Prospective, randomized, contralateral eye comparison of wavefront-guided and topography-guided LASIK

This randomized, contralateral eye-controlled clinical trial of 100 eyes of 50 patients compared wavefront-guided vs topography-guided LASIK. Postoperatively, both groups showed similar refractive results with excellent clinical outcomes and predictability.

Abstract

Purpose:

To compare the visual outcomes of eyes treated with ocular wavefront-guided (OWFG) LASIK vs topography-guided (TG) LASIK.

Setting:

Byers Eye Institute at Stanford University, Stanford, California.

Design:

Prospective, randomized, contralateral eye-controlled trial. Treatments were randomized according to ocular dominance.

Methods:

This study treated patients with myopia or compound myopic astigmatism with OWFG-LASIK (planned using the iDesign Advanced WaveScan Studio System aberrometer) in 1 eye and TG-LASIK (planned using the Contoura Vision and WaveLight Topolyzer Vario) in the fellow eye from January 2023 to April 2024. Postoperative evaluation was performed at 1, 3, 6, and 12 months postoperatively and consisted of visual acuity, manifest refraction, 5% and 25% low-contrast visual acuity, and higher-order aberrations (HOAs) (coma, trefoil, and spherical aberration).

Results:

100 eyes of 50 patients with myopia or compound myopic astigmatism were enrolled in the study and underwent successful treatments. 96 eyes of 48 patients completed 12 months of follow-up. At postoperative month 12, there were no statistically significant differences between the OWFG-LASIK and TG-LASIK groups for spherical equivalent (P > .05); HOAs, including coma, trefoil, and spherical aberrations (P > .05); proportion of eyes that had ≥20/20 uncorrected distance visual acuity (UDVA) (100% in the OWFG-LASIK group vs 98% in the TG-LASIK group); or proportion of eyes that had improved 5% and 25% low-contrast visual acuity. Eyes randomized to OWFG-LASIK had a significant greater percentage of eyes achieving UDVA of 20/12.5 compared with TG-LASIK (P = .003).

Conclusions:

OWFG LASIK and TG LASIK achieve similar refractive results with excellent clinical outcomes and excellent predictability in both groups.

Laser in situ keratomileusis (LASIK) is the most performed refractive surgery in the world, with technological advancements that have led to improved outcomes and high patient satisfaction.^1,2 Ocular wavefront-guided (OWFG) LASIK and topography-guided (TG) LASIK are 2 of the current state-of-the-art approaches for performing customized laser ablation treatments with the goals of enhanced correction of higher-order aberrations (HOAs) and improved visual outcomes. OWFG LASIK, which was U.S. Food and Drug Administration (FDA)–approved in 2003, uses an aberrometer to measure the refractive state of the whole eye and generates a wavefront map of the eye to generate the treatment plan for the excimer laser.^3,4 TG LASIK, which was FDA-approved in 2014, uses corneal topography combined with manifest refraction to generate an ablation profile for treatment.^5–7

Both OWFG LASIK and TG LASIK have shown clinical superiority compared with previous, noncustom techniques, including conventional and wavefront-optimized LASIK.^4,8,9 At time of writing, only 1 study in the refractive surgery literature has directly compared OWFG LASIK with TG LASIK in a randomized trial; Toda et al. compared 35 patients who were randomly assigned to either the OWFG LASIK or TG LASIK treatment group and found similar refractive outcomes.¹⁰ More extensive head-to-head evaluations of OWFG LASIK and TG LASIK, especially prospective trials that randomize treatment to fellow eyes of the same patient, are needed to determine differences in efficacy, safety, and predictability because comparison of visual outcomes can help guide treatment decisions. Therefore, the purpose of this study was to provide the first and largest-to-date, prospective, randomized, contralateral eye comparison of OWFG LASIK and TG LASIK.

