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Editors Selection IGR 18-3

Surgical Treatment: How does SLT work and on whom?

Comment by John Samples on:

71656 Mechanism of Action of Selective Laser Trabeculoplasty and Predictors of Response, Gulati V; Fan S; Gardner BJ et al., Investigative Ophthalmology and Visual Science, 2017; 58: 1462-1468

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This study details the first thorough investigation of aqueous humor dynamics in the common clinical procedure selective laser trabeculoplasty (SLT). Numerous papers have reported on argon laser trabeculoplasty (ALT), often attributing its effects on outflow pathway extracellular matrix to stretching or the release of cytokines, but the other types of trabeculoplasty such as ALT and micropulse laser trabeculoplasty (MDLT) have been reported on much less frequently. SLT was introduced in the late 1990s and has been increasingly popular among clinicians in the last decade, sometimes being used as firstline therapy particularly in patients who do not wish to use medications or who are likely to be non-compliant with the use of medication. SLT treatment delivers about 1% of the total energy to the trabecular meshwork compared to the amount delivered by an ALT. Yet, SLT is similar to ALT in its clinical efficacy. This raises substantial questions about its mechanisms. SLT has purportedly has different mechanisms of action from ALT.

Histological analysis has shown that SLT applications in the meshwork lack the cellular destructive and coagulative effects found in the meshwork with ALT. Prior to this study, conventional outflow facility had been reported to increase three months after SLT treatment alone with no effects on aqueous humor inflow. Other parameters of aqueous humor dynamics which can alter intraocular pressure (IOP) include episcleral venous pressure (EVP) and uveoscleral outflow. This is the first study to look at all of the aqueous humor dynamic properties in the same patients. Thirty-one patients were enrolled and 29 completed the study. None of the subjects were on any pressure lowering medications. They were either interested in SLT as first line therapy, were poor at compliance or wanted to stop current medications due to side effect or cost concerns; all of which are frequently encountered clinical situations that can make laser procedures desirable. It is interesting that 31 out of 36 consecutively evaluated candidates for the study met these criteria. The completed data set consisted of 29 subjects with 29 study eyes and 25 contralateral eyes. The latter were particularly important because over the years, contralateral IOP effects have been attributed to trabeculoplasty treatments.

As expected, SLT showed a significant decrease in both 9AM and noon time pressure measurements in the SLT treated eye at three months compared with baseline. The study did not find any statistically significant association between IOP response and demographics or treatment variables including total laser energy, angle pigmentation or percentage of laser spots with visible response. The association between young age and greater IOP response, which has previously been reported for ALT, was almost statistically significant. An interesting association with central corneal thickness also approached statistical significance but did not quite achieve it, suggesting that an additional 1.0 mmHg of pressure lowering response was associated with 25 um thinner cornea.

Methodologically, two methods were used in this study, fluorophotometry and tonography. A decrease in uveoscleral outflow after SLT was seen using the fluorophotometric method but not the tonographic method. Conceivably, as the authors speculate, a small decrease in uveoscleral outflow may reflect quantitatively that more aqueous is transiting the trabecular meshwork.

This study shows that three months after SLT IOP reduction is mediated through an increase in outflow facility. No meaningful effects of any other parameters such as episcleral venous pressure or uveoscleral outflow were found. No contralateral eye effects were found. Both a higher baseline aqueous inflow and a lower baseline outflow facility were found to be predictive of IOP response to SLT.

It might be that we will be able to predict which patients will best respond to the trabeculoplasties when we have the ability to identify who has a high baseline aqueous flow and a lower baseline outflow facility. It is intriguing that in a larger study or in a study with different glaucoma subpopulations thin cornea may be found to be associated with a better SLT response, but that did not achieve statistical significance here.

This meaningful and well-done paper really encompasses the methods that we glaucomatologists need to use to evaluate not only drugs but our other new laser, ultrasound and minimally invasive surgical procedures. Understanding mechanisms will be enhanced, as this work points out, when we have better methods of measuring episcleral venous pressure and also uveoscleral outflow.

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