FormalPara Key Summary Points

Why carry out this study?

A precise measurement of wavefront aberrations can enable clinicians to better comprehend and manage corneal higher-order aberrations (HOAs).

This study evaluates corneal HOA measurements obtained with a newly developed anterior segment optical coherence tomographer combined with a Placido topographer (MS-39 device) and their agreement with those obtained with Scheimpflug-Placido topography (Sirius device) in eyes after small-incision lenticule extraction (SMILE) treatment.

What was learned from this study?

The MS-39 device displays a high precision in anterior and total cornea aberration measurements. There was a high agreement between measurements by the MS-39 and Sirius devices, indicating that these two technologies can be used interchangeably for measuring corneal HOAs after SMILE.

Introduction

Advances and breakthroughs in wavefront aberration measurement technology can help clinicians to better understand and manage corneal higher-order aberrations (HOAs), especially for the preoperative planning of corneal refractive surgery and cataract surgery [1, 2]. An increase in corneal HOAs affects the visual quality of the human eye, inducing symptoms such as glare, halo, and decreased contrast sensitivity, whereas a reduction in HOAs increases visual quality [3]. To date, several technologies have focused on ways to use HOA analysis to reduce the wavefront aberrations of the human eye [4, 5].

The first small-incision lenticule extraction (SMILE) was performed in Germany in 2007 [6], and this surgical technique has subsequently spread worldwide and now is one of the most popular corneal refractive surgical procedures. This operation uses femtosecond laser technology and the VisuMax FS system (Carl Zeiss Meditec, Jena, Germany) to cut a refractive lens in the corneal stroma, after which the lens is removed through a small incision without the need to make a corneal flap [6]. The main advantage of this technique over laser-assisted in situ keratomileusis (LASIK) is the lack of flap-related complications. In addition, many studies have proven that SMILE is characterized by good efficacy, predictability, safety, stability, and patient comfort [7, 8]. However, it has also been reported that SMILE induces different degrees of HOAs, such as coma, spherical aberration (SA), trefoil, and astigmatism II, which might be related to decentration [7, 9, 10].

Anterior segment imaging technologies are commonly used in current clinical practice. These include the newly developed MS-39 (Costruzione Strumenti Oftalmici, Florence, Italy) anterior segment–optical coherence tomography (AS-OCT) device, which combines spectral-domain OCT with Placido disk topography (SD/OCT-Placido or MS-39 device), and the Sirius (Costruzione Strumenti Oftalmici) device, which combines a single Scheimpflug camera with Placido disk topography (Scheimpflug-Placido or Sirius device). Both instruments simultaneously measure the anterior, posterior, and total corneal surfaces [11, 12]. Several studies have investigated the repeatability, reproducibility, and agreement between corneal thickness and curvature measurements by both technologies [11, 13,14,15,16,17,18,19,20,21], but only a few have focused on corneal HOAs. To date, no studies have compared the precision of corneal HOA measurements by the SD/OCT-Placido and the agreement of these two anterior segment imaging technologies in measuring corneal HOAs in eyes with prior SMILE.

The aim of this study was to evaluate the precision of SD/OCT-Placido (MS-39) corneal HOA measurements in eyes with prior SMILE and the agreement of these measurements with measurements obtained using the Scheimpflug-Placido topography (Sirius) device.

Methods

Subjects

This prospective study was approved by the Ethics Committee of the Eye and ENT Hospital of Fudan University (Shanghai, China). Patients treated with SMILE at the Eye and ENT Hospital of Fudan University were recruited for this study, which was conducted in accordance with the tenets of the Declaration of Helsinki [22]. All patients were informed of the objectives and procedures of the study, and all provided written informed consent.

The inclusion criteria were: age > 18 years; subjective refraction stable in the past 2 years and spherical equivalent between − 10.00 D and − 1.00 D with cylinder between − 3.00 D and 0.00 D; minimum follow-up of 3 months; no use of rigid permeable contact lenses within 4 weeks or of soft contact lens within 2 weeks of enrollment; and non-contact intraocular pressure < 21 mmHg. Exclusion criteria were: any corneal diseases, such as keratoconus; previous ocular trauma or dry eye syndrome; systemic diseases, such as diabetes; any connective tissue disease affecting the eye; and history of previous ophthalmic surgery.

