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Selective laser trabeculoplasty therapy

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Figure 1. Comparison of 50 micron spot size with ALT (white arrowhead) and 400 micron spot size with SLT (white arrow)

______________________________

Dr Simon Skalicky
FRANZCO MPhil MMed (Ophthal Sci) MBBS(Hons 1) BSc(Med)
Melbourne Eye Clinic

 

To date, intraocular pressure (IOP) lowering is the only proven strategy to halt or slow progressive glaucoma yet the decision to commence or augment IOP-lowering treatment is not always easy. It can be difficult to determine if the measured IOP is the true IOP, if the patient is having large IOP fluctuations over the diurnal cycle such as night-time spikes, if the patient really has glaucoma or just suspicious discs, and if the IOP might cause disabling vision loss for the patient.

Weighed against the indication for treatment is the nature of the treatment itself: what it involves, the efficacy and likelihood of success, the cost, the side-effects and contraindications and the burden on daily life. When making decisions regarding glaucoma treatment, it is important to discuss these issues openly with our patients, outlining all the options including no treatment.

Patients with glaucoma are understandably concerned about their risk of future vision loss. Increasingly, they are presenting to optometrists and ophthalmologists better educated, requiring more detailed discussions and consultations, and wanting more autonomy in their management.

With these issues in mind, selective laser trabeculoplasty (SLT) is a useful treatment option to offer our patients. Well tolerated, minimally invasive and generally effective, the laser treatment is often used for patients with ocular hypertension or open angle glaucoma, including primary open angle glaucoma, pseudoexfoliation (PXF) glaucoma, pigment dispersion (PD) glaucoma, steroid-induced glaucoma and normal tension glaucoma.

SLT can be used alone or in combination with topical eye-drops. It is used as initial therapy, as an alternative to eye-drops for patients with local or systemic side-effects to their medication, as an adjunct to drops for established glaucoma patients not meeting their target IOPs, or for patients on maximal tolerated medical therapy to avert or delay filtration surgery.

Selective laser trabeculoplasty

SLT was first described 20 years ago and designed to selectively target pigmented cells in the trabecular meshwork (TM) and spare adjacent cells and tissues from thermal damage.1 Having largely superseded argon laser trabeculoplasty (ALT), SLT has many inherent advantages over the previous laser technology.

Compared to ALT, the spot size is larger (400 micrometres vs 50 micrometres), allowing the energy to diffuse over a larger area. This prevents harmful focus on any one point in the trabecular meshwork (Figure 1). In addition, the laser duration is much more brief, three nanoseconds (SLT) v 100 milliseconds (ALT).

The longer duration, highly-focused beam of ALT was capable of photocoagulation, resulting in potential structural damage to the trabecular meshwork.

In comparison, the laser application of SLT is too brief and too low in energy to cause significant structural damage (Figure 2A and 2B).2 SLT and ALT have a similar IOP-lowering efficacy,3 indicating that they may lower IOP through similar mechanisms and as a consequence, the coagulative TM damage with ALT may be unnecessary.4

 

40 OL SLT Figure 2A and 2B

Figure 2. A: Electronmicroscopic images of trabecular meshwork following ALT. B: Electronmicroscopic images of trabecular meshwork following SLT.

 

Despite many years of research the precise mechanism of SLT is still uncertain. SLT delivers short bursts of low-fluence laser energy to selected melanin-containing cells of the TM without damaging adjacent non-pigmented cells or structures.5 This induces cellular and biochemical changes in the TM cells, resulting in increased expression of pro-inflammatory cytokines and matrix metalloproteases.6

This pro-inflammatory drive results in recruitment of macrophages that phagocytose TM debris7 and probably causes trabecular cell division to stimulate growth of healthy TM and optimise outflow.8 Some evidence suggests SLT disrupts the integrity of tight junctions binding endothelial cells lining Schlemm’s canal, enhancing transendothelial aqueous outflow.9

The laser energy is applied using a gonioscopic mirror as a series of contiguous spots circum-linearly over the TM (Figure 3). Laser energy is generally titrated between 0.6–1.4 mJ to produce fine ‘champagne’ bubbles on application.

 

40 OL SLT Figure 3

Figure 3. Application of SLT

 

Typical treatment parameters are 50 (or 100) applications over 180 degrees (or 360 degrees). To prevent a transient IOP spike post-SLT that may occur in some patients, apraclonidine 0.5% (Iopidine; Alcon Laboratories, Inc., Fort Worth, TX, USA) is commonly given one hour before treatment.

