Fig. 1

Retinal tissue of patient #1 showing outer nuclear layer (ONL) loss with spatial correlation to ONL thinning seen on optical coherence tomography (OCT) and associated brain pathology. Left eye retinal tissue from inferior parafoveal macula (a) (H & E, original magnification X 4). This patient had a normal macula with a single druse (blue arrow) at the macula which enabled precise localization of retinal tissue. Boxes show corresponding areas of higher magnification (b, c) (original magnification X 20). This patient has some normal appearing ONL (area b, black arrow) (about 6 layers of nuclei), but area c shows an area of ONL loss (black arrow) (2–4 layers of nuclei). Other retinal layers have no abnormalities, except for typical tissue processing artifactual separation of photoreceptor segments from the ONL and partial separation of INL from the outer plexiform layer. There is no artifact affecting ONL nuclei. Full retina examination prior to expiration showed a normal appearing macula with no confounding retinal disease. OCT at that time also showed macula ONL thinning, especially at inferior macula. d shows the ETDRS grid location of inferior parafoveal OCT scans (e,  f) (green line) and of point measurements (red asterisk). e shows OCT of an age, sex, race matched normal control with normal ONL thickness in comparison to ONL thinning seen on this patient’s OCT in which the same druse (blue arrow) seen in retinal tissue is visualized (f). OCT image ONL boundaries are shown in blue and green; Heidelberg Spectralis (Franklin, MA) caliper measurements are shown. Brain pathology showed four-repeat (4R) tauopathy with threads (g), tufted astrocytes (h), tangles (g) and white matter coiled bodies within oligodendrocytes (i) consistent with progressive supranuclear palsy. MRI (j, k, l) showed prominent frontal lobe atrophy that was asymmetric and most prominent in left medial and dorsolateral frontal lobes. GCL ganglion cell layer, INL inner nuclear layer, ONL outer nuclear layer