In this study, we evaluated risk factors for macular edema secondary to RVO. RVO type was the strongest independent factor for higher CRT (CRT ≥ 440µm). Besides, disrupted ELM and EZ was found to be a significant risk factor by univariate analysis. There was no difference in gender, age, duration, systemic diseases, smoking habits, vascular endothelial function, carotid plaque and disrupted ELM, EZ, and RPE. These results indicate that patients with CRVO may potentially be more likely to suffer more serious macular edema than patients with BRVO.
Prior studies have shown that there are differences in pathological mechanisms between CRVO and BRVO. Rachel et al. reported visual acuity was generally poor at baseline (༜20/40) and decreased further over time in CRVO [21]. It has been demonstrated that CRVO eyes had a higher ischemic index and VEGF level compared with BRVO eyes [22]. Spaide et al. reported that increased VEGF would induce dilated macular capillaries and hyperpermeability [23], which may explain why patients with CRVO had a thicker central retina than BRVO.
Our study demonstrates that endothelial dysfunction and disrupted EZ associate with worse visual acuity in RVO patients. Spaide et al. reported that endothelial dysfunction is an independent risk factor for BRVO, however, CRVO and smoking patients were not included in their studies [23]. The endothelium plays an important role in vascular function and prior studies suggest that abnormal vascular endothelium and arteriosclerosis are risk factors for RVO [24, 25]. Generated from vascular endothelial cells, Nitric oxide (NO) is an important signal molecule, regulating local blood flow [26]. In RVO with endothelial dysfunction, decreased NO level might reduce the retinal blood flow and increase platelet aggregation, which may have negative effects on visual acuity [27]. In experimental BRVO eyes, decreased vitreous NO level and narrowing of retinal arteries can be observed, supporting that impairment in the release of NO may contribute to the development of hypoxia and necrosis in the affected retina [28]. However, further investigation is needed to demonstrate it.
Our studies also show that disruption of EZ correlated with poorer visual acuity. The EZ is referred to the hyperreflective band between ELM and RPE in OCT, which is used for the evaluation of photoreceptor health. Its disruption correlates with poor vision in various diseases including RVO. It is reported that photoreceptor loss and EZ loss are the predictive factors for poor visual outcome and a large extent of macular edema in RVO [5, 29]. Touka et al. evaluated quantitative EZ metrics and observed that baseline VA was inversely associated with EZ loss [30]. In long-term visits, Chatziralli et al. also reported the association between poor final visual acuity and photoreceptor disruption [20]. Kanakis et al. removed shadowing from the OCT scans and demonstrated the relationship between disruption of EZ and the areas of capillary nonperfusion [31]. Therefore, the disruption of EZ is not only caused by photoreceptor loss, but also other interconnected factors, including optical and histologic effects of both edema and ischemia. The association of EZ integrity with baseline vision which is similar to the results of previous studies paves the way for studies using OCT analysis of EZ integrity to evaluate the baseline VA in RVO patients.
Previous studies have shown that hypertension, diabetes mellitus, hyperlipidemia, carotid plaque, and cigarette smoking are associated with an increased risk of RVO [7, 8]. However, our study has shown that they are not related to the extent of clinical manifestation. The reason for this marked variance from prior studies is uncertain. Evidence supporting the direct impact of systemic disease on visual function and retinal morphology is still not sufficient. As it is a retrospective study, potential bias cannot always be eliminated, but it can nevertheless provide important results.
As with any retrospective analysis, the limitations of this study must be considered. This study is small and the results should be considered preliminary. Further assessment and research are needed to better understand the underlying pathophysiology of these retinal changes. Although other risk factors were not associated with VA and CRT at baseline, long-term follow-up and assessment of retinal architecture changes are needed. Finally, the cause of the association between endothelial dysfunction and baseline visual changes remains unknown, and further prospective human studies are required to determine the true nature of these changes.
Despite these limitations, our results highlighted some baseline features in patients with RVO-ME, which should help inpatient counseling and planning preventive management. Measuring the FMD of the brachial artery and evaluating the integrity of EZ may help earlier recognition of eyes being prone to have poor vision. Patients with CRVO tend to have more significant ME than BRVO. Our study is limited by the small sample size, therefore larger studies are required to confirm these observations.