Appendix

The selective laser trabeculoplasty laser and its role in rational glaucoma therapy

James B. Wise

Oklahoma City, OK, USA

Abstract

The selective laser trabeculoplasty (SLT) laser irradiates the trabecular meshwork with a 3-nsec pulse of light at 532-nm and a 400-µm spot size. Of 322 consecutive eyes treated with SLT, 257 met the follow-up criteria of primary open-angle (POAG) or low-tension (LTG) glaucoma, at least six weeks’ follow-up, no change in therapy after SLT, and one session of SLT. Most of the intraocular pressure (IOP) decrease occurred within six weeks of SLT, and the IOP decrease persisted for at least one year. In POAG, equal pressure decreases of 26-27% were seen in eyes with and without prior argon laser trabeculoplasty (ALT). In LTG, IOP decreased 21% to an average post-SLT IOP of 11.9 mmHg at one year. A 27% decrease in IOP occurred in 39 eyes with POAG receiving no topical glaucoma therapy before or after SLT. Surgery was required in 5% of eyes having SLT. Since POAG is due to trabecular meshwork (TM) impairment, and since current topical glaucoma medications do not improve TM function, ‘maximum rational glaucoma therapy’ consists of improving TM function with the SLT laser, improving uveoscleral outflow with a prostaglandin, and decreasing aqueous production with a long-acting betablocker, giving the drops five minutes apart in the morning. This gives 24-hour IOP coverage, excellent compliance, and the majority of IOP lowering possible with non-surgical therapy.

Introduction

Argon laser trabeculoplasty (ALT) for open-angle glaucoma (OAG) was first described in 1979,1 with confirming reports in 1981.2-4 Since then, ALT has been the subject of hundreds of reports and has been used millions of times throughout the world. ALT consists of spacing about 100 argon laser microburns of 50 µm diameter 360º around the trabecular meshwork (TM). Each microburn shrinks the collagen of the TM and creates a permanent contracted microscar. The collective shrinkage of these microscars reduces the circumference and therefore the diameter of the TM, pulling open the inter-trabecular spaces and increasing outflow.1 ALT has a failure rate of about 50% after five years, but is capable of controlling OAG for ten years or more in some eyes.5 Because ALT causes microscars in the TM, it has limited repeatability.

Address for correspondence: James B. Wise, MD, 3435 NW 56, Suite A 1010, Oklahoma City, OK 73112, USA

At the Crossings: Pediatric Ophthalmology and Strabismus, pp. 299–305

Proceedings of the 52nd Annual Symposium of the New Orleans Academy of Ophthalmology, New Orleans, LA, USA, February 14-16, 2003

edited by Robert J. Balkan, George S. Ellis Jr. and H. Sprague Eustis © 2004 Kugler Publications, The Hague, The Netherlands

The selective laser trabeculoplasty (SLT) laser uses a 532-nm wavelength, obtained from a frequency doubled q-switched neodymium-yttrium-garnet (Nd:YAG) laser, and a 3-nsec pulse to irradiate the TM with a 400-µm spot. Fifty of these confluent spots are spaced in 180º of the TM, or more recently, about 100 spots in 360º of the TM. This ultra-short pulse is only absorbed by pigment granules or pigment-containing cells in the TM,6 altering these structures so that they can be removed by macrophages. This cleans out the obstructing pigment and also stimulates re-population of the trabecular beams by new endothelial cells, increasing outflow. The very different characteristics of the two lasers are compared in Table 1. The SLT laser causes no scarring of the TM in experimental animal eyes or in human eyes.

