WRITERS Dr Bruno Lopes Cotta Barbosa and Dr de Padua Soares Bezerra

By 2040, the number of people affected by glaucoma worldwide is projected to reach 111.8 million, a 74% increase from the 64.3 million cases recorded in 2013, driven primarily by the growing elderly population.1 The prevalence of open-angle glaucoma differs across ethnic groups, with the highest rates seen in individuals of Asian descent, and notably high rates also observed in those of African descent. Additionally, people living in urban areas appear to be at a higher risk for developing primary open-angle glaucoma (POAG) compared to those in rural areas, although the reasons behind this difference remain unclear.1

POAG is a chronic, progressive optic neuropathy characterised by structural changes at the optic nerve head and retinal nerve fibre layer, without any underlying ocular diseases or congenital anomalies. These structural changes are associated with a gradual loss of the visual field and progressive degeneration of retinal ganglion cells. The prevailing theory attributes this cell damage to IOP levels that exceed the tolerance of an individual’s eye, often due to increased outflow resistance in the trabecular meshwork. The risk of developing POAG increases with higher IOP, but no definitive threshold pressure has been identified for the onset of the disease. However, a subset of patients develop POAG despite having IOP within the normal range, suggesting that the aetiology is multifactorial, potentially involving genetic predispositions and other co-existing conditions. This implies that factors beyond IOP may play a more significant role, especially in cases with normal IOP. As a result, POAG is further classified into high-pressure glaucoma and normal-pressure glaucoma to reflect these variations in disease presentation.2

As previously mentioned, the only approach to treating glaucoma is through regulating IOP. Clinicians often start with topical medications; however, it is important for healthcare professionals to recognise the challenges patients face in adhering to their prescribed topical medications. It has been observed that those in the early stages of glaucoma tend not to realise the consequences of the progression, with some engaging in a so-called ‘white coat adherence’, using their eye drops diligently only a few days before a doctor’s appointment, then discontinuing their use afterward. Other common factors for nonadherence include: psychological factors (e.g. low self-efficacy and forgetfulness), medication scheme, and difficulties with drug administration (e.g. incorrectly using the drops, patients with dementia or rheumatic diseases).3 An alternative non-surgical intervention is to treat patients using SLT. Before delving into a comparison of the effectiveness between SLT and topical medications, it is essential to first understand how this treatment works.

HOW SLT WORKS

The concept of using laser therapy to target the trabecular meshwork was first proposed by Krasnov in 1973, who believed that laser could enhance filtration by ‘puncturing’ the trabecular meshwork. The initial study on laser treatment was conducted by Worthen in 1974, using an argon laser and introducing the method as ‘laser trabeculotomy’. By1995, SLT was developed, using a 532 nm frequency-doubled, Q-switched Nd laser to selectively target melanin pigment in trabecular meshwork cells while sparing non-pigmented structures.4

The mechanisms of action for SLT are not entirely understood, but contrary to early beliefs, they do not involve perforation of the meshwork. One theory suggests that it causes circumferential contraction, opening spaces between trabecular beams. For SLT, it is further thought to trigger a rejuvenating effect on the meshwork endothelium.4 Over time, SLT has largely replaced argon laser trabeculoplasty due to its fewer adverse effects, greater ease of use, and improved repeatability, as the thermal damage caused by argon lasers limits the feasibility of repeated treatments.5

INTRAOCULAR PRESSURE CONTROL

In 2023, a Cochrane systematic review compared SLT with topical medications for IOP control. The review found no significant differences between the two treatments across multiple follow-up intervals in randomised controlled trials: six months (Katz 2012), 12 months (Glaucoma Initial Treatment Study 2020; Katz 2012; KiGIG 2021; Lai 2004; LiGHT 2019; Nagar 2005), 24 months (LiGHT 2019), 36 months (LiGHT 2019), and five years (LiGHT 2019).4 Notably, this conclusion was based on studies involving either treatment-naïve patients with ocular hypertension or open-angle glaucoma, or those previously managed with topical medications, highlighting the consistency of the findings across these distinct patient groups.

Another aspect to evaluate with IOP control is the number of individuals managing the condition effectively without the need for daily use of eye drops to lower IOP. The LiGHT study reported that 74.2% of 356 treatment-naïve patients that received SLT treatment remained drop free after three years.5 In the six-year follow-up study, 69.8% of the SLT group still remained drop free with the majority requiring only one or two SLT treatments during the study period. This total was higher in comparison to the 18.0% in the topical medication group that were drop free after six years of treatment.6

GLAUCOMA TREATMENTS AND VISUAL FIELD DETERIORATION

The LiGHT study demonstrated that treatment-naïve patients who underwent SLT, instead of starting with topical medication, experienced a lower rate of failure to stabilise visual field progression by the end of the three-year study (RR 0.65, 95% CI 0.52 to 0.81).4 The progression rates remained significantly lower in the six-year follow-up study of the same patients, with 19.6% in the SLT group compared to 26.8% in the eye drops group (P = 0.006).6 Therefore, the long-term efficacy of SLT in reducing disease progression and preserving visual function is superior to conventional tropical medications.

