Rethinking SLT: From pressure reduction to biological activation

For decades, selective laser trabeculoplasty (SLT) has been understood primarily as a pressure-lowering intervention, positioned either as an adjunct or, more recently, as a first-line therapy alternative. One milestone is the paradigm-shifting results of the LiGHT trial (ISRCTN32038223).¹ Although SLT’s clinical efficacy is well established, its underlying mechanism of action remains only partially explained.

SLT’s effect has long been attributed to selective photothermolysis of pigmented trabecular meshwork cells. Some devices use a Q-switched, frequency-doubled Nd:YAG laser (532 nm) that delivers ultra-short nanosecond pulses, allowing selective absorption of energy while minimizing or avoiding collateral thermal damage.² Other platforms—patterned SLT (PSLT) and direct SLT (DSLT)—also respect the procedure’s favourable safety profile, distinguishing it from earlier laser techniques. Yet this explanation appears insufficient to fully account for the delayed onset, sustained efficacy and variability of response observed in clinical practice.

With time, both experimental and clinical evidence suggest that SLT may not act primarily through mechanical or thermal disruption, but rather through the induction of a complex biological response within the trabecular outflow pathway.³

From a technological point of view, SLT, PSLT and DSLT all rely on variations of low-energy, short-pulse laser delivery targeting the trabecular meshwork. Although they differ in pulse sequencing, spatial distribution and delivery method—ranging from single-spot applications to patterned arrays or even non-contact approaches—their shared characteristic is the induction of a subthreshold biological response rather than a destructive effect.⁴

A more complex biological reality

When I began using SLT more than a decade ago, the conceptual model was clear—and incomplete: selective absorption by pigmented cells, minimal thermal spread and a controlled, localized effect. It was the framework I drew on in every invited lecture. Over time, however, clinical experience has suggested a more complex reality.

If the primary effect of these laser platforms is not structural disruption, the key question becomes: What biological processes are being activated? Experimental evidence indicates that laser stimulation of the trabecular meshwork induces a cascade of cellular and molecular events. These include upregulation of pro-inflammatory cytokines such as IL-1α, IL-1β and tumour necrosis factor-α, as well as the activation of matrix metalloproteinases, which play a central role in extracellular matrix remodelling.⁵ In parallel, recruitment of monocytes to the outflow pathway has been observed, contributing to increased phagocytic activity and improved aqueous humour dynamics.⁶

Recent advances in imaging show that the trabecular meshwork behaves as a dynamic structure—far removed from the fixed, rigid-layered model once assumed. Rather than representing an undesirable side effect, this controlled, low-grade inflammatory response may in fact be the therapeutic driver of the procedure. In this context, SLT can be interpreted as a form of targeted biological activation, in which a precisely delivered photonic stimulus initiates a process that ultimately restores trabecular function.⁷

Evolution of delivery and implications

Conventional SLT delivers energy through 100 individual applications over a few minutes. With the evolution toward patterned SLT, treatment delivery has become significantly faster: 32 patterned applications, each consisting of multiple micro-spots (up to 39 per pattern), allow the procedure to be completed in close to 1 minute with comparable clinical effects. Novel DSLT allows contactless delivery in seconds of exposure.

The reduction in treatment time is not merely a technical improvement. It may reflect a more efficient and homogeneous way of delivering the same biological signal, potentially leading to a more reproducible activation of the trabecular meshwork. Perhaps the key factor is not the thermal energy applied, but the local immunomodulatory stimulation induced.

Beyond IOP: Quality of life and ocular surface

Although the primary end-point of laser trabeculoplasty remains IOP reduction, its clinical impact often extends beyond pressure control. In our latest study, a successful treatment enabled many patients to reduce their topical medications, leading to meaningful improvements in ocular surface health.⁸

Rather than acting solely through mechanical or thermal modification of the trabecular meshwork, the procedure unleashes a biologically active response characterized by controlled cellular signalling, immune cell recruitment and extracellular matrix remodelling.

Chronic exposure to topical hypotensive drops (with or without preservatives) is well known to contribute to ocular surface disease, discomfort and reduced adherence,⁹ with a direct and measurable impact on patient-reported quality of life as well as on long-term treatment persistence.¹⁰ By decreasing medication burden, laser-based interventions may therefore indirectly improve quality of life, ocular comfort and adherence—factors that are central to effective glaucoma management.

