Modifications of the trabecular meshwork to increase the outflow of aqueous humor have evolved since Krasnov first reported the temporary lowering of intraocular pressure (IOP) after ‘trabeculo-puncture’ with the Q-switched ruby laser. Wise and Witter, extending the experimental work of Wickham and Worthen, popularized the argon laser technique that is used with modifications by most physicians today. Laser trabeculosplasty (LTP) increases aqueous humor outflow through the trabecular meshwork. In addition to argon laser trabeculoplasty, LTP is now also performed with solid-state and diode lasers, though research has shown argon laser trabeculoplasty (ALT) to be more effective. Clinically, LTP now involves the use of either 488 and 514.5-nm argon, 532-nm solid-state, or 810-nm diode wavelengths; differences in wavelength result in varying absorption and scattering effects.
The exact mechanism by which LTP lowers IOP is unclear. Mechanisms of action include mechanical and biomechanical theories. One proposed by Wise and Witter is that focal burns of the trabecular meshwork created with an argon laser beam of 50-μm spot size and 1000-mW power for 0.1 second cause local contraction of the meshwork tissues. A series of these burns placed 360° around the meshwork causes a circumferential shortening of the meshwork ring, pulling the inner layer of the meshwork toward the pupil and separating the trabecular sheets to increase the outflow of aqueous humor. Another is the mechanical distortion of the meshwork as a result of laser tissue modifications.
Biochemical or cellular responses of the meshwork to LTP include an increase in the replication rates of cells involved in maintaining trabecular meshwork outflow. Bylsma and co-workers found a 180% increase in trabecular cell division within 2 days of argon LTP. Parshley and co-workers investigated the extracellular matrix reaction to argon LTP and found, among other things, an increase in stromelysin expression. An increase in stromelysin activity should increase degradation of trabecular proteoglycans, in turn resulting in an increase in outflow facility Perhaps further work in these areas will find that a combination of these and other mechanisms is responsible for the clinically significant reduction in IOP seen after LTP.
The efficacy of LTP in lowering IOP has been well documented in the literature. Long-term studies, however, have shown that the efficacy of LTP decreases significantly over time, from 77% success rate at 1 year, to 49% at 5 years, and to 32% at 10 years ( Table 31-1 ). Additionally, because of the significant scarring ALT causes to the trabecular meshwork, repeat treatments are not recommended and have not proven successful clinically. Laser trabeculoplasty causes thermal coagulative damage to the uveoscleral meshwork, disruption of the the trabecular beams, and heat damage to the surrounding structural collagen fibers. This thermal damage is in part responsible for the inflammatory response, scarring of the trabecular meshwork tissue, peripheral anterior synechiae and IOP spike sometimes observed in eyes which have undergone LTP. Laser trabeculosplasty has proven successful in lowering IOP both as primary therapy and when used in conjunction with medications. Most patients continue to require medications after LTP, although one-third to one-half may be able to reduce their pre-LTP level of treatment. This may be helpful in relieving a patient of intolerable side effects from drugs such as miotics or carbonic anhydrase inhibitors (CAIs).
|Success rate 1 year after laser trabeculoplasty (%)||Success rate 4 years after laser trabeculoplasty (%)|
|Primary open-angle glaucoma||56||35|
|Aphakic primary open-angle glaucoma||51||22|
Much attention and discussion has been devoted to determining the most effective role of LTP in the glaucoma treatment paradigm that includes medical therapy and surgical intervention. Research has shown that the cost of medical therapy can be prohibitive for many patients, especially those on small fixed incomes, without medication insurance, or without adequate resources to purchase medications. Compliance with a medical regimen, especially one that includes daily use of multiple topical drops, has proven difficult for many patients. Extensive research between 1980 and 2004 has shown patient non-compliance rates of at least 25%, with most studies showing depressingly high non-compliance rates, and researchers have noted that patients are likely to discontinue long-term prescriptions as much as 76% of the time. The Glaucoma Laser Trial compared the efficacy of argon laser trabeculoplasty and timolol maleate 0.5% as initial therapy for primary open-angle glaucoma. The initial trial and subsequent follow-up study measured IOP reduction, visual field and optic nerve status in a total of 203 patients. Over an average of seven years of follow-up, eyes treated with ALT had 1.2 mmHg greater reduction in IOP ( P <0.001), and 0.6 dB greater improvement in visual field ( P <0.001). There was slightly more deterioration in the cup-to-disk ratio ( P =0.005) for eyes initially treated with topical medication. In a 2-year study comparing the efficacy of ALT and pilocarpine 2% in treating primary open-angle glaucoma, similar results were observed.
