Layout 1 Effectiveness of laser therapy among patients with open-angle glaucomaì Eur J Transl Myol 34 (4) 12931, 2024 doi: 10.4081/ejtm.2024.12931 Open-Angle Glaucoma (OAG) is one of the most common forms of glaucoma, leading to irreversible blindness globally by affecting millions of individuals. This condition is marked by progressive optic neuropathy, resulting in the degeneration of retinal ganglion cells and subsequent visual field loss.1,2 Elevated Intraocular Pressure (IOP) is the main risk factor for OAG progression, necessitating effective management strategies to prevent further optic nerve damage. Conventional treatments primarily involve topical IOP-lowering medications, which, although effective, come with challenges such as patient adherence, systemic side effects, and financial costs.3,4 Laser trabeculoplasty has become an essential intervention in OAG management, providing an alternative or comple- ment to medication. ALT was initially the standard laser treatment but had significant complications, including ther- mal damage to the Trabecular Meshwork (TM) and IOP spikes.5,6 To address these issues, Selective Laser Trabecu- loplasty (SLT) was introduced in the mid-1990s. SLT tar- gets pigmented TM cells with a lower-energy laser, mini- mizing collateral damage and offering a safer profile while effectively lowering IOP. However, the recurrence of el- evated IOP and the necessity for retreatment remain signif- icant challenges in the long-term management of OAG.7,8 Recent advancements in laser technology have positioned SLT as a promising method with fewer side effects and similar efficacy to traditional approaches. SLT employs a frequency-doubled, Q-switched Nd laser to deliver pre- cise energy bursts that selectively target pigmented cells in the trabecular meshwork, enhancing aqueous humor outflow without causing substantial thermal damage.9,10 This technique has proven effective in lowering IOP and is particularly beneficial for patients who find it difficult to adhere to pharmacological treatments. Despite the in- creasing use of SLT, comprehensive assessments of its long-term efficacy and safety across various patient pop- Abstract This study aims to evaluate the efficacy of selective laser trabeculoplasty in improving the intraocular pressure in patients diagnosed with open-angle glaucoma. A comprehensive search was performed across electronic databases, including PubMed, Scopus, and Web of Science, until June 2024, using keywords related to “selective laser trabeculoplasty” and “open-angle glaucoma.” Studies were chosen based on set eligibility criteria. Data extraction was carried out by two independent reviewers, and statistical analyses were performed using a random-effects model to calculate the pooled mean differences in IOP reduction and overall success rates. The initial search yielded 3111 articles, with 23 studies included in the systematic review and 22 in the meta- analysis. The pooled MD in IOP reduction between the SLT and control groups was -1.44 mm Hg (95% CI: -2.19 to -0.70, p <0.01). Subgroup analyses revealed a MD of -0.76 mm Hg (95% CI: -1.31 to -0.21, p <0.01) when comparing SLT to medication, and -0.42 mm Hg (95% CI: -0.64 to -0.19, p <0.01) when comparing 180-degree SLT to 360-degree SLT. The pooled success rate favored SLT with an odds ratio (OR) of 0.71 (95% CI: 0.51 to 0.99, p=0.05). There was significant heterogeneity among the studies (I²=71%). SLT is effective in lowering IOP in OAG patients, demonstrating significant efficacy compared to medication and different SLT protocols. The findings underscore SLT’s potential as a reliable treatment option. However, the observed heterogeneity underscores the necessity for standardized protocols in future research to improve comparability and verify SLT’s long-term effectiveness. Key Words: open-angle glaucoma, selective laser trabeculoplasty, intraocular pressure, meta- analysis, laser trabeculoplasty, glaucoma treatment. Eur J Transl Myol 34 (4) 12931, 2024 doi: 10.4081/ejtm.2024.12931 Effectiveness of laser therapy among patients with open-angle glaucoma: a systematic review and meta-analysis study Shima Sayanjali, Behzad Safarpour Lima Clarity Eye Institute, Vaughan, ON, Canada. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (CC BY-NC 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. - 71 - Non -co mmerc ial us e o nly Effectiveness of laser therapy among patients with open-angle glaucomaì Eur J Transl Myol 34 (4) 12931, 2024 doi: 10.4081/ejtm.2024.12931 ulations are needed. This systematic review and meta- analysis aim to consolidate existing evidence on SLT’s role in treating OAG, comparing its outcomes to other treatment modalities to provide a clearer understanding of its clinical utility. Materials and Methods The present study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline.11 Systematic search A comprehensive search was performed across Web of Science, Scopus, and PubMed, covering all available records up to June 2024. We used relevant Medical Subject Headings (MeSH) and relevant keywords, specifically tar- geting (“selective laser trabeculoplasty” OR “SLT”) AND (“open-angle glaucoma” OR “OAG”). Inclusion and eligibility The eligibility criteria was defined based on the PICO framework: Population (P): Clinical studies on human pa- tients diagnosed with OAG. Intervention (I): SLT. Compar- ison (C): Medication, argon laser therapy, and 180 vs. 360-degree SLT. Outcome (O): IOP reduction and success rate of SLT. The exclusion criteria were defined as: animal studies, case reports, studies on other types of glaucoma, studies not involving SLT, unclear or undefined SLT pro- tocols, absence of clear clinical outcomes, lack of sufficient data, and histologic and in vitro studies. Data extraction and outcome measures Data was extracted independently by two authors using a standardized data collection sheet. Any disagreements were resolved and discussed with a third author. The collected variables included: Authors’ names, publication year, de- sign, size, demographics (age, gender), SLT protocols (in- cluding laser settings and treatment parameters), Follow-up periods, Mean and standard deviation of IOP measure- ments, Success rates, Comparison groups (medication, argon laser therapy, 180 vs. 360-degree SLT). Statistical analysis and data synthesis The pooled Mean Differences (MD) in IOP reduction be- tween SLT and control groups was calculated using a ran- dom-effects model, with Hedges’ g and standard deviation estimation. The pooled success rate and Odds Ratio (OR) were determined using the meta package in R. we used the I² test to evaluate the heterogeneity. The Mantel-Haenszel method and random-effects model were applied for pooling effect sizes and calculating standard deviations. A z-test was conducted to evaluate the overall significance of the random model and the significance between subgroups. Publication bias was assessed by creating funnel plots for each group. Statistical analyses and the creation of forest and funnel plots were performed using R (R Foundation for Statistical Computing, Vienna, Austria) and RStudio (RStudio Inc., Boston, MA). Results Our initial search yielded 3,111 articles from PubMed, Sco- pus, and Web of Science, from which we eliminated 338 duplicates. After reviewing the titles and abstracts of the re- maining 2,493 records, we retrieved 94 full-text articles for further evaluation. Ultimately, 23 studies met our eligibility criteria and were included in the systematic review,3,9,12-32 with 22 of these studies also included in the meta-analysis (Figure 1). Detailed characteristics of the included studies are summarized in Table 1. The main focus of the included studies was to evaluate the effectiveness of SLT in lowering IOP in patients with open- angle glaucoma. The studies made several comparisons: SLT versus medication, SLT versus argon laser trabeculo- plasty, and 180-degree SLT versus 360-degree SLT. Varia- tions in laser settings and treatment protocols among the studies contributed to the heterogeneity of the outcomes. Pooled mean difference The pooled MD in IOP reduction between the SLT and control groups was assessed using a random-effects - 72 - Figure 1. PRISMA flow diagram of the included studies. Non -co mmerc ial us e o nly Effectiveness of laser therapy among patients with open-angle glaucomaì Eur J Transl Myol 34 (4) 12931, 2024 doi: 10.4081/ejtm.2024.12931 model. The overall MD was -1.44 mm Hg (95% CI: -2.19 to -0.70, p <0.01), demonstrating a significant decrease in IOP in the SLT groups compared to the control groups (Figures 2 and 3). There was considerable heterogeneity among the