METHODS

This single-center prospective, randomized contralateral eye-controlled clinical trial was approved by the institutional review board/ethics committee of Stanford University, and the trial was registered at ClinicalTrials.gov (NCT05588882). The study adhered to the tenets of the Declaration of Helsinki. Myopic patients with and without astigmatism were enrolled in the OWFG vs TG LASIK study after informed consent was obtained. Ocular dominance was determined by the Dolman method, and immediately before surgery, a computer program was used to randomly assign the dominant eye to receive either OWFG LASIK or TG LASIK.¹¹ In addition, the order of treatment was randomized to ensure that one-half of the patients had their OWFG eye treated first followed by the TG eye and the other one-half of the patients had their TG eye treated first followed by the OWFG eye.

Inclusion criteria included individuals aged 22 to 59 with myopia between −1.00 diopter (D) and −9.00 D with or without astigmatism less than or equal to 3.00 D. Exclusion criteria included individuals with excessively thin corneas (ie, <490 μm preoperative corneal thickness), evidence of corneal ectatic disorders or keratoconus, individuals with autoimmune disease, individuals who were nursing or pregnant, individuals with refractive error difference greater than 1.50 D between their 2 eyes, individuals with astigmatism greater than 3.00 D, or individuals with a difference of astigmatism greater than 1.00 D between their 2 eyes.

Preoperative evaluation of participants in the study consisted of a complete clinical history and eye examination, including measurement of uncorrected distance visual acuity (UDVA), manifest and cycloplegic refractions determined using the Early Treatment of Diabetic Retinopathy Study charts, 5% and 25% low-contrast visual corrected distance visual acuity (CDVA) (Precision Vision), slitlamp examination, dilated fundus examination, infrared pupillometry under photopic and scotopic conditions (Neuroptics), placido-based corneal topography (Atlas 9000, Carl Zeiss Meditec AG), corneal tomography (Pentacam, Oculus Surgical, Inc.), and wavefront aberrometry using an iDesign Advanced WaveScan Studio System (Johnson & Johnson Vision). The following were recorded preoperatively from the iDesign aberrometer: coma, trefoil, spherical aberration, and root mean square (RMS) total HOAs. Visual acuity and refractions throughout the study were completed using the Early Treatment of Diabetic Retinopathy Study standard charts. All eyes, whether undergoing OWFG LASIK or TG LASIK, underwent 6 wavefront scans, and the highest quality image was used for analysis. Wavefront aberrations were measured both before and after surgery, under physiologic (nondilated) pupil conditions, as was performed for preoperative surgical planning of OWFG ablations. Furthermore, a dilated, cycloplegic wavefront scan was completed preoperatively to account for the potential confounder of accommodation increasing the amount of measured myopia. All ocular aberrations were measured with wavefront aberrometry captured by the iDesign Advanced WaveScan Studio System (Johnson & Johnson Vision) high-resolution aberrometer. Wavefront reconstructions were performed with Fourier transformations and displayed as Zernike terms through the sixth order. Although luminance was not measured, all aberrometry measurements were performed in the same room under standardized mesopic lighting conditions. To account for the potential variability caused by measuring HOAs at different pupil diameters, all preoperative and postoperative data were normalized to a 5 mm pupil using the iDesign aberrometer software.

The same experienced surgeon (E.E.M.) performed all surgeries, treating both OWFG LASIK and TG eyes LASIK on the same day. The surgeon was informed of the treatment chosen for each patient immediately before surgery. Patients were not informed of the randomization and remained masked to which treatment modality was performed in each eye. For both the OWFG and TG LASIK procedures, a superior-hinged corneal flap was created using a 150-kHz Intralase iFS femtosecond laser (Johnson & Johnson Vision) with a flap diameter of 9.0 mm and thickness of 100 μm. OWFG treatments were planned and performed using the iDesign Advanced WaveScan Studio System aberrometer (Johnson & Johnson Vision) and Visx CustomVue Star S4 IR excimer laser (Johnson & Johnson Vision) with a nominal optical zone diameter of 6 mm. TG treatments were planned and performed using the Contoura Vision and WaveLight Topolyzer Vario (Alcon Laboratories, Inc.) and the Allegretto Wave Eye-Q 400 Hz excimer laser (Alcon Laboratories, Inc.) with a nominal optical zone diameter of 6.5 mm.

