Selective laser trabeculoplasty retreatment after prior argon laser trabeculoplasty: 1-year results

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1 Selective laser trabeculoplasty retreatment after prior argon laser trabeculoplasty: 1-year results Catherine M. Birt, MD, FRCSC ABSTRACT RÉSUMÉ Background: Argon laser trabeculoplasty (ALT) and selective laser trabeculoplasty (SLT) are treatments for open-angle glaucoma. Many patients have previously received ALT but could benefit from further treatment. The purpose of this study was to examine whether SLT provided clinical benefit for patients who had previously received complete argon treatment. Methods: This was a prospective, partially randomized, comparison study.the study compared the effect after 1 year of SLT in patients with open-angle glaucoma (primary, pigmentary, or pseudoexfoliation) who had previously received 360º of ALT with the effect of laser treatment (ALT or SLT) given for the first time in patients with this condition. Ninety-six subjects were given 180º of laser trabeculoplasty. When both eyes qualified for treatment, the first eye treated was included in the analysis.twenty-seven subjects were treated with SLT after previously receiving 360º of ALT therapy; the remainder were given their first laser treatment, 30 being randomly assigned by coin toss to receive SLT and 39 to receive ALT. Results: The mean intraocular pressure (IOP) before treatment was 21.5 mm Hg (SLT after ALT), 22.9 mm Hg (SLT), and 22.0 mm Hg (ALT), with no statistical difference among the groups (). The mean IOP at 1 year was 16.7 mm Hg (SLT after ALT), 17.1 mm Hg (SLT), and 16.4 mm Hg (ALT).The IOP for all 3 groups was statistically significantly lower than at baseline (p < 0.001), but there were no differences among the groups in this respect ().At 1 year, the percentage IOP reductions from baseline were 23% (SLT), 19.3% (SLT after ALT), and 24% (ALT). There were no differences among the groups in the number of medications used before the laser, although there was a small but statistically significant decrease in the number of medications used before or after the laser treatment in both the SLT and the SLT after ALT group, but not the ALT group. Interpretation: SLT retreatment can produce a clinically useful decrease in IOP at 1 year, similar to that obtained by ALT, in patients who have had prior argon laser treatment. SLT may be a useful adjunctive therapy when 360º of ALT has already been performed. Contexte : La trabéculoplastie au laser argon (TLA) et la trabéculoplastie sélective au laser (TSL) sont des traitements pour le glaucome à angle ouvert. Plusieurs patients qui avaient subi antérieurement une TLA pourraient bénéficier d un traitement additionnel. La présente étude a pour objet d examiner si la TSL a donné de bons résultats cliniques chez les patients qui avaient reçu auparavant un traitement complet à l argon. Méthodes : Étude comparative, prospective et partiellement randomisée. L on a comparé les effets de la TSL après 1 an chez des patients atteints de glaucome à angle ouvert (primaire, pigmentaire ou pseudoexfoliation) qui avaient subi auparavant une TLA sur 360º avec les effets du traitement au laser (TLA ou TSL) administré pour la première fois chez des patients atteints de la maladie. Quatre-vingt-seize sujets ont subi une trabéculoplastie au laser sur 180º. Lorsque le traitement devait s appliquer aux deux yeux, on a inclus le premier œil traité dans l analyse.vingt-sept sujets qui avaient subi une TLA sur 360º ont été traités par TSL; les autres ont reçu leur premier traitement au laser; 30 furent désignés au hasard, pile ou face, pour subir la TSL et les autres, la TLA. Résultats : La moyenne de pression intraoculaire (PIO) avant le traitement était de 21,5 mm Hg (TSL après TLA), 22,9 mm Hg (TSL) et 22,0 mm Hg (TLA), sans écart statistique entre les groupes (p > 0,05). La moyenne de PIO après 1 an était de 16,7 mm Hg (TSL après TLA), 17,1 mm Hg (TSL) et 16,4 mm Hg (TLA). Pour les trois groupes, la PIO était statistiquement plus faible qu au départ (p < 0,001), mais il n y avait pas d écart entre les groupes à cet égard (p > 0,05). Après 1 an, les pourcentages de réduction de la PIO par rapport au départ étaient de 23 % (TSL), 19,3 % (TSL après TLA) et 24 % (TLA). Il n y a pas eu d écart entre les groupes quant au nombre