Objective To investigate the changes in corneal topography and tear film with overnight orthokeratology treatment. Methods Twenty teenagers (40 eyes) with low and moderate myopia (-2.37±0.82)D, aged 11.8±1.8, were included in the study and fitted with Ortho-K CLs. Subjective refraction, corneal topography, tear break up time (TBUT), lipid layer patterns,tear volume (phenol red thread) and corneal fluorescein staining were checked. All of the measurements were taken at pre-wear and 1 day, 1 week, 1 month and 3 months after orthokeratology. Repeated measurement of variance analysis, Spearman correlation analysis, and Pearson correlation analysis were used in analyzing the data. Results All measurements changed significantly during the treatment: ①The degree of myopia (spherical equivalent refractions) was reduced by (-2.01±0.60)D within the first week; ②Corneal topography: corneal curvature decreased by (-1.85±0.87)D, corneal eccentricity (e value) decreased by 0.13±0.14, and the surface regularity index (SRI) increased by 1.05±0.37 within the first week after orthokeratology treatment; ③TBUT also decreased by (5.43±3.38)s at the time of the 1-week visit. After the first week, all of the above changes decreased slightly and stabilized; ④ The main lipid layer patterns which were flow and colored fringes (70%) at pre-wear, changed to mamoreal and flow patterns after treatment (80%, 95%, 90% and 62.5% at 1 day, 1 week, 1 month and 3 months, respectively); ⑤There were no significant changes in tear volume during the 3 months of orthokeratology treatment (P>0.05), except for an increase by (2.15±5.43)mm at the time of the 1-day visit; ⑥Eyes with corneal fluorescein staining increased and were mainly grade Ⅰ during the treatment; ⑦Along with the lipid layer becoming thicker, TBUT increased along with an increase in corneal fluorescein staining. A decrease in TBUT and a variation in SRI had a negative correlation with the variation in TBUT during the follow-up study (P<0.05). Conclusion All subjects have significantly re