Clinical characteristics and current treatment of age-related macular degeneration

Abstract

Age-related macular degeneration (AMD) is a multifactorial degeneration of photoreceptors and retinal pigment epithelium. The societal impact is significant, with more than 2 million individuals in the United States alone affected by advanced stages of AMD. Recent progress in our understanding of this complex disease and parallel developments in therapeutics and imaging have translated into new management paradigms in recent years. However, there are many unanswered questions, and diagnostic and prognostic precision and treatment outcomes can still be improved. In this article, we discuss the clinical features of AMD, provide correlations with modern imaging and histopathology, and present an overview of treatment strategies.

Figure 1.

Color fundus photograph of drusen in nonneovascular age-related macular degeneration. There are small (<63 µm, green arrow), intermediate (63–124 µm, yellow arrow), and large (≥125 µm [average diameter of retinal venule at the optic disc margin], red arrow) drusen.

Figure 2.

Multimodal imaging of reticular pseudodrusen (arrows). (A) Color fundus photograph showing yellowish interlacing networks that extend to the vascular arcades. (B) Red-free fundus photography most clearly demonstrates the pseudodrusen as bright spots and the interlacing networks that appear hyporeflective. (C) Fundus autofluorescence shows that the lesions are hypoautofluorescent. (D) Spectral-domain optical coherence tomography demonstrates that the pseudodrusen are located between the retina and retinal pigment epithelium (RPE), rather than the sub-RPE localization of typical drusen.

Figure 3.

Geographic atrophy in advanced nonneovascular age-related macular degeneration. (A) Color fundus photograph of central geographic atrophy. (B) The corresponding fundus autofluorescence delineates the kidney-shaped area of atrophy as hypoautofluorescent (dark). However, it also shows that the surrounding clinically normal-appearing retina is hyperautofluorescent, which indicates an accumulation of lipofuscin. (C) Over the course of the next 6 years, the geographic atrophy gradually extends to the areas that were hyperautofluorescent in (B). (Reprinted, with permission, from Schmitz-Valckenberg et al. 2009.)

Figure 4.

Classic and occult choroidal neovascularization (CNV) in neovascular age-related macular degeneration. (A) Color fundus photograph shows a greenish lesion deep to the retina (arrow). (B) Fluorescein angiography shows a focal well-demarcated hyperfluorescence of the CNV that leaks in later (C) frames. There are also scattered drusen that also appear bright. (D) Color fundus photograph shows drusen, pigmentary changes, and a diffusely mottled appearance of the retinal pigment epithelium. Fluorescein angiography demonstrates an ill-defined area of hyperfluoresence (E) that leaks diffusely in mid to late frames (F).

Figure 5.

Spectral-domain optical coherence tomography of a central fibrovascular pigment epithelial detachment (white arrow) with overlying subretinal fluid (red arrow). The inner-segment/outer-segment junction of the photoreceptors (white arrowheads) has become disrupted in the area overlying the lesion (red arrowheads).

Figure 6.

Outer retinal tubulation (arrows) and degenerative cystic cavities (arrowheads) located above a fibrovascular scar. The “en face” optical coherence tomography (OCT) demonstrates that the tubulations form a branching network. The corresponding B-scan OCT (inset) shows the tubulations as round and ovoid hyporeflective spaces with a ring of hyperreflectivity, and the degenerative cysts as sharply demarcated cavities. (Adapted, with permission, from Wolff et al. 2012.)

Figure 7.

Polypoidal choroidal vasculopathy. (A) Color fundus photograph showing two pigment epithelial detachments (PED; arrows) with circinate exudation and subretinal fluid. (B) Indocyanine green angiography showing hyperfluorescent polypoidal lesions in the choroidal vasculature (arrow). (C) The corresponding spectral domain optical coherence tomography shows the subretinal fluid (arrows) and elevation of the retinal pigment epithelium (asterisk). (Adapted, with permission, from Yonekawa 2013.)

Figure 8.

Retinal angiomatous proliferation (RAP). (A) Color fundus photograph showing focal intraretinal hemorrhage (arrow) and an underlying pigment epithelial detachment (PED) (arrowheads). There are also drusen (asterisk). (B) Fluorescein angiography shows a focal hyperfluorescence and the underlying PED. (C) Indocyanine green angiography reveals an anastomotic lesion connecting retinal vasculature (arrows). (D) Spectral-domain optical coherence tomography also shows that there is intraretinal fluid (arrowhead) in addition to the PED (white arrow). A hyperreflective focus on the surface of the PED corresponds to the RAP lesion (red arrow).