In a prospective study, Damjii et al.7 showed that, in glaucomatous eyes with no prior laser therapy, ALT and SLT produced equal pressure reduction at three and six months post-laser. In eyes with prior failed laser trabeculoplasty, SLT was more effective than repetition of ALT. At six months, SLT produced a pressure reduction of 8.4 mmHg or 33.5% reduction from the pre-laser pressure, versus a pressure reduction of 2.6 mmHg or 9% produced by a second ALT. Latina et al.8 found SLT to be equally effective in eyes with and without prior ALT. In Norway, SLT has produced control of IOP in OAG for up to four years.9

My investigation of SLT concerns a consecutive series of 322 eyes with glaucoma, starting with the first eye treated in August, 2001. To be included in the analysis, eyes had to meet four criteria: they were required to have a diagnosis of either primary open-angle glaucoma (POAG) or low-tension glaucoma (LTG); at least six weeks’ follow-up; no change in medical glaucoma therapy after SLT, including eyes with no therapy before or after SLT; and one session of therapy with the SLT laser. These criteria were fulfilled by 257 eyes. Excluded were 65

Table 1. SLT laser versus ALT: various ratios

Table 2. SLT response over time, 257 eyes with POAG or LTG

eyes, including 34 in which medical therapy had been decreased or increased after SLT, 19 eyes which had had a second SLT (but which were included in the series after their first SLT), and 12 eyes which did not have POAG or LTG, including seven eyes with chronic angle-closure glaucoma, four with pseudoexfoliation glaucoma, and one eye with pigmentary glaucoma.

Most of the time, the SLT laser produces a more gradual decrease in IOP than ALT does. Table 2 shows the average IOP at various time periods after SLT. About 80% of the IOP decrease occurs by six weeks post-SLT, with the lowest IOPs being recorded at six months post-SLT. Because the IOP curve is nearly flat from six weeks to one year post-SLT, later tables contain a ‘last IOP’ column, which records the last IOP in the time period from six weeks to one year, allowing for inclusion of all patients in that category who have had at least six weeks of follow-up.

Table 3 presents the results of 85 eyes with no prior ALT, compared to 87 eyes which had had prior ALT. All ALT treatments were at least one year prior to the SLT, and many of the ALTs took place five to 15 years prior to the SLT treatment. The pressure decrease was very similar in absolute IOP decrease and percentage IOP decrease at all time periods in the table. Only two of the eyes with no prior ALT had a second SLT, and none had a trabeculectomy, while six of the eyes with prior ALT had a second SLT and seven went on to trabeculectomy. In general, the eyes with prior ALT had had glaucoma for many years and had more advanced glaucoma damage, so that a lower IOP was required for adequate control. If this low IOP was not achieved by the SLT treatment, then additional therapy was required. In both groups, the average IOP was lowered to the 16 mmHg range by SLT, which is low enough to be safe in eyes without advanced glaucoma damage.

LTG was treated with the SLT in 86 eyes (Table 4), 39 of which had prior ALT and 12 of which had prior trabeculectomy. The average IOP at one year was 11.9 mmHg and the average last IOP showed a 21% decrease. Only two of these 86 vulnerable eyes have so far gone on to trabeculectomy.

The SLT laser seems to be effective, even in eyes with prior trabeculectomy. Table 4 records 28 such eyes, with 23 eyes having had prior ALT as well. Twelve of the eyes had LTG and 16 had POAG. A 30% average IOP decrease was obtained, and only one of these eyes underwent another trabeculectomy.

Table 5 compares 180º or 210º treatment in 87 eyes, using an average of 67 SLT spots, to one-session 360º treatment in 77 eyes, using an average of 105 SLT spots. Prior ALT had been performed in 37 eyes in the first group and in 45 eyes in the 360º therapy group. This was not a randomized comparison, as eyes with prior ALT and/or more severe glaucoma were more likely to be treated 360º. In Table

Table 3. SLT response in eyes with and without prior ALT

5, the results were similar, but as time went by, many of the eyes treated 180º when the SLT laser was first obtained, according to the recommendations in the laser manual, required re-treatment. In my extensive experience with ALT, 360º treatment is much more likely to achieve long-term IOP control, and all eyes that achieved control for five to 20 years had 360º ALT. SLT treatment 360º causes less uveitis and pressure rise than 360º ALT. I now recommend 360º SLT treatment in most eyes requiring laser therapy. This spreads the outflow burden over the whole TM, rather than just over half of it. Very heavily pigmented TMs in pigmentary glaucoma and pseudoexfoliation glaucoma respond very well to ALT, which is preferred in these less common types of glaucoma.