de médicaments utilisés au laser, bien qu il y eut une baisse, faible mais From the Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ont. Presented at the 3rd International Congress on Glaucoma Surgery, Toronto, Ont., May 25 28, 2006 Originally received Jan. 22, Revised May 3, 2007 Accepted for publication May 17, 2007 Published online Sep. 13, 2007 Correspondence to: Catherine M. Birt, MD, Department of Ophthalmology, Sunnybrook Health Sciences Centre, Room M1 302a, 2075 Bayview Ave., Toronto, ON M4N 3M5; c.birt@utoronto.ca This article has been peer-reviewed. Cet article a été évalué par les pairs. Can J Ophthalmol 2007;42:715 9 doi: /can j ophthalmol.i SLT after ALT: 1-year results Birt 715

2 Argon laser trabeculoplasty (ALT), introduced in 1979 by Wise and Witter, 1 rapidly became a standard option in the clinical management of open-angle glaucoma. Selective laser trabeculoplasty (SLT) is a new version of laser treatment for lowering intraocular pressure (IOP) in patients with chronic open-angle glaucoma. This method of treatment uses a frequency doubled, Q-switched Yag laser (Selecta II, Lumenis, Santa Clara, Calif.) rather than an argon wavelength. 2 This form of laser produces a very brief burst of laser energy that targets the melanin content of meshwork cells and selectively ablates them. This is in contrast to the thermal photocoagulation effect of argon treatment, which causes local and collateral damage. 3 Many patients have received ALT during their clinical management. A retreatment is considered to be a second application of laser to meshwork that has previously received therapy. Once 360 of angle has been treated with argon, clinicians are reluctant to retreat the angle. It is possible that treatment with SLT may provide additional benefit in this group. Early work by Latina and colleagues 2 showed SLT to have results similar to those obtained by ALT. Similarly, Damji and associates 4 found SLT results to be similar to ALT results in a group of patients of whom some had previously undergone laser therapy and some had not. The current study was intended to examine the results using the Selecta laser as a retreatment modality in patients who had had prior ALT to 360 of their trabecular meshwork compared with those who had not. METHOD statistiquement significative, du nombre de médicaments utilisés après le traitement au laser chez les deux groupes,tsl et TSL après TLA, mais pas chez le groupe TLA. Interprétation : Le traitement par TSL peut entraîner sur le plan clinique une baisse utile de la PIO après 1 an, semblable à celle obtenue par la TLA, chez les patients qui ont reçu précédemment un traitement au laser argon. La TSL peut offrir une thérapie complémentaire utile lorsque la TLA sur 360º a déjà été pratiquée. The Research Ethics Board of Sunnybrook and Women s College Health Sciences Centre approved the protocol before the beginning of data collection, and informed consent was obtained prior to the laser treatment. Patients were included in the study if they had primary open-angle glaucoma (POAG) or open-angle glaucoma secondary to either pigment dispersion (PDS) or pseudoexfoliation (PEX) requiring therapy in addition to their current medications. The therapy was recommended when patients were unable to reach their clinically determined target IOP while taking medications, were unable to tolerate the medications that were keeping the IOP at an adequate target level, or were noncompliant with medication use. The study is described as partially randomized because patients receiving their first laser therapy were randomly assigned, by means of a coin toss, to receive either SLT or ALT, but patients who had already received 360 of ALT were assigned by protocol to receive SLT. It was not considered ethically acceptable to expose patients to retreatment by argon laser of previously treated meshwork. All patients received the same prelaser and postlaser protocol. One drop of brimonidine 0.2% (Allergan, Calif.) was given 5 10 minutes before the laser treatment, and the IOP was measured 60 minutes and 24 hours afterwards to ensure that a postlaser spike in IOP would be diagnosed and managed if required. All patients were given fluoromethalone 0.1% (Allergan) drops 4 times daily for 5 days and instructed to continue their routine antiglaucoma medications. All patients had burns