Abstract
Objective
To determine the repeatability limits of corneal tomography parameters in patients with advanced and moderately thin keratoconic corneas to assist in planning thickness-based procedural interventions.
Methods
Prospective, single-centre, repeatability study. Three tomography scans using the Pentacam AXL were obtained from patients with keratoconus with thinnest corneal thickness (TCT) ≦400 µm (sub-400 group) and compared to those with TCT = 450–500 µm (450-plus group). Eyes with previous crosslinking, intraocular surgery, or acute corneal hydrops were excluded. Eyes were age and gender-matched. The within-subject standard deviations for flat keratometry (K1), steep keratometry (K2), maximal keratometry (Kmax), astigmatism and TCT were used to calculate respective repeatability limits (r). Intra-class correlation coefficients (ICC) were also analysed.
Results
The sub-400 group comprised 114 eyes from 114 participants, and the 450-plus group comprised 114 eyes from 114 participants. In the sub-400 group, TCT was amongst the least repeatable parameters (33.92 µm; ICC 0.96), compared with the 450-plus group (14.32 µm; ICC 0.99, p < 0.01). In the sub-400 group, K1 and K2 of the anterior surface were the most repeatable parameters (r 3.79 and 3.22 respectively; ICC 0.97 and 0.98 respectively) compared with the 450-plus group (r 1.17 and 0.92 respectively; and ICC 0.98 and 0.99 respectively, p < 0.01).
Conclusions
The repeatability of corneal tomography measurements is significantly reduced in sub-400 keratoconic corneas when compared to 450-plus corneas. Repeatability limits should be carefully considered when surgical interventions are planned for such patients.
Subject terms: Outcomes research, Tomography
Introduction
Keratoconus is a non-inflammatory, thinning disorder of the cornea that leads to progressive corneal irregularity, resulting in debilitating disease that may significantly affect patients’ quality of life [1, 2]. Keratoconus has been reported to occur in 1 in 2000 people worldwide [3]. Corneal tomography is integral to guiding treatment decisions in keratoconus [2], especially for interventions that are sensitive to thinnest corneal thickness (TCT) such as corneal crosslinking (CXL) and intrastromal ring segments implantation [4–7].
Patients with progressive keratoconus and corneas <400 µm are a challenging patient cohort because these patients may be at risk of UV-mediated endothelial damage in epithelium-off CXL [8] while also at increased risk of corneal hydrops. Several alternatives to epithelium-off CXL have been proposed [6], including a sub-400 protocol for keratoconic corneas with advanced thinning [5]. The selection of suitable treatment, therefore, depends on accurate measurement of corneal pachymetric and keratometric parameters and sound repeatability limits, which are the magnitude of difference between consecutive measures outside which there is a 95% chance that the difference can be attributed to real change rather than measurement noise. Similar to CXL, intrastromal ring segments are contraindicated if corneal thickness at the proposed incision site is <450 µm [7], or if keratometry is >60 dioptres (D) [4]. Knowledge of repeatability limits is therefore integral to such interventions.
The scheimflug-based Pentacam (Oculus, Wetzlar, Germany) corneal tomographer is one of the most widely available and repeatable instruments currently available commercially [9, 10]. The repeatability limits of corneal tomography parameters measured with Pentacam are known to increase with increased keratoconus disease severity [11]. However, the specific repeatability limits of corneal tomographic parameters in keratoconus with advanced thinning have not yet been quantified. Repeatability studies have largely included patient cohorts of mixed keratoconic severity resulting in smaller numbers of patients with advanced thinning in any one study [9, 12, 13].
The present study sought to compare the repeatability of anterior and posterior keratometry and pachymetry measurements obtained with the Pentacam AXL in keratoconic patients with advanced thinning to those with moderate thinning.
Method
This prospective, single-centre, repeatability study was conducted in the Keratoconus and Crosslinking Service, Department of Ophthalmology, Auckland District Health Board, University of Auckland, Auckland, New Zealand. Informed consent was obtained from all patients. This study was approved by the University of Auckland Human Participant Ethics Committee (reference number 022624) and conducted between January 2019 and June 2021. Consecutive keratoconic eyes were divided into the sub-400 group and 450-plus group, defined as a TCT of ≤400 µm and 450–500 µm, respectively (determined by at least one of the three scans obtained). Eyes were grouped by TCT only, to aid decision-making regarding TCT-based interventions. Although multiple grading systems exist, no clinically adequate classification system has been formally agreed upon [2], and thus TCT was chosen for practicality in our study. Eyes with TCT between 400–450 µm were excluded to make the delineation of the two groups clearer. Eyes with previous intraocular surgery or extraocular procedures including CXL, or previous acute corneal hydrops, were excluded. Only one eye per patient was included in any group to minimise possible bias from inter-eye correlations within the same group. Eyes in the sub-400 and 450-plus groups were matched by gender and age. In the event a match was not available, a gender-matched eye ±1 year in age was utilised.
