ORIGINAL STUDY
Optimal Selective Laser Trabeculoplasty Energy for Maximal Intraocular Pressure Reduction in Open-Angle Glaucoma Jacky W.Y. Lee, FRCSEd,*w Mandy O.M. Wong, MRCSEd,z Catherine C.L. Liu, PhD,y and Jimmy S.M. Lai, MD*
Purpose: To identify the optimal energy level to be used in selective laser trabeculoplasty (SLT) for maximal intraocular pressure (IOP) reduction in open-angle glaucoma (OAG) patients. Patients and Methods: This cohort sequentially recruited OAG subjects in Hong Kong, China during 2011 to 2012. All subjects received a single session of SLT with near confluent spots to 360 degrees of the trabecular meshwork. An initial energy of 0.8 mJ was titrated until bubble formation was just visible. The main outcomes included: change in IOP (pre-SLT to 1 mo post-SLT) and total SLT energy (SLT spots multiplied by the mean energy). For statistical analysis, only the right eye of each subject was used. Bandwidth selection by generalized cross-validation was used to determine the optimal interval and point of total SLT energy that resulted in the largest IOP reduction. Results: A total of 49 Chinese OAG subjects had a mean age of 64.2 ± 11.1 years. The pre-SLT IOP was 17.1 ± 2.9 mm Hg while on 1.9 ± 1.1 types of antiglaucoma eye drops. The mean total energy was 167.1 ± 41.4 mJ (171.5 ± 41.2 spots at 1.0 ± 0.06 mJ). The 1 month post-SLT IOP was 13.5 ± 2.8 mm Hg. The percentage of SLT success was 57.1% (28/49). The 95% confidence band by bootstrap method was plotted showing that a total energy between 214.6 and 234.9 mJ significantly decreased the IOP > 25%, with the optimal total energy at 226.1 mJ. Conclusions: A higher SLT energy, in the range of 214.6 to 234.9 mJ, seems to be associated with an improved IOP-lowering response. Further randomized control trials with treatment stratification are needed to confirm these results. Key Words: energy, selective laser trabeculoplasty, intraocular pressure, optimal, spots
(J Glaucoma 2015;24:e128–e131)
S
elective laser trabeculoplasty (SLT) was first described by Latina and Park in 1995,1 and was shown to be as effective as antiglaucoma medication in lowering intraocular pressure (IOP) by 11% to 40% in open-angle glaucoma (OAG).2–5 With minimal mechanical damage, the release of chemotactic and vasoactive agents and trabecular meshwork remodeling were postulated to be more important Received for publication March 3, 2014; accepted November 27, 2014. From the *The Department of Ophthalmology, Caritas Medical Centre; wThe Department of Ophthalmology, The University of Hong Kong; zThe Department of Ophthalmology, Queen Mary Hospital; and yDepartment of Applied Mathematics, The Hong Kong Polytechnic University, Hong Kong, SAR, People’s Republic of China. Disclosure: The authors declare no conflict of interest. Reprints: Jacky W.Y. Lee, FRCSEd, Department of Ophthalmology, Caritas Medical Centre, 111 Wing Hong Street, Kowloon, Hong Kong, SAR, People’s Republic of China (e-mail: jackywylee@ gmail.com). Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/IJG.0000000000000215
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mechanisms for IOP lowering compared with the mechanical theory.6 SLT is performed with fixed laser duration (3 ns) and spot size (400 mm). However, there is no standardized number of treatment spots or area of treatment which varies throughout the literature.7 Although a higher prelaser IOP is a consistent predictor for SLT success,8,9 laser energy was also found to be one of the factors that positively correlate with time to failure in a retrospective predictive analysis.10 Success rate of SLT treatment of 360 degrees of the trabecular meshwork was also found to be comparable with latanoprost 0.005%, but not in the groups receiving 90 or 180 degrees in a randomized controlled trial. However, the total energy in terms of the number of spots and energy per spot used in each group was not compared.11 The aim of this study is to identify the optimal energy level to be used in SLT for maximal IOP reduction in OAG patients.
