Poor compliance with drops for glaucoma has been associated with high cost, side effects, dosing regimen, and patients’ ability to remember to place drops in the eye. When patients aren’t compliant, there is a good chance their IOPs are fluctuating. Data from studies such as the Advanced Glaucoma Intervention Study (AGIS) have shown that fluctuation in IOP can be a risk factor for progression, especially in those patients with IOPs in the “normal” range.^1,2 Therefore, poor compliance can be a risk factor for progression.

Today, more than ever, there has been a focus on improving compliance and maintaining or even improving the quality of life for our glaucoma patients. Adherence in the first year of medical therapy is 51% to 56%, according to one study,³ but many of us experience even lower rates. Toxicity of the surface is a potential risk in almost all topical glaucoma medications,⁵ including prostaglandins.^6-8 Local side effects can grow worse with use over time, and this can decrease compliance.⁹ Potential systemic effects include exacerbation of existing airway disease,¹⁰ impact on blood pressure, or diabetes. We have seen an incredible proliferation in technology, specifically in the microinvasive glaucoma surgery (MIGS) space, to help decrease these risk factors and increase safety and quality of life. MIGS has helped us appreciate the impact even one medication can have on quality of life for our patients.

Over the last decade, with the introduction of selective laser trabeculoplasty (SLT; available in the United States from Lumenis [Selecta II], Ellex [Tango], and Quantel [Solutis and Optimis Fusion]) as an alternative to argon laser trabeculoplasty (ALT), there has been a renewed interest in performing laser trabeculoplasty as a first-line therapy in glaucoma. And with a growing interest in alternatives to drops, SLT has gained even more acceptance as a first-line therapy. It may even be a better alternative to drops, if a MIGS procedure is planned in the future. In fact, laser trabeculoplasty could be considered the original noninvasive glaucoma surgery. Procedures such as SLT can help control IOP safely while minimizing issues of compliance and long-term side effects. Here we will examine some of the benefits of SLT as a primary therapy.

Efficacy of SLT as a First-Line Therapy

Early studies showed trabeculoplasty as a first-line therapy is as effective as drop therapy. The Glaucoma Laser Trial (GLT), a study over 20 years old, found that ALT was as effective as medication for treating newly diagnosed open-angle glaucoma (OAG).¹⁰ The Collaborative Initial Glaucoma Treatment Study (CIGTS) demonstrated laser trabeculoplasty or trabeculectomy was at least as effective in maintaining IOP reduction in comparison with a single medication.¹¹ Many surgeons viewed ALT as a second- or third-line option because the argon laser results in thermal damage to the trabecular meshwork (TM) and canal, which limits multiple treatments. Because SLT is nondestructive to the TM and canal, repeated treatments have been shown to be safe and efficacious.¹² Unlike ALT, due to its nondestructive property, SLT also does not limit or affect the use of canal-based MIGS procedures in the future.

Katz et al published the SLT vs MED study, which was a prospective, randomized trial that found similar efficacy between SLT and eye drops as initial therapy.¹³ Sixty-nine patients (127 eyes) with OAG or ocular hypertension were randomized to 360 degrees SLT or prostaglandin analog treatment. At the 1-year final follow-up, mean IOP was 18.2 mmHg in the SLT group (6.3 mmHg reduction) and 17.7 mmHg in the medication group (7 mmHg reduction). By one year, 11 percent of the SLT eyes received additional laser, while 27 percent of the prostaglandin group required additional medication. There were no statistically significant differences between the treatment groups. In a study by McIlraith et al, there was no difference between latanoprost and SLT at 12 months. They both provided a mean reduction in IOP of 30.6% and 31%, respectively.⁵ McIlraith et al and Bovell et al also showed that SLT is not only as effective in lowering IOP as prostaglandin drugs, but also produces the same 5-year IOP-lowering results as ALT.¹⁴

Nagar et al also reported that SLT decreases pressure similarly to latanoprost. The mean IOP decrease in the SLT group was 30% from untreated baseline, which mimicked what is seen in prostaglandin analogues.¹⁵ In my experience, treating 360 degrees initially gives the greatest effect. The higher the baseline pressure, the better the response, whether in naïve patients, in patients where treatment has been washed off, or as an add-on to medications. Studies have also shown a better response when the pressure is higher and the patient is treatment naïve. As we see in patients on medications, the lower the IOP to begin with, the less response you will see. Therefore, if you perform SLT on someone already on a drop, you may not obtain that 30-percent reduction seen in previous SLT studies.¹⁶

Melamed et al also studied the safety and efficacy of SLT as a primary treatment for open-angle glaucoma patients. They tested 45 eyes of 31 patients and found that the mean IOP change was 31.6% 12 months post SLT with very few initial side effects. They concluded that SLT is a safe and effective treatment for ocular hypertension and open-angle glaucoma.¹⁷ Jindra et al performed a retrospective chart review on 1,363 and 945, respectively, of 3,013 eyes treated with SLT over 8 years. Two-tailed paired t-test was used to compare maximum pre- and post-procedure IOP and number of meds. In this large long-term series, SLT significantly lowered IOP and decreased number of meds as, primary and secondary therapy, in patients with glaucoma.¹⁸ Because fluctuation in IOP can be a risk factor for glaucoma progression, another benefit of SLT is the reduction in diurnal fluctuation across 24 hours, as seen in a 2010 study.¹⁹

