Visual Outcomes and Safety of Ray-Tracing-Guided Laser-Assisted In Situ Keratomileusis: A Systematic Review and Meta-Analysis

Abstract

Topic

The aim of this analysis was to evaluate the visual outcome and safety profile after ray-tracing-guided laser-assisted in situ keratomileusis (RTG-LASIK) for myopia with or without astigmatism.

Clinical relevance

RTG-LASIK is a modern approach in refractive surgery using only objective and automated measurements aiming to improve visual outcomes.

Methods

In this systematic literature review and meta-analysis (International Prospective Register of Systematic Reviews [PROSPERO] ID: CRD420251179631), original peer-reviewed clinical studies on the visual outcomes of RTG-LASIK in eyes with myopia ± astigmatism were included. Exclusion criteria were corneal ectasia or other ocular comorbidities, hyperopia, and ablation profile modification by the surgeon. Cochrane, Embase, PubMed, and Web of Science databases were screened on 31 October 2025. The risk of bias was assessed using the Risk of Bias in Non-Randomized Studies-of Interventions tool. Primary effect measures were the proportions of eyes achieving 20/20 uncorrected distance visual acuity (UDVA) and losing ≥ 1 line of corrected distance visual acuity (CDVA) after RTG-LASIK. Secondary outcomes included the distribution of eyes regarding preoperative CDVA and postoperative UDVA, changes in Snellen lines for CDVA and UDVA relative to preoperative CDVA, postoperative manifest refraction spherical equivalent (MRSE), higher-order aberrations (HOAs), and other refractive parameters, synthesized using a random-effects model. In addition, postoperative complications were documented.

Results

In total, 14 clinical studies with a total of 1577 eyes were included in the meta-analysis. The pooled percentage of eyes with postoperative UDVA ≥ 20/20 was 99.17% (95% confidence interval [CI]: 95.75%, 99.84%; I² = 47.4%; 14 studies; n = 1577). Loss of ≥ 1 line in CDVA after RTG-LASIK occurred in 2.21% (95% CI: 1.07%, 4.52%; I² = 38.5%; 11 studies; n = 1384). CDVA showed an improvement in nearly half of all cases. In addition, postoperative UDVA tended to improve compared with preoperative CDVA. MRSE was within 0.5 D of target refraction in 95.21% but showed a slight trend toward overcorrection. Total HOAs increased slightly by 0.087 µm (95% CI: 0.027, 0.148; I² = 97.5%; 8 studies; n = 1189), while spherical aberration and trefoil tended to decrease after RTG-LASIK. The studies reported nine refractive retreatments and a generally favorable complication profile.

Discussion

This meta-analysis suggests that RTG-LASIK may be a safe and effective procedure for improving UDVA and CDVA in selected myopic eyes in the short term, with relatively low reported complication rates. However, larger prospective studies with longer follow-up are needed to confirm these findings and better define long-term safety and efficacy.

Trial Registration

This systematic review and meta-analysis has been prospectively registered at PROSPERO (PROSPERO ID: CRD420251179631).

Supplementary Information

The online version contains supplementary material available at 10.1007/s40123-026-01376-3.

Key Summary Points

Why carry out this study?

Myopic refractive errors with or without astigmatism are highly prevalent and commonly treated with refractive procedures such as laser-assisted in situ keratomileusis (LASIK), yet optimizing visual precision and minimizing complications remain ongoing clinical needs.

Ray-tracing-guided LASIK (RTG-LASIK) is a novel, fully objective measurement-based approach that may improve refractive accuracy and visual outcomes compared with conventional methods.

What was learned from the study?

RTG-LASIK may be an effective and generally safe refractive surgery option for selected patients, with reported improvements in both uncorrected and corrected visual acuity and relatively low retreatment and complication rates.

Although small increases in higher-order aberrations and a mild trend toward overcorrection have been observed, reported refractive accuracy is encouraging. However, additional comparative trials against other customized LASIK platforms are needed to clarify relative performance, refine patient selection, and optimize treatment algorithms.

Background

Laser-assisted in situ keratomileusis (LASIK) is one of the most frequently performed and most efficacious refractive surgeries to treat refractive errors, including myopia and astigmatism [1]. With the introduction of individually customized ablation profiles such as wavefront-guided or topography-guided LASIK, the postoperative results improved significantly compared with standard ablation profiles [2–4]. Standard noncustomized ablation profiles are calculated from the manifest refraction of a patient and showed good efficacy but may lead to an increase in higher-order aberrations (HOAs) hindering optimal visual quality [5–7]. Contrarily, in customized profiles, parameters such as the wavefront or topography are commonly used in addition to subjective manifest refraction to adjust the corneal ablation profile using the Gullstrand eye model. However, they may still induce significant amount of HOAs, particularly spherical aberration, because the algorithms use the Gullstrand eye model with four standardized planes to calculate the ablation profile, which is a simplification and generalization of the eye’s anatomy to enable easier calculations. With improvements in computational capacity, a simplification (or oversimplification) of an eye model may not be necessary, and more precise individual anatomical models can be created to calculate the optimal individual ablation profile for every patient, thereby potentially improving its efficacy and reducing disadvantages such as the surgically induced HOAs.

Ortiz et al. were the first to describe geometric ray-tracing to theoretically calculate the ablation profile for LASIK using individual eye measurements to modify the Gullstrand–Legrand eye model [8]. Then, in 2008, Mrochen et al. published a study on the iterative calculation of individual corneal ablation profiles using optical ray-tracing and an individualized eye model, which is the foundation of the currently available ray-tracing-guided LASIK (RTG-LASIK) system [9].