PATIENTS AND METHODS This prospective cohort study sequentially recruited subjects from the ophthalmology clinic of a tertiary university hospital, Queen Mary Hospital, Hong Kong, China during September 2011 to September 2012. The study included subjects with unilateral or bilateral primary openangle (POAG) or normal tension glaucoma (NTG) currently on antiglaucoma eye drops. Subjects were excluded if they had preexisting corneal pathology or scars, previous argon laser trabeculoplasty or SLT treatment, or if they defaulted follow-up. OAG was defined as open angle on gonioscopy with visual field loss on the Humphrey Visual Field Analyzer as per the Hoddap-Parrish-Anderson criteria12 or retinal nerve fiber layer thinning on optical coherence tomography. POAG was defined as IOP > 21 mm Hg before treatment and NTG was defined as IOPr21 mm Hg before treatment. SLT was offered to subjects to further optimize the IOP control and reduce the medication regimen in those with poor drug compliance, intolerance to medication side effects, or inadequate response to current medications. A single session of SLT was performed by a single surgeon (J.W.Y.L.) using a Q-switched Nd:YAG laser (Ellex Solo, Ellex Medical Pty Ltd, Adelaide, SA, Australia), with an initial energy of 0.8 mJ and titrated until bubble formation was just visible. In all subjects, spots were applied in a near confluent manner to 360 degrees of the pigmented trabecular meshwork. For those with bilateral disease, both eyes were treated in the same laser session. In all treated eyes, a single drop of Alphagan P (Allergan Inc., Waco, TX) was instilled immediately after SLT and a dexamtheasone 0.1% and neomycin 0.5% combination eye drop (Dexoptic-N by Ashford Laboratories Pvt Ltd, J Glaucoma
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Volume 24, Number 5, June/July 2015
J Glaucoma
Volume 24, Number 5, June/July 2015
Santacruz (West), Mumbai (Bombay), India) was used twice daily for 1 day and was continued for a few more days only if anterior chamber reaction was detected during follow-up. Patients returned for follow-up on day 1, 1 week, and 1 month thereafter after SLT. Patients continued the same antiglaucoma drug regime for the first month after SLT and medication was subsequently titrated to achieve individual target pressures. The main outcome measures included: change in IOP (CIOP) post-SLT (difference between pre-SLT and postSLT IOP at 1 mo) and total SLT energy (number of SLT spots multiplied by the mean laser energy used). All IOP readings were measured by Goldmann applanation tonometry by a single investigator. The secondary outcome measures included: presenting IOP (without medication), IOP at day 1 and 1 week after SLT, number of type of antiglaucoma eye drops before SLT, and percentage of SLT success (IOP reductionZ20% at 1 mo post-SLT). This study adhered to the tenets of the Declaration of Helsinki. Informed patient consent and approval by the Institutional Review Board were obtained before study commencement.
Statistics For statistical analysis, only the right eye of each subject was used for analysis. A scattered plot of CIOP against total SLT energy was drawn to illustrate the obvious nonlinear association between CIOP versus SLT energy. Median regression was used to exclude outliers13 followed by a nonparametric local linear regression analysis. An Epanechnikov kernel function was taken and compared with Gauss kernel showing compatibility, signifying that the selection of kernel function had no influence on the nonparametric regression.14 Bandwidth selection by generalized cross-validation15 was used to determine the optimal interval and point of total SLT energy that resulted in the largest drop in IOP. Means were expressed as mean ± SD. An a error of 25%): energy in the interval (81.0 to 82.7 mJ) and (214.6 to 234.9 mJ). But as the former range was near the boundary of the curve, it was deemed not reliable for interpretation and excluded from further analysis. To affirm the reliability of previous results, a bootstrap method was applied to set up a confidence interval by carrying out 5000 bootstrap trials16 (Fig. 3). The 95% confidence band by bootstrap method was plotted showing that the intervals (214.6 to 234.9 mJ) significantly decreased the IOP > 25%, with the optimal total energy at 226.1 mJ (Fig. 4).
