Although microaneurysms (MAs) are a hallmark lesion of diabetic retinopathy, it is unclear why some MAs result in local neural retinal pathology while others are benign. To address this issue, longitudinal follow-up of MAs with adaptive optics scanning laser ophthalmoscopy (AOSLO) and spectral domain optical coherence tomography (SDOCT) was performed. AOSLO MA images were graded for wall hyperreflectivity (WH), wall deformability (WD), cross-sectional area and perfusion percentage. SDOCT images were graded within a 500μm zone centered on each MA for disorganization of the retinal inner layers (DRIL). Fluorescein angiography evaluated leakage in a subset. A total of 457 MAs of 102 eyes (57 subjects: mean±SD age 44±12 years, DM duration 23#x00B1;10 years, 61% male, 73% type 1 DM) were assessed over 843 visits (154 MAs with ≥1 visit and mean follow-up of 0.52#x00B1;0.35 years). At baseline, MAs with WH were larger (p≤0.0001), less perfused (p≤0.0001), and associated with DRIL (p=0.002). There was a borderline trend for such MAs to leak fluorescein (p=0.05). Over time, MAs with resolved WH had greater likelihood of DRIL improvement. Conversely, MAs that developed WH had more DRIL worsening (p=0.005). WH change vs. stability was associated with decreased perfusion over time (p≤0.0001). At baseline, WD was associated with smaller MAs (p≤0.0001) and increased perfusion (p≤0.0001), but was not related to fluorescein leakage or DRIL. WD resolution and development were associated with decreased and increased perfusion, respectively (p≤0.0001), but not with change in DRIL. These data suggest that whereas WH is a feature of more mature, larger and less perfused MAs associated with local neural pathology, WD may be present in earlier-stage MAs that are smaller and more fully perfused. Future studies will determine whether these parameters can be used to predict changes in MA size, perfusion, leakage or local neural retinal pathology over time.
J.K. Sun: Other Relationship; Self; Novartis Pharmaceuticals Corporation. Research Support; Self; Genentech, Inc., Optovue, Incorporated, Boston Micromachines Corporation, Adaptive Sensory Technology, Kalvista Pharmaceuticals, Inc.. Other Relationship; Self; Novo Nordisk Inc.. O. Abu-Qamar: None. K. Sampani: None. W. Fickweiler: None. L.P. Aiello: Consultant; Self; Novo Nordisk Inc., Sanofi Genzyme. Stock/Shareholder; Self; Kalvista Pharmaceuticals, Inc.. Consultant; Self; Kalvista Pharmaceuticals, Inc..