All patients were instructed on postoperative care after their refractive surgery, which consisted of topical prednisolone acetate 1% ophthalmic solution (PredForte, Allergan, Inc.) and topical moxifloxacin hydrochloride 0.5% ophthalmic solution (Vigamox, Alcon Laboratories, Inc.) 4 times daily for 7 days. Patients returned to the clinic for postoperative follow-up examinations on day 1, week 1, month 1, month 3, month 6, and month 12. On the postoperative day 1 visit, UDVA assessment, wavefront aberrometry, and a slitlamp examination were performed. On all subsequent postoperative visits, UDVA, manifest refraction, 5% and 25% contrast visual acuity, wavefront aberrometry, and a slitlamp examination were performed. Coma, trefoil, spherical aberration, and RMS total HOAs were recorded from the wavefront aberrometry performed at each visit.

Statistical Analysis

The main outcome measure of this clinical study was set a priori as UDVA at the 12-month postoperative visit. A sample size calculation was performed to determine that 34 patients were sufficient to confirm noninferiority of one procedure over the other with a power of 80% or more and at a 5% significance level. Secondary outcome measures included safety (defined as loss of lines of CDVA), predictability (percentage of eyes within ±0.50 D and ±1.00 D of the intended correction), changes in 5% and 25% low-contrast CDVA, and changes in HOAs. Statistical analysis was performed in R Statistical Software version (v. 4.3.0, R Foundation for Statistical Computing) and in Excel software (Microsoft Corp.). Where appropriate, comparison of means was performed according to a paired t test, 2-sided, and considered significant if the P value was less than 0.05. In addition, chi-square tests were performed on some qualitative or categorical measurements, and results were considered significant if the P value was less than 0.05. CIs were also calculated for percentages or frequencies and are reported for the 95% CI.

RESULTS

The study enrolled 100 eyes of 50 patients with myopia or compound myopic astigmatism who underwent successful OWFG LASIK in 1 eye and TG LASIK in the fellow eye, between January 2023 and April 2023. Two patients did not complete the 12-month examination and testing due to loss to follow-up; results are thus presented for 98 eyes of 48 patients who were able to complete all follow-up visits. The patient population included 24 men and 24 women with a mean age of 30.54 ± 6.44 years (range, 23 to 53 years). The preoperative patient characteristics are outlined in Table 1; there were no significant differences in refractive error or HOAs between the OWFG and TG eyes (Table 1).

Table 1.

Preoperative characteristics

Parameters	Wavefront-guided LASIK Mean ± SD (range)	Topography-guided LASIK Mean ± SD (range)	P value
Sphere (D)	−4.76 ± 2.09 (−9.25, −1.25)	−4.65 ± 2.15 (−9.00, −1.00)	.80
Cylinder (D)	0.88 ± 0.77 (0.00, 3.00)	0.80 ± 0.70 (0.00, 3.00)	.59
SE (D)	−4.32 ± 1.96 (−9.00, −1.125)	−4.25 ± 2.02 (−8.625, −0.750)	.86
Coma	0.20 ± 0.10 (0.05, 0.43)	0.17 ± 0.09 (0.01, 0.43)	.30
Trefoil	0.17 ± 0.09 (0.03, 0.43)	0.18 ± 0.09 (0.03, 0.45)	.70
SA	0.09 ± 0.14 (−0.30, 0.37)	0.09 ± 0.14 (−0.20, 0.42)	.87
HOAs (RMS)	0.36 ± 0.13 (0.12, 0.64)	0.35 ± 0.12 (0.15, 0.72)	.78

RMS = root mean square; SA = spherical aberration; SE = spherical equivalent

Safety and Efficacy

The efficacy and safety profiles of both refractive surgeries were excellent. Both OWFG and TG LASIK platforms had excellent UDVA results with no significant difference in the mean UDVA (Figure 1A). However, OWFG LASIK had a significantly greater percentage of eyes that achieved UDVA of 20/12.5 or better (52.08%) compared with TG LASIK (22.92%) (P = .003, chi-square). There was no significant difference in the mean change in CDVA between the 2 groups (Figure 1B). Only 1 eye in the TG LASIK group and none in the OWFG LASIK group lost 2 lines in CDVA (P = .32, chi-square). There were 13 eyes in the TG LASIK group that lost 1 line in CDVA compared with 6 eyes in the OWFG LASIK group (P = .11, chi-square). A similar number of eyes in both groups gained 1 line of CDVA (7 eyes in the OWFG group and 8 eyes in the TG group) (P = .80, chi-square).

