Comparison Between the Wavefront-Optimized and Custom-Q Aspheric Ablation Profiles in Myopic Eyes With Two Different Q-targets: A Contralateral Eye Study

Depósito de investigación de la Universidad de Sevilla https://idus.us.es/ “This is an Accepted Manuscript of an article published in Journal of Refractive Surgery on 2022 available at: https://doi.org/10.3928/1081597X- 20221005-01” Comparison Between the Wavefront-Optimized and Custom-Q Aspheric Ablation Profiles in Myopic Eyes With Two Different Q-targets: A Contralateral Eye Study Timoteo González-Cruces, DO, MSc; Alberto Villarrubia, MD; Álvaro Sánchez Ventosa, MD; Elisa Palacín Miranda, MD; Rosa Castillo Eslava, DO; Aurora Gomera Martinez, DO; José Alberto García Párrizas, DO; Pablo Torres Huelva, DO; Jose María Sánchez-González, DO, MSc, PhD; Antonio Cano-Ortiz, MD, PhD ABSTRACT PUROSE: To compare two aspheric ablation profiles in myopic refractive surgery using different asphericity targets. METHODS: Patients underwent laser in situ keratomileusis (LASIK) with the WaveLight EX500 laser platform (Alcon, WaveLight Laser Technologie). Asymmetric surgery was performed, programming the wavefront-optimized (WFO) ablation profile in one eye and the custom-Q (CQ) profile in the contralateral eye. The patients were divided into two groups following a systematic randomization method. The Q-target programmed for the preoperative Q group was equal to the preoperative asphericity of the CQ profile, and for the -0.6 Q-target group, the Q-target was set to -0.6. RESULTS: The study included 100 patients (200 eyes). Both groups had comparable safety and efficacy indexes greater The continuously evolving ophthalmic industry together with ongoing advances in biomedical research have made corneal refractive ablation surgery the technique of choice in low and medium myopia surgery. Several authors have reported high safety and efficacy indexes in both laser in situ keratomileusis (LASIK)1,2 and photorefractive keratectomy.3,4 However, the main challenge for clinicians and engineers is to control higher order aberrations than 1. A similar oblate shift in postoperative asphericity was seen in both groups regardless of the ablation profile and programmed Q-target. Asphericity was 0.33 ± 0.34 and 0.35 ± 0.29 (P = .18) in the preoperative Q group and 0.26 ± 0.28 and 0.26 ± 0.27 (P = .89) in the -0.6 Q-target group for WFO and CQ, respectively. A lower spherical aberration was found with CQ compared to WFO when the Q-target was set to -0.6: 0.211 ± 0.121 versus 0.144 ± 0.114 (P < .01). However, no statistically significant differences were found when the preoperative Q-target was used. CONCLUSIONS: WFO and CQ treatments are similar in terms of refractive and visual outcomes. CQ offers greater control over the increase in positive spherical aberration after myopic refractive surgery, but it does not represent an advantage over WFO in the oblate shift in postoperative asphericity regardless of the Q-target programmed. [ J Refract Surg . 2022;38(11):698-707.] (HOAs) generated by central myopic ablation, which are responsible for the decrease in visual quality and dysphotopic phenomena in mesopic environments.5 Specifically, an increase in postoperative positive spherical aberrations has been reported.6 This finding is closely associated with the oblate corneal geometry induced by refractive surgery.7,8 As a result, ablation algorithms used by excimer lasers have been implemented in the past decade, moving from standard multizone profiles to wavefront-guided or topographyguided profiles. Several studies9-11 have shown the superiority of these new patterns of guided ablation in relation to the induction of HOAs. Nonetheless, no statistically significant differences in refractive or highcontrast visual acuity have been found.12 The approach of these new guidance systems is to minimize the effect of HOAs induced by ablation surgery, generate surfaces with smoother transitions, and respect the physiological geometry of the cornea. In the same way, the latest generations of excimer laser platforms have incorporated optimized ablation patterns into their standard (not personalized) treatments to improve postoperative corneal profiles. The WaveLight excimer laser platforms, the 400-Hz and the EX500 (Alcon, WaveLight Laser Technologie AG), have a standardized treatment modality called wavefront optimized (WFO). Compared to conventional treatments, this modality performs an additional ablation in the