rate of progression as well as status within relation to each other eye impacted its rate of progression.

Researchers conducted clinical exams and OCT scans, finding that eyes with large drusen progressed faster than those with medium drusen due to fluid accumulation within larger drusen, which indicates choroidal neovascular membrane (CNVM). Genetic makeup and health of both eyes also play key roles in how fast disease will spread.

Studies have also indicated that an absence of pigment epithelial abnormalities is associated with faster rates of disease progression; however, further investigation must be performed to establish if this association relates to local or other factors.

Clinicians should understand the potential advantages of using ocular coherence tomography and fluorescein angiography for managing neovascular AMD. These tools can help identify CNVM in retina, confirm presence of fluid in vitreous cavity without further tests, monitor anti-VEGF injection effects to make sure they’re working as intended, as well as help detect patients not responding well and switch medications if necessary.

What are the benefits of neovascular AMD?

Neovascular AMD treatment can have more than just vision benefits; it can also positively influence quality of life. This is because an improved visual acuity (VA) may reduce the need for assistive devices like reading glasses. Furthermore, improved VA may give patients more independence as it allows them to participate in everyday activities like driving, cooking, shopping and socializing more easily.

Current treatments for wet age-related macular degeneration (neovascular AMD, or exudative AMD) involve intravitreal injections of anti-vascular endothelial growth factor medications to prevent further retinal damage and enhance vision acuity for those living with neovascular AMD. They form an integral component of the National Institute for Health and Care Excellence’s (NICE) guidelines on managing wet AMD.

People suffering from wet AMD typically develop it due to choroidal neovascularization. When this happens, abnormal blood vessels cause bleeding under the retina that results in rapid and dramatic loss of central vision. Changes are easily detectable with color fundus photographs and optical coherence tomography (OCT) imaging – in healthy eyes the macula should look bright and clear on these photos, with no broken anatomic structures shown by OCT imagery; but when many or very large yellow or white particles (drusen) appear under the retina it could indicate the presence of Neovascular AMD.

Drusen are tiny deposits found under the retina that appear as small holes on photographs and OCT scans. When small, drusen are harmless but as they increase in size they can block macula function leading to vision loss.

Neovascular AMD can cause central vision to blur, worsen and then eventually worsen over time. But when detected early and treated promptly, vision can remain stable or even improve.

Large clinical trials have demonstrated that anti-VEGF injections given at regular intervals can both halt progression to advanced AMD and improve visual acuity, yet without incurring severe side effects or being prohibitively expensive for many patients. Researchers are working on long-acting drug delivery systems which will reduce frequency of injections or need for visits to clinic.