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Selective Laser Trabeculoplasty: an Update REVIEW ARTICLE Selective Laser Trabeculoplasty: An Update Jeffrey B. Kennedy, MD, Jeffrey R. SooHoo, MD, Malik Y. Kahook, MD, and Leonard K. Seibold, MD Abstract: without causing significant collateral thermal damage. This pro- Selective laser trabeculoplasty (SLT) is an effective treatment cedure is typically performed using a nonmagnified, mirrored option for the reduction of intraocular pressure (IOP) in patients with ocu- goniolens such as the Latina SLT lens (Ocular Instruments, Bellevue, lar hypertension or open-angle glaucoma. The mechanism by which SLT Wash) and a methycellulose or artificial tear gel coupling solu- lowers IOP is not completely understood and is likely multifactorial. Pub- tion. The SLT laser is a 532-nm frequency-doubled Q-switched lished studies indicate that SLT is at least as effective as argon laser Nd:YAG laser, with a fixed spot size of 400 μmanddurationof trabeculoplasty or medications at lowering IOP in many forms of glau- 3 nanoseconds. The power range for treatment using currently coma. In addition to IOP reduction, SLT may decrease IOP fluctuation available laser platforms is 0.3 to 2.0 mJ, with typical treatments and can be successfully used as primary or adjunctive therapy for the man- ranging from 0.4 to 1.4 mJ. These parameters spare surrounding agement of both early and advanced glaucoma. However, SLT may not be nonpigmented cells because the pulse duration is sufficiently effective in certain forms of glaucoma, and the IOP-lowering effect seems shorter than the thermal relaxation time (1 μs) of melanin granules to wane with time. High pretreatment IOP is the strongest predictor of treat- contained in pigmented TM cells.10 ment success, even in patients with normal-tension glaucoma. Repeatabil- ity of SLT has been controversial, but recent evidence suggests that it can be successfully repeated to achieve additional or recurrent IOP reduction, MECHANISM OF ACTION even in eyes that only had a modest response to initial treatment. Adverse The mechanism by which SLT lowers IOP is not completely 14,15 events are uncommon after SLT, and the most common complications such understood and is likely multifactorial. Like argon laser as discomfort and inflammation are typically mild and transient. Further in- trabeculoplasty (ALT), it seems that SLT reduces IOP by increas- 16,17 vestigation is required to determine the optimal treatment parameters for ing outflow through the TM. Proposed mechanisms of action SLT treatment. Limited evidence suggests that SLT is cost-effective as pri- for SLT are similar to those of ALT. These theories include struc- mary therapy for patients with glaucoma. tural alteration, inflammatory response with remodeling of the ex- tracellular matrix, and stimulation of TM cell proliferative Key Words: glaucoma, selective laser trabeculoplasty, SLT, changes. Although mechanical and structural changes may ex- intraocular pressure, ocular hypertension plain some of the IOP-lowering effect of ALT, these alterations (Asia Pac J Ophthalmol 2016;5: 63–69) are not considered to play a significant role in the mechanism of SLT. When compared with ALT, SLT causes significantly less 15,18 ver the past decade, selective laser trabeculoplasty (SLT) has structural damage to the TM and Schlemm canal. Histopath- O become an established method for lowering intraocular pres- ologic analysis and scanning electron microscopy (SEM) of enu- sure (IOP) in patients with open-angle glaucoma (OAG) and ocu- cleated eyes after ALT have demonstrated crater formation and lar hypertension.1–6 The procedure can be performed in an office significant disruption of trabeculae. Similar analysis after SLT setting with minimal recovery time and with an excellent safety showed only minor damage to trabeculae and corneoscleral mesh- 3,7–9 work, with slight disruption of endothelial intracellular pigment profile. Since the procedure was first described by Latina 19 20 and Park in 1995,10 there has been considerable effort to charac- granules. Recently, SooHoo et al described light microscopy, terize the potential mechanism, efficacy, treatment method, repeat- SEM, and transmission electron microscopy findings from ca- ability, and adverse events of SLT. Regardless of the mechanism, it daver eye sections that were treated with either ALT or SLTusing is clear that SLT is effective in a wide range of patients who re- power ranging from 0.4 to 2.0 mJ. Eyes treated with ALT demon- quire IOP reduction, and several studies have characterized re- strated significant disruption of TM architecture. Eyes treated sponse rates for an extended period of time.1,2,11,12 Atestament with SLT showed normal TM architecture on light microscopy, to the role of SLT in treating glaucoma and ocular hypertension but transmission electron microscopy did show some disruption is the number of procedures performed each year (142,682 in of TM cells with cracked extracellular pigment granules even at Medicare beneficiaries in 2012).13 The aim of the study was to re- low power settings. On SEM, TM treated with