this was a multi - institute , single - group clinical trial conducted at seoul st . approval was granted by the respective institutional review boards of each institute , and a clinical trial permit was obtained from the ministry of food and drug safety . this study was carried out in accordance with the tenets of the declaration of helsinki . at the screening visits , the investigators informed the subjects of the complete details of the clinical trial , after which the subjects signed a written consent form . we then obtained demographic information , history of ocular diseases , and current disease information from each subject and determined visual acuity , refractive error , corneal topography , slit - lamp microscopy , corneal endothelial cell count , central corneal thickness ( cct ) , intraocular pressure , schirmer 's test result , and tear break - up time . the inclusion criteria for subjects were as follows : ( 1 ) age between 7 and 49 years , ( 2 ) myopic refractive error of -0.75 to -6.0 diopters ( d ) and astigmatic refractive error of 1.25 to 4.0 d , ( 3 ) radius of corneal curvature within the range of 46.00 to 39.75 d ( 7.34 to 8.5 mm ) , ( 4 ) horizontal corneal diameter larger than 11.0 mm , ( 5 ) occupation and environment allowing wear of lenses for more than 7 hours during sleep , ( 6 ) ability to follow instructions during the clinical trial , and ( 7 ) willingness to participate in the clinical trial and provide signed written consent . the exclusion criteria were : ( 1 ) schirmer test result less than 10 mm or tear break - up time shorter than 10 seconds , ( 2 ) abnormal findings during slit - lamp microscopy ; inflammation , erosions , ulcers , or angiogenesis in the cornea after wearing the lens for a 30-minute trial period , ( 3 ) allergies , ( 4 ) eye diseases that would have made participation in the trial difficult as judged by the investigator , ( 5 ) contraindication for wearing contact lenses , ( 6 ) wearing of rgp lenses within the 2 weeks prior to the screening visit , ( 7 ) diagnosed strabismus , ( 8) past corneal refractive surgery , ( 9 ) pregnancy , nursing , or planning to become pregnant , and ( 10 ) significant disease that would have made participation in the clinical trial difficult as judged by the investigator . candidates who met any one of the above criteria were excluded from the trial . at the first visit ( day 1 ) , subjects tried the toric orthokeratology lenses prescribed at the screening visit and were informed of the precautions that must be taken when wearing the lenses , as well as the potential adverse reactions . slit - lamp microscopy was performed , the refractive error was measured , and any adverse reactions to wearing the lenses were assessed . fit was confirmed during slit - lamp microscopy , along with determination of abnormal corneal findings . to confirm fit , we verified that there was pressure on the cornea , and that a space was maintained between the back of the toric orthokeratology lens and the cornea . while monitoring the changes in the kerato - conjunctiva , the ocular status in each subject 's anterior segment moderate to severe scores in this test were considered as indicators of an adverse reaction . any other clinically significant findings in the kerato - conjunctiva were also recorded as adverse reactions . in cases of poor lens all subjects were instructed to wear the lenses for an average of 7 hours during sleep and to not wear the lenses during the day . the second visit ( day 2 ) took place 1 day after wearing the toric orthokeratology lenses overnight . both uncorrected visual acuity and refractive error were measured , and slit - lamp microscopy was performed . the same tests were repeated after 1 , 2 , and 3 weeks of lens wear . on the last visit ( week 4 ) , in addition to performing the tests described above , corneal endothelial cell count and cct were measured . the toric orthokeratology lenses used in the trial were toric lk lens ( lucid korea , bonghwa , korea ) . the primary outcome measures in this study were myopic and astigmatic refractive errors after toric orthokeratology lens use . for convenience of analysis , secondary study outcomes included visual acuity , corneal curvature , time to reach the target uncorrected vision of 16 / 20 after wearing the lenses . to assess safety , slit - lamp microscopy was performed , and the ocular status score in the anterior segment was recorded . corneal endothelial cell count and cct were also measured , and the total incidence of adverse reactions was evaluated . statistical analyses of myopic and astigmatic refractive errors were performed using a two - tailed , paired t - test . for all other outcomes we used a two - tailed , paired t - test or wilcoxon 's signed - rank test as appropriate . the change in ocular status score in the anterior segment , as determined