A Systematic Review of Micropulse Laser Trabeculoplasty (MLT) in Primary Open-Angle Glaucoma (POAG) Management: Efficacy, Safety, and Future Perspectives

Abstract

Background/Objectives: Micropulse laser trabeculoplasty (MLT) is gaining attention as a non-invasive treatment option for primary open-angle glaucoma (POAG), offering an alternative to traditional surgeries and medications. This systematic review evaluates the effectiveness, safety, and potential of MLT in glaucoma management. Methods: This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The strength of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, following the 2011 Oxford Centre for Evidence-Based Medicine (OCEBM) recommendations. Results: We identified 79 articles, and after removing duplicates and screening abstracts, 56 articles were eligible for further review. A detailed full-text analysis was conducted on 26 articles, of which 15 met the predefined inclusion criteria. Conclusions: MLT shows promise as a primary or adjunctive treatment for reducing intraocular pressure (IOP) in glaucoma and ocular hypertension patients. Current evidence supports its efficacy and safety; however, additional long-term studies are needed to confirm its durability and compare its effectiveness with traditional surgical and pharmacological approaches. Standardizing treatment protocols and refining patient selection criteria could enhance MLT’s clinical value and support its broader adoption in glaucoma care.

1. Introduction

Glaucoma is a leading cause of irreversible blindness worldwide, characterized by progressive optic nerve damage and visual field loss [1]. Elevated intraocular pressure (IOP) is a major modifiable risk factor in glaucoma pathogenesis. While pharmacotherapy remains the cornerstone of glaucoma management, surgical interventions such as trabeculectomy and minimally invasive glaucoma surgeries (MIGSs) are often pursued in cases of inadequate IOP control or intolerance to medications.

Micropulse laser trabeculoplasty (MLT) has emerged as a non-invasive, repeatable treatment option for reducing IOP by enhancing aqueous outflow through the trabecular meshwork. Unlike traditional continuous-wave lasers, MLT delivers energy in short, repetitive pulses interspersed with cooling intervals. This approach minimizes thermal damage to the trabecular meshwork while promoting aqueous humor outflow.

The mechanisms of MLT involve several principles. First, MLT stimulates trabecular meshwork endothelial cells, enhancing aqueous humor outflow [2]. Second, the cooling intervals between pulses reduce collateral thermal damage to adjacent tissues [3]. Third, MLT induces biological modulation, including cytokine release and extracellular matrix remodeling, which contributes to sustained IOP reduction [4].

Selective laser trabeculoplasty (SLT) is another established laser treatment for IOP control. It employs a Q-switched frequency-doubled 532 nm Nd:YAG laser that targets pigmented trabecular cells with short bursts of energy [5]. In contrast, MLT uses a 532 nm green, a 577 nm yellow, or an 810 nm diode laser in a micropulse delivery mode. The cooling intervals in MLT minimize thermal damage, reducing inflammation and the risk of complications. Conversely, SLT produces microthermal effects at the cellular level, which can result in pigment dispersion and mild inflammation within trabecular meshwork cells, occasionally leading to intraocular pressure spikes [6,7,8].

This systematic review aims to consolidate the current evidence regarding the efficacy, safety, and future directions of MLT in glaucoma management.

2. Materials and Methods

A systematic search of the literature was conducted across PubMed, Embase, Scopus, and Cochrane Library databases to identify studies published up to 15 February 2024. The search strategy incorporated keywords such as “micropulse laser trabeculoplasty”, “MLT”, “glaucoma”, “intraocular pressure”, and “ocular hypertension”. Eligible study types included randomized controlled trials (RCTs), prospective cohort studies, retrospective analyses, and systematic reviews.

Studies were selected based on predefined eligibility criteria, focusing on interventions involving MLT for glaucoma treatment, outcomes related to intraocular pressure (IOP) reduction, safety profiles, and follow-up duration. Inclusion criteria required studies to link the micropulse laser trabeculoplasty (MLT) technique with IOP reduction in primary open-angle glaucoma (POAG). Studies reporting outcomes unrelated to IOP reduction with MLT, as well as review articles, pilot studies, case series, case reports, photo essays, and studies written in languages other than English, were excluded. Additionally, studies involving animal eyes, cadaveric eyes, and pediatric patients were excluded.

Data extraction and synthesis were independently performed by two reviewers (T.V. and F.S.), with discrepancies resolved through the consensus of a third senior consultant (F.C.). The search was limited to studies published in English but was not restricted by publication type, study design, or publication date. The complete search strategy is provided in Appendix A.

