Combination effect of optical defocus and low dose atropine in myopia control: Study protocol for a randomized clinical trial.

BACKGROUND: Myopia, characterized by excessive axial elongation of the eyeball, increases risks of having sight-threatening diseases and impose a financial burden to healthcare system. Although myopic control interventions showed their effectiveness in slowing progression, the efficacy varies between individuals and does not completely halt progression. The study aims to investigate the efficacy of combining 0.01% atropine administered twice daily with optical defocus for myopia control in schoolchildren. METHODS AND DESIGN: This is a prospective, parallel-group, single-blinded, randomized, active-control trial (ClinicalTrials.gov identifier: NCT06358755). Myopic schoolchildren with no previous myopic control interventions aged between 7 to 12 years will be recruited. They will be randomly allocated into two groups (n = 56 per group) after baseline measurement. Both groups will receive 0.01% atropine twice per day for 18 months (one drop in the morning and the other drop at night before bedtime). Defocus incorporated multiple segments (DIMS) spectacle lenses will be prescribed in atropine plus optical defocus (ATD) treatment group while single vision spectacle lenses will be given in atropine only (AT) group. Cycloplegic refraction and axial lengths will be monitored every 6 months over 18-month study period. The primary outcomes are changes in cycloplegic refraction and axial lengths relative to the baseline over the study period. DISCUSSION: The result will examine the combination effect of low dose atropine and myopic defocus on myopia control in a randomized controlled study. The findings will also explore the potential benefits of applying 0.01% atropine twice per day on myopic control and its potential side effects.

Association between long-term orthokeratology responses and corneal biomechanics.

Myopia is very prevalent worldwide, especially among Asian populations. Orthokeratology is a proven intervention to reduce myopia progression. The current study investigated association between baseline corneal biomechanics and orthokeratology responses, and changes of corneal biomechanics from long-term orthokeratology. We fitted 59 adult subjects having myopia between -4.00D to -5.00D with overnight orthokeratology. Corneal biomechanics was measured through dynamic bidirectional corneal applanation (in terms of corneal hysteresis, CH and corneal resistance factor, CRF) and corneal indentation (in terms of corneal stiffness, S and tangent modulus, E). Subjects with poor orthokeratology responses had lower E (mean 0.474 MPa) than subjects with good orthokeratology responses (mean 0.536 MPa). Successful orthokeratology for 6 months resulted in reducing CH (reduced by 5.8%) and CRF (reduced by 8.7%). Corneal stiffness was stable, but E showed an increasing trend. Among subjects with successful orthokeratology, a higher baseline S resulted in greater myopia reduction (Pearson correlation coefficient, r = 0.381, p = 0.02).

Influence of Short-Term Orthokeratology to Corneal Tangent Modulus: A Randomized Study.

PURPOSE: Influence of orthokeratology on corneal biomechanics is equivocal using Ocular Response Analyzer, ORA. Implementing indentation method, corneal tangent modulus was measured and monitored in short-term orthokeratology. MATERIALS AND METHODS: Sixteen young subjects with refractive errors between -4D to -5D sphere and astigmatism within -1.50D were recruited. One randomly selected eye wore orthokeratology lens (treatment), and the fellow eye wore conventional rigid gas permeable lens (control). Lenses were worn for 30 and 60 minutes and one night separately with a week of washout period in between. The first two visits were randomly scheduled and before the overnight visit. Eyes were kept closed during all the lens wearing periods. Corneal radius, thickness, and biomechanics (using both ORA and an indentation device) were compared between eyes prior to each visit, and then before and after lens wear. Associations between baseline corneal biomechanics and central cornea from overnight visit were investigated. RESULTS: Corneal parameters were similar in each visit before lens wear. Significant corneal flattening was observed in treatment eyes, and flattening increased with wearing time. Control eyes showed no significant corneal curvature changes. Corneal resistance factor (CRF) reduced by 0.42mmHg (± 0.68mmHg) after 30 minutes of orthokeratology treatment. Corneal hysteresis (CH) reduced by 0.42mmHg (+/- 0.63mmHg) in control eyes from overnight wear. Both eyes showed stable tangent modulus, E, throughout the study. A lower CH (r = 0.51, p = 0.046) and a higher E (r = 0.53, p = 0.037) at baseline was significantly associated with greater corneal flattening along the flattest meridian in treatment eyes. CONCLUSIONS: Short-term orthokeratology had no significant effect on corneal tangent modulus. Changes in CH and CRF could be related to their intrinsic measurement variability. Corneal tangent modulus provided another measure of corneal biomechanics. Long-term study is required to investigate predictive role of corneal biomechanics in orthokeratology.

