Abstract
Purpose
To investigate changes in contrast sensitivity (CS) and their association with Lenticule surface regularity after keratorefractive lenticule extraction (KLEx) performed with the VisuMax 800.
Patients and Methods
In total, 92 patients (184 eyes) with myopia were recruited between November and December 2024. CS was measured using the quantitative contrast sensitivity function at 1, 3 and 6 months postoperatively. The lenticules were examined using scanning electron microscopy (SEM), and the SEM images were scored using the large language model Doubao-vision-pro 32k. Correlation analysis between Lenticule surface regularity and CS was performed based on the Generalized Estimating Equations model.
Results
At 6 months postoperatively, the uncorrected distance visual acuity of all operated eyes was 20/25 or better; none of the eyes lost 1–2 lines of corrected distance visual acuity. Area under the log CS function, cutoff spatial frequency acuity and CS (3.0–18.0 cpd) significantly improved from 1 to 6 months and correlated with visual acuity and refraction (P < 0.05). Lenticule surface regularity, mainly influenced by age (β=0.204, P < 0.001) and cap thickness (β=-0.325, P < 0.001), was significantly associated with CS (3.0 cpd) at 1 and 3 months postoperatively (β=0.027, P=0.005; β=0.028, P=0.006), and with CS (6.0 cpd) at 6 months postoperatively (β=0.035, P=0.001).
Conclusion
KLEx performed with the VisuMax 800 yields excellent and stable visual outcomes at six months postoperatively and postoperative CS improved over time. Lenticule surface regularity could contribute to postoperative visual quality to a certain extent.
Keywords: KLEx, contrast sensitivity, quantitative contrast sensitivity function, lenticule surface regularity, large language model
Introduction
Refractive surgery is an effective method to enhance visual ability by reducing dependence on glasses. Keratorefractive lenticule extraction (KLEx) is a safe and effective refractive surgery for treating refractive errors.1 The latest laser version, the Visumax 800, has been applied since 2021.2 Compared with the Visumax 500, Visumax 800 offers the advantages of shorter laser scanning cycles and an eye-tracking system device.3 Moreover, reduced scanning time may improve patient comfort and reduce the overall risk of suction loss.3 The visual quality after KLEx have attracted attention.
Visual acuity is the most common postoperative examinations. Compared to visual acuity, the contrast sensitivity (CS) function assesses visual function across varying spatial frequencies and offers more refined and responsive results for evaluating visual quality. For postoperative refractive surgery, contrast sensitivity evaluation is indispensable for comprehensive visual function profiling.4 The quantitative contrast sensitivity function (qCSF) is a validated method for assessing visual quality. Unlike conventional CS testing tools such as the CSV-1000, which are limited by fixed spatial frequency intervals, lengthy testing procedures, and insufficient precision in capturing subtle visual functional changes, the qCSF adopts Bayesian information maximization algorithms to efficiently quantify contrast sensitivity at low, medium, and high spatial frequencies with superior accuracy.5 qCSF has been widely used in ophthalmology to distinguish patients with amblyopia from those with myopia,6 conduct screenings to identify age-related macular degeneration,7 and monitor visual quality variations following refractive surgery.8
Surgical results using Visumax 800 were first reported in 2023.3 Several studies2,3 have reported excellent results for refractive accuracy and analyzed changes in CS at few spatial frequencies with CSV-1000; however, no study has used qCSF to analyze CS at more comprehensive spatial frequencies or focused on the underlying factors of CS. Moreover, as the lenticule surface regularity is critical for achieving good visual quality, uneven lenticule surfaces with residual tissue bridges and cavitation defects will create irregular corneal stromal interfaces, induce intraocular light scattering, elevate higher-order aberrations, and further increase the risk of postoperative corneal haze, all of which jointly degrade visual performance.9 Therefore, this study aimed to investigate the early characteristics of CS using qCSF and explore the potential impact of lenticule surface regularity on CS.
Materials and Methods
Study and Patients
This study complied with the guidelines of the Declaration of Helsinki. The Eye and ENT Hospital (EENT) ethics board at Fudan University approved this study (No. 2024050-2). This research recruited 92 patients between November and December 2024. Written informed consent was secured from all participants before their enrollment.
The inclusion criteria were 18 to 46 years of age, myopia or myopic astigmatism with a spherical equivalent refraction (SER) between −0.00 and −9.00 diopters (D), and cylindrical refraction (CR) of 4.00 D or less. Exclusion criteria included eyes with keratoconus, corneal scars, central corneal pachymetry < 480 μm, glaucoma, retinal disease, and any other conditions that might affect the efficacy or safety of laser treatment.