The strength of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, following the 2011 Oxford Centre for Evidence-Based Medicine (OCEBM) recommendations (Table 1).

Table 1. Characteristics, quality, and level of evidence of the included studies.

Author	Year	Study Design	Study Sample (Eyes)	Entity of IOP Reduction in MLT	Comparison to Other Treatments	Grade	Level
Hirabayashi et al. [9]	2019	Retrospective review	50 MLT-treated eyes and 50 SLT-treated eyes	MLT: 2.1 ± 4.1 mm Hg; SLT: 1.8 ± 6.6 mm Hg at 6 mo	MLT had similar efficacy to SLT but fewer IOP spikes	Moderate	III
Hong et al. [10]	2019	Retrospective study	72 eyes of 72 POAG patients	Pre-MLT: 20.6 ± 5.9 mm Hg; post-MLT (6 mo): 16.5 ± 2.9 mm Hg	No IOP spikes after MLT, suggesting MLT is safe and effective for POAG	Moderate	III
Kakihara et al. [11]	2021	Retrospective study	42 eyes of 34 OAG patients	Pre-MLT: 19.1 ± 6.5 mm Hg; post-MLT (6 mo): 13.1 ± 5.0 mm Hg	Higher success rate if performed by experienced specialists; no IOP spikes after MLT	Moderate	III
Pimentel RL et al. [6]	2023	Comparative retrospective study	SLT group (45 eyes) and MLT group (37 eyes)	Mean IOP reductions from baseline in MLT groups (−5.8 ± 2.6 mm Hg, 23.4%)in the SLT (−6.0 ± 3.3 mm Hg, 24.9%) (p = 0.74)	MLT success rate: 58.7%; SLT success rate: 61.5%	Moderate	III
Rantala et al. [12]	2012	Retrospective study	40 eyes of 29 OAG patients	Pre-MLT: 21.8 ± 4.9 mm Hg; post-MLT (6 mo): 19.2 mm Hg	MLT is safe but ineffective; 97.5% failure rate for IOP (reduction by 20%)	Low	III
Robin et al. [8]	2023	Comparative retrospective study	54 eyes of 99 OAG or OHT patients	Pre-MLT: 22.8 ± 4.00 mm Hg; post-MLT (1 year): <3 mm Hg or <20% in 48% of cases	MLT has a lower incidence of IOP spikes compared to SLT and a similar success rate at 1 year	High	II
Valera-Cornejo et al. [13]	2018	Retrospective study	30 eyes of OAG patients	Pre-MLT: 15.6 ± 3.5 mm Hg; post-MLT (last follow-up): 12.8 ± 2.6 mm Hg	No IOP spikes; MLT slightly reduces IOP for a short time	Moderate	III
Abramowitz et al. [5]	2018	Prospective randomized study	69 eyes of OAG patients	Pre-MLT: 18.26 mm Hg; post-MLT (1 h): 15.15 mm Hg	MLT and SLT have similar efficacy; MLT has less discomfort during and after the procedure	High	I
Aydin Kurna S et al. [14]	2022	Retrospective study	51 eyes of POAG and PXE glaucoma patients	Pre-MLT: 22.69 ± 3.1 mm Hg; post-MLT (last follow-up): 19.08 ± 2.98 mm Hg at 12 months	No significant difference in mean IOP reductions and success rates at 12 months between MLT and SLT	Low	III
Babalola et al. [15]	2015	Retrospective study	30 eyes of 16 Nigerian patients with POAG	Pre-MLT: 18.6 mm Hg; post-MLT (1 h): 15.5 mm Hg; immediate reduction: 3.2 mm Hg (17.2%)	No serious side effects, confirming similar results in Western populations	Low	III
Lee et al. [16]	2015	Prospective cohort study	48 eyes of OAG patients	Pre-MLT: 18.5 ± 3.0 mm Hg; post-MLT (6 mo): 14.9 ± 2.5 mm Hg (19.5% reduction)	MLT reduces IOP and medication use, similar to SLT but with less inflammation	High	II
Makri et al. [17]	2018	Prospective single-center one-arm study	27 eyes of PEXG patients	Pre-MLT: 20.41 ± 1.87 mm Hg; post-MLT (12 mo): 15.74 ± 0.96 mm Hg (21.51% reduction)	MLT effectively reduces IOP in PEXG patients for 12 months without significant complications	Moderate	II
Phan et al. [18]	2021	Retrospective study	34 eyes of 19 POAG and OHTN patients	Pre-MLT: 17.47 ± 3.59 mm Hg; post-MLT (3 mo): 16.15 ± 3.75 mm Hg (7.6% reduction)	MLT is effective in reducing IOP, especially in patients with IOP >16 mm Hg and early glaucoma	Moderate	III
Sun et al. [19]	2021	Retrospective comparative cohort study	43 MLT-treated eyes and 85 SLT-treated eyes	Pre-MLT: 18.0 mm Hg; post-MLT (1y): 16.7 mm Hg (7.2% reduction)	MLT has fewer IOP spikes compared to SLT and similar overall efficacy	High	II
Yang et al. [20]	2022	Prospective single-center study	39 eyes of glaucoma or OHT patients	Pre-MLT: 21.13 ± 7.75 mm Hg; post-MLT (6 mo): 17.52 ± 4.25 mm Hg (12.0% reduction)	MLT reduces IOP significantly up to 6 months, with limited long-term efficacy	Moderate	II

