Topographic analysis of vascular changes in retrograde trans-synaptic degeneration

To investigate the vascular signatures of retrograde trans-synaptic degeneration (RTSD) on OCT and OCTA, and to assess whether these changes differ from those associated with non-arteritic anterior ischemic optic neuropathy (NAION).

This retrospective cohort study included 24 eyes with RTSD and 12 eyes with NAION. Retinal regions corresponding to visual field defects were topographically defined and compared with anatomically matched internal control regions from the fellow eye. Structural (peripapillary retinal nerve fibre layer(pRNFL), macular ganglion cell-inner plexiform layer(mGCIPL)) and vascular (peripapillary vessel density(pVD], macular vessel density(mVD)) parameters were calculated as affected-to-control ratios (%). Spearman correlation and ANCOVA were used to evaluate structure-vascular relationships and compare regression slopes between groups.

Both groups exhibited significant structural and vascular reductions in affected regions. NAION eyes demonstrated greater reductions in pRNFL, pVD, and mVD ratios compared to RTSD (all p < 0.05), while mGCIPL ratios showed a non-statistically significant difference (p = 0.065). The correlation between mGCIPL and mVD was higher in NAION (ρ = 0.815, p = 0.001) than in RTSD (ρ = 0.469, p = 0.021). Age-adjusted ANCOVA with an interaction term demonstrated that the slope of the relationship between structural thinning and vascular loss was significantly more pronounced in NAION (interaction β = -0.75, p = 0.049).

RTSD demonstrated relatively modest vascular compromise compared to NAION, which is presumed to reflect secondary changes due to reduced metabolic demand following retrograde neuronal degeneration. Quantitative structure-vascular analysis using RTSD as a reference model may aid in distinguishing secondary degeneration from primary ischemic injury in optic neuropathies.