Systemic Vascular Contributions to Inactive Dysthyroid Optic Neuropathy: Beyond Mechanical Compression

Purpose: To investigate systemic vascular contributions-spanning microvascular, macrovascular, and molecular levels-to inactive dysthyroid optic neuropathy (DON) beyond the traditional model of mechanical compression. Methods: This cross-sectional comparative study enrolled 52 patients with thyroid-associated ophthalmopathy (TAO), categorized into DON (n = 32) and non-DON (n = 20) groups with comparable orbital apex crowding, and 23 healthy controls. Participants underwent optical coherence tomography angiography (OCTA) to assess superficial macular vessel density (mVD). Systemic macrovascular status was evaluated via internal carotid artery calcification (ICAC) on computed tomography and pulse pressure (PP). Molecular assessments included blood lipids and endothelial injury markers, specifically nitric oxide (NO). Results: Patients with inactive DON exhibited significant microvascular rarefaction, with reduced mVD compared to both controls and non-DON patients (P < 0.002). DON was also associated with a higher prevalence of macrovascular pathology, including ICAC (48.3% vs. 21.7%; P = 0.017) and elevated PP (P = 0.001). At the molecular level, DON was linked to dyslipidemia (elevated triglycerides, P = 0.001; reduced high-density lipoprotein, P = 0.014) and endothelial dysfunction (lower NO; P = 0.033). Reduced mVD correlated significantly with both ICAC and PP (P < 0.033), linking systemic and ocular vascular injury. Conclusions: Inactive DON was associated with abnormalities across retinal microvascular, systemic macrovascular, and circulating biomarker domains. These findings support further investigation of a model in which systemic vascular vulnerability may interact with local orbital compression. Translational Relevance: Assessment of systemic vascular risk may complement conventional orbital evaluation in patients with DON. Prospective studies are required to determine whether optimization of thyroid and vascular status can improve prevention or treatment.