Instruments

MS-39 SD/OCT-Placido Topographer

The MS-39 (software version 4.0) is based on high-resolution SD/OCT combined with a 22-ring Placido disk. It provides anterior chamber tomography, anterior and posterior topography, and high-resolution corneal imaging using a wavelength of 845 nm. The axial resolution is 3.6 μm in tissue, while 31,232 points are measured on the anterior surface and 25,600 on the posterior surface. The wavefront represents the difference in height between the wavefront generated by the examined cornea and an ideal wavefront within the analysis diameter range. Zernike Summary is displayed by choosing the Zernike Summary from the Wave-Front menu. The corneal anterior, posterior, and total corneal HOAs are described as a Zernike polynomial map.

Sirius Scheimpflug-Placido Topographer

The Sirius (software version 3.7) instrument uses a single rotating Scheimpflug camera combined with a 22-ring Placido disk. Using a light-emitting diode (LED) light source with a wavelength of 475 nm, one scan retrieves 35,732 points on the anterior corneal surface and 30,000 points on the posterior corneal surface. The optical-path-length (OPL) difference method is used to measure the corneal anterior, posterior, and total corneal HOAs, which are described as a Zernike polynomial map [23, 24].

Measurement Procedure

The order of measurements was determined by a computer-generated random number table so as to avoid methodological bias. The measurements were taken between 10:00 a.m. and 5:00 p.m. and at least 2 h after the patient woke up. A skilled operator performed the measurements using the MS-39 and Sirius devices, and another operator performed the measurements using the MS-39 for the same subject. The measurement procedure was as follows. In the examination room, where the light was dimmed, the examiner adjusted the height of the jaw rest of the device so as to align the condyle with the marking line and then moved the patient’s forehead close to the forehead rest. During the measurement, the patient was instructed to keep both eyes open, look at the fixation point, and then blink before the measurement to ensure a smooth film tear. After each measurement, patients were asked to close their eyes for a short while. The measurements were taken three times with each device, and only scans with good image quality were included in the analysis. The MS-39 has a symbol for the quality of the keratoscopy (green for good quality, red for bad quality) and reports the coverage percentage for the Placido disc and the OCT sectional images. The Sirius also reports the quality of the acquired image, which should be over the minimum percentage required by the instrument criteria: Scheimpflug image coverage ≥ 90%; Scheimpflug image reliability ≥ 90%; corneal projection center positioning ≥ 90%; and corneal projection coverage ≥ 85%. All measurements were taken over a 6.00-mm corneal diameter and shown as the root mean square (RMS), expressed in micrometers, for the anterior and posterior corneal surfaces as well as for the total cornea. The RMS of all corneal aberrations (i.e., higher- and lower-order aberrations), all HOAs (from the 3rd to the 7th Zernike polynomials), coma, trefoil, SA, and astigmatism II were separately collected for the anterior corneal surface, posterior corneal surface, and total cornea.

Sample Size Calculation

The Power and Sample Size Calculation program (version 3.1.6, October 2018) was used for calculating the sample size. The results showed that a sample size of 44 eyes was sufficient for detecting the difference of an absolute error of 0.10 μm of corneal aberrations with a significance level (α) of 5% and power (β) of 90% [25].

Statistical Analysis

The SPSS (version 21.0; IBM Corp., Armonk, NY, USA) and MedCalc (version 19.8; MedCalc Software Inc., Mariakerke, Belgium) statistical software programs were used to perform the statistical analyses. The precision (intraobserver repeatability and interobserver reproducibility) analysis used within-subject standard deviation (Sw), test–retest repeatability (TRT), and intraclass correlation coefficient (ICC). The TRT was 2.77Sw, indicating the 95% distribution range of the difference from multiple measurements. Lower values of Sw and TRT values represent better precision. Analysis of variance (ANOVA) was used to calculate the ICC, which is a reliability coefficient; the closer the value is to 1, the higher the reliability. The average of the three measurements taken for each parameter was used for comparative purposes. The paired t-test was used to assess whether the mean difference (MD) between the corneal HOAs measured by the two devices was significantly different; a P value < 0.05 was considered to be statistically significant. Bland–Altman plots and 95% limits of agreement (LoAs) were used for agreement analysis [26]. The 95% LoAs were defined as the mean ± 1.96 standard deviations (SD) of the differences between the two measurement techniques. In addition, we calculated 95% LoA of the altered ratio of corneal aberrations, which was defined as the mean difference ± 1.96 SD. The difference was defined as the corneal aberration measured by the MS-39 minus that measured by Sirius.

