Structural Correlates of Short-wavelength and Normalized Near-infrared Fundus Autofluorescence Imaging in Choroideremia.

Abstract

Purpose : To better understand the origin and pattern of fundus autofluorescence (FAF) elicited by near-infrared (NIR) and short-wavelength (SW) excitation lights in subjects with choroideremia (CHM). To assess the utility of normalization of the NIR-FAF by the strength of the NIR reflectance (NIR-REF) signal.

Methods : Previously obtained imaging of 10 subjects (20 eyes) with CHM ages 11-60 years old at various disease stages from two sessions (6 to 29 months apart, average 16) was analyzed. 6 eyes had been previously treated as part of a gene therapy trial. The NIR-REF, SW-FAF, and NIR-FAF as well as the spectral domain optical coherence tomography (SD-OCT) images from each time point were co-registered in a semi-automated fashion. The normalized NIR-FAF (nNIR-FAF) was calculated as previously described by Cideciyan et al. A pixel value profile across the path of the horizontal SD-OCT cross section was extracted from each of the fundus imaging modalities. The horizontal extents of the islands of FAF were manually marked.

Results : nNIR-FAF provides increased relative contrast of retained islands of retinal pigment epithelium (RPE) compared to NIR-FAF, but was less than SW-FAF. In all but one subject the horizontal extent of SW-FAF and nNIR-FAF was well co-localized. SW-FAF and nNIR-FAF islands corresponded to areas with relatively preserved ellipsoid zone and RPE bands on SD-OCT. nNIR-FAF in 7 out of 10 subjects showed a wide parafoveal peak of autofluorescence which corresponded with regions of relatively preserved outer segment length. Both eyes of one young subject with early disease demonstrated annular parafoveal SW-FAF preservation surrounded by perifoveal mottled and reduced SW-FAF. There was no clear correlate to this annulus with nNIR-FAF. Corresponding OCT showed loss of interdigitation zone with preservation of other outer retinal bands.

Conclusions : Changes in NIR and SW-FAF represent structural changes of the outer retina as seen SD-OCT. These changes are well co-localized between these two modalities in most cases, however, with much lower contrast using NIR excitation especially in the setting of poor image quality. nNIR-FAF modality provides improved contrast, facilitating identification of preserved NIR-FAF. With optimized imaging conditions it may be possible to forego SW-FAF and thus spare subjects the associated discomfort and potential photochemical damage.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.