It is necessary to remind clinicians that the goal in glaucoma treatment is to slow the progression of the condition and not cure it. This fact was illustrated by a realworld study conducted across five United Kingdom ophthalmology centres with 831 patients who underwent SLT treatment. Statistically significant visual field worsening was observed over time following the SLT procedure, with an average mean deviation (MD) decrease of -0.46 dB (95% CI: -0.84 to -0.08, P = 0.018) at 12–18 months and -1.07 dB (95% CI: -1.71 to -0.43, P = 0.0013) at 24–36 months.7 This should be considered when setting treatment goals and monitoring long-term efficacy.

GLAUCOMA TREATMENTS AND QUALITY OF LIFE

The LiGHT study aimed to evaluate health-related quality of life (HRQoL) in treatment-naïve glaucoma patients over three years using the EQ-5D questionnaire alongside the glaucoma-specific GQL-15, comparing outcomes between patients treated with SLT and those using topical medications. The study found no significant difference in overall quality of life between the two treatment groups (mean difference 0.01 points, 95% CI ‐0.01 to 0.03). This conclusion was supported by a follow-up study that extended the observation period to six years (mean difference 0.01 points, 95% CI ‐0.01 to 0.04).5 However, concerns were raised regarding the sensitivity of the EQ-5D questionnaire in capturing ophthalmology-specific outcomes, as it was primarily included for the cost-utility analysis used by the UK National Health Service.5 Additionally, the GQL-15, while providing valuable insights into visual functioning, failed to address other critical aspects of living with glaucoma, including emotional wellbeing, social and financial concerns, and the inconvenience of treatment regimens, which are essential for a comprehensive quality of life assessment.8

Recognising the limitations of the LiGHT study, another research group employed the more robust glaucoma outcomes assessment tool (GOAT), which spans 342 items across 12 domains, with treatment-naïve glaucoma patients to evaluate a broader spectrum of patient experiences. This study also found no significant differences in QoL between SLT-treated and topical medication-treated patients.8 However, its findings were limited by an underpowered sample size, undermining the reliability and generalisability of its conclusions.

Overall, the evidence to date suggests that SLT and topical medications have comparable impacts on quality of life, but these findings should be interpreted cautiously. Further research is required using more sensitive, glaucoma-specific QoL instruments and adequately powered study designs to uncover any potential differences and provide a more nuanced understanding of how these treatments affect patients’ lives in the long term. This is important because certain adverse effects commonly observed with topical medications are less frequent in SLT patients, as will be discussed in the following section.

ADVERSE EFFECTS

Topical glaucoma medications have been associated with both systemic and local adverse effects, raising concerns about their broader impact on patients. Systemic effects, such as arrhythmias, congestive heart failure, and airway obstruction, have been linked to beta-blockers, while carbonic anhydrase inhibitors may contribute to thrombocytopenia. Locally, prostaglandins have been associated with undesired cosmetic changes, including eyelash growth, iris pigmentation, and skin darkening around the eyes.9 These drawbacks have led to an increased interest in alternative treatments, such as SLT, which may reduce dependency on topical medications.

The 2023 Cochrane systematic review analysed data from three randomised controlled trials (Lai 2004, LiGHT 2019, Katz 2012) involving 1,426 eyes. SLT was associated with a significantly higher risk of early IOP spikes compared to topical medications (RR 14.31, 95% CI 2.75 to 74.33).4 Yet, the authors of the review have pointed out that the wide confidence interval highlights uncertainty regarding the exact magnitude of this risk, and it therefore warrants cautious interpretation. Importantly, the review reported no instances of peripheral anterior synechiae (PAS) – a condition characterised by fibrous adhesions between the iris and cornea caused by inflammation – in either treatment group.4

Ocular surface-related complications between the two treatment groups were evaluated in the Glaucoma Initial Treatment study, which highlighted a stark reduction in ocular surface-related complications with SLT-only treatment. For instance, eyelid erythema was observed in 19.4% of the medication-only group but in none of the SLT-only patients at 24 months (absolute difference: −19.4%, p=0.002).8 Similarly, conjunctival hyperemia was significantly lower in the SLT group, with rates of 0% at both 12 and 24 months compared to 35.9% and 17.9% in the medication group (12-month AD: −35.9%, p<0.001; 24-month AD: −17.9%, p=0.045).8 These findings highlight SLT’s potential to minimise ocular surface-related complications compared to topical medications, but larger studies are necessary to confirm these benefits.

SLT has the potential to be a safer alternative to topical medications for patients in regard to systemic adverse events, but further investigation is still needed to confirm the reduction of ocular surface-related complications and the extent that SLT can provoke an IOP spike.

