Laser in situ keratomileusis (LASIK) is thought to be an effective and safe refractive surgical procedure for the high myopia [
In previous studies, “regression” was defined as a 0.25-diopter (D) or greater myopic shift occurring between follow-up visits [
We performed our research with MEDLINE, CENTRAL, EMBASE, CBM, and CNKI for randomized controlled trials (RCTs). The search terms used were “Timolol AND (myopic OR regression OR regressive)”. Furthermore, we reviewed citations in the retrieved articles to search for additional relevant studies.
There are controlled clinical trials, including retrospective studies and prospective studies such as randomized controlled trials (RCTs). There is confirmed diagnosis of high myopic, spherical equivalent (SE) ≥ −6.00 D; age of patients is 19 years or more. Studies that reported the follow-up results beyond 2 weeks concerning LASIK treatment for myopia are included. Patients were subjected to topical timolol eye drops daily for more than two weeks. Treatment with topical timolol eye drops was compared with artificial tears, placebo (vehicle), with no topical treatment. We included any RCTs that examine at least one of the following outcomes: IOP, spherical equivalent, CCT, UDVA, and CDVA. Patients had a history of other ocular diseases, especially the glaucoma, active inflammation. Outcomes or data are presented in a format that cannot be extracted for analysis. Patients had the refractive surgery but not the LASIK.
Studies were excluded based on the following criteria:
All articles were read by two independent reviewers (Xiaochen Wang and Qian Wang) independently who implemented the data extraction according to the inclusion criteria. We use a standardized form to record data on the authors of the study, year of publication, country of origin, sample size, gender, mean age, duration of follow-up, and outcome measures. The risks of bias in the included studies were assessed according to the recommended methods of the Cochrane handbook. We evaluated random sequence generation and allocation concealment (selection), masking of participants and personnel (performance bias), masking of outcome assessment (detection bias), and incomplete outcome data (attrition bias). Two authors (Xiaochen Wang and Qian Wang) independently assessed the risks of bias and any disagreements were resolved by discussion to reach a consensus among the investigators.
We used the Review Manager 5.3 to perform our meta-analysis. We calculated the weighted mean difference for continuous data. We used the SMD to analyze the results on a uniform scale. The absolute value is interpreted together with the
We identified a total of 787 titles and abstracts from the literature, and we retrieved 13 full texts for review. We finally included 6 RCTs in our systematic review and meta-analysis [
Flowchart of the trial selection process. RCT: randomized clinical trial.
A total of 398 patients with LASIK were enrolled in these studies. Table
Demographic characteristics of eligible studies.
Study |
Country | Population | Gender (male : female) | Mean age (Yr) ± SD | ||
---|---|---|---|---|---|---|
Timolol | Control | Timolol | Control | |||
Zhongwen 2014 [ |
China | 60 | NS | NS | 24.47 ± 5.45 | 25.07 ± 6.23 |
Guan 2013 [ |
China | 60 | 18 : 12 | 16 : 14 | 20.0 ± 7.50 | 22.0 ± 5.50 |
Shojaei et al. 2012 [ |
Iran | 90 | 9 : 36 | 15 : 30 | 33.31 ± 10.90 | 34.42 ± 8.57 |
Zhang et al. 2011 [ |
China | 60 | NS | NS | 25.37 ± 6.13 | 24.53 ± 2.31 |
Yang et al. 2010 [ |
China | 53 | NS | NS | NS | NS |
EI-Awady et al. 2010 [ |
Egypt | 75 | NS | NS | NS | NS |
SD: standard deviation; Yr: years; NS: data not available.
Clinical characteristics of eligible studies.
