Selective Laser Trabeculoplasty

Abstract

Selective laser trabeculoplasty (SLT) is a common ophthalmic procedure used to lower intraocular pressure. The mechanism of SLT action remains controversial but may involve the upregulation of protein expressions in the trabecular meshwork that increases outflow facility. Several prospective trials have demonstrated the safety and efficacy of SLT as both adjunctive and primary glaucoma therapy, and the utilization of SLT in stable, medically-controlled glaucoma patients may decrease medication burden and potentially improve the patients’ quality of life.

Introduction

Selective laser trabeculoplasty (SLT) is one of the most frequently performed ophthalmic procedures, by one estimate comprising approximately 40% of all glaucoma surgical interventions.¹ Prior studies have shown that trabeculoplasty reduces mean intraocular pressure (IOP) 20–30% from the baseline,^2–5 and efficacy is maintained in about 80% of patients after 2 years.⁵ Reduction of IOP occurred in approximately 80% of patients, with the remaining 20% having little or no treatment effect.⁶ Several factors have been examined to predict SLT outcomes, including baseline IOP, age, and prostaglandin analogue therapy, although the findings were inconsistent.^7–15 Several prospective trials support SLT as the first line therapy for patients with primary open angle glaucoma (POAG) and ocular hypertension.¹⁶ In this review, we aim to examine the principles, indications, techniques, and outcomes of SLT to inform ophthalmic surgeons in optimizing the use of SLT for their patients.

Principles

As of 2023, the exact mechanism by which SLT lowers IOP remains controversial.¹⁷ SLT employs the Q-switched Nd:YAG laser, which emits light with a wavelength of 532 or 1064 nanometers.¹⁸ Unlike its predecessor argon laser trabeculoplasty which results in thermal damage, SLT is thought to work by using short pulses of laser energy to target melanin-containing cells selectively in the trabecular meshwork (TM).¹⁹ Histologic examination of post-SLT eyes revealed absent or minimal structural damage to the TM structure, which favors theories suggesting that SLT lowers IOP on a cellular level without mechanical or thermal effects.^{20, 21} In cultured TM cells, SLT irradiation upregulates the expression of matrix metalloproteinases (MMPs), a large family of enzymes that degrade the constituent proteins of the extracellular matrix.^{22, 23} This leads to the proposed mechanism of increased MMPs causing extracellular matrix turnover, resulting in increased trabecular meshwork outflow. Adjunctively, SLT-treated postmortem human TM cells showed increased DNA and cellular replication, suggesting that SLT-triggered replacement of senescent TM cells was part of the procedure’s IOP-lowering mechanism.²⁴

Therapeutic indications

SLT has therapeutic indications as a first line therapy, adjunctive therapy, and replacement therapy to decrease medication burden for patients with primary and secondary open angle glaucoma and ocular hypertension.

As a first line therapy, SLT has similar efficacy compared to that of topical prostaglandin analogs. The Laser in Glaucoma and Ocular Hypertension (LiGHT) study found that 74.6% of eyes treated with primary SLT achieved medication-free pressure control at the 3-year endpoint, and the effects of SLT were greater in treatment naïve eyes.²⁵

Patients with open angle glaucoma or ocular hypertension who have received IOP lowering treatments may receive SLT as adjunctive therapy. SLT can effectively lower IOP in eyes that have previously undergone argon laser trabeculoplasty or received glaucoma surgery and can be repeated with similar efficacy.^{2, 25–29}

In patients with IOP controlled on multiple medications who may have difficulty with adherence to drops or experience adverse side effects from drops, SLT has been shown to be effective in reducing medication burden while maintaining IOP control.^30–33

Although SLT efficacy has primarily been studied in POAG and ocular hypertension, various secondary open angle glaucoma subtypes have shown favorable responses. SLT can be effective in steroid-induced glaucoma.³⁴ In pseudoexfoliative glaucoma, SLT has effects similar to those seen in POAG.^{26, 35, 36} Pigmentary glaucoma eyes can have comparable IOP reductions post SLT, however are at greater risk for post-procedure IOP spikes.³⁷ Normal-tension glaucoma eyes experience more modest IOP reductions post SLT likely due to lower baseline IOP levels.³⁰ Although SLT is not typically used to treat primary angle closure glaucoma, it may have at least a short-term IOP lowering effect in eyes with a patent iridotomy and at least 180 degrees of visible trabecular meshwork.³⁸

Contraindications for SLT include poor visualization of the trabecular meshwork, for instance in cases of extensive angle closure, peripheral anterior synechiae, and poor visualization due to cornea or patient factors. SLT is not recommended for treating neovascular glaucoma. It is not advised in cases of congenital glaucoma. Although SLT is contraindicated for uveitic glaucoma with active inflammation, quiet eyes with a remote history of uveitis and no recent inflammatory episodes may benefit.³⁹

