AO imaging offers novel data for understanding retinal disease

Reviewed by Mina Chung, MD

Dr. ChungAdaptive optics (AO) is providing new insights about retinal structure and may help to identify potential areas for treatment of retinal diseases, said Mina Chung, MD. 

“AO is a noninvasive imaging modality that uses a deformable mirror to compensate for and correct aberrations,” said Dr. Chung, associate professor of ophthalmology, Flaum Eye Institute, University of Rochester, Rochester, NY. “It allows visualization of individual photoreceptors, retinal pigment epithelial (RPE) cells, and retinal vasculature at 2-µm resolution.”

Dr. Chung added that AO can be combined with existing imaging modalities. It may be used to document and quantify changes early in disease where they are not discoverable or measurable using other modalities.

Image 1: Here is a montaged AOSLO image of retinal photoreceptors superimposed on a fundus photograph of a "normal" retina, as an example of the type of view and information clinicians can retrieve with adaptive optics. Courtesy of Mina Chung, MD.

AO also can be combined with scanning laser ophthalmoscopy (AOSLO) to provide real-time video with optical sectioning capability. It can be coupled with fundus autofluorescence, fluorescein angiography, and optical coherence tomography (OCT).

Although the area that can be imaged at one time with AO is limited, the window can be stitched together to generate a montage that contains a tremendous amount of data for an individual, Dr. Chung pointed out.

Cell count and density

Using AO, it is possible to count photoreceptor cells and calculate their density.

“Findings from calculations of AO-measured cone density versus eccentricity correlate nicely with the expected numbers from histology,” Dr. Chung said. “There is already normative data for cone density based on AO imaging,”

AO imaging in eyes with different pathologies highlights its capability for providing novel information. In a published report, Dr. Chung and colleagues used AOSLO to image the eyes of two brothers with early Stargardt disease and their unaffected parents. They compared the findings with those seen on imaging with other techniques [Song H, et al. JAMA Ophthalmol. 2015;133(10):1198-1203.]

AO revealed normal photoreceptor structure and spacing in the parents, but in the two brothers, it showed increased cone and rod spacing and a dark cone appearance in the periphery, which Dr. Chung said is thought to represent loss of the outer segments.

With AO, no foveal cones were detected in the eye of the older brother. In his sibling, the foveal cones were enlarged and reduced in density to ~25% of the normally expected value.

“OCT in the affected brothers showed loss of photoreceptor outer segments in a bull’s-eye pattern with foveal sparing, and a normal appearing peripheral photoreceptor layer,” Dr. Chung said.

Cone-like structures

Used to study eyes with advanced age-related macular degeneration, AO identified cone-like structures within areas of geographic atrophy (GA) and normal appearing cones in areas overlying drusen.

“Cone density in the GA area was calculated to be similar to that of surrounding normal-appearing retina, suggesting there may be potentially recoverable photoreceptor cells within small GA lesions,” Dr. Chung said.

Imaging with AOSLO in an eye with macular telangiectasia showed no cones within the central area of the lesion, whereas cones in the periphery appeared healthy. The technology also was used to evaluate changes in a phase 1 clinical trial where fellow eyes were randomized to receive the ciliary neurotrophic factor (CNTF)-secreting intravitreal device (NT-501 Encapsulated Cell Therapy, Neurotech) or no treatment.

Analyses of serial images taken during 24 months of follow-up in one patient showed cone densities declined by about 25% in the untreated eye but only 13% in the eye injected with the CNTF implant.

“The difference in the magnitude of the decrease was statistically significant,” Dr. Chung said. “A benefit for treatment was not detected in the analysis of other endpoints, which included visual acuity, OCT, and microperimetry. These data show the potential benefit for using AO to assess outcomes in clinical trials.”

Mina Chung, MD

E: mina_chung@urmc.rochester.edu

This article was adapted from a presentation that Dr. Chung delivered at the 2017 Retina World Congress. Dr. Chung is a consultant to Santen and WAVE Life Sciences and receives research grant support from Lowy Medical Research Institute.