DISCUSSION
RESULTS
In a retrospective study, Ayala and Chen10 treated OAG with 23 to 30 spots over 90 degrees of the trabecular meshwork and found that a higher SLT energy was significantly correlated with a longer duration of IOP reduction. On the other hand, in a retrospective review of 318 eyes of 284 OAG patients, using 100 overlapping SLT spots over 180 degrees had a poorer IOP response than those treated with nonoverlapping SLT spots over 360 degrees.17
Forty-nine Chinese adults (25 NTG and 24 POAG) were recruited for the study. The mean age was 64.2 ± 11.1 years with 25 male and 24 female subjects. All were phakic right eyes. The presenting IOP (without medication) was 19.8 ± 4.7 mm Hg. The pre-SLT IOP was 17.1 ± 2.9 mm Hg while on 1.9 ± 1.1 types of antiglaucoma eye drops. The mean number of SLT spots was 171.5 ± 41.2 and the mean energy level was 1.0 ± 0.06 mJ with a mean total energy of 167.1 ± 41.4 mJ. There were no complications from the SLT treatment and none of the subjects had clinically evident corneal edema on slit-lamp examination post-SLT. None of the subjects had anterior uveitis that lasted more than 5 days after SLT. The day 1, 1 week, 1 month IOP post-SLT were 12.2 ± 2.9, 15.3 ± 3.5, and 13.5 ± 2.8 mm Hg, respectively, while on the same antiglaucoma medication regimen as before SLT. The change in IOP at 1 month was a reduction of 20.2% ± 14.6% compared with pre-SLT IOP. The percentage of SLT success was 57.1% (28/49). Scattered plotting change in IOP versus total SLT energy revealed that the 2 parameters did not have a linear association (Fig. 1).
FIGURE 2. Fitted curve when the optimal bandwidth is selected by GCV. y-axis = Percentage of IOP reduciton (%). x-axis = Total SLT energy (mJ). GCV indicates generalized cross-validation; IOP, intraocular pressure; SLT, selective laser trabeculoplasty.
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FIGURE 3. The mean curve based on 5000 bootstrap trials for GCV optimal bandwidth. y-axis = Percentage of IOP reduciton (%). x-axis = Total SLT energy (mJ). GCV indicates generalized cross-validation; IOP, intraocular pressure; SLT, selective laser trabeculoplasty.
Thus, it seems that a greater number of spots may not be directly related to SLT success but the extent of trabecular meshwork treatment also seems to play a role. Rinke et al18 reported that a higher effectiveness was achieved with 360 degrees SLT treatment compared with 180 degrees treatment in 36 eyes with OAG.19 Likewise, Nagar et al11 reported a higher success rate with 360 degrees treatment (93 to 102 spots) compared with 180 degrees (48 to 53 spots) or 90 degrees (25 to 30 spots) treatment and that a 90degree treatment was often not effective. It is not the absolute number of spots that determine SLT response but rather the energy density (number of spots multiplied by the mean energy) delivered to the trabecular meshwork that is of importance. As SLT uses a nanosecond technology, laser energy is directed to melanosomes in the pigmented trabecular meshwork, sparing
FIGURE 4. The bootstrap confidence based on 5000 bootstrap trials for GCV optimal bandwidth. y-axis = Percentage of IOP reduciton (%). x-axis = Total SLT energy (mJ). GCV indicates generalized cross-validation; IOP, intraocular pressure; SLT, selective laser trabeculoplasty.
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adjacent nonpigmented cells making overlapping or even retreatments harmless.19 Lee and colleagues have affirmed the safety of SLT to the cornea in a series of 111 eyes treated with a mean of 166.9 ± 41.4 SLT spots at a mean energy level of 1.0 ± 0.07 mJ. The authors found no statistically significant differences in the endothelial cell count, central corneal thickness, or spherical equivalent at 1 month post-SLT treatment.20 A widely accepted definition of SLT success is a 20% or more reduction from pretreatment IOP but in cases of NTG, a 20% IOP reduction if often not adequate as per the Collaborative Normal Tension Glaucoma Study.21 Thus, in our study, we used a 25% IOP reduction as determinant of the optimal SLT energy. Conventionally, approximately 100 spots are applied to 360 degrees of the trabecular meshwork. In our series, we treated 360 degrees of the trabecular meshwork with near confluent spots and determined with statistical significance that delivering 226.1 mJ (95% confidence interval: 214.58 to 234.87 mJ) of SLT energy was likely to result in an IOP reduction of >25% from pretreatment levels. On the basis of Figures 2–4, it seems that the conventional 100 spots (or approximately 100 mJ of total energy if assuming a mean energy of 1.0 mJ) are suboptimal in bringing out the full IOP-lowering potential of SLT. Our findings are consistent with the above-described studies supporting better results with 360 degrees treatments and a greater number of treatment spots. Although the majority of studies advocate more SLT spots (or total energy), Tang et al22 found no statistical differences in SLT success between those treated with a lower energy SLT (0.3 to 0.5 mJ) versus a control group using full power (0.6 to 1.0 mJ). Several limitations exist for the current study. First, the sample size of the current study is not large comparing to previous retrospective analyses (eg, 120 eyes in the study by Ayala et al10). Second, the baseline IOP was varied among the recruited subjects, likely due to the inclusion of NTG patients. This may lead to a relatively low success rate (57.1%), and subsequently a wider confidence interval for the optimal energy range. The precision of the optimal energy range may therefore be reduced. Bootstrapping was performed to identify any possible variation in the distribution of the sample. In our opinion, the range of optimal energy level (214.6 to 234.9 mJ) is not large when applied clinically. Third, a longer post-SLT time interval could have be used to compare the success of SLT but based on Johnson et al’s23 study, the 2-week post-SLT IOP was already predictive of future IOP control at 3 months. Fourth, the topical steroids used after SLT may theoretically hinder the IOP-lowering effect but as only 2 drops of topical steroids were used in those without reactive uveitis, this was unlikely to significantly affect the post-SLT IOP. Ideally, a larger, randomized controlled study design with stratification by energy levels and glaucoma subtype would provide stronger evidence for definition of the optimal power. This is one of the few papers in the literature reporting that a higher SLT energy range (214.6 to 234.9 mJ) resulted in a more optimal IOP reduction (> 25 mm Hg).
