Age-Related
Macular
Degeneration
edited by
Jennifer I. Lim
Doheny Eye Institute
University of Southern California Keck School of Medicine
Los Angeles, California
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Foreword
Age-related macular degeneration (AMD) has become a scourge of modern, developed societies. In such groups, where improved living conditions and medical care extend human longevity, degeneration of bodily tissues slowly but relentlessly occurs as the life span increases. Sooner or later, the “warranty” on such tissues expires, and so do critically important cells that, in the case of the macula, would have allowed normal visual function if they had survived. Those cells occupy a tiny area having a diameter of only about 2 to 3 mm in human eyes. When the cells lose their function or die and disappear, sharp central visual acuity fails, and lifestyle is compromised—often severely. The ability to read, drive, recognize faces, or watch television can be impaired or lost. This group of dis- eases—AMD—has become the leading cause of visual impairment in those countries where increasingly large numbers of individuals live to a so-called “ripe old age.” Most of these senior citizens had anticipated, with pleasure, the opportunity to enjoy their mature and less frenetic years, but too many of these individuals, ravaged physically and emotionally with AMD, frequently and understandably complain that the golden years are not quite so golden. This is the human and emotional side of AMD, a group of disorders now under intense scientific and clinical scrutiny, as ably summarized herein by Dr. Jennifer Lim and her expert group of coauthors.
The chapters in this book are devoted to pathophysiology, clinical features, diagnostic tests, current and experimental therapies, rehabilitation, and research. They represent what we know today. They also tell us explicitly or by inference what we need to know tomorrow. In effect, they are cross-sectional analyses of the present state of knowledge, analogous to photos in an album, for example. Here, in this book, we have comprehensive, definitive, analytic reviews of the current state of macular affairs. Such albums and books are often informative and beautiful, but they best realize their inherent potential, as does this book, by whetting our appetite for more information, both for today as well as for tomorrow. For example, what are the precise etiology and pathophysiology of AMD? Will they change? What are the best diagnostic tests for different forms of AMD? (Parenthetically, it is historically noteworthy to realize that fluorescein angiography remains the definitive test for diagnosing the presence of choroidal neovascularization and related phenomena in AMD, despite having been developed almost half a century ago.) What are the best therapies of today and how might we improve them in the future? At present, we think primarily of thermal laser photocoagulation and photodynamic therapy.
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Foreword |
How can they be enhanced? What roles, if any, will other techniques play? Will they include low-power transpupillary thermal or x-irradiation, antiangiogenic drugs, genetic manipulation, or surgery? Will combinations of these or even newer modalities be demonstrated to be both safe and effective? Will wide-scale population-based preventive measures, including antioxidants, for example, be more important than therapeutic intervention ex post facto?
Clairvoyance is an imperfect attribute, but the largely palliative and incompletely successful treatments of today are quite frustrating. There is a compelling mandate for intense and sustained efforts to improve both treatment and prophylaxis. The crystal ball for AMD suggests that the immediate future will be characterized by refinements in today’s favored interventions, especially photodynamic therapy, but no one can really hope or believe that the therapeutic status quo will be preserved. Substantial change is a certainty. Physicians and patients appropriately demand more. The intermediate and longrange future will probably include a large number of definitive clinical trials devoted to fascinating new pharmacological agents, many of which are now in the evaluative pipeline, but many of which have not yet even been conceived. Classes of drugs will include antiangiogenic or angiostatic steroids with glucocorticoid and nonglucocorticoid qualities, as well as diverse agents to bind and inactivate cytokines and chemokines at different points in the angiogenic and vasculogenic cascades. Many will involve blockage of the actions of vascular endothelial growth factor (VEGF). Ingenious surgical approaches will also come, and some will then go, as more and more new approaches of this nature undergo clinical evaluation and gain either widespread acceptance or rejection.
Today’s requirements for “evidence-based” medical decisions invoke Darwinian selection processes for numerous known, as well as currently unknown, diagnostic and therapeutic approaches to AMD. Outstandingly good techniques, such as fluorescein angiography, will persist—at least for the foreseeable future. Less desirable ones, such as subfoveal thermal photocoagulation, for example, will be supplanted by something better, such as photodynamic therapy—at least for the moment. The accretion of scientific and clinical knowledge is usually an extremely slow process, but that is not necessarily bad because new ideas and techniques are afforded ample opportunity for dispassionate evaluation. Sudden breakthroughs, on the other hand, intellectual or technical epiphanies, are infrequent. When they do occur—such as angiography, photocoagulation, or intravitreal surgery—they abruptly create quantum leaps characterized by dramatic flourishing of new hypotheses, experiments, and clinical procedures. The world of AMD would benefit from such giant steps (such as a new class of drugs or a new physical modality or type of equipment), but, because they are unpredictable in their origin and timing, we are presently faced with the less spectacular, but important, responsibilities of initiating and sustaining more prosaic, but potentially useful research efforts.
Hopefully, more emphasis in the future will be placed on preventive approaches. Modification of relevant risk factors for AMD may prove to be much more effective, from the perspective of the public health, than therapeutic attempts aimed at a disease that has already achieved a threshold for progressive degeneration and visual impairment. Thus far, epidemiological studies have largely been inconclusive and occasionally contradictory, and we now know of only one clear-cut modifiable risk factor, namely, cigarette smoking (and possibly systemic hypertension).
Foreword |
v |
The influences of race and heredity remain tantalizing, and it will be important to understand why some races are protected from severe visual loss in AMD and why others are not. Moreover, the major influence of heredity is inescapable, but we now know only that this influence is complex, and it may be even more complex than anticipated because of a multiplicity of unknown contributory environmental and other genetic factors. We do know the genes responsible for a previously enigmatic group of juvenile forms of inherited macular degeneration, such as the eponymously interesting diseases named for Best, Stargardt, Doyne, and Sorsby, but there appears to be no universally accepted or substantive relationship between any of these single-gene, rare Mendelian traits and the far more common AMD, which has no clear-cut Mendelian transmission pattern, but currently affects millions of aging individuals.
The march of time related to scientific progress is ceaseless, and this is certainly true of research related to AMD. Darwinian selection of the best new ideas will inevitably emerge, allowing an evolutionary approach to enhanced understanding and improved treatment or prophylaxis. Should we be fortunate enough to witness a bona fide revolution or breakthrough in ideas related to AMD, such an advance is likely to emanate from those scientists and clinicians meeting Louis Pasteur’s observation that “chance favors the prepared mind.” It is toward that goal—the creation of the prepared mind—that Dr. Lim has fashioned this valuable compendium of the way things are—for now!!
Morton F. Goldberg, M.D.
Director and William Holland Wilmer Professor of Ophthalmology
The Wilmer Eye Institute
Baltimore, Maryland