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    Fundus autofluorescence imaging betters armamentarium

    Can map other fluorophores associated with diseases in outer retina, subneurosensory space

    Simultaneous recording of confocal scanning laser ophthalmoscopy (cSLO) images and spectral domain high-resolution optical coherence tomography (OCT) scans is possible with an instrument (Spectralis HRA+OCT, Heidelberg Engineering) that offers several cSLO imaging modes.

    These imaging modalities include a recently developed method known as fundus autofluorescence (FAF) imaging, which is used to record the topographic distribution of lipofuscin (LF) in the retinal pigment epithelium (RPE). FAF also can map other fluorophores that may be associated with diseases in the outer retina and the subneurosensory space, according to Frank G. Holz, MD, chairman and professor, Department of Ophthalmology, University of Bonn, Germany.

    FAF imaging can be useful in understanding pathophysiologic mechanisms, diagnostics, phenotype-genotype correlation, identification of predictive markers for disease progression, and monitoring of novel therapies, said Dr. Holz. He was a co-author of a recently published review of FAF (Retina. 28:385-409) and also gave a presentation on the subject at the annual meeting of the American Academy of Ophthalmology in New Orleans last year.

    Excessive LF accumulation in the RPE is a common downstream pathogenic pathway in various monogenetic and complex retinal diseases, Dr. Holz said, and the FAF signal is mainly derived from this LF accumulation. Because metabolic changes in the RPE can be mapped in vivo with the FAF imaging component of the HRA+OCT, the information it provides surpasses that attained from conventional imaging techniques, he added.

    FAF imaging can be used to detect autofluorescent material in the RPE and within the retina, revealing pathophysiologic alternations, and it may show underlying defects in both cross-sectional and longitudinal analyses, Dr. Holz said. Thus, FAF imaging not only could have diagnostic but also therapeutic value in measuring the response to treatment of macular and diffuse retinal dystrophies.

    It also could have phenotyping applications. It has been shown, for example, that FAF densities are absent or minimal in patients with early-onset severe retinal dystrophy associated with mutations on both alleles of RPE65, an enzyme necessary in the production of visual pigments. When the enzyme is absent and visual pigment generation ceases, LF production becomes based on retinoids. The lack of an FAF signal or a decreased signal would be consistent with this biochemical defect and thus could be a clinical marker of this genotype, Dr. Holz explained.

    FAF also has clinical application in age-related macular degeneration (AMD), as AMD may result in an increased FAF signal because of RPE in the junctional zone preceding enlargement of geographic atrophy, Dr. Holz said. A newly developed classification system for the variability of FAF findings in early AMD has revealed that there is relatively poor correlation between visible alterations on fundus photographs and FAF changes. Therefore, the FAF changes may indicate that diseased areas and abnormalities are more widespread than was previously apparent and that these changes may precede the development of visible lesions as the disease progresses.

    Ultimately, the FAF classification system could be used to identify risk factors for progression as well as to design and monitor interventional trials and identify genes associated with certain AMD manifestations, Dr. Holz added.

    Research is also under way on the FAF alterations in pigment epithelial detachments, central serous chorioretinopathy, chorioretinal inflammatory disorders, vitelliform macular dystrophy type 2 (Best disease), and pseudoxanthoma elasticum.

    Other imaging modes available in the retinal imaging device include fluorescein angiography, indocyanine green angiography, red-free, and infrared.

    The instrument also can record images simultaneously, such as simultaneous cSLO and spectral-domain OCT or FAF-imaging and high resolution spectral domain OCT. With this tool, pixel-to-pixel correlation is possible in both imaging modes.

    "If I see something on the two-dimensional SLO image, I can pinpoint the area," Dr. Holz said. "And if I ask what is the underlying morphological change in the retina or the retinal pigment epithelium, I can then at this very same site get the OCT to look at the underlying alternation."

    In the era of interventional therapy for AMD and other diseases associated with macular edema, this feature allows the clinician to make OCT scans at the same sites when the patient comes back for follow-ups and monitoring, Dr. Holz said. This is important because the change in central retinal thickness helps determine whether the patient needs additional treatments.

    With earlier versions of OCT, it was impossible to be sure that the same location was measured during different exams, making it difficult to ascertain whether the eye had improved or worsened, he added.

    A great advantage of the instrument is its automated eye tracker, according to Dr. Holz. This component follows eye movements by performing a continuous reference scan of the retina. When the eye moves, the location of the scan also changes, improving the ability to track changes over time. Individual images can be corrected for high resolution and real-time averaging of images, which provides more information than individual scans.

    In all, the instrument will be valuable as a diagnostic and monitoring device for retinal and macular diseases, Dr. Holz concluded.

    Nancy Groves
    Nancy Groves is a freelance medical writer.

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