Figure 1.

Standard graphs comparing OWFG LASIK with TG LASIK. A: UDVA outcomes at 12 months for OWFG-LASIK and TG-LASIK. B: Change in CDVA for OWFG LASIK and TG LASIK at 12 months. C: Distribution of achieved spherical equivalent refraction compared with attempted spherical equivalent refraction for OWFG LASIK at 12 months. D: Distribution of achieved spherical equivalent refraction compared with attempted spherical equivalent refraction for TG LASIK at 12 months. E: Spherical equivalent refraction accuracy at 12 months. F: Comparison of stability of spherical equivalent refraction from 1 to 12 months after OWFG LASIK and TG LASIK. OWFG = ocular wavefront-guided; TG = topography-guided

Refractive Error, Predictability, and Stability

There was no significant difference in mean spherical equivalent between OWFG LASIK and TG LASIK (P > .05) for the preoperative visit and all postoperative visits (Table 2). There was a significant difference in spherical error at postoperative months 1 and 3 that was not detected at the preoperative visit nor later postoperative visits, and a significant difference in cylindrical error at postoperative month 3 that was likewise not significant in earlier visits nor later postoperative visits. There was good predictability with strong correlations between the attempted spherical equivalent and achieved spherical equivalent for both the OWFG LASIK and TG LASIK groups (Figure 1C and D). Eyes in both groups achieved excellent spherical equivalent refraction accuracy, with 100% of eyes in both the OWFG LASIK and TG LASIK groups achieving a spherical equivalent within 1.00 D of the intended target, and with 98% and 100% for OWFG LASIK and TG LASIK eyes, respectively, achieving a spherical equivalent within 0.50 D of the intended target (Figure 1E). Eyes in both the OWFG LASIK and TG LASIK groups had excellent stability, with low percentages of eyes having a change in spherical equivalent by >0.50 D between months 3 and 12 in the OWFG and TG cohorts (4.25% vs 4.17%, respectively) (Figure 1F).

Table 2.

Postoperative refractive characteristics

Parameters	Wavefront-guided LASIK Mean ± SD	Topography-guided LASIK Mean ± SD	P value
Postop month 1 (N = 50)
Sphere (D)	−0.05 ± 0.26	−0.16 ± 0.29	.04*
Cylinder (D)	0.13 ± 0.18	0.18 ± 0.24	.24
SE (D)	0.02 ± 0.27	−0.07 ± 0.28	.11
Coma	0.25 ± 0.15	0.21 ± 0.12	.19
Trefoil	0.13 ± 0.08	0.11 ± 0.07	.18
SA	0.12 ± 0.18	0.14 ± 0.17	.53
HOAs (RMS)	0.43 ± 0.15	0.40 ± 0.14	.31
Postop month 3 (N = 50)
Sphere (D)	−0.09 ± 0.29	−0.23 ± 0.27	.01*
Cylinder (D)	0.15 ± 0.17	0.23 ± 0.24	.04*
SE (D)	−0.02 ± 0.31	−0.12 ± 0.28	.10
Coma	0.24 ± 0.14	0.23 ± 0.14	.74
Trefoil	0.12 ± 0.08	0.13 ± 0.07	.62
SA	0.14 ± 0.18	0.15 ± 0.17	.77
HOAs (RMS)	0.41 ± 0.17	0.41 ± 0.16	.92
Postop month 6 (N = 50)
Sphere (D)	−0.04 ± 0.31	−0.12 ± 0.27	.17
Cylinder (D)	0.16 ± 0.21	0.21 ± 0.25	.27
SE (D)	0.04 ± 0.29	−0.02 ± 0.26	.32
Coma	0.26 ± 0.17	0.20 ± 0.12	.06
Trefoil	0.13 ± 0.07	0.13 ± 0.07	.57
SA	0.15 ± 0.18	0.14 ± 0.18	.68
HOAs (RMS)	0.45 ± 0.16	0.40 ± 0.14	.09
Postop month 12 (N = 48)
Sphere (D)	−0.06 ± 0.27	−0.15 ± 0.26	.09
Cylinder (D)	0.25 ± 0.27	0.22 ± 0.26	.63
SE (D)	0.06 ± 0.26	−0.04 ± 0.28	.06
Coma	0.26 ± 0.16	0.20 ± 0.12	.09
Trefoil	0.12 ± 0.07	0.12 ± 0.06	.97
SA	0.12 ± 0.20	0.11 ± 0.16	.85
HOAs (RMS)	0.43 ± 0.19	0.38 ± 0.15	.17

