Highlights
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Children treated with orthokeratology are likely to develop pigmented arcs.
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The sector I2 on wide epithelial thickness map has the highest association with pigmented arc severity.
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The wide epithelial thickness map can be a usable tool for new generation orthokeratology development including pigmented arc–free lens.
Abstract
Purpose
To determine the intensity of corneal pigmented arc in orthokeratology (ortho-k)-treated children and its correlation with wide epithelial thickness map (ETM) obtained through anterior segment optical coherent tomography (AS-OCT).
Methods
This retrospective case series reviews medical records of children who received ortho-k treatment for myopia control. Intensity of ortho-k-associated pigmented arc after wearing ortho-k lens more than 12 months and its correlation with each sector/zone of wide ETM obtained by AS-OCT was explored. Pigmented arcs were further divided into apparent and unapparent groups, and the clinical differences between groups were determined.
Results
This study included 57 eyes of 29 children (mean age, 11.4 years, range 9–15); after initiating ortho-k treatment, the incidence of the corneal pigmented arc was 91.2% with mean lens wear duration of 26.1 months. Intensity of pigmented arc was significantly correlated with lens wear duration, target power, baseline degree of myopia, C zone and sectors I2, I3 and IT3 on wide ETM. Comparison between apparent and unapparent groups showed the same significant results except for C zone. After adjusting for lens wear duration and target power, sector I2 has the highest association with pigmented arc severity.
Conclusion
Children treated with ortho-k are likely to develop ortho-k-associated pigmented arcs. The new wide ETM of AS-OCT can provide important information regarding the intensity of pigmented arc in these children. This can support customized pigmented arc-free ortho-k treatment for children in the future.
1
Introduction
The number of children receiving self-paid orthokeratology (ortho-k) therapy for myopia control is increasing [ ]. Ortho-k corrects refractive errors in patients with myopia by using reverse-geometry rigid gas permeable lenses [ ]. After routine overnight use, ortho-k lenses can flatten the central cornea while steepening the peripheral cornea, such that vision is clear during the day without correction [ ]. In addition to achieving temporary improvement in unaided daytime visual acuity, studies have reported that using ortho-k can slow myopia progression [ ]. Ortho-k lenses can reshape the cornea by changing the corneal epithelium [ ], and this effect can be stabilized after 1–3 months of lens wear [ ]. Although wearing ortho-k lenses can slow myopia progression and correct refractive errors [ ], they are associated with corneal complications, such as corneal pigmented arc, superficial corneal epithelial damage, and corneal ulcer [ ].
Few studies have focused on the development and resolution of pigmented arcs in ortho-k-treated children [ ]. Cho et al. [ ] determined the pigmented arc incidence and intensity in a small number of ortho-k-treated adults and children, and found the intensity of pigmented arc was correlated with lens wear duration, ortho-k target power and patient’s baseline degree of myopia. Since myopia usually stabilizes after adulthood, the duration of lens wear among children is expected to be longer [ , ]. Therefore, the positive correlation between lens wear duration and intensity pigmented arc merits attention and caution [ , ]. Cho et al. also described that 2 ortho-k-treated patients who wore ortho-k lenses for approximately 1 year had their pigmented arcs disappear after cessation of ortho-k lens use for 2 months [ ]. However, these studies did not analyse the cornea epithelium directly, and the long-term effect of the ortho-k-associated pigmented arc on the cornea remains unknown. Efforts should be made to prevent pigmented arc development to further improve the safety of ortho-k treatment, especially among children.
The precise aetiology of the pigmented arc remains unclear. It can occur after iron deposition in the basal layer of the corneal epithelium, which may be due to a sudden change in the corneal curvature with subsequent pooling of tears in the reverse curve coverage area [ , , ]. Furthermore, the pigmented arc is usually dominant in the inferior part, though the reason for this also remains unclear [ , ]. In sum, the inferior part of the reverse curve may play the most important role on the intensity of pigmented arc. However, clinicians are rarely able to modify the reverse curve design due to patents on each ortho-k product.
