Retinal thinning is frequently observed in patients who exhibited persistent CRVO without recurrent ME. Previous studies also revealed inner retinal layer thinning among CRVO patients [9, 10]. However, longitudinal analyses of changes in the inner retinal layer have rarely been reported, and no analyses of outer retinal layer thickness have been reported thus far. The present study investigated longitudinal changes in each retinal layer thickness in patients with CRVO without recurrent ME over 3 years, revealing significant reductions over time in the GCC, INL, OPL, and ONL. Additionally, changes in the GCC, OPL, and ONL were significantly associated with BCVA.

At baseline, GCC thickness was significantly thinner in the CRVO group than in the control group. Because of its high vascularity, the GCC is expected to rapidly respond to anti-VEGF treatment, exhibiting drastic changes in thickness. The rich vasculature of this layer is presumed to play an important role in its formation and structural maintenance; CRVO-induced hypoperfusion may contribute to its thinning. Additionally, its high oxygen demand increases vulnerability to hypoxic damage, leading to early retinal thinning. In contrast, the INL, OPL, and INL in the CRVO group tended to display increased thickness compared with the control group, although these findings were not statistically significant. Because these layers exhibit less vascularity or avascularity, they may require longer intervals to recover baseline thickness compared to the GCC. The PRL and RPE, which receive a portion of their oxygen supply from the choroid, did not exhibit significant differences between the two groups or changes over time.

The GCC, thinner in the CRVO group than in the control group from a relatively early stage after ME resolution, continued to display significant thinning over 3 years. Previous longitudinal studies have demonstrated sustained inner retinal damage due to vascular diseases, such as diabetes or hypertension [12, 13]. However, continued inner retinal damage in CRVO has rarely been reported. CRVO-affected retinas appear to experience continuous inner retinal damage, despite the absence of ME recurrence. Therefore, these changes should be considered when analyzing inner retinal layer thickness in CRVO patients. Notably, Roh et al. [14] reported that parafoveal inner retinal thinning after ME resolution by anti-VEGF treatment was predictive of a lower risk of ME recurrence in CRVO. Since we included patients who did not experience ME recurrence for an extended interval, many patients with advanced inner retinal thinning may have been present among the CRVO patients in this study.

A previous study showed that 12.6% of CRVO patients exhibited retinal atrophy, predominantly in the IPL to ONL, 6 months after ME resolution [9]. Although the study revealed thinning of the IPL, INL, OPL, and ONL in a small subset of patients, the examination period was short. In contrast, the present study demonstrated significant decreases in INL, OPL, and ONL thicknesses over 3 years. These decreases may be involved in the process of ME recovery but could also result from retinal damage because thickness changes were negatively associated with BCVA. Thinning of these layers may be associated with severe impairment of the deep retinal capillary plexus in CRVO eyes due to hypoxic damage caused by impaired deep retinal capillary plexus [15]. These layers exhibited slower and less pronounced changes compared with the GCC. Notably, the rate of thickness reduction in these layers decreased each year. Unlike the continuously decreasing GCC thickness, these layers appeared to partially plateau after thinning. Therefore, although the INL, OPL, and ONL were also affected by CRVO, the GCC is likely to experience the greatest long-term impact.

Previous studies have demonstrated significant associations between inner retinal layer thickness and visual acuity in CRVO patients. Cicinelli et al. [16] found that reduced inner retinal thickness was correlated with worse visual acuity after ME resolution in RVO patients. Similarly, Zheng et al. [17] identified a significant association between mean GC-IPL thickness and visual acuity in RVO eyes with resolved ME. Consistent with these findings, our study demonstrated that changes in the GCC were significantly associated with BCVA. Changes in the OPL and ONL also were significantly associated with BCVA; these relationships have not been previously reported. These results indicate that the continuous thinning of each retinal layer due to sustained damage by CRVO, despite ME resolution, may adversely affect visual function. Because the OPL and ONL tend to stabilize after 2 years, continued thinning in the GCC may have more pronounced long-term impacts on visual function. Further longitudinal studies with over extended intervals are required to confirm this hypothesis.

This study had several limitations. First, its retrospective nature inevitably led to selection bias. Secondly, the absence of assessments (e.g., visual field tests, color vision evaluations, and contrast sensitivity analyses) limited our ability to comprehensively evaluate changes in visual function associated with altered retinal layer thicknesses. Third, due to a substantial amount of missing data, we were unable to conduct a comparative analysis with the contralateral eyes of the CRVO group. Fourth, we were unable to assess the microvasculature status of each retinal capillary plexus using OCT angiography, which could be associated with changes in retinal thickness. Nevertheless, the strength of the present study lies in its longitudinal analysis, which revealed sustained damage to each retinal layer over 3 years in patients with resolved ME after CRVO; this phenomenon has not previously been reported.