The glaucoma treatment paradigm is evolving, driven both by new and emerging therapies and by growing dissatisfaction with the status quo. Topical medical therapy has served patients well for more than 150 years; despite its many limitations, it has remained the preferred first-line treatment because alternative options carried even greater drawbacks. Today, the development of selective laser trabeculoplasty (SLT), sustained-release drug delivery platforms, and minimally invasive glaucoma surgeries provides an array of new options, allowing clinicians to reconsider the traditional treatment paradigm and improve both clinical outcomes and quality of life for patients with glaucoma.
Medical Therapy and Its Limitations
Topical medical therapy has long been the first-line approach for managing newly diagnosed primary open-angle glaucoma (POAG), ever since physostigmine was first isolated from the calabar bean more than 150 years ago.1 Since that time, numerous classes of intraocular pressure (IOP)–lowering drugs have been developed, each with distinct mechanisms of action, providing clinicians with a wide range of options to facilitate individualized medical management of glaucoma.2 These medications undergo rigorous development through phase 3 clinical trials to characterize their efficacy and safety, and numerous landmark studies have demonstrated that topical medications can delay or prevent both the onset and progression of glaucoma.3-5
Topical medical therapy is not without limitations, however. The most significant limitation is a high rate of nonadherence,6-8 which increases the risk of disease progression.6,9,10 Tolerability is another important concern. All medications have side effects, some of which are severe or bothersome enough to negatively impact adherence. One notable consequence of chronic topical therapy is the development of ocular surface disease, which affects 30% to 70% of glaucoma patients,11-14 may require additional medications to manage, and adversely impacts quality of life.15,16
Given these limitations, why has medical therapy endured as the primary treatment for newly diagnosed glaucoma? The answer is that, despite its drawbacks, medical therapy has historically been more effective than available alternatives. Primary laser therapy using argon laser trabeculoplasty17 and primary surgical approaches5,18 have been considered, but studies have not demonstrated sufficient advantages to drive a paradigm shift until recently.
The development of SLT and the findings of the recent landmark Laser in Glaucoma and Ocular Hypertension (LiGHT) trial have provided clinicians with the tools to move beyond primary medical therapy. SLT overcomes nearly all the limitations of topical medications and represents an important first step toward a new glaucoma treatment paradigm that offers patients the real possibility of a drop-free lifetime of glaucoma care.
SLT and the LiGHT Trial
Selective laser trabeculoplasty delivers energy via a Q-switched, frequency-doubled 532-nm Nd:YAG laser directly to the trabecular meshwork, where increased resistance to aqueous outflow—arising from both age and the glaucoma disease process—leads to elevated IOP. The procedure is quick, well tolerated, effective, and safe. In the recent LiGHT trial, more than 700 participants with newly diagnosed mild-to-moderate POAG or ocular hypertension (OHT) who had not previously received treatment were randomly assigned to receive either primary SLT or primary medical therapy.19
Over 6 years, mean IOP was slightly higher in the SLT group compared with the medication group. However, the risks of glaucoma progression, the need for glaucoma surgery, and the need for cataract surgery were all significantly lower among participants who received primary SLT. This apparent paradox is likely explained by adherence: some participants typically took medications faithfully only immediately before study visits, whereas SLT provided more consistent IOP control over time, resulting in improved long-term outcomes.
Notably, 56% of participants treated with primary SLT maintained well-controlled IOP with no further interventions—including no repeat SLT—at 6 years. When repeat SLT treatments are included, the 6-year medication-free success rate rose to 70%. In other words, nearly three-quarters of patients who received primary SLT, with repeat treatments as needed, did not require a single IOP-lowering eye drop for at least 6 years.
The LiGHT trial also highlighted the safety of primary SLT. Ocular side effects were significantly more common with medical therapy than with SLT. Across almost 1,000 SLT procedures performed over 6 years, there were no sight-threatening complications, and only a single eye required intervention for a post-SLT IOP spike.