Different studies have yielded various success rates for LTP. In one study ( Fig. 31-1 ), initial IOP reductions of 7–10 mmHg were not maintained through long-term follow-up. At 5 years after treatment, only 30–60% of patients maintained adequate IOP control.
Argon LTP is effective in most forms of open-angle glaucoma. It is rarely effective in cases of trauma or inflammation and often aggravates inflammation. It may be effective after failed filtering surgery. Laser trabeculoplasty is more effective in older patients with POAG; the effect diminishes in patients younger than 40 years of age. Dramatically lowered IOP, sometimes greater than 20 mmHg, may occur in patients with pseudoexfoliation glaucoma, but the effect may be brief so these patients continue to require close monitoring. Pigmentary glaucoma also responds unpredictably and may have lower long-term success rates than POAG.
RETREATMENT OF A PREVIOUSLY LASER-TREATED ANGLE
Repeat argon LTP is often not advised. If considered for patients who have previously received treatment to 360° of the angle, the patient should be warned that filtering surgery may be required soon after the retreatment if it is unsuccessful.
It is clear that LTP can postpone filtering surgery in patients on maximum medical therapy who would benefit from and who achieve a 9–10-mmHg decrease in IOP. However, if a greater decrease is needed because of advanced glaucomatous damage, filtering surgery should be considered first.
SELECTIVE LASER TRABECULOPLASTY
In contrast to argon, solid-state, and diode laser pulse durations for LTP of 0.1 seconds, recent advances in trabeculoplasty have utilized lasers with short pulse durations of 3–10 ns. Selective laser trabeculoplasty (SLT), based on the principle of selective photothermolysis, relies on selective absorption of a short laser pulse to generate and spatially confine heat to pigmented targets within trabecular meshwork cells. Selective laser trabeculoplasty uses a Q-switched, frequency-doubled 532-nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser. Q-switching of the laser allows for a single, extremely brief, high-power light pulse to be delivered to the target tissue. The short duration of the pulse is critical in preventing collateral damage to the surrounding tissues. The energy level of available lasers varies between 0.2 and 1.7 mJ.
An advantage of SLT over LTP performed with larger pulsed lasers is that there is much less thermal damage to the trabecular meshwork. Preserving the trabecular meshwork may become important in the near future as surgical techniques are developed to operate directly on Schlemm’s canal or the juxtacanalicular trabecular meshwork, the region considered responsible for most of the outflow obstruction that causes open-angle glaucoma. Thermal LTP would preclude these patients from the new procedures, as their trabecular meshwork and Schlemm’s canal would be damaged.
The exact mechanism behind SLT remains unclear. Histopathologic evaluation of the trabecular meshwork in eyes treated with both ALT and SLT showed coagulative damage to the trabecular meshwork after ALT but not SLT. However, two main theories exist which attempt to explain the IOP-lowering effect. One mechanical theory states that SLT results in a stretching of the trabecular meshwork beams. Another states that the trabecular meshwork beams are separated and their mobility is increased following SLT. The biological theory states that SLT causes the release of chemical mediators and stimulates endothelial cell replication. In fact, it is likely that a combination of both mechanical and biological mechanisms causes the IOP decrease seen after LTP.
Preoperatively, the patient maintains their usual medication regimen. Additionally, the surgeon may choose to use pilocarpine 2% 30 minutes to 1 hour prior to the LTP procedure, which can help to further expose the trabecular meshwork and prevent IOP spikes. Topical α 2 agonists are the most effective preventive for postlaser IOP spikes. Topical fluorescein, often used in conjunction with Goldmann applanation tonometry, is a chromophore for most LTP wavelengths; therefore, preoperative IOP is measured with a tonometer not requiring fluroescein or a suitable time period is allowed to elapse between IOP measurement and laser treatment. The procedure is performed under topical anesthetic.