Every participant received a series of ophthalmological examinations, including slit-lamp biomicroscopy, manifested refraction (RT-5100, Nidek Technologies, Japan), axial length (IOLMaster; Carl Zeiss Meditec AG, Jena, Germany), corneal topography (Pentacam HR, Oculus Optikgeräte, Wetzlar, Germany), and intraocular pressure (Tonoref II, Nidek, Japan) measurement.
Surgical Procedure
A standard surgical procedure was performed by the same surgeon using the Visumax 800 platform (Carl Zeiss Meditec AG, Jena, Germany). Surgical parameters included a 2000 kHz repetition rate, cut energy between 130 nJ and 135 nJ, cap thickness between 110 and 130 μm, 7.6 mm cap diameter, optical zone between 6.0 and 6.8 mm, and the lateral incision angle is 90° with a length of 2 mm. All patients were routinely administered 0.1% fluorometholone eye drops, 0.5% levofloxacin eye drops, and sodium hyaluronate eye drops postoperatively. Routine re-examinations were conducted at 1 day, 1 week, 1 month, 3 months and 6 months postoperatively.
qCSF Test
In this study, qCSF tests were performed using an NEC P403 monitor (Gension and Waltai Digital Video System Co. Ltd., China)10 at 1, 3 and 6 months postoperatively. All tests were implemented under standardized uniform conditions: visual stimuli were presented horizontally 3 meters away from participants inside a dark examination room, all assessments were conducted under uncorrected monocular viewing. Testing was conducted separately for each eye: one eye remained uncovered for measurement while the fellow eye was blocked, then the second eye was examined using the same uniform setup. The sequence of spatial frequency measurements was fixed for all patients to eliminate order bias. All the calculations were automated using a computer program throughout the process, including the area under the log CS function (AULCSF), cutoff spatial frequency (CSF) acuity, and CS (log units) at 1.0, 1.5, 3.0, 6.0, 12.0, and 18.0 cycles per degree (cpd).
Lenticule Surface Regularity
The lenticules of subjects were enrolled using a random sampling method, with consideration given to the distribution of age and refractive status to ensure that the sample covered different age groups and a range of refractive errors. All candidate lenticules underwent rigorous quality screening; those with mechanical damage such as obvious scratches during surgery were excluded. Finally, 28 eyes from 28 subjects were included as the analysis sample. These lenticules were scanned using a scanning electron microscope (SEM) at four magnifications (100×, 200×, 400×, and 800×). The front and back surfaces of the lenticules were subjected to bilateral imaging.
The new evaluation criteria for Lenticule surface regularity in this study (Table 1) were developed by adjusting and optimizing the scoring criteria by Zhao et al.9 All anonymized SEM micrographs of stromal lenticules, stripped of any patient identifiers and clinical grouping information, were imported into the vision large language model Doubao-vision-pro 32k for automated image recognition and quantitative scoring. The full standardized grading rubric shown in Table 1 was input as prompt instructions to guide consistent scoring across all specimens. The fundamental workflow of vision LLM-mediated lenticule morphological assessment was preliminarily described in our prior research.11 Representative SEM images of Lenticule surfaces with varying degrees of surface regularity are shown in Figure 1A–L.
Table 1.
The New Evaluation Criteria for Lenticule Surface Regularity
| Criterion and Magnification | Appearance | Scores | |
|---|---|---|---|
| A1 | Surface relief,100X | A Very smooth To Very rough |
10 to 1 |
| A2 | Surface relief,200 X | A Very smooth To Very rough |
10 to 1 |
| B1 | Regularity of surface structure,400X | Completely regular To Not regular |
6 to 1 |
| B2 | Regularity of surface structure, 800 X | Completely regular To Not regular |
6 to 1 |
| C1 | Portion of surface irregular, 400X | < 10% of cut surface | 4 |
| 11–25% of cut surface | 3 | ||
| 26–50% of cut surface | 2 | ||
| >50% of cut surface | 1 | ||
| C2 | Portion of surface irregular, 800 X | < 10% of cut surface | 4 |
| 11–25% of cut surface | 3 | ||
| 26–50% of cut surface | 2 | ||
| >50% of cut surface | 1 |
Notes: A1, the criterion for evaluating surface relief at 100× magnification; A2, the criterion for evaluating surface relief at 200× magnification; B1, the criterion for evaluating regularity of surface structure at 400× magnification; B2, the criterion for evaluating regularity of surface structure at 800× magnification; C1, the criterion for evaluating the portion of the cut surface showing irregular structures at 400× magnification; C2, the criterion for evaluating the portion of the cut surface showing irregular structures at 800× magnification.
Figure 1.
Representative scanning electron microscopy (SEM) micrographs of SMILE stromal lenticules captured at four magnifications. (A) (100×), (B) (200×), (C) (400×), and (D) (800×) correspond to No. 3, with a total score of 20 points; (E) (100×), (F) (200×), (G) (400×), and (H) (800×) correspond to No. 20, with a total score of 16 points; (I) (100×), (J) (200×), (K) (400×), and (L) (800×) correspond to No. 30, with a total score of 12 points.