Anterior segment optical coherence tomography (AS-OCT) is a noncontact technique which generates high-resolution cross-sectional imaging of cornea tissue using low-coherence interferometry [ ]. Studies have reported that AS-OCT can accurately measure the corneal epithelial thickness after wearing ortho-k lenses [ , ]. However, these studies used an epithelial thickness map covering only the central 6 mm cornea of ortho-k-treated patients [ , ], but the entire ortho-k lens was above 10 mm in diameter. This limited their applications on peripheral corneal change after ortho-k treatment. By using newly released software for the AS-OCT device (Avanti RTVue XR; Optovue, Inc., Fremont, CA, USA), the 3-dimensional corneal epithelial structure up to 9 mm in diameter and a wide epithelial thickness map (ETM) can be generated. A recent study demonstrated that the intensity of pigmented arc was correlated with some key epithelial thickness parameters in ortho-k-treated patient under wide-field pachymetry scan pattern obtained from this AS-OCT [ ]. Nevertheless, the precise relationship between the sector/zone on wide ETM and the intensity of pigmented arc in ortho-k-treated children remains unclear. Since the relationship between wide ETM and intensity of pigmented arc may be a direct reference for developing customized pigmented arc-free ortho-k treatment. This study determines the correlation between the intensity of pigmented arc and wide ETM using AS-OCT measurements.
2
Materials and methods
2.1
Patients
This retrospective case series includes children aged 9–15 years who had received ortho-k treatment for myopia control for the first time, enrolled from the ortho-k continuous follow-up (OKCFU) open cohort database. The database follows patients with continuous ortho-k use and it contains the complete medical records and detailed examinations of patients who had received ortho-k treatment at the Keelung Chang Gung Memorial Hospital, Keelung, Taiwan since January 2015. The study was approved by the Institutional Review Board of Chang Gung Memorial Hospital (Approval No.: 201800215b0) and followed the tenets of the Declaration of Helsinki.
2.2
Exclusion criteria
Excluded patients included those who (1) wore their ortho-k lenses overnight for <90 % of the follow-up period, (2) developed complications after wearing ortho-k lenses, (3) discontinued lens wear for >1 week, (4) were lost to follow-up in < 12 months after initiation of ortho-k treatment, (5) did not receive AS-OCT more than 6 months after initiation of ortho-k treatment, or (7) wore ortho-k lenses of brands other than DreimLens® (Brighten Optix Co., Taiwan).
2.3
Ocular examination
All patients received scheduled ocular examinations before and after initiating ortho-k treatments. The pre-treatment tests included best-corrected visual acuity, baseline degree of myopia measured after complete cycloplegia together with corneal power (Auto Ref/Keratometer ARK-1a/ARK-1; Nidek, Gamagori, Aichi, Japan), slit-lamp biomicroscopy (BQ 900, Haag-Streit AG, Koeniz, Switzerland), corneal topography (Orbscan IIz; Bausch & Lomb, Rochester, New York, USA), external eye photography and axial length measurement (IOLMaster 500, Carl Zeiss Meditec AG, Jena, Germany). The post-treatment tests included best-corrected and uncorrected distance visual acuity measurement, slit-lamp biomicroscopy before and after fluorescence staining of the cornea, and periodical axial length measurements according to the physicians’ experience. AS-OCT (Optovue RTVue XR Avanti, Optovue Inc., Fremont, CA, USA) with a 9-mm wide pachymetry scan for wide ETM was applied to examine the eyes of children after at least 6 months of ortho-k lens wear. The latest measured wide ETM of each patient was collected for analysis.
2.4
Ortho-k lenses
All patients were treated with ortho-k lenses by DreimLens® (Brighten Optix Co., Taiwan), including non- and astigmatism-design lenses. Astigmatism-design lenses were prescribed for children to achieve better centration when necessary. The ortho-k lenses had a reverse-geometry design. The overall and back-optical-zone diameters of the ortho-k lenses were 10.2–10.8 and 6 mm, respectively, and the peripheral zone width was 0.4 mm. The prescription included only target power, diameter and alignment curve power (two alignment curve powers for astigmatism-design lenses). Other lens design parameters were not adjusted. The target power was prescribed with a full correction power measured by sum of the power measured by an auto refractometer (ARK-1a; Nidek, Aichi, Japan) and the power of trial ortho-k lens after complete cycloplegia. All studied patients had uncorrected visual acuity exceeding 18/20 one month after initiation of lens wear. All ortho-k treatments were prescribed by one of three ophthalmologists (C. F. Liu (49 eyes), C. C. Sun (4 eyes), and H. M. Chen (4 eyes)).