In vivo measurement of regional corneal tangent modulus.

Currently available clinical devices are unable to measure corneal biomechanics other than at the central region. Corneal stiffness (S), thickness, and radius of curvature was measured at the central cornea (primary fixation) and 3 mm from the temporal limbus (primary and nasal fixations). The corneal tangent modulus (E) of 25 healthy subjects was calculated from these data. After confirming normality, repeated measures analysis of variance (RMANOVA) revealed significant difference in S (F(2, 48) = 21.36, p < 0.001) at different corneal regions and direction of fixations. E also varied significantly at different corneal regions and direction of fixations (RMANOVA: F(2, 48) = 23.06, p < 0.001). A higher S and a lower E were observed at the temporal region compared with the corneal centre. Nasal fixation further increased S and E values compared with primary fixation. Due to the specific arrangement of corneal collagen fibrils, heterogeneity of corneal biomechanical properties is expected. In future clinical practice, localized corneal biomechanical alternation and measurement might assist corneal disease detection and post-surgery management. In addition, practitioners should be aware of the fixation effect on corneal biomechanical measurement.

High myopes have lower normalised corneal tangent moduli (less 'stiff' corneas) than low myopes.

PURPOSE: To compare corneal tangent moduli between low and high myopes. METHODS: Corneal hysteresis (CH) and corneal resistance factor (CRF) of 32 low and 32 high myopes were obtained using an Ocular Response Analyzer, followed by a corneal indentation device that measured corneal stiffness. Corneal topography, pachymetry, Goldmann applanation tonometry intraocular pressure (GAT-IOP), and corneal compensated intraocular pressure (IOPcc) were also obtained. Corneal tangent modulus was calculated on the basis of corneal stiffness, central corneal thickness and corneal radius. Comparisons between groups and associations between corneal biomechanical and ocular parameters were performed. RESULTS: Corneal tangent moduli were positively correlated with GAT-IOP (R2 = 0.078, p = 0.025), and IOPcc (R2 = 0.12, p = 0.006). Despite similarity in corneal thickness and radius, high myopes exhibited a significantly higher IOPcc (16.4 ± 2.51 mmHg) than low myopes (13.1 ± 1.96 mmHg; t(62) = -5.57, p < 0.0001). Both groups had similar corneal stiffness (0.063 ± 0.0085 and 0.063 ± 0.0079 N mm-1 for low and high myopes, respectively) and CRF (9.6 ± 1.58 and 9.5 ± 1.90 mmHg for low and high myopes, respectively). Moreover, high myopes exhibited a significantly lower CH (9.5 ± 1.51 mmHg) than low myopes (10.6 ± 1.38 mmHg; t(62) = 2.92, p = 0.005). After normalising corneal tangent moduli to the mean intraocular pressure in normal eyes (15.5 mmHg) using IOPcc, high myopes showed a significantly lower corneal tangent moduli (0.47 ± 0.087 MPa) than low myopes (0.57 ± 0.099 MPa; t(62) = 4.17, p < 0.0001). CONCLUSIONS: High myopes had lower normalised corneal tangent moduli than low myopes, which indicated that their corneas were less stiff. This is the first in vivo study comparing elastic moduli of the cornea in different refractive groups. Further studies are warranted to understand whether a less stiff cornea is a cause for or an outcome from myopia development.