Results

A total of 56 patients (56 eyes from 26 men and 30 women, respectively) with an average (± SD) age of 28.23 ± 5.87 (range 18–40) years were included in this study. The mean preoperative spherical magnitude was − 4.61 ± 1.74 (range − 2.25 to − 8.25) D, and the mean preoperative cylinder magnitude was − 0.64 ± 0.36 (range − 1.75 to − 0.25) D. The corrected distance visual acuity (CDVA) was ≥ 1.0 in all eyes. The diameter of the cutting optical zone (OZ) was 6.2–6.8 mm, and the average cutting depth was 109.59 ± 21.52 (75–143) μm.

Precision

The intraobserver repeatability of the MS-39 measurements is reported in Table 1 (anterior corneal surface), Table 2 (posterior corneal surface), and Table 3 (total cornea surface). The Sw of all measurements was < 0.07 μm, and the TRT was ≤ 0.16 μm. ICCs were > 0.899 for most anterior and total corneal parameters except for trefoil (ICC = 0.642–0.729). Regarding the posterior corneal parameters, ICCs varied from 0.088 to 0.966 in different aberrometric parameters, with the values for HOAs RMS, astigmatism II, coma, and trefoil < 0.718. Meanwhile, the ICCs for total RMS and SA were > 0.728. Tables 4, 5, 6 show the interobserver reproducibility of the MS-39 measurements. For all parameters, the Sw was ≤ 0.04 μm, and the TRT ≤ 0.11 μm. The ICCs ranged from 0.846 to 0.989, from 0.432 to 0.972, and from 0.798 to 0.985 for the anterior, posterior, and total corneal aberrations parameters, respectively.

Table 1 Intraobserver repeatability outcomes for anterior corneal aberrations obtained using the MS-39 device
Full size table
Table 2 Intraobserver repeatability outcomes for posterior corneal aberrations obtained using the MS-39 device
Full size table
Table 3 Intraobserver repeatability outcomes for total corneal aberrations obtained using the MS-39 device
Full size table
Table 4 Interobserver reproducibility outcomes for anterior corneal aberrations obtained using the MS-39 device
Full size table
Table 5 Interobserver reproducibility outcomes for posterior corneal aberrations obtained using the MS-39 device
Full size table
Table 6 Interobserver reproducibility outcomes for total corneal aberrations obtained using the MS-39 device
Full size table

Difference and Agreement

Table 7 summarizes the mean differences and agreement of the anterior, posterior, and total corneal aberrations measured by the MS-39 and Sirius devices. Figure 1 shows the differences in measurements between the MS-39 and Sirius devices. Violin plots allow for a better distribution and probability density of the data, with the larger the area of a region, the greater the probability of distribution around a value. The HOAs, coma, and SA on the anterior cornea surface measure on the Sirus device were all lower than those measured on the MS-39 device (P < 0.001). On the posterior corneal surface, all measurements provided by the MS-39 device were lower than those provided by the Sirius device (P < 0.001). Regarding total corneal measurements, the MS-39 device yielded lower trefoil and astigmatism II values than the Sirius device (P > 0.01). The results showed that the anterior and posterior surface ranges and regional areas were similar, but that the posterior surface area differed slightly. Figures 2, 3, and 4 show Bland–Altman plots of the anterior, posterior, and total corneal total RMS, HOAs RMS, coma, trefoil, SA, and astigmatism II, respectively. Numerically, the 95% LoA of the corneal HOAs fell within a narrow range except for posterior total RMS. The proportion of changes in the anterior cornea from high to low occurred in coma, total RMS, HOAs RMS, trefoil, SA, and astigmatism II, with the 95% LoAs being − 0.12 to 0.2 μm, − 0.13 to 0.18 μm, − 0.09 to 0.17 μm, − 0.09 to 0.12 μm, − 0.05 to 0.09 μm, and − 0.07 to 0.05 μm, respectively. For the posterior cornea, the total RMS, HOAs RMS, trefoil, coma, SA, and astigmatism II showed 95% LoAs of − 0.2 to -0.01 μm, − 0.16 to 0.01 μm, − 0.08 to 0.04 μm, − 0.14 to 0.04 μm, − 0.09 to 0.05 μm, and − 0.04 to 0.03 μm, respectively. For total cornea, coma, total RMS, HOAs RMS, trefoil, SA, and astigmatism II demonstrated 95% LoAs of − 0.15 to 0.22 μm, − 0.13 to 0.21 μm, − 0.15 to 0.18 μm, − 0.16 to 0.15 μm, − 0.08 to 0.09 μm, and − 0.08 to 0.06 μm, respectively.