Abbreviation: SEM, scanning electron microscopy.
Statistical Analysis
Data analysis and visualization were performed using SPSS (version 20.0; SPSS Inc., Chicago, IL, USA) and GraphPad Prism 10.1 (GraphPad Software, LLC., San Diego, CA, USA). Demographic and measurement parameters were summarized with descriptive statistics and are presented as mean ± standard deviation (SD) with range. The correlation and influencing factor analysis among variables were conducted based on the Generalized Estimating Equations model to control for the effect of binocular data. The unique patient identification number was set as the clustering subject variable, and ocular side was defined as the within-subject repeated factor to account for interocular correlation within each individual. An exchangeable working correlation structure was adopted to assume uniform correlation between the two eyes of one participant. Robust sandwich covariance matrix estimators were selected for all models to obtain stable parameter estimates. Statistical significance was set at P<0.05.
Results
In this study, 92 patients (184 eyes) were enrolled. The male-to-female ratio of the enrolled participants was 41:51. The baseline values are listed in Table 2.
Table 2.
The Baseline of Preoperative Characteristics
| Characteristic | Mean±SD | Range |
|---|---|---|
| Age (Years) | 31.63±5.68 | 18 to 46 |
| Gender (Male/Female) | 41/51 | |
| CDVA (logMAR) | 0.00±0.02 | −0.1 to 0.1 |
| SR (D) | −4.11±1.63 | −7.75 to −0.75 |
| CR (D) | −0.82±0.67 | −4 to 0 |
| SER(D) | −4.52±1.67 | −8.63 to −0.88 |
| PS (mm) (lamp off) | 6.84±0.75 | 5 to 8.7 |
| Flat K (D) | 42.33±1.50 | 38.4 to 46.8 |
| Steep K (D) | 43.53±1.60 | 39.9 to 49.4 |
| CCT (µm) | 545.85±26.39 | 494 to 609 |
| IOP(mmHg) | 14.65±2.14 | 10 to 21.4 |
| AL (mm) | 25.66±1.07 | 23.58 to 28.66 |
Abbreviations: AL,axial length; CCT,central corneal thickness; CDVA,preoperative corrected distance visual acuity; CR,cylindrical refraction; D,diopter; logMAR,logarithm of the minimal angle of resolution; IOP,intraocular pressure; PS,pupil size; SER,spherical equivalent refraction; SR,spherical refraction.
Visual and Refractive Outcomes
At 6 months postoperatively, the uncorrected distance visual acuity (UDVA) of all operated eyes was 20/25 or better; none of the eyes lost 1–2 lines of corrected distance visual acuity (CDVA) (Figure 2A and B). Figure 2C shows the differences between the attempted and achieved SER correction. The mean SER was +0.15±0.25 D, with 95% of the eyes within ±0.50 D and 100% of the eyes within ±1.00 D (Figure 2D). Regarding astigmatism, the mean value was −0.24±0.24 D, with 97% of the eyes within ±0.50 D and 100% within ±1.00 D (Figure 2E). Surgical stability remained favorable from 1 to 6 months postoperatively (Figure 2F).
Figure 2.
Refractive outcomes for patients after KLEx with Visumax 800. Postoperative UDVA (A). Postoperative changes in Snellen lines of CDVA (B). Attempted vs achieved SER (C). Accuracy of SER(D). Postoperative refractive astigmatism (E). Stability of SER (F).
Abbreviations: KLEx, keratorefractive lenticule extraction; CDVA,corrected distance visual acuity; SER, spherical equivalent refraction; UDVA, uncorrected distance visual acuity.
Postoperative CS
AULCSF, CSF acuity, and CS (3.0–18.0 cpd) showed significant changes from 1 to 6 months postoperatively (P<0.05), and also exhibited significant changes from 3 to 6 months postoperatively (P<0.05). Except for CS (3.0 cpd), the aforementioned indicators exhibited no significant changes from 1 month to 3 months postoperatively. No significant differences were observed in CS (1.0 and 1.5 cpd) among the time points of 1, 3 and 6 months postoperatively (Figure 3).
Figure 3.
Changes in quantitative contrast sensitivity function (qCSF) parameters over the 6-month follow-up period after surgery. Violin plots show the distribution of qCSF parameters at 1 month (post-1m, blue), 3 months (post-3m, light purple), and 6 months (post-6m, pink) postoperatively. (A) Area under the log contrast sensitivity function (AULCSF). (B) CSF acuity. (C) Contrast sensitivity (CS) at 1.0cycles per degree (cpd). (D) CS at 1.5 cpd. (E) CS at 3.0 cpd. (F) CS at 6.0 cpd. (G) CS at 12.0 cpd. (H) CS at 18.0 cpd.
