ESASO Course Series. Basel, Karger, 2020, vol 11, pp 1–8 (DOI: 10.1159/000485295)
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Optical Coherence Tomography Angiography in Dry Age-Related Macular Degeneration
Malvika Aryaa Adnan Saifuddina, b Nadia K. Waheeda
a New England Eye Center, Tufts Medical Center, Boston, MA, USA; b The Aga Khan University Hospital, Karachi, Pakistan
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Abstract
Dry age-related macular degeneration (AMD) is characterized by changes in the outer retina, retinal pigment epithelium (RPE), and choroid. Optical coherence tomography angiography (OCTA) has proven instrumental in analyzing these changes and further understanding the pathogenesis of AMD. Early and intermediate AMD have been shown to be associated with choroidal thinning, choriocapillaris (CC) alterations under drusen, and intraretinal vascular depletion. OCTA of geographic atrophy (GA), the late stage of dry AMD, has demonstrated CC loss under the lesion itself and decreased CC flow speeds around the area of atrophy, suggesting a key role of the CC in GA pathogenesis. Much still remains to be understood about dry AMD, with an ongoing debate of whether initial changes occur in the CC, RPE, or photoreceptor layer. By allowing investigation of retinal and choroidal vascular flow changes associated with dry AMD, OCTA may pave the way for improved prediction, detection, and monitoring of dry AMD disease progression.
© 2020 S. Karger AG, Basel
Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population in developed countries, and accounts for nearly 8.7% of blindness worldwide [1]. It is estimated that 30–50 million people are affected by AMD around the world, a number only anticipated to increase in the coming years.
The pathogenesis of AMD has been linked to a multitude of factors, including increasing age, oxidative stress, inflammation, genetics, mitochondrial factors, ischemia, and environmental contributors [2, 3]. AMD is characterized by angiogenesis, drusen formation, and local complementary and inflammatory responses [4]. The inciting event of dry AMD, however, still remains to be determined. Dry AMD involves changes in the photoreceptor cells, retinal pigment epithelium (RPE), and choroid, but it is still unclear where the initial change takes place. Theories suggest that there may be a primary dysfunction of the photoreceptor cells, or that a defective RPE may lead to photoreceptor cell damage. Fairly recently, however, choroidal changes have also been discovered to be associated with the occurrence of dry AMD, an area that is still being explored with great interest [5–9].
Classification of AMD
Clinically, AMD is classified into three categories: early, intermediate, and late AMD. Normal aging may involve the formation of a few drusen, less than 63 μm in size, between the RPE and Bruch’s membrane, which have not been shown to increase the risk of development of AMD [10]. Drusen consist of hydrophobic extracellular focal deposits of lipofuscin, photoreceptor debris, and inflammatory components [11, 12]. Early AMD is characterized by drusen between 63 and 125 µm in size with no pigmentary changes. Pigmentary abnormalities, due to RPE alterations, or larger-sized drusen, at greater than 125 µm, indicate progression to intermediate AMD [13]. Overall, drusen size is an important predictive marker, as small drusen less than 63 µm are unlikely to progress to late AMD [13]. The risk of developing late AMD increases with increasing drusen size [14]. The development of neovascularization and/or geographic atrophy (GA) defines late AMD. GA, still under the umbrella of dry AMD, is characterized by subretinal drusen and loss of photoreceptors, RPE, and choriocapillaris (CC). Atrophy is usually confined to a particular region, hence the term “geographic atrophy,” and often a clear-cut boundary between affected RPE and adjacent normal, unaffected RPE may be visualized. GA has also been associated with outer retinal changes and atrophy and alteration of choroidal vessels [15, 16]. The presence of neovascularization in late AMD is often referred to as exudative, or wet, AMD.
Overall, both wet AMD and dry AMD are associated with poor visual outcomes. While wet AMD accounts for only 10% of patients with AMD, it is the reason for 90% of AMD-related blindness. The advent of intravitreal anti-vascular endothelial growth factor (VEGF) injections has revolutionized the treatment of wet AMD, greatly improving visual outcomes [17, 18]. However, it has been questioned whether anti-VEGF injections result in the progression to outer retinal and macular atrophy [9, 19].
Multimodal Imaging of AMD
Prior to the introduction of fundus autofluorescence, color fundus photography was the gold standard for evaluation of AMD [20, 21]. More recently, fundus autofluorescence has been used in the evaluation of patients with dry AMD, and especially to measure and to prognosticate macular atrophy [22, 23]. However, the paradigm is slowly shifting in the favor of optical coherence tomography (OCT) [20, 24]. OCT has been used to qualitatively evaluate for dry AMD, as well as to measure drusen volume, which is associated with risk of progression of dry AMD [25]. It can also be used to evaluate the characteristics of drusen that are associated with a higher risk of progression to advanced dry AMD, as well as exudative AMD [26, 27]. Moreover, OCT can also be used to look for reticular pseudodrusen (RPD), which have been associated with a higher risk of choroidal atrophy and of progression of AMD [28–30]. The en face image generated after a volumetric scan can be used to delineate areas of atrophy, with sub-RPE illumination serving to highlight the area of atrophy [31, 32].
More recently, OCT angiography (OCTA) has also been used in the evaluation of patients with AMD. The changes seen on OCTA in the various stages of the disease are described below.