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 extracellular 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 cellular 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 treatment (<20% IOP lowering at 12 months). At 12 months after repeat 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. The difference between lowering effect. The initial study by Latina et al demonstrated the groups was not statistically significant. This suggests that re- a mean IOP reduction of 23.8% at 26 weeks after a single treat- peat SLT treatment could be considered even in patients who ment. Since then, multiple randomized controlled trials have eval- had only a modest response to initial SLT therapy. uated both the long-term IOP-lowering efficacy of SLT and how In primary OAG (POAG) patients, Avery et al45 also found the effect compares with ALT and medical therapy. Long-term similar mean IOP reduction and treatment success rates (IOP re- studies evaluating the IOP reduction of SLT have shown a mean duction of 20%) in the primary and repeat SLT treatment of IOP reduction of 21.8% to 29.4% at 6 months,28–31 16.9% to 5,30,32–34 5,30,35 42 eyes. Furthermore, the mean duration of success in repeat 31.9% at 12 months, 7.7% to 27.8% at 2 years, treatment (13.1 months) was nearly double than that of initial 24.5% to 25.1% at 3 years,5,30 23.1% to 29.3% at 4 years,5,30 46 2,30 30 treatment (6.9 months). Similarly, Hong et al studied repeat 22.6% to 32.1% at 5 years, and 22.8% at 6 years. However, SLT in 44 OAG eyes where the initial treatment failed after SLT is not effective in all patients, and its IOP-lowering effect de- 6 months or more. After 3 months, there was no significant differ- creases with time in most patients. Selective laser trabeculoplasty ence in IOP reduction and success rates between the initial and re- reduces IOP by at least 20% in 66.7% to 75% of eyes at peat treatments. The timing of repeat treatment also did not 6months,31,36,37 58% to 94% at 12 months,5,30,33,38,39 40% to 5,30,35 5,30,39,40 impact treatment efficacy. 85% at 2 years, 38% to 74% at 3 years, 38% to 49 5,30,40 29,39,40 Ayala investigated the impact of treatment location on re- 68% at 4 years, and 11.1% to 31% at 5 years. Sur- peat SLT in patients with POAG and pseudoexfoliation glaucoma vival analysis indicates that the time for 50% of eyes to fail after 5,40 (PXG). Eyes that previously underwent treatment of the inferior treatment with SLT is approximately 2 years. 180 degrees of TM were randomized to have retreatment over Multiple randomized controlled trials have consistently con- the previously treated 180 degrees of TM or a second treatment cluded that there is no significant difference between the IOP re- of the 180 degrees of untreated TM. There was no significant dif- ductions of SLT and ALT. Similarly, 2 recent meta-analyses ference in the IOP-lowering effect between the 2 groups, which concluded that SLT is noninferior to both ALT and topical med- further supports the possibility that retreatment may provide a ical therapy. However, 1 meta-analysis found that SLT was asso- similar IOP-lowering effect to primary treatment. ciated with greater reductions in IOP and medication compared with ALT.3,4,41 Poor adherence to prescribed treatment regimens remains EFFECT OF SLT ON IOP FLUCTUATION a significant barrier to effective IOP control in patients with glau- Although its true impact is still poorly understood, IOP fluc- coma.42,43 Unlike medical therapy, SLT is not dependent on tuation has been shown to be an independent risk factor for patient adherence and may reduce the number of topical medica- glaucomatous progression.50 Treatments that can suppress these tions required to achieve adequate IOP reduction. A recent study fluctuations may be of benefit in addition to absolute IOP reduc- by Lee et al44 analyzed the effect of adjuvant SLT therapy in pa- tion. The ability of SLT to minimize fluctuations is becoming tients with medically controlled glaucoma. Six months after treat- more evident. Nagar et al37 showed that treatment with SLT re- ment with SLT, patients had a significantly lower IOP compared sulted in a 41% reduction in IOP fluctuation in patients with with baseline and the medication-only group. Patients treated with OAG and ocular hypertension, although this reduction was less SLT required fewer medications to maintain their IOP goal. There than the effect observed in patients treated with latanoprost was no difference in the Glaucoma Quality of Life 15 scores or (67%). The reduction in intervisit IOP fluctuation has also been Comparison of Ophthalmic Medications for Tolerability Survey shown to be greater after 360-degree SLT treatment when com- scores compared with baseline or control. This indicates that pared with 180-degree treatment.11 SLT can effectively lower IOP and reduce medication require- The development of a continuous strain gauge contact ments without significantly impacting quality of life. lens sensor (CLS) known as the Triggerfish device (Sensimed,

