Cortical Atrophy Predicts Visual Performance in Long-Term Central Retinal Disease; GCL, pRNFL and Cortical Thickness Are Key Biomarkers

Abstract

Purpose The aim of this study was to assess both retinal and cortical structure in a cohort of patients with long-term acquired central retinal disease in order to identify potential disease biomarkers and to explore the relationship between the anterior and posterior visual pathways. Methods Fourteen participants diagnosed with long-term central retinal disease underwent structural assessments of the retina using spectral-domain optical coherence tomography, including macular ganglion cell layer (GCL) and peripapillary retinal nerve fiber layer (pRNFL) thickness. Structural magnetic resonance imaging was used to measure visual cortex, including cortical volume of the entire occipital lobe and cortical thickness of the occipital pole and calcarine sulcus, representing the central and peripheral retina, respectively. Results Mean thickness was significantly reduced in both the macular GCL and the inferior temporal pRNFL across patients. Cortical thickness was significantly reduced in both the occipital pole and calcarine sulcus, representing the central and peripheral retina, respectively. Disease duration significantly correlated with GCL thickness with a large effect size, whereas a medium effect size suggests the possibility that cortical thickness in the occipital pole may correlate with visual acuity. Conclusions Long-term central retinal disease is associated with significant structural changes to both the retina and the brain. Exploratory analysis suggests that monitoring GCL thickness may be a sensitive biomarker of disease progression and reductions in visual cortical thickness may be associated with reduced visual acuity. Although this study is limited by its heterogeneous population, larger cohort studies would be needed to better establish some of the relationships detected between disease dependent structural properties of the anterior and posterior visual pathway given the effect sizes reported in our exploratory analysis.

Assessing the structure of the posterior visual pathway in bilateral macular degeneration

“…These results support and extend previous cross-sectional studies, which have highlighted reductions associated with natural ageing, and also largely supports previous work reporting a thinning of cortex in the posterior visual pathway in MD 1 , 3 , 5 , 8 , 10 , 12 , 16 , 17 . The group data for cortical thickness support earlier work in our lab; Hanson et al 17 followed a group of unilateral AMD patients and found a reduction in volume of the occipital lobe, driven by cortical thinning in the occipital pole.…”

“…The group data for cortical thickness support earlier work in our lab; Hanson et al 17 followed a group of unilateral AMD patients and found a reduction in volume of the occipital lobe, driven by cortical thinning in the occipital pole. Furthermore, in a separate cohort of bilateral wet-AMD patients, Hanson et al 16 found the occipital pole and calcarine sulcus both showed significant thinning. Here, we report cortical thinning in the same ROIs in a different cohort of bilateral MD patients.…”

“…Our ROIs were taken from FreeSurfer’s Destrieux atlas which are not restricted to V1, but we also collapsed across a larger portion of the peripheral field representations. We opted for the Destrieux atlas ROIs to keep consistent with those used to explore cortical thickness and myelin density changes, but also to keep consistent with other work published in the lab 16 , 17 . When looking at individual tract profiles in Yoshimine et al 22 , it does appear that AMD patients on average exhibited lower FA in the peripheral representations in a portion of the tract, however it did not reach significance.…”

“…As the human population is ageing, and most ophthalmic pathologies develop late in life, we need to understand the nature of changes in the entire visual pathway, from eye to brain, but particularly in AMD given it is currently the leading cause of blindness in the developed world 65 , 66 . As highlighted by Hanson et al 16 , determining which features of eye disease drive atrophy in the posterior visual pathway is important, as plasticity will be brought into question—is the mature brain capable of responding appropriately if visual function were restored? We also need to determine whether it is sufficient to treat the eye alone, or whether we need to incorporate additional neuroprotective strategies to prevent or slow the cortical changes.…”

“…ROIs were defined using FreeSurfer’s Destrieux anatomical atlas 29 . We used the occipital pole (parcellation index = 42) and the calcarine sulcus (parcellation index = 44) consistent with those used by Hanson et al 16 , 17 . These ROIs were used for cortical thickness and myelin density analyses and are shown on the inflated surface in Fig.…”