Cerebral Modifications and Visual Pathway Reorganization in Maculopathy: A Systematic Review

Abstract

Background: Macular degeneration (MD) is one of the most frequent causes of visual deficit, resulting in alterations affecting not only the retina but also the entire visual pathway up to the brain areas. This would seem related not just to signal deprivation but also to a compensatory neuronal reorganization, having significant implications in terms of potential rehabilitation of the patient and therapeutic perspectives. Objective: This paper aimed to outline, by analyzing the existing literature, the current understanding of brain structural and functional changes detected with neuroimaging techniques in subjects affected by juvenile and age-related maculopathy. Methods: Articles using various typologies of central nervous system (CNS) imaging in at least six patients affected by juvenile or age-related maculopathy were considered. A total of 142 were initially screened. Non-pertinent articles and duplicates were rejected. Finally, 19 articles, including 649 patients, were identified. Results: In these sources, both structural and functional modifications were found in MD subjects' CNS. Changes in visual cortex gray matter volume were observed in both age-related MD (AMD) and juvenile MD (JMD); in particular, an involvement of not only its posterior part but also the anterior one suggests further causes besides an input-deprivation mechanism only. White matter degeneration was also found, more severe in JMD than in AMD. Moreover, functional analysis revealed differences in cortical activation patterns between MD and controls, suggesting neuronal circuit reorganization. Interestingly, attention and oculomotor training allowed better visual performances and correlated to a stronger cortical activation, even of the area normally receiving inputs from lesioned macula. Conclusion: In MD, structural and functional changes in cerebral circuits and visual pathway can happen, involving both cerebral volume and activation patterns. These modifications, possibly due to neuronal plasticity (already observed and described for several brain areas), can allow patients to compensate for macular damage and gives therapeutic perspectives which could be achievable through an association between oculomotor training and biochemical stimulation of neuronal plasticity.

Cerebral Modifications in Glaucoma and Macular Degeneration: Analysis of Current Evidence in Literature and Their Implications on Therapeutic Perspectives

“…The reduction in the volume of grey and white matter has been explained as a consequence of a trans-synaptic degeneration related to central retinal damage, and distributed in a retinotopic way at a cerebral level. 6 The increase in grey matter observed by Olivo is likely to have a compensatory meaning, since this area is involved in eye movement, and particularly in the adaptation of hand-eye coordination.…”

“… 110 , 111 These methods certainly benefit from a morpho-functional reorganization of brain circuits at the head of the visual processing, which can thus compensate for the damage consequent to the pathology; to date, the occurrence of such an eventuality, based on neuronal plasticity mechanisms and on the activation of normally silent secondary connections, seems to be plausible even if the evidence is not yet definitive. 5 , 6 However, it should be pointed out that other therapeutic perspectives, which may be available in the near future, such as retinal ganglion cell transplantation, 112 retinal prostheses, 113 , 114 stem cell therapy 115 and genetic therapy 116 need instead the guarantee of an unaltered connectivity between retina and the brain which, if not maintained, could even result in a failure not allowing, once the retinal integrity is restored, the correct processing of the visual signal. It is therefore needed to summarise the current evidence regarding the morphological and functional alterations affecting the CNS in patients suffering from glaucoma and macular degeneration, and to compare the distribution of these alterations in the two pathologies deriving so the implications they could have on current rehabilitation techniques and future therapeutic possibilities.…”

“…122,128 Whether at least some of these morpho-functional alterations could be a sign not only of degeneration but also of occurred remodelling based on neuroplasticity is still under discussion. In the context of these pathologies, the evidence of remodelling has already been suggested, 5,6 but to date there is no definitive evidence that these changes may reflect a real plasticity of the adult CNS following the pathological insult, rather than a simpler adaptation through the activation of normally silent collateral and secondary circuits. Obtaining definitive evidence in this area would have great repercussions in a therapeutic perspective: as discussed above, if a remodelling would certainly be useful within a rehabilitation path aimed at maximising the residual visual capacity and compensating for the lost one, a modification of the nervous circuits between retina and the brain, and between the different brain areas, could on the contrary compromise the potential results of therapeutic approaches still in development (cell therapy, gene therapy, transplantation and retinal prosthesis) which, in order to restore the functioning of the damaged retina, would require an intact downstream neuronal circuitry for the correct processing of the visual signal.…”

“…There is much evidence to suggest that the alterations resulting from these two pathologies are not limited to the retina alone, but also affect the central nervous system in both structural and functional terms. 5 , 6 It is our aim, with this review, to summarise and compare the data currently available in the literature concerning the modifications occurring at the CNS level, to identify their likely causes and to discuss the implications they may have in the context of existing or developing rehabilitation and therapeutic strategies.…”

Cognitive Dysfunctions in Glaucoma: An Overview of Morpho-Functional Mechanisms and the Impact on Higher-Order Visual Function

“…Similar changes may occur also in inherited retinal dystrophies, where white matter network changes and cortical remapping have been described (Olivo et al, 2015;Ferreira et al, 2016;Rita Machado et al, 2017). If visual system changes occur in the first stages to try to compensate the progressive visual degeneration, the later stages of retinal diseases are characterized by extensive morpho-functional impairment also of the intracranial visual system (Nuzzi et al, 2020). Although still poorly investigated, the profound interconnection between the eye and CNS may have extremely important implications for a deeper understanding of visual processing mechanisms and for ocular and CNS diseases.…”