The repeatability of SLT allows us to feel comfortable offering SLT first line; if the IOP does eventually rise, we are still able to repeat it. A study by Hong et al showed that the IOP-lowering effect of the first SLT treatment was the same as the second laser repeated after at least 6 months.²⁰ Data from a multicenter trial presented at the American Glaucoma Society 2011 meeting and showed similar findings with a larger study population.²¹ It was found that the final IOP was equivalent after the initial and repeat SLT, and when baselines were matched, the magnitude of IOP lowering was almost identical.

Cost

Cost can dramatically impact our patients’ ability to stay on long-term drop therapy, not to mention impact the health care system. However, Seider et al demonstrated SLT becomes less costly than most brand-name medications within 1 year and less costly than generic latanoprost and generic timolol after 13 and 40 months, respectively.²² Similarly, a 2012 study compared the cost of SLT to prostaglandin analogs in the treatment of newly diagnosed OAG.²³ The authors found that laser trabeculoplasty provided a cost saving of $2,645 per quality-adjusted life year compared to prostaglandin analogs. According to the Canadian Journal of Ophthalmology, 3-year savings of SLT vs. monotherapy is $580.²⁴ Cantor et al found that the 5-year cost of SLT was $4,838 compared to $6,571 for medication and that SLT has been shown to provide a cost savings of about $1,700 for patients who need 2 to 4 medications over 5 years of treatment.²⁵ The study calculated that the 5-year cumulative costs of laser trabeculoplasty were approximately $4,838, compared to $6,571 for medications and $6,363 for filtration surgery. First-line therapy with SLT is also associated with a lower mean cost of treatment over 5 years ($4,949) compared with medication alone ($6,553) and surgery ($6,386).

Adverse Event Profile

Another advantage of SLT is the favorable side-effect profile compared to medications. The most common adverse event is postoperative inflammation, which is generally mild and usually treated with observation or a topical or systemic nonsteroidal anti-inflammatory. The incidence of an IOP spike is 5% or less (even with 360-degree treatment) and is usually self-limiting. In patients with excessive angle pigmentation, such as pigment dispersion glaucoma and pseudoexfoliation glaucoma, I use lower power levels and consider 180-degree treatment. Transient hyperemia is also common which is self-limiting as well.

Traditionally, glaucoma therapy has focused on areas outside of the natural outflow pathway (uveoscleral outflow or deceased aqueous humor production). In time, this can further restrict the flow through the natural pathways.²⁶ This is likely why we find SLT is most effective in a virgin eye that has not received any medications. Drops containing the preservative benzalkonium chloride can induce toxicity and associated adverse effects. This can result in compromised ocular tolerance, patient comfort, and thus compliance. Preservatives can also have toxic effects on the conjunctiva. Limiting the use of these medications may preserve the health of the conjunctiva, which may be helpful if filtering surgery or tube surgery is needed in the future. Using SLT can avoid these adverse events and increase the chance of surgical success.

Potential as a Diagnostic Tool

Currently, there are no preoperative noninvasive diagnostic tools to provide us the location and dynamics of outflow resistance. With SLT, we might gain some information on the outflow resistance of each patient. SLT applies selective photothermolysis to pigmented cells in the TM, which releases inflammatory mediators, such as macrophages and cytokines. This increases aqueous outflow through the TM and the inner wall of Schlemm canal.

If SLT has a significant effect, we may infer the TM could be the main area of resistance. If SLT is not effective, this might tell us that resistance is in the canal or in the distal collector channels. We are only now starting to understand the potential diagnostic benefit of SLT as a first-line therapy. It is interesting to explore the notion that SLT may not only help us better understand a patient’s pathology, we might be able to use that information to select the best MIGS intervention for a given patient.

Primary SLT also may have the potential of preventing further collapse of the TM and the Schlemm canal, and although there is no published evidence yet, maintaining flow through the natural outflow system might allow for better response for the MIGS natural outflow procedures. More studies are needed to determine the validity of these early hypotheses.

Summary

The art of glaucoma care is not only in diagnosing the disease, but also in keeping the IOP at target while maximizing our patient’s quality of life. Glaucoma is a progressive optic neuropathy and accounts for 8% of global blindness. The earlier we treat and the better we maintain consistent control of their IOP, the better chance we have of preventing blindness. While drop therapy will likely always play a significant role in the management of our patients, glaucoma is rapidly becoming a procedure-based disease. When objectively examining the overall risk/benefit profile of primary SLT, it is easy to see why the paradigm is shifting. GP

References

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Inder Paul Singh, MD, is a glaucoma specialist at the Eye Centers of Racine and Kenosha, in Wisconsin. Dr. Singh reports financial relationships with Ellex, Alcon, Allergan, New World Medical, Bausch + Lomb, Shire, Aerie, and Sun Ophthalmics. Reach him at ipsingh@amazingeye.com.