2.5
Optical coherence tomography
Fourier-domain OCT with a corneal adaptor module was used. Fig. 1 A and B demonstrate the wide ETM of left eye on a patient obtained by the AS-OCT. The system works at the wavelength of 830 nm and provides an axial resolution of 5 μm and a transverse resolution of 15 μm. The wide ETMs were generated by an experienced technician using a wide-field pachymetry scan pattern (PachymetryWide Scan, RTVue XR software version 2017.1.0.151. eight radial lines with 9-mm scan length, 1056 axial scans each radial line, repeated four times) that centred on the pupil [ , , ]. The epithelial thickness was calculated as the distance between the air–tear interface (first curve) and the epithelium–Bowman’s layer boundary (second curve). OCT image processing and verification were conducted by adjusting the first and second curves to fit the real corneal contour, according to the manufacturer’s guidelines. The wide ETMs were also used to check all scanning lines matching the real contour of different layers by the disappearance of the central island on the map ( Fig. 1 B). S.Y. Peng verified all scanning lines with caution [ ].
A wide ETM with 9 mm diameter was generated and automatically divided by the system into a central 2-mm zone and 3 circular ringed areas by diameter. These were denoted as C zone (central 2-mm circular zone), R1 (paracentral 2–5 mm), R2 (mid-peripheral 5–7 mm), and R3 (peripheral 7–9 mm). R1, R2, and R3 were further divided into 8 sectors each. Each sector was named with reference to a previous study [ ], as illustrated in Fig. 1 C. The average epithelial thickness of each sector/zone was recorded for further statistical analysis.
2.6
Pigmented arc grading
The all pigmented arcs were graded by C. F. Liu at each patient visit. Pigmented arcs were directly graded using a slit lamp with narrow decentered slit white beam without filter and wide-beam with blue light according to the scale in Cho et al. [ ]. In brief, grade 0 represents no detectable pigmented arc; grade 1, arcs detectable under white light, but not visible with blue light; grade 2, arcs easily observed under both white and blue light but with ill-defined margins; and grade 3, arcs very easily observed under both white and blue light and have well-defined margins. Patients were further divided into two groups according to the severity of pigmented arcs: apparent (grades 2 and 3, blue-light detectable) and unapparent pigmented arc (grades 0 and 1, blue-light undetectable) groups for further analysis.
2.7
Statistical analysis
The data were analysed using SPSS (version 20.0; SPSS, Chicago, IL, USA). Statistical significance was defined using a 2-tailed P value of <0.05. The intensity of pigmented arc after initiation of ortho-k lens wear and its correlation with epithelial thickness of each sector/zone on wide ETM as well as ortho-k treatment parameters were determined using Spearman correlation test. Patients were divided into 2 groups according to intensity of the pigmented arc: apparent (grades 2 and 3) and unapparent (grades 0 and 1) pigmented arc groups. Categorical and continuous data were analysed using chi-square and independent-samples t tests, respectively. Fisher’s exact test was used when 1 or more of the cells in the chi-square test had an expected value of <5. The significant variables obtained from correlation analysis and two groups comparison results were further analysed with univariate and multivariable binary logistic regression adjusted for lens wear duration and target power (using only target power instead of adjusting together with baseline degree of myopia due to high correlation between them, ρ = 0.925, P < 0.001, Spearman correlation test). The apparent and unapparent pigmented arc groups were served as dependent variable.
3
Results
Medical records for 88 eyes of 46 children were reviewed. Fifteen eyes from 8 children were excluded because they were lost to follow-up before 12 months after ortho-k treatment; 12 eyes from 7 children were excluded due to <90 % overnight ortho-k lens wear for the follow-up period; 2 eyes of 1 child were excluded due to a suspected infection; and 2 eyes of 1 child were excluded due to insufficient AS-OCT data. A total of 57 eyes from 29 patients (age range, 9–15 years) were included in the final analysis.
Table 1 summarizes demographic and ortho-k treatment data of studied patients. Mean age of patients was 11.4 (range, 9–15) years. After initiating ortho-k lens, the incidence of the corneal pigment arc was 91.2 % with the mean lens wear duration of 26.1 months.