using slit - lamp microscopy , was input into a split table ( frequency , ratio ) and analyzed using bowker 's test . for all statistics , a p - value < 0.05 was considered significant . for missing values and when subjects dropped out before the trial was completed , the data from the subject was not included in our analysis . at the screening visits , the investigators informed the subjects of the complete details of the clinical trial , after which the subjects signed a written consent form . we then obtained demographic information , history of ocular diseases , and current disease information from each subject and determined visual acuity , refractive error , corneal topography , slit - lamp microscopy , corneal endothelial cell count , central corneal thickness ( cct ) , intraocular pressure , schirmer 's test result , and tear break - up time . the inclusion criteria for subjects were as follows : ( 1 ) age between 7 and 49 years , ( 2 ) myopic refractive error of -0.75 to -6.0 diopters ( d ) and astigmatic refractive error of 1.25 to 4.0 d , ( 3 ) radius of corneal curvature within the range of 46.00 to 39.75 d ( 7.34 to 8.5 mm ) , ( 4 ) horizontal corneal diameter larger than 11.0 mm , ( 5 ) occupation and environment allowing wear of lenses for more than 7 hours during sleep , ( 6 ) ability to follow instructions during the clinical trial , and ( 7 ) willingness to participate in the clinical trial and provide signed written consent . the exclusion criteria were : ( 1 ) schirmer test result less than 10 mm or tear break - up time shorter than 10 seconds , ( 2 ) abnormal findings during slit - lamp microscopy ; inflammation , erosions , ulcers , or angiogenesis in the cornea after wearing the lens for a 30-minute trial period , ( 3 ) allergies , ( 4 ) eye diseases that would have made participation in the trial difficult as judged by the investigator , ( 5 ) contraindication for wearing contact lenses , ( 6 ) wearing of rgp lenses within the 2 weeks prior to the screening visit , ( 7 ) diagnosed strabismus , ( 8) past corneal refractive surgery , ( 9 ) pregnancy , nursing , or planning to become pregnant , and ( 10 ) significant disease that would have made participation in the clinical trial difficult as judged by the investigator . at the first visit ( day 1 ) , subjects tried the toric orthokeratology lenses prescribed at the screening visit and were informed of the precautions that must be taken when wearing the lenses , as well as the potential adverse reactions . slit - lamp microscopy was performed , the refractive error was measured , and any adverse reactions to wearing the lenses were assessed . fit was confirmed during slit - lamp microscopy , along with determination of abnormal corneal findings . to confirm fit , we verified that there was pressure on the cornea , and that a space was maintained between the back of the toric orthokeratology lens and the cornea . while monitoring the changes in the kerato - conjunctiva , the ocular status in each subject 's anterior segment moderate to severe scores in this test were considered as indicators of an adverse reaction . any other clinically significant findings in the kerato - conjunctiva were also recorded as adverse reactions . in cases of poor lens all subjects were instructed to wear the lenses for an average of 7 hours during sleep and to not wear the lenses during the day . the second visit ( day 2 ) took place 1 day after wearing the toric orthokeratology lenses overnight . both uncorrected visual acuity and refractive error were measured , and slit - lamp microscopy was performed . the same tests were repeated after 1 , 2 , and 3 weeks of lens wear . on the last visit ( week 4 ) , in addition to performing the tests described above , corneal endothelial cell count and cct were measured . the toric orthokeratology lenses used in the trial were toric lk lens ( lucid korea , bonghwa , korea ) . the primary outcome measures in this study were myopic and astigmatic refractive errors after toric orthokeratology lens use . for convenience of analysis , the astigmatic refractive error represented only corneal astigmatism not lenticular astigmatism . secondary study outcomes included visual acuity , corneal curvature , time to reach the target uncorrected vision of 16 / 20 after wearing the lenses . to assess safety , slit - lamp microscopy was performed , and the ocular status score in the anterior segment was recorded . corneal endothelial cell count and cct statistical analyses of myopic and astigmatic refractive errors were performed using a two - tailed , paired t - test . for all other outcomes we used a two - tailed , paired t - test or wilcoxon 's signed - rank test as appropriate . the change in ocular status score in the anterior segment , as determined using slit - lamp microscopy , was input into a split table ( frequency , ratio ) and analyzed using bowker 's test . for all statistics , a p - value < 0.05 was considered significant . for missing values and when subjects dropped out before the trial was completed , the data from the subject was not included in our analysis . in this clinical trial , a total of 79 eyes ( 44 subjects ) were screened at one of two trial - conducting institutes ; 40 eyes ( 21 subjects , 50.63% ) were excluded after screening , leaving a total of 39 eyes ( 23 subjects , 49.37% ) to be tested after lens use . details of the subjects ' eyes at registration are presented as a schematic diagram in fig . the mean age was 21.81  8.89 years , with a range of 7 to 39 years . there were no pregnancies among the 19 women of childbearing age that were included in the study . the mean myopic refractive error changed from -3.65  1.62 to -1.05  1.64 d after wearing the lenses for 4 weeks , which constituted a statistically significant decrease of 2.60  2.21 d ( p < 0.001 ) . the correction of myopia by toric or - thokeratology lenses resulted in a superior refractive state ( table 2 and fig . the mean astigmatic refractive error changed from 2.07  0.83 to 1.44  0.99 d after wearing the lenses for 4 weeks , which constituted a statistically significant decrease of 0.63  0.98 d ( p = 0.001 ) . the correction of astigmatism by toric orthokeratology lenses resulted in a superior refractive state ( table 2 and fig . the mean uncorrected and corrected visual acuities at the screening visit were 2.14  0.80 and 0.05  0.13 logmar , respectively . the equivalent values after wearing the toric orthokeratology lenses for 4 weeks were 0.12  0.30 and 0.01  0.04 logarithm of the minimal angle of resolution ( logmar ) , respectively . the difference in uncorrected visual acuity was -2.03  0.91 logmar , which was statistically significant ( p < 0.001 ) . the difference in corrected visual acuity was -0.04  0.14 logmar , which was not statistically significant ( p = 0.156 ) ( table 3 ) . after wearing the lenses for 1 week , corrected visual acuity was greater than 16 / 20 in 29 eyes ( 93.55% ) . all of the eyes achieved a corrected visual acuity greater than 16 / 20 after wearing the lenses for 2 weeks . at the screening visit , the mean corneal curvature was 42.54  1.06 d , and the mean corneal diameter was 11.78  0.28 mm . after wearing the toric orthokeratology lenses for 4 weeks , the mean corneal curvature was 40.92  1.38 d and the mean corneal diameter was 11.76  0.35 mm . a representative topographic pattern of corneal astigmatism is shown in fig . 4a and 4b . after treatment , the difference in corneal curvature was -1.62  0.96 d , which was statistically significant ( p < 0.001 ) . however , the difference in corneal diameter was -0.02  0.35 mm , which was not statistically significant ( p = 0.710 ) . the mean cct values before and after wearing the lenses were 560.21  38.64 and 545.76  61.37 m , respectively . the mean difference was -14.45  37.46 m , which constituted a statistically significant decrease ( p = 0.047 ) ( table 4 ) . cells / mm , which increased by 40.72  207.67 cells / mm to 3,237.28  277.25 cells / mm after 4 weeks of toric orthokeratology lens use . however , this difference was not statistically significant ( p = 0.300 ) . the difference in hexagonality was -0.07  12.07 , which was also not statistically significant ( p = 0.976 ) . the coefficient of variation before and after wearing the lenses was 0.31  0.05 and 0.33  0.07 . the difference of 0.02  0.06 was statistically significant ( p = 0.027 ) ( table 4 ) . the efron grading scale scores during the trial were normal for all eyes in all categories except for  corneal staining ,  in which 38 eyes ( 97.44% ) were normal , and one eye ( 2.56% ) was graded as trace before wearing the lenses . after 4 weeks of lens use , 25 eyes ( 80.65% ) were normal , four eyes ( 12.90% ) were graded as trace , and two eyes ( 6.45% ) were graded as mild . the difference in grading before and after lens use was not statistically significant ( p = 0.815 ) . a total of five adverse reactions developed in five subjects , consisting of one case of conjunctival hyperemia ( 3.23% ) , one case of  foreign body sensation in the eyes ( 3.23% ) , and two cases of , the adverse reactions ceased after the patients were prescribed additional artificial tears and were provided additional education regarding the proper wear and removal of the lenses . the mean myopic refractive error changed from -3.65  1.62 to -1.05  1.64 d after wearing the lenses for 4 weeks , which constituted a statistically significant decrease of 2.60  2.21 d ( p < 0.001 ) . the correction of myopia by toric or - thokeratology lenses resulted in a superior refractive state ( table 2 and fig . the mean astigmatic refractive error changed from 2.07  0.83 to 1.44  0.99 d after wearing the lenses for 4 