Impact of the LiGHT Trial
The findings of the LiGHT trial have provided the evidence necessary to support a paradigm shift from primary topical medical therapy to primary SLT for patients with newly diagnosed mild-to-moderate POAG or OHT. The trial was conducted in the United Kingdom, and its results led the UK National Health Service to adopt SLT as the preferred first-line therapy for incident cases of POAG and high-risk OHT.20 Although the United States does not have a national health service to drive nationwide changes in practice through policy, a similar shift is underway. The most recent edition of the American Academy of Ophthalmology’s Preferred Practice Pattern for Primary Open-Angle Glaucoma now recommends SLT as first-line therapy.21
Beyond the clear evidence of efficacy and safety, other factors are expected to drive adoption of the SLT-first approach. One such factor is the development and commercialization of direct SLT (DSLT), which delivers laser energy directly through the eye wall to the trabecular meshwork without requiring a mirrored contact lens. DSLT is faster than standard SLT, requires no coupling agent, and allows for quicker visual recovery, improving patient experience. The commercial device (Voyager DSLT; Alcon) automatically aligns and focuses on the ocular surface, identifies the limbal region for treatment, and delivers 120 laser spots in under 2 seconds with gaze tracking to ensure energy is applied only to the target tissue. In a randomized clinical trial, DSLT achieved IOP reductions at 6 and 12 months nearly identical to those with standard SLT, without clinically relevant safety concerns.22
Another factor supporting SLT adoption in the United States is the ongoing expansion of the optometric scope of practice: 12 states now permit optometrists to perform SLT. The user-friendly Voyager DSLT platform is expected to further increase access, allowing more patients nationwide to benefit from the procedure.
What’s Next for SLT: The COAST Trial
With SLT use increasing, questions remain about optimizing the procedure to improve long-term outcomes. In treatment-naïve eyes, the median duration of IOP control from primary SLT is approximately 6 years.19,23,24 Although repeat SLT can be performed safely once the initial effect wanes, repeated therapy is often delayed until IOP rises—a “rescue” approach—which may contribute to SLT exhaustion. This approach is analogous to the pro re nata (PRN) regimen in retinal disease, where delaying anti-VEGF treatment until disease reactivation led to diminishing returns. Treat-and-extend regimens in retina, by contrast, maintain structural and functional outcomes by retreating before deterioration occurs.
The Clarifying the Optimal Application of SLT Therapy (COAST) trial, of which I am chair, seeks to apply these lessons from retina to glaucoma. Supported by the National Eye Institute, COAST is ongoing at 29 clinical centers across the United States. The trial addresses whether SLT maintenance therapy can delay or prevent SLT exhaustion more effectively than rescue therapy.
COAST consists of 2 sequential trials: in Trial 1, patients with newly diagnosed mild-to-moderate POAG or OHT receive either standard-energy or low-energy SLT and are followed for 12 months. Those who achieve and maintain individualized target IOP are re-randomized in Trial 2 to receive either PRN retreatment or annual low-energy SLT as maintenance therapy. The rationale for annual low-energy SLT is supported by existing data suggesting that preemptive retreatment may extend medication-free IOP control.25
Trial 1 of COAST is already complete and found that, as initial therapy, standard-energy SLT is more effective than low-energy SLT in achieving and maintaining IOP control over 12 months. COAST participants now receive standard-energy SLT at study entry and 12 months later are randomized into Trial 2. Our hypothesis is that, after an initial “loading dose” of standard-energy SLT (analogous to multiple monthly anti-VEGF injections in retinal therapy), annual low-energy maintenance therapy will improve long-term medication-free survival compared with PRN rescue therapy, the current standard of care. COAST is ongoing, and patients may be referred to study sites listed at www.COASTtrial.org.
Conclusion
Primary medical therapy for glaucoma has served patients for more than 150 years. Emerging evidence supports a paradigm shift to primary SLT, which addresses many limitations of medical therapy, including adherence and tolerability. The LiGHT trial demonstrated superior long-term outcomes with SLT vs medications in newly diagnosed mild-to-moderate POAG or OHT. Treatment with SLT is expected to increase due to the LiGHT findings, the development of DSLT, and expanded optometric scope of practice. The COAST trial will further clarify the optimal SLT strategy to prevent or delay SLT exhaustion and enable patients to avoid topical medications for as long as possible. GP
References
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