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Fundus autofluorescence imaging may help predict AMD progression
Combining autofluorescence imaging and optical coherence tomography is useful in tracking morphological changes, physicians say.
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Fundus autofluorescence patterns observed using confocal scanning laser ophthalmoscopy may be linked to disease progression in patients with age-related macular degeneration and may thereby help clinicians determine appropriate therapeutic courses in the future.
“The amount of focal increased autofluorescence that you see in the macular area gives you good correlation with how the disease is going to progress,” R. Theodore Smith, MD, PhD, told Ocular Surgery News in a telephone interview.
Autofluorescence patterns can indicate the probable progression of both the wet and dry forms of AMD; however, this form of imaging might be more valuable in studying the dry form, which Frank G. Holz, MD, called the next big challenge for retina specialists.
“There’s a huge population with dry AMD and especially with late dry AMD,” Dr. Holz said.
“In the atrophic late stage of AMD, [fundus autofluorescence] has helped us to better understand the role of excessive accumulations of lipofuscin in the retinal pigment epithelium and its relevance for the occurrence of cell death,” he said.
Dry AMD and lipofuscin accumulation
In a study published in American Journal of Ophthalmology, Dr. Holz and colleagues evaluated the relationship between autofluorescence patterns, geographic atrophy and disease progression in 195 eyes of 129 patients with AMD.
The investigators found that levels of lipofuscin in the retinal pigment epithelium and its topographic distribution often relate to progression of the disease, in that lipofuscin can indicate areas of eventual cell death. Geographic atrophy rates could therefore be predicted by various abnormal baseline autofluorescence patterns.
“We have noted that in areas where there’s a higher autofluorescence signal indicating excessive amounts of lipofuscin, that this retinal site will undergo cell death and will cause an absolute scotoma,” Dr. Holz said.
“In designing clinical trials that test new pharmacologic interventions, [fundus autofluorescence] is helpful in distinguishing progressers from slow progressers,” he said. “We came up with a classification that allows us to distinguish between those patients that have a fast enlargement of the atrophic patches as opposed to those that have a rather slow enlargement.”
Dr. Smith said he does not believe that areas of lipofuscin accumulation indicate where cells will die but rather that the overall lipofuscin level seen in autofluorescence images indicates how the disease will progress.
“The lipofuscin deposits, if you follow them with time, may or may not become atrophic, but the total amount of hyper-autofluorescence in the macula does seem to be a marker for overall disease activity and does give some indication as to how rapidly things are going to progress,” he said.
Wet AMD and reticular patterns
Dr. Smith and colleagues have retrospectively studied the relationship between reticular patterns of autofluorescence and choroidal neovascularization. They currently have a prospective study under way, he noted.
 An elderly woman presented with choroidal neovascularization in the left eye and soft drusen in the right eye. (A) The autofluorescence image in the right eye shows central hyper- and hypo-autofluorescence consistent with soft drusen and early focal atrophy. There is a striking reticular autofluorescence pattern below the superior arcade. (B) Color photo of the right eye. (C) Red free photo of the right eye. Both show subtle reticular pseudodrusen in the right eye superiorly in the same distribution as the reticular autofluorescence. CNV developed 6 months later in the right eye. Images: Smith RT  Fundus autofluorescence image (upper left) showing a markedly decreased signal in the area of geographic atrophy (fundus photograph lower right). This corresponds with the reflectance image (lower left) in which deep large choroidal vessels are seen in the atrophic patch. The green line indicates the location of the high-resolution OCT scan (upper right) in the SLO images. Microstructural alterations are visualized in the perilesional, the junctional and the atrophic zone. Images: Holz FG |
In a study published in Investigative Ophthalmology and Visual Science, they showed that reticular hyperautofluorescence appears to be a marker for reticular pseudodrusen, which are known to be associated with CNV. Specifically, in 55 fellow eyes of patients with unilateral CNV, the investigators found a high occurrence of reticular autofluorescence and reticular pseudodrusen.
“It’s a striking autofluorescence pattern that looks like alternating dark and light spots,” Dr. Smith said.
“It looks like there’s been some spotty damage to the [retinal pigment epithelium], and we’re thinking perhaps that’s an inflammatory sign or even an infectious agent, which has caused damage over a certain area of the macula,” he said.
The presence of these reticular patterns may help clinicians determine whether or not an eye will develop CNV.
“If you see a patient with that finding in one or either eye and particularly in a high-risk fellow eye when the patient already has choroidal neovascularization in one eye, then it appears that the likelihood that that eye is headed toward CNV is even greater than it would be otherwise,” Dr. Smith said.
Autofluorescence plus OCT
Dr. Holz said fundus autofluorescence imaging can be even more effective in evaluating AMD progression when it is combined with optical coherence tomography, as with the Spectralis HRA+OCT (Heidelberg Engineering).
“With the simultaneous recordings of high-resolution OCT, it is possible to evaluate corresponding morphological substrates, ie, underlying microstructural changes in the retina and the retinal pigment epithelium,” Dr. Holz said.
The Spectralis HRA+OCT, approved by the U.S. Food and Drug Administration in 2006, is also capable of combining spectral domain OCT with fluorescein angiography, indocyanine green angiography, infrared imaging and blue reflectance imaging, according to a press release from Heidelberg.
“The device has a so-called eye tracking system that compensates for eye movement during the recording of the images,” Dr. Holz said. “This firstly helps to generate mean images and, thus, to obtain higher quality images with less noise and secondly [allows] precise correlations of changes that are seen.”
For more information:
- Frank G. Holz, MD, can be reached at the Department of Ophthalmology, University of Bonn, Ernst-Abbe-Strasse 2, D-53127 Bonn, Germany; 49-228-287-15647; e-mail: frank.holz@ukb.uni-bonn.de. Dr. Holz is a consultant to Heidelberg Engineering.
- R. Theodore Smith, MD, PhD, can be reached at Columbia University Medical Center, 635 W. 168th St., Room 314, New York, NY 10032; 212-283-5222; e-mail: rts1@columbia.edu. Dr. Smith has no direct financial interest in the products discussed in this article, nor is he a paid consultant for any companies mentioned.
- Heidelberg Engineering Inc., maker of the Spectralis HRA+OCT, can be reached at 1499 Poinsettia Ave., Suite 160, Vista, CA 92081; 760-598-3770; fax: 760-598-3060; Web site: www.heidelbergengineering.com.
References:
- Holz FG, Bindewald-Wittich A, et al. Progression of geographic atrophy and impact of fundus autofluorescence patterns in age-related macular degeneration. Am J Ophthalmol. 2007;143:463-472.
- Smith RT, Chan JK, et al. Autofluorescence characteristics of early, atrophic, and high-risk fellow eyes in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2006;47:5495-5504.
- Jessica Loughery is an OSN Correspondent based in Philadelphia.