Efficacy and Safety of Topical Timolol Eye Drops in the Treatment of Myopic Regression after Laser In Situ Keratomileusis: A Systematic Review and Meta-Analysis

Methodological quality of the review: Medium confidence

Author: Xiaochen Wang, Guiqiu Zhao, Jing Lin, Nan Jiang, Qian Wang, and Qiang Xu

Region: China, Iran, Egypt

Sector: Myopia

Subsector: Myopia treatment

Equity focus: No

Study population: Adults

Type of programme: Community based (home treatment and follow-up)

Review type: Other review

Quantitative synthesis method: Systematic review and meta-analysis

Qualitative synthesis method: Not applicable

Background: Laser in situ keratomileusis (LASIK) is thought to be an effective and safe refractive surgical procedure for high myopia. Along with the continuous renewal of equipment instruments and the continuous improvement of surgical technique, most postoperative patients obtain satisfactory results. However, at least 28 per cent of refractive surgery patients still experience myopic regression. Timolol provides ocular comfort and lubrication, and also increases retinal and optic nerve perfusion. It can reduce IOP by decreasing aqueous humor production and has no obvious side effects. A number of clinical trials had been conducted to evaluate timolol’s effectiveness and safety. However, the results were inconsistent.

Objectives: The aim of this study was to assess the efficacy and safety of timolol in the treatment of myopic regression after laser in situ keratomileusis (LASIK).

Main findings: A total of six RCTs with 398 patients with LASIK was included in this systematic review and meta-analysis. The mean age of participants was 24.24 years, and 49.5% were male. The follow-up period ranged from seven days to 12 months. Four studies used 0.5% timolol. Topical timolol was prescribed twice daily in five studies, excepting only one study. The mean pre-LASIK SE is -7.575D. Results on the final refractive spherical equivalent after being treated for three months, six months, and 12 months shows that there was a statistically significant difference between the two groups in the follow-up for three months (SMD=0.58, 95% CI=0.31 to 0.85; ?< 0.0001). Analysis on intraocular pressure shows a significant difference between the two groups (SMD=-0.39, 95% CI=-0.75 to -0.03; ?²=45%; ?=0.03). Two studies reported UDVA; analysis shows that there were significant differences between the two groups in the follow-up for six months (MD=-0.02; 95% CI=−0.04 to 0.00; ?=0.05) and 12 months (MD=0.15; 95% CI=0.07 to 0.23; ?=0.0002). The same results were observed on CDVA where a significant difference was found between the two groups in the follow-up for 12 months (MD=0.03; 95% CI=0 to 0.05; ?=0.20). No significant publication bias was demonstrated in the funnel plot.

Based on findings, authors note that topical timolol could be an effective treatment for reduction of myopic regression, especially the spherical errors after myopic LASIK. Further RCTs with larger sample sizes for these trials are warranted to determine the efficacy and limitation for myopic regression after LASIK.

Methodology:

Inclusion criteria consisted of: 1) controlled clinical trials, including retrospective studies and prospective studies, such as randomised controlled trials (RCTs). 2) There is confirmed diagnosis of high myopic, spherical equivalent (SE) ≥-6.00 D; age of patients is 19 years or more. 3) Studies that reported the follow-up results beyond two weeks concerning LASIK treatment for myopia are included. 4) Patients were subjected to topical timolol eye drops daily for more than two weeks. 5) Treatment with topical timolol eye drops was compared with artificial tears, placebo (vehicle), with no topical treatment. 6) We included any RCTs that examine at least one of the following outcomes: IOP, spherical equivalent, CCT, UDVA, and CDVA. The research was performed with Medline, CENTRAL, Embase, CBM and CNKI for randomised 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. All articles were read by two independent reviewers (Xiaochen Wang and Qian Wang) who implemented the data extraction according to the inclusion criteria. The risks of bias in the included studies were assessed according to the recommended methods of the Cochrane Handbook. Analysis: The Review Manager 5.3 was used to perform our meta-analysis. Authors calculated the weighted mean difference for continuous data. We used the SMD to analyse the results on a uniform scale. We evaluated the statistical heterogeneity by Cochrane ?² tests and qualified it by calculating the ?² statistic.

Applicability/external validity: Regarding external validity, the authors reported that this meta-analysis just included six trials, which is not enough to analyse the outcome and makes it easy to produce bias. The heterogeneities of SE and IOP were not explained due to different surgical techniques, methods of measurement, or follow-up periods in different trials. This affects the applicability of the results in other settings with different techniques in place.

Geographic focus: Not discussed.

Summary of quality assessment:

Overall, medium confidence was attributed to this review’s findings, as authors did not conduct thorough searches of the literature to ensure that all potentially relevant studies were identified.