Patient demographic and clinical information were collected, including: age, gender, ethnicity, eye laterality, previous ocular surgery and procedures, previous corneal hydrops, presence of corneal scarring, and current contact lens wear. The presence of corneal hydrops and corneal scarring were assessed by slit lamp biomicroscopy. As there are no agreed timeframes for duration of contact lens discontinuation [14], contact lens wearers were instructed to refrain from use for 48 h before corneal tomography for consistency with our previous study [15]. Tomography was performed using the Pentacam AXL at the standard resolution (25 images per scan) in a darkened room by one of two experienced investigators (AG and LA). Patients were instructed to blink immediately before each scan was acquired, and three consecutive scans of each eye were obtained within 15 min. Scans were assessed qualitatively by the investigators for eyelid, centration or movement-related artefacts. The following corneal tomography parameters were analysed in this study: maximal corneal power (Kmax), simulated flat (K1) and steep (K2) keratometry of the anterior and posterior corneal surfaces (K1A, K2A, K1P, K2P, respectively), astigmatism in the anterior corneal surface (ASTIG), and corneal pachymetry at the thinnest point.
Eyes were also staged using the Topographic Keratoconus Classification (TKC) system to provide a second classification source to verify that eyes allocated to the 450-plus group would also be classified as moderate severity by TKC, and eyes allocated to the sub-400 group would also be classified as advanced severity by TKC. TKC values were obtained from the Pentacam and ranged between five categorical stages: 0 (normal) to 4 (severe). The highest TKC value for each eye from three scans was used to compare its effect on repeatability. Where the TKC value was between two stages, severity was rounded up to the higher stage.
The repeatability of corneal tomography measurements in the sub-400 group was compared to that in the 450-plus group. Based on these findings, two sub-group analyses were subsequently conducted. Firstly, as TCT varied significantly in the sub-400 group, the sub-400 group was bisected into severe thinning and very severe thinning sub-groups for further comparison. These were defined as eyes with a TCT of 331–400 µm and ≤330 µm, respectively (as determined by at least one of the three scans obtained). Secondly, scan quality can often be reduced in advanced keratoconus, and the inclusion of such scans varies between studies [9, 11, 12, 16–22]. To facilitate the comparison of the present study findings with other published studies, the repeatability of corneal tomography measurements in the sub-400 group was reanalysed using only eyes with a Quality Specification (QS) value of “OK” in all three scans.
Sample size calculation
The investigators aimed to include at least 96 eyes in both the study and control groups to produce less than 10% uncertainty in the repeatability and reproducibility of the results [23].
Statistical analysis
Statistical analysis was conducted using SPSS version 27 (IBM, Chicago, Illinois, USA). The Kolmogorov–Smirnov test was used to test for data normality. Gross outliers in the repeated measurements of each parameter in each eye were identified using the Z-score for the standard deviation. If the Z-score was ≥5 or ≤−5, the eyes were excluded from the analysis of the implicated parameter.
To determine the repeatability of tomography measurements, the following were calculated for each parameter within each comparison group: within-subject standard deviation (Sw), precision (1.96 × Sw), repeatability limit (2.77 × Sw) [24], coefficient of variation (CV) and intraclass correlation coefficient (ICC). ICC values between 0.75–0.89 were deemed to indicate good repeatability, while ICCs of ≥0.90 were excellent [25].
Differences in categorical variables were assessed using the Chi-Squared test and the independent samples t-test was used for continuous variables. The Pearson correlation coefficient was used to determine the correlation between Kmax and TCT and the standard deviation of the three measurements taken for each subject. A p value of <0.05 was deemed statistically significant.
