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Meta-analysis of selective laser trabeculoplasty versus topical medication in the treatment of open-angle glaucoma
© Li et al. 2015
Received: 27 February 2015
Accepted: 28 July 2015
Published: 19 August 2015
The aim of this study was to examine possible differences in clinical outcomes between selective laser trabeculoplasty (SLT) and topical medication in the treatment of open-angle glaucoma.
Pertinent prospective comparative controlled trials comparing SLT with medication were selected through extensive searches of the PubMed, Embase, Web of Science, Chinese Biomedicine Database, and the Cochrane Controlled Trials Register database from their inception up to March 2014. Efficacy estimates were measured by their weighted mean difference (WMD) to calculate the intraocular pressure reduction (IOPR) from baseline to endpoint and by the odds ratio (OR) to determine success rates.
Five prospective studies, which met the predefined criteria, were included in the meta-analysis. Four studies were randomized clinical trials and one study was a prospective non-randomized clinical trial. There were a total of 492 eyes of 366 patients with open-angle glaucoma. Four studies involving 325 eyes compared SLT with medication in terms of the IOPR. The WMD of the IOPR from the baseline was 0.6 (95 % confidence intervals: −0.24,1.43) when comparing SLT with medication. No statistical heterogeneity was observed between studies (χ2 = 1.30, P = 0.75, I2 = 0.0 %). All five studies reported success rates, with a pooled OR of 0.84 (95 % confidence intervals: 0.42, 1.68), which was not statistically significant. No statistical heterogeneity was observed between studies (χ2 = 5.98, P = 0.200, I2 = 33.1 %). Subgroup and sensitivity analysis confirmed the high stability of the meta-analysis results.
Both SLT and topical medication demonstrate similar success rates and effectiveness in lowering intraocular pressure in patients with open-angle glaucoma.
Glaucoma is a leading cause of blindness worldwide . It is estimated that more than 60 million people had glaucoma in 2010, 8.4 million of whom are bilaterally blind as a result of the disease.There are 79.6 million people around the world who will have glaucoma by 2020, and 74 % of them will have open-angle glaucoma (OAG) . Lowering the intraocular pressure (IOP) is still the goal of OAG treatment and remains the most effective way to prevent the development and progression of glaucoma. Currently, there are three methods available to achieve this goal: medication, laser treatments, and surgery .
Medication therapy is typically the first approach for reducing IOP. Currently, many kinds of potently hypotensive topical medicines are available for controlling IOP . However, medications have potential disadvantages. Patients must tolerate drug side effects, repeated application of drugs and ongoing medical costs . The introduction of selective laser trabeculoplasty (SLT) provided a new non-invasive choice for the reduction of IOP in eyes with OAG . This treatment consists of the application of laser spots in the trabecular meshwork which leads to an increase in the outflow facility and, consequently, decreases IOP.
In a previous Cochrane systematic review on laser trabeculoplasty, only one study comparing SLT with medication was included, which prevented the meta-analysis at that time . In a recent meta-analysis comparing SLT with argon laser trabeculoplasty (ALT) in the treatment of OAG, the role of medication also was not evaluated . Thus,the effectiveness of SLT compared to contemporary medication requires further investigation. Recently, McAlinden et al.  reviewed the IOP-lowering effect when comparing SLT to other glaucoma treatment options. In that article, the author only described the effects of SLT and did not perform a meta-analysis.
Currently, several published clinical trials have compared the efficacy and safety of SLT with medical therapy [9–13]. For example, Lai et al.  reported that the IOP-lowering effect of SLT in Chinese patients is comparable with topical medications. However, these studies had modest sample sizes and conveyed inconclusive results. To date, no consensus has been reached on this topic. Previously, we conducted a meta-analysis comparing SLT with ALT; the results reveal that SLT has similar efficacy to ALT with a similar constellation of side effects . To our knowledge, the data comparing SLT with topical medication in the treatment of OAG has not been systematically evaluated and reported. Therefore, we conducted a systematic review and meta-analysis of all published prospective clinical trials to assess the outcomes of SLT versus medication in the treatment of OAG.
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was used as a guide to conduct the study, including the strategies for searching, analysis, the presentation of results, potential bias, interpretation, and writing (Additional file 1: Table S1) .