Switzerland) has led to new insights regarding the 24-hour IOP treated with 270-degree SLT. Patients were subdivided into 3 fluctuations after SLT. The CLS measures strain at the limbus in groups on the basis of angle pigmentation. Mean IOP fell by response to ocular volume changes as a surrogate for IOP, thus 2.06, 2.46, and 4.75 mm Hg in subgroups with low, marked, and having the units of mVEq rather than mm Hg. Lee et al51 de- high angle pigmentation, respectively. Although the absolute described 18 patients with normal-tension glaucoma (NTG) who crease in IOP was less in the patients with low pigmentation, this were treated with 360-degree SLT. The 24-hour IOP pattern was decrease may still be clinically significant and patients with lightly monitored with the CLS before and 1 month after SLT treatment. pigmented angles may still be candidates for SLT. At 1 month, 44% of patients had achieved treatment success (20% IOP reduction). Raw data from the CLS were put into a cosinor model to assess 24-hour variability. Patients with success- Optimal Treatment Parameters ful SLT treatment had a reduction in the amplitude of the modeled Typical SLT treatment parameters are 50 (or 100) applica- function by 24.6%. Patients who had unsuccessful treatment tions over 180 degrees (or 360 degrees) of the angle, and laser (<20% IOP lowering from baseline) had a 19.2% increase in the energy ranges from 0.6 to 1.4 mJ, typically titrated to the for- amplitude of the modeled function. Higher CLS pattern variability mation of microbubbles.18,36 Several studies and subsequent was also observed in the failure group. meta-analysis have found no significant difference in the IOP- Tojo et al52 prospectively analyzed 10 patients with NTG lowering effect after treatment with either 180- or 360-degree who were treated with 360-degree SLT. The 24-hour IOP pattern SLT.29,38,41 Contrary to this, 1 retrospective analysis found greater was similarly monitored with a wireless CLS. At 3 months, IOP IOP reductions, lower mean IOP, and greater success rates after was significantly lowered from 13.5 ± 2.5 mm Hg at baseline to 360-degree treatment compared with 180 degrees.12 Asecond 11.3 ± 2.4 mm Hg. The range of IOP pattern fluctuation was not study also found that 360-degree treatment was more likely to significantly changed during the diurnal period or the entire achieve lesser IOP fluctuations, despite similar mean IOP reduc- 24-hour period. However, the range of IOP fluctuations during tion.11 Although there may only be subtle differences in efficacy the nocturnal period significantly decreased from 290 ± 86 mVEq between 180- and 360-degree treatment, it seems that 90-degree before SLT to 199 ± 31 mVEq after SLT treatment (P =0.014). SLT is likely inferior to 180-degree treatment.38 This suggests that SLT may reduce nocturnal IOP fluctuations. Limited (and conflicting) data are available regarding the optimal power settings for SLT treatment. Tang et al58 described 74 patients who received 360-degree SLT treatment (100 spots) with either standard energy settings (0.6–1.0 mJ) or half power OPTIMIZING THE EFFICACY OF SLT settings (0.3–0.5 mJ). There was no difference in the IOP- lowering effect between the groups at 1-year follow-up. Postoper- Predictors of Successful SLT Treatment ative IOP spike occurred in 3 patients in the full power group, and Several studies have shown that the strongest predictor of peripheral anterior synechiae (PAS) formation occurred in success after SLT treatment is a higher preoperative IOP.36,53 Mul- 1 patient in the same group. No complications were observed in tiple other factors have been investigated yet were not found to be the half power group. The authors suggest that patients treated significant predictors of success including age, sex, race, glau- with lower power had fewer complications and equivalent IOP re- coma type, previous ALT, concurrent antiglaucoma eye drops duction; therefore, lower power settings may be safer. Electron mi- (including PGAs), TM pigmentation, angle grade, lens status, croscopy of SLT-treated cadaver eyes has shown that tissue and central corneal thickness.36,53 Several recent studies have destruction may occur after SLT at high power (2.0 mJ).20 reexamined some of the factors that may impact SLT outcomes. Lee et al found that higher total power applied to the TM dur- Seymenoglu et al54 confirmed previous findings that lens ing SLT led to greater IOP reduction in a cohort of 49 patients status (phakic vs pseudophakic) does not affect the success rate with OAG.59 The laser energy and number of spots applied in this of SLT. Woo et al29 described the 5-year success rates of SLT (de- study were significantly greater than conventional 360-degree fined as 20% reduction