Author: Wan, Kin
Title: Structural changes in the anterior eye associated with long term orthokeratology using different compression factors
Advisors: Cho, Pauline (SO)
Wolffsohn, James (SO)
Orr, Janis (SO)
Degree: Ph.D.
Year: 2021
Award: FHSS Faculty Distinguished Thesis Award (2021/22)
Subject: Orthokeratology
Contact lenses
Hong Kong Polytechnic University -- Dissertations
Department: School of Optometry
Pages: 211 pages : color illustrations
Language: English
Abstract: Background : The high and rapid rise in the prevalence of myopia has led to increased interest in the development of interventions to slow axial elongation in myopic children. Although orthokeratology (ortho-k) has been shown to be the most promising optical intervention, the potential factors affecting the treatment outcome (refractive correction and myopia control effectiveness), and its long-term effects on the thickness of various corneal layers, and corneal biomechanical properties in children are still unclear. A new technique, optical coherence tomography (OCT) allows high-resolution cross-sectional images across the cornea to be captured within seconds. This makes the investigation of long-term thickness changes in the various corneal layers in children possible. Analysis of the waveform signal generated by the Ocular Response Analyzer (ORA) could potentially provide more information and monitor more precise long-term corneal biomechanical changes induced by ortho-k lens wear. In addition to slowing axial elongation, ortho-k can temporally reduce refractive errors and provide clear daytime vision. However, studies have shown that the targeted reduction may not be achieved in some cases and the conventional compression factor (Jessen factor) employed by current ortho-k lens designs may not be sufficient. Theoretically, by increasing the compression factor, it may be possible to reduce the likelihood of under-correction in ortho-k. In addition, characteristics of corneal topographical changes induced by ortho-k lens wear have been shown to be associated with effectiveness of myopia control: a larger reduction in myopia may lead to slower axial elongation. Increasing the compression factor is likely to manipulate corneal topographical characteristics, which may enhance the retardation of axial elongation. Currently, the effects of increased compression factors are unclear. Objectives : 1. To investigate differences in characteristics of ortho-k subjects who demonstrated fast axial elongation compared to those with slow elongation. 2. To investigate long-term changes in corneal biomechanical properties induced by ortho-k lens wear. 3. To determine the effect of long-term ortho-k lens wear on the corneal epithelial layer and corneal thickness in children. 4. To investigate the characteristics of ortho-k subjects who could achieve the targeted correction, compared with those who could not. 5. To investigate the effects on safety, lens performance, refractive correction, axial elongation, corneal (overall and sub-layers) thickness, and biomechanical properties of children wearing ortho-k lenses with increased compression factor of 1.00 D. Methods : Five studies were conducted on myopic children to address the above objectives. 1. A retrospective study to investigate differences in characteristics of children who demonstrated fast axial elongation compared with slow elongation. (Addressing objective 1) 2. A study to investigate the repeatability of the waveform signal parameters derived from Ocular Response Analyser (ORA) measurement. (Addressing objectives 1, 2, 4, and 5) 3. A study to develop a novel algorithm for automatic corneal, overall, and sublayer thickness measurements from the images obtained from the anterior OCT and the repeatability of this technique. (Addressing objectives 1, 2, and 4) 4. A short-term self-controlled study to investigate corneal responses and the refractive changes in ortho-k treatment using lenses of conventional (CCF) and increased compression factor (ICF). (Addressing objectives 4 and 5) 5. A 2-year longitudinal study to investigate the long-term anterior segment changes induced by wearing CCF and ICF ortho-k lenses. (Addressing objectives 1, 2, 3, and 5)
Results : Study 1. There were no significant differences in baseline demographics between control and ortho-k group (p > 0.1010). Axial elongation was significantly associated with initial age in both control (p = 0.0122) and ortho-k group (p = 0.0151). In the control group, as well as age, corneal hysteresis (CH) was associated with axial elongation (p = 0.0181) but in the ortho-k group (p = 0.1136). Subjects with fast progression (10 subjects with the fastest axial elongation in each group) were significantly younger than those with slow progression (10 subjects with the slowest axial elongation) for both the control and ortho-k groups (p < 0.05). No significant difference in age was found between the fast-progressing and slow-progressing subjects in each sub-group (p > 0.99). There were significant differences in CH and corneal resistance factor (CRF) among the four sub-groups (p < 0.05) after controlling for potential covariates (age, central corneal thickness, and intraocular pressure). Significantly lower CH and CRF were observed in the fast-progressing control subjects (p < 0.05), but not in their counterparts in the ortho-k group (p > 0.99). Study 2. There were no significant differences in demographic data between the control and ortho-k groups (p > 0.2821). No statistically significant between-group differences for any of the waveform signal parameters were found (p > 0.05). Based on intraclass correlations [ICCs (95% confidence interval, CI)], CH [0.92 (0.83 ­ 0.96)] and CRF [0.96 (0.90 - 0.98)] yielded excellent agreement. For waveform signal parameters, h2, h21, p1area, p1area1, p2area, and p2area1 yielded moderate to excellent agreement [ICCs (95% CI) of 0.82 - 0.85 (0.61 - 0.93)]. However, Bland-Altman plots showed a relatively wide spread of between-measure variation. The mean differences (95% limits of agreement, LoA) were [-3.64 (-101 to 94), h2], [­2.43 (-67.56 to 62.70), h21], [111 (-723.02 to 946), p1area], [102 (-334 to 539), p1area1], [24.89 (-718 to 768), p2area] and [-3.26 (-350 to 343), p2area1]. No significant between-measurement differences were observed (p > 0.05). Study 3. There were no significant between-measure differences in overall corneal and epithelial thickness at any of the locations along the horizontal 6 mm cornea (at 0.5 mm intervals) (p > 0.1233). The mean between-measure differences were less than 0.27 µm for both corneal and epithelial thickness at either the central 3 mm or mid-peripheral (4 - 6 mm) cornea. The 95% LoA were -5.10 to 5.01 µm (central corneal thickness), -6.21 to 6.73 µm (mid-peripheral corneal thickness), -3.48 to 3.72 µm (central epithelial thickness), and -3.35 to 2.80 µm (mid-peripheral epithelial thickness). Study 4. A faster rate of refractive reduction (p < 0.0001) was observed in eyes fitted with ICF ortho-k. A higher portion of ICF eyes had achieved full correction (residual spherical equivalence refraction ≥ -0.50 D) at the 1-week visit (p=0.0169). The between-eye outcome at 4-week visit was not significant (p = 0.6425). No significant between-eye differences in corneal staining (both coverage and depth) were observed (p > 0.05). Treatment zone diameter (TZD), as shown by the corneal topographical changes at the 4-week visit, was significantly smaller in ICF eyes (p = 0.0221). The width of the annular steepened zone (ASZ) was significantly wider in ICF eyes (p = 0.0290). CRF and intraocular pressure decreased significantly after one month of ortho-k lens wear (p < 0.0001), although no significant changes were observed in CH, h2, h21, p1area, p1area1, p2area, or p2area (p > 0.0612). No significant between-eye differences were noted for corneal biomechanical properties and intraocular pressure (p > 0.05). At the 1-week visit, the central corneal and epithelial thicknesses were significantly thinner than baseline and remained thinner at subsequent post-ortho-k visits (p < 0.0001). Central epithelial thickness was significantly thinner in ICF eyes than in CCF eyes at 2-week and subsequent visits (p < 0.0201). ICF eyes that did not achieve their target correction showed higher baseline refractive errors. Study 5. Mild over-correction was maintained throughout the whole study period in the ICF subjects, whereas CCF subjects became mildly myopic by the 12­month visit. Between-group differences in manifest sphere was significant at the 12­month visit and thereafter (p < 0.0122). Axial elongation was 34% slower in the ICF group, compared to the CCF group at the end of the 2-year lens wear period (p < 0.0001). The central epithelium became significantly thinner at the 6-month and subsequent visits and the mid-peripheral epithelium significantly thicker at the 12­month and subsequent visits (p < 0.0001) in both ortho-k groups, but there were no significant differences between the two groups (p > 0.2038). No significant changes and between-group differences were observed in corneal biomechanical properties (p > 0.05), or corneal health (p > 0.2821). The averaged maximum tangential power changes at ASZ, as showed by the corneal topographical changes, were significantly higher in the ICF group at the 6-month (p = 0.0160) and 18-month (p = 0.0183) visit. Subjects showing relatively fast axial elongation were younger, the second peak of the waveform signal generated by ORA had a different profile, and a higher plus power of manifest refractive error. The difference in the profile could indicate poor energy damping ability of the cornea (or the eye) in fast progressing subjects. Conclusions : Subjects who were fast progressors showed statistically significant differences in baseline corneal biomechanical properties compared to relatively slow progressors. These differences might imply a cornea with a poorer ability in dissipating energy. However, no firm conclusion could be drawn because of the substantial between-measure variability of the ORA measurements. Long-term (two years) ortho-k lens wear induced no significant corneal biomechanical changes in terms of the parameters generated by the ORA but induced central epithelial thinning and mid-peripheral epithelial thickening. Central epithelial thinning occurred before the onset of peripheral thickening. By comparing the magnitude of changes in thickness of the whole cornea and the epithelium, it appeared that the origin of changes at central and mid-peripheral cornea was likely to be from the epithelium. ICF eyes that could not achieve the target reduction within a month had higher baseline refractive errors. First fit success rate, corneal health, short-term refractive changes, long-term corneal topographical characteristics, long-term corneal biomechanical properties, and long-term corneal thickness within the central 6 mm did not significantly differ between ICF and CCF groups. However, the effectiveness in slowing axial elongation was enhanced with ICF over the 2-year period of treatment.
Rights: All rights reserved
Access: open access

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