Literature search and trial selection
Studies were identified and retrieved through a systematic search of PubMed, Embase, the Web of Science, the Chinese Biomedicine Database, and the Cochrane Controlled Trials Register database from their inception up to March 2014. Periodical literature update was performed and the most recent literature retrieving was at June 30, 2015. However, no new original articles comparing SLT to medication was identified. Keywords used in identifying relevant researches included ‘selective laser trabeculoplasty’, ‘Yag laser trabeculoplasty’, ‘selective laser trabeculectomy’, ‘Nd:YAG’, ‘SLT’, ‘glaucoma’, and ‘ocular hypertension’. Searches were performed by combining the keywords or their relevant abbreviations and truncations. No restriction was applied for language or year of publication. The websites of professional associations and Google Scholar were also searched for additional information. Moreover, a manual search was performed by checking the reference lists of all retrieved trials to identify studies not yet included in the computerized databases. Eligible studies were prospective randomized or non-randomized comparative controlled trials, which compared the use of SLT and topical anti-glaucoma medications in adult patients with any form of naïve OAG or ocular hypertension (OHT).
Data extraction and outcome measures
The information on author, age, sex, country, duration, sample size, type of glaucoma, study design, and other outcome data were extracted. The incidence of transient post-laser IOP spikes, sustained IOP elevation, anterior chamber reaction, discomfort, redness, and pain were recorded. For studies with overlaps of population, the latest one were included in the final analysis. Given that the effectiveness of OAG treatment is often assessed by the intraocular pressure reduction (IOPR) and percent of intraocular pressure reduction (IOPR %), the primary efficacy outcomes were the IOPR and IOPR % from the baseline to the end of follow up. The secondary efficacy outcome was the success rate. Success was defined as IOPR ≥ 3 mm Hg and/or IOPR % ≥20 % . The adverse events in each intervention were also reviewed.
Assessment of methodology quality
The Downs and Blacks scale, which could evaluate both randomized and non-randomized studies, were used for assessment of the clinical trials . The system comprises 27 items distributed between five subscales regarding reporting (10 items), external validity (three items), bias (seven items), confounding (six items), and power (one item). Any discrepancy in the qualitative assessment between the two observers was discussed and a consensus was reached. The total score of each trial was expressed as a percentage of the maximum achievable score. Studies' methodological quality was assessed as excellent, good, fair, or poor when the total score was ≥20, from 15 to 19, from 11 to 14, and ≤10, respectively .
The intent-to-treat analyses were used in each outcome. Additionally, data was combined using an inverse variance random-effects model regardless of heterogeneity .The weighted mean difference (WMD) was calculated for continuous outcomes while the odds ratio (OR) was estimated for dichotomous outcomes. All results were given with 95 % confidence intervals (CIs). Heterogeneity was checked using Cochran's Q statistic and the P-value. I2 metrics, which quantify heterogeneity irrespective of the number of studies, were also reported . Studies with an I2 value of greater than 50 % were considered significant heterogeneity. A P-value of less than 0.05 was considered statistically significant. The statistical analysis was performed using Stata SE 12.0 (Stata Corporation LP, College Station, TX, USA).
Sensitivity analysis and publication bias
We also performed subgroup analysis in terms of the medications used within the medication group. In addition, we investigated the influence of a single study on the overall pooled estimate by omitting one study in each turn. To detect publication biases, we visually examined asymmetry in funnel plots. Furthermore, the Begg’s and Egger’s measures were calculated.
Characteristics and quality assessment of the included studies
Characteristics of prospective comparative controlled trials comparing SLT with topical medication
NO. of eyes (SLT/med)
Definition of success
Degrees of SLT/
26.8 ± 5.6 /26.2 ± 4.2
IOP ≤ 21 mmHg
Topical beta-blocker, pilocarpine, dorzolamide latanoprost as monotherapy or in combination
0.4 ± 0.2/ 0.5 ± 0.2
1.0 ± 0.1 mJ
POAG, OHT, PDS, PEX
IOPR% ≥ 20 %
Latanoprost 0.005 %
POAG, OHT, PDS, PEX
OP ≤ 22 mmHg
Latanoprost 0.005 %
0.5 ± 0.2/ 0.6 ± 0.2
26.1 ± 4.0 /22.8 ± 4.5
IOPR% ≥ 20 %
Latanoprost 0.005 %
25.0 ± 2.2 /24.5 ± 2.2
POAG, PEX, OHT
Arrived target IOP
360 followed by 180 0.2-1.2 mJ
Topical prostaglandin analog, β-blocker, brimonidine, carbonic anhydrase inhibitor, in combination
Quality scoring components for five clinical trials included in the meta-analysis
Quality score component
First Author (year)
Subgroup analysis of IOP reduction from the baseline and success rate comparing SLT with medication
No. of studies
Test for Heterogeneity
Test for Overall Effect
Concerning adverse events, three studies reported the types and incidences. However, we did not perform a meta-analysis because there were so few cases.In general, adverse events were transient and minor. Transient post-laser IOP spikein some patients was observed. There were no patients with sustained IOP elevation after SLT. Other common side effects, namely, anterior chamber reaction, discomfort, redness, and pain were also described as transient and without sequelae in all studies.
