Introduction
Topical medications for the initial treatment of primary open-angle glaucoma have historically been the gold standard. However, numerous studies demonstrate that selective laser trabeculoplasty should be considered as a first-line option. This paper focuses on the question: should selective laser trabeculoplasty supplant topical medical therapy as the initial first-line treatment for lowering intraocular pressure in patients with primary open-angle glaucoma and ocular hypertension?
When deciding which approach to use, efficacy, safety, and patient-centric issues must all be taken into consideration. This article will present the evidence-based arguments for and against each treatment option, with the goal being a broader understanding of the risks and benefits of each approach. Using this knowledge, the initial treatment that is best suited for each patient can then be reliably developed. The argument for using selective laser trabeculoplasty as the best initial treatment option will be presented first, followed by the argument for continuing to use topical medical therapy for this purpose. Factors supporting each approach will then be summarized in the final section.
Point: Selective Laser Trabeculoplasty as Primary Treatment for Primary Open Angle Glaucoma and Ocular Hypertension
The current primary open-angle glaucoma management paradigm involves first-line treatment with at least once-daily topical drops to lower intraocular pressure. However, there has recently been a shift in the thinking of contemporary management of primary open-angle glaucoma toward using selective laser trabeculoplasty more often as a first-line treatment. The “drop first” paradigm has largely prioritized safety over efficacy, and it evolved long before the discovery of safer first-line, less invasive surgical procedures.
One of the biggest issues with medication remains poor compliance and adverse drug reactions. Studies show that even the most compliant patients will be nonadherent up to 70% of the time.1 Consequences of nonadherence have been well documented as leading to faster rates of visual field progression, an increased number of complications, and higher health care costs.2 Although relatively safe, adverse drug reactions, especially with respect to their impact on the ocular surface, continue to be a major drawback to daily topical medications. We know that glaucoma and ocular surface disease commonly coexist, with up to 60% of patients with glaucoma suffering from dry eye.3 Not to mention, the most used prostaglandin analogues are responsible for several changes to the ocular adnexa including upper eyelid ptosis, tightening of eyelids, orbital fat atrophy, hyperpigmentation, and conjunctival injection, to name a few.4
The efficacy of laser trabeculoplasty as a first-line treatment was first documented in the Glaucoma Laser Trial in 1989. The Glaucoma Laser Trial demonstrated that argon laser trabeculoplasty was at least as efficacious as initially treating an eye with timolol and that those in the argon laser trabeculoplasty group had less progression of the visual field and optic nerve head disease compared with those taking medications.5 At the time, we did not witness a paradigm shift in the contemporary management of glaucoma, likely because argon laser trabeculoplasty causes more permanent damage and scarring in the trabecular meshwork from photocoagulation of the tissue. Selective laser trabeculoplasty is a safer alternative to argon laser trabeculoplasty and has demonstrated at least equal intraocular pressure–lowering efficacy to argon laser trabeculoplasty, with little to no damage to the trabecular meshwork.6 Selective laser trabeculoplasty causes fewer side effects and more long-term success from repeated treatments compared with both drops and argon laser trabeculoplasty.6 Although prostaglandin analogues and selective laser trabeculoplasty use different primary mechanisms and target different outflow pathways, the similarities in the biological changes they induce, such as increased matrix metalloproteinase activity and extracellular matrix remodeling, highlight a common strategy in lowering intraocular pressure by enhancing the eye’s fluid drainage capacity.7–9 Another similarity between the prostaglandins and selective laser trabeculoplasty is the intraocular pressure–lowering response, which is approximately 30% when used as a first line treatment.8,10,11
Further, the results from the Lasers in Glaucoma and Ocular Hypertension (LiGHT) study validated the benefits of first-line selective laser trabeculoplasty. The study investigated quality of life, efficacy, and safety between the 2 groups of patients because the surveys were measuring health-related quality of life. The 2 groups were measured to have the same impacts on quality of life but did not differ in quality of life. This was attributed to the fact that the survey used was evaluating the impact that the disease of glaucoma—not the impact of glaucoma treatment—has on the quality of life of patients with glaucoma. However, there were more ophthalmic drop–related adverse effects in the drug group. The study also demonstrated that after 3 years, patients with first-line selective laser trabeculoplasty, compared with those using topical drops, demonstrated (1) fewer diurnal fluctuations, (2) more eyes at target intraocular pressure, (3) less disease progression, and (4) less cost to the health care system.11
The 6-year extension study concluded that the benefits of selective laser trabeculoplasty remain persistent until at least 6 years and that 70% of the individuals in the selective laser trabeculoplasty group remained drop-free. There was also less need for glaucoma surgery and cataract surgery.12 It should be noted that the results seen in the LiGHT study may have also outperformed other studies investigating selective laser trabeculoplasty as first-line treatment in patients undergoing a washout period. This suggests that the benefits of selective laser trabeculoplasty may be more profound in eyes that have never been on drops to begin with.13,14
Selective laser trabeculoplasty has also shown benefit in patients with normal-tension glaucoma. Overall, it is expected that intraocular pressure lowering will be less in patients with lower baseline intraocular pressure for both topical therapy and selective laser trabeculoplasty and the mean intraocular pressure reduction from selective laser trabeculoplasty varies between 12% and 16% in patients with normal-tension glaucoma.15 However, studies have also shown that patients with normal-tension glaucoma that undergo selective laser trabeculoplasty will benefit from a reduced number of drops added after treatment to meet target intraocular pressure, 24-hour intraocular pressure lowering, and a decrease in intraocular pressure fluctuations at nighttime.15–17 Nocturnal intraocular pressure spikes are an important consideration in the progression of normal-tension glaucoma, and therefore, a treatment that has known benefit to intraocular pressure reductions during that time is still a valuable treatment option in this group.
