Quantitative Analysis of Retrograde Trans-Synaptic Retinal Degeneration Based on Lesion Topography

Retrograde trans-synaptic retinal degeneration (RTSD) occurs after injury to the postgeniculate visual pathways, and the distribution of retinal thinning mirrors the pattern of visual field defects (VFDs), which reflects the topographical organization of the visual pathway. We aimed to quantitatively assess how RTSD evolves over time in a topographically specific manner based on lesion location and to identify factors associated with its progression.

This longitudinal cohort study included patients with RTSD caused by structural lesions in the visual pathway, including 29 patients who have had a stroke and 22 with tumors. Optical coherence tomography was used to measure the thickness of the peripapillary retinal nerve fiber layer (pRNFL) and the macular ganglion cell-inner plexiform layer (mGCIPL) in RTSD and non-RTSD areas, defined by the side and VFD patterns. A mixed-effects model was applied to evaluate the longitudinal changes in pRNFL and mGCIPL thickness over the follow-up period and to identify associated factors.

In the RTSD area, the estimated rate of pRNFL thinning was 6.44 µm/log year (95% confidence interval [CI], 4.85-8.02 µm/log year), whereas the estimated rate of mGCIPL thinning was 5.44 µm/log year (95% CI, 4.66-6.21 µm/log year). Thinning was most pronounced during the first 4 years, after which the rate of thinning slowed and stabilized at 0.33 µm/year (95% CI, -0.30 to 0.97 µm/year) for pRNFL and 0.31 µm/year (95% CI, 0.06-0.56 µm/year) for mGCIPL. The thinning rates in the RTSD area were significantly faster than those in the non-RTSD area (pRNFL: 3.50 µm/log year [95% CI, 2.30-4.70 µm/log year], P = 0.005; mGCIPL: 0.29 µm/log year [95% CI, -0.14 to 0.72 µm/log year], P < 0.001). Older age, male sex, and more severe VFD were associated with faster RTSD progression. Regarding the causes, RTSD progression did not differ significantly between stroke and tumor, but hemorrhagic stroke and malignant tumors (glioblastoma, metastatic) showed faster thinning than ischemic stroke and meningioma, respectively.

RTSD progression was pronounced in both the pRNFL and mGCIPL during the first 4 years, with greater severity observed in areas topographically linked to the brain lesion. Although RTSD developed regardless of lesion etiology, older age, male gender, severe VFD, intracerebral hemorrhage, and malignant tumors were associated with significantly faster progression.