3. Results

A total of 79 articles were identified. Following the removal of duplicates and screening of abstracts, 56 articles remained. Subsequently, a comprehensive full-text review of 26 articles was conducted. Ultimately, 15 articles met the predefined inclusion criteria (Appendix B). All the studies evaluated the efficacy of MLT in primary open-angle glaucoma (POAG), pseudoexfoliative glaucoma (PXG), and ocular hypertension (OHT). Across various study designs, MLT consistently demonstrated a significant reduction in IOP. Adverse events associated with MLT were generally mild and transient, including intraocular inflammation, transient IOP spikes, and corneal epithelial defects. Long-term follow-up data on the durability of IOP reduction post-MLT are limited but suggest sustained efficacy over months to years. Figure 1 summarizes the research approach applied in this systematic review within a flowchart.

Figure 1. Flowchart of the literature search and selection according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA).

The specific papers with determining reasons for inclusion or exclusion of the full-text reviewed articles are reported in Appendix B.

4. Discussion

Laser trabeculoplasty techniques have long been recognized as safe, non-invasive, and repeatable methods for reducing intraocular pressure (IOP) in glaucoma patients. Micropulse laser trabeculoplasty (MLT), introduced in 2005, employs a 15% duty cycle targeting the anterior trabecular meshwork. This technique minimizes thermal tissue damage, postoperative inflammation, and peripheral anterior synechiae (PAS) formation compared to conventional laser trabeculoplasty (CLT) [21].

Several studies have assessed the efficacy and safety of MLT. In 2015, Lee et al. conducted a prospective cohort study on 48 eyes with primary open-angle glaucoma (POAG), including normal tension glaucoma (IOP < 21 mm Hg). A single session of 360° MLT significantly reduced IOP at all follow-up intervals up to six months and decreased glaucoma medication use. At the six-month follow-up, 20% of patients achieved IOP lowering and 21% reduced their medication use. No significant side effects were observed [16].

In a retrospective review by Valera-Cornejo et al., in 2018, 30 eyes treated with 360° MLT showed a ≥ 20% IOP reduction in 35% and 41% of cases at three and six months, respectively. A trend toward greater IOP reduction with higher baseline IOP was observed, although this was not statistically significant due to the small sample size [13].

In 2019, Hong et al. evaluated the outcomes of MLT in 72 eyes, reporting a 20% IOP decrease from baseline across a 24-week follow-up. The study also found reduced medication use and no significant inflammation [10]. Another study by Phan et al. in 2019 stratified outcomes based on baseline IOP and glaucoma severity. Patients with higher initial IOP and early-stage glaucoma experienced significant IOP reductions, while those with advanced glaucoma did not [18].

Yang et al., in 2022, documented sustained IOP reductions at one day, three months, and six months post-treatment in 39 eyes. However, at 36 months, only 21.88% of patients achieved a ≥ 20% reduction, indicating MLT’s diminishing efficacy over time [20].

The role of operator expertise has also been highlighted. In a study by Kakihara et al., MLT efficacy was greater when performed by experienced glaucoma specialists. This underscores the need for further investigation into the impact of operator expertise on treatment outcomes [11].

