Reduced retinal microvascular density in patients with mixed connective tissue disease: an exploratory pilot study on the interplay between aging, renal function, and complement system

Background: Mixed connective tissue disease (MCTD) is a systemic autoimmune disease with overlapping features with systemic lupus erythematosus, systemic sclerosis, and inflammatory idiopathic myopathies, characterized by anti-U1-RNP antibodies. Although subclinical retinal microvascular changes have been described in other connective tissue diseases, such data are lacking in patients with MCTD. Methods: We performed a cross-sectional exploratory pilot study including patients with a defined diagnosis of MCTD according to one of the sets of classification criteria and age- and sex-matched healthy controls (HC), with elderly individuals equally distributed. Data on disease duration, renal function (creatinine and eGFR), and complement levels (C3 and C4) were recorded. All participants underwent optical coherence tomography angiography (OCT-A) to evaluate retinal vessel density (VD) using parafoveal, perifoveal, and foveal scans, whole images, and foveal avascular zones (FAZs). Nailfold videocapillaroscopy (NVC) was performed in patients with MCTD on four fingers of both hands to assess microangiopathy patterns. Results: Patients with MCTD (n = 20, mean age 60.6 ± 11.4 years, 85% females) showed a significant reduction in both superficial and deep retinal VD across all evaluated regions compared with 20 HC. In patients with MCTD, deep retinal VD was inversely correlated with disease duration (r = −0.6, P = 0.0003) and directly correlated with eGFR (r = 0.4, P = 0.05). In patients with MCTD, C3 levels were positively correlated with age (r = 0.4, P = 0.03) and superficial parafoveal VD (r = 0.5, P = 0.008). In MCTD, NVC abnormalities, including non-specific microangiopathy and scleroderma patterns, occurred in 60% (n = 12) of cases and did not correlated with OCT-A findings. Conclusion: Patients with MCTD present subclinical retinal microvascular abnormalities detectable by OCT-A. Our hypothesis-generating study suggests that retinal vascular changes may be linked to disease duration, renal function, and complement levels. OCT-A may be a useful tool for assessing MCTD.