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To evaluate the effect of lipid- versus sodium hyaluronate-based eye drops on optical quality and ocular surface parameters.Sixty eyes of 30 patients with mild-to-moderate dry eye disease were included in a prospective randomized study. Each patient received either lipid- or sodium hyaluronate-based eye drops. Ocular symptom scores, breakup time, Schirmer test, fluorescein staining, noncontact meibography, and aberrometry were evaluated before and after 3 months of therapy.At the 3-month visit, a statistically significant improvement (P ≤ 0.05) was noted in both groups on the Schirmer test, breakup time, ocular surface staining, and symptom score. In the lipid group, patients with progressive meibomian gland (MG) loss (>50%) showed a significantly greater increase in their corneal higher-order (HO) Strehl ratio (0.25 ± 0.26 vs. −0.01 ± 0.25, P = 0.02) and modulation transfer function (MTF) (0.12 ± 0.17 vs. −0.02 ± 0.06, P = 0.03) than patients with less advanced MG disease. In the lipid group, a significant positive correlation was noted between the MG dropout rate and improvement in Schirmer values [Spearman correlation coefficient (CC): 0.79], corneal HO Strehl (CC: 0.75), and HO modulation transfer function (CC: 0.6), but a significant negative correlation was noted between the MG dropout rate and the HO root mean square (CC: −0.73).Lipid-containing artificial tears seem to be superior to sodium hyaluronate-containing drops in terms of improving HO aberrations and optical quality in patients with significant MG dysfunction.