Technique

A thorough glaucoma assessment and detailed gonioscopy exam should be performed prior to considering SLT as a treatment. Pre-procedure IOP lowering drops have been found to reduce the risk of a post-procedure IOP spike; however, there is no consensus regarding the regimen.⁴⁰ Commonly used drops include apraclonidine or brimonidine 15 minutes to 1 hour prior to treatment. Miotic drops such as 1–4% pilocarpine 45 minutes to 1 hour prior to treatment may be used as well. Topical anesthetic drops are given immediately prior to the treatment, and typically a single mirror gonioscopic contact lens with a coupling gel is used. A frequency-doubled Q-switched 532 nm Nd:YAG laser with 400-micron spot size and 3 nS pulse duration is utilized with initial power set between 0.4 mJ and 0.8 mJ and final power ranging from 0.2 to 1.7 mJ per shot. The power is titrated throughout the procedure for optimal energy delivery by increasing the energy by 0.1 mJ increments until small cavitation bubbles are produced, then lowering by 0.1 mJ such that bubbles are observed 30–50% of the time.⁴¹ The laser beam is aimed at the entire trabecular meshwork and applied as adjacent but not overlapping shots over 90 to 360 degrees of the trabecular meshwork with 20–25 shots per 90 degrees. The IOP is measured about 30–60 minutes after treatment, and any IOP spike should be treated with a plan for a shorter follow up period.

There is conflicting evidence regarding the efficacy of treating 180 vs 360 degrees of trabecular meshwork. Some have found a significant treatment effect, including fewer diurnal IOP fluctuations with greater degrees of treatment,^42–44 whereas others have found no significant difference.^{45, 46} A recent meta-analysis concluded that there is no significant difference in treatment effect based on degrees of treatment.⁴⁷ Studies regarding different power levels have found greater IOP reduction with higher power but more post laser complications.⁴⁸

Post-procedure care

There is no consensus regarding post-procedure care for SLT. The most common adverse effects include post-procedure IOP spike and inflammation. Some practitioners prescribe a short course of 4–7 days of an anti-inflammatory topical drop such as a nonsteroidal anti-inflammatory drug (NSAID) or steroid, though others prescribe no drops. If there is no post-procedure IOP spike, patients can be seen within 2–6 weeks following the procedure. A longer follow-up period may be helpful for assessing SLT effect.

IOP spikes tend to occur within 24 hours post SLT and can typically be treated on the same day of the procedure. Pre-procedure IOP lowering drops have been shown to reduce the incidence of post-procedure IOP spikes within 2–24 hours following SLT with moderate evidence supporting the use of apraclonidine, brimonidine, and pilocarpine.⁴⁰ If the patient is already on glaucoma treatment, the regimen is typically continued until an IOP lowering effect from SLT becomes apparent, typically at least 4–6 weeks post procedure.

There is ongoing debate regarding the treatment of post-procedure inflammation. One theory supports mild inflammation as integral to the mechanism by which SLT induces trabecular meshwork remodeling and IOP reduction.^{49, 50} However, too much inflammation may promote unwanted fibrosis. A number of studies have found no significant benefit with the use of post-procedure anti-inflammatory drops.^{26, 31, 51} This is in contrast to the Steroid After Laser Trabeculoplasty (SALT) trial, a double-masked, randomized, placebo-controlled trial which found significantly lower IOP at 3 months following SLT for patients treated with NSAID or steroid drops compared to placebo alone.⁵² The SALT trial included 96 eyes of 85 patients randomized to 0.5% ketorolac, 1.0% prednisolone, or saline tears four times a day for 5 days following SLT and found significant IOP reductions at 3 months post SLT with the ketorolac treated eyes having the greatest IOP reduction and saline tears the least. Due to the conflicting evidence, there remains a lack of consensus regarding post-operative anti-inflammatory treatment, and current practice centers upon individualized treatment with consideration for baseline IOP and risk factors for post-procedure inflammation.

Outcomes and predictors of success

SLT has been primarily compared to topical monotherapy or as a supplementary treatment in various types of open angle glaucoma. Larger studies have primarily focused on POAG and ocular hypertension.

One of the largest randomized controlled trials evaluating the efficacy, safety, and cost-effectiveness of SLT compared to topical prostaglandin analog monotherapy was the Laser in Glaucoma and ocular Hypertension (LiGHT) study. The LiGHT study used individualized and adjustable target IOP measurements for the open angle glaucoma patients as a target for treatment success rather than a one-size-fits-all 20% reduction from baseline IOP. At the end of the follow-up period, 95% of SLT-first eyes achieved the target IOP, and 78.2% of those eyes required no additional drops for IOP control. The study’s results support SLT as a first-line treatment for open angle glaucoma and ocular hypertension. The SLT-first group had fewer longer term side effects, fewer cataract surgeries, zero trabeculectomy surgeries, and slower rates of visual field progression compared to the prostaglandin first group.^{16, 25} SLT resulted in a slightly greater though not statistically significant quality-adjusted life-year gain at lower cost compared to medical therapy.

