Major ReviewEvaluation of Age-related Macular Degeneration With Optical Coherence Tomography
Introduction
Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in people aged 50 years or older in the developed world.21, 180 Several groups have proposed classification systems of AMD.16, 24, 41, 129, 239 We will follow the “International” classification system, though we recognize that classification systems are likely to continue to evolve as new technologies emerge.16 The clinical hallmark of “early” AMD is the deposition of acellular, polymorphous material—termed drusen—between the retinal pigment epithelium (RPE) and Bruch’s membrane.9, 103, 256 Focal retinal pigmentary abnormalities are also commonly seen in patients with early AMD. Patients with early AMD are frequently asymptomatic; the development of “late” AMD, however, is typically associated with visual loss.93 In one form of late AMD, alterations in the RPE accumulate, resulting in the loss of large areas of RPE and outer retina, a phenomenon termed geographic atrophy (GA).42 In the other form of late AMD, the accumulation of drusen and RPE abnormalities results in growth of abnormal blood vessels from the choroid. This process, termed choroidal neovascularization (CNV), is the pathognomonic feature of “neovascular” or “wet” AMD.94 Growth of abnormal blood vessels originating in the retina has also been identified in a distinct subset of patients with neovascular AMD—such lesions are commonly referred to as “retinal angiomatous proliferation” (RAP).249
In recent years, major advances have been made in the treatment of AMD.22, 213 The development of anti-angiogenic agents such as ranibizumab and bevacizumab (Lucentis and Avastin, respectively; Genentech, South San Francisco, CA), has offered the first hope of significant visual improvement for patients that develop neovascular AMD.25, 159, 195, 238 Advances have also been made in our understanding of GA pathophysiology, with many potential therapeutic agents being evaluated in preliminary clinical trials.257 In line with these advances, a new imaging modality—optical coherence tomography (OCT)—has emerged as an essential adjunct for the diagnosis and monitoring of patients with AMD.26, 44, 115
OCT, first described by Huang et al in 1991, allows high-resolution cross-sectional (tomographic) images of the neurosensory retina and deeper structures to be obtained in a non-invasive manner.96 OCT works by measuring the properties of light waves reflected from and scattered by tissue (analogous to measurement of sound waves in ultrasonography). As the wavelength of light is much shorter than that of sound, OCT produces images with much higher resolution than that of ultrasound. Utilization of light instead of sound presents a number of technical challenges, however—in particular, the speed of light exceeds that of sound by a factor of 150,000, making direct measurement of optical “echoes” impossible. In OCT systems, this hurdle is overcome through the use of a technique called interferometry.199 In interferometry, a beam of light is divided into a measuring beam and a reference beam. The reconvergence of light reflected from the tissue of interest and light reflected from a reference path produces characteristic patterns of interference that are dependent on the mismatch between the reflected waves. Because the time delay and amplitude of one of the waves (i.e., the reference path) is known, the time delay and intensity of light returning from the sample tissue may then be extracted from the interference pattern.
Commercially available OCT systems are now capable of obtaining retinal images with an axial resolution of approximately 3–8 μm, and a transverse resolution of approximately 15–20 μm; thus OCT is often dubbed in vivo “clinical biopsy”.123, 127 OCT has been widely adopted for the management of vitreoretinal disorders, and nowhere more so than for the evaluation of AMD, a change driven in large part by the need for frequent anti-angiogenic therapy in patients with neovascular AMD.26 The ability to accurately interpret OCT images is thus critical for retina specialists and important for comprehensive ophthalmologists. Despite this, the relatively recent introduction of OCT and, as a result, the relative absence of formal training, coupled with rapid evolution of the technology, may make OCT image interpretation difficult. These problems are compounded by the phenotypically heterogeneous nature of AMD and its complex morphology as visualized using OCT.105 Therefore, we summarize the current understanding of OCT image interpretation in patients with AMD, and describe how OCT can best be applied to the management of these patients in clinical practice.