Study |
Study design | Conc. of timolol (%) | Timolol regimen and duration | Follow-up |
|
| ||
---|---|---|---|---|---|---|---|---|
Timolol | Control | Timolol | Control | |||||
Zhongwen 2014 [ |
Prospective | 0.5 | Twice a day for 1 mo | 1 wk/1 mo/ |
−7.00 ± 0.77 | −7.32 ± 1.10 | 16.33 ± 2.69 | 16.90 ± 3.00 |
Guan 2013 [ |
NS | 0.5 | Twice a day for 3 mo | 3 mo | −5.85 ± 2.52 | −5.64 ± 2.31 | 14.65 ± 2.35 | 15.45±2.13 |
Shojaei et al. 2012 [ |
Prospective | 0.5 | Twice a day for 6 mo | 3 mo/6 mo/ |
−8.10 ± 3.41 | −4.87 ± 1.88 | 12.73 ± 1.43 | 12.38 ± 1.65 |
Zhang et al. 2011 [ |
Prospective | 0.5 | Twice a day for 1 mo | 1 wk/1 mo/ |
−4.94 ± 1.09 | 24.53 ± 2.31 | 15.22 ± 1.78 | 15.11 ± 2.53 |
Yang et al. 2010 [ |
NS | 0.025 | Twice a day for 2 wk | 2 wk | −7.01 ± 3.04 | −6.53 ± 2.40 | NS | NS |
EI-Awady et al. 2010 [ |
Prospective | 0.1 | Once a day for 12 mo | 12 mo | NS | NS | NS | NS |
SD: standard deviation; Yr: years; mo: months; wk: weeks; Conc.: concentration; NS: data not available.
Figures
(a) Risk of bias summary: authors’ judgments about each risk of bias item for each included risk. (b) Risk of bias graph: authors’ judgments about each risk of bias item presented as percentages across all included studies.
Four studies reported the final refractive spherical equivalent after being treated for 3 months, 6 months, and 12 months, respectively, and used the random effects model to analyze the data for heterogeneity (
Forest plot comparing the spherical equivalent refraction in timolol and control groups. SD: standard deviation; IV: inverse variance; CI: confidence interval.
The data of the central corneal thickness were used the fixed effects model to analyze the heterogeneity (
Comparison of central corneal thickness in patients with myopic regression after LASIK.
There were 2 studies [
Intraocular pressure in timolol and controls groups.
Each of the 2 studies reported the logMAR UDVA that used the fixed effects model to analyze the data for heterogeneity (
Comparison of logMAR UDVA between the two groups in different time.
There were 2 studies [
Comparison of logMAR CDVA between the two groups in two studies.
Some outcomes displayed great heterogeneity. The heterogeneities of SE and IOP were significant, and dropping eligible studies by hand and metaregression have not provided good results. Maybe it is because of the different measure tools. No significant publication bias was demonstrated in the funnel plot.
Meta-analysis attempts to analyze and combine the results of previous reports [
As a common clinical phenomenon, refractive regression can affect the predictability, efficiency, and long-term stability of refractive surgery and lead to deterioration in visual performance and even seriously affect the surgical curative effect and patients’ satisfaction. So the prevention and treatment of refractive back after the surgery are very important to the quality of patient’s life in the future. Nevertheless, there are no unified and effective methods in the treatment of myopic regression. Secondary surgery is an inacceptable method for patients and doctors; both of them have very big challenge. In contrast, effective drug treatment is a lower risk more easily accepted by patients.
There have been many factors which associated with myopic regression after LASIK, including preoperative refraction [
Timolol as a kind of commonly used ocular hypotensive agent has a good clinical effect. So far, however, because of LASIK postoperative corneal shape to the process and the fact that its mechanism is not clear, when we use timolol postoperatively, the use of the drug dose and time have not yet been determined. So this meta-analysis for the effects of timolol for prevention and treatment of refractive regression made a systematic review.
The results of this meta-analysis show that we can use the timolol eye drops to prevent and treat myopic patients undergoing LASIK and occurring refractive regression. The SE in 5 trials mentioned have statistical differences between the timolol groups and the controlled groups (
This meta-analysis still has some limitations. First, the studies only have six trials; it is not enough to analyse the outcome and it is easy to produce bias. In addition, some parameters had relatively large heterogeneity. The heterogeneities of SE and IOP were not explained due to different surgical techniques, different methods of measurement, or different follow-up periods in different trials. However, we still believe that the results of this meta-analysis are useful, because the meta-analysis includes a relative large number of studies and cases which provide a strong power and the consonance of previous results and sensitivity analysis.
In conclusion, timolol was effective for reduction and improvement of myopic regression especially the spherical errors after myopic LASIK. Importantly, further RCTs with large sample size are needed and the search for more effective and cheaper interventions for this trial would be necessary.
The authors have no financial relationship with any organization.
This study was supported by the Key Project of Natural Science Foundation of Shandong Province (ZR2012HZ001), the Specialized Research Fund for the Doctoral Program of Higher Education (20123706110003), the Youth Project of Natural Science Foundation of Shandong Province (ZR2013HQ007), and National Natural Science Foundation of China (81470609 and 81170825).