RTG-LASIK aims to increase refractive accuracy as well as safety while minimizing surgically induced HOAs, especially spherical aberrations. In 2025, RTG-LASIK was approved by the Food and Drug Administration (FDA; premarket approval application no. P020050/S043) for treatment of a manifest refraction spherical equivalent (MRSE) between −1.0 D and −9.0 D, a manifest refractive sphere up to −8.0 D, and a manifest refractive astigmatism up to −3.0 D at the spectacle plane, respectively [10]. To perform ray-tracing for patients, an individual eye model is created by combining Scheimpflug tomography data, including anterior chamber depth, axial length measurements, and wavefront data, into an individualized eye model (termed “Eyevatar” by the manufacturer). The algorithm uses ray-tracing in this individualized model combined with expected wound and epithelial remodeling healing patterns and potential biomechanical changes to calculate individual LASIK ablation profiles [11].

The first two clinical studies on RTG-LASIK used an older version of the algorithm using measurements of different devices [12, 13]. More modern studies are able to calculate the ablation profile using objective parameters from a single diagnostic device (WaveLight Plus/InnovEyes Sightmap System, Alcon Laboratories, Fort Worth, TX, USA) without the need for a subjective manifest refraction.

However, the efficacy and safety of the novel RTG-LASIK for treating myopic and astigmatic refractive errors have only been studied in small studies, producing promising but varying results.

Thus, the aim of this meta-analysis was to determine the efficacy and safety of RTG-LASIK in eyes with myopia and astigmatism.

Methods

Search Strategy

This meta-analysis and systematic literature review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Supplementary Fig. S1) and was registered in The International Prospective Register of Systematic Reviews (PROSPERO; ID: CRD420251179631). This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. Inclusion criteria were randomized controlled trials (RCTs), nonrandomized controlled clinical trials, cohort studies, or case series that analyzed the efficacy and safety of RTG-LASIK in adult patients with myopia with or without astigmatism. Exclusion criteria were the presence of hyperopia, other ocular comorbidities such as corneal ectatic diseases, prior ocular surgery, pregnant or breastfeeding women, preoperative corrected distance visual acuity (CDVA) below 20/32, both primary outcomes not reported, as well as a focus on other refractive procedures or manual surgeon modifications of the automatically calculated ablation profiles. Additionally, narrative reviews, ex vivo experiments, animal experiments, case reports, study protocols, and surgical techniques without reported or measured clinical outcomes were excluded. Astigmatism correction accuracy analysis included only studies that reported their results according to the standardized graphs by Dupps et al. [14]. Other modalities of astigmatism reporting were excluded.

We conducted a systematic literature search in Cochrane, Embase, PubMed, and Web of Science databases until 31 October 2025 using the following search terms: ((Ray-tracing[Title/Abstract]) OR (Ray tracing[Title/Abstract]) OR (Ray-tracing-guided[Title/Abstract]) OR (Ray trace[Title/Abstract]) OR (Ray trace guided[Title/Abstract]) OR (Ray-trace guided[Title/Abstract])) AND ((laser in-situ keratomileusis[Title/Abstract]) OR (laser in situ keratomileusis[Title/Abstract]) OR (laser-in-situ-keratomileusis[Title/Abstract]) OR (laser-in-situ keratomileusis [Title/Abstract]) OR (LASIK[Title/Abstract])) OR (InnovEyes[Title/Abstract]) OR (WaveLight Plus[Title/Abstract]). The search queries are shown in Supplementary Fig. S2. The search was restricted to peer-reviewed articles written in English or German. Two independent reviewers (M.F. and V.A.A.) screened each record independently, and disagreements were resolved by the blinded assessment of a third reviewer (H.-S.S.). Data were collected from the included studies by both reviewers independently, stored in Excel (Microsoft Co., Redmond, WA, USA), and compared afterward to prevent documentation errors.

Risk of Bias and Certainty Assessment

To assess the risk of bias, both reviewers (M.F. and V.A.A.) independently applied the Risk of Bias in Non-Randomized Studies-of Interventions (ROBINS-I) tool on all included studies, since the aim of the review was the follow-up evaluation of a cohort after an intervention without the necessity of a comparison group. Disagreements were resolved by the assessment of another researcher (H.-S.S.), who was blinded to the previous decisions. As a possible confounding factor, the level of preoperative MRSE was assessed. The assessment of evidence certainty of the primary outcome was performed by both reviewers (M.F. and V.A.A.) independently using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.

Effect Measures and Synthesis

The primary effect measures were the percentage of eyes achieving 20/20 uncorrected distance visual acuity (UDVA) to assess efficacy and the percentage of eyes losing one or more lines in CDVA to assess safety after RTG-LASIK. The time frame was the longest available follow-up in each respective study where the majority of patients (over 90% of the initial population) were still included. No weighting of follow-up durations was incorporated in the outcome synthesis.

Secondary outcomes were presented using a template similar to the standard refractive surgery reporting graphs [14] These included distributions of eyes by cumulative preoperative CDVA and postoperative UDVA; changes in Snellen lines for both CDVA and UDVA relative to preoperative CDVA; postoperative MRSE and manifest refractive astigmatism; and the angle of error for postoperative astigmatism. For each parameter, both percentages and the number of eyes in each category were documented. Additionally, pre- and postoperative higher-order aberrations (HOAs) were analyzed, including the root mean square (RMS) values for total HOAs, total coma, and spherical aberration. When two pupil diameters were reported for HOA assessment, the larger value was selected for data synthesis to capture the maximal magnitude of aberrations, given that HOAs generally increase with pupil diameter and that pupil size was not consistently reported across all included studies. For each ratio-scaled outcome, we extracted the measurements reported before surgery, the values from the most recent postoperative assessment, and the corresponding mean change together with the standard deviation. Studies that did not provide preoperative or postoperative information for a specific secondary endpoint were not included in the quantitative synthesis for that outcome. Reports of follow-up examinations that did not contain data for all eyes originally included in the study were excluded from the analysis at the study level. If studies did not directly report the change in continuous outcomes together with the associated standard error, these measures were derived from available individual patient data when possible. When individual data were not accessible, the required estimates were obtained from reported confidence intervals (CIs) [15]. If CIs were also not available, the changes of a parameter were calculated using the reported summary values before and after surgery in combination with the formulas for within-group mean differences described by Borenstein et al. [16]. If no correlation coefficients were available, we assumed a moderate correlation between pre- and postoperative values of r = 0.5 due to the paired structure of the data. If studies only reported their results divided into subgroups (e.g., low myopia and high myopia), the means and standard deviations were summarized using the Cochrane formulae [15]. Additionally, the number of patients and eyes, age, gender distribution, follow-up interval, and reported complications were extracted. If data on secondary endpoints were partially missing, the corresponding author of the respective study was contacted to provide the missing data.

