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III. Asking the Right Question in Laser Trabeculoplasty: “Which Patient”, not “Which Laser”?
652
Surv Ophthalmol 53 (6) November--December 2008
RAMULU AND PARRISH
III. ASKING THE RIGHT QUESTION IN LASER TRABECULOPLASTY: ‘‘WHICH PATIENT’’, NOT ‘‘WHICH LASER’’? Pradeep Y. Ramulu, MD,PhD,1 and Richard K. Parrish, MD2 1
Wilmer Eye Institute, Dept. of Ophthalmology, Johns Hopkins School of Medicine, Baltmore, Maryland, USA; and Bascom Palmer Eye Institute, Dept. of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, USA 2
The introduction of the Q-switched Nd:YAG laser for selective laser trabeculoplasty (SLT) has raised questions regarding its role in the management of patients with glaucoma. We believe that the most important issue regarding laser trabeculoplasty (LTP) treatment should not be which laser to use, but rather which patients would most benefit from its application. The merits and limitations of SLT have already been presented in the other articles (Argon Laser Trabeculoplasty: The Gold Standard and Selective Laser Trabeculoplasty: A Better Alternative) and, in our opinion, no clinically meaningful differences have been convincingly demonstrated between SLT and argon laser trabeculoplasty (ALT). Both ALT and SLT lower intraocular pressure (IOP) in patients with open-angle, pseudoexfoliation, and however, pigmentary glaucoma;3,4,8,12,14,15,17,21 currently reported randomized clinical trials that compare the results of the two laser systems are severely limited by small sample sizes, short duration of follow-up, or both.6,7,22
The Rebirth of LTP Irrespective of the relative merits of these two laser systems, ophthalmologists now widely use SLT for the treatment of glaucoma. Recent data from the United States and Canada show a remarkable resurgence of laser trabeculoplasty.18,19 Medicare data showed a 57% decrease in LTP between 1995 and 2001 after the introduction of several new classes of IOPlowering medicines.19 From 2002 to 2004, however, LTP volume doubled, corresponding to the time SLT became available for clinical use in North America. These data do not define why laser treatments were being performed, and the surge in LTP use may reflect increased use as primary therapy in newly diagnosed patients, as supplemental therapy in patients with advanced disease, as repeat procedures after other laser treatments, or as a replacement for medical therapy. The surge in LTP utilization makes a review of which patients are likely to benefit from this procedure particularly timely and relevant.
LTP in Advanced Disease: Not All It’s Made Out to Be The paradox of LTP is that it is most attractive to patients when it is least likely to affect their ultimate treatment course, and least attractive when it is most likely to affect their treatment course. A very low-risk laser treatment as an alternative to incisional surgery is likely to be accepted in patients with advanced disease, although this may not be in their best interests. Data from the Advanced Glaucoma Intervention Study (AGIS) is often used to justify the use of LTP in patients who have failed medical therapy, although its applicability to clinical practice today is limited. Two-thirds of AGIS patients who received LTP as an initial therapy avoided treatment failure at 5 years and nearly half avoided treatment failure at 10 years, but failures were registered only when a patient dropped below the same study eligibility criteria.1,2 Thus, many patients who had very little response to LTP were not considered failures, even though they may have received minimal IOP-lowering. Additionally, patients treated in AGIS were on maximal medical therapy at the time of enrollment, which predated the introduction of prostaglandin analogs, topical carbonic anhydrase inhibitors, and alpha adrenergic agonists. Study investigators were allowed to use newly introduced medications over the study period—so that some ‘‘successes’’ probably resulted from, or were at least prolonged by, the addition of newer, more effective medicines. Despite these caveats, failure rates were still significant in some patient subgroups. For example, 70-year-old study participants with a baseline IOP of 36 mm Hg had a nearly 90% failure rate at 5 years, and 70-year-old patients with an initial IOP of 27 mm Hg had a nearly 60% failure rate at 5 years. The IOP-lowering effects of LTP with current maximal medical therapy would likely be poorer than those reported by long-term follow-up in AGIS. Juzych retrospectively compared ALT and SLT in patients on maximum medical therapy and a baseline
653
VIEWPOINTS 3
IOP of 23 mm Hg. Success was defined as a 20% lowering of IOP.11 Both lasers failed in over 40% of patients by 1 year, and over 60% of patients by 3 years. Song used the same success criteria to evaluate the results of SLT in patients on maximal medical therapy and a mean IOP of 18.20 Over 90% failed to achieve 20% lowering of IOP at 14.5 months, and patients with lower IOP were more likely to fail. These data suggest that LTP is generally a poor option for patients on currently employed maximal medical therapy, particularly those who are well above target or requiring low final pressures. Patients with advanced disease who choose LTP should understand that long-term success is unlikely, and that incisional surgery will most likely be required.
