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Clinical Crossroads | Clinician's Corner

A 76-Year-Old Man With Macular Degeneration

Jorge G. Arroyo, MD, MPH, Discussant
JAMA. 2006;295(20):2394-2406. doi:10.1001/jama.295.20.2394.
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DR SHIP: Dr G is a 76-year-old semiretired surgeon. He is married, lives in the New York metropolitan area, and has indemnity insurance and Medicare.

Dr G's ophthalmologic history was notable for mild myopia, bilateral drusen, and an episode of self-limited central serous retinopathy in the left eye at the age of 38 years. Approximately 3 years ago, he noted subtle vision changes. These symptoms progressed over a 2-month period and he saw his general ophthalmologist. He was found to have mild nuclear sclerotic cataracts (right greater than left), corrected visual acuity of 20/40 in the right eye and 20/25 in the left eye, and an exudative retinal detachment in the right eye. He was referred to a retinal specialist that day.

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Figure 1. Macula Lutea and Ocular Structures With Age-Related Macular Degeneration (AMD)
Graphic Jump Location

A, Fundus photograph of normal retina.The macula is the central part of the retina delimited by the superior temporal and inferior temporal retinal vascular arcades. The fovea is about the size of the optic nerve (diameter, 1500 μm) and is centered on the foveola (diameter, 350 μm). The foveola is the thinnest part of the retina. It is devoid of ganglion cells and is responsible for the most acute detailed vision. B, Cross section of normal retina, choroid, and sclera. A photon of light must penetrate all of the layers of the retina before being absorbed and converted into a neural signal by the photoreceptor outer segments. This retinal transparency results from the structured organization and orientation of the retinal cell bodies and processes. The retinal photoreceptors and retinal pigment epithelium (RPE) are metabolically active cells that depend on the choroidal vasculature to supply oxygen and nutrients and remove metabolic waste. C, Dry AMD or nonneovascular AMD is characterized by nodular, hard drusen, with sharp edges, diffuse soft drusen, and RPE hyperplasia and hyperpigmentation. Histologically, drusenoid material is found between the RPE and the RPE basement membrane (basal laminar deposits) and/or between the RPE basement membrane and the collagenous layer of Bruch membrane (basal linear deposits). The risk for progression to wet or neovascular AMD increases with increasing number and size of drusen and the presence of RPE pigmentary abnormalities. Wet AMD or neovascular AMD is characterized by the intrusion of abnormal new vessels from the choroid into the subretinal (type 2) and/or sub-RPE (type 1) space. In some cases, neovascularization may originate from the retinal vessels (not shown), with or without a choroidal component. Choroidal neovascularization often exudes fluid and/or hemorrhage into the subretinal and/or sub-RPE space.

Figure 2. Types of Drusen in Age-Related Macular Degeneration (AMD)
Graphic Jump Location

A, Hard drusen are small, well-defined, homogeneous, yellowish deposits (also known as basal laminar deposits) found under the macula or retinal periphery. These small lesions (<63 μm) are not associated with an increased risk of AMD. B, Soft drusen are medium and large, heterogeneous, yellowish deposits with ill-defined borders that are associated with AMD. They may result in a focal elevation of the retinal pigment epithelium (RPE) called a pigment epithelial detachment. Note the subtle RPE mottling near the fovea. The presence of medium-size drusen (>63 μm) in both eyes or large drusen (>125 μm) in one or both eyes and/or pigmentary disturbance (hyperpigmentation or hypopigmentation) in one or both eyes is associated with an increasing risk of advanced AMD and severe vision loss: 0.5% (no risk factors), 3% (1 risk factor), 12% (2 risk factors), 25% (3 risk factors), and 50% (4 risk factors) over a 5-year period.1 C, Calcific drusen are crystalline, refractile, subretinal yellowish lesions that may appear late in AMD. These lesions are typically associated with an increased risk of progression to advanced AMD.

Figure 3. Geographic Atrophy of the Retinal Pigment Epithelium (GARPE), Neovascular or Wet Age-Related Macular Degeneration (AMD), and Classic Subretinal Choroidal Neovascularization
Graphic Jump Location

A, Geographic atrophy of the retina and underlying RPE associated with AMD. Involvement of the center of the fovea by GARPE constitutes advanced AMD and typically is associated with severe vision loss. B, Neovascular or wet AMD with subretinal fluid and hemorrhage in the macula of a patient with sudden visual distortion and loss. These findings are typically due to a choroidal neovascular membrane leaking fluid (subretinal fluid) and bleeding (subretinal hemorrhage) under the retina. C, Fluorescein angiogram showing classic subretinal choroidal neovascularization. Fluorescein dye is injected in the antecubital vein, enters the retinal and choroidal circulation, and is imaged using a high-resolution fundus camera. Subretinal lesions that hyperfluoresce early in the angiogram and leak late in the angiogram as seen in this image are consistent with choroidal neovascularization, which is the sine qua non of neovascular AMD.

Figure 4. Artist Representation of the Acute Central Vision Distortion and Loss Associated With Subretinal Fluid From a Choroidal Neovascular Membrane in Age-Related Macular Degeneration (AMD)
Graphic Jump Location

The central vision becomes distorted, straight lines become curved (metamorphopsia), images may appear smaller (micropsia) or larger (macropsia), a grayish spot often obscures the central vision (central scotoma). Central visual distortion and blurring is one of the earliest symptoms associated with wet AMD and should prompt urgent ophthalmologic evaluation within 24 to 48 hours. Photograph reproduced with permission by Carole Uminski, Beth Israel Deaconess Medical Center, Boston, Mass.

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