Long distance retrograde degeneration of the retino-geniculo-cortical pathway in homonymous hemianopia

Abstract

Long-distance retrograde degeneration of the retino-geniculo-cortical pathway has been described in humans and animal models following injury to the brain. In this study, we used optical coherence tomography (OCT) to measure the severity and timing of retrograde degeneration after post-chiasmal visual pathway lesions in patients with homonymous hemianopia. We performed a retrospective study of 69 patients with homonymous hemianopia and analyzed high quality OCT macular ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL). Patients with lesions involving the optic tract and thalamus were included in the anterior group, while patients with lesions of the occipital lobe were included in the posterior group. Statistical significance was determined using Mann-Whitney U test and Wilcoxon test. We found that in patients with homonymous hemianopia, those with anterior lesion exhibited earlier and more severe thinning compared with the posterior group. In fact, thinning can occur within 2 months after insult in the anterior group. Within 6 months of onset, the anterior group exhibited about 5 times more hemi-macular GCC thinning than those with acquired lesions of the posterior visual pathway (P = 0.0023). Although the severity of hemi-macular GCC thinning was different, the majority of hemi-macular thinning occurred within the first 6 months in both groups. Beyond 2 years, thinning in those with acquired anterior and posterior lesions was minimal, except in a small number of patients with multiple insults to the occipital lobe. In conclusion, using OCT, we measured the severity and rate of long-distance, retrograde degeneration in patients with homonymous hemianopia. Homonymous hemi-macular thinning after optic tract and thalamic injury was more severe and occurred earlier compared with thinning after occipital lobe insult via trans-synaptic degeneration. The presence of severe hemi-macular degeneration on OCT provides objective evidence that localizes the lesion to the post-chiasmal anterior visual pathway.

The natural history of homonymous hemianopia revisited

“…Such a pattern is suggestive of initial resolution of cytotoxic edema and inflammation, followed by the development and increasing impact of trans-synaptic retrograde degeneration. [15][16][17][18][19][20][21][22][23][24][25] In trans-synaptic retrograde degeneration, the loss of targets in primary visual cortex leads sequentially to the death of relay neurons in the ipsilesional dorsal lateral geniculate nucleus of the thalamus, and then to the loss of retinal ganglion cells in the affected portion of both eyes. [15][16][17][18][19][20][21][22][23][24][25] Our results are thus consistent with the temporality of trans-synaptic retrograde degeneration: experiments in non-human primates have found histological evidence of degenerative changes as early as 100 days after occipital lesioning, 18 and optical coherence tomography in humans has found thinning of the retinal nerve fiber layer in the affected retinal region as early as one month post-stroke.…”

“…[15][16][17][18][19][20][21][22][23][24][25] In trans-synaptic retrograde degeneration, the loss of targets in primary visual cortex leads sequentially to the death of relay neurons in the ipsilesional dorsal lateral geniculate nucleus of the thalamus, and then to the loss of retinal ganglion cells in the affected portion of both eyes. [15][16][17][18][19][20][21][22][23][24][25] Our results are thus consistent with the temporality of trans-synaptic retrograde degeneration: experiments in non-human primates have found histological evidence of degenerative changes as early as 100 days after occipital lesioning, 18 and optical coherence tomography in humans has found thinning of the retinal nerve fiber layer in the affected retinal region as early as one month post-stroke. 20 Loss of these early visual sensory substrates could constrain the effectiveness of visual restoration treatments 34,35 ; a recent study of vision training therapy after stroke found that training-induced recovery of visual fields in the chronic post-stroke period was indeed limited by shrinkage of the optic tracts.…”

“…In a small study of chronic HH (>6 months post-stroke), the usual care group showed worsening of Humphrey visual fields (HVFs) over time. 14 Although humans are known to experience trans-synaptic retrograde degeneration of early visual pathways after occipital strokes, [15][16][17][18][19][20][21][22][23][24][25] testing the hypothesis that this is associated with slowly degrading vision requires a non-binary analysis of visual defects. Here, we conducted a retrospective review of reliable HVFs in occipital stroke patients, evaluating HVF change longitudinally, within subject, to revisit and parametrize the progression of HH defects.…”