Choroidal Imaging in Dry Age-Related Macular Degeneration

Introduction

Age-related macular degeneration (AMD) affects 7–8 million people in the United States (US) with a prevalence of 6.5% in persons aged 40 years and older, and it is the most common cause of blindness in the Western world. In the 1990s, the prevalence of late-stage AMD (comprising atrophic or neovascular forms) was estimated to be 1.6% in the US, with similar prevalence at that time outside of the US with rates of 1.7% in the Netherlands, 1.9% in Australia, and 1.1% in Italy. In 2005–08, the prevalence of the severe dry form of AMD in the US was estimated to be about 0.8% in the National Health and Nutrition Examination Survey.

Increased age, diet, and smoking are the major known risk factors, and inflammatory mediators such as complement factors and vascular endothelial growth factor (VEGF) may play a role in pathogenesis. As the population ages, the prevalence of AMD-related eye disease will increase, which may present a major healthcare burden. AMD is classified into the dry, nonexudative, nonneovascular form and the wet, exudative, and neovascular type. Wet AMD is currently treated with intravitreal injections of anti-VEGF medication to reduce progressive vision loss due to choroidal neovascularization (CNV) and prevent permanent damage from macular scarring. In dry AMD, vitamin supplementation with the Age Related Eye Disease Study (AREDS) 2 formulation has been shown to reduce the risk of developing advanced AMD. Clinical trials are currently evaluating medications that may halt or reverse vision loss due to severe dry AMD.

In the early stages of dry AMD, vision loss is rare. This early stage is characterized in the AREDS study by at least 15 small (<63 μm) yellow subretinal deposits called drusen, less than 20 medium-sized (63–125 μm) indistinct drusen, and/or retinal pigment epithelium (RPE) changes such as hyper- or hypopigmentation. The presence of at least one large (>125 μm) druse, more than 20 medium-sized drusen, and/or noncentrally involving geographic atrophy (GA) represents the intermediate stage of AMD. Larger drusen may then coalesce into drusenoid RPE detachments (RPED), which can progress to be GA, characterized by variable loss of photoreceptors and RPE. The presence of GA involving the central macula or CNV represents the advanced form of AMD, which typically results in decreased vision and loss of fixation.

The long and short posterior ciliary arteries are the major blood supply to the choroid. Modifications of the choroidal anatomy occur in dry AMD, including loss or narrowing of the choriocapillaris layer which becomes more pronounced in later stages of the disease. Furthermore, decreased choroidal blood flow in the fovea has been associated with increased drusen extent, and the distribution of drusen has been shown to be closely related to areas of choriocapillaris dropout. Histopathological analysis has shown that the choriocapillaris becomes less dense, narrowed, retracted away from Bruch’s membrane, widened by the intercapillary pillars, and defenestrated. Inflammatory cells fill the space formerly occupied by choriocapillaris. One study of 325 eyes compared the choroidal thickness between eyes with intermediate AMD, eyes with advanced AMD, and control eyes without AMD. Choroidal thickness was significantly reduced in eyes with advanced AMD compared with control eyes. However, after adjusting for age, no statistical significance was found between the three groups. Analysis demonstrated that choroidal thickness decreased with advancing age, confirming that age is a confounding factor in the debate of whether or not choroidal thinning occurs in AMD.

Choroidal Imaging of Dry Age-Related Macular Degeneration

Fundus Photography

Color or red-free fundus photographs ( Figs. 6.1–6.5 ) provide a view of the retina similar to clinical examination. Typical drusen in AMD are yellow deposits between the RPE and Bruch’s membrane. Drusen are the earliest sign of dry AMD and are made up of lipids, resulting from the incomplete disposal of shed photoreceptor discs and cellular waste products. There are several types of drusen with different levels of risk. Drusen can be small, hard, round, distinct, and scattered far apart from each other. This type may not create vision problems for a long time and may not even be an indication of macular degeneration. Drusen can become larger, softer, and closer together. Their edges are less distinct. When drusen are at this stage, there is a greater risk for developing wet AMD and secondary vision loss. These drusen can also disrupt the layers of the retina and lead to RPED.

Hard drusen appear as yellowish-white pin-point lesions, while soft drusen are larger and may appear less distinct or confluent. Soft drusen range in size from 63 to 1000 μm in diameter. In contrast to hard and soft drusen, basal laminar drusen (cuticular drusen) are clusters of 50–75 μm subretinal or sub-RPE deposits and subretinal drusenoid deposits (reticular pseudodrusen) are light gray interconnected collections just above the RPE that may be much more extensive than typical drusen. Reticular pseudodrusen may be very subtle and harder to appreciate using ophthalmoscopy or color fundus photograph. However, scanning laser ophthalmoscopy with near-infrared reflectance demonstrates subtle changes in gray-scale tones, making reticular pseudodrusen appear darker than surrounding retina. Cuticular drusen and reticular pseudodrusen tend to be located more peripherally at the arcades compared to drusen that accumulate in the foveal region.

Different light filters aid in differentiating the drusen subtypes. Blue light filters aid in detecting reticular pseudodrusen as the subjacent RPE absorbs blue light, thus making a dark background in contrast to the reticular pseudodrusen. Conversely, in red light, soft drusen appear more obvious. Using a red-free filter can help to differentiate drusen from exudates and hemorrhage, as blood appears dark using the red-free filter, while drusen and RPE loss remain lighter in hue.

As the RPE is a darkly pigmented layer, loss of the RPE in GA can be seen as lighter areas in the macula. The deeper choroidal vessels may be more easily visualized beneath areas of GA. GA can look similar to age-related choroidal atrophy (ARCA) in which the choriocapillaris and choroidal vessels are lost and the remaining vessels appear to enlarge, but a few key differences can distinguish the two diseases. GA is usually well defined, and the associated RPE loss allows the underlying choroidal vessels to be more easily visible. In contrast, ARCA shows generalized choroidal thinning.