| Parameters | Cases (n = 57) |
|---|---|
| Starting age (years old) (range) | 11.4 ± 1.9 (9–15) |
| Gender (male: female) | 15: 14 |
| Target power (D) (range) | 3.44 ± 1.28 (1.50–6.00) |
| Diameter (mm) (range) | 10.56 ± 0.15 (10.20–10.80) |
| Alignment curve a (D) (range) | 42.60 ± 1.10 (39.50–45.25) |
| Initial apical radius b (D) (range) | 42.88 ± 1.14 (39.63–45.63) |
| Baseline degree of myopia c (D) (range) | 3.63 ± 1.66 (1.38–7.63) |
| Astigmatism-design lens (yes: no) (eye) | 28: 29 |
| Mean AS-OCT exam time point (months) (range) | 21.0 ± 6.9 (10.5–36.7) |
| Lens wear duration (months) (range) | 26.1 ± 7.2 (12.6–39.3) |
| Incidence of pigmented arc (%) | 91.2 |
a Astigmatism prescription using average alignment curve power for calculation.
b Initial apical radius was calculated as the average of the flattest and steepest corneal apical radius.
c Baseline degree of myopia was calculated as a spherical equivalent.
Table 2 summarizes the correlation of pigmented arc with each sector/zone of epithelial thickness parameters and ortho-k treatment data. Intensity of the observed pigmented arc was significantly positively correlated with epithelial thickness of sectors I2, I3, and IT3 and negatively correlated with that of C zone. It was also positively and significantly correlated with lens wear duration, ortho-k target power and patient’s baseline degree of myopia.
| Mean ± SD | ρ | P value | |
|---|---|---|---|
| AS-OCT wide epithelial thickness map | |||
| Central 2 mm (μm) | 45.1 ± 4.0 | −0.354 | 0.007 * |
| R1 (2−5 mm) | |||
| S1 (μm) | 53.0 ± 5.6 | 0.237 | 0.076 |
| SN1 (μm) | 53.7 ± 5.2 | 0.084 | 0.536 |
| N1 (μm) | 52.7 ± 5.5 | −0.148 | 0.272 |
| IN1 (μm) | 51.7 ± 5.9 | −0.116 | 0.391 |
| I1 (μm) | 50.0 ± 5.8 | −0.007 | 0.961 |
| IT1 (μm) | 48.5 ± 5.8 | −0.152 | 0.259 |
| T1 (μm) | 48.9 ± 5.5 | −0.196 | 0.144 |
| ST1 (μm) | 51.0 ± 5.5 | 0.087 | 0.521 |
| R2 (5−7 mm) | |||
| S2 (μm) | 50.8 ± 5.0 | 0.152 | 0.260 |
| SN2 (μm) | 52.2 ± 4.3 | 0.140 | 0.300 |
| N2 (μm) | 53.7 ± 4.5 | −0.047 | 0.731 |
| IN2 (μm) | 55.8 ± 4.8 | 0.213 | 0.112 |
| I2 (μm) | 57.3 ± 6.1 | 0.414 | 0.001 * |
| IT2 (μm) | 56.3 ± 5.2 | 0.226 | 0.091 |
| T2 (μm) | 54.3 ± 5.5 | 0.027 | 0.843 |
| ST2 (μm) | 52.3 ± 5.7 | 0.032 | 0.814 |
| R3 (7−9 mm) | |||
| S3 (μm) | 44.2 ± 5.7 | 0.085 | 0.527 |
| SN3 (μm) | 45.8 ± 4.5 | 0.124 | 0.359 |
| N3 (μm) | 51.8 ± 4.1 | 0.064 | 0.638 |
| IN3 (μm) | 54.1 ± 4.3 | 0.207 | 0.122 |
| I3 (μm) | 55.7 ± 4.2 | 0.451 | 0.001 * |
| IT3 (μm) | 55.8 ± 4.7 | 0.315 | 0.017 * |
| T3 (μm) | 53.2 ± 5.1 | 0.186 | 0.127 |
| ST3 (μm) | 48.3 ± 5.0 | 0.150 | 0.266 |
| Ortho-k treatment parameters | |||
| Starting age (years old) | 11.4 ± 1.9 | 0.109 | 0.420 |
| Lens wear duration (months) | 26.1 ± 7.2 | 0.519 | 0.001 * |
| Target power (D) | 3.44 ± 1.28 | 0.441 | 0.001 * |
| Diameter (mm) | 10.56 ± 0.15 | 0.086 | 0.523 |
| Alignment curve a (D) | 42.60 ± 1.10 | 0.058 | 0.668 |
| Initial apical radius b (D) | 42.88 ± 1.14 | 0.125 | 0.354 |
| Baseline degree of myopia c (D) | 3.63 ± 1.66 | 0.459 | 0.001 * |
| Compression d (D) | −0.28 ± 0.33 | −0.075 | 0.580 |
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