Results
One hundred and fourteen keratoconic eyes from 114 patients were included in the sub-400 group and 114 keratoconic eyes from 114 patients were included in the 450-plus group. Demographic details of participants are shown in Table 1. Mean age, gender, and eye laterality in both groups were similar. More eyes with advanced thinning had evidence of scarring compared to eyes with moderate keratoconus (56% vs. 9%, p < 0.01).
Table 1.
Demographics of patients included in the study.
| Advanced keratoconus (TCT ≤ 400 µm) n = 114 | Moderate keratoconus (TCT > 450–500 µm) n = 114 | p value | |
|---|---|---|---|
| Eyes (n) | 114 | 114 | – |
| Males (n) | 68 (59.65%) | 68 (59.65%) | – |
| Mean age (years, ±SD) | 25.76 ± 7.92 | 25.76 ± 8.23 | 0.96 |
| Right Eye (n) | 52 (45.61%) | 60 (52.63%) | 0.29 |
| Corneal scarring (n) | 64 (56.14%) | 10 (8.77%) | <0.001 |
| Contact lens wear (n) | 33 (28.95%) | 15 (13.16%) | 0.003 |
| Mean TKC value (0 = normal, 4 = severe) | 3.62 | 2.49 | <0.001 |
TKC topographic keratoconus classification.
Due to outliers in the sub-400 group, measurements from one eye were excluded in the analysis of K1P and K2P, from two eyes for K1A and TCT, and from three eyes for Kmax. In the 450-plus group, measurements from one eye were excluded in the analysis of Kmax, K1A, K2A, K1P, K2P, ASTIG and TCT.
The repeatability of all parameters was lower in the sub-400 group than in the 450-plus group (Table 2). The most repeatable parameters in both of these groups were flat and steep simulated keratometry of the anterior surface (K1A and K2A, respectively). All parameters in both groups had good to excellent reliability, with ICC ≥ 0.78.
Table 2.
Repeatability of keratometry and pachymetry measurements in keratoconic eyes with advanced and moderate thinning.
| Parameter | Mean ± SD | Repeatability limit | CV (%) | ICC | ICC 95% CI |
|---|---|---|---|---|---|
| Advanced thinning with TCT ≤ 400 µm (sub-400 group) | |||||
| Kmax (D) | 72.66 ± 1.42 | 6.25 | 1.89 | 0.96 | 0.94–0.97 |
| K1A (D) | 57.98 ± 0.80 | 3.79 | 1.35 | 0.97 | 0.96–0.98 |
| K2A (D) | 63.39 ± 0.79 | 3.22 | 1.25 | 0.98 | 0.98–0.99 |
| K1P (D) | 8.85 ± 0.21 | 1.01 | 2.42 | 0.94 | 0.93–0.96 |
| K2P (D) | 9.91 ± 0.22 | 0.97 | 2.22 | 0.95 | 0.93–0.96 |
| ASTIG (D) | 5.69 ± 0.97 | 3.83 | 22.76 | 0.84 | 0.79–0.88 |
| TCT (µm) | 355.63 ± 9.30 | 33.92 | 2.50 | 0.92 | 0.89–0.96 |
| Moderate thinning with TCT 450–500 µm (450-plus group) | |||||
| Kmax (D) | 54.34 ± 0.39 | 1.69 | 0.64 | 0.99 | 0.78–0.99 |
| K1A (D) | 45.07 ± 0.26 | 1.17 | 0.58 | 0.98 | 0.98–0.99 |
| K2A (D) | 48.90 ± 0.24 | 0.92 | 0.47 | 0.99 | 0.99–0.99 |
| K1P (D) | 6.57 ± 0.07 | 0.27 | 0.99 | 0.98 | 0.97–0.98 |
| K2P (D) | 7.37 ± 0.07 | 0.23 | 0.88 | 0.99 | 0.98–0.99 |
| ASTIG (D) | 3.83 ± 0.33 | 1.23 | 12.25 | 0.97 | 0.96–0.98 |
| TCT (µm) | 470.80 ± 3.66 | 14.32 | 0.78 | 0.92 | 0.90–0.95 |
SD standard deviation, CV coefficient of variation, ICC intraclass correlation coefficient, D dioptre, K1A flat keratometry of anterior surface, K2A steep keratometry of anterior surface, K1P flat keratometry of posterior surface, K2P steep keratometry of posterior surface, ASTIG astigmatism, TCT thinnest corneal thickness.
