Improved contrast of subretinal structures using polarization analysis.

Age-related macular degeneration (AMD) is the leading cause of blindness in the adult population of the United States.1 In AMD, the diseased tissues lie beneath the highly reflective vitreoretinal interface, plus many layers of other retinal cells, making it difficult to visualize the early changes in this disease. As a result, the reported incidence of subretinal changes both in patients with AMD and in aged normal subjects is much higher in histologic studies than in clinical and epidemiologic studies. Histology has been used to show that the early stages of AMD are marked by thickening of Bruch’s membrane, the development of basal linear deposits,2–5 and the development of drusen too small to be detected clinically. 6–10 Widespread or diffuse subretinal changes have been conclusively shown to occur long before donors have reached the age associated with clinical disease.6,9 These findings, together with the extremely gradual progression of early stages, suggest that age-related maculopathy (ARM) and AMD may begin during middle age, if not sooner. Accurate assessment and improved quantification of early stages of the disease is of growing importance for studies of affected family members and evaluating the effectiveness of proposed earlier treatments, such as vitamin supplementation.11 In ARM, direct measurement of these early changes to the RPE and Bruch’s membrane is difficult because of the relatively low contrast of small drusen and other subretinal deposits, especially in the presence of age-related decreases in lens transparency and pupil size. In recent years, infrared imaging has been used to improve the visibility of subretinal changes such as drusen and hyperpigmentation in both middle-aged and elderly subjects without clinical signs of disease.12,13 There is excellent spatial correspondence of drusen appearing on infrared images with the drusen that appeared in images produced by other methods.14 These advanced digital imaging techniques have been used successfully, with large numbers of patients in a clinical setting.15,16 Thus, although infrared confocal imaging has been shown to be superior to color fundus imaging (Miura M, et al. IOVS 2001;42:ARVO Abstract 3800),17 the standard method for most clinical studies remains color fundus photography because of the lack of reliable commercial instrumentation. Detection of disease by imaging is a problem of determining the most relevant properties of the tissue of interest and then optimizing the technique. A simple model of the optical properties of the healthy human retina and RPE consists of a stack of layers containing well-ordered and contiguous cells and their processes,18 but this model fails to describe a retina with ARM or AMD. As the disease progresses, Bruch’s membrane thickens.4,7,17–21 It becomes less ordered, and as a result there is an overall increase in light scattering from this layer.12 On a finer scale there are features such as drusen, hyperpigmentation, pigment clumping, and eventually atrophy or exudation. These changes occur beneath the brighter neural layers of the retina, which return a high proportion of light, which has been either specularly reflected or singly scattered. Thus, in the early stages of the disease, the total amount of scattered light returned to the detector is relatively low, and standard imaging modalities do not provide a high-contrast image of early changes, even with near infrared light and confocal imaging. Sampling multiply scattered light and eliminating the directly backscattered light causes the deeper layers and pathologic tissues to be viewed in increased contrast.12–14,16,22–23 To form an image using multiply scattered light, the primary method has been to minimize the directly backscattered light in a confocal scanning laser ophthalmoscope (SLO)25 by the use of an annular aperture and infrared illumination.12,26 Other techniques have also been developed to form an image from multiply scattered light—for instance, by displacing the light source out of alignment with the confocal aperture, as in multiply scattered light tomography.16 The current work tests the use of polarimetry for forming a retinal image from predominantly multiply scattered light and compares the resultant contrast to images formed from directly backscattered light. Light that is singly scattered off superficial layers retains polarization, whereas light that has been scattered multiple times becomes depolarized.27,28 By removing the polarization-preserving component of the light returning from the ocular fundus, regardless of the source, it is possible to calculate the spatial distribution of the multiply scattered (i.e., depolarized) light on a pixel-by-pixel basis29–33 (Burns, et al. IOVS 2001;42: ARVO Abstract 3808; Mellem-Kairala M, et al., IOVS 2002;43: ARVO E-Abstract 245), to test the hypothesis that contrast of subretinal features is increased for depolarized light imaging.