September 2010, Issue 45
Distinguishing Age-related Macular Degeneration from Other Macular Conditions
Anita Agarwal, MD
Associate Professor of Ophthalmology
Retina, Vitreous and Uveitis
Vanderbilt Eye Institute
More patients carry the diagnosis of age-related macular degeneration (AMD) than suffer from it. It is important to make every effort to consider other conditions before labeling a patient as having AMD.
Drusen and retinal pigmentary changes are typical features of early and intermediate AMD; however, cuticular or basal laminar drusen resemble AMD drusen (Figure 1).
Cuticular drusen are characterized by early age of onset, distinct and well demarcated edges, and sometimes the presence of numerous drusen both in the macula and around the arcades, occasionally arranged in clusters; most importantly, the hallmark of cuticular drusen is the fluorescein angiographic appearance of punctate hyperfluorescence of the drusen very early in the angiogram, more numerous than discernable on fundus photos, and late fading of the drusen (Figure 2).
Autofluorescence shows a central hypoautofluorescent dot surrounded by a ring of hyperautofluorescence in a majority of cases, unless the cuticular drusen are very small.
Pigment mottling and orange clumps are features of chronic or resolved recurrent idiopathic central serous chorioretinopathy (ICSC). Fluorescein angiography with gravity assisted window defects and characteristic autofluorescence imaging help in differentiating ICSC from AMD (Figure 3).
Pattern dystrophy and AMD may be differentiated by age at presentation (younger in pattern dystrophy); fluorescein angiography helps when the classic halo of hyperfluorescence, characteristic of pattern dystrophy, is observed (Figures 4 and 5). One should examine patients closely for senile streaks radiating from the optic disc; patients with this finding may have a mild form of pseudoxanthoma elasticum (PXE). Pigment mottling in the macula from pattern dystrophy often accompanies the streaks in PXE.
Figures 4, 5
Myopic choroidal neovascularization is often interpreted as AMD, especially if the patient has had refractive surgery or cataract extraction. Rather than frank yellow drusen of AMD, features consistent with a myopic fundus include a temporal crescent adjacent to the optic disc, blond fundus, and presence of lacquer cracks.
Reticular pseudodrusen, more recently termed subretinal drusen deposits, are usually seen straddling the arcades, more often along the superior than the inferior arcades, and sometimes nasal to the disc. They may be observed in isolation or accompany other features of AMD (Figure 6).
Geographic atrophy is a feature of late AMD, but may also be observed in mitochondrial myopathies (MELAS, MERRF & MIDD) and central areolar choroidal dystrophy. Occasionally Stargardt's flecks and atrophy may be mistaken for AMD. A silent or dark choroid on angiography and the typical pisciform flecks help differentiate Stargardt's flecks from drusen (Figure 7).
Idiopathic polypoidal vasculopathy may occur in both dark and lightly pigmented individuals and is characterized by retinal pigment epithelial detachments and subretinal blood. Examination may also demonstrate orange nodules and lack of drusen; the appearance of polyps on indocyanine green angiography may be necessary to confirm the diagnosis. Ocular histoplasmosis should be suspected if the patient has pigmented type 2 neovascularization, or if the location of the neovascularization is juxtapapillary. Absence of drusen in the macula and presence of midperipheral chorioretinal scars in the same or fellow eye is a useful finding. Idiopathic type 2 juxtafoveal telangiectasis is bilateral, presents most often in the 5th decade of life and may be difficult to diagnose unless one carefully observes the gray color of the fovea and subtle vascular changes. In the mid stage of the disease, these patients may have shiny crystals and stellate pigment figures; in the late stage, patients may have subretinal neovascularization and subretinal blood. Optical coherence tomography demonstrates relative foveal thinning and few lacunae until subretinal neovascularization develops when the fovea thickens or develops subretinal fluid (Figure 8).
Other rare conditions that may be mistaken for AMD are Malattia leventinese, North Carolina Macular dystrophy, late stage of Best's disease and Sorsby's fundus dystrophy. These conditions are dominantly inherited; thus, patients with these conditions may have a family history, and are typically symptomatic earlier in life. It is important to remember that some patients with other macular disease such as pattern dystrophy or cuticular drusen may develop AMD later in life. With the trend towards personalized medicine, increasing availability of newer treatments and prophylactic measures, and the dire visual consequence of macular disease in a significant number of patients, it is important to make the correct diagnosis for appropriate counseling and management.