Age-related macular degeneration (AMD) is a progressive retinal disorder and a leading cause of irreversible blindness among elderly individuals, impacting millions of people globally. This review synthesizes the current understanding of the cellular and molecular signaling mechanisms driving AMD, with a focus on the distinct pathophysiological features of dry and wet AMD subtypes. Key mechanisms include oxidative stress, inflammation, lipid metabolism dysregulation, and immune dysregulation, all of which converge on the retinal pigment epithelium (RPE) as a central player in disease initiation and progression. In dry AMD, oxidative damage, mitochondrial dysfunction, and lipofuscin accumulation impair RPE function, contributing to drusen formation and geographic atrophy. In wet AMD, vascular endothelial growth factor-mediated angiogenesis, coupled with inflammation and endothelial metabolic reprogramming, drives choroidal neovascularization. This article integrates findings from multiomics approaches and highlights the potential of artificial intelligence in elucidating AMD pathogenesis and advancing personalized therapies. Future research directions emphasize targeting these molecular pathways to develop innovative treatments, offering hope for improved management of this debilitating condition.

Background/Objectives: The objective of this study is to evaluate the association between retinal ischemic perivascular lesions (RIPLs) and cardiovascular diseases (CVDs) among patients diagnosed with severe carotid artery stenosis (SCAS). Methods: Consecutive patients (123 patients) with SCAS were included and underwent swept-source optical coherence tomography angiography (SS-OCTA). Retinal structural and blood flow parameters of the macular region were calculated and compared between patients with and without CVD. The prevalence of RIPLs confirmed on B-scan images was compared between patients with and without CVD. The relationship between RIPLs and CVD in patients with SCAS was explored using multivariate logistic regression analysis. Subgroup analysis was conducted to evaluate the relationship between ipsilateral RIPLs, contralateral RIPLs, and bilateral RIPLs and CVD. Results: Of the 123 patients with SCAS, 61 patients (49.6%) had a history of CVD. The CVD group had lower vessel density in the superficial and deep retinal vascular complexes, thinner inner retinal thickness, and thicker outer retinal thickness compared with the non-CVD group. A higher prevalence of RIPLs was found in the CVD group compared to the non-CVD group (55.7% vs. 30.6%, p = 0.006). The presence of RIPLs was significantly associated with CVD in SCAS patients (OR = 3.953 [1.695–9.219], p = 0.001) after adjusting for covariates. Subgroup analysis revealed greatest risk of bilateral RIPLs for CVD (OR = 7.383 [1.749–30.393], p = 0.006), followed by contralateral RIPLs (OR = 4.024 [1.432–11.306], p = 0.008) and ipsilateral RIPLs (OR = 2.951 [1.258–6.921], p = 0.013). Conclusions: The presence of RIPLs is significantly associated with CVD in SCAS patients. Findings of this research demonstrated that evaluation of RIPLs may help identify high-risk SCAS patients and facilitate special medical care for this group of patients.