By Netan Choudhry, M.D, FRCSC and Jennifer George
Fundus autofluorescence (FAF) is a rapid, noninvasive imaging technology used for predicting the health of the retinal pigment epithelium. Autofluorescence is typically defined as a fluorescent emission originating from endogenous fluorophores when excited with a specific wavelenth of radiation1. The “auto” in autofluorescence is used to distinguish it from the fluorescent emission obtained from the use of exogenous dyes or markers. AF detection requires a barrier filter to exclude the reflectance signal from the excitation emission, without which an overlapping detection of reflectance and AF signals occurs, known as “pseudofluorescence”2.
With the emergence of autofluorescence technologies, FAF has become one of the leading imaging modalities in evaluating retinal disease. Fundus autofluorescence most often refers to the emission obtained from lipofuscin (LF) in the retinal pigment epithelium (RPE). Lipofuscin, a pigment associated with aging, is composed of 10 different fluorophores. Most important among these fluorophores is a pyridinium biretinoid called A2E (N-retinyl-N-retinyldene ethanolamine), which results from the normal visual cycle3. A2E is not degraded by the RPE and as such accumulates in the aging eye. Fundus autofluorescence is, therefore, able to detect LF and provide information on the metabolic health of RPE in addition to its functionality.
Several instruments are used to detect the FAF signal, including modified fundus cameras and the confocal scanner laser ophthalmoloscope (cSLO). The FAF imaging modality assists eyecare providers in the evaluation of diseases involved in the RPE, such as retinal dystrophies, degenerations and infectious uveitis. FAF can also prove useful in the diagnosis of age-related macular degeneration (ARMD), a condition which may result in a high FAF signal. These changes in FAF could indicate whether the disease is more advanced than previously determined.
In a clinical setting, when evaluating autofluorescence images, areas of increased fluorescence are referred to as hyperautofluorescent (hyperAF), while areas of decreased fluorescence are termed hypoautofluorescent (hypoAF). Areas of hyperAF indicate increased lipofuscin, as seen with drusen in ARMD. The presence of fluid beneath the retina can also appear hyperAF. Within the retina, hypoAF regions represent areas of RPE damage or loss. This can be seen in dry ARMD eyes with geographic atrophy, in which the atrophic region appears ‘dark’ or hypoAF.
Fundus autofluorescence is being actively studied world-wide with respect to its ability to provide prognostic information about numerous diseases, including dry ARMD. Several varieties of geographic atrophy (GA) have been identified via their FAF patterns. Longitudinal studies have subsequently revealed that the various presentations of GA progress at different rates, thereby allowing early characterization and identification of aggressive disease.
As FAF technology continues to evolve, there will be a growth in our understanding of retinal diseases as well as our ability to direct treatment accordingly. This non-invasive imaging modality stands in its own category and offers a new look at many commonly seen and in some cases, misunderstood, diseases. The future of ophthalmic imaging is bright and offers a glimpse into better visual outcomes for patients.
[1] Schmitz-Valckenberg S et al. „Fundus authofluorescence imaging: review and perspectives.” Retina, 2008; 28(3): 385-409.
[2] Machemer R et al. “Pseudofluorescence- a problem in interpretation of fluorescein angiograms.” American Journal of Ophthalmology, 1970; 70(1): 1-10.
[3] Eldred GE and Lasky MR. “Retinal age pigments generated by self-assembling lysosomotropic detergents.” Nature, 1993; 361(6414): 724-726.