Relationship Between Postoperative Visual Outcomes and CS
Aulcsf and CSF acuity showed correlations with visual acuity and refractive status at almost all corresponding time points postoperatively. For CS (1.0 and 1.5 cpd), only CS (1.5 cpd) exhibited a weak negative correlation with CDVA at 1 month postoperatively, with no significant correlations observed in all other cases. Regarding CS (3.0–18.0 cpd), their correlations at 6 months postoperatively gradually weakened compared with those at 1 and 3 months postoperatively (Figure 4).
Figure 4.
The correlation heat map between postoperative CS and visual and refractive outcomes. Color intensity corresponds to the magnitude of correlation coefficients. Statistical significance thresholds are annotated: *P < 0.05, **P < 0.01, ***P < 0.001.
Abbreviations: qCSF, quantitative contrast sensitivity function; AULCSF, area under log CSF; CSF, cutoff spatial frequency; cpd, cycles per degree; D, diopter; UDVA, uncorrected distance visual acuity; CDVA, corrected distance visual acuity; SER, spherical equivalent refraction.
Surface Morphology of the Lenticules
Regarding the surface regularity of the lenticules, the highest score was 20 (Figure 1A–D), the intermediate level was 16 (Figure 1E–H), and the lowest score was 12 (Figure 1I–L). Determinant analysis of Lenticule surface regularity showed age (β=0.204, P < 0.001), steep K(β=-0.420, P=0.040), central corneal thickness (β=-0. 033, P=0.010) and cap thickness (β=-0.325, P < 0.001) were significantly associated with the Lenticule surface regularity (Table 3).
Table 3.
GEE-Based Univariate Linear Regression of Lenticule Surface Regularity
| Characteristic | β | Wald χ2 | P value |
|---|---|---|---|
| Age (Years) | 0.204 | 26.586 | <0.001*** |
| Gender (Male/Female) | −1.362 | 3.136 | 0.077 |
| SR (D) | 0.008 | 0.002 | 0.696 |
| CR (D) | 0.662 | 1.292 | 0.256 |
| PS (mm) (lamp off) | 0.027 | 0.005 | 0.946 |
| Flat K (D) | −0.184 | 0.652 | 0.419 |
| Steep K (D) | −0.420 | 4.207 | 0.040* |
| CCT (µm) | −0.033 | 6.639 | 0.010* |
| IOP(mmHg) | −0.225 | 2.350 | 0.125 |
| AL (mm) | 0.787 | 3.224 | 0.073 |
| Optical zone (mm) | −0.092 | 0.001 | 0.970 |
| Cap thickness (µm) | −0.325 | 37.568 | <0.001*** |
| Lenticule thickness (µm) | 0.023 | 2.920 | 0.088 |
Notes: *Represents P < 0.05, ***represents P < 0.001.
Abbreviations: AL,axial length; CCT,central corneal thickness; CR,cylindrical refraction; IOP,intraocular pressure; PS,pupil size;SR,spherical refraction.
Influence of Lenticule Surface Regularity on Postoperative CS
One month postoperatively, Lenticule surface regularity was significantly associated with CS (3.0cpd) (β=0.027, P=0.005). Three months postoperatively, Lenticule surface regularity was significantly correlated with CSF acuity (β=0.709, P=0.026) and CS (3.0cpd) (β=0.028, P=0.006). Six months postoperatively, Lenticule surface regularity has a correlation with CS (6.0cpd) (β=0.035, P=0.001) (Table 4).
Table 4.
Correlation Analysis Between Lenticule Surface Regularity and CS at Three Time Points
| qCSF Parameters | 1 Month After Surgery | 3 Months After Surgery | 6 Months After Surgery | ||||||
|---|---|---|---|---|---|---|---|---|---|
| β | Wald χ2 | p value | β | Wald χ2 | p value | β | Wald χ2 | p value | |
| AULCSF | 0.016 | 1.011 | 0.315 | 0.013 | 0.046 | 0.435 | −0.009 | 0.563 | 0.453 |
| CSF acuity | 1.190 | 1.446 | 0.229 | 0.709 | 4.974 | 0.026* | −0.216 | 0.155 | 0.694 |
| CS (1.0cpd) | −0.010 | 0.187 | 0.666 | 0.023 | 1.860 | 0.173 | 0.013 | 1.495 | 0.221 |
| CS (1.5cpd) | 0.010 | 0.295 | 0.587 | 0.030 | 4.112 | 0.043 | 0.019 | 1.521 | 0.218 |
| CS (3.0cpd) | 0.027 | 8.045 | 0.005** | 0.028 | 7.587 | 0.006** | 0.002 | 0.013 | 0.908 |
| CS (6.0cpd) | 0.023 | 1.031 | 0.310 | 0.001 | 0.001 | 0.974 | 0.035 | 10.873 | 0.001** |
| CS (12.0cpd) | −0.003 | 0.013 | 0.909 | −0.003 | 0.020 | 0.888 | −0.019 | 0.904 | 0.342 |
| CS (18.0cpd) | 0.007 | 0.098 | 0.754 | 0.023 | 3.771 | 0.052 | −0.008 | 0.077 | 0.781 |
Notes: *Represents P < 0.05, **represents P < 0.01.