high power view pertinent findings and conclusions from the existing litera- (2.0 mJ) showed more obvious tissue destruction with scrolling ture on SLTwith a more in-depth focus on recent developments. of TM tissue. This suggests that treatment with SLT does have the potential to cause structural damage to the TM and that dose titration remains important. BASIC PRINCIPLES The biological theory of SLT action proposes that the laser modifies cellular activity and cytokine release to allow for greater Selective laser trabeculoplasty is based on the principle of aqueous outflow through the TM. Multiple biologic and biochem- selective thermolysis, in which radiation energy applied to the ical changes have been observed in the TM after laser treatment. trabecular meshwork (TM) selectively targets pigmented cells Significant changes in TM expression of genes involved with cellu- lar motility and intercellular connections, among others, have been From the University of Colorado School of Medicine, Department of Ophthal- identified via microarray analysis after treatment.21 Increased levels mology, Aurora, CO. α β Received for publication October 3, 2015; accepted November 26, 2015. of interleukin 1 , interleukin 1 , tumor necrosis factor alpha, and The authors have no funding or conflicts of interest to declare. interleukin 8 have been observed in cultures of SLT-treated TM Reprints: Leonard K. Seibold, MD, Department of Ophthalmology, University cells.15,22 Aqueous humor concentrations of endothelin-123 and of Colorado School of Medicine, 1675 Aurora Court, F731 Aurora, CO. lipid peroxide24 have also been found to be increased in rabbit E-mail: [email protected]. Copyright © 2016 by Asia Pacific Academy of Ophthalmology studies. The altered expression of these cytokines and chemokines ISSN: 2162-0989 may increase outflow facility through the juxtacanalicular mesh- DOI: 10.1097/APO.0000000000000175 work. Monocytes are also recruited to the TM after SLT, likely Asia-Pacific Journal of Ophthalmology • Volume 5, Number 1, January/February 2016 www.apjo.org 63 Copyright © 2016 Asia Pacific Academy of Ophthalmology. Unauthorized reproduction of this article is prohibited. Kennedy et al Asia-Pacific Journal of Ophthalmology • Volume 5, Number 1, January/February 2016 in response to secreted chemokines. The recruited monocytes may REPEATABILITY OF SLT secrete additional cytokines, which can alter tissue permeability, 25 Because SLT causes minimal structural changes to the TM, and may also phagocytize debris obstructing TM outflow. retreatment may be a viable option in patients that need further IOP Expression of matrix metalloproteinases is upregulated in 15,22 26 reduction. Although this was initially more of a theoretical advan- TM cells after treatment with ALT. Recently, Lee et al dem- tage of SLT over ALT, the body of evidence supporting the effi- onstrated increased expression of matrix metalloproteinase-3 in cacy of repeat SLT is growing. Several retrospective studies have cultured TM cells treated with SLT. Matrix metalloproteinase re- demonstrated an IOP-lowering effect of retreatment with SLT, modeling of the extracellular matrix may also lead to increased even after primary treatment failure.45–47 outflow capacity and decreased IOP. Increased trabecular DNA In a study by Khouri et al,48 45 eyes of 25 subjects with OAG replication and cell division have been observed after treatment were treated with repeat 360-degree SLT a mean ± SD of 28.3 ± of human corneoscleral explants with ALT, and it has been sug- 12.7 months after initial SLT. Patients receiving repeat SLT in this gested that remodeling of the TM may lead to improved outflow 27 study were included regardless of their initial response to SLT. At facility. However, these studies have not yet been repeated 24 months after repeat treatment, 29% of patients achieved IOP with SLT. 14 reduction of at least 20% and 39% of eyes achieved IOP reduction Alvarado et al showed that exposure to factors secreted by of at least 15%, which was not significantly different from the laser-treated TM cells in culture produced an increase in the per- 24-month success rates of the initial SLT treatment. In another meability of Schlemm canal cells and a disassembly of intracellu- study by the same group,47 51 eyes with OAG were treated with lar junctions. This change was similar to the effect produced by repeat 360-degree SLTa mean of 26 months after initial treatment. the exposure of Schlemm canal cells to prostaglandin analogs Analysis was stratified into patients who had a successful re- (PGAs), suggesting that laser trabeculoplasty and treatment with sponse (S1) to initial treatment (20% IOP lowering at 12 months) PGAs may share a common mechanism. and those who had a modest response (M1) to initial SLT treat- ment (<20% IOP lowering at 12 months). At 12 months after re- peat treatment, mean IOP was significantly lowered in both EFFICACY OF PRIMARY SLT groups, with 52% of the S1 group and 39% of the M1 group In patients with OAG, SLT provides a significant IOP- 28 achieving more than 20% IOP reduction.
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