A meta-analysis of randomized controlled trials assessing SLT versus topical medication in treatment-naïve patients with open angle glaucoma found no difference between laser and medication-only treatment.⁴⁷ SLT-treated eyes had a lower medication burden compared to eyes that were started on drops first, a finding concordant with other meta-analyses.^{53, 54} The meta-analysis by Zhou et al including 2859 eyes found that different modalities of SLT (270 degree, 360 degree, low-energy 360-degree, transscleral 360-degree, new laser trabeculoplasty) resulted in similar reductions in IOP.

Real world experience with retrospective studies have shed light on the clinical applicability of SLT. Using the IRIS® Registry with a sample size of 380,957 eyes, Chang and colleagues found an overall response rate of 36.9%; subgroup analysis of those with baseline IOP >24 mmHg showed 68.8% response, while risk factors for nonresponse include angle recession, uveitis, and aphakia.³² Approximately 75% of nonresponders with at least one medication at baseline, regardless pre-treatment IOP, reduced at least one medication post-treatment, justifying the use of SLT to reduce medication burden in medically controlled patients.³² Using the same dataset, the authors performed a survival analysis of responders and noted younger age and uveitis to be independent risk factors for failures, while glaucoma severity and surgeon experience seemed to confer no effect on overall survival.³³ Eyes that were not on any medications at baseline remained medication-free for a mean of 317.6 days following treatment.³³

A retrospective study by Ansari found that SLT had a 10-year success rate of 72% (success defined as 20% reduction of IOP from the baseline and IOP <19 mmHg) among 108 treatment-naïve eyes of 54 patients with mild POAG.⁵⁵ The study cohort had minimal visual field progression and no need for glaucoma surgery over 10 years. The study found that treatment failure was most common at 3 years, and, over the study period, 60% of patients required an additional SLT. A retrospective study by Khawaja et al conducted at five ophthalmology teaching institutions in the United Kingdom including 831 SLT-treated eyes found significant IOP reductions initially, but 55% of eyes met failure criteria (IOP >21mmHg or <20% reduction from the baseline, increase in glaucoma medications, subsequent glaucoma procedure including repeat SLT) within 1 year, increasing to 82% of eyes by 3 years.⁵⁶ Higher starting IOP was correlated with success whereas patient age, concurrent use of IOP drops, and baseline visual field mean deviation had no correlation with outcomes. Another retrospective study conducted in Brazil by Abe et al with similar failure criteria reported failure of SLT at 3 years at 54%.⁵⁷ Among patients who had medically controlled IOP prior to SLT, success was 49% at 36 months with 37% remaining off any drops.

Predictors of SLT success have been studied. A higher starting baseline IOP has been found by several studies to correlate with greater IOP reduction following SLT.^{16, 32, 33, 56–58} The association of SLT success with other factors such as age, glaucoma severity, type of glaucoma, trabecular meshwork pigmentation, or type of post-procedure eye drop regimen is less definitive as conflicting results have been reported.^{32, 33, 56, 57}

Safety and repeatability

SLT has low complication rates and is generally well tolerated.⁵⁹ Most complications are self-limited and include mild conjunctival injection, foreign body sensation or mild pain, anterior chamber inflammation, or transient IOP increase. Uncommon adverse effects of SLT include hyphema, choroidal effusion, macular edema, corneal haze, and changes in refractive error.⁶⁰ If SLT causes a significant IOP spike or severe inflammation, it should not be repeated or performed in the fellow eye. Inflammation after SLT is usually mild and self-limited, peaking around 2–3 days following the procedure.³⁷ Post-procedure IOP spikes have been reported with an incidence up to 28%.⁶¹ IOP spikes greater than 5–6 mmHg above the baseline tend to be observed in eyes with a more heavily pigmented trabecular meshwork.^{2, 37} A prospective study of 64 patients did not find macular thickness to change following SLT,⁵⁹ but eyes with pre-existing macular edema may worsen post procedure.^{62, 63}

Because of the low energy and relative lack of tissue damage, SLT can be safely repeated.^{16, 64, 65} Furthermore, repeating SLT within 1 year can be more efficacious than a delayed repeat procedure.²⁹ Repeat SLT may have a potential additive effect, achieving greater absolute IOP reductions compared to a single treatment with comparable durability of effect.⁶⁵

Conclusion

• SLT is safe and effective for POAG and secondary OAG including pseudoexfoliation, pigment dispersion, steroid response glaucoma and ocular hypertension, achieving both target IOP and reducing VF progression, need for filtering glaucoma surgery, and medication burden.

• The mechanism of SLT is not well understood, though it is believed to involve extracellular matrix remodeling and increased cellular turnover at the trabecular meshwork.

• SLT may be offered as first-line therapy in some POAG and ocular hypertension patients.

• Patient selection with pre-procedure goniotomy and careful SLT technique are key.

• Higher pre-procedure IOP is correlated with a higher likelihood of treatment response.

• Pre SLT drop regimen should include alpha-agonist or pilocarpine to prevent IOP spike.

• Post SLT drop regimen is controversial; some use no drops, some use NSAIDs or steroids.

• SLT can be repeated safely, and potentially with greater efficacy.

• SLT can reduce medication burden.

• SLT has the potential to improve patient quality of life.