given over the inferior 180 of the trabecular meshwork with the energy setting at either 0.7 or 0.8 mj for the Selecta laser and between 700 and 850 mw for the Argon laser. If both eyes were eligible for inclusion in the analysis, the first eye treated was chosen. Effectiveness was assessed at 6 weeks, at 4 5 months after the treatment, and at 1 year. RESULTS Ninety-six patients with open-angle glaucoma (primary, pseudoexfoliative, or pigmentary) for whom laser therapy was recommended in order to better control IOP were given 180 of laser trabeculoplasty. Of these patients, 27 had previously had 360 of argon therapy, 30 were having their first laser treatment with the Selecta laser, and 39 were receiving argon therapy for the first time. The mean time interval between the completion of previous treatment with the Argon laser and the first session of the Selecta laser was (SD 126.7) days, with a minimum of 54 days and a maximum of In the first group (SLT after ALT) 4 patients of the 27 went on to receive a trabeculectomy; in the second group (SLT only) 5 patients of the 30 received a later trabeculectomy; and in the third group (ALT only) 7 patients of the 35 went on to receive further laser therapy to the second 180 of the angle, and 1 proceeded to trabeculectomy. The decision to proceed to surgery, rather than further laser therapy (such as following a failed SLT with an ALT) was dictated by the target pressure requirements for most of the patients. On occasion the development of a visually significant cataract made a combined filtration and cataract extraction surgery the best option for the patient. 716 CAN J OPHTHALMOL VOL. 42, NO. 5, 2007

3 The follow-up for these patients ceased at the time that further therapy was instituted. The results were examined using χ 2 analysis for the nonparametric data, and ANOVA or paired t tests for the parametric data. There were no differences among the 3 groups in terms of the mean age or the distribution of sex, race, or eye selected for inclusion. There were no differences among the 3 in the number of medications used before or after the laser treatment (Table 1). There were no differences among the groups in the distribution either of diagnosis (POAG, PEX, PDS) or of the types of medication used (Tables 2 and 3). There was a small but statistically significant decrease in the mean number of medications used 1 year later in both the SLT only and the SLT after ALT groups, but not in the ALT only group. There were no complications requiring treatment beyond the standard postprocedure protocol in any patient in any of the 3 groups. There was a statistically significant decrease in mean IOP for all 3 groups from the prelaser IOP level to the mean IOP at both 4.5 months and 1 year. There were no statistically significant differences among the 3 groups at either time interval (Table 4) or between the percentage decrease in IOP (Table 5). INTERPRETATION SLT is a potentially useful addition to the techniques available for glaucoma therapy. 5 The main advantage of SLT over traditional argon laser techniques is considered to be the selective targeting of the pigmented trabecular meshwork cells, avoiding thermal damage to nonpigmented cells or other local structures, such as the scleral beams of the meshwork tissue. 6 Furthermore, the repeated Table 1 Demographic distribution of patients undergoing laser trabeculoplasty SLT only (n = 30) SLT after ALT (n = 27) ALT only (n = 39) among groups Parameter Sex F = 15 F = 13 F = 18 2 = 0.10 M = 15 M = 14 M = 21 Race A = 6 A = 3 A = 4 2 = 2.55 B = 1 B = 2 B = 1 W = 23 W = 22 W = 34 Eye OD = 20 OD = 13 OD = 21 2 = 4.46 OS = 10 OS = 14 OS = 18 Mean age (SD) years 64.0 (13.9) 72.4 (8.6) 70. (10.8) F = 4.55 p < 0.05 Mean (SD) no. 2.9 (1.2) 2.8 (1.2) 2.8 (1.2) F = 0.07 medications prelaser Mean (SD) no. 2.2 (1.6) 2.3 (1.6) 2.9 (1.2) F = 2.4 medications postlaser Mean no. medications t = 2.9 t = 2.4 t = 1.4 Pre vs. post p = p = 0.02 Note: SLT, selective laser trabeculoplasty; ALT, argon laser trabeculopasty; F, female; M, male; A, Asian; B, black; W, white; F, critical value for the analysis of variance; t, critical value for the Student s t test. Table 2 Distribution of diagnosis of open-angle glaucoma (OAG) Diagnosis SLT only SLT after ALT ALT only among groups POAG = 2.8 PEX PDS Note: SLT, selective laser trabeculoplasty; ALT, argon laser trabeculoplasty; POAG, primary open-angle glaucoma; PEX, OAG secondary to pseudoexfoliation; PDS, OAG secondary to pigment dispersion. use of ALT is limited, and more than 1 treatment of 360 is rarely used because of concerns about lesser clinical efficacy and increased risk of scarring and loss of outflow. 