Loss of cone outer-segments and thickening of photoreceptor layer in multiple sclerosis: The Belfast Eye and Multiple Sclerosis Study

Introduction
Multiple Sclerosis (MS) causes progressive neurodegeneration characterised by inflammation and demyelination of neurons. MS also affects the visual system with evidence of inner retinal degeneration and optic nerve damage; however, this does not fully explain vision loss experienced by patients.

Objectives
The Belfast Eye and Multiple Sclerosis (BEAMS) study aimed to investigate if outer retinal cells display changes in MS.

Methods
Sixteen patients with MS and 24 controls were enrolled. All patients underwent Optical Coherence Tomography (OCT; Heidelberg, Spectralis) and Adaptive Optics (AO; Imagine-Eyes, RTX1) imaging. OCT analysis used in-built automatic segmentation software (Heyex; aberrations manually corrected) for peripapillary retinal nerve fibre layer (pRNFL), macular ganglion cell layer-inner plexiform layer (GCIPL), and photoreceptor layer (PRL) thicknesses (photoreceptor inner and outer segments). AO images were analysed semi-automatically using the segmentation algorithm (AODetect) and manually corrected. Data were analysed using SPSS and GraphPad.

Results
There was a significant thinning of the pRNFL (p<0.0001) and macular GCIPL in patients with optic neuritis (ON) (p<0.0001) and a significant thickening of the PRL in patients with ON (p<0.0001). There was also a significant decrease of cone outer-segment densities in patients compared to controls (p<0.0001) independent of optic neuritis (MSON vs MSnON p>0.9).

Conclusions
We report here for the first time, significant thickening of the photoreceptor layer and loss of cone numbers in patients with MS. These results highlight the involvement of the outer retina in the pathophysiology of MS.