Diurnal Variation of Corneal Tangent Modulus in Normal Chinese.

PURPOSE: The aim of this study was to investigate the diurnal variation of corneal tangent modulus, measured using a novel corneal indentation device, in healthy Chinese subjects. METHODS: The central corneal thickness (CCT), mean central corneal radius (meanK), intraocular pressure (IOP), and corneal stiffness of 25 young adults aged 21 to 25 years (23.0 ± 1.0 yrs) were measured at 3-hour intervals from 09:00 to 21:00 in the course of 1 day. Corneal tangent modulus was calculated on the basis of corneal stiffness, CCT, and meanK. Repeated-measures analyses of variance were performed to compare the diurnal changes in ocular parameters over time. RESULTS: Significant diurnal variations were observed in CCT and IOP (P < 0.001 and P = 0.025, respectively). Both parameters showed a decreasing trend throughout the day. MeanK and corneal stiffness did not show any significant diurnal changes (P = 0.251 and P = 0.516, respectively). Mean corneal tangent modulus across all measurements was 0.047 ± 0.085 MPa, and its diurnal rhythm ranged from 0.469 to 0.485 MPa. The variation was nonsignificant (P = 0.526). CONCLUSIONS: The elastic properties of the cornea in healthy Chinese subjects were stable during wake time. The present study shows that the corneal indentation device obtains stable corneal biomechanics similar to other clinical devices. Future studies investigating the differences in corneal biomechanics among patients with various ocular conditions are warranted.

Repeatability of a novel corneal indentation device for corneal biomechanical measurement.

PURPOSE: The aim of the study was to evaluate the repeatability of a new device for measuring corneal biomechanics. METHODS: Twenty-nine normal subjects aged 20-28 years (23.4 ± 1.7 years) underwent measurements of corneal stiffness and tangent elastic modulus using a novel corneal indentation device. Corneal topography, axial biometry and Goldmann applanation tonometry were also performed during the visit. Subjects returned after about 1 week, at approximately the same time, and with the corneal biomechanics, corneal topography and Goldmann applanation tonometry measured again. Both the intrasession and intersession repeatability was assessed. RESULTS: Both the corneal stiffness and tangent elastic modulus demonstrated good intrasession repeatability (corneal stiffness: coefficient of variation = 7.32%, intraclass correlation coefficient = 0.75; tangent elastic modulus: coefficient of variation = 7.34%, intraclass correlation coefficient = 0.84). The mean modulus after normalised to normal intraocular pressure of 15.5 mmHg was 0.755 ± 0.159 MPa. There was no significant difference between the two visits (paired t-tests: p > 0.05). The repeatability [1.96 times the standard deviation (S.D.) of the intersession difference] of the corneal stiffness and the tangent elastic modulus was 0.0022 N mm(-1) and 0.197 MPa, respectively. CONCLUSION: The corneal indentation device has good intrasession and intersession repeatability. It has good potential to measure corneal biomechanics clinically, even at different corneal regions.

Correction on the distortion of Scheimpflug imaging for dynamic central corneal thickness.

The measurement of central corneal thickness (CCT) is important in ophthalmology. Most studies concerned the value at normal status, while rare ones focused on its dynamic changing. The commercial Corvis ST is the only commercial device currently available to visualize the two-dimensional image of dynamic corneal profiles during an air puff indentation. However, the directly observed CCT involves the Scheimpflug distortion, thus misleading the clinical diagnosis. This study aimed to correct the distortion for better measuring the dynamic CCTs. The optical path was first derived to consider the influence of factors on the use of Covis ST. A correction method was then proposed to estimate the CCT at any time during air puff indentation. Simulation results demonstrated the feasibility of the intuitive-feasible calibration for measuring the stationary CCT and indicated the necessity of correction when air puffed. Experiments on three contact lenses and four human corneas verified the prediction that the CCT would be underestimated when the improper calibration was conducted for air and overestimated when it was conducted on contact lenses made of polymethylmethacrylate. Using the proposed method, the CCT was finally observed to increase by 66 ± 34 µm at highest concavity in 48 normal human corneas.