in IOP from baseline) and found no SLT treatment, with a mean ± SD total energy application of significant difference in success rate on the basis of the number 167.1 ± 41.4 mJ (171.5 ± 41.2 spots at 1.0 ± 0.06 mJ). Patients of preoperative glaucoma eye drops patients were using. There treated with total energy in the range of 214.6 to 234.9 mJ were was, however, an increased likelihood of patients requiring a sec- found to have a greater IOP-lowering response, with the optimal ond procedure (SLT or trabeculectomy) during the 5-year follow- total energy at 226.1 mJ. Similarly, Habib et al60 also evaluated up period in those who were taking 2 or more preoperative IOP- the effect of total laser power applied on IOP reduction. All pa- lowering drops. Lee et al55 described contradictory results after tients were treated with 360-degree SLT, with a mean of 102 treat- analysis of 111 eyes treated with 360-degree SLT, finding that ment spots. Analysis was divided into patients who received low the use of 3 topical IOP-lowering medications was associated with (<85 mJ), medium (85–105 mJ), or high (>105 mJ) energy SLT. SLT failure (odds ratio, 0.1; P = 0.02). This study also demon- At all time points up to 36-month follow-up, there was a signifi- strated that retinal nerve fiber layer thickness, use of a topical car- cant positive correlation between higher energy application and bonic anhydrase inhibitor, and postoperative day 1 IOP were the amount of IOP lowering. Kaplan-Meier analysis also showed associated with SLT success. that patients receiving low-energy treatment were less likely to Successful treatment in 1 eye may also suggest a higher like- sustain a 20% IOP reduction from baseline. lihood of successful treatment of the contralateral eye.56 In a study Further investigation is required to determine the optimal of 42 patients who were treated with bilateral 360-degree SLT, treatment parameters to maximize the IOP-lowering effect of 42.9% of patients had bilateral success, 38.1% had bilateral non- SLT while maintaining an acceptable safety profile. success, and 19.0% had unilateral success. Success was defined as a 20% or more reduction in IOP from baseline 1 month after treatment. There was also a significant correlation between the re- Postoperative Management After SLT sponses to SLT in both eyes. Many studies have described the empirical use of post-SLTanti- Increased angle pigmentation may correlate with SLT effi- inflammatory topical medications, although there is little evidence cacy.57 In a study by Wasyluk et al,57 63 eyes of 53 patients were to support this. Treatment with topical steroids or nonsteroidal

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 anti-inflammatory agents after SLT has not been shown to cause a Primary Angle-Closure Glaucoma 61 significant reduction in inflammation or improved efficacy. Most patients with primary angle closure (PAC) or PAC glau- Symptomatic or asymptomatic anterior chamber inflammation 18,28,38,62 coma (PACG) require additional therapy to maintain IOP con- may occur but usually resolves without treatment. Re- trol,70 and recent evidence suggests that SLT may be a viable cently, a randomized double-masked, placebo-controlled clinical treatment option for these patients. In a study of 100 patients with trial evaluated patients treated with 1% prednisolone acetate, PAC or PACG who had been treated with laser peripheral ketorolac tromethamine 0.5%, or carboxymethyl cellulose sodium iridotomy and subsequently had at least 180 degrees of open an- 1.5% artificial tears (placebo) 4 times per day for 5 days after 63 gle, patients were randomized to receive further treatment with ei- SLT. No significant difference in IOP-lowering effect was ob- ther SLT or PGA.71 The mean ± SD extent of angle treatment in served among the groups up to 1 year after treatment. In addition, the SLT group was 322 degrees. Mean ± SD IOP was lowered anterior chamber inflammation scores at 1 hour, 2 days, and from 23.5 ± 2.5 to 19.5 ± 0.8 mm Hg (16.9% reduction) in the 1 month after SLT treatment were not significantly different SLT group and from 22.4 ± 2.5 to 18.2 ± 0.7 mm Hg (18.5% re- among any of the treatment arms. duction) in the PGA group at 6 months. The difference in IOP reduction was not statistically significant (P =0.78).Asmallbut significant decrease in the mean endothelial cell count from base- Where Does SLT Fit Into the Treatment Algorithm? line was reported in the SLT group (4.8% decrease; P =0.001). With several medical, surgical, and laser options available to One patient in the SLT group had a transient IOP spike after treat- lower IOP, the algorithm for advancing therapy in patients with ment. No other adverse events, such as persistent uveitis or an in- glaucoma is not well defined. Meta-analyses of data compiled crease in PAS, were noted in eyes that underwent SLT. More data from multiple