Abbreviations: CS, contrast sensitivity; CSF, contrast sensitivity function; qCSF, quantitative contrast sensitivity function.
Discussion
Observing postoperative visual quality is important for evaluating surgical outcomes and ensuring optimal postoperative visual function. As a key indicator, CS facilitates a comprehensive and detailed assessment of the postoperative visual system, providing critical evidence for clinical efficacy evaluation and personalized intervention. To the best of our knowledge, this study is the first to use qCSF to observe early postoperative changes in CS following KLEx with Visumax 800. Additionally, the factors influencing Lenticule surface regularity and the impact of such regularity on CS were investigated.
Regarding the visual and refractive outcomes, we found that KLEx with Visumax 800 is safe and effective in the early postoperative period, which is similar to some studies.2,3,11–14 Moreover, compared with Visumax 500, Visumax 800 provides a better lenticule scanning quality,11 a better intraoperative experience,15 higher precision in correcting astigmatism >2 D,14 lower total higher-order aberrations,16 and less residual astigmatism.17 Lee et al18,19 also investigated the differences among refractive lens exchange, femtosecond LASIK (FS-LASIK), and KLEx with Visumax 800, demonstrating similar visual and refractive outcomes, whereas FS-LASIK was associated with a higher incidence of dry eye syndrome postoperatively.
This study observed that AULCSF, CSF acuity, and CS (3.0 cpd–18.0 cpd) showed significant improvement from 1 to 6 months postoperatively, and also exhibited significant changes from 3 to 6 months postoperatively; however, no significant changes were observed from 1 to 3 months postoperatively. Additionally, improvements in visual and refractive outcomes at 1, 3 and 6 months postoperatively were significantly and positively correlated with improvements in AULCSF, CSF acuity, and CS at medium-to-high spatial frequencies. Yue et al20 observed a positive correlation between SER improvement and AULCSF improvement 7 days after KLEx with Visumax 500, which is consistent with our findings. Ganesh et al15 observed no significant change in CS at medium-to-high spatial frequencies from preoperatively to 3 months postoperatively, whereas Sekundo et al,2 incorporating data from a large sample (473 eyes) and observing up to 6 months postoperatively, discovered a significant improvement in CS at medium-to-high spatial frequencies from preoperatively to 6 months postoperatively. Collectively, these findings suggest that the visual quality after KLEx with Visumax 800 improves over time, and CS is highly likely to recover to or even exceed the preoperative level at 6 months postoperatively.
Femtosecond lasers generate lenticules by delivering laser pulses at specific corneal depths to cleave the tissue through pulse fragmentation. Numerous studies21–24 have demonstrated that low pulse energy and high laser frequency are closely related to high-quality lenticules. In this study, all patients undergoing surgery had the same laser frequency and energy, thereby eliminating the influence of pulse energy and laser frequency on lenticule quality. Tissue bridges refer to residual fibers between the corneal stromal interfaces after femtosecond laser cutting, with a greater number of tissue bridges associated with increased microLenticule surface irregularity.9,23 Our findings showed that older age was correlated with more regular Lenticule surfaces. With increasing age, the water content of the corneal stroma decreases,25 and natural crosslinking of collagen fibers in the stroma (including non-enzymatic glycosylation crosslinking) occurs,26,27 leading to denser and more regular fiber structures. This facilitates continuous cutting of surfaces during laser application, reduces tissue bridge formation at stromal interfaces, and results in more regular Lenticule surfaces. Additionally, younger patients have a higher proportion of elastic fiber components in the cornea,28 which may result in local fiber residues due to tissue elastic recoil during laser cutting, increasing tissue bridge formation at stromal interfaces and leading to more irregular Lenticule surfaces.
In this study, we also discovered that smaller cap thickness were associated with more regular Lenticule surfaces. Sarayba et al21 discovered that thin flaps (<120–130 μm) resulted in smoother corneal stromal bed surfaces than did thick flaps (>140 μm) in FS-LASIK. Weng et al29 set four different cap thicknesses (120, 130, 140, and 150 μm) in KLEx with Visumax 500 and observed that Lenticule surface regularity decreased with increasing cap thickness, consistent with the results of the present study. Collagen fibers in the anterior one-third of the corneal stroma are more densely arranged than those in the posterior two-thirds.30,31 A thinner cap means that the Lenticule cutting layer is closer to the anterior stroma, leading to a more uniform fiber fracture during laser cutting, reduced tissue bridge formation at the stromal interfaces, and more regular Lenticule surfaces.