Table 7 Mean difference, paired t test and 95% limits of agreement between the MS-39 and Sirius devices
Full size table
Fig. 1
figure 1

Violin plots between measurements by the MS-39 and Sirius devices in terms of total, anterior, and posterior corneal aberrations. The area represents the probability of distribution around a value. The top and bottom black dotted lines represent the interquartile range, while the middle black line is the median limbus. Statistical comparison between two devices was performed using paired t test. Asterisks indicate a significant difference at *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001; ns, not significant p > 0.05

Full size image
Fig. 2
figure 2

Bland–Altman plot of the total RMS and higher-order root mean square (RMS) for the MS-39 and Sirius devices in terms of total, anterior, and posterior corneal aberrations. The solid line represents the mean difference. The dotted lines represent the upper and lower 95% limits of agreement (LoAs). Z Zernike

Full size image
Fig. 3
figure 3

Bland–Altman plot of the coma and trefoil for the MS-39 and Sirius devices in terms of total, anterior, and posterior corneal aberrations. The solid line represents the mean difference. The dotted lines represent the upper and lower 95% LoAs. Z Zernike

Full size image
Fig. 4
figure 4

Bland–Altman plot of the spherical aberration and astigmatism II for the MS-39 and Sirius devices in terms of total, anterior, and posterior corneal aberrations. The solid line represents the mean difference. The dotted lines on the side represent the upper and lower 95% LoAs. Ast Astigmatism, SA spherical aberration, Z Zernike

Full size image

Discussion

Accurate measurement of corneal HOAs is critical to an objective evaluation of the cornea's optical quality [6, 7, 17, 27]. The MS-39 is a high-resolution anterior segment OCT device that provides a variety of anterior segment parameters, including anterior, posterior, and total corneal curvatures, corneal thickness, anterior chamber depth, as well as HOAs. Previous studies have confirmed a high repeatability for most measured anterior segment parameters in healthy, keratoconus, and post-refractive eyes [19,20,21]. However, to the best of our knowledge, our study is the first prospective study that has evaluated the precision of MS-39 measurements of corneal HOAs in eyes after SMILE and compared them with measurements taken with the Sirius device.

Similar to other corneal refractive surgeries, SMILE increases corneal HOAs, such as SA and coma. Zhang et al. [28] used Sirius to measure the total corneal HOAs RMS, SA, and coma at 3 months after SMILE over a diameter of 5.0 mm, and found values of 0.46 ± 0.18 μm, 0.22 ± 0.08 μm and 0.25 ± 0.11 μm, respectively; these were significantly higher than those before SMILE (0.24 ± 0.06 μm, 0.10 ± 0.04 μm and 0.1 ± 0.06 μm, respectively). The authors of a number of studies have pointed out that the increase in corneal HOAs after SMILE was mainly related to the deviation between the center of the ablated corneal stroma and the center of the pupil [9, 10]. In addition, the results of the present study showed that total corneal HOAs RMS, SA, and coma measured by MS-39 were 0.60 ± 0.18 μm, 0.36 ± 0.15 μm and 0.34 ± 0.16 μm, respectively. Jin et al. [29] evaluated total corneal aberration at 3 months using the Pentacam HR (a high-resolution rotating Scheimpflug camera system for anterior segment analysis; Oculus Optikgeräte GmbH; Wetzlar, Germany) after SMILE at a diameter of 6.0 mm, reporting HOAs RMS and SA of 0.99 ± 0.28 μm and 0.42 ± 0.14 μm, respectively; these values are significantly larger than the results of the current study. Siedlecki et al. [30] measured the total corneal HOAs RMS, SA, and coma at 3 months after SMILE at a diameter of 6.0 mm: these were 0.54 ± 0.09 μm, 0.29 ± 0.14 μm and 0.32 ± 0.17 μm, respectively. These measurements for HOAs RMS, SA, and coma were lower than those reported in the present study.