In the sub-400 group, there was a significant positive correlation between the standard deviation of the three measurements of Kmax and the mean of the three Kmax measurements (r = 0.27, p < 0.01, Fig. 1A) and a significant negative correlation between the standard deviation of the three measurements of TCT and the mean of the three TCT measurements (r = −0.37, p < 0.01, Fig. 1B). In the 450-plus group, there was a significant positive correlation between the standard deviation of the three measurements of Kmax and the mean of the three Kmax measurements (r = 0.42, p < 0.01, Fig. 1C) but no significant correlation between the standard deviation of the three measurements of TCT and the mean of the three TCT measurements (r = −0.19, p = 0.05, Fig. 1D). In both advanced and moderate keratoconus, there was a statistically significant positive correlation between the standard deviation of the three measurements of K1A and the mean of the three K1A measurements (p < 0.05). The correlation between the standard deviation of the three measurements for K2A and ASTIG and their respective means from the three measurements were both positively significant in moderate keratoconus (p < 0.05) but insignificant in advanced keratoconus. For K1P and K2P, there was no statistically significant correlation between the respective standard deviation of the three measurements and the respective means of the three measurements in either the advanced or moderate keratoconus group.
Fig. 1. Pearson’s correlation analysis in various degrees of keratoconus.
Pearson’s correlation analysis in advanced (red; A and B) and moderate (blue; C and D) keratoconus between the standard deviation of the three measurements and mean of the three maximal keratometry (Kmax) measurements (A and C) and mean of the three thinnest corneal thickness (TCT) measurements (B and D).
Sub-group analysis: very severe thinning (TCT ≤ 330 µm) versus severe thinning (TCT 331–400 µm)
Of the 114 eyes with advanced keratoconus in the sub-400 group, 27 had very severe thinning (TCT ≤ 330 µm), and 87 had severe thinning (TCT 331–400 µm). K1A and K2A remained the most repeatable parameters in both sub-groups (Table 3). TCT, K1A and ASTIG were less repeatable in the very severe thinning group (all p ≤ 0.05). The difference in the repeatability of Kmax, K2A, K1P, K2P were not statistically significant between the two groups (p = 0.28, 0.18, 0.15 and 0.11 respectively).
Table 3.
Repeatability for keratometry and pachymetry measurements in eyes with very severe corneal thinning versus severe corneal thinning.
| Parameter | Mean ± SD | Repeatability limit | CV (%) | ICC | ICC 95% CI |
|---|---|---|---|---|---|
| Very severe thinning with TCT ≤ 330 µm (n = 27) | |||||
| Kmax (D) | 81.29 ± 2.28 | 8.10 | 2.82 | 0.94 | 0.89–0.97 |
| K1A (D) | 65.85 ± 1.52 | 5.43 | 2.35 | 0.98 | 0.95–0.99 |
| K2A (D) | 70.17 ± 1.14 | 4.05 | 1.60 | 0.99 | 0.98–0.99 |
| K1P (D) | 10.27 ± 0.33 | 1.41 | 3.24 | 0.96 | 0.93–0.98 |
| K2P (D) | 11.34 ± 0.36 | 1.28 | 3.17 | 0.96 | 0.92–0.98 |
| ASTIG (D) | 5.28 ± 1.83 | 6.50 | 39.03 | 0.82 | 0.66–0.91 |
| TCT (µm) | 292.68 ± 17.01 | 57.72 | 5.74 | 0.86 | 0.71–0.93 |
| Severe thinning with TCT 331–400 µm (n = 87) | |||||
| Kmax (D) | 70.25 ± 1.18 | 5.63 | 1.64 | 0.99 | 0.98–0.99 |
| K1A (D) | 55.68 ± 0.57 | 3.11 | 1.04 | 0.99 | 0.99–0.99 |
| K2A (D) | 61.32 ± 0.69 | 2.93 | 1.15 | 0.99 | 0.99–0.99 |
| K1P (D) | 8.43 ± 0.18 | 0.87 | 2.22 | 0.98 | 0.97–0.99 |
| K2P (D) | 9.50 ± 0.19 | 0.87 | 1.98 | 0.98 | 0.97–0.98 |
| ASTIG (D) | 5.77 ± 0.72 | 2.49 | 18.44 | 0.97 | 0.96–0.98 |
| TCT (µm) | 374.66 ± 5.66 | 22.16 | 1.52 | 0.95 | 0.93–0.96 |
SD standard deviation, CV coefficient of variation, ICC intraclass correlation coefficient, D dioptre, K1A flat keratometry of anterior surface, K2A steep keratometry of anterior surface, K1P flat keratometry of posterior surface, K2P steep keratometry of posterior surface, ASTIG astigmatism, TCT thinnest corneal thickness.