7 The results of repeated treatments with SLT have not been reported in the literature. This study attempts to examine the safety and effectiveness of SLT given to previously ALT-treated meshwork, which is not quite the same thing. The first clinical study of SLT, by Latina et al., 2 reported results in a group of patients of whom some were receiving their first laser treatment and some had previously had ALT. Both groups of patients showed clinical response to the SLT, with mean IOP reductions of 5.8 and 6.0 mm Hg, respectively. Damji et al. 4 also included some patients who had previously received ALT and found on a post-hoc analysis that that subgroup of patients responded better to SLT than to retreatment with ALT, with decreases of 6.8 vs. 3.6 mm Hg, respectively. These encouraging early results were duplicated by other authors, several of whom have reported responses at 6 months of follow-up. Kajiya et al. 8 found an average IOP lowering effect of SLT of 8.8 mm Hg, and Gracner 9 reported IOP reductions of 22.5% for SLT. Martinez-de-la- Casa et al. 10 found equivalent effectiveness of argon and selective trabeculoplasty (19.5% vs. 22.2% IOP reduction, respectively). These studies, however, did not specifically examine patients who were receiving a retreatment. Longer-term follow-up studies are still relatively uncommon in the SLT literature. The Latina and Gulati 5 and Damji et al. 4 papers each followed patients for Table 3 Distribution of medications used* Medication SLT only SLT after ALT ALT only among groups -blocker = 6.1 CAI agonist PG Pilocarpine *Patients may have received more than one type of drops. Note: SLT, selective laser trabeculoplasty; ALT, argon laser trabeculoplasty; CAI, carbonic anhydrase inhibitors; -agonist, adrenergic agonists; PG, prostaglandins. Table 4 Comparison of intraocular pressure before and after laser trabeculoplasty Mean (SD) IOP Period of follow-up SLT only SLT after ALT ALT only among groups Before laser 22.9 (4.2) 21.5 (4.3) 22.0 (5.3) F = 0.74 trabeculoplasty 17.6 (3.8) 17.3 (5.1) 18.1 (4.2) F = 0.00 At 4.5 mo. follow-up At 1 y. follow-up 17.7 (4.0) 16.7 (4.0) 16.4 (3.6) F = 0.28 Note: IOP, intraocular pressure; SLT, selective laser trabeculoplasty; ALT, argon laser trabeculoplasty; mo., month; y., year. Table 5 Comparison of follow-up percentage decrease in intraocular pressure by type of laser trabeculoplasty Mean (SD) percentage IOP decrease Period of follow-up SLT only SLT after ALT ALT only among groups Postlaser 4.5 mo (16.5) 14.9 (30.4) 19.2 (14.9) F = 0.79 Postlaser 1 y (3.8) 19.3 (4.5) 24.1 (2.5) F = 0.49 Note: IOP, intraocular pressure; SLT, selective laser trabeculoplasty; ALT, argon laser trabeculoplasty; mo., month; y., year. CAN J OPHTHALMOL VOL. 42, NO

4 6 months. A recent paper, however, examined the results of a prospective, nonrandomized clinical series of 52 eyes. 11 The authors reported that the average decrease of IOP at 1 year was 6.0 mm Hg (24.3%) and 6.33 mm Hg (29.3%) at 4 years. However, a Kaplan-Meier survival curve showed a 1-year success rate of 60%, which decreased to 53% at 2 years and 44% at 3 and 4 years. The paper concludes that the effects of SLT wane over time but that the treatment is still effective over an extended period. Juzych et al. 12 described a retrospective review of patients receiving either SLT or ALT with a mean followup time of over 30 months for each group and some patients followed for up to 5 years. The mean percentage decrease in IOP at 1 year was 18.1% for both the patient groups. There were no significant differences in long-term success rate between the 2 treatment modalities, and no difference was seen whether or not the patient had received ALT prior to the study treatment. One-year data were reported by Bovell et al. 13 in a comparison of the effectiveness of ALT vs. SLT. They found no statistically significant differences in the change of IOP among their randomized groups. When comparing the time to treatment failure in SLT or ALT treated patients, Pan 14 found no