periphery to correct the positive spherical aberration induced by central myopic correction.13 The next level of customization in refractive treatment offered by this platform is custom-Q (CQ). In this option, the ablation pattern is determined by the topographic parameters of each patient and allows the surgeon to establish a target asphericity in each case. Although the CQ profile is presented as a higher degree of personalization in treatment, its advantage over standardized patterns is controversial in the scientific literature. Although some authors have suggested that CQ treatment is superior to WFO when the programmed target asphericity is -0.6,14 others have not found statistically significant differences between the two procedures.9 In addition, the possibility of setting a custom asphericity target with the CQ mode creates the need to define an optimal asphericity target. Intra-subject randomized comparative studies are necessary to avoid all possible biases and to determine the best approach to programming target values in the CQ modality. This study aimed to determine an optimal asphericity target and to compare the WFO ablation profile with the CQ profile using two different Q-targets. PATIENTS AND METHODS A prospective randomized cohort study of 200 eyes of 100 myopic patients who underwent LASIK surgery at Hospital La Arruzafa, Cordoba, Spain, was conducted from February to December 2021. All patients had surgery with the aspheric WFO and CQ ablation profiles of the WaveLight EX500 laser platform. A systematic randomization method was used in which patients with an evennumbered medical record underwent surgery with the CQ profile in their right eye and the WFO profile in their left eye. Those with an odd-numbered medical record underwent WFO in their right eye and CQ in their left eye. In the first 50 patients (100 eyes) included in the study (preoperative Q group), the postoperative Q- target was programmed to be equal to the preoperative physiological Q in the eye in which the CQ treatment was performed. A second group of 50 patients (100 eyes) (-0.6 Q-target group) underwent CQ treatment with a final Q-target of -0.6 (independent of delta DQ = Q-target – preoperative Q) in one eye and WFO in the contralateral eye. The manufacturer recommends a maximum final target of Q equal to -0.6. As a result, DQ was not used as a target. In this latter group, an adjustment in the CQ treatment nomogram was made to compensate for the increased central ablation (myopic hypercorrection) that results from an increase in corneal prolaticity. The sphere target needed to be modified to match the central ablation depth generated before the increased Q-target. Inclusion criteria were: patients older than 21 years of age with refractive stability (at least 2 years), manifest refraction spherical equivalent between -6.00 and -0.50 diopters (D) and astigmatism of 3.00 D or less, healthy eyes, normal intraocular pressure (10 to 21 mm Hg), and corrected distance visual acuity (CDVA) of at least 0.10 logMAR. All patients were instructed to discontinue contact lens use for at least 1 week for soft lenses and 1 month for rigid gas permeable contact lenses prior to baseline examination. Exclusion criteria were: anisometropia greater than 1.00 D in the spherical equivalent, previous eye surgery, irregular astigmatism, corneal thickness of less than 500 µm, highest topographic elevation point on the posterior corneal surface, within the 3-mm area around the thinnest point on pachymetry, greater than 16 µm (Pentacam AXL; Oculus Optikgeräte GmbH), or any topographic suspicion of corneal ectasia. All patients signed an informed consent after an explanation of the nature and possible consequences of the study and were made aware of surgical (photorefractive keratectomy or Implantable Collamer Lens [STAAR Surgical] surgery) and non-surgical (glasses or contact lenses) alternatives to correct their myopia. The study was approved by the ethics committee of Reina Sofia Hospital, Cordoba, Spain, and adhered to the tenets of the Declaration of Helsinki. The preoperative examination consisted of manifest cycloplegic and noncycloplegic refraction, Scheimpflug corneal tomography (Pentacam AXL), corneal reflection topography (Topolyzer Vario; Alcon Laboratories, Inc), pupillometry (Colvard infrared pupillometer; OASIS Medical, Inc), Goldmann applanation tonometry, slitlamp inspection of the anterior segment, and mydriatic examination of the posterior