LTP in Early Disease: Should We Be Using It More? Patient acceptance of LTP as initial treatment for early disease is often poor, even if this is an option that many ophthalmologists would choose for themselves. This will likely continue as long as patients believe that eye drops are the standard treatment for glaucoma, or until we can demonstrate more effective laser therapy. The Glaucoma Laser Trial and other studies have shown that LTP will lower IOP only 20% in about 60% of patients.4,6 After 2 years of follow-up, most patients required supplemental medical therapy, even to achieve a modest 20% lowering of IOP.4 Therefore, laser is likely only a temporary reprieve from eye drops. Additionally, LTP does not guarantee that the process of glaucomatous optic neuropathy will be halted.16 Both the ALT and medical groups had similar rates of disease progression in the GLT,4 and the Early Manifest Glaucoma Trial (EMGT) demonstrated that initial treatment with ALT and timolol maleate led to progression in a substantial percentage of patients.9,13 It is not surprising that patients often opt for medical therapy in view of their fear of the unknown and our guarded prognoses. The invariable need to spend time debunking myths regarding the use of lasers in ophthalmology often leads ophthalmologists to abandon the discussion altogether and perpetuates a vicious cycle that results in even lower rates of LTP for initial glaucoma management. We recommend abiding by the American Academy of Ophthalmology Preferred Practice Pattern and offering LTP, either as ALT or SLT, as a primary treatment for early disease.5 Even though some patients will respond poorly or not at all, most will at least benefit from a reduced load of IOP-lowering drops over the next several years, and some will have a prolonged period off medicines. Twenty percent
of patients in the GLT were able to remain off drops for a period of 7 years.3 Long-term success has been reported for SLT as well,21 and the drop-free window for SLT may be even longer if repeat treatments are effective. Our patients should not be denied this very low risk intervention with an opportunity for a prolonged period without eye drops, side effects, prescription charges, or trips to the pharmacy. It is important to remember which patients are unlikely to benefit from LTP, even as a primary treatment for early disease. These include those with little or no trabecular meshwork pigmentation (some evidence suggests that this is less true for SLT10); young patients; patients with certain types of glaucoma, such as extensive angle-closure, neovascular, inflammatory, ICE syndrome, or increased episcleral venous pressure; patients with very high IOP; and patients who are already well-controlled and asymptomatic on medical therapy. Selective laser trabeculoplasty has clearly renewed an interest in the use of LTP. We recommend channeling this interest toward identifying and treating patients who would most likely benefit from LTP, either SLT or ALT, and avoiding its use in those at high risk of failure.