Table 6 shows SLT results in eyes receiving no medical glaucoma therapy before or after SLT. Most of these eyes had received topical glaucoma therapy in the past, but were unable to tolerate it. Eyes intolerant of therapy were taken off therapy for at least three weeks if receiving beta-blockers or prostaglandins, and for at least one week if receiving short-acting medications such as brimonidine or topical carbonic anhydrase inhibitors (CAIs), before treatment with SLT. Most eyes had been off therapy for three months or more, and ten eyes had never received a drop of glaucoma therapy. A 23% IOP decrease occurred in eyes with LTG, and a 27% IOP decrease occurred in the three groups containing POAG alone or POAG plus LTG. Only one eye, from the never-medicated group, required medical therapy. It was well controlled by SLT plus latanoprost.

Eighteen eyes were re-treated with SLT. All had initial 180º treatment. Of these

Table 6. No glaucoma medical therapy before or after SLT. All LTG plus all POAG, POAG with or without prior ALT, LTG, and POAG with no ALT

18 eyes, five had the other 180º treated, while the other 13 eyes were treated 360º, including the area of previous SLT. An average IOP drop of 15% was obtained, and three eyes required trabeculectomy. In early retreatment after ALT, failure is common, while in eyes which have been successful for several years after ALT and then fail, re-treatment with ALT is usually successful again. Some eyes will simply not respond to laser treatment or re-treatment. The true test of SLT repeatability will come three or four years later, if SLT then shows late loss of control.

Of 357 eyes treated with SLT by me from August 2001 to the end of 2002, with no eyes being excluded, 18 required trabeculectomy. Four of these eyes were in the group of 12 excluded from IOP analysis because they did not have POAG or LTG, and this group included some very damaged TMs. Of the other 345 eyes, 14, or 4.1%, required surgery. Thirteen eyes had far advanced glaucoma, and while their IOP decreased, it did not reach the target IOP. Eight eyes had a poor response, with a post-SLT IOP greater than 24 mmHg. While not all eyes receiving SLT were surgical candidates, many did avoid surgery after SLT.

My experience with the SLT laser indicates that it is effective and well tolerated. It is usually effective in any glaucoma with an open angle, including eyes with prior ALT, prior trabeculectomy, and even some eyes with prior diode laser cyclophotocoagulation. Most of the IOP decrease occurs six weeks after SLT, and control persists for at least one year. After SLT, an average IOP decrease of 26% to an average of about 16 mmHg occurred in POAG, and an average IOP decrease of 21% to an average of 11.9 mmHg at one year occurred in LTG. In eyes on no glaucoma therapy before or after SLT, an IOP decrease of 27% occurred in POAG and of 23% in LTG.

The current medical therapy of glaucoma has several significant weaknesses. Although impairment of TM outflow is the primary cause of POAG, current medical therapy does not address this. The topical medications commonly used are either aqueous secretion inhibitors (beta-blockers, brimonidine, topical CAIs) or uveoscleral outflow enhancers (prostaglandins). Only the rarely used and poorly tolerated miotics increase outflow through the TM. Glaucoma therapy must be effective 24 hours a day, but many medications (betaxolol, brimonidine, topical CAIs, unaprostone) are short-acting and must be applied two or three times a day. If any such drops are missed (and they will be missed), then IOP spikes will occur. Only the non-specific beta-blockers (timolol, levobunolol) and major prostaglandins (latanoprost, bimatoprost, travaprost) are true once-a-day medications, and they should therefore be preferred.

