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.
Triggianese P, Capparelli E, et al. • Frontiers in immunology • 2026
Patients with MCTD present subclinical retinal microvascular abnormalities detectable by OCT-A, with retinal vascular changes linked to disease duration, renal function, and complement levels.
Key Findings
Results
Patients with MCTD showed significant reductions in both superficial and deep retinal vessel density across all evaluated regions compared with healthy controls.
Study included 20 MCTD patients (mean age 60.6 ± 11.4 years, 85% females) and 20 age- and sex-matched healthy controls.
Reductions were observed in parafoveal, perifoveal, and foveal scans, whole images, and foveal avascular zones (FAZs).
Both superficial and deep capillary plexus vessel density were significantly reduced.
Elderly individuals were equally distributed between groups to control for age effects.
Results
Deep retinal vessel density in MCTD patients was inversely correlated with disease duration.
Correlation coefficient r = -0.6, P = 0.0003.
This suggests that longer disease duration is associated with greater loss of deep retinal microvascular density.
This finding was specific to the deep retinal vascular layer.
Results
Deep retinal vessel density in MCTD patients was directly correlated with estimated glomerular filtration rate (eGFR).
Correlation coefficient r = 0.4, P = 0.05.
Higher eGFR (better renal function) was associated with higher deep retinal vessel density.
Renal function data collected included both creatinine and eGFR measurements.
Results
C3 complement levels were positively correlated with both age and superficial parafoveal vessel density in MCTD patients.
C3 levels correlated with age: r = 0.4, P = 0.03.
C3 levels correlated with superficial parafoveal vessel density: r = 0.5, P = 0.008.
Both C3 and C4 complement levels were recorded for all MCTD patients.
This suggests a potential interplay between complement system activity and retinal microvascular integrity.
Results
Nailfold videocapillaroscopy abnormalities were present in 60% of MCTD patients but did not correlate with OCT-A findings.
NVC abnormalities occurred in 12 out of 20 MCTD patients (60%).
Abnormalities included non-specific microangiopathy and scleroderma patterns.
NVC was performed on four fingers of both hands.
The absence of correlation between NVC and OCT-A findings suggests retinal and peripheral microvascular involvement may represent distinct pathological processes in MCTD.
Background
OCT-A was used as the imaging modality to detect subclinical retinal microvascular changes in MCTD, a population not previously studied with this technique.
This was a cross-sectional exploratory pilot study design.
Prior to this study, subclinical retinal microvascular data were lacking specifically in MCTD patients, though such changes had been described in other connective tissue diseases.
OCT-A evaluated vessel density using parafoveal, perifoveal, and foveal scans, whole images, and FAZs.
The authors describe the study as 'hypothesis-generating.'
Triggianese P, Capparelli E, D'Antonio A, Nesi C, Lombardo M, Kroegler B, et al.. (2026). 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.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1724780