studies (I²=71%, τ²=0.6742, p <0.01). Further subgroup analysis revealed varying MDs: For SLT versus medication, the MD was -0.76 mm Hg (95% CI: -1.31 to -0.21, p <0.01), indicating a statistically signifi- cant IOP reduction. For SLT versus ALT, the MD was -1.30 mm Hg (95% CI: -3.77 to 1.17, p=0.14), which was not statistically significant. For 180-degree SLT versus 360-degree SLT, the MD was -0.42 mm Hg (95% CI: -0.64 to -0.19, p <0.01), also showing a statistically sig- nificant reduction in IOP. Pooled success rate The overall success rate of SLT was evaluated, and the pooled odds ratio (OR) was calculated. The random-ef- fects model indicated an OR of 0.71 (95% CI: 0.51 to 0.99, p=0.05), signifying a statistically significant higher success rate for SLT compared to control treatments (Fig- ures 4 and 5). Significant heterogeneity was observed among the studies (I²=73%, τ²=0.3277, p <0.01). Sub- group analyses provided the following ORs. For SLT versus medication, the OR was 1.46 (95% CI: 0.88 to 2.40, p=0.14), which was not statistically signifi- cant. For SLT versus ALT, the OR was 1.34 (95% CI: 0.73 to 2.45, p=0.33), also not statistically significant. For 180- degree SLT versus 360-degree SLT, the OR was 0.56 - 73 - Table 1. Detailed characteristics of the included studies. Author Year Country Design Eyes FD Age M/F Comparison Control Lai et al.20 2004 China RCT 58 60 51.9 13/16 SLT vs M Various Nagar et al.25 2004 UK RCT 167 10.3 63 77/90 SLT vs M Latanoprost Nagar et al.21 2008 UK RCT 40 4-6 66.4 21/19 SLT vs M Latanoprost Goyal et al.15 2009 UK RCT 37 1 57-67 - 180 vs 360 360 as control Prasad et al.3 2009 USA ROS 41 1-24 65 18/23 180 vs 360 360 as control Bovell et al.23 2011 Canada RCT 176 36-50 69.5 72/104 SLT vs ALT ALT as control Katz et al.31 2012 USA RCT 127 9-12 - 28/41 SLT vs M Various Rosenfeld et al.18 2012 Israel RCT 52 12 71.9 25/27 SLT vs ALT ALT as control Shibata et al.12 2012 Japan ROS 69 17.9-19.5 66.4-70.2 35/34 180 vs 360 360 as control Kent et al.26 2015 Canada RCT 76 6 73 - SLT vs ALT ALT as control Kaplowitz et al.27 2016 USA RCT - 24 62.8-70.3 13/24 SLT vs TLT TLT as control Gazzard et al.30 2019 UK RCT 1230 36 62.7-63.4 397/321 SLT vs M Various Ozen et al.14 2020 Turkey POS 52 6 62.3 28/24 180 vs 360 360 as control Nirappel et al.16 2021 USA RCS 258 1.5-24 18-97 215/238 180 vs 360 360 as control Philippin et al.29 2021 Tanzania RCT 339 12 65.09 118/83 SLT vs M Timolol Wong et al.17 2021 Hong Kong RCT 132 12 - - SLT vs PS-SLT SLT as control Christie et al.24 2023 Denmark RCT 144 12 60 77/67 SLT vs M Bimatoprost as control Dahlgren et al. (i)9 2023 Sweden RCT 199 6 70-73 - 180 vs 360 360 as control Dahlgren et al. (ii)9 2023 Sweden RCT 201 6 70-73 - 180 vs 360 360 as control Michaelov et al.28 2022 Australia RCT 80 12 66.5 - 180 vs 360 360 as control Pimentel et al.32 2023 Brazil ROS 98 12 61.-62.7 42/56 SLT vs MLT MLT as control Robin et al.13 2023 USA RCS 131 6-12 65.2 63/68 SLT vs MLT MLT as control Schmidl et al.19 2023 Austria RCCS 25 3 72-73 16-Sep SLT vs ALT ALT as control Martini et al.22 2024 France ROS 73 12 77.7 29/44 SLT vs M iStent as control Non -co mmerc ial us e o nly Effectiveness of laser therapy among patients with open-angle glaucomaì Eur J Transl Myol 34 (4) 12931, 2024 doi: 10.4081/ejtm.2024.12931 (95% CI: 0.20 to 2.51, p=0.43), which was not statistically significant. Potential publication bias was assessed through funnel plots for the included studies. The observed asymmetry in the funnel plots suggests the presence of publication bias, which may affect the reliability of the pooled estimates. Discussion We aimed at evaluating the efficacy of SLT in improving IOP in patients with OAG. We analyzed multiple studies that compared SLT with other treatments, including medi- cation, ALT, and varying SLT protocols (180-degree versus 360-degree). Our findings indicated that SLT significantly reduces IOP, with an overall MDof -1.44 mm Hg (95% CI: -2.19 to -0.70, p <0.01) compared to control groups. Sub- group analyses showed a statistically significant IOP reduc- tion for SLT versus medication and for 180-degree versus 360-degree SLT. However, the comparison between SLT and ALT did not reach statistical significance. Furthermore, the pooled success rate demonstrated a higher success rate for SLT relative to control treatments, despite