Assessment of Corneal Biomechanical Changes After Discontinuation of Long-Term Orthokeratology: A 2-Year Prospective Study

Abstract

Purpose: This study investigated the long-term changes in the corneal biomechanical properties (CBPs) during and shortly after orthokeratology (ortho-k). We further explored the associations between selected CBPs and the effectiveness of ortho-k in mitigating axial elongation in patients with myopia.

Methods: This prospective 25-month follow-up study included children ages 8 to 16 years with low to moderate myopia undergoing ortho-k treatment. They underwent 24 months of ortho-k followed by 1-month discontinuation. Their ocular biometric parameters and CBPs were monitored throughout the study. Axial length was measured at baseline, at 1 month, and then every 6 months after ortho-k treatment.

Results: Dynamic changes in CBPs were observed during the 24-month ortho-k treatment. Parameters such as the stiffness parameter at the first applanation time (SP-A1), biomechanically corrected intraocular pressure, and Ambrósio's relational horizontal thickness showed initial reductions. After the 1-month discontinuation, most CBPs returned to baseline levels, except biomechanically corrected intraocular pressure and SP-A1. Multiple linear regression analysis revealed that differences in the deformation amplitude ratio or SP-A1 during the initial 2 weeks independently predicted axial elongation at 1 and 2 years after treatment initiation.

Conclusions: Long-term ortho-k treatment may lead to sequential variations in CBPs; however, most of these variations may be reversed within 1 month of discontinuation. Further, changes in the deformation amplitude ratio or SP-A1 values during the early stages of treatment may predict subsequent axial elongation.

Translational Relevance: This study highlights the value of corneal biomechanics in guiding myopia control during orthokeratology treatment in clinical practice.

Introduction

Orthokeratology (ortho-k) is an effective clinical approach that employs custom-designed rigid contact lenses to temporarily alleviate myopia. This technique involves the creation of a flat optical zone along with an elevated peripheral reshaping zone, which increases corneal refractive power.^1–7 Although the exact mechanism underlying myopia control by ortho-k remains unclear, researchers commonly hypothesize that it promotes a transition from a state of relative hyperopic peripheral defocus to relative myopic defocus in myopic eyes.⁸ The treatment effects of ortho-k, including corneal power shift,^9,10 treatment-zone sizing,^11,12 and changes in the epithelial thickness of certain sectors,¹³ are linked to its ability to induce corneal reshaping and alter the optical properties of the eye. The cornea has biomechanical properties such as elasticity and viscosity, and these can change with any disruption or modification of stromal structure.¹⁴ Therefore, the deformation caused by ortho-k can alter the physical dimensions and biomechanical properties of the cornea.^15,16 Understanding these biomechanical changes is essential to assessing the safety and efficacy of ortho-k treatment and its long-term effects on corneal health and visual outcomes. 

In Taiwan, ortho-k wearers usually replace their lenses every year. A 1-month discontinuation provides an opportunity to refit new lenses and make the necessary adjustments to the fitting profile. This ensures that the new lenses provide optimal vision correction and comfort. The 1-month discontinuation also offers a window to evaluate the long-term safety and effects of ortho-k treatment. By monitoring changes in corneal shape, thickness, and biomechanical properties during this period, clinicians can identify potential adverse effects that may not be apparent during continuous lens wear. 

The Corvis ST (OCULUS, Wetzlar, Germany) is a corneal biomechanical instrument equipped with an ultrahigh-speed Scheimpflug camera designed to capture the dynamic deformation of the cornea during an in vivo air pulse.¹⁷ Recent research¹⁸ has demonstrated the commendable repeatability of corneal biomechanical parameters (CBPs) in individuals undergoing ortho-k treatment when assessed using the Corvis ST. Correlations between CBPs and factors such as age, refraction, axial length (AL), and pre- and post-keratometry measurements have also been established.¹⁸ Subsequently, the Corvis ST has emerged as a valuable device for analyzing CBPs in individuals undergoing ortho-k treatment. A recent study suggested that the reshaping of the cornea and the effects on its biomechanical properties, in turn, affect the effectiveness of ortho-k in myopia control.¹⁹ 

