Therapeutic Approaches with Intravitreal Injections in Geographic Atrophy Secondary to Age-Related Macular Degeneration: Current Drugs and Potential Molecules

Abstract

The present review focuses on recent clinical trials that analyze the efficacy of intravitreal therapeutic agents for the treatment of dry age-related macular degeneration (AMD), such as neuroprotective drugs, and complement inhibitors, also called immunomodulatory or anti-inflammatory agents. A systematic literature search was performed to identify randomized controlled trials published prior to January 2019. Patients affected by dry AMD treated with intravitreal therapeutic agents were included. Changes in the correct visual acuity and reduction in geographic atrophy progression were evaluated. Several new drugs have shown promising results, including those targeting the complement cascade and neuroprotective agents. The potential action of the two groups of drugs is to block complement cascade upregulation of immunomodulating agents, and to prevent the degeneration and apoptosis of ganglion cells for the neuroprotectors, respectively. Our analysis indicates that finding treatments for dry AMD will require continued collaboration among researchers to identify additional molecular targets and to fully interrogate the utility of pluripotent stem cells for personalized therapy.

<p>Complement system and age-related macular degeneration: drugs and challenges</p>

“…Repeated injection of anti-vascular endothelial growth factor (VEGF) has become a well-recognized therapy for patients with wet AMD. However, there is no effective treatment yet for dry AMD to slowdown the progression5 while it occupies approximately 90% of the AMD patients.

Figure 1Clinical manifestations of age-related macular degeneration. ( A ) Images of optical coherence tomogram (OCT) (above) of choroidal neovascularization (CNV).

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Complement-Mediated Microglial Phagocytosis and Pathological Changes in the Development and Degeneration of the Visual System

“…Anti-human C5 monoclonal antibodies [eculizumab (intravenous injection) (146) or LFG316 (intravitreal injections), summarized in (152)] did not decrease GA growth rate. Administration of an anti-C5 RNA aptamer [ARC 1905 (intravitreal injection)] with the vascular endothelial growth factor inhibitor ranibizumab preserved visual acuity better than ranibizumab alone in a phase 2a clinical trial [summarized in (152)]. Finally, lampalizumab, an anti-factor D alternative pathway inhibitor (156), failed to reduce the growth of GA in two phase 3 clinical trials for AMD when administered intravitreally (147), despite having achieved significance in a subgroup of dry AMD patients with complement factor I risk variants.…”

Looking ahead in retinal disease management: highlights of the 2019 angiogenesis, exudation and degeneration symposium

“…GA is also commonly associated with nAMD, being observed in over 90% of nAMD eyes treated with anti-VEGF agents for 7 years [5]. The most promising future treatment approaches involve inhibition of specific components of the complement cascade, an inflammatory pathway believed to be a key driver of AMD pathogenesis [15].…”