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fMRI of Retina-Originated Phosphenes Experienced by Patients with Leber Congenital Amaurosis
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    A phenomenon characterized by the experience of seeing light without any light actually entering the eye is called phosphenes or photopsias. Phosphenes can occur spontaneously or via induction by external stimuli. Previous reports regarding phosphenes have primarily focused on externally induced phosphenes such as by applying alternating or direct current to the cortex. A few of these reports used functional magnetic resonance (fMRI) to study activations induced by cortical phosphenes. However, there are no fMRI reports on spontaneous phosphenes originating from the retina and the resulting pattern of cortical activations. We performed fMRI during a reversing checkerboard paradigm in three LCA patients who underwent unilateral gene therapy and reported experiencing frequent phosphene on a daily basis. We observed bilateral cortical activation covering the entire visual cortices when patients reported experiencing phosphenes. In contrast, in the absence of phosphenes, activation was regulated by patient's visual ability and demonstrated improved cortical activation due to gene therapy. These fMRI results illustrate the potential impact of phosphene perception on visual function and they may explain some of the variability that clinicians find in visual function testing in retinal degeneration. Although we did not perform correlations between visual function and phosphenes, we hope data presented here raises awareness of this phenomenon and its potential effect on visual function and the implications for clinical testing. We recommend a thorough history for phosphene experiences be taken in patients with retinal disease who are candidates for gene or molecular therapy. Lastly, these data illustrate the potential power of fMRI as an outcome measure of gene therapy and the negative impact phosphenes may have on vision testing. fMRI has proven to be a sensitive, non-invasive, and reproducible test paradigm for these purposes and can complement standard visual function testing.

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    8DP1EY023177/DP/NCCDPHP CDC HHS/United States
    DP1 EY023177/EY/NEI NIH HHS/United States
    R21 EY020662/EY/NEI NIH HHS/United States
    R21EY020662/EY/NEI NIH HHS/United States
    R24 EY019861/EY/NEI NIH HHS/United States
    R24EY019861/EY/NEI NIH HHS/United States
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