Sub-group analysis using only scans with a QS value of “OK”
A significantly lower proportion of scans had a QS value of “OK” in the sub-400 group, 124 of 342 scans (36.3%), compared to 249 of 342 scans (72.8%) in the 450-plus group (p < 0.01). In the sub-400 group, 30 eyes had triple OK – a QS value of “OK” for all three scans (Supplementary Table 1). The eyes in the ‘sub-400 triple OK’ group had a mean Kmax of 12.12 D less than those in the sub-400 group with scans of mixed QS values (including scans with zero, one or two scans with “OK” QS values). All parameters were equally or more repeatable in the ‘sub-400 triple OK’ group compared to the ‘sub-400 mixed QS value’ group. K1A and K2A were amongst the most repeatable measures in both sub-groups (ICC 0.99 and 0.99 in the ‘sub-400 triple OK’ group; and 0.99 and 0.99 in the ‘sub-400 mixed QS value’ group). The respective repeatability limits of Kmax, K1A, K2A, K1P, K2P, ASTIG and TCT were 2.85 D, 0.77 D, 1.48 D, 0.26 D, 0.22 D, 1.53 D and 10.58 µm in the ‘sub-400 triple OK’ group.
Discussion
This study examined the repeatability of corneal tomographic parameters in patients with keratoconus with advanced corneal thinning in a real-world setting.
The results of the study demonstrate that the repeatability limits of all corneal tomography parameters increased with increased disease severity. Repeatability limits were higher in very severe keratoconus (TCT ≤ 330 µm) versus severe keratoconus (TCT 331–400 µm), which were collectively (sub-400 group; TCT ≤ 400 µm) higher than in eyes with moderate thinning (450-plus group; TCT 450–500 µm) [11]. The absolute repeatability limits for Kmax and TCT in our study (Table 2) were higher than those reported by other investigators [9, 11, 12, 15–22, 26], which ranged between 0.86–1.66 D and 8.26–28.15 µm, respectively (Supplementary Table 2). However, the repeatability limits of K1A, K2A, K1P, K2P and ASTIG in our study were similar to those reported in the literature, ranging between 0.51–2.08, 0.48–1.56, 0.27–0.55, 0.16–0.51 (Supplementary Table 3) and 1.05–1.93 [11, 17], respectively. The severity of keratoconus was greater in our study and is likely to be one of the reasons for the increased repeatability limits of Kmax and TCT.
Another reason for decreased repeatability in our study is the inclusion of scans without all “OK” QS values. When only scans with “OK” QS values were analysed, repeatability limits were reduced for all parameters compared to those with mixed QS value scores (Supplementary Table 1). This difference may be confounded by the lower severity of keratoconus in the QS value “OK” only group (mean Kmax and TCT of 63.82 D and 401.33 µm in this subgroup compared to 72.66 D and 355.63 µm in advanced keratoconus group that included all scans (sub-400 group)). Obtaining corneal tomography scans with a QS value of “OK” is often challenging in patients with advanced keratoconus due to fixation losses from poor visual acuity or intolerance to scans due to light sensitivity. Pentacam algorithms in more advanced keratoconus are also likely to perform more poorly – for both image acquisition and algorithmic parameter generation. When acquiring images, the auto-align feature of the device often cannot detect where to scan, necessitating the need to align and initiate scans manually. Furthermore, corneas tend to be more scarred in advanced disease, which can impair the consistent reading of tissue boundaries and thus affect how algorithms read measurements and generate numeric values.
Nevertheless, scans can be of adequate quality if there are enough data points to generate a tomography map. Thus, this study did not exclude scans without a QS value of “OK” for its primary analyses. While obtaining scans with a QS value of “OK” would be optimal, it is not always practical. Therefore, we propose that scans should be assessed qualitatively and interpreted in the context of the degree of variability. Alternatively, using mean measurements from multiple scans [27] may be useful in advanced keratoconus instead of relying solely on the QS value and a single scan.