weeks , which constituted a statistically significant decrease of 0.63  0.98 d ( p = 0.001 ) . the correction of astigmatism by toric orthokeratology lenses resulted in a superior refractive state ( table 2 and fig . the mean uncorrected and corrected visual acuities at the screening visit were 2.14  0.80 and 0.05  0.13 logmar , respectively . the equivalent values after wearing the toric orthokeratology lenses for 4 weeks were 0.12  0.30 and 0.01  0.04 logarithm of the minimal angle of resolution ( logmar ) , respectively . the difference in uncorrected visual acuity was -2.03  0.91 logmar , which was statistically significant ( p < 0.001 ) . the difference in corrected visual acuity was -0.04  0.14 logmar , which was not statistically significant ( p = 0.156 ) ( table 3 ) . after wearing the lenses for 1 week , corrected visual acuity was greater than 16 / 20 in 29 eyes ( 93.55% ) . all of the eyes achieved a corrected visual acuity greater than 16 / 20 after wearing the lenses for 2 weeks . at the screening visit , the mean corneal curvature was 42.54  1.06 d , and the mean corneal diameter was 11.78  0.28 mm . after wearing the toric orthokeratology lenses for 4 weeks , the mean corneal curvature was 40.92  1.38 d and the mean corneal diameter was 11.76  0.35 mm . a representative topographic pattern of corneal astigmatism is shown in fig . 4a and 4b . after treatment , the difference in corneal curvature was -1.62  0.96 d , which was statistically significant ( p < 0.001 ) . however , the difference in corneal diameter was -0.02  0.35 mm , which was not statistically significant ( p = 0.710 ) . the mean cct values before and after wearing the lenses were 560.21  38.64 and 545.76  61.37 m , respectively . the mean difference was -14.45  37.46 m , which constituted a statistically significant decrease ( p = 0.047 ) ( table 4 ) . the mean corneal endothelial cell count at the screening visit was 3,196.55  237.80 cells / mm , which increased by 40.72  207.67 cells / mm to 3,237.28  277.25 cells / mm after 4 weeks of toric orthokeratology lens use . the difference in hexagonality was -0.07  12.07 , which was also not statistically significant ( p = 0.976 ) . the coefficient of variation before and after wearing the lenses was 0.31  0.05 and 0.33  0.07 . the difference of 0.02  0.06 was statistically significant ( p = 0.027 ) ( table 4 ) . the efron grading scale scores during the trial were normal for all eyes in all categories except for  corneal staining ,  in which 38 eyes ( 97.44% ) were normal , and one eye ( 2.56% ) was graded as trace before wearing the lenses . after 4 weeks of lens use , 25 eyes ( 80.65% ) were normal , four eyes ( 12.90% ) were graded as trace , and two eyes ( 6.45% ) were graded as mild . the difference in grading before and after lens use was not statistically significant ( p = 0.815 ) . a total of five adverse reactions developed in five subjects , consisting of one case of conjunctival hyperemia ( 3.23% ) , one case of  foreign body sensation in the eyes ( 3.23% ) , and two cases of , the adverse reactions ceased after the patients were prescribed additional artificial tears and were provided additional education regarding the proper wear and removal of the lenses . with the introduction of orthokeratology by wesley and jessen in the early 1960s , many clinicians and researchers have attempted to correct myopia using rigid contact lenses ; however , these attempts have been limited by patient discomfort and hypoxic corneal damage . the development of rgp lens material combined with advancements in contact lens manufacturing technology has led to the development of overnight orthokeratology , which enables patients to wear myopia - correcting contact lenses during sleep . in overnight orthokeratology , the reverse - geometry lens is designed with both a flatter central curvature and steeper peripheral curvature such that a tear reservoir can be formed , and the lens is precisely placed in the corneal center . in 2000 , nichols et al . reported that overnight orthokeratology by the programmed application of rgp contact lenses with a reverse geometrical design is an effective means of temporarily reducing myopia . furthermore , they suggested a possible mechanism of corneal remodeling through central corneal thinning . a number of clinical trials to date have concluded that orthokeratology can effectively reduce moderate to high myopia , and control the progression of myopia . in addition , several reports have addressed the correction of astigmatism using orthokeratology lenses , although these effects are typically insufficient due to lens decentration . to address the issue of decentration , chen et al .   