References 1. ___: The Advanced Glaucoma Intervention Study (AGIS): 11. Risk factors for failure of trabeculectomy and argon laser trabeculoplasty. Am J Ophthalmol 134:481--98, 2002 2. ___: The Advanced Glaucoma Intervention Study (AGIS): 4. Comparison of treatment outcomes within race. Seven-year results. Ophthalmology 105:1146--64, 1998 3. ___: The Glaucoma Laser Trial (GLT) and glaucoma laser trial follow-up study: 7. Results. Glaucoma Laser Trial Research Group. Am J Ophthalmol 120:718--31, 1995 4. ___: The Glaucoma Laser Trial (GLT). 2. Results of argon laser trabeculoplasty versus topical medicines. The Glaucoma Laser Trial Research Group. Ophthalmology 97:1403--13, 1990 5. American Academy of Ophthalmology: Preferred Practice Pattern, Primary Open Angle Glaucoma, 2006, San Francisco, CA 6. Damji KF, Bovell AM, Hodge WG, et al: Selective laser trabeculoplasty versus argon laser trabeculoplasty: results from a 1-year randomised clinical trial. Br J Ophthalmol 90: 1490--4, 2006 7. Damji KF, Shah KC, Rock WJ, et al: Selective laser trabeculoplasty v argon laser trabeculoplasty: a prospective randomised clinical trial. Br J Ophthalmol 83:718--22, 1999 8. Francis BA, Ianchulev T, Schofield JK, et al: Selective laser trabeculoplasty as a replacement for medical therapy in open-angle glaucoma. Am J Ophthalmol 140:524--5, 2005 9. Heijl A, Leske MC, Bengtsson B, et al: Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol 120: 1268--79, 2002 10. Hodge WG, Damji KF, Rock W, et al: Baseline IOP predicts selective laser trabeculoplasty success at 1 year posttreatment: results from a randomised clinical trial. Br J Ophthalmol 89:1157--60, 2005 11. Juzych MS, Chopra V, Banitt MR, et al: Comparison of longterm outcomes of selective laser trabeculoplasty versus argon laser trabeculoplasty in open-angle glaucoma. Ophthalmology 111:1853--9, 2004
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Surv Ophthalmol 53 (6) November--December 2008
12. Latina MA, Sibayan SA, Shin DH, et al: Q-switched 532-nm Nd:YAG laser trabeculoplasty (selective laser trabeculoplasty): a multicenter, pilot, clinical study. Ophthalmology 105:2082--8, discussion 2089--90, 1998 13. Leske MC, Heijl A, Hussein M, et al: Factors for glaucoma progression and the effect of treatment: the early manifest glaucoma trial. Arch Ophthalmol 121:48--56, 2003 14. McIlraith I, Strasfeld M, Colev G, et al: Selective laser trabeculoplasty as initial and adjunctive treatment for openangle glaucoma. J Glaucoma 15:124--30, 2006 15. Melamed S: Ben Simon GJ, Levkovitch-Verbin H: Selective laser trabeculoplasty as primary treatment for open-angle glaucoma: a prospective, nonrandomized pilot study. Arch Ophthalmol 121:957--60, 2003 16. Migdal C, Gregory W, Hitchings R: Long-term functional outcome after early surgery compared with laser and medicine in open-angle glaucoma. Ophthalmology 101: 1651--6, discussion 1657, 1994 17. 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 89:1413--7, 2005
RAMULU AND PARRISH 18. Rachmiel R, Trope GE, Chipman ML, et al: Laser trabeculoplasty trends with the introduction of new medical treatments and selective laser trabeculoplasty. J Glaucoma 15:306--9, 2006 19. Ramulu P, Corcoran K, Corcoran S, et al: Utilization of various glaucoma surgeries and procedures in Medicare beneficiaries from 1995 to 2004. Ophthalmology 114:2265-70, 2007 20. Song J, Lee PP, Epstein DL, et al: High failure rate associated with 180 degrees selective laser trabeculoplasty. J Glaucoma 14:400--8, 2005 21. Weinand FS, Althen F: Long-term clinical results of selective laser trabeculoplasty in the treatment of primary open angle glaucoma. Eur J Ophthalmol 16:100--4, 2006 22. Zhao JC, Grosskreutz CL, Pasquale LR: Argon versus selective laser trabeculoplasty in the treatment of open angle glaucoma. Int Ophthalmol Clin 45:97--106, 2005 The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article. Reprint address: Richard K. Parrish, MD, Bascom Palmer Eye Institute, 900 NW 17 th Street, Miami, FL 33136. doi: 10.1016/j.survophthal.2008.09.002
Surv Ophthalmol 53 (6) November--December 2008
RAMULU AND PARRISH
III. ASKING THE RIGHT QUESTION IN LASER TRABECULOPLASTY: ‘‘WHICH PATIENT’’, NOT ‘‘WHICH LASER’’? Pradeep Y. Ramulu, MD,PhD,1 and Richard K. Parrish, MD2 1
Wilmer Eye Institute, Dept. of Ophthalmology, Johns Hopkins School of Medicine, Baltmore, Maryland, USA; and Bascom Palmer Eye Institute, Dept. of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, USA 2