pole. All procedures were performed according to pachymetric safety criteria: stro- 0 ±1 mal corneal bed of greater than 300 µm and a percent tissue altered index of less than 0.40. The patients were examined 1 day and 1 month after surgery. At the 1-month postoperative visit, all preoperative examinations were repeated. The visual and topographic parameters analyzed were: uncorrected distance visual acuity (UDVA), residual spherical equivalent and refractive astigmatism, asphericity (Q) at 6 mm and total corneal aberration at 6 mm as the root mean square (RMS) spherical aberration (Z4 ), RMS total coma aberration (Z3 ), and RMS HOAs. SURGICAL TECHNIQUE All procedures were performed by experienced surgeons using topical anesthesia (double anesthetic, tetracaine 0.1% and oxybuprocaine 0.4%, Colircusi; Alcon Laboratories, Inc). Antibiotics were used preoperatively, consisting of one drop of moxifloxacin (Vigamox; Alcon Laboratories, Inc) every 5 minutes starting 20 minutes before surgery. An IntraLase iFS femtosecond laser (Abbott Medical Optics) was used to create the corneal flap. In all cases, the programmed flap thickness was 110 µm, with a superior hinge, energy of 0.80 µJ, and programmed diameter varying between 8 and 9.2 mm depending on the white-to-white diameter. The Allegretto WaveLight EX500 laser platform, a flying-spot laser with a less than 0.95 spot diameter, was used for photoablation with an initial energy of 1.52 mJ. Infrared images of the iris were captured with the Topolyzer Vario topographer to control static and dynamic cyclotorsion during surgery. In addition, the physiological Q-value provided preoperatively by the Topolyzer was taken as reference to personalize aspheric treatment. All treatments were centered on the pupil and all surgeries were programmed for emmetropia using the treatment nomogram provided by the manufacturer. Antibiotic and corticosteroid treatment consisted of one drop of 0.1% dexamethasone and 0.3% tobramycin (Tobradex; Novartis) every 4 hours during the first week after surgery. STATISTICAL ANALYSIS Microsoft Excel software (Microsoft Corporation) was used for the database compiled and IBM SPSS Statistics software, version 25 (SPSS, Inc), for the analysis of described and inferential statistics. A paired two-sided t test or Wilcoxon signed-rank test was performed between the different variables, depending on the parametric or non-parametric nature of the data. The Shapiro-Wilk test was used to check the distribution of the sample. An inferential study of the baseline parameters was done to verify the homogeneity of the preoperative variables and to avoid possible intra-subject bias. RESULTS In the preoperative study of homogeneity in the contralateral eyes for both the preoperative Q group (mean age: 29.60 ± 6.07 years) and -0.6 Q-target group (mean age: 32.28 ± 7.62 years), no intrasubject differences were found in any of the parameters evaluated ( Table 1 ). In terms of postoperative visual analysis, both groups had a similar safety index for both ablation profiles regardless of the programmed Q-target. The safety index was 1.08 ± 0.13 and 1.08 ± 0.16 (P = .95) in the preoperative Q group and 1.04 ± 0.14 and 1.01 ± 0.14 (P = .17) in the -0.6 Q-target group for the eyes treated with WFO and CQ, respectively. In addition, nearly 90% of the eyes in both groups had a postoperative CDVA equal to or greater than the preoperative value and no eye lost more than two lines of visual acuity ( Figure 1 ). The loss of one line of visual acuity is considered normal because it may be associated with the inherent variability of the test. Regarding postoperative UDVA, between 96% and 98% of the eyes in both groups remained within one line of preoperative CDVA ( Figures 2-3 ). The efficacy index was 1.08 ± 0.19 and 1.08 ± 0.21 (P = .85) in the preoperative Q group and 1.02 ± 0.19 and 1.00 ± 0.20 (P = .49) in the -0.6 Q-target group for the eyes treated with WFO and CQ, respectively. The refractive results were also similar in both groups for both treatment profiles ( Figure 4 ). All eyes included in the study had a refractive result within ±1.00 D. In the preoperative Q group, 94% of the eyes treated with WFO and 98% of those treated with CQ were within ±0.50 D, whereas in the -0.6 Q-target group, 98% of the eyes treated with WFO and 90% of those treated with CQ were within ±0.50 D ( Figure 5 ). Postoperative spherical equivalent refraction obtained in the -0.6 Q-target group showed a worse