Section snippets
Qualitative Image Analysis
Light waves traveling through tissue can be reflected, scattered, or absorbed at each tissue interface; as a result, the multi-layered structure of the retina is particularly amenable to assessment using OCT (Fig. 1, Fig. 2).199 Care must be taken when making assumptions about the correlation between OCT images and retinal histological sections, however, as the strength of backscattered light is related to its angle of incidence on the area of interest. Therefore, structures running obliquely
Retinal Imaging with Spectral Domain Technology
The newer generation of commercial OCT systems is often described as “spectral domain” or “Fourier domain” OCT. Spectral domain OCT systems use spectral interferometry and a mathematical function called Fourier transformation to assess interference patterns as a function of frequency. In older “time domain” systems, such as Stratus OCT, these patterns are assessed as a function of time.30, 244 Thus, light scattered from different depths within the tissue can be measured simultaneously, and
Drusen
Until the advent of high-speed spectral domain technology, evaluation of drusen with OCT was often difficult as motion artifacts commonly resulted in apparent undulation of the RPE, mimicking the appearance of drusen.88, 185, 194 On spectral domain OCT, small and intermediate-size drusen may be more clearly seen as discrete areas of RPE elevation with variable reflectivity, reflecting the variable composition of the underlying material.73, 125 In larger drusen, or drusenoid pigment epithelium
Features of Geographic Atrophy on Optical Coherence Tomography
In GA, confluent areas of RPE atrophy are accompanied by loss of the overlying photoreceptors and varying degrees of choriocapillaris loss seen on fluorescein angiography. These changes are often preceded by dehydration and calcification of local drusen.43, 94, 232 On OCT, GA appears as areas of sharply demarcated choroidal hyperreflectivity from loss of the overlying RPE (atrophy from causes other than AMD [e.g., from confluent laser photocoagulation] may have a similar appearance) (Fig. 7).246
Features of Neovascular Age-Related Macular Degeneration on Optical Coherence Tomography
In neovascular AMD abnormal blood vessels develop from the choroidal circulation, pass anteriorly through breaks in Bruch’s membrane, and then proliferate in the sub-RPE or subretinal space.82 As the CNV lesion proliferates, the structural immaturity of its vessels commonly results in fluid exudation and hemorrhage, leading to the formation of pathologic “compartments” between the RPE and Bruch’s membrane (PED) and between the neurosensory retina and the RPE (serous retinal detachment).4, 119
Polypoidal Choroidal Vasculopathy
In 1990 Yannuzzi et al suggested the term “idiopathic polypoidal choroidal vasculopathy" (PCV) for a disorder characterized by multiple serosanguineous PEDs, commonly seen in black and Asian populations, and previously described as the “posterior uveal bleeding syndrome.”131, 251 This disorder was initially felt to be a distinct entity with its own risk factors and clinical course; the disease spectrum has been greatly expanded, however, with many authorities now considering PCV to be an
Diagnosis and Initiation of Therapy
Traditionally, fluorescein angiography (FA) has been required for the diagnosis of neovascular AMD;1, 22 with the advent of OCT, however, some question this dogma.206, 233 In elderly patients complaining of acute or subacute unilateral visual loss, the combination of biomicroscopic (e.g., drusen, macular hemorrhage, subretinal fibrosis) and tomographic (e.g., PED, subretinal hyperreflective material, subretinal fluid) findings often allows a diagnosis of neovascular AMD to be made with
Future Directions and Conclusion
OCT has clearly revolutionized the assessment of patients with AMD and other macular disorders; nevertheless, the full potential of OCT for chorioretinal imaging remains to be realized. Current commercial OCT systems, based on spectral domain technology, allow dense scanning of the macula with high axial resolution;112 as with older systems based on time domain technology, however, the transverse resolution of spectral domain OCT is limited by the optics of the eye.44 As a result OCT platforms
Method of Literature Search
References for this review were identified through a comprehensive literature search of the electronic MEDLINE database (1966–2011) using the Pubmed search service. Further articles, abstracts, and textbook references generated from reviewing the bibliographies of the initial search were selectively included. To ensure the up-to-date nature of our review article, current issues of Archives of Ophthalmology, Surveys of Ophthalmology, American Journal of Ophthalmology, Ophthalmology, British
Disclosure
Dr Sadda is a co-inventor of Doheny intellectual property related to optical coherence tomography that has been licensed by Topcon Medical Systems, and is a member of the scientific advisory board for Heidelberg Engineering. Dr Sadda also receives research support from Carl Zeiss Meditec, Optos, and Optovue, Inc. He also served as a consultant for Genentech, Inc. and Allergan, Inc. Dr Tufail has been on advisory boards for Novartis, Pfizer, GSK, Thrombogenics, Bayer, and Allergan. Dr Patel has
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