It provides tangible, visible evidence of disease progression, where before there was only guesswork.
Diagnostic instrumentation that provides autofluorescence capabilities is helping clinicians diagnose retinal conditions earlier by showing abnormalities that are often invisible to standard fundus photography and ophthalmoscopy.
How it works
Autofluorescence (AF) is caused by the presence of lipofuscin, an aging pigment fluorophore thought to be produced by the outer segments of the photoreceptors and stored at the level of the retinal pigment epithelium (RPE), according to Jerome Sherman, OD, FAAO, a Primary Care Optometry News Editorial Board member. It is defined as the spontaneous emission of a wavelength of light by a substance, such as lipofuscin, after illumination with light of a different wavelength. AF uses the excitation of fluorophores, which are inherent in the retina, and also a barrier filter, which blocks most of the light that would reflect off the retina in a typical photo, he said. Different AF systems use different excitation sources and barrier filters, but all demonstrate a uniform glow to the normal retina.
John A. McCall Jr.
“AF often reveals when a disorder is progressing before the cells have actually died,” explained PCON Editorial Board member John A. McCall Jr., OD, in an interview.
Two abnormal states of lipofuscin exist, Sherman told PCON, hyperautofluorescence (hyper AF) and hypoautofluorescence (hypo AF).
“In hyper AF, the image in the area that’s affected will be brighter than the corresponding normal zones, and this is typically thought to be due to the increased metabolic activity of the retinal pigment epithelium,” he said. “In a sense, you can think of this hyperautofluorescence as a way to tell us about sick retinal pigment epithelial cells.”
This helps clinicians determine whether retinal diseases are latent or about to progress, McCall added.
“In contrast, with hypoautofluorescence, there’s no normal glow of the fluorescence; it’s actually just completely dark or even black,” Dr. Sherman said. “This suggests that there’s no lipofuscin present because the retinal pigment epithelial cells have died, along with the corresponding photoreceptors.”
Lipofuscin cells, in normal, healthy patients, show luminance in themselves, and will appear gray in the images. However, in instances of hyperautofluorescence, which indicates metabolically active, sick RPE cells, lipofuscin will glow brightly. And if the condition of these hyperautofluorescent cells is not reversed, they can become hypoautofluorescent, which essentially means that they have died, Sherman said.
SriniVas R. Sadda
According to a presentation by SriniVas R. Sadda, MD, associate professor of ophthalmology, University of Southern California, at Retina 2012 earlier this year, the use of AF in a clinical environment can aid in the diagnosis of retinal dystrophies (Best’s disease, Stargardt’s disease, cone dystrophy, retinitis pigmentosa, etc.), central serous retinopathy, hydroxychloroquine toxicity, parafoveal telangiectasis and age-related macular degeneration, among others. It is noninvasive, allows monitoring for disease progression – such as areas of RPE disturbance or atrophy – and can help explain vision loss by identifying subtle atrophy.
“Let’s say we’re following somebody with macular degeneration or geographic retinal atrophy,” McCall said. “You want to know if it is arrested. Has it already reached its maximum dropout or is it about to spread? Am I controlling it, or is it about to go south? Autofluorescence fills in that gap of previous guesswork.
“If you see a lot of drusen around the macula in dry macular degeneration, but no luminance, then it indicates that nothing will happen fast,” he continued. “If you see a lot of drusen around the macula with a lot of luminance around it, then things are going south and you should take appropriate measures to try to shore up that macula.”
The ultra-widefield autofluorescent images reveal symmetric findings in each eye that are characteristic of inherited retinal degenerations. The macula region of both eyes is hypo-AF and is surrounded by a hyper-AF annulus, suggesting that the macula lesions will enlarge in time. The far peripheral retina reveals various depths of hypo-AF lesions and also has a hyper-AF border nasally, suggesting that it, too, is enlarging. The midperipheral retinal zones reveal the normal AF glow. Vision will be further compromised, as the macula lesions expand outwardly and the far peripheral areas of degeneration expand inwardly.
Images: Sherman J
In cases of suspected optic nerve head drusen, Sherman said AF will most often demonstrate intense hyper AF of the disc drusen.
“It is possible for the disc drusen to be so buried that they are not detected with AF, but quite unusual,” he added.
In cases of diabetic retinopathy, when blot hemorrhages are observed, the standard course for many clinicians is to look for activity in the macula, McCall said. Using AF to look for luminance in the macula can provide a clear view of the situation and, when combined with OCT, will indicate whether you need to take action.
With geographic atrophy, a random pattern may appear on the retina for a long time, and then it may begin progressing again, he added. “But when will it start progressing? Luminance will show you that,” McCall said.
“The geographic atrophy that’s already taken out the retina will be black, and the retina that’s OK will be a neutral gray color,” he continued. “But when it begins to shine in luminance, that means there is activity, and you want to explore all options to stop it prior to it taking the macula.”
When differentially diagnosing a metabolically active melanoma vs. an inert choroidal nevus, Sherman said nevi are invisible with AF because the RPE is intact, but melanomas are typically hyper AF.
Another boon to AF’s ability to provide earlier diagnoses, according to Sherman, is conjecture that activity in the peripheral retina, which AF indicates, can be a warning sign to looming AMD.
“In age-related macular degeneration, there are often abnormalities of the RPE, and autofluorescence allows us to see them,” he said. “We sometimes get a granular appearance over the RPE, some light spots and some dark spots. Often, these changes could be in the mid- and far periphery and they’re not detected with standard clinical examinations. So we get additional information.”
Research is currently being conducted to study peripheral abnormalities in AMD because some of the peripheral changes may actually pre-date the abnormality of the macula itself, he added.
“The general rule is if you can diagnose something early, and there’s available treatment, you want to treat it as early as possible,” Sherman said.
Autofluorescence is available from Heidelberg Engineering, Optos, Topcon, Carl Zeiss Meditec and Cannon, Dr. Sherman said.
According to Sadda, another way to create an AF signal is through the use of the flash fundus camera. This camera can image the entire retinal area at once with a single flash using green light and no confocal optics. The green light filter is used to reduce the contribution of the lens to the AF, he said.
This inexpensive technique only requires outfitting a fundus camera with the appropriate filters, but may produce less detailed images and be affected more by lighting irregularities, Sadda said. – by Daniel R. Morgan
For more information:
- John A. McCall Jr., OD, a member of the Primary Care Optometry News Editorial Board and senior vice president of vendor relations for Vision Source, is in private practice in Crockett, Texas. He can be reached at 711 East Goliad Ave., Crockett, TX 75835; (936) 544-3763; email@example.com.
- SriniVas R. Sadda, MD, is associate professor of ophthalmology at the University of Southern California, Los Angeles. He can be reached at (323) 442-6335; firstname.lastname@example.org.
- Jerome Sherman, OD, FAAO, a member of the Primary Care Optometry News Editorial Board, is a Distinguished Teaching Professor at the State University of New York College of Optometry and in private practice at the Eye Institute and Laser Center. He can be reached at, 33 West 42nd St., New York, NY 10306; (212) 938-5862; email@example.com.
- Disclosures: McCall has no relevant financial interests. Sadda has received research grants from Carl Zeiss Meditec, Optovue and Optos; is a consultant to Heidleberg; and receives royalties from Topcon Medical Systems. Sherman lectures and consults for Optos, Zeiss and Topcon.