REFERENCES 1. Latina MA, Park C. Selective targeting of trabecular meshwork cells: in vitro studies of pulsed and CW laser interactions. Exp Eye Res. 1995;60:359–371.
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2. Stein JD, Challa P. Mechanisms of action and efficacy of argon laser trabeculoplasty and selective laser trabeculoplasty. Curr Opin Ophthalmol. 2007;18:140–145. 3. Wong MO, Lee JW, Choy BN, et al. Systematic review and meta-analysis on the efficacy of selective laser trabeculoplasty in open-angle glaucoma. Surv Ophthalmol. 2015;60:36–50. 4. Lee JW, Gangwani RA, Chan JC, et al. Prospective study on the efficacy of treating normal tension glaucoma with a single session of selective laser trabeculoplasty. J Glaucoma. 2014. [Epub ahead of print] DOI: 10.1097/IJG.0000000000000089. 5. Lee JW, Chan CW, Wong MO, et al. A randomized control trial to evaluate the effect of adjuvant selective laser trabeculoplasty versus medication alone in primary open-angle glaucoma: preliminary results. Clin Ophthalmol. 2014;8:1987–1992. 6. Latina MA, Gulati V. Selective laser trabeculoplasty: stimulating the meshwork to mend its ways. Int Ophthalmol Clin. 2004;44:93–103. 7. Samples JR, Singh K, Lin SC, et al. Laser trabeculoplasty for open-angle glaucoma: a report by the american academy of ophthalmology. Ophthalmology. 2011;118:2296–2302. 8. Lee JW, Liu CC, Chan J, et al. Predictors of success in selective laser trabeculoplasty for primary open angle glaucoma in Chinese. Clin Ophthalmol. 2014;8:1787–1791. 9. Lee JW, Liu CC, Chan JC, et al. Predictors of success in selective laser trabeculoplasty for chinese open-angle glaucoma. J Glaucoma. 2014;23:321–325. 10. Ayala M, Chen E. Predictive factors of success in selective laser trabeculoplasty (SLT) treatment. Clin Ophthalmol. 2011;5: 573–576. 11. Nagar M, Ogunyomade A, O’Brart DP, et al. A randomised, prospective study comparing selective laser trabeculoplasty with latanoprost for the control of intraocular pressure in ocular hypertension and open angle glaucoma. Br J Ophthalmol. 2005;89:1413–1417.
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12. Hodapp E, Parrish RK II, Anderson DR. Clinical Decisions in Glaucoma. St Louis, MO: The CV Mosby Co.; 1993:52–61. 13. Yu K, Jones MC. Local linear quantile regression. J Am Stat Assoc. 1998;93:228–237. 14. Fan J, Gijbels I. Local Polynomial Modeling and its Applications. London: Chapman and Hall; 1996:46–55. 15. Ruppert D, Sheather SJ, Wand MP. An effective bandwidth selector for local least squares regression. J Am Stat Assoc. 1995;90:1257–1270. 16. Efron B, Tibshirani RJ. An Introduction to the Bootstrap Monographs on Statistics and Applied Probability 57. New York, NY: Chapman and Hall; 1993:153–199. 17. George MK, Emerson JW, Cheema SA, et al. Evaluation of a modified protocol for selective laser trabeculoplasty. J Glaucoma. 2008;17:197–202. 18. Rinke AR, Hughes BA, Juzych MS, et al. The Effectiveness of 180 Degree versus 360 Degree SLT at 3 Months. Invest Ophthalmol Vis Sci. 2005;46: E-Abstract 116. 19. Barkana Y, Belkin M. Selective laser trabeculoplasty. Surv Ophthalmol. 2007;52:634–654. 20. Lee JW, Chan JC, Chang RT, et al. Corneal changes after a single session of selective laser trabeculoplasty for open-angle glaucoma. Eye (Lond). 2014;28:47–52. 21. Collaborative Normal-Tension Glaucoma Study Group. The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Collaborative Normal-Tension Glaucoma Study Group. Am J Ophthalmol. 1998;126:498–505. 22. Tang M, Fu Y, Fu MS, et al. The efficacy of low-energy selective laser trabeculoplasty. Ophthalmic Surg Lasers Imaging. 2011;42:59–63. 23. Johnson PB, Katz LJ, Rhee DJ. Selective laser trabeculoplasty: predictive value of early intraocular pressure measurements for success at 3 months. Br J Ophthalmol. 2006;90:741–743.
