SLT may be a good first-choice treatment for glaucomatous eyes

Laser could be an effective alternative to medical therapy, with fewer compliance issues and side effects.

Issue: May 2012

ByAndrea Gabai, MD

ByDaniele Veritti, MD

Daniele Veritti

We all know how important compliance is in glaucoma medical treatment. Good compliance, however, is often challenged by the patient’s ability to regularly and correctly instill prescribed eye drops. Poor motivation, forgetfulness associated with aging and incorrect instillation techniques can contribute to bad IOP control.

With IOP as a main risk factor for glaucoma, we can directly act to find ways to control IOP and limit glaucomatous damage progression. So, is there any way to keep IOP within an acceptable range without a stringent treatment regimen?

Laser could be the answer. Argon laser trabeculoplasty has treated open-angle glaucoma for many years. However, its use is associated with undesirable effects such as trabecular meshwork thermal damage. This collateral phenomenon leads to scarring and synechiae formation, thus compromising the possibility of repeated treatment.

SLT

More recently, selective laser trabeculoplasty has been shown to represent a viable approach: the ability to preserve the meshwork from thermal damage and, like ALT, increase the aqueous outflow. SLT pulses are characterized by low energy (0.8 mJ to 1.2 mJ) and short duration (approximately 3 nanoseconds). This allows surgeons to selectively target pigmented cells and reduce energy dissipation to the surrounding tissue.

SLT was first described by Latina and Park in 1995, when they analyzed the effects of different laser sources on cultures of pigmented and non-pigmented trabecular meshwork cells. They observed the intracellular fracture of melanin granules and rupture of lysosomal membranes in the pigmented trabecular meshwork cells in absence of ultrastructural damage in adjacent non-pigmented cells. The safety of SLT has also been observed at a molecular level. It does not induce up-regulation of expression of genes responsible for cellular damage or apoptosis, according to a study by Izzotti and colleagues.

The energy delivery in SLT is so rapid that the thermal relaxation time of the pigmented trabecular meshwork is never reached. This produces an extremely fast temperature rise, causing the water around melanosomes to evaporate with formation of microbubbles. What exactly produces the IOP reduction has not yet been discovered. Gene expression modulation seems to play a key role. A group of authors reported the complex changes in genomic expression produced by SLT on the trabecular meshwork in the absence of phenotypic damage detectable by electron microscopy. These changes involve clusters of genes modulating the meshwork cells, matrix tropism, degree of stretching and, consequently, the aqueous outflow. These genes act on “cell motility, intercellular connections, extracellular matrix production, protein repair, DNA repair, membrane repair, reactive oxygen species production, glutamate toxicity, antioxidant activities, and inflammation,” Izzotti and colleagues said.

Also at a molecular level, Alvarado and colleagues reported the increase of monocytes and permeabilizing cytokines they observed in vitro in trabecular tissue irradiated by a nanosecond laser, which is similar to SLT. In this experience, the authors observed the enhancement in permeability of Schlemm’s canal endothelial cells when exposed to cytokines even in absence of irradiation. This phenomenon could explain the better aqueous outflow and subsequent IOP reduction. SLT has proven suitable for all types of open-angle glaucoma (primary, pseudoexfoliative, pigmentary) when an intact trabecular meshwork is present. In angle-closure glaucoma, this kind of laser should be considered only if patients’ iridotomies are still present and a sufficient extent of trabecular meshwork is visible by gonioscopy.

When compared with ALT in studies, SLT has shown a similar efficacy in reducing IOP. Thus, SLT is preferable because of the sparing of non-target cells. Furthermore, SLT is repeatable in patients who had previously received a 360· treatment and a subsequent IOP reduction, a study found.

First-choice treatment

The role of SLT as a first-choice treatment, allowing patients to avoid topical medications, has been the object of several studies. Prostaglandin analogues appear to be the only competitors to SLT because both of these treatments act on IOP by increasing aqueous outflow, whereas drugs such as beta blockers and carbonic anhydrase inhibitors are more active by reducing production of outflow.

Positive outcomes have been proved in relatively small groups of patients affected by primary open-angle glaucoma. Some authors reported SLT and nightly topical prostaglandin analogues to have comparable results in a 10- to 12-month follow-up period, with laser presenting advantages in terms of treatment frequency.

An interesting experience from Alvarado and colleagues was with 24 eyes. The eyes received a prostaglandin analogue treatment phase followed by a washout period and SLT treatment. These two approaches demonstrated similar IOP reduction.