Statistical Analysis

As considerable heterogeneity between the studies was expected, the pooled outcome measure was calculated using a generalized linear mixed model with random effects and logit transformation. Clopper–Pearson interval was used to calculate the CI for individual study results as no uncertainty measures were provided for proportional data in all included studies. Results from a fixed-effects model and random-effects models without studies published before 2020 (which used an earlier RTG-LASIK algorithm and an older laser platform [Allegretto Wave Eye-Q, WaveLight GmbH, Erlangen, Germany]) and without studies with serious risk of bias were supplemented as a sensitivity analysis. Heterogeneity was statistically assessed by calculating the I² statistic. The presence of publication bias was assessed by a funnel plot of the logit-transformed proportion of the number of eyes reaching a postoperative UDVA ≥ 20/20 and the Egger’s test for asymmetry. All analyses were performed using R version 4.5.1 (meta package version 8.2–1) [17].

Results

Study Selection

The literature search yielded a total of 303 results across all the abovementioned databases. As shown in the Consolidated Standards of Reporting Trials (CONSORT) flow chart (Fig. 1), 151 duplicate records were removed, and the titles and abstracts of 152 studies were screened. After excluding 118 records for not analyzing RTG-LASIK, 34 reports were retrieved for full-text review. After excluding 20 studies owing to fulfillment of the exclusion criteria, 14 studies with a total of 1577 eyes from 861 patients were included in the meta-analysis. Out of the excluded studies, two studies investigated RTG-LASIK for the correction of myopia and astigmatism, but they reported treatment plan modifications by the surgeon owing to high disagreements between the objectively calculated ablation profile and the subjective refraction [18, 19]. In addition, two excluded studies investigated RTG-LASIK as well but focused on epithelial changes and HOAs and did not report sufficient visual outcomes to be eligible for this meta-analysis [20, 21]. Data were extracted from subgroup-level data and synthesized in three studies [12, 22, 23]. No study provided individual-level data. Two corresponding authors provided missing data upon request [24, 25]. We included one study where the results of three subgroups were reported with modification of the ablation profile by the surgeon in one group. This group was excluded from the meta-analysis owing to fulfillment of the exclusion criteria, while the other two groups were synthesized and included into the meta-analysis because they used the automatically calculated ablation profile [22].

Fig. 1.

Consolidated Standards of Reporting Trials (CONSORT) diagram: flowchart of literature search and study selection

Characteristics of the Included Studies

The mean age of the participants ranged from 26.4 years to 36 years (missing data in two studies [22, 26]). The median follow-up period was 3 months (minimum, 3 months; maximum, 24 months). Two publications [12, 13] contained data from studies performed before 2020 using the Allegretto Wave Eye-Q laser system, while the other studies contained newer data using the automated RTG-LASIK system with the Alcon WaveLight EX500. Other study characteristics are presented in Table 1.

Table 1.

Characteristics of the included studies

Year	Author	Country	Study type	Design	N eyes (patients)	Mean age ± SD	Percentage of female and male individuals	Included follow-up	Flap preparation	Excimer laser
2024	Cao et al.	China	RCT	Prospective	35 (19)	27.37 ± 5.9 years	47%/53%	3 months	NR	WaveLight EX500 (Alcon)
2013	Cummings et al.	Ireland	Cohort study	Retrospective	47 (26)	30.7 ± 6.5 years	38%/62%	6 months	Microkeratome	Allegretto Wave Eye-Q 400 Hz Excimer laser (WaveLight/Alcon)
2023	He et al.	Australia	Cohort study	Retrospective	400 (200)	30.87 ± 5.4 years	58%/42%	3 months	Femtosecond laser	WaveLight EX500 (Alcon)
2020	Kanellopoulos	Greece, USA	Cohort study	Retrospective	40 (20)	36 ± 7.8 years	NR	6 months	Femtosecond laser	WaveLight EX500 (Alcon)
2024	Kanellopoulos	Greece, USA	Cohort study	Retrospective	40 (20)	29.95 ± 7.5 years	60%/40%	24 months	Femtosecond laser	WaveLight EX500 (Alcon)
2024	Kanellopoulos et al.	Germany, Greece, Australia	Cohort study	Prospective	212 (106)	30.3 ± 4.9 years	57%/43%	3 months	Femtosecond laser	WaveLight EX500 (Alcon)
2025	Khoramnia et al.	Germany	RCT	Prospective	30 (30)	33.6 ± 7.1 years	53%/47%	3 months	Femtosecond laser	WaveLight EX500 (Alcon)
2025	Luo et al.	China	Cohort study	Retrospective	77 (42)	26.4 ± 5.7 years	75%/25%	3 months	Femtosecond laser	WaveLight EX500 (Alcon)
2025	Luo et al.	China	Cohort study	Retrospective	65 (33)	27.3 ± 5.2 years	72%/28%	6 months	Femtosecond laser	WaveLight EX500 (Alcon)
2012	Schumacher et al.	Switzerland, Ireland, Germany	Cohort study	Prospective	111 (71)	33.5 ± 7.6 years	62%/38%	3 months	Microkeratome (81%), femtosecond laser (19%)	Allegretto Eye-Q (70%) or Concerto (30%, both WaveLight)
2025	Sitto et al.	USA	Cohort study	Prospective	336 (168)	33.3 ± 7 years	63%/37%	12 months	NR	WaveLight EX500 (Alcon)
2025	Tan et al.	China	Cohort study	Retrospective	118 (61)	26.64 ± 5.8 years	72%/28%	3 months	Femtosecond laser	WaveLight EX500 (Alcon)
2025	Thananjeyan et al.	Australia	Cohort study	Retrospective	32 (31)	NR	NR	3 months	Femtosecond laser	WaveLight EX500 (Alcon)
2024	Yuan et al.	China	RCT	Prospective	34 (34)	NR	85%/15%	3 months	Femtosecond laser	WaveLight EX500 (Alcon)