The repeatability limits of different tomographic parameters quantified in this study have important implications for both the application of CXL in patients with advanced keratoconus as well as monitoring progression of disease. Parameters such as TCT are pivotal when deciding whether to offer CXL to patients with keratoconus. Knowing the repeatability limits reported in our study can help practitioners make informed decisions about the type of CXL protocol utilised from the beginning of the CXL procedure. For example, in patients with corneas bordering a TCT of 400 µm, practitioners may choose to utilise hypoosmolar riboflavin [28] or a sub-400 protocol [6] from the outset, rather than switching mid-procedure.
Our study found that K1A, K2A, K1P and K2P had equivalent or better repeatability than TCT in both the sub-400 and 450-plus groups. This can be explained by the fact that these parameters represent more global measurements of the corneal surface rather than single-point parameters like TCT and thus, are expected to be more repeatable. Therefore, it is more logical to utilise newer progression analysis systems, such as ABCD [29], that incorporate more repeatable parameters.
This study had several limitations, including differences in contact lens wear between the sub-400 and 450-plus groups, as well as the lack of inter-investigator reproducibility assessment. Firstly, corneal warpage can take one to eight weeks to stabilise [30–32]. However, it is often impractical to request patients with advanced keratoconus, who are often reliant on contact lenses, to avoid contact lenses for such prolonged periods. Secondly, the effects of any residual corneal warpage is likely to be consistent across scans, as scans were conducted within a 15 min timeframe. Thus, while absolute keratometry and pachymetry values may be affected, repeatability measures are unlikely to be significantly affected. Secondly, while the repeatability of TCT is likely more important than reproducibility in surgical planning, the assessment of progression is likely to be influenced more by reproducibility as it is assessed over time and potentially by different examiners [11]. Future studies should investigate the reproducibility of corneal tomography parameters using the Pentacam in keratoconus.
In conclusion, this study quantified the repeatability limits of corneal tomographic parameters in keratoconic patients with moderate and advanced corneal thinning, which has implications for the safe application of CXL and identifying disease progression. When assessing patients with advanced thinning (TCT ≤ 400 µm), clinicians should strive to obtain scans with “OK” quality value if possible and, if unable after several attempts, assess the variability between scans to discern the most likely values of parameters. Utilising the mean of several measurements – ideally after acquiring a minimum of three scans – may also be helpful. Practitioners should utilise newer progression analysis systems that incorporate more repeatable parameters.
Summary
What was known before
The repeatability of keratometry and pachymetry measured with Pentacam tomography is suspected to be poor in advanced keratoconus but repeatability limits have not been quantified in a cohort of exclusively thin keratoconic corneas.
What this study adds
This study quantifies repeatability limits for maximal keratometry, anterior and posterior keratometry and minimum pachymetry in advanced keratoconus with corneas thinner than 400 um. Patients with advanced keratoconus and corneas thinner or equal to 330 um had worse repeatability compared to corneas 331–400 um and corneas thicker than 450 um.
Supplementary information
Author contributions
AG, CM and MZ were responsible for study design. HW, AG, LA were responsible for data collection. HW was responsible for data collation. HW, AG and YL were responsible for statistical analyses. HW was responsible for manuscript preparation. HW, AG, IC, LA, CN, MZ were responsible for manuscript refinement.
Data availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
The online version contains supplementary material available at 10.1038/s41433-023-02528-6.
