Ephraim Friedman

Ocular Blood Flow Velocity in Age-related Macular Degeneration

BACKGROUND Changes in the structure of the ocular blood vessels associated with age-related macular degeneration (AMD) have been described in some detail, but comparatively little is known of the concomitant circulatory changes. The goal of this study is to evaluate changes in the ocular circulation that may be associated with AMD. METHODS Ocular blood flow velocities and vessel pulsatilities were measured in volunteers with and without AMD using a color Doppler imaging unit. Spectral analyses were recorded from the ophthalmic artery, central retinal artery and vein, the temporal and nasal short posterior ciliary arteries, and the four vortex veins. RESULTS Adjusting for age, pulsatility indices of all arteries were higher in subjects with AMD (central retinal artery [P = 0.02]; temporal and nasal short posterior ciliary arteries [P = 0.06 and 0.002, respectively]; and ophthalmic artery [P = 0.24]). End-diastolic blood flow velocity of the short posterior ciliary arteries tended to decrease in the presence of AMD. CONCLUSIONS The combination of increased pulsatility and decreased velocity of the short posterior ciliary arteries, observed in the presence of AMD, are interpreted as evidence of increased vascular resistance. The clinical signs of AMD may be related to degradation of the metabolic transport function of the retinal pigment epithelium, resulting from impaired choroidal perfusion.

A HEMODYNAMIC MODEL OF THE PATHOGENESIS OF AGE-RELATED MACULAR DEGENERATION

The clinical message of this editorial is that age-related macular degeneration may be a vascular disorder. It may be a manifestation of the hemodynamic consequence of the process of lipoid infiltration that, when it involves other organs such as those of the cardiovascular or cerebrovascular systems, is called atherosclerosis. The hemodynamic model presented here postulates that in age-related macular degeneration, the increase in resistance to the flow of blood in the choroid is caused by an age-related and diet-related decrease in the compliance of the sclera. It proposes that the form of age-related macular degeneration produced may depend on the relative resistances of the ophthalmic and cerebral circulations. A decrease in perfusion, leading to the atrophic form of age-related macular degeneration, is the outcome if the resistance of the cerebral circulation is relatively lower than that of choroid. Conversely, a relatively greater increase in the increase in the hydrostatic pressure in the choroidal vessels, leading to the exudative form of the disorder.

The role of the atherosclerotic process in the pathogenesis of age-related macular degeneration.

T HE CAUSE OF AGE-RELATED MACULAR DEGENERAtion is unknown. In an editorial1 published in the November 1997 issue of the American Journal of Ophthalmology, I proposed that age-related macular degeneration is a vascular disorder, the hemodynamic sequela of atherosclerotic changes affecting the eye. New information regarding the nature and source of the lipids in Bruch membrane and in drusen prompts refinement of the hypothesis. Arteriosclerosis refers to the group of disorders that have in common thickening and loss of elasticity of the arterial wall. It is so universal as to be considered part of “normal” aging. Atherosclerosis, the most common form of arteriosclerosis, is less universal, and is influenced by genetic, dietary, and other environmental factors. It is characterized by lipid deposition (the atherotic component) and vessel stiffening (the sclerotic component).2 The deposition of lipid involves the extracellular trapping of small lipid particles enriched in cholesterol esters in the intima of large arteries.3 The resulting loss of elasticity is caused by increased lesion collagen and destruction of medial elastin. The hemodynamic model, proposed earlier,1 is revised and designated the vascular model (Figure 1), to reflect the roles proposed for both structural and hemodynamic factors in the pathogenesis of age-related macular degeneration. The vascular model proposes that age-related macular degeneration is the result of the accumulation of lipid in the sclera4 and in Bruch membrane,5,6 progressively increasing the stiffness of these tissues7,8 and increasing the postcapillary resistance9 of the choroidal vasculature, situated between the progressively noncompliant sclera and noncompressable contents of the globe. In addition to decreasing choroidal blood flow, the increase in resistance tends to elevate the hydrostatic pressure10 of the choriocapillaris, enhancing leakage and deposition of extracellular proteins and lipids, particularly in the posterior pole. These deposits take the form of basal deposits within Bruch membrane and of drusen between the inner surface of Bruch membrane and the retinal pigment epithelium. Basal deposits and large drusen can compromise the overlying retinal pigment epithelium,11,12 causing pigment clumping, and confluent drusen can cause geographic atrophy of the retinal pigment epithelium. These are the clinical signs of the non–neovascular form of age-related macular degeneration. Retinal pigment epithelium cell dysfunction is proposed to be the result of the process not its cause. The progressive deposition of lipid in Bruch membrane results in the degeneration of elastin and collagen,12 calcification,13 and the upregulation of vascular endothelial growth factor.14 Whether the upregulation of vascular endothelial growth factor is the result of ischemia, hypoxia, or nonspecific tissue damage is not clear. In either case, the vascular model proposes that it is the combination of high choriocapillary pressure, breaks in a calcified Bruch membrane, and vascular endothelial growth factor that is responsible for the growth of new vessels into the subretinal space. The model also suggests that retinal pigment epithelial detachments,15 polypoidal choroidal vasculopathy,16 and choroidal neovascularization are pathogenetic variations of the neovascular form of agerelated macular degeneration. Which variation develops may depend on the level of the intravascular pressure and the relative structural integrity, permeability, and hydraulic conductivity of Bruch membrane. If the choriocapillary pressure is relatively low, the non–neovascular form of age-related macular degeneration will result. If the pressure is elevated, but Bruch membrane is relatively intact, polypoidal choroidal vasculopathy or retinal pigment epithelial detachments may result. Choroidal neovascularization is the outcome if a calcified Bruch membrane is fragmented in the presence of an elevated intravascular pressure. The vascular model proposes that numerous, large, confluent drusen are “risk factors” for choroidal neovascularization, in the sense that they are ophthalAccepted for publication Jun 19, 2000. From the Department of Ophthalmology, Harvard Medical School Retina Service, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts. This work was supported in part by The Solman Friedman Research Fund, Boston, Massachusetts; The Harold Alfond Research Fund, Boston, Massachusetts; and The Ben Wunsch Research Fund, Boston, Massachusetts. Reprint requests to Ephraim Friedman, MD, Massachusetts Eye and Ear Infirmary, 243 Charles St, Boston, MA 02114; fax: (978) 927-3506; e-mail: efriedman@MEEI.harvard.edu

