Background <p>To examine the prevalence of retinal ischemic perivascular lesions (RIPLs) in the fellow eye of patients with retinal vein occlusion (RVO) and investigate their relationship with systemic vascular diseases.</p> Methods <p>In this retrospective case–control observational study, 91 fellow eyes of RVO patients (91 eyes) and the eyes of 63 age-matched healthy (63 eyes) volunteers were evaluated. RIPLs were assessed by examining cross-sectional scans from 6 × 6&#xa0;mm optical coherence tomography angiography (OCTA). Quadrantal superficial capillary plexus (SCP) and deep capillary plexus (DCP) were quantitatively analyzed in the RIPL areas. The relationship between vascular diseases (hypertension, diabetes, coronary artery disease, carotid stenosis, atrial fibrillation, stroke, myocardial infarction) in participants and RIPL was also investigated.</p> Results <p>RIPLs were found in 25 eyes (27.4%) of RVO patients and five eyes (7.9%) in the control group (p = 0.018). There were statistically significant differences in DCP VD (%) in the superior (p = 0.024) and inferior (p = 0.044) temporal quadrants, where RIPLs were more common. RVO in the fellow eye was associated with a 5-fold increase in the possibility of the presence of RIPL compared with controls (OR = 5.00, 95% CI = 1.01- 15.11). Presence of RIPLs was associated with 5.13-fold higher odds of carotid artery stenosis (OR = 5.13, 95% CI = 1.02- 28.25) and 4.94-fold higher odds of a history of myocardial infarction (OR = 4.94, 95% CI = 1.24- 58.25).</p> Conclusion <p>RIPL, a subclinical retinal ischemic lesion, was found at rates almost 3.5 times higher in the fellow eye of RVO patients. These lesions are significantly associated with carotid artery stenosis and a history of myocardial infarction. RIPL may be an ophthalmological indicator that can be used for systemic macrovascular disease.</p>