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Purpose The purpose of this study was to determine the change in over-refraction, if any, after a scleral lens settled on the eye for 6-8 h. Methods Sixteen patients of varying refractive errors and normal corneal curvatures (measured with Pentacam™ Oculus) were fitted with trial Mini-Scleral Design (MSD) scleral lenses (15.8 mm diameter) in one eye. The sagittal depths of the scleral lenses were selected by adding 350 μm to the corneal sagittal heights measured at a chord length of 15 mm with the Visante™ optical coherence tomographer (OCT) anterior segment scans and picking the closest available trial lens in the set. Initial measurements were taken 30 min after lens insertion and included an auto-refraction, subjective refraction, and best sphere refraction over the contact lens. Visual acuities and Visante™ OCT anterior segment scans were also taken. These measurements were repeated after 6-8 h of lens wear. Results Over the trial wearing period, the average change in the spherical component of the over-refraction was +0.06 D (S.D. 0.17) ( p = 0.16). The average change in cylinder was +0.04 D (S.D. 0.19) ( p = 0.33). The average absolute change in axis was 1.06° (S.D. 12.11) ( p = 0.74). The average change in best sphere was +0.13 ± 0.30 D ( p = 0.12). There was no significant change in visual acuity with the best sphere over-refraction over the 6-8 h wearing period. There was a significant change in central corneal clearance over the wearing period of 83 μm (S.D. 22) ( p < 0.0001). Conclusion Despite a significant change in the central corneal clearance due to thinning of the fluid reservoir as the scleral lens settled (an average decrease of 83 μm after wearing the lenses for 6-8 h), there was not a statistically significant change in the subjective over-refraction (sphere, cylinder, and axis) or best sphere or visual acuity. This study has confirmed that there is no link between reduction in central corneal clearance and change in over-refraction for average corneas. [ABSTRACT FROM AUTHOR]