The past, present, and future of exudative age-related macular degeneration treatment

Abstract

Treatment of exudative age-related macular degeneration has been revolutionized within the last 6 years with the introduction of vascular endothelial growth factor neutralizing agents. Previously popular “destructive treatments,” such as laser photocoagulation and photodynamic treatment have either been abandoned or used as an adjunct to pharmacotherapy. Despite the increase in vision after antivascular endothelial growth factor (VEGF) agents, they require repetitive and costly intravitreal injections that also carry the inherit risks of infection, retinal tears, and detachment. Several new and more potent VEGF inhibitors are at different stages of development. The goal of evolving pharmacotherapy is to preserve the therapeutic effect while reducing or eliminating the discomfort of intravitreal drug delivery, as well as identify new therapeutic targets. Complement inhibitors, immunomodulators, integrin inhibitors are a few of the new class of drugs that are expected to be in our armamentarium soon. Current medications act to decrease leakage through abnormal subretinal choroidal vasculature and promote involution. However, these medications are only effective in treating the active stage of the choroidal neovascular membrane. Restoration of vision of a large number of patients with involuted choroidal neovascular membranes is warranted. For this purpose, tissue engineering techniques have been employed to reconstruct the subretinal anatomy. Discovery of biomarkers, pharmacogenetics, and very specific targeting holds the promise of increased potency and safety in the future.

Photonanomedicine: a convergence of photodynamic therapy and nanotechnology

“…To date, PDT using Visudyne ® has saved the vision of millions of patients with retinal pathologies, and has been shown to work even more effectively using combination strategies. 26 As discussed earlier, the liposomal PNM formulation Visudyne ® pushes the boundaries of typical nanotherapeutics in that it enables the regulation of spatiotemporal control over treatment induction, and thus bears huge clinical potential with regards to the impact this regulated approach can have on combination cancer therapies. 8, 27 The immediate clinical impact of Visudyne ® is further evidenced in the ongoing clinical trials for pancreatic cancers.…”

Present and Possible Therapies for Age-Related Macular Degeneration

“…Despite such interventions aiming to inhibit further pathological angiogenesis, some studies have demonstrated that they play no active role in reestablishing an optimum interface between the principle ocular regions required for central vision [ 38 ]. Rather, such treatments, at best, lead to the formation of a disciform scar which only augments the loss of vision due to its physical presence disrupting the above interface.…”

“…Rather, such treatments, at best, lead to the formation of a disciform scar which only augments the loss of vision due to its physical presence disrupting the above interface. In addition to this, present treatments only provide therapeutic benefit to those with the active form of neovascular AMD, therefore being futile and redundant for those who have already lost their vision [ 38 ]. With such significant limits, further research is being conducted on novel options which address the aforementioned issues.…”

“…One method of achieving this is to combine existing anti-VEGF therapies with other treatment modalities. The first example of this was the combination of ranibizumab with photodynamic therapy (PDT); PDT refers to the intravenous injection of the photosensitive drug verteporfin which, upon activation by laser light, induces injury to endothelial cells within retinal vasculature with subsequent thrombosis of said vessels [ 38 ]. Although promising, a collation of results from several studies, deemed as the SUMMIT trials, have shown that combination therapy provided no significant reduction in the frequency of injections required [ 28 ].…”

Personalized Medicine in Ophthalmology: From Pharmacogenetic Biomarkers to Therapeutic and Dosage Optimization

“…As discussed previously, anti-VEGF drugs are the most common drugs used in the treatment of AMD [ 180 ], and recent studies utilizing nanoemulsion and polymeric micelle delivery of these drugs continue to show improved clinical utility. Polymeric micelles containing the anti-VEGF drug EYE001 and bevacizumab both resulted in sustained delivery eye for AMD treatment [ 181 , 182 ].…”