NA, not applicable; NR, not reported; RCT, randomized controlled trial

Comparison with Other LASIK Protocols

Five studies compared RTG-LASIK with other LASIK protocols. In comparison with wavefront-optimized LASIK, RTG-LASIK achieved a higher percentage of eyes with UDVA ≥ 20/20 and an equal to or lower percentage of eyes with a CDVA loss ≥ 1 line [12, 27]. In comparison with wavefront-guided LASIK, RTG-LASIK had a slightly lower percentage of eyes with an UDVA ≥ 20/20 but performed better in higher visual acuity levels (20/16 and 20/12.5) [12]. In this study, RTG-LASIK and wavefront-guided LASIK did not result in a loss of CDVA [12]. In comparison with topography-guided LASIK, RTG-LASIK achieved a higher percentage of eyes with UDVA ≥ 20/20 [12, 28]. The percentage of eyes with ≥ 1 line lost in CDVA with RTG-LASIK was better than topography-guided LASIK in one study [12] and worse when comparing the premarket approval trials [29]. In comparison with Q-value-adjusted LASIK, RTG-LASIK achieved a slightly higher percentage of eyes with UDVA ≥ 20/20 [25, 26] and a lower percentages with a loss ≥ 1 line in CDVA [26]. However, only three of these studies were RCTs, and other comparisons should be interpreted with caution [24, 26, 27].

Risk of Bias and Certainty of Evidence

An overview of the assessment of the ROBINS-I risk-of-bias tool as well as the certainty of the evidence is presented in Table 2. Overall, 3 studies were prospective RCTs [24, 26, 27], whereas 11 cohort studies were included [11–13, 22, 23, 25, 29–33]. The majority of the studies included (57.1%, eight studies) were retrospective. The overall risk of bias was graded “low risk of bias” in two studies [26, 27], “moderate” in nine studies [11–13, 22–25, 29, 30], and “serious” in three studies [31–33] (all due to exclusion of patients with adverse events from study results). The certainty of the evidence according to GRADE for the main outcome was “high certainty” in three studies [24, 26, 27], “low certainty” in eight studies [11–13, 22, 23, 25, 29, 30], and “very low certainty” in three studies [31–33] (all downgraded owing to a serious overall risk of bias in the ROBINS-I risk-of-bias tool).

Table 2.

Overview of the assessment of the ROBINS-I risk-of-bias tool and the certainty of evidence of the included studies

Year	Author	Bias due to confounding	Bias in classification of interventions	Bias in participant selection	Bias due to missing data	Bias in measurement of the outcome	Bias in selection of reported result	Overall risk of bias	Certainty of the evidence (GRADE)
2024	Cao et al.	Low	Low	Moderate	Low	Low	Low	Moderate	High certainty
2013	Cummings et al.	Low	Low	Low	Moderatea	Moderate	Low	Moderate	Low certainty
2023	He et al.	Low	Low	Low	Low	Moderate	Low	Moderate	Low certainty
2020	Kanellopoulos	Low	Low	Low	Low	Moderate	Low	Moderate	Low certainty
2024	Kanellopoulos	Low	Low	Moderate	Low	Moderate	Low	Moderate	Low certainty
2024	Kanellopoulos et al.	Low	Low	Seriousb	Low	Moderate	Low	Serious	Very low certaintyc
2025	Khoramnia et al.	Low	Low	Low	Low	Low	Low	Low	High certainty
2025	Luo et al.	Low	Low	Seriousb	Low	Moderate	Low	Serious	Very low certaintyc
2025	Luo et al.	Low	Low	Seriousb	Low	Moderate	Low	Serious	Very low certaintyc
2012	Schumacher et al.	Low	Low	Moderate	Low	Moderate	Low	Moderate	Low certainty
2025	Sitto et al.	Low	Low	Low	Low	Moderate	Low	Moderate	Low certainty
2025	Tan et al.	Low	Low	Low	Low	Moderate	Low	Moderate	Low certainty
2025	Thananjeyan et al.	Low	Low	Low	Low	Moderate	Low	Moderate	Low certainty
2024	Yuan et al.	Low	Low	Low	Low	Low	Low	Low	High certainty