When aqueous production, and therefore aqueous outflow through the TM, is severely reduced, as after cyclodialysis, TM function will become severely im-

paired. If a cyclodialysis is surgically repaired, restoring aqueous production, very high IOP typically occurs because of poor TM function. Current medical glaucoma therapy to some extent mimics the effect of cyclodialyis. The aqueous secretion inhibitors, especially in combination, markedly reduce aqueous production. The prostaglandins shunt the remaining aqueous humor around the TM and out through the uveoscleral outflow pathway. In addition, preservatives such as benzalkonium are toxic to the ocular surface and possibly to the TM as well. These theoretical considerations suggest that medical glaucoma therapy as currently practiced may cause TM damage over the years.

The SLT laser directly improves TM function and causes no scarring. Because of the problems with medical therapy discussed above, a strong argument can be made for using the SLT laser as the primary therapy for glaucoma, with medications being used only if SLT does not achieve the target IOP six weeks post-laser. Also, ALT and SLT are covered by insurance plans, while expensive eye drops are often not covered. Patients in the glaucoma age group are often taking expensive multiple systemic medications, and since their eye drops are irritating and do not improve their vision, compliance with medical glaucoma therapy may not occur.

SLT as primary therapy offers many advantages. It directly treats the primary glaucoma lesion which is TM impairment, it eliminates compliance problems, it eliminates the irritation and allergies of topical medications, and it eliminates toxicity from preservatives. It is effective 24 hours a day for years. In theory, cleaning out the TM and increasing aqueous flow through the TM may actually be beneficial to the TM.

If topical medical therapy does become necessary, I propose the concept of ‘maximum rational medical therapy’. This consists of increasing TM outflow with 360º SLT, increasing uveoscleral outflow with a major prostaglandin such as latanoprost, and reducing aqueous production with a long-acting beta-blocker such as levobunolol. This gives three synergistic modes of action with only two drops per day. The drops should be given five minutes apart each morning. This combination is usually well tolerated, not too expensive, and has excellent compliance. It will produce the majority of the IOP lowering obtainable with non-surgical therapy. I have many patients well controlled by this ‘maximum rational medical therapy’.

Once maximum rational therapy is being given, additional therapy can only consist of short-acting aqueous suppressors given two or three times a day. These are very expensive and unlikely to improve 24-hour control very much. Glaucoma is a life-time disease, and therapy must be affordable and tolerable. If the target IOP is not being obtained by ‘maximum rational medical therapy’ and the eye is showing evidence of progressive glaucoma damage, trabeculectomy should be considered rather than multi-drug, multi-dose additional medical therapy.

References

1.Wise JB, Witter SL: Argon laser treatment of open-angle glaucoma. Arch Ophthalmol 97:319322, 1979

2.Wise JB: Long-term control of adult open-angle glaucoma by argon laser treatment. Ophthalmology 88:197-202, 1981

3.Schwartz AL, Whitten ME, Bleiman B, Martin D: Argon laser trabecular surgery in uncontrolled open-angle glaucoma. Ophthalmology 88:203-212, 1981

4.Wilensky JT, Jampol LM: Laser therapy for open-angle glaucoma. Ophthalmology 88:213217, 1981

5.Wise JB: Ten-year results of laser trabeculoplasty: does the laser avoid glaucoma surgery or merely defer it? Eye 1:45-50, 1987

6.Latina MA, Park C: Selective targeting of trabecular meshwork cells: in vitro studies of pulsed and CW laser interactions. Exp Eye Res 60:359-372, 1995

7.Damjii KF, Shah KC, Rock WJ et al: Selective laser trabeculoplasty versus argon laser trabeculoplasty: a prospective randomized clinical trial. Br J Ophthalmol 83:718-722, 1999

8.Latina MA, Sibayan SA, Shin DH, Noecker RJ, Marcellino G: Q-switched 532-nm Nd:YAG laser trabeculoplasty (Selective laser trabeculoplasty): a multicenter, pilot, clinical study. Ophthalmology 105:2082-2088, 1998

9.Private communication to Lumenis, Inc