Corneal Stiffness and Tangent Modulus to Predict the Rate of Corneal Curvature Change in Corneal Reshaping Therapy
Phase: NA
Conditions: Myopia
Sponsor: The Hong Kong Polytechnic University

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Corneal Biomechanics and Corneal Reshaping Therapy 
NCT02719535 
March 25 2016 
 
(a) Introduction 
Myopia is highly prevalent in Asian populations, especially Chinese populations [1], and now 
affects Americans and Europeans as well.[2-3] Low to moderate myopia is not a major 
concern, but high myopia (more than 6D) is associated with retinopathy and glaucoma and is 
an economic burden on society.[4] 
 
Various treatment options have been proposed to reduce the progression of myopia, including 
the use of pharmaceutical agents and different types of corrective lenses. [5-8] Corneal 
reshaping, also called orthokeratology, is an intervention with proven efficacy in retarding 
myopia progression.[10] 
 
In orthokeratology, the corneal curvature is altered after a patient wears the lenses. The 
effective treatment range is usually not more than 5D of myopia and not more than 1.5D of 
astigmatism. In addition, orthokeratology can be slow or ineffective in some patients. This 
may be related to the pre-treatment corneal parameters such as the apical radius and 
eccentricity.[11] Corneal biomechanical properties may also be a factor, but accurate 
measurement of the influence is difficult.  
 
Most interventions for myopia control begin in early childhood. After commencement of the 
treatment, several years of continual monitoring is required to confirm its efficacy. If the 
intervention is eventually ineffective, then the time would have been wasted. The goal of the 
proposed study is to investigate whether corneal biomechanics are predictive of successful 
orthokeratology. If pre-treatment corneal biomechanics combined with other conventional 
corneal parameters do not indicate successful orthokeratology, patients can be advised to try 
other more effective interventions earlier. 
 
(b) Objectives 
1. To monitor the changes of corneal biomechanics from long-term (6 months) successful 
orthokeratology 
2. To determine if corneal biomechanics is predictive of the rate of orthokeratology  
 
(c) Methods 
Subjects 
Young, healthy, myopic adults with no history of long-term contact lens wear and ocular 
disease were recruited. Subjects who occasionally wear soft lenses (such as for sports) were 
eligible. The inclusion criteria included myopia between -4.00D and -5.00D sphere, and with-
the-rule astigmatism (axis 180  30) of not more than 1.50D, where the spherical equivalent 
was between -4.00D to -5.75D. The difference in myopia between the two eyes was within 
1D for both the sphere and cylinder components. The inclusion criterion in refractive error 
for this study is to eliminate the confounding factor for orthokeratology caused by a wide 
refractive range. The best-corrected visual acuity was at least 0.10 logMAR in each eye when 
measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) charts (Prevision 
Vision, La Salle, IL) under a normal room lighting condition.  
 
Procedures 

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The following baseline data were collected: non-cycloplegic manifest refraction, ocular 
biometry through partial coherence interferometry (Zeiss IOLMaster; Zeiss Humphrey, 
Dublin, CA), corneal topography (Medmont E300, Medmont Pty Ltd., Vermont, VIC, 
Australia), corneal thickness through swept-source optical coherence tomography (Casia SS-
1000, Tomey, Nagoya, Japan), and corneal biomechanics using an Ocular Response Analyzer 
(ORA; Reichert Inc., USA).  
 
Five valid axial length measurements were captured using the IOLMaster, and an average 
reading was generated for analysis. In corneal topography, three images (scores higher than 
95) were automatically captured. The mean value of the simulated steepest and flattest 
keratometry readings was used for analysis. Corneal thickness was measured using a “3D 
Corneal Map” scan by the swept-source optical coherence tomography. Three automated 
measurements were obtained for each scan while the subject focused on a central target inside 
the instrument. In ORA, three acquisitions were obtained each with a waveform score of at 
least 6.0. Corneal hysteresis (CH), corneal resistance factor (CRF), and corneal-compensated 
intraocular pressure (IOPcc) were measured. 
 
After all non-contact procedures, the cornea was anesthetized using one drop of 0.4% 
benoxinate. Intraocular pressure was measured using Goldmann applanation tonometry 
(GAT) followed by corneal biomechanics by using a corneal indentation device. Two GAT 
readings were taken and the mean result was used for analysis. The indenter first touched the 
central cornea. After the pre-load was stabilized (through an audible sound), the indenter 
moved forwards and backwards at 12mm/s to indent the cornea by 1mm. The indentation was 
completed in less than 0.25 seconds. The corneal stiffness was read from the device and the 
tangent modulus was calculated from the corneal radius of curvature and central thickness. 
Three corneal indentations were obtained, and the average was used for analysis. 
 
Lenses used  
After the suitability for wearing corneal reshaping lenses was confirmed through slit-lamp 
biomicroscopy, subjects were fitted with orthokeratology lenses. The lenses used were 
reverse geometry lenses (Menicon Z Night contact lens) made of super high gas permeable 
material (Menicon Z, DK 163 ISO). Lens fitting was based on the manufacturer’s instructions 
(Easy Fit Software, Menicon Co Ltd., Nagoya, Japan) according to ocular information, 
including corneal topography, non-cycloplegic manifest refraction, and horizontal visible lens 
diameter. Lens fitting was assessed with fluorescein. An optimal fluorescein pattern consisted 
of 3 to 4mm of central touch, 1 to 1.5mm of mid-peripheral pooling and 1 to 1.5mm of 
peripheral alignment. A bull’s eye fluorescein pattern was considered an optimum fit.  
 
Wearing schedule 
After a successful trial fit, a delivery visit was arranged. The subjects were returned to the 
clinic after an overnight lens wear. The same fluorescein pattern was maintained after 
overnight orthokeratology. The subjects wore the lenses every night and they were required 
to return regularly. Further follow-up visits were taken place after the first week, 1 month, 3 
months and 6 months of lens wear. Each visit was within two hours after waking up in the 
morning and the lenses being removed. 
 
In addition to corneal topography, corneal thickness, and corneal biomechanics 
measurements (using both ORA and corneal indentation device), subjective refraction and 
ocular biometry were included in all follow-up visits. Both the habitual and best-corrected 
visual acuities were measured.  

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Ethics clearance was obtained from the institutional review board of The Hong Kong 
Polytechnic University. Informed consent was obtained from all participants included in the 
study. This study was registered at ClinicalTrials.gov (NCT02719535, registered March 25, 
2016) and in the University of Hong Kong HKU Clinical Trials Register (HKUCTR-1957, 
registered Feb 1, 2016). 
 
Analysis of data 
The corneal parameters and refractive error obtained in each aftercare visit were compared 
with the baseline data. Data of one eye of each subject who completed the 6-month 
orthokeratology were analyzed, with the eye with residual sphere closer to plano at the 6-
month visit being selected. If the residual sphere was the same in both eyes, then the eye with 
less residual astigmatism was selected. For subjects with the same residual refractive errors in 
both eyes, the right eye was selected. Normality was checked using the Shapiro-Wilks test. 
Repeated-measure analysis of variance or the Friedman test were used to compare changes in 
ocular parameters throughout the study, that is, from baseline to the end of the 6-month 
orthokeratology. Baseline ocular parameters that could best predict myopia reduction were 
identified through linear regression (Pearson or Spearman). Reduction of sphere at the 6-
month visit was used as the dependent outcome response, and the various baseline ocular 
parameters were treated as independent predictors. All data analysis and graphical 
presentation were completed using SigmaPlot 13 (Systat Software, Inc.).  
 
(d) References 
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