randomized controlled trials have demonstrated that are needed to determine the long-term safety and efficacy of SLT SLT provides equivalent IOP reduction in comparison with both in patients with angle-closure glaucoma. ALT and medical therapy.3,4,35,40,41 In addition, SLT has been shown to be equivalent to PGA as the initial treatment for glau- Pseudoexfoliation Glaucoma 32 coma or ocular hypertension, and SLT may also be an effective In patients with PXG, SLT has a similar IOP-lowering effi- treatment for patients with more advanced glaucoma. Schlote and cacy, failure rate, and adverse event profile compared with pa- 64 Kynigopoulos demonstrated that SLT provides successful IOP- tients with other types of OAG.1,7,72,73 In a recent randomized lowering effects (>20% reduction in IOP from pretreatment and trial of 76 eyes, SLTand ALTwere found to have similar efficacy IOP ≤ 21 mm Hg) in 63% of patients with early glaucoma and in patients with PXG.31 In patients with PXG, a mean reduction in 59% of patients with advanced glaucoma. Patients with advanced IOP after SLT has been reported as 31.5% at 12 months,73 16.6% glaucoma in this study had a mean ± SD IOP of 14.8 ± 2.4 mm Hg at 16 months,62 and 31.4% at 18 months.1 One retrospective re- at 12 months after treatment, with 50% of these eyes achieving port found greater IOP reduction (−6.1 vs −4.4 mm Hg) and suc- IOP of less than 18 mm Hg and a 30% or more reduction in IOP. cess rates (78% vs 54%) in PXG eyes compared with POAG eyes A Cochrane database review showed that ALT is less effective at at 1 year.8 However, there is some evidence that the IOP-lowering controlling IOP than trabeculectomy at both 6 months and 2 years effect of SLT may not last as long in patients with PXG.1,74 The 65 of follow-up. However, there are currently no data available di- presence of pseudoexfoliation does not seem to be a risk factor rectly comparing the efficacy of SLT and filtering surgery. for IOP spikes or complications after SLT.8,72

Pigmentary Glaucoma SELECTIVE LASER TRABECULOPLASTY IN Patients with pigmentary glaucoma (PG) have similar success SPECIFIC TYPES OF GLAUCOMA rates with SLT as patients with other types of OAG.53,62 In a recent Normal-Tension Glaucoma long-term study of 30 eyes with PG treated with 180-degree SLT, the success rate after 12 months was 85%, after 24 months was More evidence is becoming available that SLT can have a 67%, after 36 months was 44%, and after 48 months was 14%. significant IOP-lowering effect in patients with NTG, albeit with The mean time to failure after SLTwas 27.4 months. In this study, a smaller absolute reduction in IOP. The use of SLT in NTG has 2 patients had transient IOP spikes and prolonged inflammation, been limited historically because of the fact that the most reliable 75 66–68 which resolved without long-term sequelae. Other studies have predictor of success is a higher preoperative IOP. Lee et al suggested that there may be an increased complication rate after treated 45 NTG eyes with 360-degree SLT after a 1-month medi- SLT in patients with highly pigmented TM. Koucheki and cation washout. Medication was restarted at postoperative month Hashemi62 described a significantly higher rate of mild pain and 1 and titrated to achieve a goal of 30% IOP reduction from pre- inflammation and a post-SLT IOP spike of 6 mm Hg or greater, SLT levels. Baseline and pre-SLT (after washout) IOP levels were along with a greater need for surgical intervention in patients with compared with postoperative week 1 and postoperative months 3, PG, when compared with POAG and PXF. In a case series of 6, 12, and 24. Mean IOP was significantly lowered from pre-SLT 4 patients with post-SLT IOP spikes lasting 4 days to 3 months, IOP and from baseline at all time intervals other than 1 week. At 3 had PG and the other had a heavily pigmented angle. Three of 6 months, IOP was lowered by 19.7% from baseline with a 27% these patients eventually required trabeculectomy. The authors decrease in medication use. At 1 and 2 years, mean IOP was suggest that lower power settings may be necessary in patients lowered 15% and 11 % from baseline with 27% and 41.1% re- with heavily pigmented angles.76 ductions in mean medication use, respectively. In a separate report, the same group investigated predictors of SLT success in NTG.69 Higher preoperative IOP and a lower postoperative IOP Steroid-Induced Glaucoma at 1 week after SLTwere correlated with treatment success. As de- Although there are limited data available, SLT seems to ef- scribed earlier in this review, SLT has also been shown to reduce fectively lower IOP in patients with steroid-induced glaucoma nocturnal IOP pattern fluctuation in patients with NTG as mea- and may even help prevent IOP spikes from subsequent steroid sured by a wireless CLS.52 treatment. A small study evaluating patients after 360-degree SLT