Corneal deformation measurement using Scheimpflug noncontact tonometry.

PURPOSE: To determine the intraexaminer repeatability and intersession reproducibility of corneal deformation measurement using Scheimpflug noncontact tonometry (Corvis ST) on normal subjects. METHODS: Thirty-seven adults aged 20 to 48 years were invited to have their corneal deformation and curvature measurements taken using Corvis ST and Pentacam, respectively. Three consecutive measurements were taken for each instrument between 9:00 and 11:00 AM for intraexaminer repeatability analysis. Participants returned between 3:00 and 5:00 PM the same day for intersession reproducibility analysis. RESULTS: The most repeatable corneal parameter measured by Corvis ST was central corneal thickness ([CCT] ICC, 0.96; precision, 10.85 µm; repeatability, 15.34 µm; CV, 1.01%), followed by deformation amplitude ([DA] ICC, 0.80; precision, 0.08 mm; repeatability, 0.13 mm; CV, 4.33%), first applanation time ([1st A-time] ICC, 0.77; precision, 0.22 milliseconds; repeatability, 0.31 milliseconds; CV, 1.42), and intraocular pressure ([IOP] ICC, 0.75; precision, 1.39 mm Hg; repeatability, 1.97 mm Hg; CV, 4.98). Other parameters showed poor repeatability. The DA and 1st A-time showed good intersession reproducibility. The 95% limits of agreement were +0.13 to -0.13 mm for DA and +0.27 to -0.33 milliseconds for 1st A-time. The DA was negatively correlated with central corneal thickness (r = -0.53, p < 0.001) but not with corneal curvatures (flattest curvature, r = 0.13, p = 0.46; steepest curvature, r = 0.05, p = 0.75). CONCLUSIONS: Corneal deformation parameters DA and 1st A-time were repeatable and reproducible. A thinner cornea was associated with a higher corneal deformation. Measurement of DA serves as an indicator of corneal biomechanical properties.

Repeatability of corneal biomechanical measurements in children wearing spectacles and orthokeratology lenses.

PURPOSE: To determine the repeatability of corneal hysteresis (CH) and corneal resistance factor (CRF) measurements in children wearing spectacles and children under orthokeratology (ortho-k) therapy using the Ocular Response Analyzer (ORA). METHODS: CH and CRF were measured twice at a 10-min interval using ORA on the same day in both eyes of 25 children (mean age = 10.6 ± 1.2 years) wearing spectacles and 34 children (mean age = 10.9 ± 1.0 years) wearing ortho-k lenses. Four measurements were obtained from each eye in each set of measurements. Only data from the right eyes were analyzed. RESULTS: No significant between-measurement differences in CH and CRF were found in either group of subjects (paired t-tests, p > 0.05) and no correlations were found between the mean differences and their means (Pearson's correlations, -0.09 < r < 0.21, 0.24 < p < 0.85). The 95% limits of agreement (LA) were -1.87 mmHg to +2.59 mmHg and -1.53 mmHg to +1.41 mmHg for CH and -1.86 mmHg to +2.22 mmHg and -1.45 mmHg to +1.57 mmHg for CRF in the spectacle and ortho-k groups, respectively. A significant between-group difference in CRF was found (unpaired t-tests, p = 0.02). CONCLUSIONS: Repeatability of CH and CRF measurements using the ORA is within ± 2 mmHg in children wearing spectacles or ortho-k lenses. We suggest that the ORA can be used to monitor long-term corneal biomechanical changes during ortho-k treatment.