SURGICAL INTERVENTION RATES FOLLOWING INITIAL GLAUCOMA TREATMENT

The LiGHT study showed that, during a threeyear follow-up period, none of the patients in the SLT group (n = 356) needed surgical intervention to control IOP, whereas 11 patients in the topical medication group (n = 362) required trabeculectomy due to disease progression or uncontrolled IOP.5 In the extended follow-up over six years, the trend continued, with only 2.4% (13 eyes) in the SLT group needing trabeculectomy, compared to 5.8% (32 eyes) in the topical medication group. Additionally, the SLT group had fewer phacoemulsification procedures (57 vs 95).6 In conclusion, SLT reduced the need for surgical intervention up to six years after initiating the treatment in comparison to topical medications.

It is also interesting to understand the current management trends after treating patients with SLT. A real-world study from five UK ophthalmology centres with 831 glaucoma patients demonstrated that at the 12–18-month follow-up, 53 out of 439 eyes (12.1%) required a secondary glaucoma procedure and by the 24–36-month followup, this proportion increased significantly, with 63 out of 243 eyes (25.9%) undergoing additional surgical interventions. Notably, repeated SLT accounted for 34% of secondary procedures at 12–18 months and 36.5% at 24–36 months.7 These findings indicate that clinicians tend to opt for a second round of SLT before advancing to more invasive surgical options, such as iStent implantation or trabeculectomy. The potential effectiveness of repeated SLT as a management strategy for glaucoma is explored in the following section.

REPEATABILITY OF SLT

The mechanism of SLT, which causes minimal structural changes to the trabecular meshwork compared to argon laser treatment, makes it a viable option for retreatment. Khouri et al. evaluated 45 eyes treated with repeat SLT regardless of their response to the initial SLT, finding no significant difference in success rates between initial and repeat treatments after 24 months.10,11 In a subsequent study, the same research group analysed the impact of initial SLT response on repeat treatment outcomes in 51 eyes, categorising them into those achieving at least a 20% IOP reduction and those who did not. They concluded that there was no significant difference in success rates between the two groups (52% vs 39%).10,11 Similarly, studies by Avery et al., Francis et al, Durr et al., and Hong et al. reported no significant differences in success rates between initial and repeat SLT treatments.10,11

Further supporting this, the LiGHT trial conducted a post-hoc analysis on 115 eyes, showing an adjusted absolute IOP reduction at two months (adjusting for IOP before initial or repeat laser) was greater after repeat SLT (adjusted mean difference, -1.1 mmHg, 95% CI, -1.7 to -0.5 mmHg). The study observed no significant difference between the 34 eyes that had early failures (<2 months after their first SLT) versus 81 later failures (>2 months after their first SLT) with a mean difference of 0.3 mmHg (95% CI, -1.1 to 1.8 mmHg). It was also observed that 67% of 115 eyes remained topical medication-free at 18 months.12

Overall, current studies report that repeating SLT treatment is a viable and effective option for long-term glaucoma management, achieving consistent success rates and significant IOP reductions regardless of the initial response.

Cost-effectiveness Analysis

The LiGHT trial is the first multicentre random control trial using real-world data to compare the cost-effectiveness of SLT versus topical medication in 718 treatmentnaïve patients for POAG and ocular hypertension. Previous studies on this topic relied on assumptions and simulations rather than direct patient data, which limits their generalisability to different healthcare systems and reduces the accuracy of the reported outcomes. The cost-effectiveness analysis in the LiGHT study considered both direct healthcare costs (e.g., the SLT procedure, ongoing medication, followup visits, and surgical interventions) and indirect costs (e.g., adverse events from medication use). The primary assessment was based on quality-adjusted life years (QALYs), derived from the EQ-5D-5L questionnaires, which measured patients’ overall health-related quality of life. The study used the incremental cost-effectiveness ratio (ICER) to compare the additional cost per QALY gained between SLT and topical medication, applying a willingness-to-pay (WTP) threshold of £20,000 to £30,000 per QALY – a standard range established by the UK’s National Institute for Health and Care Excellence (NICE) for assessing healthcare interventions. The findings revealed a 97% probability that SLT was more cost-effective than topical medication at a WTP of £20,000 per QALY. Including non-eye-related costs, SLT was cheaper but not significantly so, with a 68% cost-effectiveness probability, but the study claimed that self-reported data and costly unrelated events like cancer may have biased the outcome. In conclusion, the study’s cost-effectiveness analysis supported the claim that SLT could potentially lead to substantial cost savings for healthcare systems as an alternative to topical medication.5

CONCLUSION

Based on current evidence, SLT is a strong first-line treatment for glaucoma, offering comparable efficacy to topical medications in controlling IOP while reducing longterm costs. Studies show that SLT patients experience less visual decline, fewer ocular surface side effects, and require fewer surgical interventions than those on medications. Despite concerns about complications such as peripheral anterior synechiae, SLT has not been associated with significantly higher rates. With its cost-effectiveness, safety, and effectiveness, SLT is a promising option for glaucoma management.

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