Topical anti-inflammatory drops are generally not administered as the induction of an inflammatory response may be beneficial for the IOP-lowering effect of SLT. Several studies have compared outcomes following 90 degree, 180 degree and 360 degree treatment, and there is a trend suggesting that greater treatment area results in a greater and more reliable IOP reduction, although differences in IOP lowering between 180 degree and 360 degree treatment are not consistently found.10-13

SLT has a good success rate when first applied, resulting in an average IOP reduction of 15-30 per cent in most patients; however 15-25 per cent of patients either do not respond or minimally respond to the therapy.14,15 This efficacy is comparable to monotherapy with topical prostaglandins or beta-blockers.14

Four randomised control trials have compared SLT to medical therapy, and 10 randomised control trials have compared SLT to ALT. Meta-analyses of these studies showed that there was no statistically significant difference in treatment success or IOP reduction.14,16 The strongest predictor of success for SLT is high baseline (pre-treatment) IOP;17 yet SLT can still be effective for patients with normal tension glaucoma or patients on multiple topical medications. SLT is probably effective in reducing diurnal IOP fluctuation, although how it compares to topical medical therapy in this regard is uncertain.12

If successful, the effect of SLT is likely to reduce over time, resulting in an eventual IOP rise. On average the treatment lasts from two to three years but the range of length of treatment response can vary from six months to more than five years.18 It is critical that this fact is explained to patients who therefore need ongoing monitoring, ideally six-monthly.

The danger of using SLT to reduce IOP is that if the patient has the impression that once treated, the IOP will stay permanently lowered, an asymptomatic rise in IOP as the laser wears off can cause optic nerve damage if not monitored. SLT is repeatable, provided it had a significant effect on the first treatment; however, the efficacy of subsequent treatments is less than when first applied.

SLT has few side-effects. Commonly redness, discomfort or photophobia may occur after SLT but these symptoms resolve within a few days without treatment. Rarely, an IOP spike can occur immediately following SLT. This is more common in eyes with PXF, PD glaucoma, 360-degree treatment in one session or otherwise very damaged TM. The incidence of such spikes is significantly lower than following ALT and can be minimised by the pre-treatment use of IOP-lowering topical medication.14

Peripheral anterior synechiae can occur rarely following SLT (one to three per cent); likewise the incidence following SLT is less than following ALT.15 Transient deposits on the corneal endothelium and even occasional interstitial corneal stromal inflammation can occur following SLT, both of which resolve spontaneously.19 Rarely, SLT treatment can result in reactivation of herpetic corneal disease, and should be used with caution in patients with a history of herpetic keratitis.

Compared to daily eye-drops, SLT avoids the complex issues of treatment adherence20 and is probably gentler on the surface of the eye than long-term use of preserved topical medications. There is considerable interest in how SLT compares to prostaglandin monotherapy as initial treatment for glaucoma in terms of treatment efficacy, ocular discomfort, quality of life issues, prevention of glaucomatous progression and cost to the patient and society.

Health economic modelling varies considerably in different countries; however, modelling performed in a Canadian health-care settings suggest it is cost-effective compared to topical medical therapy, especially compared to multi-agent therapy.21

To compare SLT to topical medication as the initial treatment for glaucoma an international, multicentre RCT (the Glaucoma Initial Treatment Study) based mainly in Australia is underway.22 At the time of writing this article, results from this study have not yet been published.

Conclusion

Minimally invasive, well-tolerated and generally successful, SLT is an increasingly popular treatment alternative to topical medications for patients with ocular hypertension or open angle glaucoma. It is probably as effective as a single topical medication, and can be used either as a sole treatment or in addition to eye-drops.

SLT does not rely on patients adhering to a daily eye-drop regimen, and averts ocular surface side-effects related to drop toxicity. The common adverse effects related to SLT, redness and discomfort, are transient and self-limiting. SLT is not uniformly effective in all eyes. The IOP-lowering effect of SLT reduces over time; this must be explained clearly to our patients who therefore need ongoing six-monthly monitoring. Although the treatment is repeatable, subsequent treatments are generally not as effective in lowering IOP as the first treatment.

SLT may be cost-effective compared to therapy with topical medication but we await key RCT data to evaluate the health economic impact of SLT treatment for glaucoma.