The introduction of the Q-switched Nd:YAG laser for selective laser trabeculoplasty (SLT) has raised questions regarding its role in the management of patients with glaucoma. We believe that the most important issue regarding laser trabeculoplasty (LTP) treatment should not be which laser to use, but rather which patients would most benefit from its application. The merits and limitations of SLT have already been presented in the other articles (Argon Laser Trabeculoplasty: The Gold Standard and Selective Laser Trabeculoplasty: A Better Alternative) and, in our opinion, no clinically meaningful differences have been convincingly demonstrated between SLT and argon laser trabeculoplasty (ALT). Both ALT and SLT lower intraocular pressure (IOP) in patients with open-angle, pseudoexfoliation, and however, pigmentary glaucoma;3,4,8,12,14,15,17,21 currently reported randomized clinical trials that compare the results of the two laser systems are severely limited by small sample sizes, short duration of follow-up, or both.6,7,22
The Rebirth of LTP Irrespective of the relative merits of these two laser systems, ophthalmologists now widely use SLT for the treatment of glaucoma. Recent data from the United States and Canada show a remarkable resurgence of laser trabeculoplasty.18,19 Medicare data showed a 57% decrease in LTP between 1995 and 2001 after the introduction of several new classes of IOPlowering medicines.19 From 2002 to 2004, however, LTP volume doubled, corresponding to the time SLT became available for clinical use in North America. These data do not define why laser treatments were being performed, and the surge in LTP use may reflect increased use as primary therapy in newly diagnosed patients, as supplemental therapy in patients with advanced disease, as repeat procedures after other laser treatments, or as a replacement for medical therapy. The surge in LTP utilization makes a review of which patients are likely to benefit from this procedure particularly timely and relevant.
LTP in Advanced Disease: Not All It’s Made Out to Be The paradox of LTP is that it is most attractive to patients when it is least likely to affect their ultimate treatment course, and least attractive when it is most likely to affect their treatment course. A very low-risk laser treatment as an alternative to incisional surgery is likely to be accepted in patients with advanced disease, although this may not be in their best interests. Data from the Advanced Glaucoma Intervention Study (AGIS) is often used to justify the use of LTP in patients who have failed medical therapy, although its applicability to clinical practice today is limited. Two-thirds of AGIS patients who received LTP as an initial therapy avoided treatment failure at 5 years and nearly half avoided treatment failure at 10 years, but failures were registered only when a patient dropped below the same study eligibility criteria.1,2 Thus, many patients who had very little response to LTP were not considered failures, even though they may have received minimal IOP-lowering. Additionally, patients treated in AGIS were on maximal medical therapy at the time of enrollment, which predated the introduction of prostaglandin analogs, topical carbonic anhydrase inhibitors, and alpha adrenergic agonists. Study investigators were allowed to use newly introduced medications over the study period—so that some ‘‘successes’’ probably resulted from, or were at least prolonged by, the addition of newer, more effective medicines. Despite these caveats, failure rates were still significant in some patient subgroups. For example, 70-year-old study participants with a baseline IOP of 36 mm Hg had a nearly 90% failure rate at 5 years, and 70-year-old patients with an initial IOP of 27 mm Hg had a nearly 60% failure rate at 5 years. The IOP-lowering effects of LTP with current maximal medical therapy would likely be poorer than those reported by long-term follow-up in AGIS. Juzych retrospectively compared ALT and SLT in patients on maximum medical therapy and a baseline
653
VIEWPOINTS 3
IOP of 23 mm Hg. Success was defined as a 20% lowering of IOP.11 Both lasers failed in over 40% of patients by 1 year, and over 60% of patients by 3 years. Song used the same success criteria to evaluate the results of SLT in patients on maximal medical therapy and a mean IOP of 18.20 Over 90% failed to achieve 20% lowering of IOP at 14.5 months, and patients with lower IOP were more likely to fail. These data suggest that LTP is generally a poor option for patients on currently employed maximal medical therapy, particularly those who are well above target or requiring low final pressures. Patients with advanced disease who choose LTP should understand that long-term success is unlikely, and that incisional surgery will most likely be required.