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e131
Optimal Selective Laser Trabeculoplasty Energy for Maximal Intraocular Pressure Reduction in Open-Angle Glaucoma Jacky W.Y. Lee, FRCSEd,*w Mandy O.M. Wong, MRCSEd,z Catherine C.L. Liu, PhD,y and Jimmy S.M. Lai, MD*
Purpose: To identify the optimal energy level to be used in selective laser trabeculoplasty (SLT) for maximal intraocular pressure (IOP) reduction in open-angle glaucoma (OAG) patients. Patients and Methods: This cohort sequentially recruited OAG subjects in Hong Kong, China during 2011 to 2012. All subjects received a single session of SLT with near confluent spots to 360 degrees of the trabecular meshwork. An initial energy of 0.8 mJ was titrated until bubble formation was just visible. The main outcomes included: change in IOP (pre-SLT to 1 mo post-SLT) and total SLT energy (SLT spots multiplied by the mean energy). For statistical analysis, only the right eye of each subject was used. Bandwidth selection by generalized cross-validation was used to determine the optimal interval and point of total SLT energy that resulted in the largest IOP reduction. Results: A total of 49 Chinese OAG subjects had a mean age of 64.2 ± 11.1 years. The pre-SLT IOP was 17.1 ± 2.9 mm Hg while on 1.9 ± 1.1 types of antiglaucoma eye drops. The mean total energy was 167.1 ± 41.4 mJ (171.5 ± 41.2 spots at 1.0 ± 0.06 mJ). The 1 month post-SLT IOP was 13.5 ± 2.8 mm Hg. The percentage of SLT success was 57.1% (28/49). The 95% confidence band by bootstrap method was plotted showing that a total energy between 214.6 and 234.9 mJ significantly decreased the IOP > 25%, with the optimal total energy at 226.1 mJ. Conclusions: A higher SLT energy, in the range of 214.6 to 234.9 mJ, seems to be associated with an improved IOP-lowering response. Further randomized control trials with treatment stratification are needed to confirm these results. Key Words: energy, selective laser trabeculoplasty, intraocular pressure, optimal, spots
(J Glaucoma 2015;24:e128–e131)
S
elective laser trabeculoplasty (SLT) was first described by Latina and Park in 1995,1 and was shown to be as effective as antiglaucoma medication in lowering intraocular pressure (IOP) by 11% to 40% in open-angle glaucoma (OAG).2–5 With minimal mechanical damage, the release of chemotactic and vasoactive agents and trabecular meshwork remodeling were postulated to be more important Received for publication March 3, 2014; accepted November 27, 2014. From the *The Department of Ophthalmology, Caritas Medical Centre; wThe Department of Ophthalmology, The University of Hong Kong; zThe Department of Ophthalmology, Queen Mary Hospital; and yDepartment of Applied Mathematics, The Hong Kong Polytechnic University, Hong Kong, SAR, People’s Republic of China. Disclosure: The authors declare no conflict of interest. Reprints: Jacky W.Y. Lee, FRCSEd, Department of Ophthalmology, Caritas Medical Centre, 111 Wing Hong Street, Kowloon, Hong Kong, SAR, People’s Republic of China (e-mail: jackywylee@ gmail.com). Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/IJG.0000000000000215
e128 | www.glaucomajournal.com
mechanisms for IOP lowering compared with the mechanical theory.6 SLT is performed with fixed laser duration (3 ns) and spot size (400 mm). However, there is no standardized number of treatment spots or area of treatment which varies throughout the literature.7 Although a higher prelaser IOP is a consistent predictor for SLT success,8,9 laser energy was also found to be one of the factors that positively correlate with time to failure in a retrospective predictive analysis.10 Success rate of SLT treatment of 360 degrees of the trabecular meshwork was also found to be comparable with latanoprost 0.005%, but not in the groups receiving 90 or 180 degrees in a randomized controlled trial. However, the total energy in terms of the number of spots and energy per spot used in each group was not compared.11 The aim of this study is to identify the optimal energy level to be used in SLT for maximal IOP reduction in OAG patients.