Furthermore, we analyzed the Lenticule surface regularity and its potential impact on CS. Our findings showed that more regular Lenticule surfaces were significantly associated with improved medium spatial frequency CS, which is most relevant to daily life,32 at 1.3 and 6 months postoperatively. Kunert et al23 and Damgaard et al33 reported that Lenticule quality significantly correlated with postoperative visual acuity and complications such as corneal opacity. Vinciguerra et al34,35 also revealed a positive correlation between postoperative visual acuity and Lenticule surface regularity, which is consistent with the results of this study. Rough Lenticule surfaces may affect postoperative visual outcomes by inducing inflammatory responses36 or promoting corneal stromal cell accumulation and transformation into fibroblasts.23 Netto et al36 performed FS-LASIK in rabbits and conducted histopathological examinations of corneal tissues, revealing early postoperative inflammation, the severity of which correlated with corneal stromal quality. Kunert et al23 suggested that rough stromal beds lead to cytokine accumulation in the corneal stroma, whereas Salomao et al37 observed that elevated TGF-β concentrations promote myofibroblast differentiation, producing abnormal collagen and causing corneal opacity. Therefore, ensuring the regularity of the Lenticule surface and corneal stromal bed is crucial for achieving favorable early postoperative visual function and patient experience in refractive surgery.
This study had some limitations. First, it focused only on early postoperative changes, the long-term effects warrant further observation. Second, preoperative CS data was not collected. Thirdly, we used CS as a subjective indicator to reflect visual quality without incorporating objective metrics. Fourthly, the quantitative analysis of lenticule surface regularity was performed on a small subset of 28 lenticules, accounting for merely 15% of the total 184 eyes. The relatively low proportion of analyzable lenticules may reduce the generalizability of our findings, and future large-sample studies are needed to verify our conclusions.
Conclusion
In conclusion, KLEx performed with the VisuMax 800 yields excellent and stable visual outcomes at six months postoperatively and early postoperative CS improved over time. Lenticule surface regularity could contribute to postoperative visual quality to a certain extent.
Acknowledgments
The authors thank the large language model Doubao for its assistance with this research and all the patients for their participation. All authors confirm the originality and accuracy of the content in this manuscript. The authors take full responsibility for the integrity of the entire manuscript, including the accuracy of all cited references.
Funding Statement
1. National Key Research and Development Program of China (2024YFC2510805);2. National Natural Science Foundation of China (Grant No. 82271119,82471116);3. Shanghai Oriental Talent Plan Youth Program (QNKJ2024055);4. Shanghai Hospital Development Center Foundation (SHDC12025144).
Disclosure
The authors report no conflicts of interest in this work.
References
- 1.Sekundo W, Kunert KS, Blum M. Small incision corneal refractive surgery using the small incision lenticule extraction (SMILE) procedure for the correction of myopia and myopic astigmatism: results of a 6 month prospective study. Br J Ophthalmol. 2011;95(3):335–12. doi: 10.1136/bjo.2009.174284 [DOI] [PubMed] [Google Scholar]
- 2.Sekundo W, Chang JSM, Ganesh S, Hjortdal J, Wiltfang R. Keratorefractive lenticule extraction for myopia and myopic astigmatism with the VISUMAX 800: 6-month outcomes of a prospective multi-center post-market clinical follow-up study. J Refract Surg. 2025;41(3):e264–e271. doi: 10.3928/1081597x-20250204-03 [DOI] [PubMed] [Google Scholar]
- 3.Reinstein DZ, Archer TJ, Potter JG, Gupta R, Wiltfang R. refractive and visual outcomes of SMILE for compound myopic astigmatism with the VISUMAX 800. J Refract Surg. 2023;39(5):294–301. doi: 10.3928/1081597x-20230301-02 [DOI] [PubMed] [Google Scholar]
