Retrograde trans-synaptic retinal ganglion cell loss identified by optical coherence tomography

Abstract

There is experimental evidence of trans-synaptic retrograde degeneration of retinal ganglion cells following retrogeniculate visual pathway lesions in primate studies. Retinal nerve fibre loss in congenital homonymous hemianopia in humans is well recognized from clinical observation but the findings in acquired lesions have been controversial. Forty-eight persons were recruited and divided into three groups. Two groups were patients with retrogeniculate lesions. In the first group, the occipital damage had occurred during childhood or in adult life whilst the lesions in the second group were congenital. Inclusion criteria for the retrogeniculate lesions included: age >18 years at time of testing; homonymous hemianopia; no other ophthalmic or neurological disorder; and neuroimaging demonstration of occipital lobe damage. The third group had normal visual function. Measurement of the thickness of the peripapillary retinal nerve fibre layer by optical coherence tomography has been carried out in both eyes of each subject. The primary outcome is the peripapillary retinal nerve fibre layer thickness (RNT) in microns. The mean RNT in the eyes with temporal hemianopia (here called the 'crossing-fibre defect' eyes) is 79.8 mu (SD = 35.1 mu) in the acquired and 72.7 mu (SD = 33.2 mu) in the congenital. The mean RNT in eyes with nasal hemianopia (here called the 'non-crossing-fibre defect' eyes) is 83 mu (SD = 29.5 mu) in the acquired and 73.4 mu (SD = 26 mu) in the congenital. In the control group, the RNT measured 101.4 mu (SD = 36.6 mu) for the left eyes and 100.8 mu (SD = 35.4 mu) for the right eyes. In both crossing-fibre defect eyes and non-crossing-fibre defect eyes the mean RNT is significantly greater in the controls than in the hemianopia groups (P < 0.001). These data confirm that there is thinning of the retinal nerve fibre layer following both congenital and acquired lesions of the retrogeniculate visual pathway in humans. This is most likely to represent retinal ganglion cell loss in both congential and acquired groups. Furthermore the magnitude of the thinning is similar in both groups despite the fact that clinical observation has consistently found evidence of RNT thinning in cases of congenital but not in cases of acquired pathology. The data have also been analysed in 12 sectors around the optic disc: it has been shown that the RNT thinning follows the known trajectories of the crossing and non-crossing retinal ganglion cell axons approaching the disc.

Alzheimer’s disease: A review of its visual system neuropathology. Optical coherence tomography—a potential role as a study tool in vivo

“…Evidence from OCT studies also supports a role for TRD in disorders of the posterior visual pathway [34,35,67,68] with visual field defects in these disorders correlating best with macular GCL thickness than with RNFL thickness [67,68]. Likewise, OCT findings in AD suggest the contribution of TRD in the pathophysiology of visual changes.…”

“…Fletcher et al (1988) described optic disc pallor and band atrophy in individuals with congenital occipital lesions. Initially it was believed that TRD in the visual pathway occurred only in individuals with congenital (prenatal) occipital lobe lesions [33], although recent studies have also provided evidence that TRD of RGC can also occur in patients with acquired occipital lobe lesions [34][35][36].…”

Macular ganglion cell–inner plexiform layer thinning in patients with visual field defect that respects the vertical meridian

“…We compared the superotemporal and superior GCIPL macular sectors and superior arcuate subfield pRNFL sector of the right eye in patients with left inferior quadrant VF defects because the thinning of retinal nerve fibers was seen predominantly in the arcuate area among the superior hemifield pRNFL sectors, although retinal nerve fibers from the nasal retina remain. [2] The superior and superonasal GCIPL sectors and superior non-arcuate subfield pRNFL sector of the left eye were compared because there was total loss of fibers in the nasal region and partial loss of fibers in the temporal region of the optic disc (Fig. 1) [2].…”

“…[2] The superior and superonasal GCIPL sectors and superior non-arcuate subfield pRNFL sector of the left eye were compared because there was total loss of fibers in the nasal region and partial loss of fibers in the temporal region of the optic disc (Fig. 1) [2]. In patients with left superior quadrant VF defects, we compared the inferotemporal and inferior GCIPL macular sectors and inferior arcuate subfield pRNFL (clock-hours 5 to 8) sectors of the right eye.…”

“…Optical coherence tomography (OCT) studies have revealed peripapillary retinal nerve fiber layer (pRNFL) loss in patients with various types of cerebral damage, including damage to the frontal, parietal, temporal, and occipital lobes [1], [2], [5], [6]. However, the ganglion cells on the temporal retina of the fovea primarily send their exons to the superior and inferior sectors of the optic nerve head (ONH), including the temporal sector.…”