predictability (8 percentage points) for the CQ treatment (target -0.6) in comparison with the standard treatment WFO. Concerning topographic and aberrometric analysis, no differences were found between the two ablation profiles in either group. Postoperative asphericity displayed a similar oblate shift in both groups regardlessof the ablation profile and the programmed Q-target. CQ treatment showed a lower spherical aberration compared to WFO when the Q-target programmed was -0.6: 0.211 ± 0.121 versus 0.144 ± 0.114, respectively (P < .01). However, no statistically significant differences were found between ablation profiles when the preoperative Q-target was used ( Table 2 ). DISCUSSION The mathematical characterization of the anterior corneal surface may resemble a conical section that is primarily defined by the apical radius of curvature and a peripheral flattening factor called the Q-factor. In virgin corneas, this flattening factor is negative (Q < 0), which describes a prolate ellipse where the apical radius is less than the peripheral radius. In patients who Figure 3. Uncorrected distance visual acuity (UDVA). CDVA = corrected distance visual acuity have undergone myopic LASIK, the central cornea is flattened to reduce the total dioptric power. As a result, the physiological geometry of the cornea changes from a prolate (Q-factor < 0) to an oblate (Q-factor > 0) shape. This trend toward a positive increase in asphericity is closely related to the amount of corneal tissue removed. In addition, this oblate shift produces an increase in positive spherical aberration, which contributes to the presence of glare, halos, and dysphotopic phenomena that decrease vision quality in these patients. The Allegretto WaveLight laser has two aspheric ablation profiles designed to minimize the oblate shift induced by myopic ablation. WFO has a non-personalized aspheric profile, based on theoretical eye models, that performs up to 35% ablation in the midperiphery of the optical zone compared to conventional treatments, with the aim of achieving a smoother transition zone.15 The removed tissue in the midperiphery increases as the myopic treatment increases regardless of the initial topographic values, reaching up to 11 µm for a sphere of -8.00 D. This treatment does not increase the depth of central ablation compared to classic profiles but its shape. The CQ profile is based on the same aspheric ablation principle; however, it considers the topographic features provided by the Topolyzer topographer in each case. It also enables the surgeon to customize the treatment by adjusting the Q-target. Several studies have compared visual and topographic results between these two myopic ablation profiles, but conclusions remain controversial. Tawfik et al14 found greater asphericity control in the CQ group compared to the WFO group, showing postoperative mean Q-values of 0.03 ± 0.77 and 0.06 ± 0.44, respectively. Nevertheless, although statistically significant differences were shown (P = .02), they were not clinically relevant. In addition, the small differences between the two groups (mean WFO Q – mean CQ profile Q = 0.03) compared to the large dispersion of data (effect size) suggests that the conclusions were not supported by the results, because the statistical power of the hypothesis contrast was far from ideal. A large sample would be needed to achieve robust statistical power. Similarly, Stojanovic et al16 found greater asphericity control when performing CQ compared to WFO, but the differences between both groups were only marginally statistically significant (P = .049). Mai et al17 found no statistically significant differences in asphericity, HOAs, or refractive outcomes between both groups, programming a Q-target equal to the preoperative Q-value. Regarding hyperopia treatment, Amigó et al18 obtained better results in terms of spherical aberration and postoperative asphericity in the customized group, programming a Q-target of 0, compared to the WFO group. These authors obtained a spherical aberration value in the aspheric-customized LASIK group of 0.04 ± 0.18 µm versus -0.39 ± 0.23 for the WFO profile, whereas postoperative asphericity was -0.04 ± 0.25 µm and -0.52 ± 0.22, respectively (P .05). In the current study of contralateral myopic eyes, the authors found no statistically significant differences between postoperative oblate shift for either aspheric treatment (WFO or CQ) regardless of the programmed Q-target. In the preoperative