Outer Retinal Dysfunction in the Absence of Structural Abnormalities in Multiple Sclerosis

Purpose Recent evidence suggests structural changes distal to the inner retina in multiple sclerosis (MS) patients. The functional correlates of these proposed structural abnormalities remain unclear. We investigated outer retinal function and structure in MS patients, and quantified to what extent outer retinal structure influenced function in these patients. Methods Outer retinal function was assessed using the full-field and multifocal electroretinogram (ERG/MF-ERG), whereas retinal structure was assessed using spectral-domain optical coherence tomography (OCT). Results were compared with preexisting normative data. The relationships between electrophysiology parameters and the OCT values corresponding to the proposed cellular origins of the ERG and MF-ERG were analyzed. Results Most electrophysiological responses were delayed in MS patients, independently of optic neuritis (ON). Inner retinal thickness and volumes were reduced, and inner nuclear layer volume marginally increased, in eyes with previous ON; all other OCT parameters were normal. OCT results correlated with ERG amplitudes, but not with ERG peak times or any MF-ERG parameters. Conclusions We recorded outer retinal dysfunction without detectable abnormalities of the corresponding retinal layers in MS patients, not ascribable to retrograde degeneration following ON. The findings complement a growing body of literature reporting primary retinal abnormalities distal to the ganglion cell-inner plexiform layer complex in MS patients, with our data suggesting that this may be a more widespread phenomenon than previously thought. ERG may be of more utility in detecting retinal dysfunction in MS patients than MF-ERG. Analysis of peak times, rather than response amplitudes, is recommended.