For refractive surgery or the accurate diagnosis and treatment of various eye diseases, it is crucial to accurately evaluate the characteristics and morphology of both the anterior and posterior surfaces. A recent scanning high-resolution swept-source OCT (SS-OCT), the ANTERION (Heidelberg Engineering GmbH, Heidelberg, Germany), has been found to provide high repeatability of anterior and posterior HOAs and SA (ICC > 0.99) at 3 mm [31]. The current findings also pointed out high precision for both anterior and total corneal measurements, except for trefoil. To the contrary, most ICC values from the posterior corneal surface measurements were < 0.9 (except for total RMS). The results from some previous studies based on other principles have confirmed better repeatability for the anterior surface than for the posterior corneal surface in terms of corneal aberrations measurements. Bayhan et al. [14] used the Scheimpflug–Placido system and found moderate to high repeatability for anterior corneal aberrations in normal eyes and keratoconus eyes. Similar results were found in previous studies of patients after SMILE with the Scheimpflug–Placido system, with ICCs ranging from 0.305 to 0.957, and good precision values were only found for total RMS, coma, and spherical aberration [32]. However, for HOAs RMS, trefoil, and astigmatism II, more limited ICCs were obtained for the posterior corneal surface. Similar results were also reported in the studies by Piñero et al. [33] and De Jong et al. [16], as Scheimpflug imaging provided good repeatability in measuring the posterior corneal surface, except for astigmatism II and trefoil, in the healthy eye. These results suggested good repeatability in measuring total RMS and SA on the posterior corneal surface but limited repeatability in measuring HOAs RMS, trefoil, and astigmatism II, which might be due to the small posterior surface aberrations and sensitivity to minor variations.

The MS-39 device showed excellent reproducibility for measurements of anterior and total cornea aberrations, with all ICCs > 0.9 (except for trefoil). Also, the ICCs of total RMS and SA were 0.972 and 0.927 for posterior corneal aberrations, indicating excellent interobserver reproducibility. To date, only a limited number of studies have focused on the reproducibility of aberration measurements. McAlinden et al. [34] evaluated the reproducibility with Scheimpflug imaging and found high aberration outputs in the anterior and total surface, with the posterior outputs being the least precise. The earliest studies using Scheimpflug imaging showed coma, coma-like, and HOA RMS with acceptable reproducibility of posterior corneal aberrations [35]. The posterior corneal, total RMS and coma imaging also indicated excellent interobserver reproducibility using the Scheimpflug-Placido topographer [32]. Inconsistencies in the results may originate from differences in the subjects enrolled in the study. Compared to the aberration principles of other instruments, such as the Hartmann-Shack sensor (KR-1 W, Topcon Corp., Tokyo, Japan) or ray tracing (iTrace Technologies, Silicon Valley, CA, USA), our results showed better reproducibility for the corneal HOAs. Xu et al. [25] reported that ICC values of SA, HOA, coma, and trefoil were ≤ 0.804, while 2.77Sw values were > 0.06 μm. Whole-eye aberration measurement devices are affected by a relatively higher number of influencing factors, such as altered pupil accommodation, eye movement, and refractive medium.