RMS = root mean square; SA = spherical aberration; SE = spherical equivalent

^*Statistically significant

Contrast Sensitivity

Eyes in both OWFG and TG groups had comparable 5% and 25% CDVA at the preoperative visit (Figure 2). Regarding <5% low-contrast sensitivity at 12 months postoperatively, there were a similar number of eyes in the 2 groups that achieved a CDVA 20/80 or better (P = .674, chi-square) and 20/63 or better (P = .75, chi-square). For <25% low-contrast sensitivity at 12 months postoperatively, there were more eyes in the OWFG group that achieved a CDVA of 20/50 or better (P = .17) and 20/40 or better (P = .18) compared with eyes the TG group, but the differences between the 2 groups were not statistically significant.

Figure 2.

Graphs comparing low-contrast CDVA for OWFG LASIK and TG LASIK at 12 months. A: <5% low-contrast CDVA. B: <25% low-contrast CDVA.

Higher-Order Aberrations

There were no statistically significant differences in the average HOAs (RMS) between the 2 groups (Table 2). At the preoperative and all postoperative visits, there was no significant difference with coma, trefoil, and spherical aberration between the OWFG and TG treatment groups (Table 2).

DISCUSSION

To the authors' knowledge, this is the first prospective, contralateral eye-randomized study comparing OWFG LASIK and TG LASIK in the refractive surgery literature, and our results demonstrated excellent and comparable visual outcomes in both treatment groups at 12 months postoperatively. These findings are similar to results from Toda et al. who performed a prospective study comparing 35 patients who were randomly assigned to either the OWFG LASIK or TG LASIK treatment group, and found that outcomes of UDVA, CDVA, refractive characteristics, and HOAs were not significantly different between the 2 groups at 1 and 3 months postoperative, although OWFG LASIK patients had higher contrast sensitivity and reported milder subjective symptoms compared with the TG LASIK group.¹⁰ Previous retrospective comparisons of OWFG and TG laser platforms have also noted excellent results about efficacy, accuracy, and stability.^12,13

In this study, there was a significantly greater number of eyes in the OWFG LASIK group that achieved an UDVA of 20/12.5 or better after 1 year compared with eyes that underwent TG LASIK. Previous studies have noted UDVA correlates highly with and is the strongest predictor of patient satisfaction after LASIK, and thus, an advantage of achieving an excellent vs standard visual outcome with OWFG LASIK is noteworthy when considering patient satisfaction.^1,12,14 Lower preoperative corneal astigmatism has been correlated with excellent levels of visual acuity, although in our study, there was no significant difference in astigmatism between the 2 treatment groups and the number of eyes achieving 20/10 or better was similar for OWFG and TG eyes.¹⁵

OWFG LASIK and TG LASIK have each demonstrated small increases in HOAs in previous studies, although both approaches have shown clinical superiority in reducing postoperative HOAs compared with conventional wavefront-optimized LASIK.^{6,8,13,14,16,17} Regarding HOA outcomes in this study, we found that in both OWFG and TG eyes, RMS, spherical aberration, and coma were increased at 12 months compared with preoperative, while there was a decrease in trefoil. These results align with the well-established observation that the HOAs, minus trefoil, tend to increase after LASIK, and that the goal of customized ablation is to minimize this increase in HOAs.^16–19 Comparing the measurements of coma, trefoil, spherical aberration, and RMS between OWFG and TG eyes at preoperative or subsequent postoperative visits in our study, however, showed that the 2 platforms were essentially equivalent in their effect on HOAs at all postoperative visits after surgery.