substantial heterogeneity among the included studies. A prospective randomized clinical trial compared the effec- tiveness of SLT and ALT in pseudophakic glaucoma pa- tients. Over a 12-month period, the study observed no significant differences in IOP-lowering effects between SLT and ALT. At the final checkup, the mean IOP reduction was 3.23 mm Hg for ALT and 4.30 mm Hg for SLT, supporting our findings that SLT effectively reduces IOP.9,28,30 Ho- wever, unlike our meta-analysis, which found a statistically significant IOP reduction with SLT compared to controls, Rosenfeld et al. did not find a significant difference between SLT and ALT. This suggests that while SLT is effective, its relative advantage over ALT may vary based on patient populations and study designs.9,28,30,33,34 A randomized controlled trial compared the efficacy of 180- degree and 360-degree SLT in patients with OAG and glau- coma suspects. The results indicated that 360-degree SLT was more effective in lowering IOP, with reductions of 21.5 - 74 - Figure 2. The pooled mean difference between SLT and alternative treatments. Non -co mmerc ial us e o nly Effectiveness of laser therapy among patients with open-angle glaucomaì Eur J Transl Myol 34 (4) 12931, 2024 doi: 10.4081/ejtm.2024.12931 mm Hg for 180-degree SLT and 19.9 mm Hg for 360-de- gree SLT at a 1-year follow-up. This finding is in line with our subgroup analysis, which also demonstrated a statisti- cally significant greater IOP reduction with 360-degree SLT compared to 180-degree SLT. Gazzard et al. conducted two studies on the efficacy of SLT for OAG treatment. In their 2019 study, they found that SLT was as effective as medi- cation in reducing IOP over a 3-year period.3,18 Their 2023 study further confirmed these results, showing sustained IOP reduction with SLT over an extended follow-up period. These findings are consistent with our meta-analysis, which showed a MD in IOP reduction of -0.76 mm Hg (95% CI: -1.31 to -0.21, p <0.01) for SLT compared to medication. The agreement across various studies underscores the reli- ability of SLT as a treatment option for OAG, particularly for patients who struggle with medication adherence.9,28,30 When comparing our results to previous meta-analyses, we observe both similarities and differences. One comprehen- sive network meta-analysis evaluated the effectiveness of various laser trabeculoplasty techniques, including SLT and - 75 - Figure 3. Funnel plot of the mean difference between SLT and alternative treatments. Figure 4. Forest plot of the succus rate and ORs between SLT and alternative treatments. Non -co mmerc ial us e o nly Effectiveness of laser therapy among patients with open-angle glaucomaì Eur J Transl Myol 34 (4) 12931, 2024 doi: 10.4081/ejtm.2024.12931 ALT, for treating OAG. This study found no statistically significant differences in IOP reduction between any pairs of interventions, consistent with our finding of no signifi- cant difference between SLT and ALT (MD -1.30 mm Hg, 95% CI: -3.77 to 1.17, p=0.14). However, the study re- ported that 180-degree SLT significantly reduced medicat- ion use compared to ALT at 12 months (MD -0.28, 95% CI: -0.50 to -0.06, p=0.014), which aligns with our subgroup analysis findings.35-38 Another study by Sun et al. similarly supported the equiv- alence of SLT to medication in terms of IOP reduction. This consistency is demonstrated in our findings, where SLT ver- sus medication showed a statistically significant IOP reduc- tion (MD -0.76 mm Hg, 95%CI: -1.31 to -0.21, p <0.01). They also explored the efficacy of newer laser technologies, such as MLT and PSLT, which were not specifically ad- dressed in our analysis. Their results suggested these newer forms of LT are comparable in effectiveness to traditional SLT, indicating potential alternatives for clinical practice. Both studies underscored significant heterogeneity among included studies, a factor also noted in our systematic re- view (I²=71%). This variability can be attributed to differ- ences in study designs, patient populations, laser settings, and follow-up durations. The two studies emphasized the need for standardized protocols in future research to mini- mize heterogeneity and enhance comparability. The consis- tency of findings across our study and these meta-analyses confirms SLT’s role as a