To our knowledge, current evidence is limited regarding sequential alterations in CBPs assessed using the Corvis ST and their association with myopia control in ortho-k users. Additionally, studies investigating changes in CBPs after the discontinuation of ortho-k treatment are lacking. Previous studies have been limited by their cross-sectional designs¹⁹ and non-assessment of CBP changes after discontinuation.²⁰ 

Therefore, we conducted this prospective study to evaluate the serial changes in CBPs during 2 years of ortho-k treatment followed by 1 month of discontinuation. We also analyzed the relationship between CBP changes and axial elongation during ortho-k treatment. This study aimed to provide valuable insights into the dynamics of CBPs and their impact on myopia control in ortho-k users using longitudinal data obtained via assessments after treatment discontinuation. 

Methods

Study Design

This prospective 25-month follow-up study enrolled participants from October 2018 to April 2019 at the Hualian Tzu Chi Hospital in Taiwan, where baseline and follow-up examinations were conducted. It was conducted in accordance with the tenets of the Declaration of Helsinki and approved by the Institutional Ethical Committee Review Board of Hualien Tzu-Chi General Hospital (IRB approval number: IRB109-261-A). It is officially registered at ClinicalTrials.gov (registration number: NCT05090592). Every child involved in the follow-up received clear information and understood the study protocol. All participants and their parents or legal guardians formally acknowledged and signed a written informed consent form before participating in the study. 

Participants

Children 8 to 16 years old with low to moderate myopia undergoing ortho-k treatment were eligible for enrollment in this study. Participants with a history of systemic or ocular pathology, strabismus, or amblyopia; significant astigmatism (>3.50 diopters [D]); or previous use of myopia control treatment strategies were excluded from the study. Additionally, participants who were lost to follow-up, did not comply with continuous ortho-k lens wearing, failed to adhere to the test procedures/schedules, or had incomplete data were excluded from the analysis. Before initiating ortho-k treatment, several baseline ocular examinations were conducted. These included slit-lamp microscopy of the anterior and posterior eye segments, AL measurement, cycloplegic refraction, corneal topography, assessment of CBPs, and measurement of uncorrected and corrected visual acuity. 

Follow-up visits were scheduled at specific intervals following the initiation of ortho-k treatment. These intervals were at 1 week, 2 weeks, and 1 month, followed by every 3 months after lens delivery. During these visits, the participants underwent comprehensive ocular assessments to monitor treatment progress and any potential changes in ocular parameters. After 24 months of follow-up, ortho-k lens fitting was discontinued for 1 month for lens replacement. During this interval, assessments, including AL measurement, cycloplegic refraction, corneal topography, and evaluation of CBPs, were conducted to examine changes following the 2-week and 1-month discontinuation. 

Ortho-k Lenses

The ortho-k lenses used in this study (Taiwan Macro Vision Corporation, Taipei, Taiwan) had oxygen permeability (Dk) of 85 × 10⁻¹¹ cm³O₂/cm²s, 0.22-mm central thickness, and 10.6-mm diameter. The fitting profile is summarized as follows. We used fluorescein staining to observe the centration of the ortho-k lens, with a thin annular layer of tears trapped in the reverse curve forming a bull's-eye configuration. Good centration with appropriate tightness was defined as mild upward movement of the ortho-k lens after blinking. The same practitioner (CJC) fitted all ortho-k lenses using standardized criteria. All patients were advised to wear their ortho-k lenses every night for at least 8 consecutive hours. We followed the patients at 1 week, 2 weeks, and 1 month, followed by every 3 months after lens delivery. Notably, all patients who reported ocular discomfort were educated at an earlier visit. 