^aFor the 6-month follow-up

^bExclusion of patients with adverse events

^cDowngraded owing to serious overall risk of bias

NA, not applicable; NR, not reported

Results of Synthesis

The pooled percentage of eyes reaching a postoperative UDVA of 20/20 after RTG-LASIK was 99.17% (95% confidence interval [CI]: 95.75%, 99.84%; I² = 47.4%; 14 studies; n = 1577 eyes, Fig. 2A). As shown in Fig. 3A, the postoperative UDVA tended to be better than preoperative CDVA over 20/20 Snellen visual acuity. More eyes gained ≥ 1 line in UDVA than lost ≥ 1 line Snellen visual acuity compared with preoperative CDVA (Fig. 3B). Only 1.39% (95% CI: 0.87%, 2.23%; I² = 0.0%; 9 studies; n = 1221 eyes) lost two lines and 0.08% (95% CI: 0.01%, 0.60%; I² = 0.0%; 8 studies; n = 1186 eyes) lost three lines of UDVA compared with preoperative CDVA. The pooled percentage of eyes losing ≥ 1 line in CDVA postoperatively was 2.21% (95% CI: 1.07%, 4.52%; I² = 38.5%; 11 studies; n = 1384 eyes, Fig. 2B). Nearly half of all included eyes gained ≥ 1 line in CDVA after RTG-LASIK, and 48.2% experienced no change in CDVA (Fig. 3C).

Fig. 2.

Forest plots of the primary outcomes of this meta-analysis on the refractive outcomes after ray-tracing-guided laser-assisted in situ keratomileusis (LASIK) for the treatment of myopia with or without astigmatism. A Percentage of eyes with a postoperative uncorrected distance visual acuity (UDVA) of ≥ 20/20 Snellen lines. B Percentage of eyes with a postoperative loss of ≥ 1 Snellen lines of corrected distance visual acuity (CDVA)

Fig. 3.

Postoperative refractive outcomes after ray-tracing-guided laser-assisted in situ keratomileusis (LASIK) for the treatment of myopia with or without astigmatism. A Cumulative postoperative uncorrected distance visual acuity (UDVA) compared with preoperative corrected distance visual acuity (CDVA). B Difference in Snellen lines between preoperative CDVA and postoperative UDVA. C Difference in Snellen lines between pre- and postoperative CDVA. Error bars represent the 95% confidence interval. n, number of eyes included

The postoperative MRSE was within 0.5 D and 1.0 D of the target refraction in 95.21% (95% CI: 89.61%, 97.9%; I² = 84.3%; 12 studies; n = 1427 eyes) and 99.77% (95% CI: 97.78%, 100%; I² = 57.9%; 11 studies; n = 1380 eyes), respectively. There was a slight trend toward overcorrection with 34.51% (95% CI: 25.54%, 44.75%; I² = 86.3%; eight studies; n = 893 eyes) having a postoperative MRSE between + 0.14 and + 0.5 D and 4.80% (95% CI: 2.11%, 10.57%; I² = 83.2%; eight studies; n = 893 eyes) having a postoperative MRSE between + 0.51 and + 1.0 D above the target refraction (Fig. 4A). As shown in Fig. 4B, there is some study-level variation in the accuracy of attempted versus achieved MRSE. However, the linear equations are evenly distributed around the dashed blue line, which indicates perfect accuracy, and are not crossing the ±0.5 D boundaries.

Fig. 4.

Accuracy of manifest refraction spherical equivalent (MRSE) relative to intended target refraction after ray-tracing-guided laser-assisted in situ keratomileusis (LASIK) for the treatment of myopia with or without astigmatism. A Distribution of postoperative deviation in MRSE from the intended target refraction. B Correlation between attempted MRSE correction and achieved MRSE correction. All available linear equations are depicted with the length according to the range of correction for the respective study. The thickness of each line corresponds to the number of eyes included. Dashed green line: ±0.5 diopter; dashed pink line: ±1.0 diopter. D, diopter

In terms of postoperative refractive astigmatism, 93.56% of all included eyes had residual astigmatism within 0.5 D (95% CI: 88.93%, 96.33%; I² = 82.8%; 11 studies; n = 1387 eyes) and 99.97% within 1.0 D (95% CI: 77.10%, 100%; I² = 0%; 10 studies; n = 1051 eyes). As shown in Fig. 5A, 79.76% had a residual astigmatism of 0.25 D or lower (95% CI: 74.91%, 83.89%; I² = 60.0%; ten studies; n = 1051 eyes). The proportion of eyes with an angle of error over +15° and under −15° after astigmatism correction was 0.45% (95% CI: 0.03%, 5.84%; I² = 0%; five studies; n = 382 eyes) and 1.38% (95% CI: 0.38%, 4.89%; I² = 0%; five studies; n = 382 eyes), respectively (Fig. 5B). The target-induced astigmatism vector correlated well with the surgically induced astigmatism vector in most studies, as shown in Fig. 5C. However, He et al. observed a trend toward astigmatism overcorrection in their study [23].

Fig. 5.

Refractive astigmatism after ray-tracing-guided laser-assisted in situ keratomileusis (LASIK) for the treatment of myopia with astigmatism. A Distribution of pre- and postoperative refractive astigmatism. B Distribution of the angle of error of the refractive astigmatism. C Correlation between attempted-induced astigmatism vector and surgically induced astigmatism vector. All available linear equations are depicted with the length according to the range of astigmatism for the respective study. The thickness of each line corresponds to the number of eyes included. Dashed green line: ± 0.5 diopter; dashed pink line: ± 1.0 diopter. Error bars represent the 95% confidence interval. D, diopter; N, number of eyes included

As shown in Fig. 6A, the RMS of total HOAs increased slightly by 0.087 µm (95% CI: 0.027, 0.148; I² = 97.5%; eight studies; n = 1189 eyes) after RTG-LASIK. Spherical aberration did not change significantly with a tendency to decrease by −0.022 µm (95% CI: −0.063, 0.020; I² = 92.1%; seven studies; n = 853 eyes, Fig. 6B). Total coma increased by 0.106 µm (95% CI: 0.034, 0.178; I² = 98.1%; six studies; n = 818 eyes, Fig. 6C), while total trefoil decreased by −0.014 µm (95% CI: −0.027, −0.001; I² = 74.7%; three studies; n = 319 eyes, Fig. 6D).