LTP in Early Disease: Should We Be Using It More? Patient acceptance of LTP as initial treatment for early disease is often poor, even if this is an option that many ophthalmologists would choose for themselves. This will likely continue as long as patients believe that eye drops are the standard treatment for glaucoma, or until we can demonstrate more effective laser therapy. The Glaucoma Laser Trial and other studies have shown that LTP will lower IOP only 20% in about 60% of patients.4,6 After 2 years of follow-up, most patients required supplemental medical therapy, even to achieve a modest 20% lowering of IOP.4 Therefore, laser is likely only a temporary reprieve from eye drops. Additionally, LTP does not guarantee that the process of glaucomatous optic neuropathy will be halted.16 Both the ALT and medical groups had similar rates of disease progression in the GLT,4 and the Early Manifest Glaucoma Trial (EMGT) demonstrated that initial treatment with ALT and timolol maleate led to progression in a substantial percentage of patients.9,13 It is not surprising that patients often opt for medical therapy in view of their fear of the unknown and our guarded prognoses. The invariable need to spend time debunking myths regarding the use of lasers in ophthalmology often leads ophthalmologists to abandon the discussion altogether and perpetuates a vicious cycle that results in even lower rates of LTP for initial glaucoma management. We recommend abiding by the American Academy of Ophthalmology Preferred Practice Pattern and offering LTP, either as ALT or SLT, as a primary treatment for early disease.5 Even though some patients will respond poorly or not at all, most will at least benefit from a reduced load of IOP-lowering drops over the next several years, and some will have a prolonged period off medicines. Twenty percent
of patients in the GLT were able to remain off drops for a period of 7 years.3 Long-term success has been reported for SLT as well,21 and the drop-free window for SLT may be even longer if repeat treatments are effective. Our patients should not be denied this very low risk intervention with an opportunity for a prolonged period without eye drops, side effects, prescription charges, or trips to the pharmacy. It is important to remember which patients are unlikely to benefit from LTP, even as a primary treatment for early disease. These include those with little or no trabecular meshwork pigmentation (some evidence suggests that this is less true for SLT10); young patients; patients with certain types of glaucoma, such as extensive angle-closure, neovascular, inflammatory, ICE syndrome, or increased episcleral venous pressure; patients with very high IOP; and patients who are already well-controlled and asymptomatic on medical therapy. Selective laser trabeculoplasty has clearly renewed an interest in the use of LTP. We recommend channeling this interest toward identifying and treating patients who would most likely benefit from LTP, either SLT or ALT, and avoiding its use in those at high risk of failure.
