Elsevier

Survey of Ophthalmology

Volume 43, Issue 2, September–October 1998, Pages 134-146
Survey of Ophthalmology

CURRENT RESEARCH
Age-Related Macular Degeneration: A Review of Experimental Treatments

https://doi.org/10.1016/S0039-6257(98)00014-9Get rights and content

Abstract

Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the USA. Laser photocoagulation of choroidal neovascular membranes (CNVMs) in exudative AMD is currently the only well-studied and widely accepted treatment modality. It is beneficial for only a small minority of patients who show well-demarcated “classic” CNVMs, and it destroys normal retinal tissue, creates a scotoma, and is associated with an unacceptably high CNVM persistence and recurrence rate. Consequently, investigators have attempted to develop new modalities for treatment of CNVMs. These treatment modalities can be grouped into four major categories: photodynamic therapy; pharmacologic inhibition of CNVM formation with antiangiogenic agents; surgical intervention, including excision of subfoveal CNVMs; and radiation therapy. All of these experimental treatment modalities are directed toward destroying CNVMs, the end result of the exudative process, and all have limitations. The ideal treatment of the future must be based on the pathogenesis of the disease at a stage well before CNVMs develop. Investigations in nonexudative AMD are currently focusing on several major areas. Epidemiologic factors, such as genetics, sunlight, and nutrition, are being evaluated in several large studies, including the Age-Related Eye Disease Study, with the possibility of ultimately limiting the risk of AMD through behavior modification. Laser treatment of drusen is being evaluated as a means of limiting the risk of CNVM formation, although mixed results have been reported in the small number of studies to date. Choroidal perfusion abnormalities have been described in AMD, and some investigators postulate that altering blood flow may limit the risk of CNVM formation. No perfusion-treatment trials have been completed to date.

Section snippets

Limitations of Current Treatment Modalities

Nonexudative AMD is much more common than exudative AMD and is commonly a precursor of exudative AMD. The nonexudative form involves a variety of presentations, including hard drusen, soft drusen, and geographic (areolar) atrophy of the RPE. Hard drusen are associated with localized dysfunction of the RPE, whereas soft drusen are associated with diffuse dysfunction of the RPE.21 Although more commonly associated with exudative AMD, severe visual loss can occur from nonexudative AMD,

Experimental Treatments for Exudative AMD

Because of the limited efficacy of laser photocoagulation and the small number of patients who are eligible for treatment, investigators are attempting to develop new modalities to treat CNVMs. These experimental treatment modalities can be classified into four major categories: photodynamic, pharmacologic, surgical, and radiation. Nearly all of these treatments have shown limited promise, and many have not been tested in animal models of choroidal neovascularization. In addition, many of these

Experimental treatment for nonexudative amd

All the treatments currently being pursued for AMD aim to destroy CNVMs, the end result of the exudative process. The treatment of the future, however, must be based on the pathogenesis of the disease at a stage well before CNVMs develop. In spite of much study, however, the pathogenesis of AMD remains unclear.

Summary

Age-related macular degeneration is the most common irreversible cause of severe visual loss in the USA. Laser photocoagulation, which represents the only treatment modality well studied in randomized, controlled prospective clinical trials, is limited in applicability and long-term control. Experimental modalities currently being evaluated show some promise but must undergo rigorous, prospective, randomized clinical trials before they are widely accepted. Most of these experimental treatments

Method of Literature Search

Literature selection for this article was based on a MEDLINE search covering the past 30 years for all articles, using key word combinations including age-related macular degeneration, macular photocoagulation study, photodynamic therapy, growth factor, interferon, thalidomide, steroid, surgery, radiation therapy, epidemiology, laser, and blood flow. For review of topics not yet published, literature selection was also based on review of abstracts from the annual meeting of the Association for

Acknowledgements

Supported, in part, by grants from Project Development Program, Research and Sponsored Programs, Indiana University at Indianapolis; The Indiana Lions’ Club; Research to Prevent Blindness, Inc.; and National Institutes of Health grant EY10801.

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