- 4.Jung H, Han SU, Kim S, et al. Comparison of two different contrast sensitivity devices in young adults with normal visual acuity with or without refractive surgery. Sci Rep. 2022;12(1):12882. doi: 10.1038/s41598-022-16855-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Dorr M, Elze T, Wang H, Lu ZL, Bex PJ, Lesmes LA. New precision metrics for contrast sensitivity testing. IEEE J Biomed Health Inf. 2018;22(3):919–925. doi: 10.1109/jbhi.2017.2708745 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Jia W, Zhou J, Lu ZL, Lesmes LA, Huang CB. Discriminating anisometropic amblyopia from myopia based on interocular inhibition. Vision Res. 2015;114:135–141. doi: 10.1016/j.visres.2015.02.003 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Wai KM, Vingopoulos F, Garg I, et al. Contrast sensitivity function in patients with macular disease and good visual acuity. Br J Ophthalmol. 2022;106(6):839–844. doi: 10.1136/bjophthalmol-2020-318494 [DOI] [PubMed] [Google Scholar]
- 8.Gao H, Miles TP, Troche R, Murdoch DM, Koefoed VF, Cason JB. Quality of vision following LASIK and PRK-MMC for treatment of myopia. Mil Med. 2022;187(9–10):e1051–e1058. doi: 10.1093/milmed/usab071 [DOI] [PubMed] [Google Scholar]
- 9.Zhao Y, Li M, Sun L, Zhao J, Chen Y, Zhou X. Lenticule quality after continuous curvilinear lenticulerrhexis in SMILE evaluated with scanning electron microscopy. J Refract Surg. 2015;31(11):732–735. doi: 10.3928/1081597x-20151029-01 [DOI] [PubMed] [Google Scholar]
- 10.Ye Y, Aruma A, Zhao W, Lu ZL, Zhou X, Zhao J. A novel quick contrast sensitivity function test in Chinese adults with myopia and its related parameters. Graefes Arch Clin Exp Ophthalmol. 2023;261(7):2071–2080. doi: 10.1007/s00417-023-06010-7 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Hu J, Bao Y, Wang Z, et al. Comparison of lenticular scanning quality and visual outcomes of keratorefractive lenticule extraction between VisuMax 800 and 500 systems. J Cataract Refract Surg. 2026. doi: 10.1097/j.jcrs.0000000000001927 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Chung JP, Paul RA. Visual and refractive outcomes of myopic lenticule extraction with the Zeiss VisuMax 500 and 800 systems. Clin Ophthalmol. 2025;19:4951–4956. doi: 10.2147/opth.S559787 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Cung HS, Tran LHT, Tran TN. Three-month outcomes of SMILE Pro with the VISUMAX 800 for myopic astigmatism in a large population. Clin Ophthalmol. 2025;19:417–425. doi: 10.2147/opth.S502915 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Varman A, Varman A, Balakumar D. Comparison of visual and refractive outcomes of keratorefractive lenticule extraction for compound myopic astigmatism between VisuMax and VISUMAX 800. Clin Ophthalmol. 2024;18:3557–3566. doi: 10.2147/opth.S492552 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Ganesh S, Brar S, Swamy DT. Comparison of clinical outcomes and patient satisfaction following SMILE performed with the VisuMax 800 in One Eye and VisuMax 500 in the contralateral eye. J Refract Surg. 2025;41(1):e14–e21. doi: 10.3928/1081597x-20241113-02 [DOI] [PubMed] [Google Scholar]
- 16.Yoo TK, Kim D, Kim JS, et al. Comparison of early visual outcomes after SMILE using VISUMAX 800 and VISUMAX 500 for myopia: a retrospective matched case-control study. Sci Rep. 2024;14(1):11989. doi: 10.1038/s41598-024-62354-y [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Lee CY, Lian LB, Chen HC, et al. The outcomes of first-generation (visumax 500) and second-generation (Visumax 800) keratorefractive lenticule extraction surgeries for astigmatism. Sci Rep. 2024;14(1):22224. doi: 10.1038/s41598-024-73303-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Lee CY, Chen HC, Yang SF, et al. Comparison between topographic-based and manifest-based astigmatism corrections in the second (Visumax 800)-generation keratorefractive Lenticule extraction surgery: a real-world study. Diagnostics. 2025;15(1). doi: 10.3390/diagnostics15010098 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Lee CY, Yang SF, Lian IB, Chen HC, Huang JY, Chang CK. The efficiency, predictability and safety between custom-Q Femotsecond laser in situ keratomileusis and second (Visumax 800) generation keratorefractive lenticule extraction surgery. Diagnostics. 2025;15(5):634. doi: 10.3390/diagnostics15050634 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Yue P, Wang Z, Wu D, Zhang H, Zhang P. The effect of small incision lenticule extraction on contrast sensitivity. Front Neurosci. 2023;17:1132681. doi: 10.3389/fnins.2023.1132681 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Sarayba MA, Ignacio TS, Binder PS, Tran DB. Comparative study of stromal bed quality by using mechanical, IntraLase femtosecond laser 15- and 30-kHz microkeratomes. Cornea. 2007;26(4):446–451. doi: 10.1097/ICO.0b013e318033e7cc [DOI] [PubMed] [Google Scholar]