Technological advances in surgical planning may also influence outcomes of customized ablation. For example, the Phorcides Analytical Engine (Phorcides LLC) is a new surgical planning software for TG LASIK that uses geographic imaging software to more precisely characterize irregularities on the anterior corneal surface and incorporates additional refractive data into algorithms to automatically generate an objective treatment recommendation. Recent studies have reported improved refractive outcomes when performing TG LASIK planned with the Phorcides Analytical Engine compared with conventional measurements with preoperative manifest refraction and topography.^5,20,21 Traditionally, performing TG LASIK is more time-consuming than OWFG LASIK due to the additional measurements and calculations required for TG ablation in contrast to OWFG technology, which is generally easier to use. However, automated software such as the Phorcides Analytical Engine can streamline treatment with TG LASIK and may equalize the 2 platforms in practical use and preoperative surgical planning. Subsequent comparative clinical trials of OWFG LASIK and TG LASIK should investigate outcomes in the setting of using software programs that both automate surgical planning and have been shown to improve refractive outcomes.

There were various limitations to this study. First, this study was conducted at a single institution involving outcomes from a single experienced refractive surgeon, which had the advantage of removing any potential effect of intersurgeon variability but may limit the generalizability of these results. Otherwise, the use of the recommended treatment settings for both OWFG LASIK and TG LASIK was used, and the results are likely generalizable. Second, this study was conducted using the Allegretto Wave EyeQ 400 Hz Excimer Laser, which is not the most current model of the device. The more recent WaveLight EX500 excimer laser is the current model and has been found to perform similarly to the Allegretto Wave Eye-Q excimer laser system, with the primary difference between them being the frequency of the laser pulse (500 Hz for EX500 vs 400 Hz for Eye-Q).²²

Future clinical trials comparing OWFG LASIK and TG LASIK should repeat the methodology in this study with updated laser platforms. Other future directions include comparing OWFG and TG LASIK prospectively for the treatment of hyperopia and hyperopic astigmatism, incorporating new surgical planning software such as the Phorcides Analytical Engine, and comparing subjective measures of quality of vision between OWFG and TG LASIK.

We conclude that the results of this study, which to our knowledge, is the first prospective, randomized, contralateral eye comparison of OWFG LASIK and TG LASIK, demonstrate that both customized ablation platforms are similarly predictable and effective, and produce excellent visual outcomes regarding refractive characteristics, HOAs, and contrast sensitivity.

WHAT WAS KNOWN

• Ocular wavefront-guided (OWFG) LASIK and topography-guided (TG) LASIK are 2 of the current state-of-the-art approaches of performing customized laser keratorefractive surgery.

• Both OWFG LASIK and TG LASIK have each been shown to have superior outcomes when compared with conventional and wavefront-optimized LASIK.

• Comparison of visual outcomes with OWFG LASIK vs TG LASIK can help guide treatment decisions for patients.

WHAT THIS PAPER ADDS

• This is the second and largest prospective, randomized clinical trial (to our knowledge), and the first with contralateral eye treatment randomization, comparing visual outcomes of OWFG LASIK vs TG LASIK.

• Eyes randomized to OWFG LASIK had a significant greater percentage of eyes achieving an UDVA of 20/12.5 compared with TG LASIK at 12 months postoperatively.

• OWFG LASIK and TG LASIK had statistically similar 12-month postoperative refractive results regarding spherical equivalent, HOAs, and low-contrast visual acuity.