Silent Retinal Neurodegeneration in Multiple Sclerosis: Structural Evidence from Clinically Unaffected Eyes Using...

Area of Science:

• Ophthalmology
• Neuroscience
• Medical Imaging

Background:

• Retinal optical coherence tomography (OCT) is a key biomarker for neurodegeneration in multiple sclerosis (MS).
• Eyes without overt optic neuritis (ON) are often grouped as 'clinically unaffected' despite varied patient histories.
• Subtle structural and microvascular differences in these eyes remain under investigation.

Purpose of the Study:

• To compare structural and microvascular changes in MS eyes without prior optic neuritis (never-ON) versus fellow eyes after unilateral ON.
• To assess if these 'clinically unaffected' eyes differ from healthy controls using swept-source OCT (SS-OCT) and OCT angiography (OCTA).
• To determine the sensitivity of structural OCT measures versus microvascular indices in detecting subclinical retinal damage.

Main Methods:

• A cross-sectional study involving 126 clinically unaffected MS eyes (96 never-ON, 30 fellow eyes) and 118 healthy controls.
• SS-OCT was used to measure retinal thickness: ganglion cell-inner plexiform layer (GCIPL), peripapillary RNFL (pRNFL), and macular RNFL (mRNFL).
• OCT angiography (OCTA) assessed superficial vascular plexus (SVP) vessel density. Statistical analysis included generalized estimating equations with FDR correction.

Main Results:

• Both never-ON and fellow eyes exhibited significant retinal thinning compared to controls, despite normal visual acuity.
• A stepwise gradient in GCIPL thickness was observed: controls > never-ON eyes > fellow eyes (FDR q=0.020).
• pRNFL and mRNFL showed a similar pattern. No significant differences in OCTA-measured microvascular density were found between groups.

Conclusions:

• Clinically unaffected eyes in MS are structurally compromised, not normal.
• Fellow eyes following unilateral ON demonstrate a greater degree of silent retinal damage than never-ON eyes.
• Separate analysis of these distinct MS eye phenotypes is crucial for imaging research; structural OCT, especially GCIPL, is more sensitive than microvascular measures for subclinical detection.