- 22.Sarayba MA, Ignacio TS, Tran DB, Binder PS. A 60 kHz IntraLase femtosecond laser creates a smoother LASIK stromal bed surface compared to a zyoptix XP mechanical microkeratome in human donor eyes. J Refract Surg. 2007;23(4):331–337. doi: 10.3928/1081-597x-20070401-04 [DOI] [PubMed] [Google Scholar]
- 23.Kunert KS, Blum M, Duncker GI, Sietmann R, Heichel J. Surface quality of human corneal lenticules after femtosecond laser surgery for myopia comparing different laser parameters. Graefes Arch Clin Exp Ophthalmol. 2011;249(9):1417–1424. doi: 10.1007/s00417-010-1578-4 [DOI] [PubMed] [Google Scholar]
- 24.Lubatschowski H. Overview of commercially available femtosecond lasers in refractive surgery. J Refract Surg. 2008;24(1):S102–7. doi: 10.3928/1081597x-20080101-18 [DOI] [PubMed] [Google Scholar]
- 25.Malik NS, Moss SJ, Ahmed N, Furth AJ, Wall RS, Meek KM. Ageing of the human corneal stroma: structural and biochemical changes. Biochim et Biophys Acta. 1992;1138(3):222–228. doi: 10.1016/0925-4439(92)90041-K [DOI] [PubMed] [Google Scholar]
- 26.Zou C, Wang S, Huang F, Zhang YA. Advanced glycation end products and ultrastructural changes in corneas of long-term streptozotocin-induced diabetic monkeys. Cornea. 2012;31(12):1455–1459. doi: 10.1097/ICO.0b013e3182490907 [DOI] [PubMed] [Google Scholar]
- 27.Brummer G, Littlechild S, McCall S, Zhang Y, Conrad GW. The role of nonenzymatic glycation and carbonyls in collagen cross-linking for the treatment of keratoconus. Invest Ophthalmol Vis Sci. 2011;52(9):6363–6369. doi: 10.1167/iovs.11-7585 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Cartwright NEK, Tyrer JR, Marshall J. Age-related differences in the elasticity of the human cornea. Invest Ophthalmol Visual Sci. 2011;52(7):4324–4329. doi: 10.1167/iovs.09-4798 [DOI] [PubMed] [Google Scholar]
- 29.Weng S, Liu M, Yang X, et al. Evaluation of human corneal lenticule quality after SMILE with different cap thicknesses using scanning electron microscopy. Cornea. 2018;37(1):59–65. doi: 10.1097/ico.0000000000001404 [DOI] [PubMed] [Google Scholar]
- 30.Müller LJ, Pels E, Vrensen GF. The specific architecture of the anterior stroma accounts for maintenance of corneal curvature. Br J Ophthalmol. 2001;85(4):437–443. doi: 10.1136/bjo.85.4.437 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Bron AJ. The architecture of the corneal stroma. Br J Ophthalmol. 2001;85(4):379–381. doi: 10.1136/bjo.85.4.379 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Bulens C. Application of Contrast Sensitivity in Clinical Neurology [Ph.D. thesis]. 1988. Available from: http://hdl.handle.net/1765/51052 [DOI] [PubMed] [Google Scholar]
- 33.Damgaard IB, Riau AK, Liu YC, Tey ML, Yam GH, Mehta JS. Reshaping and customization of SMILE-derived biological lenticules for intrastromal implantation. Invest Ophthalmol Vis Sci. 2018;59(6):2555–2563. doi: 10.1167/iovs.17-23427 [DOI] [PubMed] [Google Scholar]
- 34.Vinciguerra P, Azzolini M, Airaghi P, Radice P, De Molfetta V. Effect of decreasing surface and interface irregularities after photorefractive keratectomy and laser in situ keratomileusis on optical and functional outcomes. J Refract Surg. 1998;14(2 Suppl):S199–203. doi: 10.3928/1081-597x-19980401-12 [DOI] [PubMed] [Google Scholar]
- 35.Vinciguerra P, Azzolini M, Radice P, Sborgia M, De Molfetta V. A method for examining surface and interface irregularities after photorefractive keratectomy and laser in situ keratomileusis: predictor of optical and functional outcomes. J Refract Surg. 1998;14(2 Suppl):S204–6. doi: 10.3928/1081-597x-19980401-13 [DOI] [PubMed] [Google Scholar]
- 36.Netto MV, Mohan RR, Medeiros FW, et al. Femtosecond laser and microkeratome corneal flaps: comparison of stromal wound healing and inflammation. J Refract Surg. 2007;23(7):667–676. doi: 10.3928/1081-597x-20070901-05 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Salomao MQ, Wilson SE. Corneal molecular and cellular biology update for the refractive surgeon. J Refract Surg. 2009;25(5):459–466. doi: 10.3928/1081597x-20090422-09 [DOI] [PMC free article] [PubMed] [Google Scholar]