Digital Indocyanine-green Angilography in Chorioretinal Disorders

The authors performed digital indocyanine-green angiography in 37 patients with chorioretinal disorders. Eighteen patients had choroidal neovascularization, 7 patients had atrophic age-related maculopathy, and 12 patients had uncommon choroidal and retinal disorders. A Topcon indocyanine-green camera was integrated with a digital (1024-line resolution) angiography system. Compared with conventional video or photographic indocyanine-green angiography, this technique offers enhanced image resolution, the possibility of direct qualitative comparison with fluorescein angiography, image archiving, hard-copy generation, and tracing capabilities to plan laser treatment strategies and monitor the adequacy of laser therapy after surgery.

Increased scleral rigidity and age-related macular degeneration

The coefficient of scleral rigidity of the eyes of 29 patients with age-related macular degeneration (ARMD) was significantly higher than the rigidity of 25 control patients, frequency matched for age. The data suggest that an increased scleral rigidity may be a significant risk factor for the development of the disorder.

Scleral Rigidity, Venous Obstruction, and Age-Related Macular Degeneration: A Working Hypothesis

It is proposed, as a working hypothesis, that age-related macular degeneration is caused by a progressive increase in the rigidity of the sclera, gradual obstruction the vortex veins, and decompensation of the choroidal venous system of the posterior pole. The hypothesis accounts for all of the clinical signs characteristic of the disorder and defines its relationship to senescence. The biophysical, epidemiologic and therapeutic implications are assessed.

Central retinal vein occlusion in a patient with thrombotic thrombocytopenic purpura.

PURPOSE To describe the occurrence of central retinal vein occlusion in a patient with thrombotic thrombocytopenic purpura. METHODS Case report. RESULTS A 52-year-old woman developed central retinal vein occlusion in the acute phase of thrombotic thrombocytopenic purpura, followed by iris neovascularization only 1 month after the onset of central retinal vein occlusion. Color Doppler imaging of the affected eye showed an increased resistive index of the central retinal artery and reduced blood flow velocity of the central retinal vein compared to the fellow eye. CONCLUSION We describe a rare association between central retinal vein occlusion and thrombotic thrombocytopenic purpura with rapid evolution of iris neovascularization. Our case demonstrates that close ophthalmologic attention is important in thrombotic thrombocytopenic purpura.

Your Sight: Folklore, Fact and Common Sense

This book, written by a professional writer specializing in books and articles on science and medicine, is difficult to categorize in terms of either the audience for which it was written or the function it was intended to serve. The jacket indicates that the book was intended as a laymans guide to good eyesight and the care and protection of eyes. Although a few pages are devoted to some practical considerations about the prevention and treatment of eye disease, most of the book consists of a potpourri of miscellaneous information about the eye. There is a little history, a little mythology, and some anatomy and physiology. Most of the text is devoted to a description of a variety of fairly common ocular disorders. The author has done an excellent job of researching and presenting his material, which is surprisingly accurate and sophisticated despite the fact that he himself is a