Changes in cellular structures revealed by ultra-high resolution retinal imaging in optic neuropathies

PURPOSE. To study the integrity of inner and outer retinal layers in patients with various types of optic neuropathy by using high-resolution imaging modalities. METHODS. Three high-resolution imaging systems constructed at the University of California Davis were used to acquire retinal images from patients with optic neuropathy: (1) adaptive optics (AO)-flood-illuminated fundus camera, (2) high-resolution Fourier domain optical coherence tomography (FDOCT), and (3) adaptive optics-Fourier domain optical coherence tomography (AO-FDOCT). The AO fundus camera provides en face images of photoreceptors whereas cross-sectional images (B-scans) of the retina are obtained with both FDOCT and AO-FDOCT. From the volumetric FDOCT data sets, detailed thickness maps of a three-layer complex consisting of the nerve fiber (NF), ganglion cell (GC), and inner plexiform (IP) layers were created. The number of visible cones in the en face images of photoreceptors was then compared with visual sensitivity maps from Humphrey visual field (HVF; Carl Zeiss Meditec, Inc., Dublin, CA) testing, as well as FDOCT and AO-FDOCT images, including the thickness maps of the NF GC-IP layer complex. Five types of optic neuropathy were studied: (1) optic neuritis with multiple sclerosis (MS), (2) idiopathic intracranial hypertension (pseudotumor cerebri), (3) nonarteritic anterior ischemic optic neuropathy (NAION), (4) optic nerve head drusen with NAION, and (5) systemic lupus erythematosus with MS and arthritis. RESULTS. With permanent visual field loss and thinning of the NF-GC-IP layer complex, cone photoreceptors showed structural changes, making them less reflective, which caused the appearance of dark spaces in the en face images (hence, reduced number of visible cones) and indistinct outer retinal layers in OCT images. However, when the visual field loss was only transient, with a normal NF-GC-IP layer complex, there were no detectable abnormalities in cone photoreceptors (i.e., they were densely packed and had distinct photoreceptor layering in the OCT images). CONCLUSIONS. Cone photoreceptors show structural changes when there is permanent damage to overlying inner retinal layers. There was a positive relation between the thickness of the three-layer inner retinal complex, visual sensitivity, and integrity of the cone mosaic.