Fig. 6.

Pre- to postoperative change in higher-order aberrations (HOAs) after ray-tracing-guided laser-assisted in situ keratomileusis (LASIK) for the treatment of myopia with or without astigmatism. A Change in total HOAs. B Change in spherical aberration. C Change in coma. D Change in trefoil. CI, confidence interval

Summary statistics and effect estimates with corresponding confidence intervals for all outcomes and studies are shown as forest plots in Supplementary Figs. S3–S7.

Sensitivity Analysis

Multiple sensitivity analyses were performed. First, a fixed-effects model resulted in slightly worse percentages of eyes reaching a postoperative UDVA ≥ 20/20 (96.58%; 95% CI: 95.56%, 97.37%; I² = 47.4%; 14 studies; n = 1577 eyes) and losing one or more lines in CDVA (3.03%; 95% CI: 2.25%, 4.08%; I² = 38.5%; 11 studies; n = 1384 eyes) compared with the random-effects model. Secondly, a random-effects meta-analysis with exclusion of the two publications containing data older than 2020 using an earlier RTG-LASIK algorithm [12, 13] resulted in slightly better percentages of eyes reaching a postoperative UDVA ≥ 20/20 (99.53%; 95% CI: 96.76%, 99.93%; I² = 0.0%; 12 studies; n = 1419 eyes) and losing one or more lines in CDVA (1.85%; 95% CI: 0.70%, 4.80%; I² = 49.1%; 9 studies; n = 1226 eyes) after RTG-LASIK. Thirdly, a random-effects meta-analysis with exclusion of the three publications with a serious risk of bias and very low certainty of evidence [31–33] resulted in a similar percentage of eyes reaching a postoperative UDVA ≥ 20/20 (98.91%; 95% CI: 93.56%, 99.82%; I² = 35.1%; 11 studies; n = 1223 eyes) and a worse percentage of eyes losing one or more lines in CDVA (3.65%; 95% CI: 2.25%, 5.87%; I² = 28.9%; 8 studies; n = 1030 eyes) after RTG-LASIK.

Complications

Overall, 7 out of 14 studies did not report on complications (407 eyes, Supplementary Table S1) [11, 22, 24, 25, 30, 32, 33]. Two of these studies excluded cases with complications during the 3-month follow-up interval from their study [32, 33]. Three studies reported no complications in their study (464 eyes) [23, 26, 27]. Across the remaining four studies (706 eyes), the reported safety outcomes were generally favorable, with most adverse events being transient and resolving without long-term implications or need for retreatment. Cummings et al. observed one case of moderate dry eye affecting refractive outcome, which resolved by 6 months, and noted no complications at 6 or 12 months, although two eyes required retreatment for undercorrection by 12 months [12]. Kanellopoulos et al. documented a single non-procedure-related foreign body event and a transient CDVA loss of two or more lines in three eyes during early follow-up, all of which resolved by the third month after RTG-LASIK [31]. In addition, one case with an adverse event was excluded from their analysis. Schumacher et al. reported one early retreatment due to dissatisfaction leading to exclusion, transient diffuse lamellar keratitis in four eyes on the first postoperative day that resolved after 1 month, and one case of corneal epithelial ingrowth that resolved by 3 months [13]. Six eyes underwent retreatment for refractive over- or undercorrection by the third month. The parameters for retreatment were not reported. In the largest dataset of a study reporting complications, Sitto et al. found that 37 eyes experienced ocular complications in the study period, including corneal flap-related issues in 11 eyes, dry eye symptoms in 3 eyes, need for punctal plug insertion in 2 eyes, and diffuse lamellar keratitis in 3 eyes [29]. Serious adverse events occurred in four eyes, including retinal tears in two eyes, and no retreatments were performed during the study period.

Publication Bias

As shown in Fig. 7, the funnel plot showed a dense distribution in studies with a higher standard error and four outliers with a smaller standard error reporting a worse visual outcome. Two of the outliers are older studies presenting data before the development of the automated RTG-LASIK system [12, 13]. Egger’s test for asymmetry resulted in a statistically significant asymmetry (p = 0.005), indicating a significant publication bias.

Fig. 7.

Funnel plot of the proportion of eyes reaching a postoperative uncorrected distance visual acuity (UDVA) of 20/20 Snellen lines after ray-tracing-guided laser-assisted in situ keratomileusis (LASIK) for the treatment of myopia with or without astigmatism

Discussion

This meta-analysis indicates that RTG-LASIK is associated with favorable visual outcomes, with 99.17% of all eyes achieving UDVA ≥ 20/20 in the included studies on patients with myopia ± astigmatism and no other ocular comorbidities. While 2.21% lost ≥ 1 line in CDVA postoperatively, more eyes gained a line than lost a line in UDVA compared with preoperative CDVA, and nearly half of all eyes gained at least one line in CDVA. The postoperative MRSE and astigmatism showed high accuracy to the target refraction with a minimal trend toward overcorrection. In addition, spherical aberration and trefoil decreased marginally, and total HOAs and coma only increased slightly.