References
- 1.Kennedy RH, Bourne WM, Dyer JA. A 48-year clinical and epidemiologic study of keratoconus. Am J Ophthalmol. 1986;101:267–73. doi: 10.1016/0002-9394(86)90817-2. [DOI] [PubMed] [Google Scholar]
- 2.Meyer JJ, Gokul A, Vellara HR, Prime Z, McGhee CNJ. Repeatability and agreement of Orbscan II. Pentacam HR, and Galilei tomography systems in corneas with Keratoconus. Am J Ophthalmol. 2017;175:122–8. doi: 10.1016/j.ajo.2016.12.003. [DOI] [PubMed] [Google Scholar]
- 3.McAlinden C, Khadka J, Pesudovs K. Precision (repeatability and reproducibility) studies and sample-size calculation. J Cataract Refractive Surg. 2015;41:2598–604. doi: 10.1016/j.jcrs.2015.06.029. [DOI] [PubMed] [Google Scholar]
- 4.Li Y, Gokul A, McGhee C, Ziaei M. Repeatability and agreement of biometric measurements using spectral domain anterior segment optical coherence tomography and Scheimpflug tomography in keratoconus. Plos One. 2021;16:e0248659. doi: 10.1371/journal.pone.0248659. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Kumar P, Ali M, Reddy J, Vaddavalli P. Short-term changes in topometric indices after discontinuation of rigid gas permeable lens wear in keratoconic eyes. Indian J Ophthalmol. 2020;68:2911–7. doi: 10.4103/ijo.IJO_1522_20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Guber I, McAlinden C, Majo F, Bergin C. Identifying more reliable parameters for the detection of change during the follow-up of mild to moderate keratoconus patients. Eye Vis. 2017;4:24. doi: 10.1186/s40662-017-0089-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Hashemi H, Mehravaran S, Asgari S. The effect of corneal cross-linking on the anterior and posterior parameters of the cornea: a prospective repeatability study. Rom J Ophthalmol. 2019;63:68–74. doi: 10.22336/rjo.2019.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Shetty R, Arora V, Jayadev C, Nuijts RM, Kumar M, Puttaiah NK, et al. Repeatability and agreement of three Scheimpflug-based imaging systems for measuring anterior segment parameters in keratoconus. Invest Ophthalmol Vis Sci. 2014;55:5263–8. doi: 10.1167/iovs.14-15055. [DOI] [PubMed] [Google Scholar]
- 9.Bland JM, Altman DG. Measurement error. BMJ. 1996;313:744. doi: 10.1136/bmj.313.7059.744. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Hashemi H, Firoozabadi MR, Mehravaran S, Gorouhi F. Corneal stability after discontinued soft contact lens wear. Cont Lens Anterior Eye. 2008;31:122–5. doi: 10.1016/j.clae.2008.02.001. [DOI] [PubMed] [Google Scholar]
- 11.Gustafsson I, Bergström A, Myers AC, Ivarsen A, Hjortdal J. Association between keratoconus disease severity and repeatability in measurements of parameters for the assessment of progressive disease. PloS One. 2020;15:e0228992. doi: 10.1371/journal.pone.0228992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Inc AT. Professional use information manual for correction of myopia and astigmatism associated with keratoconus using Intacs® Corneal Implants: Physician Booklet. http://intacsforkeratoconus.com/wp-content/uploads/2015/05/Intacs-for-Keratoconus-11400-11600.pdf.
- 13.Belin M, Kundu G, Shetty N, Gupta K, Mullick R, Thakur P. ABCD: a new classification for keratoconus. Indian J Ophthalmol. 2020;68:2831–4. doi: 10.4103/ijo.IJO_2078_20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Koo TK, Li MY. A guideline of selecting and reporting intraclass correlation coefficients for reliability research. J Chiropr Med. 2016;15:155–63. doi: 10.1016/j.jcm.2016.02.012. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Ziaei M, Barsam A, Shamie N, Vroman D, Kim T, Donnenfeld ED, et al. Reshaping procedures for the surgical management of corneal ectasia. J Cataract Refractive Surg. 2015;41:842–72. doi: 10.1016/j.jcrs.2015.03.010. [DOI] [PubMed] [Google Scholar]
- 16.Shalaby HS, Gharieb HM, Othman IS. Repeatability and interchangeability of topometric, anterior chamber and corneal wavefront data between two Scheimpflug camera devices. Clin Ophthalmol. 2020;5:3801–10. doi: 10.2147/OPTH.S274303. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Sideroudi H, Labiris G, Giarmoulakis A, Bougatsou N, Mikropoulos D, Kozobolis V. Repeatability, reliability and reproducibility of posterior curvature and wavefront aberrations in keratoconic and cross-linked corneas. Clin Exp Optom. 2013;96:547–56. doi: 10.1111/cxo.12044. [DOI] [PubMed] [Google Scholar]