We are finally starting to see paradigm shift in the contemporary management of primary open-angle glaucoma with evidence pointing toward first-line laser treatment and away from first-line drop therapy. The UK NICE Glaucoma treatment guidelines now list first-line selective laser trabeculoplasty as standard of care.18 It is prudent to note that patient selection for selective laser trabeculoplasty is still an important consideration, as it may not be appropriate for everyone with glaucoma, and that ongoing management of a patient is still required after selective laser trabeculoplasty to establish progression and response to the treatment. Regardless, selective laser trabeculoplasty has demonstrated immense potential in keeping some patients drug-free and in slowing down the risk of functional vision loss. The logistics of selective laser trabeculoplasty as a first-line treatment may not be currently feasible in many health care systems, but this will hopefully start to change as acceptance of selective laser trabeculoplasty as first-line treatment becomes more widespread.
Counterpoint: Medical Therapy as Primary Treatment for Primary Open-Angle Glaucoma and Ocular Hypertension
The clinical risk-benefit ratio has long favored the use of topical medication over surgical intervention as the first line of treatment for lowering intraocular pressure in primary open-angle glaucoma and ocular hypertension.19 Recent evidence, however, has begun to challenge the medicine-first approach. As mentioned above, support for selective laser trabeculoplasty as an initial treatment is being endorsed owing to its effective intraocular pressure–lowering capability, excellent safety record, and elimination of problems related to treatment adherence and ocular surface compromise. Even more importantly, the LiGHT trial showed that first-line selective laser trabeculoplasty can provide better disease control than standard topical medical treatment.12
Despite this support for selective laser trabeculoplasty as a first-line treatment option, however, an argument can still be made for maintaining topical medication as a primary first-line approach. Prostaglandin analogues, the standard initial first-line medical option, have a long and successful track record.20,21 These agents are well tolerated and remarkably safe, require only once-daily dosing, and have well-proven intraocular pressure–lowering efficacy.19,22–24 Although some clinical trials show that intraocular pressure–lowering efficacy is similar between selective laser trabeculoplasty and prostaglandin analogue agents, other trials show superior efficacy with prostaglandin analogue agents.12,25–27 Additionally, studies have shown that selective laser trabeculoplasty suffers from a larger percentage of nonresponders compared with prostaglandin analogue treatment, and selective laser trabeculoplasty treatment effect is well known to deteriorate with time.10,24,28–30 Studies evaluating 24-hour intraocular pressure–lowering treatment efficacy also show that prostaglandin analogue agents may be more effective than selective laser trabeculoplasty for reducing intraocular pressure diurnal fluctuations and reducing peak intraocular pressure in the nocturnal period.29,31 It is also significant that after latanoprost was initially introduced in 1997, studies showed that the number of invasive glaucoma surgeries dramatically decreased, apparently because of the enhanced disease stability associated with this medication.32–35 Together, this evidence validates the continued use of prostaglandin analogue agents as a primary initial treatment in primary open-angle glaucoma and ocular hypertension.
Topical medical treatment may also be a particularly good option for first-line treatment in patients characterized by intraocular pressure in the statistically normal range (normal-tension glaucoma). Several studies show that selective laser trabeculoplasty treatment response depends on baseline intraocular pressure, with increasing treatment response directly associated with increasing baseline intraocular pressure.36–38 Accordingly, selective laser trabeculoplasty treatment response is rather modest for eyes with low baseline intraocular pressure.39,40 These small treatment responses also make them difficult to reliably detect owing to inherent tonometry measurement variability.41 On the other hand, prostaglandin analogue treatment has been shown to achieve greater intraocular pressure lowering and less intraocular pressure fluctuation compared with selective laser trabeculoplasty in patients with normal-tension glaucoma.26,42 Moreover, there is some evidence suggesting that topical brimonidine may provide glaucoma neuroprotection that exceeds its intraocular pressure–lowering efficacy, with some authors suggesting that this agent should be considered for a primary role in treatment of normal-tension glaucoma.43 Finally, there are theoretical advantages to using rho-kinase inhibitors to reduce intraocular pressure in normal-tension glaucoma because this drug class can lower episcleral venous pressure, which allows for a lower intraocular pressure than can be achieved by selective laser trabeculoplasty or other classes of medications.44,45 Collectively, these lines of evidence suggest that topical medical treatments may have important and unique advantages over selective laser trabeculoplasty as a primary treatment approach in normal-tension glaucoma.
