THE FUTURE OF AMD AND IMAGING

Qualitative and quantitative information obtained with multimodal spectral domain-optical coherence tomography (SD-OCT) imaging technology is providing new opportunities for determining the pathophysiological mechanisms of age-related macular degeneration (AMD) and for predicting disease progression.

Speaking at the 14th EURETINA Congress in London, Ursula Schmidt-Erfurth MD, Professor and Head, Department of Ophthalmology, Medical University of Vienna, Austria, described the advantages of incorporating polarisation sensitivity (PS) and adaptive optics (AO) into SD-OCT and the use of these advanced imaging technologies for identifying and measuring pathological changes in AMD, including features of the retinal pigment epithelium (RPE), drusen, geographic atrophy and photoreceptor disease.

Interest in enhanced imaging of the RPE relates to the fact that it is considered the key structure in AMD pathology, said Dr Schmidt-Erfurth. “If we look early to the disease process, we see the retina still looks perfect, but there is already extensive change in the RPE. So, both compartments are important, and there may be a time sequence of events when disease is forming,” she explained.

Scrambling Property

Polarisation-sensitive optical coherence tomography (PS-OCT) uses the intrinsic polarisation scrambling property of the RPE to selectively distinguish it from other retinal structures. Unlike SD-OCT, PS-OCT can identify the RPE cells and not just differentiate the RPE. In addition, because the depolarising appearance of the RPE is caused by intracellular melanin-containing organelles – melanosomes, melanolipofuscin and melanolysosomes – PS-OCT provides information on RPE biology that can help in understanding the pathophysiology of AMD.

Discussing the use of PS-OCT for studying specific pathological features of AMD, Dr Schmidt-Erfurth reviewed its application for imaging and quantification of drusen. Although drusen can be imaged with SD-OCT and quantified using a manual segmentation technique, PS-OCT allows for an automated segmentation algorithm. A study comparing the manual SD-OCT and automated PS-OCT techniques using data from patients with early AMD validated the automated PS-OCT analysis as a reliable and time-saving tool for measuring drusen size and volume.

“We can now use the PS-OCT drusen segmentation algorithm with multiple raster B scans, which show the contour of the RPE, to generate a three-dimensional drusen map that corresponds tightly with the clinical picture of the drusen on colour fundus photography. However, PS-OCT is objective, more precise, able to detect small drusen and gives reliable measurements, so that when it is repeated we can determine progression over time,” Dr Schmidt-Erfurth said.

Taking advantage of that capability to study the long-term natural history of drusen development, Dr Schmidt-Erfurth and colleagues performed an integrated analysis of data from three years of follow-up in 56 eyes. The results showed that drusen volume increased linearly over time, and the researchers calculated a doubling time. Looking at the temporal changes in drusen volume in individual patients showed a sudden, precipitous regression of drusen volume occurred just before the development of choroidal neovascularization or geographic atrophy.

Noting that different types of drusen differ in their impact on RPE integrity, Dr Schmidt-Erfurth noted that research with PS-OCT indicates that the qualitative information it provides about drusen morphology may also have relevance for determining disease progression.

“Our findings suggest that PS-OCT holds promise as a prognostic tool for identifying risk for progression to advanced AMD. We believe this method, which relies on quantitative data sets, is a much more precise prognostic indicator than genetic risk calculation and gives insight into the mechanisms of RPE pathology,” said Dr Schmidt-Erfurth.

Geographic atrophy imaging

Dr Schmidt-Erfurth explained that depending on the segmentation algorithm used, the PS-OCT en-face images can also be used to depict borders of geographic atrophy. Another comparison study demonstrated the reproducibility of an automated PS-OCT segmentation algorithm for quantifying areas of geographic atrophy and showed that the results correlated with those obtained using fundus autofluorescence (FAF).

“FAF has been the gold standard modality for visualisation and quantification of geographic atrophy, but it gives a two-dimensional map. PS-OCT gives 3D topography and a very nice histological relief of the cellular changes,” she said.

In addition, Dr Schmidt-Erfurth noted that PS-OCT provides comprehensive, detailed information on all layers of the ocular fundus in eyes with geographic atrophy with a single three-dimensional data set.

“PS-OCT can provide integrated multimodal information comparable to that obtained using FAF, IR and standard SD-OCT performed separately,” she said.

Discussing imaging and quantification of photoreceptor disease, Dr Schmidt-Erfurth said that visualisation of foveal rods and cones becomes possible by combining AO with SD-OCT as the technique offers resolution of 1.5 x 5 microns.

“This is the imaging of the future, and it is important because we need to understand which parts of the photoreceptors are damaged first in order to understand the pathophysiological sequence of AMD progression,” she said.

Ursula Schmidt-Erfurth:

ursula.schmidt-erfurth@meduniwien.ac.at