Compared with a smaller meta-analysis by Fares et al., which analyzed the refractive outcomes after wavefront-guided and non-wavefront-guided LASIK and found percentages between 67% and 100% of eyes reaching ≥ 20/20 UDVA, the present meta-analysis found better results for RTG-LASIK (99.17%) [34]. Cheng et al. compared topography-guided LASIK with wavefront-optimized LASIK and observed that 90.85% (387/426 eyes) and 89.91% (383/426 eyes) of all eyes reached an UDVA ≥ 20/20, respectively, which is also inferior to the percentage after RTG-LASIK [35]. Another meta-analysis comparing microkeratome and femtosecond wavefront-guided LASIK found a lower proportion of eyes within ± 0.5 D of the target refraction (89.76 and 92.5%, respectively) compared with the present data (95.21%; 95% CI: 89.61%, 97.9%; I² = 84.3%; 12 studies; n = 1427 eyes) [36]. Some of the studies included herein analyzed the efficacy and safety of RTG-LASIK compared with other customized LASIK ablation profiles, as shown in the Results section [12, 24, 25, 27–29]. These preliminary short-term comparative studies reported favorable results for RTG-LASIK in terms of UDVA and lost lines in CDVA compared with wavefront-optimized LASIK, topography-guided LASIK, and Q-value-adjusted LASIK, as well as similar results compared with wavefront-guided LASIK. One of the key benefits of RTG-LASIK over prior customized treatment strategies is the automated calculation of the ablation profile without the incorporation of manifest subjective refraction. This minimizes the risk for transcription errors and could lead to a more standardized and faster process. Yet, the quality and number of patients included in these comparative studies remain limited, and a significant publication bias was found for the main outcome in the included studies. In addition, the present meta-analysis does not include a direct control group. A formal subgroup analysis comparing RTG-LASIK with other ablation strategies such as wavefront-guided or topography-guided LASIK was not feasible because the currently available comparative studies are few and show substantial heterogeneity in study design, patient populations, and reported outcomes. Consequently, the comparisons discussed above rely on results from separate studies and should be interpreted with caution. Future randomized and comparative studies will be necessary to enable more robust meta-analytic comparisons between RTG-LASIK and established treatment profiles.

The preliminary favorable visual results observed herein may be due to numerous factors. An obvious potential culprit is the further individualization of the ablation profiles with consideration of more ocular variables in the objective RTG-LASIK approach optimizing the outcomes [9, 11]. As this approach incorporates wavefront data to minimize HOAs, especially spherical aberrations, the better visual outcome may be explained by a lower degree of postoperative HOAs compared with older customized ablation profiles [23]. The present meta-analysis showed a small increase in total HOAs (0.087 µm), which falls below the 0.1 µm level suggested by Xu et al. as clinically relevant [37]. Moreover, spherical aberrations and trefoil even decreased marginally after RTG-LASIK, which may reduce the amount of starburst symptoms [19]. However, all HOA results showed high heterogeneity between studies, which may be explained by varying measurement conditions (e.g., pupil diameter, device setup, algorithm version, transition zone diameter) and warrants further research. Nevertheless, the importance of minimizing postoperative HOAs is also supported by the similar refractive results after wavefront-guided LASIK, which also included the patient-specific HOAs [12].

Another hypothesis proposed by Kanellopoulos takes the width of the transitional zone of the ablation profile around the optical zone into account [30]. The author writes that older ablation profiles used an optical zone of 6.5 mm with a transitional zone up to 1.5 mm, whereas the transitional zone in RTG-LASIK was set at 2.5 mm in all studies published after 2020. A smaller transitional zone may lead to a steeper step in corneal curvature toward the corneal periphery, possibly increasing postoperative HOAs and dysphotopsia, whereas a wider transitional zone may lead to a more regular postoperative corneal shape with reduced spherical aberrations [38]. This may also be one of the reasons, in addition to an older algorithm and the usage of multiple devices, for the slightly worse results reported after RTG-LASIK in studies published before 2020, as they only used a 1 mm transitional zone [12, 13]. However, a larger ablation profile diameter also increases the amount of ablated corneal tissue according to Munnerlyn et al. [39], as evidenced by some of the included studies, which found RTG-LASIK ablation depth to be larger than other LASIK protocols [25–27, 33]. While the improvements in visual results are desirable, long-term risk of corneal ectasia due to increased corneal tissue ablation needs to be monitored. However, currently there is no report of corneal ectasia after RTG-LASIK in the included studies.

In total, nine refractive retreatments were reported along with other complications commonly associated with LASIK such as diffuse lamellar keratitis, epithelial ingrowth, or dry eye [36]. Other adverse events included two retinal tears [29] as well as transient losses in CDVA. Of note, half of all included studies did not report on complications, and three studies even excluded patients with severe adverse events. Therefore, there could be an underestimation of the incidence of adverse events due to inconsistent complication reporting. However, as the complication outcomes of all LASIK ablation profiles may be more associated with the surgical manipulation of corneal tissue during LASIK than the distribution of corneal tissue ablation, RTG-LASIK may have similar complication rates to other customized ablation profiles. Nevertheless, further studies on adverse events after RTG-LASIK are imperative to better understand its safety profile.

Despite the promising automated, objective, and individualized approach of RTG-LASIK, there are significant challenges to address. First, the process of dealing with discrepancies over 0.75 D between subjective and wavefront MRSE remains disputed. Currently, the FDA-approved RTG-LASIK for “patients with magnitude of the spherical equivalent (SE) difference between the Manifest Refraction (MRSE) and the Sightmap-measured refraction SE being less than 0.75D” [10]. This discrepancy was found in nearly half of all patients in the study by Yuan et al. [26] and may occur due to accommodation during the examination with the Wavelight Plus/InnovEyes Sightmap device, possibly leading to a myopic shift [22, 40]. Accommodation may occur despite the built-in fogging function of the device owing to an insensitivity of patients in this regard [24]. This may be the cause of the slight trend toward overcorrection in terms of MRSE found in this meta-analysis. Notably, the magnitude of overcorrection reported across studies is small and may be clinically well tolerated in many patients. One proposed strategy to mitigate this effect is the use of cycloplegic wavefront and refraction measurements, as suggested by Thananjeyan et al. [22]. However, this approach may influence the corneal vertex position or lead to discrepancies in the real-life setting distance refraction [29, 41]. Another option may be to modify the automatically calculated ablation profile by the surgeon. There have been four studies to date that utilized a surgeon-modified ablation profile [18, 19, 22, 24]. The initial results are promising, even improving the excellent standard RTG-LASIK outcomes [24]. Yet, independently conducted RCTs are needed to support the results of surgeon-modified approaches or to develop alternative strategies to minimize refractive inaccuracies.