Q group, the mean postoperative asphericity was 0.33 ± 0.34 and 0.35 ± 0.29 for the eyes treated with WFO and CQ, respectively (P = .184). In the -0.6 Q-target group, the results were identical: 0.26 ± 0.28 and 0.26 ± 0.27 for the eyes treated with WFO and CQ, respectively (P = .889). The outcomes obtained suggest that customized treatment offers no advantage over conventional WFO treatment in terms of postoperative control of oblate aspheric shift. A common finding in all published studies is the increase in asphericity reported in the postoperative period despite the use of aspheric profiles independently of the programmed Q- target.14,16,17,19 The discrepancy between postoperative topographic observations and theoretical predictions is known. Several authors have recognized the difficulty of interpreting asphericity valuesafter myopic refractive surgery20,21: the asphericity value is highly dependent on the diameter of analysis, where a more prolate surface (Q < 0) is obtained when the area of analysis increases in distance from the corneal vertex.13 Furthermore, asphericity is not symmetrical in the four main hemimeridians. There may be differences of up to 0.50 points between the hemimeridians, so their average may not represent the actual corneal asphericity.22 The anterior corneal surface may also undergo modifications after ablation due to biomechanical changes and epithelial remodeling not predicted by theoretical models. Gatinel et al21 found a linear relationship between the apical radius value and the Q-value, and therefore the measurement of asphericity in patients treated with refractive surgery may be conditioned by apical corneal flattening. Although the conical section is a good ap- proximation to the corneal profile, it does not accurately represent the anterior corneal surface, and its differences should be defined through the RMS error of curvature.23 Due to the drawbacks in the quantification of anatomical corneal changes through topographic findings, Amigó et al20 suggested the analysis of corneal spherical aberration as a good indicator of the change produced in the Q-factor after surgery. Aberrometric outcomes from published research with WFO and CQ aspheric profiles show no statistically significant differences in spherical aberration before and after surgery,18 unlike other conventional classic profiles. The results of this study show a slight increase in positive spherical aberration in patients treated with WFO. However, the eyes in the preoperative Q group treated with CQ (target Q equal to preoperative Q) showed no statistically significant differences with preoperative values: 0.182 ± 0.068 µm preoperatively versus 0.199 ± 0.117 µm postoperatively (P = .194). In addition, the eyes in the -0.6 Q-target group obtained positive spherical aberration values lower than the preoperative values: 0.191 ± 0.062 µm preoperatively versus 0.144 ± 0.114 µm postoperatively (P = .006). This indeed demonstrates the power of these aspheric profiles in controlling HOAs and in not inducing positive spherical aberration despite postoperative oblate shift. The current study has some limitations, such as the short-term follow-up and cross-sectional design. Furthermore, stratification of change in Q-value (pre-post) based on level of attempted myopic correction was not evaluated. Nonetheless, to the best of our knowledge, this is the first study to compare WFO and CQ treatment with two different Q-targets. In addition, the study had a larger sample size than previous comparative studies of both aspheric ablation profiles. Further research with evaluation of total ocular aberrometry and a longer follow-up period is required. WFO and CQ treatments are similar with respect to refractive and visual outcomes. CQ provides greater control over the increase in positive spherical aberration after myopic refractive surgery. However, it does not represent an advantage over WFO in the oblate shift in postoperative asphericity regardless of the programmed Q-target. REFERENCES 1. Yuen LH, Chan WK, Koh J, Mehta JS, Tan DTA; SingLasik Research Group. A 10-year prospective audit of LASIK outcomes for myopia in 37,932 eyes at a single institution in Asia. Ophthalmology. 2010;117(6):1236-1244.e1. https://doi. org/10.1016/j.ophtha.2009.10.042 PMID:20153899 2. Zhang Y, Shen Q, Jia Y, Zhou D, Zhou J. Clinical outcomes of SMILE and FS-LASIK used to treat myopia: a meta-analysis. 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