The time course of retrograde trans-synaptic degeneration following occipital lobe damage in humans

Abstract

Following damage to the human post-geniculate visual pathway retrograde trans-synaptic degeneration of the optic nerve fibres occurs. It has been known for some time from investigations carried out in primates that a decline in the number of retinal ganglion cells follows occipital lobectomy. However, this is not detectable in all species studied and whether this occurs in humans was controversial until recent studies that have shown that following lesions of the occipital lobe, the retinal nerve fibre layer thickness measured by optical coherence tomography is reduced and corresponding shrinkage of the optic tract can be demonstrated by magnetic resonance imaging. The time course of the degeneration in humans is, however, unknown. In the present study, we have used optical coherence tomography to demonstrate for the first time progressive thinning of the retinal nerve fibre layer following occipital lobe/optic radiation damage due to stroke. First, in a group of 38 patients the measurement was taken on a single occasion at a known time interval since the stroke, ranging from 6 days to 67 years. Here, a negative straight line relationship (linear regression r = 0.54, P < 0.001) was found between nerve fibre layer thickness and elapsed time since injury in log years, giving a rate of decline of 9.08 µm per log year after adjusting for age. This indicates a decelerating rate of loss that differs from the rate of decline found with chronological age in this same group, which shows a steady rate of thinning by 0.4 µm per year (P = 0.006) after adjusting for duration of the disease. In a second study serial measurements were taken following the acute event in a group of seven patients with homonymous hemianopia; here a negative straight line relationship was found between time and nerve fibre layer thickness in micrometres over a period of data collection beginning at a mean of 36.9 days post-stroke (range 5-112) and ending at a mean of 426.6 days post-stroke (range 170-917). Evidence from clinical observation (funduscopy) suggested that retrograde trans-synaptic degeneration occurred in humans only where the damage to the post-geniculate pathway occurred prenatally. The results reported herein add weight to the previous demonstration that this type of degeneration does indeed occur in the human visual system by showing that it can be monitored over time and hence may provide a model for trans-synaptic degeneration in the human central nervous system.

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

“…ENERALLY, damage to the human central nervous system leads to retrograde trans-synaptic degeneration [1]- [4]. 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].…”

Relative Afferent Pupillary Defects in Homonymous Visual Field Defects Caused by Stroke of the Occipital Lobe Using Pupillometer

“…Recently, it has been reported that retinal thinning possibly due to RTSD is present in humans, as determined using OCT in patients with HVFDs due to lesions not involving the optic tract and LGN. 8–10,24,25 In our previous study, we reported that the inner retina corresponding to the blind visual fields demonstrated thinning within a few years after the onset of occipital damage using spectral-domain OCT. 9 Some of the patients who developed a post-geniculate lesion within 1 year of evaluation did not show inner macular thinning by OCT. 26 Meier et al found that the retinal nerve fibre layer of a patient with HVFD due to an occipital lobe abscess was thinned but no RAPD was noted after 2 years. 10 Conversely, small RAPD due to HVFDs has been detected immediately after stroke, when no retinal atrophy should be present.…”

“…In recent years, retrograde trans-synaptic degeneration (RTSD) in the patients with HVFDs has reported that the thickness of the inner layer of the retina is thinned, 8,9 but the relationship with pupillary light reflex is not clarified. If retinal ganglion cells are damaged due to RTSD, there could be corresponding pupillary defects.…”