Hugo Chow-Wing-Bom^1,2 (), Matteo Lisi³, Noah Benson⁴, Patrick Yu-Wai-Man^1,5,6,7, Frederic Dick^1,2, Roni Maimon-Mor¹, Tessa Dekker^1,2; ¹University College London, UK, ²Birkbeck-UCL Centre for NeuroImaging, London, UK, ³Royal Holloway University of London, UK, ⁴University of Washington, USA, ⁵University of Cambridge, UK, ⁶Cambridge University Hospitals NHS Foundation Trust, UK, ⁷Moorfields Eye Hospital NHS Foundation Trust, London, UK

Assessing visual function across the visual field is very challenging when vision is severely impaired because dense central scotomas limit the ability to keep the eyes comfortably fixed on a central target, and therefore the precise stimulation of retinal loci. Functional magnetic resonance imaging (fMRI), combined with structure-based retinotopic atlases could be valuable tools for measuring visual function alongside standard behavioral perimetry approaches in such cases, because the retina can be passively stimulated without the need for accurate fixation. We investigate the use of this approach for assessing severe visual field loss in Leber Hereditary Optic Neuropathy (LHON). LHON is a mitochondrial disease causing acute loss of retinal ganglion cells, leading to severe central vision loss, often extending up to 10-15 degrees of eccentricity. Building on our previous fMRI work showing variations in cortical contrast sensitivity across a large visual field (40deg) in normal-sighted individuals, we used our brain-based approach to map visual field loss in 10 LHON patients. Our initial approach combined population receptive field (pRF) modelling with the modelling of BOLD modulations to large-field contrast-varying sinusoidal gratings, to quantify cortical contrast sensitivity across eccentricities and visual field quadrants. To apply this to severely sight impaired patients, we estimated retinotopic tuning of visual cortex using a fixation-free, structure-based atlas linking cortical activity to visual space locations (i.e., Benson retinotopic template), with additional model-based eccentricity scaling. Our results show that this approach accurately maps V1 contrast sensitivity to visual field loss, showing alignment with behavioral perimetry maps. This objective cortical mapping could offer new insights into how disease progression and recovery in severe sight loss impact visual information processing, including potential responses to gene therapy, which are emerging as potential treatment options for LHON.

Acknowledgements: Supported by Moorfields Eye Charity (GR001315; London, UK) and the Birkbeck-UCL Centre for NeuroImaging (BUCNI; London, UK).