Abstract
Damage to the primary visual cortex (V1) causes homonymous visual field loss affecting both eyes. Multiple reports have shown that V1 damage initiates trans-synaptic retrograde degeneration. Here, we examined the time-course of degeneration at the level of the inner retina, and asked if visual restoration training impacts its progression. We recruited 48 participants (59±10yrs, 37/48 males) 3-379 months after occipital stroke, and 6 visually-intact controls (52±14yrs, 1/6 male). The location, size, and severity of visual defects were derived from 24-2 Humphrey automated perimetry and we measured ganglion cell and inner plexiform layer (GCL-IPL) thicknesses on either side of the fovea [corresponding to blind versus intact hemifields] using optical coherence tomography (OCT). A laterality index (LI) was computed from OCT-derived measurements to account for individual variance in retinal thickness. Patients then underwent home-training for 6 months on a direction discrimination task. Half were randomized to train in their blind field and the other half in their intact hemifield, after which Humphreys and OCTs were repeated. Pre-training, blind-field GCL-IPLs were thinner than intact-side GCL-IPL (paired t-test, p<0.0001), generating more positive LI values than in controls (unpaired t-test, p<0.0001), and which increased with time since stroke (p=0.0002, R2=0.2736). Participants trained in their intact field exhibited further GCL-IPL thinning (paired t-test, p=0.008) and increased LI (paired t-test, p=0.009) when re-measured post-training, suggesting progression of the degeneration. Participants trained in their blind field did not. Thus, GCL-IPL shrinkage is evident on retinal imaging after stroke-induced V1 damage, showing gradual worsening over time. Progression persists during intact-field training, but appears to be halted during blind-field training. This raises the intriguing possibility that training interventions previously shown to reduce the severity and size of visual field defects may confer retina-specific protection against retrograde degeneration.