COMMENTARY

Age-Related Macular Degeneration: 5 Things to Know

William C. Ou; Charles C. Wykoff, MD, PhD

Disclosures

December 14, 2018

Age-related macular degeneration (AMD) is a chronic disease of the macula that remains a leading cause of irreversible vision loss around the world.

Broadly, AMD is classified into "dry" and "wet" forms. Dry AMD encompasses a wide spectrum of pathology ranging from the presence of clinically silent deposits under the retina within the macula, known as drusen, to the severe manifestation of geographic atrophy of the retinal pigment epithelium and photoreceptors. Wet (or neovascular) AMD is characterized by growth of abnormal blood vessels from the retina itself, or more commonly the underlying choroid into the subretinal space, leading to fluid leakage or subretinal hemorrhage (choroidal neovascularization [CNV]). Although wet AMD develops in only 10%-15% of eyes with AMD, it is responsible for a disproportionately large fraction of severe vision loss among AMD patients.[1,2]

Between 2012 and 2050, the number of Americans aged 65 years and older is expected to almost double, from 43 million to 84 million.[3] Given that AMD is almost exclusively a disease of those older than 50 years, these projections suggest that the burden of this disease will also rise dramatically over the coming decades.[4]

In light of the social, economic, and psychological consequences that vision loss has for patients and caregivers, here are five issues to be aware of related to AMD.

1. Anti-Vascular Endothelial Growth Factor (VEGF) Agents Are Effective, but Most Patients Require Ongoing Dosing

Beginning with the US Food and Drug Administration (FDA) approval of ranibizumab in 2006, intravitreally administered agents that target VEGF-A have become the indisputable first-line treatment for wet AMD. Two other such agents are aflibercept, approved by the FDA in 2011, and bevacizumab, commonly used off-label. Multiple clinical trials have demonstrated that treatment with anti-VEGF agents dramatically improves anatomic and visual outcomes in most appropriately treated patients.[5,6,7,8,9,10]

Anti-VEGF agents are not a cure for AMD, however, and most patients require ongoing, indefinite dosing to maintain control over exudative disease activity and optimize long-term outcomes. Although there has been considerable interest in dosing strategies that reduce treatment burden, multiple lines of evidence support the concept that consistent and persistent dosing regimens maximize ultimate visual outcomes.[8,9,10] Indeed, in the absence of consistent injections, visual acuity outcomes in the long term (5+ years) have been quite disappointing.[11,12]

To combat the tremendous challenge of long-term monthly or every-other-month dosing, one strategy is simply to engineer more-potent VEGF inhibitors. Two such potential agents are brolucizumab[13] and abicipar pegol,[14] both of which have undergone phase 3 trials for wet AMD. Another is faricimab,[15] which will soon enter phase 3 based on promising phase 2 results. Although complete data regarding these agents are not yet publicly available, there is optimism that they may allow for a reduced treatment burden (eg, more frequent ability to achieve quarterly intervals between dosing), which may afford improved compliance and optimization of long-term outcomes.

Another option lies in medical device development, namely a surgically implanted, refillable port delivery system designed to release an anti-VEGF pharmaceutical into the vitreous cavity in a continuous fashion.[16] On the basis of positive phase 2 results, such a device has recently entered phase 3 and may ultimately provide an attractive alternative to repeated intravitreal injections.

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