Neurochemical markers of degeneration in the visual cortex after vision loss from Stargardt macular dystrophy

Stargardt macular dystrophy (STGD1) causes progressive degeneration of the photoreceptors in the retina, predominantly affecting the central macula. A focal region of vision loss in STGD1 is projected into a localised region of the primary visual cortex (V1). There are therapies in development that allow functional restoration of the retina, but it is unclear how the visual cortex will process restored visual input in adulthood. Loss of visual input will influence cortical processing, leading to degeneration that would be reflected in the local chemical environment. This study explores if vision loss from STGD1 affects in vivo neurochemistry by using high resolution Magnetic Resonance Spectroscopy Imaging (MRSI). STGD1 (n=16, mean age 34.0 ± 15.1 SD) were compared to normally sighted controls (n=14, mean age 38.7 ± 14.6 SD). A MRSI slab (resolution = 5x5x15mm, FOV=240x240x15mm) was placed in the occipital lobe. For each participant, neurochemical concentrations relative to total creatine were quantified in voxels constrained within V1 (defined by the Juelich atlas), averaged across voxels, and then compared between groups. The concentrations were then correlated with the extent of disease severity through visual field loss in STGD1 patients. Myo-inositol (a marker for glial cell proliferation) was higher within V1 in STGD1 compared to controls (t(28)=2.69; p=.012) and correlated with the extent of vision loss (higher concentrations related to greater loss; r(17)=-.68; p<.001). Glutamate (marker for neuronal function) (r(22)=.47; p=.022) and NAA (marker for neuronal integrity) (r(12)=.61 ;p=.020) correlated with the extent of vision loss (lower concentrations related to greater loss). These findings show a significant change in neurochemical concentrations related to glial and neuronal integrity in adults with vision loss compared to those without. The capacity for the visual cortex to process restored input should be considered alongside potential visual restoration therapies, as their effectiveness could be hindered by cortical degeneration.