Measurements and Follow-Up

During the initial consultation, all patients underwent a comprehensive ocular health examination and complete cycloplegic assessment. Following the application of three drops of 1% tropicamide for 30 minutes, the KR-800 Auto Kerato-Refractometer (Topcon, Tokyo, Japan) was used for cycloplegic autorefraction, corneal power, and keratometry. AL data were acquired using an AL-Scan optical biometer (Nidek, Tokyo, Japan). Each measurement was repeated three times, and the resultant mean values were recorded. Follow-ups were scheduled at 1 week, 2 weeks, and 1 month, followed by every 3 months after lens delivery. AL measurements were performed at baseline, 1 month, and every 6 months after lens fitting. Inspections of the lens and lens case conditions at the location for ortho-k and all examinations were completed before 11 AM and within 2 hours of removal of the contact lenses. 

The Corvis ST (Type 72100) is a sophisticated instrument designed to measure CBPs using an ultra-high-speed Scheimpflug camera. Patients were instructed to position their chin on the chinrest and fixate on the internal red target. Before the examination, they were asked to blink twice to evenly distribute the tear film across the ocular surface. Each patient underwent three assessments at 5-minute intervals. To ensure measurement accuracy, only high-quality images were selected for further analysis. Corvis measurements were performed at baseline, 2 weeks, and 1 month, followed by every 6 months after lens delivery. After 24 months of follow-up, ortho-k lens fitting was discontinued for 1 month, and Corvis measurements were performed at 2 weeks and 1 month after discontinuation. The Corvis ST captures detailed images of the corneal response to a controlled air puff, allowing for precise assessment of corneal deformation dynamics in real time. Thus, more than 30 biomechanical parameters can be assessed, including the following: biomechanically corrected intraocular pressure (bIOP), the adjusted eye pressure reading; stress–strain index (SSI), which indicates corneal elasticity and stiffness; deformation amplitude (DA) ratio, which measures corneal flexibility; integrated inverse concave radius (Integr Radius), which assesses corneal curvature strength; Ambrósio's relational thickness horizontal (ARTh), which evaluates the risk of corneal thinning; and the stiffness parameter at the first applanation time (SP-A1), which is the corneal stiffness at the first deformation. These CBPs are crucial for understanding how ortho-k lenses reshape the cornea and influence its biomechanical properties. The reshaping of the cornea and the effects on its biomechanical properties, in turn, affect the effectiveness of ortho-k in myopia control.¹⁹ 

Statistical Analyses

All statistical analyses were performed using SPSS Statistics 21.0 (IBM, Chicago, IL), and only data from the right eye were used. Data are expressed as frequencies, proportions, or means ± standard deviations, depending on the characteristics of each item. The Shapiro–Wilk test was used to test whether a continuous variable followed a normal distribution. A paired t-test or Wilcoxon signed-rank test was used to determine significant changes in each CBP from the baseline to each follow-up visit. Trend analysis was also used to assess the effect of time on each CBP. Multiple linear regression was used to establish a predictive model for AL growth during the follow-up. In this study, two-tailed P values < 0.05 were considered statistically significant. We employed G*Power 3.1.9.2 (Heinrich Heine Universität Düsseldorf, Düsseldorf, Germany) to determine the requisite sample size for our study. The parameters were configured as follows: an effect size of 0.20, significance level (α) of 0.05, statistical power (1–β) of 0.80, one group, six measurements, a correlation coefficient of 0.5 among repeated measures, and a non-sphericity correction of 1, yielding an estimated sample size of 28. Accounting for an anticipated dropout rate of 20%, we aimed to enroll a minimum of 35 patients with myopia. 

Results

Baseline Characteristics

During our study, 63 patients were eligible at the baseline visit, and 26 were excluded for not complying with the test procedures or schedule or not cooperating with the continuous wearing of ortho-k lenses. Table 1 presents the demographic, baseline ocular, and biomechanical characteristics of the participants. Thirty-seven participants were included. They included 19 males (51.4%) and had a mean age of 11.43 ± 2.13 years. Their mean spherical equivalent (SE) was −2.85 ± 1.42 D, and their mean AL was 24.45 ± 0.86 mm. To prevent inter-eye correlations from influencing the results of the analysis, only measurement data from the right eye of each participant were included in the study. 