 

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

2. 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: 773-739.

3. Wang W, He M, Zhou M, Zhang X. Selective laser trabeculoplasty versus argon laser trabeculoplasty in patients with open-angle glaucoma: a systematic review and meta-analysis. PloS One 2013; 8: e84270.

4. Stein JD, Challa P. Mechanisms of action and efficacy of argon laser trabeculoplasty and selective laser trabeculoplasty. Cur Opinion Ophthal 2007; 18: 140-145.

5. Latina MA, de Leon JM. Selective laser trabeculoplasty. Ophthal Clinics Nth Amer 2005; 18: 409-419, vi.

6. Bradley JM, Anderssohn AM, Colvis CM et al. Mediation of laser trabeculoplasty-induced matrix metalloproteinase expression by IL-1beta and TNFalpha. Invest Ophthalmol Vis Sci 2000; 41: 422-430.

7. Alvarado JA, Katz LJ, Trivedi S, Shifera AS. Monocyte modulation of aqueous outflow and recruitment to the trabecular meshwork following selective laser trabeculoplasty. Arch Ophthalmol 2010; 128: 731-737.

8. Dueker DK, Norberg M, Johnson DH, Tschumper RC, Feeney-Burns L. Stimulation of cell division by argon and Nd:YAG laser trabeculoplasty in cynomolgus monkeys. Invest Ophthalmol Vis Sci 1990; 31: 115-124.

9.  Alvarado JA, Iguchi R, Martinez J, Trivedi S, Shifera AS. Similar effects of selective laser trabeculoplasty and prostaglandin analogs on the permeability of cultured Schlemm canal cells. Amer J Ophthalmol 2010; 150: 254-264.

10. 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. Brit J Ophthalmol 2005; 89: 1413-1417.

11. Goyal S, Beltran-Agullo L, Rashid S et al. Effect of primary selective laser trabeculoplasty on tonographic outflow facility: a randomised clinical trial. Brit J Ophthalmol 2010; 94: 1443-1447.

12. Nagar M, Luhishi E, Shah N. Intraocular pressure control and fluctuation: the effect of treatment with selective laser trabeculoplasty. Brit J Ophthalmol 2009; 93: 497-501.

13.  Prasad N, Murthy S, Dagianis JJ, Latina MA. A comparison of the intervisit intraocular pressure fluctuation after 180 and 360 degrees of selective laser trabeculoplasty (SLT) as a primary therapy in primary open angle glaucoma and ocular hypertension. J Glaucoma 2009; 18: 157-160.

14. Wong MO, Lee JW, Choy BN, Chan JC, Lai JS. Systematic review and meta-analysis on the efficacy of selective laser trabeculoplasty in open-angle glaucoma. Surv Ophthalmol 2015; 60: 36-50.

15. Leahy KE, White AJ. Selective laser trabeculoplasty: current perspectives. Clin Ophthalmol 2015; 9: 833-841.

16. McAlinden C. Selective laser trabeculoplasty (SLT) vs other treatment modalities for glaucoma: systematic review. Eye 2014; 28: 249-258.

17. 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. Brit J Ophthalmol 2005; 89: 1157-1160.

18. Lai JS, Chua JK, Tham CC, Lam DS. Five-year follow up of selective laser trabeculoplasty in Chinese eyes. Clin Exp Ophthalmol 2004; 32: 368-372.

19. White AJ, Mukherjee A, Hanspal I, Sarkies NJ, Martin KR, Shah P. Acute transient corneal endothelial changes following selective laser trabeculoplasty. Clin Exp Ophthalmol 2013; 41: 435-441.

20. Skalicky SE, Goldberg I. Adherence and persistence: the challenges for glaucoma medical therapy. Asia-Pacific J Ophthal 2013; 2: 356-361.

21. Lee R, Hutnik CM. Projected cost comparison of selective laser trabeculoplasty versus glaucoma medication in the Ontario Health Insurance Plan. Canadian J Ophthal (J Canadien d’Ophtalmologie) 2006; 41: 449-456.

22. Lamoureux EL, McIntosh R, Constantinou M et al. Comparing the effectiveness of selective laser trabeculoplasty with topical medication as initial treatment (the Glaucoma Initial Treatment Study): study protocol for a randomised controlled trial. Trials 2015; 16: 406.

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