Second, RTG-LASIK requires more objectively measured data in sufficient quality than other customized LASIK techniques to perform accurate ray-tracing leading to a more time-consuming process and a higher dependency on patient compliance and pupil diameter. Thananjeyan et al. reported that the necessary pupil size of ≥ 5 mm for calculation of the 6.5 mm optical treatment zone was reached in 96% of all cases in a scotopic setting [22]. In other cases, the inability to acquire high-quality data in patients (e.g., with high HOAs) rendered them ineligible for RTG-LASIK [11]. Further developments in device technology (e.g., by incorporating optical coherence tomography) may increase the reliability of measurements and thus the number of eligible patients.

Third, despite the good results in correcting astigmatism with a residual refractive cylinder within 0.5 D in 93.56% of 1387 eyes, a trend toward overcorrection in eyes with higher preoperative astigmatism was observed. He et al. included 175 eyes with myopic astigmatism of up to 4.4 D in their study and found a slope of 1.13 (right eyes) and 1.11 (left eyes) for the correlation regression line between target-induced astigmatism vector and surgically induced astigmatism vector [23]. In contrast, the other four studies found a more accurate correlation between 0.97 and 1.01 (n = 207 eyes) [27, 31–33]. Therefore, additional studies are needed to determine whether there is a reproduceable trend of overcorrection in eyes with higher astigmatism necessitating further adjustments to the ablation protocol.

This meta-analysis is subject to potential limitations. RTG-LASIK is a novel procedure and therefore only a limited number of studies, mostly industry-sponsored ones, with a short follow-up (median: 3 months) are currently available. Most included studies are retrospective and employ no randomization or comparison with other treatment procedures. Thus, the overall certainty of evidence is low, with moderate-to-serious bias in many included studies and signs of publication bias in the available literature. No individual-level data were available in any study and therefore, the clustered nature of the data due to inclusion of both eyes of a patient in some studies could not be sufficiently addressed. This likely leads to falsely narrow confidence intervals in all primary and secondary endpoints and could significantly impact the overall interpretation of the synthesized data. Future studies should either publish the individual-level data or randomly select one eye for study inclusion to enable data synthesis without the introduction of a clustered data bias. In addition, the pupil diameter to analyze HOAs was heterogeneous in the included studies, limiting the generalizability of the synthesized results. Another limitation is the missing report of effect sizes and correlation coefficients in some of the included studies. In these studies, the change in HOAs and the respective standard error had to be individually calculated assuming a moderate within-group correlation (r = 0.5) owing to the pre–post nature of the data. A higher within-group correlation in reality would result in lower CIs and vice versa. Lastly, RTG-LASIK is currently only available for myopia with or without astigmatism without other ocular comorbidities, but not for hyperopia or more complicated refractive populations, indicating the need for further development.

Conclusions

Current evidence suggests that RTG-LASIK may be a safe and individualized refractive option for myopia with or without astigmatism, demonstrating favorable short-term visual and refractive outcomes in selected populations. Reported results indicate improvements in postoperative UDVA, in some cases exceeding preoperative CDVA, along with reductions in spherical aberrations and trefoil and only small increases in total HOAs. A slight trend toward overcorrection in MRSE and astigmatism has been observed and warrants further investigation. However, interpretation of these findings is limited by clustered data, short follow-up, predominantly retrospective study designs, heterogeneity in HOA results, and evidence of publication bias, which restrict external validity. Prospective trials and randomized controlled studies with longer follow-up are needed to confirm these outcomes and to compare automated RTG-LASIK protocols with earlier customized approaches and surgeon-modified techniques.

Supplementary Information

Below is the link to the electronic supplementary material.

Author Contributions

Maximilian Friedrich: conceptualization, data curation, formal analysis, investigation, methodology, project administration, visualization, and writing—original draft; Victor A. Augustin: conceptualization, data curation, formal analysis, investigation, methodology, project administration, visualization, and writing—original draft; Gerd U. Auffarth: data curation, funding acquisition, project administration, resources, supervision, and writing—review and editing; Ramin Khoramnia: data curation, formal analysis, investigation, and writing—review and editing; Hyeck-Soo Son: conceptualization, data curation, formal analysis, investigation, methodology, project administration, resources, supervision, visualization, and writing—review and editing.

Funding

No funding or sponsorship was received for this study or publication of this article.

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Conflicts of Interest

Victor A. Augustin reports research grants from Kowa Co. and travel grants from Roche Holding AG outside the submitted work. Gerd U. Auffarth reports lecture fees and/or research grants from Johnson & Johnson Vision, Alcon Laboratories, Carl Zeiss Meditec AG, Hoya Corp., Kowa Co., Ltd., Afidera, Teleon Ltd., Rayner Intraocular Lenses Ltd., Oculus Optikgeräte GmbH, Ophthec BV, Santen, Contamac, Cristalens, Elios, Eyebright, Fluoron, Hanita, and Biotech; and nonfinancial support from EyeYon and Hanita outside the submitted work. Ramin Khoramnia reports lecture fees and research grants from Alcon, Heidelberg Engineering, Johnson & Johnson Vision, Carl Zeiss Meditec AG, Hoya Corp., and Teleon Ltd., outside the submitted work. Maximilian Friedrich and Hyeck-Soo Son have nothing to disclose.

Ethical Approval

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.