Loss of Cone Outer-segments and Thickening of Photoreceptor Layers in Multiple Sclerosis: The Belfast Eye and Multiple Sclerosis Study

Abstract

Purpose : Multiple Sclerosis (MS) causes progressive neurodegeneration characterised by demyelination of neurons and axonal loss. MS also affects the visual system with evidence of inner retinal degeneration; however, this does not fully explain vision loss experienced by patients. The Belfast Eye and Multiple Sclerosis (BEAMS) study aims to investigate if outer retina photoreceptor cells display changes in MS.

Methods : Sixteen patients with MS and 24 controls were enrolled. All patients underwent OCT (Heidelberg Spectralis) and AO (Imagine-Eyes RTX1). OCT analysis used in-built HEYEX automatic segmentation software (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 by the cone segmentation algorithm (AODetect) and manually corrected. Images were captured at 2, 4 and 6-degree eccentricity. Control (ctrl) participants were compared to patients with MS with optic neuritis (MSON) or without optic neuritis (MSnON). Data were analysed using SPSS and GraphPad Prism.

Results : Results identified significant thinning of the pRNFL (Ctrl 106.63±1.60; MSON 89.08±3.94 p<0.0001; MSnON 106.54±2.81) and macular GCIPL (Ctrl 73.19±1.24; MSON 61.48±1.91; p<0.0001; MSnON 71.21±1.30). No significant differences were observed in MSnON compared to ctrl. In contrast, there was significant thickening of the PRL in patients with MS (Ctrl: 66.24±0.29; MSON 68.76±0.58 p<0.0001; MSnON 67.67±0.46 p=0.011). After analysing the AO images, we found a significant decrease of cone outer-segment densities in patients with both MSON and MSnON compared to ctrl at 2, 2.5 and 3 degrees (MSON p<0.0001; MSnON p=0.0002). At >3 degrees the cone densities remained significantly lower in MSON (p=0.0002) but not in MSnON (p=0.0614).

Conclusions : OCT analysis in the BEAMS study replicates the previously reported thinning of the inner retinal layers. However, we report here for the first time, significant thickening of the photoreceptor layer on OCT, a loss of cone outer segments in patients on images from AO in patients with MS. These results highlight a potential involvement of the outer retina in the pathophysiology of MS changes that could become a marker for monitoring the progression of MS.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.