Sensitivity analysis and publication bias
Results of leave-one-out sensitivity analyses
Test for Heterogeneity
Test for Overall Effect
Summary of finding table of the overall quality of evidence according to GRADE
(95 % CI)
(95 % CI)
Quality of evidence
0.60 (−0.24, 1.43)
−1.90 % (−5.00 %,1.10 %)
Introduced in 1995 by Park and Latina , SLT provided a new choice for the reduction of IOP in eyes with OAG. SLT is easy to perform and well tolerated by patients.However, the efficacy and safety of SLT versus topical medications for OAG remain unclear. In the preliminary published studies, SLT was used as an adjunct therapy to medication . Later, several studies suggested that SLT may serve as the primary therapy for OAG [22–26]. Comparisons of SLT and medication were done in the remaining trials, but there is still not enough evidence to determine which is the best choice .
In this meta-analysis, we reviewed five prospective comparative controlled trials. The results reveal that SLT is as effective as medication in regard to the control of IOP, which is consistent with a previous review . Also, no heterogeneity was observed across the studies.In addition, SLT and medication are similar in their success rates. The results from our subgroup and sensitivity analyses were quite similar and robust.
The exact mechanisms of SLT lowering IOP are not known. There are three prevailing theories, namely, the mechanical theory, the biologic theory, and the cell theory [27, 28] .According to the mechanical theory, contraction and shrinkage of trabecular beams caused by SLT exerts a pull on surrounding beams, which opens up the intertrabecular spaces.The biologic theory proposes that laser energy causes tissue injury with a resultant cascade of events. Macrophages are attracted and alter the secreted extracellular matrix, allowing an increased aqueous outflow.The cellular theory suggests that SLT applications stimulate cell division in the anterior trabecular meshwork, providing pluripotent cells for the repopulation of sites with laser therapy. These cells produce different extracellular matrices, enhancing the aqueous outflow. Additionally, there may be other mechanisms of action of SLT. It has been reported that exposure to factors secreted by lasered Schlemm canal cells and lasered trabecular meshwork cells and the application of prostaglandin analogs induced junction disassembly while increasing the permeability of Schlemm canal cells . Recently, Chen et al.  determined the effect of travoprost (a drug similar to latanoprost) on Schlemm’s canal in healthy human eyes using fourier-domain optical coherence tomography. They observed that travoprost induced the expansion of Schlemm’s canal lumen. These findings suggest that SLT and latanoprost might share a common mechanism that likely mediated their similar IOP lowering effects.
The results of this meta-analysis must be interpreted cautiously in light of the strengths and limitations of the included trials. A key strength is the fact that all the studies included in this meta-analysis were published by established centers of excellence using a prospective comparative controlled design and all of them were well-performed and of high quality. Despite our rigorous methodology, some limitations of the current study should not be ignored. First, we cannot fully exclude publication bias. The number of included studies is insufficient to carry out statistical testing to detect publication bias. In addition, we did not attempt to gain access to unpublished results. Second, our analyses of IOPR, IOPR %, and success rate were based on data pooled from trials of different durations. This was due to the lack of data reported in all phases of follow-up and may have a potential impact on our results.Third, when discussing treatment result, it is important to realize that the criteria used to define success varies between studies. Differences between studies may also exist with respect to the diagnostic criteria for glaucoma and the severity of the disease. Fourth, none of the identified studies provided a cost-effectiveness analysis; thus, a prospective randomized clinical trial comparing the cost of SLT to medication is required. The effectsof SLT on other outcome measuressuch as delaying the need for surgery in people with early glaucoma were not assessed. This may be an interesting focus for future studies.
In conclusion, the present meta-analysis suggests that SLT appears to be similar to medication in lowering intraocular pressures in patients with open angle glaucoma. Despite our rigorous methodology, the inherent limitations of the included studies should be considered, and conclusions drawn from our pooled results should be interpreted with caution. Future large-volume, well-designed RCTs with extensive follow-up are awaited to confirm and update the findings of this analysis.
This study was supported by the Science and Technology Program of Guangdong Province, China (2013B020400003) ,and the Science and Technology Program of Guangzhou, China (15570001).
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