Retinal Ischemic Perivascular Lesions: An Exploratory Study of Their Potential as Biomarkers for Cardiovascular Disease

<b>Background/Objectives</b>: This exploratory study aimed to assess the prevalence of retinal ischemic perivascular lesions (RIPLs) in individuals with cardiovascular disease (CVD) or associated risk factors and to investigate their potential role as non-invasive biomarkers of systemic ischemia using optical coherence tomography (OCT). <b>Methods</b>: A prospective observational study was conducted between July and October 2022. A total of 665 participants aged 40-90 years underwent macular OCT imaging using the Topcon Maestro 2 system. Participants were classified into two groups: those with ischemic CVD or risk factors (<i>n</i> = 297) and healthy individuals without cardiovascular conditions (<i>n</i> = 368). RIPLs were defined by inner nuclear layer thinning and outer nuclear layer expansion in perivascular regions and were identified by masked consensus of three independent evaluators. <b>Results</b>: The overall prevalence of RIPLs was 0.75% (five cases), exclusively observed in the diseased group (1.68%), with no cases identified among healthy individuals (<i>p</i> = 0.044). Stratified analysis showed an increase in RIPL prevalence with age, reaching 2.24% in the 70-79 years cohort. Statistically significant associations were found between RIPLs and hypertension, dyslipidemia, ischemic heart disease, and thrombosis (all <i>p</i> < 0.001). No significant association was observed with sex, myocardial infarction, or RIPL presence as an independent predictor (<i>p</i> = 0.08). <b>Conclusions</b>: Their identification through OCT during routine ophthalmologic examinations highlights a possible new avenue for early cardiovascular risk stratification. Nevertheless, the extremely low number of RIPL cases detected (only five out of six hundred and sixty-five participants; 0.75%) significantly limits the statistical power of the analysis and precludes strong conclusions. These findings should be regarded as preliminary and hypothesis-generating, requiring confirmation in larger, more diverse populations.