MLT has also been evaluated in pseudoexfoliation glaucoma (PEXG). In 2019, Makri et al. treated 27 PEXG eyes with inadequate IOP control using prostaglandin analogs, reporting significant IOP reductions up to 12 months, with 52.17% of cases achieving a ≥20% reduction [17]. Similarly, Aydin Kurna et al. assessed 180° MLT in 51 eyes with uncontrolled POAG or PEXG, achieving IOP reduction in 34–42% of cases during follow-ups of up to 48 months. A significant correlation was observed between baseline IOP and treatment success, while age and laser power showed no correlation [14].

Comparisons between MLT and selective laser trabeculoplasty (SLT) reveal distinct advantages and limitations. Hirabayashi et al. reported similar success rates for MLT (44%) and SLT (40%) in a cohort of 100 eyes. MLT showed consistent efficacy regardless of age or baseline IOP and did not induce IOP spikes, unlike SLT [9,22]. Pimentel et al. found SLT to be slightly more effective at 12 months in achieving an IOP ≤ 21 mm Hg with ≥20% reduction, although MLT demonstrated comparable overall efficacy [6]. Sun et al. observed greater IOP reductions with SLT at early follow-ups, but similar long-term outcomes between the two techniques [19]. Table 2 summarizes the differences between MLT and SLT in POAG treatment.

Table 2. Advantages of MLT in comparison to SLT.

Characteristic	MLT	SLT
Mechanism	Micropulse energy with cooling intervals	Microthermal effects on pigmented cells
Efficacy	Comparable to SLT	Proven effectiveness
Safety	Lower inflammation; fewer complications	Mild inflammation possible
Repeatability	High; no cumulative damage	High but limited by potential effects
Recovery	Quicker recovery; less discomfort	May require anti-inflammatory treatment

Studies suggest that MLT may cause less inflammation and fewer IOP spikes post-treatment compared to SLT, making it a safer option for some patients [5,8].

In conclusion, MLT presents a promising, less invasive alternative to traditional methods for managing glaucoma and ocular hypertension, particularly in patients at risk of post-treatment complications. However, further research is needed to optimize treatment protocols, assess long-term efficacy, and clarify inter-operator variability.

Although there is now sufficient evidence to consider MLT a safe and effective treatment for glaucoma patients, several areas remain worthy of further investigation. These include determining optimal treatment parameters such as laser energy settings, the number of laser applications, and retreatment intervals. Additionally, many studies conducted to date have limitations that may affect their results. These include retrospective designs that may introduce selection bias, small sample sizes, short follow-up periods, a lack of randomization, and the absence of control groups in some cases.

Patient selection criteria, including baseline IOP, glaucoma subtype, and prior treatment history, may also influence the likelihood of treatment success. Therefore, future studies should aim to include more homogeneous cohorts to enhance the reliability of findings.

Future research directions should focus on prospective, comparative studies to elucidate the mechanisms underlying MLT’s IOP-lowering effects, explore combination therapy approaches, and assess the cost-effectiveness of MLT compared to standard treatments.

5. Conclusions

MLT represents a valuable adjunctive or primary treatment option for lowering IOP in patients with glaucoma or ocular hypertension. While existing evidence supports its efficacy and safety profile, further long-term studies are warranted to establish its durability and comparative effectiveness relative to traditional surgical and pharmacological interventions. The standardization of treatment protocols and refinement of patient selection criteria may enhance the clinical utility of MLT and pave the way for its widespread adoption in glaucoma management.

One key area of future research is the identification of patient profiles most likely to benefit from MLT. While current evidence supports its use across various glaucoma subtypes, differences in individual responses suggest that factors such as baseline intraocular pressure, angle anatomy, and disease progression rates may influence outcomes. Longitudinal studies with diverse patient populations are needed to develop predictive models for tailoring MLT to individual needs.

Another promising avenue for investigation is the integration of MLT with pharmacological and surgical interventions. Understanding the synergistic effects of MLT with medications such as prostaglandin analogues or its role as a bridge therapy before more invasive procedures could optimize treatment algorithms. Randomized controlled trials should evaluate the efficacy and safety of such combination approaches, particularly in patients with advanced or refractory glaucoma.

Finally, economic considerations are critical for the widespread adoption of MLT. Comprehensive cost-effectiveness analyses comparing MLT with other treatment modalities, including traditional laser trabeculoplasty and newer surgical options, are essential. These studies should consider not only direct costs but also the long-term economic impact of reduced medication use and delayed progression to invasive surgeries.