- 18.Gomes JA, Tan D, Rapuano CJ, Belin MW, Ambrósio R, Jr, Guell JL, et al. Global consensus on keratoconus and ectatic diseases. Cornea. 2015;34:359–69. doi: 10.1097/ICO.0000000000000408. [DOI] [PubMed] [Google Scholar]
- 19.Kreps EO, Jimenez-Garcia M, Issarti I, Claerhout I, Koppen C, Rozema JJ. Repeatability of the pentacam HR in various grades of keratoconus. Am J Ophthalmol. 2020;219:154–62. doi: 10.1016/j.ajo.2020.06.013. [DOI] [PubMed] [Google Scholar]
- 20.Raiskup F, Spoerl E. Corneal cross-linking with hypo-osmolar riboflavin solution in thin keratoconic corneas. Am J Ophthalmol. 2011;152:28–32.e1. doi: 10.1016/j.ajo.2011.01.016. [DOI] [PubMed] [Google Scholar]
- 21.Kosekahya P, Koc M, Caglayan M, Kiziltoprak H, Atilgan CU, Yilmazbas P. Repeatability and reliability of ectasia display and topometric indices with the Scheimpflug system in normal and keratoconic eyes. J Cataract Refract Surg. 2018;44:63–70. doi: 10.1016/j.jcrs.2017.10.042. [DOI] [PubMed] [Google Scholar]
- 22.Hafezi F, Kling S, Gilardoni F, Hafezi N, Hillen M, Abrishamchi R, et al. Individualized corneal cross-linking with riboflavin and UV-A in ultrathin corneas: the Sub400 protocol. Am J Ophthalmol. 2021;224:133–42. doi: 10.1016/j.ajo.2020.12.011. [DOI] [PubMed] [Google Scholar]
- 23.de Luis Eguileor B, Escudero Argaluza J, Pijoán Zubizarreta JI, Santamaria Carro A, Etxebarria, Ecenarro J. Evaluation of the reliability and repeatability of Scheimpflug system measurement in keratoconus. Cornea. 2018;37:177–81. doi: 10.1097/ICO.0000000000001373. [DOI] [PubMed] [Google Scholar]
- 24.de Luis Eguileor B, Arriola-Villalobos P, Pijoan Zubizarreta JI, Feijoo Lera R, Santamaria Carro A, Diaz-Valle D, et al. Multicentre study: reliability and repeatability of Scheimpflug system measurement in keratoconus. Brit J Ophthalmol. 2021;105:22–6. doi: 10.1136/bjophthalmol-2019-314954. [DOI] [PubMed] [Google Scholar]
- 25.Deshmukh R, Hafezi F, Kymionis GD, Kling S, Shah R, Padmanabhan P, et al. Current concepts in crosslinking thin corneas. Indian J Ophthalmol. 2019;67:8–15. doi: 10.4103/ijo.IJO_1403_18. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Neuhann S, Schuh A, Krause D, Liegl R, Schmelter V, Kreutzer T, et al. Comparison of variables measured with a Scheimpflug device for evaluation of progression and detection of keratoconus. Sci Rep. 2020;10:19308. doi: 10.1038/s41598-020-76020-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Xiaohong W, McCulley JP, Bowman RW, Cavanagh HD. Time to resolution of contact lens-induced corneal warpage prior to refractive surgery. CLAO J. 2002;28:169–71. doi: 10.1097/01.ICL.0000018042.02034.AB. [DOI] [PubMed] [Google Scholar]
- 28.Seiler TG, Mueller M, Mendes, Baiao T. Repeatability and comparison of corneal tomography in mild to severe keratoconus between the anterior segment OCT MS-39 and pentacam HR. J Refract Surg. 2022;38:250–5. doi: 10.3928/1081597X-20220114-02. [DOI] [PubMed] [Google Scholar]
- 29.Lin J. A critical review on the kinetics, efficacy, safety, nonlinear law and optimal protocols of corneal crosslinking. J Ophthalmol Vis Neurosci. 2018;3:1–10. https://scientonline.org/open-access/a-critical-review-on-the-kinetics-efficacy-safety-nonlinear-law-and-optimal-protocols-of-corneal-crosslinking.pdf.
- 30.Goudie C, Tatham A, Davies R, Sifton A, Wright M. The effect of the timing of the cessation of contact lens use on the results of biometry. Eye. 2018;32:1048–54. doi: 10.1038/s41433-018-0019-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Torquetti L, Sandes J. Ferrara intrastromal corneal ring segments. Int J Keratoconus Ectatic Corneal Dis. 201;5:114–27.
- 32.Szalai E, Berta A, Hassan Z, Módis L. Reliability and repeatability of swept-source Fourier-domain optical coherence tomography and Scheimpflug imaging in keratoconus. J Cataract Refract Surg. 2012;38:485–94. doi: 10.1016/j.jcrs.2011.10.027. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.