Redefining success and the role of SLT

In this context, the concept of success in SLT should not be limited exclusively to IOP reduction. It may be appropriate to consider it as part of a broader therapeutic strategy—one that encompasses trabecular homeostasis, reduces pharmacologic burden and allows recovery of ocular surface integrity.

When viewed through this lens, modern trabeculoplasty may represent more than a step in the treatment algorithm. It may function as an early intervention that can prime and restore trabecular function from the outset. Preventive strategies based on biological conditioning are widely accepted across medicine. Healthcare professionals routinely prepare physiological systems to respond more effectively before disease progresses. In glaucoma, there is a compelling case for interventions that may biologically reinforce the system responsible for maintaining IOP homeostasis.

This raises the question not only of how SLT works but also when it should be used. As our understanding of glaucoma continues to evolve, it is increasingly plausible that laser-based interventions occupy a more central role than previously appreciated. Perhaps the true significance of SLT is not only that it lowers IOP, but that it may represent one of the first clinically relevant examples of targeted photonic immunomodulation in ophthalmology.

Reconsidering SLT in this light does not simply refine an existing technique—it invites a broader redefinition of what laser therapy in glaucoma actually is.

Francisco Fernando Suñe, MD

E: [email protected]

Francisco Fernando Suñe, MD, is a glaucoma subspecialist and anterior segment surgeon at Hospital General Mateu Orfila and Clínica Juaneda in Menorca, Spain. He is a member of the Argentine Council of Ophthalmology, the Spanish Glaucoma Society and the European Society of Cataract and Refractive Surgeons.

The author is conducting a prospective clinical study in collaboration with a device manufacturer. No financial conflicts of interest related to the content of this article are reported.

References

1. Gazzard G, Konstantakopoulou E, Garway-Heath D, et al; LiGHT Trial Study Group. Selective laser trabeculoplasty versus eye drops for first-line treatment of ocular hypertension and glaucoma (LiGHT): a multicentre randomized controlled trial. Lancet. 2019;393(10180):1505-1516. doi:10.1016/S0140-6736(18)32213-X

2. 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. doi:10.1016/s0014-4835(05)80093-4

3. Kagan DB, Gorfinkel NS, Hutnik CML. Mechanisms of selective laser trabeculoplasty: a review. Clin Exp Ophthalmol. 2014;42(7):675-681. doi:10.1111/ceo.12281

4. Sacks Z, Katz LJ, Gazzard G, et al. A proposal for the use of a fixed low-energy selective laser trabeculoplasty for open angle glaucoma. J Glaucoma. 2024;33(1):1-7. doi:10.1097/IJG.0000000000002306

5. Alvarado JA, Yeh RF, Franse-Carman L, Marcellino G, Brownstein MJ. Interactions between endothelia of the trabecular meshwork and of Schlemm’s canal: a new insight into the regulation of aqueous outflow in the eye. Trans Am Ophthalmol Soc. 2005;103:148-163.

6. 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(6):731-737. doi:10.1001/archophthalmol.2010.85

7. Melamed S, Pei J, Epstein DL. Delayed response to argon laser trabeculoplasty in monkeys: morphological and morphometric analysis. Arch Ophthalmol. 1986;104(7):1078-1083. doi:10.1001/archopht.1986.01050190136053

8. Abe RY, Maestrini HA, Guedes GB, et al. Real-world data from selective laser trabeculoplasty in Brazil. Sci Rep. 2022;12(1):1923. doi:10.1038/s41598-022-05699-6

9. Leung EW, Medeiros FA, Weinreb RN. Prevalence of ocular surface disease in glaucoma patients. J Glaucoma. 2008;17(5):350-355. doi:10.1097/IJG.0b013e31815c5f4f

10. Skalicky SE, Martin KR, Fenwick E, Crowston JG, Goldberg I, McCluskey P. Cataract and quality of life in patients with glaucoma. Clin Exp Ophthalmol. 2015;43(4):335-341. doi:10.1111/ceo.12454