References 1. ___: The Advanced Glaucoma Intervention Study (AGIS): 11. Risk factors for failure of trabeculectomy and argon laser trabeculoplasty. Am J Ophthalmol 134:481--98, 2002 2. ___: The Advanced Glaucoma Intervention Study (AGIS): 4. Comparison of treatment outcomes within race. Seven-year results. Ophthalmology 105:1146--64, 1998 3. ___: The Glaucoma Laser Trial (GLT) and glaucoma laser trial follow-up study: 7. Results. Glaucoma Laser Trial Research Group. Am J Ophthalmol 120:718--31, 1995 4. ___: The Glaucoma Laser Trial (GLT). 2. Results of argon laser trabeculoplasty versus topical medicines. The Glaucoma Laser Trial Research Group. Ophthalmology 97:1403--13, 1990 5. American Academy of Ophthalmology: Preferred Practice Pattern, Primary Open Angle Glaucoma, 2006, San Francisco, CA 6. Damji KF, Bovell AM, Hodge WG, et al: Selective laser trabeculoplasty versus argon laser trabeculoplasty: results from a 1-year randomised clinical trial. Br J Ophthalmol 90: 1490--4, 2006 7. Damji KF, Shah KC, Rock WJ, et al: Selective laser trabeculoplasty v argon laser trabeculoplasty: a prospective randomised clinical trial. Br J Ophthalmol 83:718--22, 1999 8. Francis BA, Ianchulev T, Schofield JK, et al: Selective laser trabeculoplasty as a replacement for medical therapy in open-angle glaucoma. Am J Ophthalmol 140:524--5, 2005 9. Heijl A, Leske MC, Bengtsson B, et al: Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol 120: 1268--79, 2002 10. Hodge WG, Damji KF, Rock W, et al: Baseline IOP predicts selective laser trabeculoplasty success at 1 year posttreatment: results from a randomised clinical trial. Br J Ophthalmol 89:1157--60, 2005 11. Juzych MS, Chopra V, Banitt MR, et al: Comparison of longterm outcomes of selective laser trabeculoplasty versus argon laser trabeculoplasty in open-angle glaucoma. Ophthalmology 111:1853--9, 2004
654
Surv Ophthalmol 53 (6) November--December 2008
12. Latina MA, Sibayan SA, Shin DH, et al: Q-switched 532-nm Nd:YAG laser trabeculoplasty (selective laser trabeculoplasty): a multicenter, pilot, clinical study. Ophthalmology 105:2082--8, discussion 2089--90, 1998 13. Leske MC, Heijl A, Hussein M, et al: Factors for glaucoma progression and the effect of treatment: the early manifest glaucoma trial. Arch Ophthalmol 121:48--56, 2003 14. McIlraith I, Strasfeld M, Colev G, et al: Selective laser trabeculoplasty as initial and adjunctive treatment for openangle glaucoma. J Glaucoma 15:124--30, 2006 15. Melamed S: Ben Simon GJ, Levkovitch-Verbin H: Selective laser trabeculoplasty as primary treatment for open-angle glaucoma: a prospective, nonrandomized pilot study. Arch Ophthalmol 121:957--60, 2003 16. Migdal C, Gregory W, Hitchings R: Long-term functional outcome after early surgery compared with laser and medicine in open-angle glaucoma. Ophthalmology 101: 1651--6, discussion 1657, 1994 17. 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 89:1413--7, 2005
RAMULU AND PARRISH 18. Rachmiel R, Trope GE, Chipman ML, et al: Laser trabeculoplasty trends with the introduction of new medical treatments and selective laser trabeculoplasty. J Glaucoma 15:306--9, 2006 19. Ramulu P, Corcoran K, Corcoran S, et al: Utilization of various glaucoma surgeries and procedures in Medicare beneficiaries from 1995 to 2004. Ophthalmology 114:2265-70, 2007 20. Song J, Lee PP, Epstein DL, et al: High failure rate associated with 180 degrees selective laser trabeculoplasty. J Glaucoma 14:400--8, 2005 21. Weinand FS, Althen F: Long-term clinical results of selective laser trabeculoplasty in the treatment of primary open angle glaucoma. Eur J Ophthalmol 16:100--4, 2006 22. Zhao JC, Grosskreutz CL, Pasquale LR: Argon versus selective laser trabeculoplasty in the treatment of open angle glaucoma. Int Ophthalmol Clin 45:97--106, 2005 The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article. Reprint address: Richard K. Parrish, MD, Bascom Palmer Eye Institute, 900 NW 17 th Street, Miami, FL 33136. doi: 10.1016/j.survophthal.2008.09.002