Pearl

Implantation of retinal prosthesis holds promise to restore ambulatory vision for AMD and other degenerative retinal disorders.

Summary

AMD is the leading cause of significant visual loss to affect the elderly population within the United States. The nonexudative subtype is the most commonly seen type, and can lead to overall visual diminution significantly affecting QOL functions in the patient population. The spectrum of non exudative can vary widely from drusen subtype, pigmentary alterations, and with the degree of subsequent atrophy of the RPE and choriocapillaris. Although modifiable risk factors such as cigarette smoking and the utilization of vitamin and antioxidant supplementation have been clearly delineated, pharmacologic intervention in the management of nonexudative AMD currently has not. However, with the plethora of clinical trials targeting a variety of downstream pathways and with various methods of drug delivery including surgical implantation, there will be a greater arsenal to modify and potentially reverse further vision loss in the near future for patients with nonexudative AMD.

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Key Points

•The treatment of neovascular age-related macular degeneration (AMD) will continue to evolve dramatically.

•Researchers are working to find new therapeutics targeting important pathways involved in angiogenesis, including:

–Vascular endothelial growth factor (VEGF) inhibition

–Vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor inhibition (PDGFR), including tyrosine kinase inhibitors, RNA interference, and vaccine therapy

–Radiation therapy utilizing novel local approaches of delivery

–Antiinflammatory and immunosuppressive pathways, including inhibition of complement, tumor necrosis factor alpha (TNFa), and mammalian target of rapamycin (mTOR)

–Gene therapy, transferring genes for pigment epithelial-derived growth factor (PEDF) and potent VEGF binders

–Other pathways, including the nicotinic acetylcholine receptor pathway antagonism, blockade of cell membrane ion trans-

C.P. Shah (*)

Ophthalmic Consultants of Boston, 50 Staniford Street, Suite 600, Boston, MA 02114, USA

e-mail: cpshah@eyeboston.com

port, disruption of microtubule formation, integrin inhibition, neuroprotection, and inhibition of sphingosine-1-phosphate

•Combining existing and future therapies that affect distinctly separate pathways in the pathogenesis of neovascular AMD, coupled with enhanced drug delivery technologies, may continue to enhance visual outcomes while reducing treatment burdens.

Introduction

The only thing certain about the future of neovascular age-related macular degeneration (AMD) is its evolution. Ophthalmologists have witnessed dramatic and accelerated growth in the management of this disease since the Macular Photocoagulation Study began enrolling patients in 1979. Treatment options have evolved from laser photocoagulation to photodynamic therapy to intravitreal anti-vascular endothelial growth factor (VEGF) agents, with a commensurate improvement in efficacy. The shortand longterm future is sure to hold many new therapeutic options with even better outcomes.

At the time of this writing, monotherapy with intravitreal anti-VEGF agents, namely ranibizumab and bevacizumab, remained the standard of care for neovascular AMD. Future therapies will likely target different pathways in the pathogenesis of choroidal neovascularization (CNV). Combination treatments will affect multiple