According to some studies, SLT has a more prolonged efficacy in eyes that received a higher amount of energy during the laser treatment and in patients who received it at a younger age, whereas the amount of IOP reduction seems more consistent with a higher baseline IOP. These results indicate that it is not rational anymore to think of medications as the only viable first-line treatment for glaucoma cases that could benefit from a safe and less demanding treatment.

SLT has been demonstrated to be effective through finely targeted molecular processes that do not compromise trabecular meshwork integrity, not even at the microscopic level. Therefore, surgeons should consider starting treatment of newly diagnosed glaucoma cases with SLT, especially because a longer efficacy can be expected.

References:

Alvarado JA, Alvarado RG, Yeh RF, Franse-Carman L, Marcellino GR, Brownstein MJ. A new insight into the cellular regulation of aqueous outflow: how trabecular meshwork endothelial cells drive a mechanism that regulates the permeability of Schlemm’s canal endothelial cells. Br J Ophthalmol. 2005;89(11):1500-1505.

Ayala M, Chen E. Comparison of selective laser trabeculoplasty (SLT) in primary open angle glaucoma and pseudoexfoliation glaucoma. Clin Ophthalmol. 2011;5:1469-1473.

Ayala M, Chen E. Predictive factors of success in selective laser trabeculoplasty (SLT) treatment. Clin Ophthalmol. 2011;5:573-576.

Damji KF, Shah KC, Rock WJ, Bains HS, Hodge WG. Selective laser trabeculoplasty v argon laser trabeculoplasty: a prospective randomised clinical trial. Br J Ophthalmol. 1999;83(6):718-722.

Ho CL, Lai JS, Aquino MV, et al. Selective laser trabeculoplasty for primary angle closure with persistently elevated intraocular pressure after iridotomy. J Glaucoma. 2009;18(7):563-566.

Hodge WG, Damji KF, Rock W, Buhrmann R, Bovell AM, Pan Y. Baseline IOP predicts selective laser trabeculoplasty success at 1 year post-treatment: results from a randomised clinical trial. Br J Ophthalmol. 2005;89(9):1157-1160.

Hong BK, Winer JC, Martone JF, Wand M, Altman B, Shields B. Repeat selective laser trabeculoplasty. J Glaucoma. 2009;18(3):180-183.

Izzotti A, Longobardi M, Cartiglia C, Rathschuler F, Saccà SC. Trabecular meshwork gene expression after selective laser trabeculoplasty. PLoS One. 2011;6(7):e20110.

Juzych MS, Chopra V, Banitt MR, et al. Comparison of long-term outcomes of selective laser trabeculoplasty versus argon laser trabeculoplasty in open-angle glaucoma. Ophthalmology. 2004;111(10):1853-1859.

Koucheki B, Hashemi H. Selective laser trabeculoplasty in the treatment of open-angle glaucoma. J Glaucoma. 2012;21(1):65-70.

Kramer TR, Noecker RJ. Comparison of the morphologic changes after selective laser trabeculoplasty and argon laser trabeculoplasty in human eye bank eyes. Ophthalmology. 2001;108(4):773-779.

Latina MA, Park C. Selective targeting of trabecular meshwork cells: in vitro studies of pulsed and CW laser interactions. Exp Eye Res. 1995;60(4):359-371.

Mao AJ, Pan XJ, McIlraith I, Strasfeld M, Colev G, Hutnik C. Development of a prediction rule to estimate the probability of acceptable intraocular pressure reduction after selective laser trabeculoplasty in open-angle glaucoma and ocular hypertension. J Glaucoma. 2008;17(6):449-454.

McIlraith I, Strasfeld M, Colev G, Hutnik CM. Selective laser trabeculoplasty as initial and adjunctive treatment for open-angle glaucoma. J Glaucoma. 2006;15(2):124-130.

Nagar M, Ogunyomade A, O’Brart DP, Howes F, Marshall J. A randomised, prospective study comparing selective laser trabeculoplasty with latanoprost for the control of intraocular pressure in ocular hypertension and open angle glaucoma. Br J Ophthalmol. 2005;89(11):1413-1417.

For more information:

Daniele Veritti, MD, can be reached at Department of Ophthalmology, University of Udine, p.le S. Maria della Misericordia, 33100 Udine, Italy 33100; +39-0432-559907; email: verittidaniele@gmail.com.

Disclosures: Dr. Veritti and Dr. Gabai have no relevant financial disclosures.