reliable and effective treatment for OAG, while highlighting areas for further investigation, particularly regarding the long-term efficacy and optimal treatment parameters of newer LT techniques.35,36,39-41 The inclusion of multiple subgroup analyses allowed for a detailed understanding of SLT’s relative efficacy against various treatments and protocols. However, the study also had limitations, such as the significant heterogeneity. It can be explained by the variability of study designs, sample size, laser settings, and follow-up durations. Additionally, potential publication bias, as suggested by asymmetry in funnel plots, may have influenced the robustness of the pooled estimates. Future research should aim to standardize study protocols and address potential biases to further val- idate SLT’s efficacy. Conclusions Our systematic review and meta-analysis study aimed at evaluating the effectiveness of laser trabeculoplasty in the treatment of glaucoma. Based on our results, SLT is leads to reliable treatment outcomes reducing IOP among those with OAG. SLT demonstrates significant IOP reduction compared to control treatments, with 360-degree SLT showing greater efficacy than 180-degree SLT. These find- ings are consistent with individual studies and other meta- analyses, reinforcing SLT’s role as a reliable treatment option. However, the significant heterogeneity among studies highlights the need for standardized protocols in fu- ture research. Despite these limitations, our study supports the use of SLT in managing OAG. List of abbreviations IOP, Elevated Intraocular Pressure SLT, selective laser trabeculoplasty OAG, Open-Angle Glaucoma TM, Trabecular Meshwork PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses MD, Mean Differences OR, Odds Ratio Conflict of interest The authors declare no potential conflict of interest, and all authors confirm accuracy. Ethics approval Not applicable. Availability of data and materials All data generated or analyzed during this study are in- cluded in this published article. Acknowledgement We would like to extend our sincere thanks to Dr. Baseer Khan, MD, Ophthalmologist, FRCS(C), and the team at Clarity Eye Institute, Vaughan, ON, Canada, for their in- valuable support and contributions to this study. Corresponding author Behzad Safarpour Lima, Clarity Eye Institute, Vaughan, ON, Canada. Tel.: 0016478303430. - 76 - Figure 5. Funnel plot of ORs between SLT and alter- native treatments. Non -co mmerc ial us e o nly Effectiveness of laser therapy among patients with open-angle glaucomaì Eur J Transl Myol 34 (4) 12931, 2024 doi: 10.4081/ejtm.2024.12931 ORCID ID: 0009-0004-7364-1201 E-mail: behzadsafarpourlima@gmail.com Shima Sayanjali ORCID ID: 0009-0002-0013-7245 E-mail: drshimasayanjali@gmail.com References 1. Tawfique K, Khademi P, Quérat L, Khadamy JChen EP. Comparison between 90-degree and 360-degree se- lective laser trabeculoplasty (SLT): A 2-year follow-up. Acta Ophthalmologica 2019;97:427-9. 2. Ayala M, Chen E. Comparison of selective laser trabe- culoplasty (SLT) in primary open angle glaucoma and pseudoexfoliation glaucoma. Clin Ophthalmol 2011;5: 1469-73. 3. Prasad N, Murthy S, Dagianis JJ, Latina MA. A com- parison of the intervisit intraocular pressure fluctuation after 180 and 360 degrees of selective laser trabeculo- plasty (SLT) as a primary therapy in primary open angle glaucoma and ocular hypertension. J Glaucoma 2009;18:157-60. 4. 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Identifying baseline predictors of selective laser trabeculoplasty effectiveness: an alter- native mathematical approach. Cureus 2024;16:e54116. 40. Hallaj S, Sinha S, Mehran NA, et al. Intraocular pres- sure profile following selective laser trabeculoplasty in pigmentary and primary open-angle glaucoma. Eur J Ophthalmol 2024. doi: 10.1177/11206721241237305. Epub ahead of print. 41. Kurnaz E. Selective laser trabeculoplasty in the treat- ment of juvenile open angle glaucoma patients under 25 years of age. Int Ophthalmol 2024;44:201. Disclaimer All claims expressed in this article are solely those of the authors and do not necessarily represent those of their af- filiated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Submitted: 16 August 2024. Accepted: 20 September 2024. Early access: 22 October 2024. - 78 - Non -co mmerc ial us e o nly