Table 1.

 

Demographic Data of the Study Population (n = 37)

 

Changes in CBPs After 2 Years and After 1-Month Discontinuation of Ortho-k Lens Treatment

The serial changes in the CBPs are shown in the Figure. Following lens treatment, several CBPs, including central corneal thickness (CCT), bIOP, Integr radius, and ARTh, demonstrated significant changes at the 2-week follow-up (Table 2). Over the 2 years of ortho-k treatment, bIOP, ARTh, and SP-A1 demonstrated a decreasing trend. Changes in CBPs after cessation are summarized in Table 3. Significant decrements in CCT, bIOP, ARTh, and SP-A1 were observed 2 weeks after treatment cessation. Most CBPs, except bIOP and SP-A1, returned to baseline levels at 1 month after discontinuation. 

Figure.

 

Serial changes in corneal biomechanical properties during 24 months of ortho-k treatment followed by 1-month discontinuation.

Table 2.

 

Changes in Biomechanical Parameters Before and After Orthokeratology Lens Wear During 2-Year Follow-Up

 

Table 3.

 

Corneal Biomechanical Changes From Baseline to 1 Month After Discontinuation

 

Prediction Model for Axial Elongation Using CBPs

Multiple linear regression analysis was conducted to develop a predictive model for AL growth during the follow-up (1 year and 2 years), incorporating various CBPs such as CCT, bIOP, SSI, DA ratio, Integr Radius, ARTh, and SP-A1. A simple linear regression model was initially employed for AL elongation at 1 and 2 years. CBP covariates at baseline, 2 weeks, and 1 month and changes observed at 2 weeks and 1 month were incorporated. Only covariates demonstrating marginal significance (P < 0.1) were considered for inclusion in the subsequent multiple linear regression analysis (Supplementary Table S1). The prediction model (Table 4) used only Integr Radius at baseline, Integr Radius at 2 weeks, and changes in the DA ratio and SP-A1 at 2 weeks. The R² values for the prediction model were 0.549 and 0.579 for AL increment at 1 year and 2 years, respectively. For both models, changes in the DA ratio and SP-A1 at 2 weeks were significantly associated with axial elongation of the eye. 

Table 4.

 

Multiple Linear Regression Model for Axial Elongation at 1 Year and 2 Years

 

Discussion

In this prospective study spanning 25 months (24 months of ortho-k treatment and 1 month of discontinuation), sequential changes in CBPs were observed. These led to several key findings. First, dynamic changes in CBPs, including decreasing trends in SP-A1, bIOP, and ARTh, were identified during the 24 months of ortho-k treatment. Second, most CBPs, except bIOP and SP-A1, reverted to baseline levels after 1 month but not after 2 weeks of discontinuation. Finally, the difference in the DA ratio or SP-A1 at 2 weeks was independently correlated with axial elongation at 1 and 2 years. 

The study identified significant changes in CBPs, including CCT, bIOP, Integr Radius, and ARTh, following 2 weeks of ortho-k treatment. Decreasing trends of the SP-A1, bIOP, and ARTh values were observed during the 2-year ortho-k treatment. A previous 24-month prospective study indicated substantial fluctuations in CBPs within the first week, followed by stability throughout a 2-year follow-up.²⁰ This stability may be attributed to the rapid adaptability of the epithelial cells that establishes a renewed equilibrium of intercellular forces. However, certain CBPs, such as SSI and ARTh, were not assessed in the previous study²⁰ despite their demonstrated repeatability for ortho-k users. Additional insights were provided by a 12-month study, which revealed that most CBP changes occurred approximately 6 months after ortho-k lens wear, with the values stabilizing thereafter.²¹ In contrast, the current study observed dynamic alterations in CBPs such as SP-A1, bIOP, and ARTh throughout the 2-year ortho-k treatment. The corneal epithelium is the main structure affected by the mechanical forces exerted by ortho-k lenses. However, previous research has indicated that stromal thickness and cell density are also affected, and epithelial changes are more prominent in the central area but stromal changes are more pronounced in the paracentral and peripheral areas.^22–24 Previous study²⁵ has suggested that stromal thickening may be due to an overnight edematous response. The positive pressure behind the lens may have a “clamping effect” that inhibits overnight central corneal swelling, resulting in gradual residual thickening in the stromal midperiphery.²⁵ This phenomenon may explain the ongoing changes in certain CBPs during ortho-k treatment. 

