Fundus Imaging of AMD

›There are various methods of imaging the fundus. Each method has strengths and weaknesses in what it can show. There is no one method that is best to image all we need to know about the fundus.

›Photographic records of the fundus are very helpful during follow-up examinations and also serve as a resource for research. Component channels of the color photograph can be individually inspected.

›Autofluorescence imaging reveals not only the topographic structure of the retinal pigment epithelial monolayer, but also supplies information such that inferences about the health of the RPE can be made.

›Optical coherence tomography is a valuable tool that gives anatomic cross-sectional information about the retina, retinal pigment epithelium, and choroid.

›Fluorescein and indocyanine green angiography are the standards for diagnosing choroidal neovascularization.

R.F. Spaide

Vitreous-Retina-Macula Consultants of New York, Manhattan Eye, Ear, and Throat Hospital,

New York, NY, USA

e-mail: rickspaide@yahoo.com

The advancement of the study of retinal diseases has been highly dependent on the expanding ability to image the ocular fundus. Monochromatic and color photography provided a means to photographically record the fundus. The advent of fluorescein angiography afforded ophthalmologists with a way to investigate and document vascular anatomy and physiology in ways previously unattainable [1]. Indocyanine green angiography augmented our capability to image the ocular circulation, particularly in the choroid [2]. With these dyes, we could obtain indirect information about other layers of the fundus, particularly the retinal pigment epithelium (RPE). These indirect methods included looking for increased or decreased transmission of underlying choroidal fluorescence, assessing the amount of staining and leakage, and using stereoscopic clues to try to determine the contour at the level of the RPE. Autofluorescence imaging [3], using several interrelated physiologic principles, provided the ability for clinicians to evaluate the RPE and outer retina in both an anatomic and functional basis. Optical coherence tomography (OCT) vastly improved our resolving power in imaging the anatomy of the retina and the RPE, but in its earlier iterations did not offer much in terms of functional imaging. Later implementation of OCT allowed visualization of the choroid in a number of diseases, particularly age-related macular degeneration (AMD). Each of these imaging methods will be discussed in isolation, much the same way tennis instruction is divided into forehand, backhand, volley, and the like, but in practical use, they are all employed simultaneously.

9.2Color Photography

Fundus cameras originally had 35-mm camera backs that were loaded with film. Images were recorded on film, the film was developed, and then had to be placed in the appropriate patient’s records. With the improving capabilities of charged coupled devices (CCDs), the increased speed of personal computers, and the tremendous decrease in cost of information storage, digital photography became not only cheaper, but better than film-based imaging for many modalities. Color image quality is judged by several factors including color accuracy, resolution, noise, dynamic range, and sensitivity. The spatial resolution of film is similar to that of high-quality scientific CCDs, but the other parameters are generally better with CCDs as compared with film. An equally if not more important aspect of digital imaging is that if an image has poor quality, it can instantly be retaken. High-resolution color photography is a practical way to record baseline and follow-up images of patients with AMD. Color photographs inherently are composed of red, green, and blue images, which can be deconstructed for analysis. The green channel of the color photograph is essentially equivalent to a conventional monochromatic image.

9.3Monochromatic Photography

When film was used to record fundus images, it was common to take a picture of the eye with a green filter in place of the light path. For some peculiar reason, this green filter monochromatic light was called “red-free” photography. Green light has the advantage of making small hemorrhages appear dark. When digital imaging started, color CCD cameras were expensive and had poor resolution. Monochromatic CCDs had a higher resolution for any given cost, and therefore, monochromatic photographs continued to be used. With the advent of high-resolution color CCDs, there is little reason to get a “red-free” photograph, especially since the green channel of a color photograph can be inspected. Other wavelengths of light may be more useful. A particular type of drusen, first called reticular pseudodrusen, are much easier to see with either infrared or blue light as compared with red or green monochromatic photography. One way to take a photograph with blue light (actually blue-green light) is to use the excitation filter for fluorescein angiography without using the barrier filter. This is a common technique to evaluate patients for the presence of reticular pseudodrusen, now termed

subretinal drusenoid deposits. It is easy to separate the principal color components of a color photograph into the red, green, and blue channels, and this latter way has become another common way to look for subretinal drusenoid deposits (Fig. 9.1).

The commercial scanning laser ophthalmoscopes (SLOs), as manufactured by Heidelberg Engineering, use near-infrared light to image the fundus. The reflectance characteristics of fundus structures are much different with near-infrared light as compared with visible light. The optic nerve is not particularly reflective in near-infrared light and consequently appears dark. Melanin absorbs visible light, particularly blue light; near-infrared light is not absorbed as much by melanin. In addition, melanin is a good reflector of infrared light, and consequently, pigmented scars can appear bright. Subretinal drusenoid deposits are readily visible with SLO examination (Fig. 9.2).

9.4Autofluorescence Imaging

Autofluorescent imaging of the ocular fundus relies on the stimulated emission of light from molecules, chiefly lipofuscin, in the retinal pigment epithelium [4–6]. Lipofuscin is a diverse group of molecular species [6], yellow to brown in color that accumulates in all post-mitotic cells, from the oxidative breakdown and rearrangement of a number of different molecules including polyunsaturated fatty acids and proteins. Lipofuscin in the RPE is novel because of the source of the components of lipofuscin, which is the outer segments of the photoreceptors.

The main component of lipofuscin in RPE cells is A2E, which is formed from two molecules of transretinal and one molecule of phosphatidylethanolamine. Components of lipofuscin inhibit lysosomal protein degradation [7], are photoreactive [8], are capable of producing a variety of reactive oxygen species and other radicals [5], are amphiphilic, may induce apoptosis of the RPE [9], and mediate blue light–induced RPE apoptosis [10]. Precursors of A2E, such as A2PE-H2, A2PE, and A2-rhodopsin, all of which are autofluorescent, form in outer segments prior to phagocytosis by the RPE [11, 12]. Because of the lack of direct apposition of the photoreceptor outer segments with the RPE and the inherent delay in phagocytosis, greater yields of A2-PE by the reaction product between all- trans-retinal and phosphatidylethanolamine are possible. In addition, the A2E and its precursors are potentially susceptible to oxidative damage [13, 14]

Fig. 9.1 Modern digital color imaging provides high-resolution images of the fundus and the color photograph shown can be split into the three constituent color channels: red, green, and blue.

Note the drusen present in this eye are more easily seen in the blue channel, consistent with the presence of reticular pseudodrusen, which were renamed subretinal drusenoid deposits