In current study, subjects with smaller TZS and larger TZD benefited from a greater slowing of myopia progression with 12 months orthokeratology. Multiple regression showed that initial age, baseline SE and TZD were significantly associated with axial growth.
Initial age and baseline spherical equivalent
Many studies have examined factors that influence axial growth during orthokeratology treatment, and initial age and baseline SE have been reported to be critical factors in affecting axial growth. In our study, both initial age and baseline SE were significantly correlated with axial growth in multiple linear regression (Table), with older children and greater baseline SE associated with smaller axial growth. Other studies have reported differing associations. Zhong et al. reported that initial age did not affect axial length growth on 32 children aged 9–14 years old in a 24-month follow-up study.24 In contrast, Rubido et al. reported that initial age is significantly negatively correlated with axial length growth,25 and Wang et al. demonstrated that older initial age at the onset of orthokeratology lens wear was correlated with reduced axial growth in myopic children.26 The current study agreed with the results of the studies by Wang et al. and Rubido et al. and demonstrated that initial age significantly affected myopia control in orthokeratology treatment.
The association between axial growth and baseline SE has also been debated. In studies that reported a significant negative correlation between axial growth and baseline SE, the subjects had a wider baseline SE range, typically between -6.0 and -1.0 D.26, 27 In studies that reported a lack of association between baseline SE and axial length growth, the subject's baseline SE was in a limited middle range, mostly between -4.0 and -1.0 D.8, 28 In our current study, we found that older initial age and greater baseline SE were beneficial in slowing the progression of myopia in children receiving orthokeratology treatment for twelve months follow up.
Treatment zone decentration
TZD is a common phenomenon in orthokeratology clinical practice and is difficult to avoid. Many factors may contribute to TZD, such as corneal asymmetry, lens fitting, lens diameter, corneal astigmatism.29-31Smaller lens diameter and greater corneal astigmatism are more likely to result in lens offset and TZD.31 Traditional orthokeratology guidelines encourage clinicians to pursue perfect centering with a bull’s-eye pattern during orthokeratology lens fitting. In traditional orthokeratology practice, there is no clear guideline on how much TZD should be allowed and how hard one should push for perfect centering.
In the current study, the mean TZD was 0.52 ± 0.22 mm (range 0.05–1.24 mm) which was in line with previous studies. Li et al. reported a mean TZD of 0.68 ± 0.35 mm (range 0.05–1.49 mm) from a study of 106 subjects,21 and Chen et al. reported a mean TZD of 0.72 ± 0.26 mm (range 0–1.34 mm).31 In the current study where 352 subjects were analyzed, we found that the TZD was significantly negatively correlated with axial growth (Figure 2C, P < 0.001), and our study, therefore, provides evidence to clarify the relationship between TZD and the slowing of myopia progression with orthokeratology treatment for twelve months follow-up. subjects increased TZD was beneficial in controlling myopia, with relatively larger TZD associated with smaller axial growth (Figure 4A). Nevertheless, we state that the trends between TZD and axial growth would need a longer period of study to confirm. We do not suggest deliberate decentration of the orthokeratology lens, as large TZD can cause visual discomfort, such as ghosting and visual fatigue.32, 33 It is important to identify subjective sensations caused by TZD and then decide whether it is necessary to adjust the lens parameters.
Treatment zone size combined with treatment zone decentration
TZS and TZD were two previously neglected factors for myopia control effectiveness, compared with the known factors such as initial age and SE at baseline. We found that in subjects with smaller TZS, larger TZD was associated with the smallest axial growth (0.06 mm per year, Figure 4A). In subjects with larger TZS, smaller TZD was associated with the largest axial growth (0.23 mm per year, Figure 4A). There was no axial growth difference between subjects with both smaller TZS and smaller TZD and those with both larger TZS and larger TZD (P = 0.3212, Figure 4A). When multiple linear regression was used to control for the contribution from initial age and baseline SE, only TZD was significantly associated with axial growth. The reason for TZS being excluded by multiple regression may be that only one design of orthokeratology lens was used in the current study (Euclid, back optic zone diameter is 6.2mm), which may result in a large range of TZS (6.89–15.7 mm2, radius 1.48 to 2.24mm) with continuous boundary. Two different orthokeratology lens designs (different in TZ diameter and same total lens diameter) should be included in further research. Multiple linear regression is necessary to identify the factors that independently influence axial growth.
The potential mechanism
The mechanism of orthokeratology in control of myopia progression is still not clear. We hypothesized that orthokeratology induces myopia defocus in relative peripheral refractive error interfering the axial length growth pattern as “peripheral refraction theory”, which has been recognized by most researchers.34-36 Cho et al.37 hypothesized that the greater the corneal reshaping effect, the greater peripheral myopic defocus, the higher the regulation efficacy in retarding myopia progression. Yang et al.38 suggested that areal summed corneal power shift (ASCPS) in a 4 mm area was a potential predictor of axial elongation in orthokeratology treatment. Wang et al.19 agreed that a maximum value of post-treatment corneal relative power (PCRP) resulted in a higher probability of effective axial elongation control. Zhong measured the relative corneal refractive power shift (RCRPS) in the nasal, temporal, and inferior axes and found that the maximum changes were negatively correlated with 2-year axial growth.24 With a decentered treatment zone or a smaller treatment size, the reverse zone which has positive RCRPS moves closer to the apex. This could lead to a larger summed RCRPS within a 4 mm area, which agrees with the study by Yang et al.38Given the same pupil size, TZD, and a smaller TZS, the summed RCRPS within the pupillary zone would be much greater in corneal power profiles, which would agree with the larger pupil size often associated with smaller axial growth.18 We speculate that a smaller TZ and a higher decentered one will move the mid-peripheral ring inside the pupil if it is of the appropriate size, inducing higher optical changes that may be beneficial for myopia control in the subjects receiving orthokeratology treatment. However, in current retrospective study we did not measure the pupil size and RCRPS directly, we will incorporate these factors in the further prospective study. Another potential mechanism may be that corneal shape asymmetry is increased with orthokeratology TZD. Corneal shape asymmetry increases higher-order corneal aberrations.18, 39 Hiraoka et al. found that increased corneal coma was significantly associated with decreased axial growth in orthokeratology treatment.22