An additional treatment consideration is differential access to selective laser trabeculoplasty and medical agents. Generally, broad availability exists for topical medications in developed countries, whereas access to laser treatment is more restricted.46–48 Given increasing US ophthalmology workforce shortages and increased disease burden due to aging of the population, this access is expected to further deteriorate unless optometric scope of practice further expands.49,50 Notably, optometric providers already deliver a substantial proportion of glaucoma care in the United States, and optometry offers greater geographic distribution than ophthalmology.51,52 When considering that the future preferred selective laser trabeculoplasty treatment paradigm could include annual selective laser trabeculoplasty treatment sessions,53 use of optometry is compulsory if selective laser trabeculoplasty is to assume the preferred primary treatment role for primary open-angle glaucoma and ocular hypertension. Analogously, the United Kingdom is addressing similar selective laser trabeculoplasty access problems by providing training for optometrists to deliver selective laser trabeculoplasty treatments in the United Kingdom.54 Until selective laser trabeculoplasty becomes more accessible, initial medical treatment will remain a primary treatment for many patients.
It is well known that chronic use of topical medications is associated with symptoms of ocular discomfort and permanent changes to anterior segment anatomy and physiology for some patients.55 In particular, prostaglandin analogue agents have been associated with chronic ocular surface and peri-orbital changes.20 Yet, despite these recognized adverse events, clinical trials that have directly compared quality-of-life scores between patients assigned to initial medical versus selective laser trabeculoplasty treatment have not found clinically significant between-group differences in quality of life.12,26,40 These findings suggest that the well-known chronic ocular surface and peri-orbital changes that can occur in patients using prostaglandin analogues do not cause sweeping systematic effects on quality of life. These findings are consistent with reports indicating that prostaglandin analogues are generally well tolerated and support broad use of these agents. Accordingly, when deciding whether selective laser trabeculoplasty or topical medication is the best initial treatment for any individual patient, the quality-of-life findings from available research imply that neither option is superior to the other.
Finally, despite 20 years of published evidence about selective laser trabeculoplasty, studies investigating selective laser trabeculoplasty as an initial first-line treatment remain limited.12,26,29 The LiGHT trial was a well-designed and powerful study that demonstrated compelling results, but it is a singular investigation, and no other study has proved that initial selective laser trabeculoplasty achieves equal or superior glaucoma disease control compared with initial medication treatment. Because disease control is the primary objective of glaucoma management, confirmatory evidence supporting this finding would be welcome and valuable. Furthermore, much more needs to be learned about selective laser trabeculoplasty, including its operative mechanisms and how post-treatment 24-hour intraocular pressure profiles are associated with longitudinal structural and functional stability. Research-based guidance about optimal selective laser trabeculoplasty treatment and surveillance paradigms are needed, as are additional studies comparing the effect of selective laser trabeculoplasty in eyes that are and are not treatment naive.46,56 Studies examining selective laser trabeculoplasty efficacy stratified by disease stage and the mechanisms for selective laser trabeculoplasty nonresponse and tachyphylaxis are also required. In summary, much remains unknown about selective laser trabeculoplasty, particularly as an initial intraocular pressure–lowering treatment. Accordingly, clinicians should continue to use all clinical data along with patient preference to guide individualized treatment plans so that glaucoma management can be optimized for each patient.
Conclusion
Both medical therapy and selective laser trabeculoplasty for the initial management of primary open-angle glaucoma and ocular hypertension are great options as first-line therapy. Individualizing treatment recommendation based on a myriad of factors is important. Intraocular pressure–lowering drops have a myriad of long-term safety and efficacy data, which may be a strong benefit to some patients and practitioners. Patients with intraocular pressure already in the statistically normal range may experience a great pressure reduction from medical therapy first. Conversely, patients with drop intolerance and poor adherence may do better with selective laser trabeculoplasty as first-line therapy.
Framing the conversation around selective laser trabeculoplasty is essential, using the term surgery sparingly and simply describing the procedure. Discussing results from key studies regarding safety and efficacy of selective laser trabeculoplasty can bolster patient confidence, as can confirming that it is covered by insurance. Many patients struggle with selecting the initial modality of treatment while in the examination chair. Reassuring the patient that even if they chose medications first does not mean selective laser trabeculoplasty is not an option if they encounter drop issues and emphasizing that having selective laser trabeculoplasty first does not necessarily mean that they will avoid medication is important.
Ultimately, maintaining an open dialogue with our patients, providing education on risks and benefits of both selective laser trabeculoplasty and medication, and tailoring the treatment plan based on the clinical profile of each patient will promote positive patient outcomes.