Regarding discontinuation effects, some studies^26,27 have reported a reversal of corneal topography toward baseline after ortho-k lens cessation. However, one study²⁸ reported that flat and steep keratometry values remained significantly different from the baseline following 1-month discontinuation after 3-year ortho-k treatment. In our study, keratometry values returned to baseline at 1 month after ortho-k treatment discontinuation (P = 0.115). Evidence regarding the recovery of CBPs after long-term ortho-k lens treatment is lacking. Our study showed that most CBPs, except bIOP and SP-A1, reverted to baseline values after 1 month but not after 2 weeks of discontinuation. This suggests the responsiveness of the cornea to external stresses induced by ortho-k and subsequent restoration to its original state and affirms the reversibility of the effects of prolonged ortho-k use. 

Several studies^19–21,29 have established a link between baseline or post-treatment CBPs and myopia control using ortho-k lenses. Xiang et al.²⁰ revealed that the maximum deformation amplitude was an independent factor for axial elongation in a 2-year prospective study. In a cross-sectional study, Li et al.¹⁹ showed a smaller ARTh after ortho-k treatment, indicating a better refractive state and slower AL progression, which could predict ortho-k treatment outcomes. Zhang et al.²¹ assessed dynamic corneal response parameters across different ages of patients with myopia using ortho-k lenses with the Corvis ST. Their study demonstrated that baseline ARTh and post-treatment CBPs, such as SSI and peak distance with the maximum amount of corneal movement, at 6 months were correlated with 1-year AL growth. The present study aimed to predict axial elongation of the eye using baseline and 2-week CBP values, as well as their 2-week changes. The findings indicated that the difference in the DA ratio or SP-A1 at 2 weeks was independently associated with the 1- and 2-year axial elongation, with a potentially stronger association observed for the DA ratio. A smaller reduction in the DA ratio at 2 weeks appears to be linked to better axial elongation control. These results may guide clinicians to optimize ortho-k treatment, as CBPs assessed with the Corvis ST can play a pivotal role in predicting AL progression. 

This study has several limitations. First, the sample in our study was small, which led us to refrain from conducting subgroup analyses to prevent further reducing the sample size. This decision was made to maintain the statistical robustness of the findings. Future studies with larger samples and the ability to conduct subgroup analyses should provide additional insights. Second, our examination focused on dynamic changes in CBPs over 24 months of lens wear, followed by a 1-month discontinuation. More data may be accrued with a longer duration of discontinuation, which could induce an AL rebound effect and not align with the ethical principles of myopia control. Finally, our study predominantly involved Chinese children, and caution should be exercised when generalizing these findings to other ethnic groups and geographical regions. Further multi-ethnic studies are essential to validate the applicability of our results across diverse populations. 

In conclusion, our study identified sequential changes in CBPs over 24 months after ortho-k treatment. Most CBPs returned to baseline levels at 1 month after discontinuation following long-term ortho-k treatment. Additionally, changes in the DA ratio or SP-A1 levels at 2 weeks may be linked to axial elongation of the eye at 1 and 2 years. These findings highlight the potential impact of ortho-k on corneal biomechanics and its implications for myopia control. 

Acknowledgments

Supported by a grant from the Hualien Tzu Chi Hospital (TCRD111-033). 

Disclosure: H.-R. Tsai, None; J.-H. Wang, None; C.-J. Chiu, None