PATIENTS AND METHODS This prospective cohort study sequentially recruited subjects from the ophthalmology clinic of a tertiary university hospital, Queen Mary Hospital, Hong Kong, China during September 2011 to September 2012. The study included subjects with unilateral or bilateral primary openangle (POAG) or normal tension glaucoma (NTG) currently on antiglaucoma eye drops. Subjects were excluded if they had preexisting corneal pathology or scars, previous argon laser trabeculoplasty or SLT treatment, or if they defaulted follow-up. OAG was defined as open angle on gonioscopy with visual field loss on the Humphrey Visual Field Analyzer as per the Hoddap-Parrish-Anderson criteria12 or retinal nerve fiber layer thinning on optical coherence tomography. POAG was defined as IOP > 21 mm Hg before treatment and NTG was defined as IOPr21 mm Hg before treatment. SLT was offered to subjects to further optimize the IOP control and reduce the medication regimen in those with poor drug compliance, intolerance to medication side effects, or inadequate response to current medications. A single session of SLT was performed by a single surgeon (J.W.Y.L.) using a Q-switched Nd:YAG laser (Ellex Solo, Ellex Medical Pty Ltd, Adelaide, SA, Australia), with an initial energy of 0.8 mJ and titrated until bubble formation was just visible. In all subjects, spots were applied in a near confluent manner to 360 degrees of the pigmented trabecular meshwork. For those with bilateral disease, both eyes were treated in the same laser session. In all treated eyes, a single drop of Alphagan P (Allergan Inc., Waco, TX) was instilled immediately after SLT and a dexamtheasone 0.1% and neomycin 0.5% combination eye drop (Dexoptic-N by Ashford Laboratories Pvt Ltd, J Glaucoma
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Volume 24, Number 5, June/July 2015
J Glaucoma
Volume 24, Number 5, June/July 2015
Santacruz (West), Mumbai (Bombay), India) was used twice daily for 1 day and was continued for a few more days only if anterior chamber reaction was detected during follow-up. Patients returned for follow-up on day 1, 1 week, and 1 month thereafter after SLT. Patients continued the same antiglaucoma drug regime for the first month after SLT and medication was subsequently titrated to achieve individual target pressures. The main outcome measures included: change in IOP (CIOP) post-SLT (difference between pre-SLT and postSLT IOP at 1 mo) and total SLT energy (number of SLT spots multiplied by the mean laser energy used). All IOP readings were measured by Goldmann applanation tonometry by a single investigator. The secondary outcome measures included: presenting IOP (without medication), IOP at day 1 and 1 week after SLT, number of type of antiglaucoma eye drops before SLT, and percentage of SLT success (IOP reductionZ20% at 1 mo post-SLT). This study adhered to the tenets of the Declaration of Helsinki. Informed patient consent and approval by the Institutional Review Board were obtained before study commencement.
Statistics For statistical analysis, only the right eye of each subject was used for analysis. A scattered plot of CIOP against total SLT energy was drawn to illustrate the obvious nonlinear association between CIOP versus SLT energy. Median regression was used to exclude outliers13 followed by a nonparametric local linear regression analysis. An Epanechnikov kernel function was taken and compared with Gauss kernel showing compatibility, signifying that the selection of kernel function had no influence on the nonparametric regression.14 Bandwidth selection by generalized cross-validation15 was used to determine the optimal interval and point of total SLT energy that resulted in the largest drop in IOP. Means were expressed as mean ± SD. An a error of 25%): energy in the interval (81.0 to 82.7 mJ) and (214.6 to 234.9 mJ). But as the former range was near the boundary of the curve, it was deemed not reliable for interpretation and excluded from further analysis. To affirm the reliability of previous results, a bootstrap method was applied to set up a confidence interval by carrying out 5000 bootstrap trials16 (Fig. 3). The 95% confidence band by bootstrap method was plotted showing that the intervals (214.6 to 234.9 mJ) significantly decreased the IOP > 25%, with the optimal total energy at 226.1 mJ (Fig. 4).
