Metabolic mapping: Application images RPE

Boston-Blue laser autofluorescence (BluePeak, Heidelberg Engineering), a noninvasive method of viewing the retinal pigment epithelium (RPE), has important clinical applications in the study of geographic atrophy and other retinal diseases. This technology is now available on five spectral-domain optical coherence tomography (SD-OCT) models (Spectralis, Heidelberg Engineering).

"More and more clinicians and investigators are coming to appreciate the benefits of SD-OCT, and now they have the opportunity to have both SD-OCT and fundus autofluorescence," said Jeffrey S. Heier, MD, a vitreoretinal specialist who has been involved in studies of geographic atrophy, age-related macular degeneration (AMD), and autofluorescence.

"[The technology] gives you two very valuable tools for treating patients with AMD and unexplained vision loss," he continued, and noted that it also will be useful in evaluating emerging therapeutic agents for geographic atrophy.

"Roughly 7 million individuals in the United States have a degree of dry AMD at risk of progression to advanced AMD and vision loss, and if we can find means of either altering progression or reversing vision loss, or both, it would have a huge impact," said Dr. Heier, who is affiliated with Ophthalmic Consultants of Boston.

Autofluorescence imaging uses a solid-state blue laser (488 nm) for excitation; emissions are recorded above 500 nm with a barrier filter. Although this technology has been known for more than 10 years, its importance was not fully appreciated before recent advances in the treatment of wet AMD such as anti-vascular endothelial growth factor agents. Several issues have emerged along with these therapeutic developments, Dr. Heier said.

"We've tackled wet AMD, and we've started to see that even if we treat the wet AMD, there are a number of patients who still lose vision due to the progression of dry AMD," he said. "In addition, we've started to look at the patients who have dry AMD in the advanced form, such as geographic atrophy, which is best appreciated with fundus autofluorescence."

Approaches to autofluorescence

Several approaches to autofluorescence have been developed, but this particular proprietary blue laser technology has been especially well studied, according to Dr. Heier.

Frank G. Holz, MD, of the University of Bonn, Germany, a leading researcher in this area, has performed a number of studies using fundus autofluorescence to determine characteristics that can predict whether patients are at greater or lower risk of progression of geographic atrophy. The work of Dr. Holz includes the FAM Study (Prospective Natural History Study of Fundus Autofluorescence Imaging in Age-Related Macular Degeneration Using Confocal Scanning Laser Ophthalmoscopy).

The GAP Study (The Natural History of Geographic Atrophy Progression) further demonstrated the characteristics associated with a high risk of progression. Each of these studies utilized the proprietary blue laser autofluorescence technology.

"These findings are potentially huge," Dr. Heier said. "We've known that with autofluorescence you could see certain characteristics, but the ability to recognize prognostic characteristics that may enable us to do these studies in much shorter time frames could allow important treatments to reach patients years faster.

"It was originally felt that to do studies of geographic atrophy you'd need anywhere from two to five years just because of the degree of progression," Dr. Heier added. "But what Dr. Holz and the GAP study have shown us is that certain characteristics may have a level of progression over a single year, and if the appropriate patients are selected you have a strong chance of being able to show benefit over a much shorter time frame."

Dr. Holz presented an update on blue laser fundus autofluorescence at the recent Retina Congress meeting.

Blue laser technology also helps clinicians evaluate the health of the underlying RPE. Investigators such as Alan Bird, MD, of Moorfields Eye Hospital, London, advocate the importance of looking at autofluorescence prior to initiating therapy for wet AMD because the health of the RPE is critical to visual gain. Patients who may have significant disease but healthy RPE on autofluorescence are capable of visual gain, while those who may not have appeared to have such dramatic disease but did not have healthy RPE are incapable of significant visual gain.

"That can affect study and clinical outcomes, and from a more basic standpoint it can tell you whether a patient can [have improvement] or not," Dr. Heier concluded. "The hope and expectation is that autofluorescence will enable us to address individual patient needs [more appropriately]. The combination of fluorescein, autofluorescence, and OCT will help us understand much more about which patients are likely to [have a response] and [to] what treatments . . . as advances in treatments for dry and also wet AMD continue."