statistical differences between the time to failure between the 2 groups. Song et al. 15 studied the success of SLT up to 14.5 months in a tertiary clinic population and found failure rates of between 68% and 74%, depending on the success criterion. By comparison, Francis et al. 16 reported that use of SLT could reduce the number of medications required and keep IOP at target levels in 87% of their patients at 1 year, and Hodge et al. 17 found that 59.7% of their patients had an IOP reduction of over 20% at 1 year. The only factor that predicted success in their patients was prelaser IOP, with an odds ratio of One study examined the efficacy of SLT as compared with medications and found similar IOP control with fewer medications required in the laser-treated eye at 5 years of follow-up. 18 However, this study used both eyes of each patient, randomly assigned to the 2 interventions, and hoped to decrease the crossover effect of medications by the use of nasolacrimal occlusion. Cvenkel 19 reported 1-year follow-up data that showed a tendency for the IOP to increase over time. Although the selective laser is thought to work by selective targeting of pigment granules within the meshwork, 7 the role of the level of pigmentation of the meshwork, as seen clinically, remains unclear. One case study of 4 patients who presented with post-trabeculoplasty IOP elevations reported that all had heavily pigmented trabecular meshwork, and 2 had had previous argon trabeculoplasty. Caution in this type of patient was recommended. 20 Some authors have stated that therapeutic results are independent of the degree of meshwork pigmentation, 21 whereas others have found a relation between success and pigmentary levels. 22 However, the study by Chen et al. compared SLT over 90 and 180 and may not provide a direct comparison with the other work. Another group reported greater effect, a further 2.8 mm Hg decrease, with 360 treatment as compared retrospectively with those who had received 180 treatment. 23 Nagar et al. 24 found that treatment of 90 was ineffective, but there were no statistical differences between 180 and 360 treatments. Most studies, however, have used the 180 treatment of trabecular meshwork that became standard for ALT therapy. Interest in use of the SLT technique as a primary therapy has also been growing in the ophthalmic community. This refers to use of the laser as a first-line therapy without the use of topical medications instead of as an adjunct technique when medical therapy is inadequate or not tolerated. One nonrandomized study reported 3-month follow-up on 45 eyes of 31 patients, with 5 eyes followed to 18 months, and found a mean 30% decrease in IOP, from 25.5 to 17.9 mm Hg. 25 A longer term study found a mean decrease of 7.7 mm Hg (30%) at 18 months in 45 eyes of 31 patients. 26 Medications were added when necessary. A recent study with a 1-year follow-up compared SLT as primary therapy with a control group treated with latanoprost and showed similar absolute and percentage reductions in IOP in the 2 groups. 27 The current study shows that patients who have completed 360 of previous laser trabeculoplasty with the argon laser can still benefit from selective laser treatment, showing decreases in IOP very similar to those of patients who were naïve to prior laser therapy. Possible biases exist in these results. The study population was not randomized to receive either SLT or ALT after ALT, although the naïve patients were randomly assigned to laser type. The sample is small, although comparable to other published reports, and the 1-year follow-up is fairly short. Furthermore, the naïve patients receiving SLT were significantly younger than the other groups. It is not surprising that the patients receiving SLT after prior ALT would be the oldest group, as they could be considered to be later in the disease, having previously required intervention. In conclusion, since it is known that retreatment with the argon laser must be done cautiously, if at all, to avoid excessive scarring and intractable IOP rises, 28 it is encouraging to have available another modality of treatment that may be intrinsically safer for use in this challenging patient population. REFERENCES 1. Wise JB, Witter SL. Argon laser therapy for open-angle glaucoma. A pilot study. 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