DISCUSSION
RESULTS
In a retrospective study, Ayala and Chen10 treated OAG with 23 to 30 spots over 90 degrees of the trabecular meshwork and found that a higher SLT energy was significantly correlated with a longer duration of IOP reduction. On the other hand, in a retrospective review of 318 eyes of 284 OAG patients, using 100 overlapping SLT spots over 180 degrees had a poorer IOP response than those treated with nonoverlapping SLT spots over 360 degrees.17
Forty-nine Chinese adults (25 NTG and 24 POAG) were recruited for the study. The mean age was 64.2 ± 11.1 years with 25 male and 24 female subjects. All were phakic right eyes. The presenting IOP (without medication) was 19.8 ± 4.7 mm Hg. The pre-SLT IOP was 17.1 ± 2.9 mm Hg while on 1.9 ± 1.1 types of antiglaucoma eye drops. The mean number of SLT spots was 171.5 ± 41.2 and the mean energy level was 1.0 ± 0.06 mJ with a mean total energy of 167.1 ± 41.4 mJ. There were no complications from the SLT treatment and none of the subjects had clinically evident corneal edema on slit-lamp examination post-SLT. None of the subjects had anterior uveitis that lasted more than 5 days after SLT. The day 1, 1 week, 1 month IOP post-SLT were 12.2 ± 2.9, 15.3 ± 3.5, and 13.5 ± 2.8 mm Hg, respectively, while on the same antiglaucoma medication regimen as before SLT. The change in IOP at 1 month was a reduction of 20.2% ± 14.6% compared with pre-SLT IOP. The percentage of SLT success was 57.1% (28/49). Scattered plotting change in IOP versus total SLT energy revealed that the 2 parameters did not have a linear association (Fig. 1).
FIGURE 2. Fitted curve when the optimal bandwidth is selected by GCV. y-axis = Percentage of IOP reduciton (%). x-axis = Total SLT energy (mJ). GCV indicates generalized cross-validation; IOP, intraocular pressure; SLT, selective laser trabeculoplasty.
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2015 Wolters Kluwer Health, Inc. All rights reserved. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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J Glaucoma
FIGURE 3. The mean curve based on 5000 bootstrap trials for GCV optimal bandwidth. y-axis = Percentage of IOP reduciton (%). x-axis = Total SLT energy (mJ). GCV indicates generalized cross-validation; IOP, intraocular pressure; SLT, selective laser trabeculoplasty.
Thus, it seems that a greater number of spots may not be directly related to SLT success but the extent of trabecular meshwork treatment also seems to play a role. Rinke et al18 reported that a higher effectiveness was achieved with 360 degrees SLT treatment compared with 180 degrees treatment in 36 eyes with OAG.19 Likewise, Nagar et al11 reported a higher success rate with 360 degrees treatment (93 to 102 spots) compared with 180 degrees (48 to 53 spots) or 90 degrees (25 to 30 spots) treatment and that a 90degree treatment was often not effective. It is not the absolute number of spots that determine SLT response but rather the energy density (number of spots multiplied by the mean energy) delivered to the trabecular meshwork that is of importance. As SLT uses a nanosecond technology, laser energy is directed to melanosomes in the pigmented trabecular meshwork, sparing
FIGURE 4. The bootstrap confidence based on 5000 bootstrap trials for GCV optimal bandwidth. y-axis = Percentage of IOP reduciton (%). x-axis = Total SLT energy (mJ). GCV indicates generalized cross-validation; IOP, intraocular pressure; SLT, selective laser trabeculoplasty.