No studies are currently evaluating the agreement between MS-39 measurements of corneal aberrations and those by other devices. Recent studies have reported agreement between the Anterion and Pentacam HR devices for corneal aberrations in healthy subjects [36, 37]. Pérez–Bartolomé et al. [36] indicated that vertical coma and RMS HOA values had good agreement, as the 95% LoAs ranged from − 0.37 to 0.308 μm and from − 0.27 to 0.305 μm, respectively. Gim et al. [37] demonstrated that almost all HOAs had an acceptable agreement, except for the horizontal trefoil, and the 95% LoAs were − 0.43 to 0.32 μm. Previous studies have also confirmed the agreement between different Scheimpflug cameras. Piccinini and colleagues [17] measured the total corneal HOAs RMS and SA of healthy subjects and compared the measurements taken by the Pentacam HR and the dual-rotating Scheimpflug camera combined with the Placido disk Galilei G4 (Ziemer Ophthalmic Systems AG, Port, Switzerland), reporting that the 95% LoAs were − 0.536 to 1.08 μm and − 0.159 to 0.159 μm, respectively. Accordingly, the measurements from the two Scheimpflug cameras could not be considered interchangeable. Conversely, the values of the current study were − 0.15 to 0.18 μm and − 0.08 to 0.09 μm, respectively. Our results for 95% LoAs of HOAs RMS and SA were lower than those reported by Piccinini et al. [17] and Aramberri et al. [13], who evaluated the values from the Pentacam HR and Galilei G2 devices in healthy subjects and reported that the 95% LoAs of total corneal HOAs RMS and SA were − 0.85 to − 0.12 μm and − 0.12 to 0.09 μm, respectively, which is similar to those of Piccinini et al. [17]. In addition, other studies have evaluated the agreement of other technologies. In current study, the MS-39 and Sirius devices showed statistically significant differences when measuring almost all anterior and posterior aberrations, as well as a few other total corneal parameters, such as total RMS, coma and astigmatism II; the measurements of the remaining parameters did not significantly differ [38,39,40].

In order to assess whether measurements can be considered accurate in the clinical setting, it is necessary to understand the quantitative changes in the wavefront aberrations according to the alterations in the visual quality. Just-noticeable difference (JND) has been used to reveal that wavefront aberrations increase when subjective visual quality changes occur [27, 41, 42]. Atchison and colleagues [42] used a 0.1 LogMAR target and found that at a pupil diameter of 6.0 mm, the SA, coma, and trefoil increased by 0.07, 0.15, and 0.19 μm, respectively, when the patients reported a blur. Jungnickel et al. [41] reported that with a pupil diameter of 5.0 mm, coma and trefoil increased by 0.059 and 0.108 μm, respectively, when the visual quality decreased. The results of the present study showed that the 95% LoAs were narrower, thus suggesting that the two instruments can be used interchangeably in the clinical setting.

The high agreement of corneal HOAs measurements taken by the MS-39 and Sirius devices after SMILE may be due to the same principles being used for the anterior surface measurement and the corneal aberration calculation methods. The MS-39 and Sirius devices obtain the anterior corneal data from the Placido-disk and the Scheimpflug camera or SD/OCT imaging. However, aberration measurements are also influenced by many factors. Theoretically, the tear film influences HOAs [43]. Still, such an influence is pronounced with instruments based on the Placido technology, which works by reflection, as opposed to that of Scheimpflug imaging. Other potential reasons include obstruction of the eyelids, eye movements, and physiological changes in the corneal HOAs [27]. In addition, the largest change in the ratio in coma, trefoil, and astigmatism II might be attributable to the small mean value, which causes a small change but has a huge impact on the ratio.

The present study has a number of limitations. First, we only measured the corneal HOAs of the patients after SMILE and did not compare them to those of the same patients before the operation. In our future studies, we plan to follow up patients with SMILE to observe the changes in corneal HOAs and compare consistent changes before and after surgery. Furthermore, we will focus on the changes of agreement for corneal HOAs at different follow-up time points after SMILE. Comparing the effects of different sizes of corneal incisions and different optical zones on corneal HOAs measured by these two devices is another direction we plan to follow. Finally, since there is no accepted gold standard for the clinical corneal aberration measurement [38], our results only indicate a high agreement between the two technologies after the SMILE.

Conclusion

In conclusion, the present study showed that after SMILE, the new AS-OCT device combined with Placido corneal topography, the MS-39 device, displays high precision in both anterior and total corneal measurements but lower precision in posterior corneal measurements, especially for HOAs RMS, astigmatism II, coma, and trefoil. Together, the agreement of all the measured parameters was high between the MS-39 and Sirius devices.