Corneal Surface Ablation Laser Refractive Surgery for the Correction of Myopia: A Network Meta-analysis

Methodological quality of the review: High confidence

Author: Daizong Wen; Ruixue Tu; Ian Flitcroft; Qinmei Wang; Yingying Huang; Benhao Song; Ayong Yu; Liang Hu; Yune Zhao; Fangjun Bao; Ye Yu; Hengli Lian; Louis Hoffart; Robert Lee Kramm; Eirini Skiadaresi; David O’Brart; Ioannis Pallikaris; John Marshall; Colm McAlinden; Jinhai Huang

Region: Czech Republic, Turkey, Oman, Brazil, Italy, Iran, China, Germany, Mexico, Ireland, USA, UK

Sector: Myopia

Subsector: Myopia treatment through surgery

Equity focus: No

Study population: Adults

Type of programme: Community based

Review type: Other review

Quantitative synthesis method: Systematic review and meta-analysis

Qualitative synthesis method: Not applicable

Background: Uncorrected refractive error is the leading cause of visual impairment throughout the world. Laser corneal refractive surgery is an effective alternative to the correction of refractive errors with spectacles or contact lenses, especially for myopia. Photorefractive keratectomy (PRK), which involves mechanically debriding the central corneal epithelium and then photoablating the underlying stromal surface, was the first of these techniques described. During the past two decades, other surface ablation procedures have been developed to try to overcome some of the limitations of PRK, while retaining its advantages. A fundamental difference between the various surface ablative techniques is the method of epithelial removal. Although these new approaches to surface laser ablation offer apparent theoretical improvements over traditional PRK, they each have different advantages and disadvantages. Although several conventional pairwise meta-analyses of the four surface refractive ablation procedures (PRK, LASEK, epi-LASIK, and T-PRK) have been published, 20 to 23 of these publications share several limitations.

Objectives: To systematically compare the efficacy, predictability, safety, postoperative haze, pain scores and epithelial healing time of four corneal surface ablation procedures.

Main findings: After screening the studies, 18 were included in the network meta-analysis. A total of 1,399 eyes that underwent one of the four different interventions were evaluated: 606 eyes in the PRK group, 616 eyes in the LASEK group, 105 eyes in the epi-LASIK group, and 72 eyes in the T-PRK group. Of the included 18 trials, five (27.8%) recruited participants from Europe, seven (38.9%) recruited participants from Asia, four (22.2%) recruited participants from North America, and two (11.1%) recruited participants from Brazil. In relation to the complete outcome data, almost 25% of trials were rated as “high risk of bias” (four trials, 22.2%), but most were rated as “low risk of bias” (11 trials, 61.1%). Across the outcomes of the network meta-analysis, we found eight comparisons (15.7% of all comparisons) of high quality, 28 (54.9%) of moderate quality, and 15 (29.4%) of low quality. The results of postoperative haze, pain scores and epithelial healing time based on direct comparisons was reported in six trials with the haze scores. There was a statistically significant difference between LASEK and PRK (WMD=-0.19, 95% CI=-0.37 to -0.01), whereas high heterogeneity was observed between LASEK and PRK (I2=88.9%). Six studies reported postoperative pain scores. Analysis of the postoperative pain scores at days 1 and 3 shows statistically significant differences between PRK and T-PRK at day 1 (WMD=1.24, 95% CI=1.00 to CI=-2.10 to -0.36), PRK and epi-LASIK at day 3 (WMD=-2.16, 95% CI=-3.55 to -.77), and PRK and T-PRK at day 3 (WMD=0.48, 95% CI=0.23 to 0.73). There was no high heterogeneity for all comparisons (I2< 50%). Twelve studies reported epithelial healing time. A statistically significant difference was found between PRK and T-PRK (WMD=1.57, 95% CI =1.33 to 1.75). We also found high heterogeneity between PRK and epi-LASIK (I2=91.4%), PRK and LASEK (I2=97.1%), and LASEK and epi-LASIK (I2=76.6%). On the combination of Direct and Indirect Comparisons, regarding the primary outcomes, there were no statistically significant differences in any comparison in terms of efficacy, safety and predictability (P>.05). For the postoperative haze scores in direct comparison of LASEK and PRK (WMD=-0.19, 95% CrI=-0.37 to -0.01, I2=88.9%), there was a statistically significant difference. When removing any single article, I2 values were all still greater than 65% and the result turned to no statistically significant difference except when removing Ghanem et al.35 (WMD=-0.25, 95% CrI=-0.44 to -0.07, I2=84.8%).

Methodology: Inclusion criteria consisted of: 1) patients with myopia; 2) interventions: PRK, T-PRK, LASEK, or epi-LASIK; 3) comparisons: two or more laser corneal surface ablation techniques (as listed above); 4) at least one of the following outcomes: efficacy, safety, predictability, postoperative haze, pain and epithelial healing time; and 5) study design: RCTs.

A systematic literature review was conducted using PubMed, Embase, the Cochrane Library and the U.S. trial registry ( for RCTs published up to June 2018 without language restrictions. Manual examination of reference lists of clinical trials, related meta-analyses and systematic reviews to identify relevant studies was performed. Screening was performed by two independent investigators. Two investigators independently extracted information into an electronic database, including the participant and intervention characteristics, outcomes and quantitative results for treatment effects. To appraise the study quality, the Cochrane Collaboration risk-of-bias method was used. Two investigators also independently assessed the quality of the body of evidence for outcomes within the network meta-analysis according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method as very low, low, moderate, or high. Traditional pairwise meta-analyses for direct comparisons using random-effects models was performed. For binary outcomes, relative effect sizes were calculated as odds ratios (ORs) with 95% confidence intervals (CIs). STATA was used to analyse data.

Applicability/external validity: Regarding the external validity, the authors reported that their findings are only applicable to the treatment of myopia without the use of MMC. Additional evaluation of the comparative safety and effectiveness of corneal surface laser refractive surgery with and without MMC is warranted. They further added that this meta-analysis was specifically designed to compare different corneal surface ablation techniques rather than excimer laser ablation profiles.

Geographic focus: Not discussed.

Summary of quality assessment: Overall, high confidence was attributed to this review, as authors used appropriate and reliable methodology with detailed analysis.

Publication Source:

Wen D, Tu R, Flitcroft I, Wang Q, Huang Y, Song B, Yu Y. Corneal surface ablation laser refractive surgery for the correction of myopia: a network meta-analysis. J Refract Surg. 2018 Nov 1;34(11):726-735.