examined the efficacy of toric orthokeratology in correcting myopia combined with moderate to high astigmatism . in their study , subjects aged 6 to 12 years with myopia of 0.50 to 5.00 d and with with - the - rule astigmatism of 1.25 to 3.50 d were fitted with toric orthokeratology lenses . they reported that manifest myopia was significantly reduced from 2.53  1.31 to 0.41  0.43 d ( p < 0.001 ) , and that astigmatism was also decreased from 1.91  0.64 to 0.40  0.39 d ( p < 0.001 ) after 1 month of lens wear . similarly , in 2013 , chen et al .   conducted a non - randomized clinical study in which toric orthokeratology was found to effectively control myopia in children with accompanying moderate - to - high astigmatism . to our knowledge , this is the first prospective , multi - center clinical trial to have investigated the effectiveness of toric orthokeratology in korea . specifically , we evaluated the effectiveness and safety of toric orthokeratology lenses in patients with both myopia and astigmatism . patients wore the toric orthokeratology lenses during sleep for an average of 7 hours and for up to 4 weeks ( 28 days ) . the results showed than overnight toric orthokeratology reduced both myopia and astigmatism , although the degree of chance in astigmatism was relatively small . we attributed this small change to a weakened effect of the toric orthokeratology lenses to reshape the cornea during the night , as the subjects in this study visited our institute primarily in the afternoon . thus , additional studies regarding the clinical effectiveness of toric orthokeratology in correcting astigmatism are needed . unlike astigmatism , uncorrected visual acuity was significantly improved in our study , although there was no change in corrected visual acuity . thus , our results suggest that toric orthokeratology lenses do not change the ocular features associated with corrected visual acuity , which reflects the safety of this approach . a number of studies have suggested that various ocular parameters ( corneal thickness in particular ) are modifiable or predictive values for myopic reduction in orthokeratology . in 2000 , lui and edwards   reported that cct is the most predictive value of myopic reduction based on the results of a randomized controlled clinical trial involving 14 subjects who wore orthokeratology lenses during the daytime . specifically , they suggested that a thicker initial central cornea is associated with a greater reduction in myopia . .   conducted a meta - analysis that included a total of 10 studies with 339 eyes from 239 patients in order to assess the change to cct by orthokeratology lens use in myopic patients . they found that cct was reduced significantly between 1 day and 1 week , and that the most significant reduction occurred between 1 day and 1 month . in our study , cct was significantly decreased ( p = 0.005 ) after 4 weeks of lens wear but remained within the normal range . this might have been due to the reverse - geometry lens pressing down on the corneal center , causing rearrangement of the epithelium . among the five adverse reactions noted in five subjects during our trial , reactions exclusively concerning the lenses comprised four cases ( 12.90% ) , all of which were mild in nature and recovered fully . according to silt - lamp microscopy and other examinations of ocular parameters , there were no significant changes except for the cct and coefficient of variation , although cct remained within the normal range after 4 weeks . on the other hand , the change in coefficient of variation was considered to be a common effect of all types of contact lenses on corneal polymegathism , and the extent of the increase was not large relative to that noted in other studies . together , these data indicate that use of toric orthokeratology lenses does not cause any significant changes in ocular conditions . on the basis of these findings , our results suggest that toric orthokeratology lenses do not have any serious harmful effects . one limitation of this clinical trial was that the follow - up period was only 4 weeks . based on our results , the purpose of these studies should be to elucidate further aspects and complications of toric orthokeratology , such as maintenance of lens centration or changes in ocular features . in conclusion , the effectiveness of toric orthokeratology lenses in correcting myopia combined with astigmatism was verified statistically . orthokeratology lenses are currently limited to the correction of myopia ; however , our results provide an experimental basis for broadening the scope of orthokeratology lenses to include the correction of astigmatism . importantly , there were no notable adverse reactions or significant abnormal findings caused by use of toric orthokeratology lenses as determined by silt - lamp microscopy and other examinations . therefore , toric orthokeratology can be considered an effective and safe treatment for correcting visual acuity in patients with combined myopia and astigmatism .