Copyright © 2016 Asia Pacific Academy of Ophthalmology. Unauthorized reproduction of this article is prohibited. Asia-Pacific Journal of Ophthalmology • Volume 5, Number 1, January/February 2016 SLT: An Update included 10 patients with steroid-induced glaucoma and found a therapy (laser without topical medication), rather than as second- 35.9% reduction in IOP 12 months after treatment.77 Another line treatment (laser and topical medications together), for POAG small prospective study prophylactically treated patients who had would lead to significant healthcare system cost savings even if IOP 21 mm Hg or greater with 180-degree SLT before subtenon tri- the cost of trabeculoplasty were triple the rate at the time of amcinolone injection for diabetic macular edema. No patients publication. These cost savings would increase over time as the treated with SLT required IOP-lowering medications, whereas population and economic burden of glaucoma increases.92 An 50% of patients who received triamcinolone injection alone re- economic model of the Canadian healthcare system also suggests quired IOP-lowering medications during the 6-month follow-up.78 that SLT as primary therapy is cost-effective, with SLT becoming less expensive than monodrug, bidrug, and tridrug therapy on the basis of mean yearly medication costs by year 2 after treatment.93 ADVERSE EVENTS AFTER SLT However, the economics of providing medications and services Mild, transient adverse effects such as redness, photophobia, vary widely from country to country, making it difficult to draw and discomfort have been described after SLT with reported inci- generalized conclusions. Further analysis of the cost-effectiveness dences ranging from 0% to 65.7%.4 These are presumed secondary of SLT at different disease stages is still needed. to transient anterior chamber inflammation and usually resolve without treatment.1,9,36 However, recently Klamann et al9 studied 64 patients treated with 360-degree SLT and did not observe any CONCLUSIONS anterior chamber cell or flare or vitreous haze at 24 hours or 14 days Selective laser trabeculoplasty is an effective treatment op- after treatment. As described previously, prophylactic treatment tion for the reduction of IOP in patients with ocular hypertension with topical anti-inflammatory agents has not been shown to result and OAG. Based on published data, SLT is at least as effective as in greater efficacy or lower incidence of adverse effects.63 Atran- ALT and medications. It reduces IOP fluctuation and can be suc- sient IOP increase of 5 mm Hg or greater has been reported in cessfully used as primary or adjunct therapy for the management 0% to 28% eyes.2,7,12,28,31,32,38,73 TheincreaseinIOPusuallyre- of both early and advanced disease. However, SLT is not effective solves quickly with or without treatment, often within 24 hours. in all forms of glaucoma, and the IOP-lowering effect of SLT de- As detailed previously, a series of 4 cases of severe IOP spike creases over time. High pretreatment IOP is the strongest predictor was reported in patients with highly pigmented angle structures; of SLT success, even in patients with NTG. There is evidence that thus, caution should be exercised in these patients.76 A systematic SLT can successfully be repeated to achieve additional or recur- review found that prophylactic treatment with IOP-lowering medi- rent IOP reduction, even in eyes that only had a modest response cation reduced the incidence of transient IOP elevation.4 to initial treatment. The repeatability is attributed to the lack of Peripheral anterior synechiae have been described but occur thermal damage associated with this form of laser trabeculoplasty. rarely after SLT. In a systematic review of 12 studies, PAS were Adverse events are uncommon after SLT, and the most common observed in 2 eyes in 2 separate studies (1.1% and 2.85% of eyes), complications are mild and transient. The available evidence sug- whereas none were observed in the other 10 studies.4 A recent gests that SLT is cost-effective as primary treatment for glaucoma. case series also reported 2 cases of significant PAS formation as a late complication of repeat SLT.79 Cystoid macular edema is rare after SLT but has been described in 4 patients.80–82 However, a REFERENCES prospective study of 64 eyes evaluating macular thickness as mea- 1. Gracner T. Intraocular pressure response of capsular glaucoma and primary sured by optical coherence tomography using the Early Treatment open-angle glaucoma to selective Nd:YAG laser trabeculoplasty: a of Diabetic Retinopathy Study protocol did not find any change prospective, comparative clinical trial. Eur J Ophthalmol.2002;12: in macular thickness after SLT.9 There are several case reports 287–292. describing less common adverse effects after SLT including 2. Lai JS, Chua JK, Tham CC, et al. 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