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adjacent nonpigmented cells making overlapping or even retreatments harmless.19 Lee and colleagues have affirmed the safety of SLT to the cornea in a series of 111 eyes treated with a mean of 166.9 ± 41.4 SLT spots at a mean energy level of 1.0 ± 0.07 mJ. The authors found no statistically significant differences in the endothelial cell count, central corneal thickness, or spherical equivalent at 1 month post-SLT treatment.20 A widely accepted definition of SLT success is a 20% or more reduction from pretreatment IOP but in cases of NTG, a 20% IOP reduction if often not adequate as per the Collaborative Normal Tension Glaucoma Study.21 Thus, in our study, we used a 25% IOP reduction as determinant of the optimal SLT energy. Conventionally, approximately 100 spots are applied to 360 degrees of the trabecular meshwork. In our series, we treated 360 degrees of the trabecular meshwork with near confluent spots and determined with statistical significance that delivering 226.1 mJ (95% confidence interval: 214.58 to 234.87 mJ) of SLT energy was likely to result in an IOP reduction of >25% from pretreatment levels. On the basis of Figures 2–4, it seems that the conventional 100 spots (or approximately 100 mJ of total energy if assuming a mean energy of 1.0 mJ) are suboptimal in bringing out the full IOP-lowering potential of SLT. Our findings are consistent with the above-described studies supporting better results with 360 degrees treatments and a greater number of treatment spots. Although the majority of studies advocate more SLT spots (or total energy), Tang et al22 found no statistical differences in SLT success between those treated with a lower energy SLT (0.3 to 0.5 mJ) versus a control group using full power (0.6 to 1.0 mJ). Several limitations exist for the current study. First, the sample size of the current study is not large comparing to previous retrospective analyses (eg, 120 eyes in the study by Ayala et al10). Second, the baseline IOP was varied among the recruited subjects, likely due to the inclusion of NTG patients. This may lead to a relatively low success rate (57.1%), and subsequently a wider confidence interval for the optimal energy range. The precision of the optimal energy range may therefore be reduced. Bootstrapping was performed to identify any possible variation in the distribution of the sample. In our opinion, the range of optimal energy level (214.6 to 234.9 mJ) is not large when applied clinically. Third, a longer post-SLT time interval could have be used to compare the success of SLT but based on Johnson et al’s23 study, the 2-week post-SLT IOP was already predictive of future IOP control at 3 months. Fourth, the topical steroids used after SLT may theoretically hinder the IOP-lowering effect but as only 2 drops of topical steroids were used in those without reactive uveitis, this was unlikely to significantly affect the post-SLT IOP. Ideally, a larger, randomized controlled study design with stratification by energy levels and glaucoma subtype would provide stronger evidence for definition of the optimal power. This is one of the few papers in the literature reporting that a higher SLT energy range (214.6 to 234.9 mJ) resulted in a more optimal IOP reduction (> 25 mm Hg).
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Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Glaucoma
Volume 24, Number 5, June/July 2015
2. Stein JD, Challa P. Mechanisms of action and efficacy of argon laser trabeculoplasty and selective laser trabeculoplasty. Curr Opin Ophthalmol. 2007;18:140–145. 3. Wong MO, Lee JW, Choy BN, et al. Systematic review and meta-analysis on the efficacy of selective laser trabeculoplasty in open-angle glaucoma. Surv Ophthalmol. 2015;60:36–50. 4. Lee JW, Gangwani RA, Chan JC, et al. Prospective study on the efficacy of treating normal tension glaucoma with a single session of selective laser trabeculoplasty. J Glaucoma. 2014. [Epub ahead of print] DOI: 10.1097/IJG.0000000000000089. 5. Lee JW, Chan CW, Wong MO, et al. A randomized control trial to evaluate the effect of adjuvant selective laser trabeculoplasty versus medication alone in primary open-angle glaucoma: preliminary results. Clin Ophthalmol. 2014;8:1987–1992. 6. Latina MA, Gulati V. Selective laser trabeculoplasty: stimulating the meshwork to mend its ways. Int Ophthalmol Clin. 2004;44:93–103. 7. Samples JR, Singh K, Lin SC, et al. Laser trabeculoplasty for open-angle glaucoma: a report by the american academy of ophthalmology. Ophthalmology. 2011;118:2296–2302. 8. Lee JW, Liu CC, Chan J, et al. Predictors of success in selective laser trabeculoplasty for primary open angle glaucoma in Chinese. Clin Ophthalmol. 2014;8:1787–1791. 9. Lee JW, Liu CC, Chan JC, et al. Predictors of success in selective laser trabeculoplasty for chinese open-angle glaucoma. J Glaucoma. 2014;23:321–325. 10. Ayala M, Chen E. Predictive factors of success in selective laser trabeculoplasty (SLT) treatment. Clin Ophthalmol. 2011;5: 573–576. 11. Nagar M, Ogunyomade A, O’Brart DP, et al. A randomised, prospective study comparing selective laser trabeculoplasty with latanoprost for the control of intraocular pressure in ocular hypertension and open angle glaucoma. Br J Ophthalmol. 2005;89:1413–1417.
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SLT Energy for Maximal IOP Reduction in OAG Patients
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