General preparation for LTP should be the same as that for any laser treatment of the anterior segment (see Ch. 29 ). While the patient is seated at the laser–slit-lamp system, a coated three-mirror Goldmann gonioscopy lens or a specially constructed trabeculoplasty lens such as the Ritch or Karichoff lens is attached to the eye with methylcellulose gonioscopy solution (e.g. Goniosol®). For SLT, a Latina or other suitable SLT lens is used to view the angle. The surgeon examines the entire circumference of the angle to ensure proper orientation in the trabecular meshwork and good visibility of the angle structures. In order to identify markers, it can be helpful to locate a pigmented portion of the trabecular meshwork or the scleral spur (see Ch. 6 ). The helium–neon aiming beam is focused onto the pigmented trabecular meshwork.
The laser delivery system is first calibrated to ensure a focal spot of 50 μm. This 50μm spot is used with 0.1 second exposure time. The power is titrated to the visible effect. In an eye with moderate or average trabecular pigmentation, the initial power of 400–500 mW is increased in 100-mW increments (to a maximum of 1000 mW) until a slight blanching effect occurs or small bubbles form at the point of laser impact. Less energy is required for more heavily pigmented angles. Reducing the power below 500 mW in lightly pigmented eyes, however, seems to decrease the treatment’s effectiveness.
Orientation may be difficult in patients with little or no pigment in the angle. The surgeon should clearly identify the region between the anterior border of the ciliary body and Schwalbe’s line. The middle of the trabecular meshwork lies near the midpoint of this region. If possible the scleral spur should be identified and visualized 360°. Pigmentation anterior to Schwalbe’s line may resemble trabecular pigmentation and confuse the surgeon. Identifying and following the scleral spur helps to eliminate this confusion. The lens is held so that the laser beam is focused clearly as a sharp circular spot. Asking the patient to gaze toward the mirror (e.g., if the mirror is to the right during the examination the patient is asked to look to the right) may assist in viewing the angle, especially when the iris is convex. Poor or astigmatic focusing diffuses the laser energy and increases tissue damage unnecessarily. Although treatment at the level of the ciliary body, scleral spur, posterior meshwork, and anterior meshwork have all been proposed, fewer complications and equal effectiveness result from treating at the junction of the trabecular pigment band and anterior meshwork ( Fig. 31-2 ).
Laser applications are then positioned 3–4° apart so that approximately 20–25 spots are created per quadrant. Debate continues over how many quadrants should be treated. There is less postoperative inflammatory response and fewer pressure spikes when there are fewer spots. Most physicians advise initial treatment of 180°. If only 180° is treated, the patient is re-evaluated in 4–6 weeks. If the IOP drop is inadequate, the remaining 180° is treated. If the IOP drop is adequate, the patient is observed until a lower IOP is necessary, at which time the second 180° is treated. A few patients will achieve a substantial drop in IOP with a second 180° treatment, even though treatment of the first 180° was disappointing. When considering eyes that have had the second 180° treated, there appears to be little difference between the long-term efficacy of initial treatment of 180° and 360° ( Fig. 31-3 ).
The patient should be closely monitored on the day of surgery and on the first postoperative day for pressure spikes and iritis. The final effect of LTP may not be evident for 4–6 weeks.
Selective laser trabeculoplasty.
The 400-μm spot size – compared to the 50-μm spot size of ALT ( Fig. 31-4 ) – covers most of the angle structures and iris root. However, the short pulse duration enables selective absorption by the intracellular melanin target. The other, non-pigmented, tissues irradiated by the beam are not affected.
The energy level for SLT treatment is set initially at 0.8 mJ. A test pulse is delivered at the set energy. If the surgeon visualizes bubble formation like that typically associated with ALT, pulse energy is decreased in 0.1-mJ intervals until minimal bubble formation is detected. Once the suitable pulse energy is determined, treatment proceeds in single-pulse mode. In eyes with varying degrees of trabecular meshwork pigmentation, more bubble formation may be observed intermittently throughout the procedure. If more bubble formation occurs, pulse energy is decreased appropriately.
Recommended procedure protocols for SLT are in flux and vary from treatment of 180° with 50 spots, to 360° with 100 spots, evenly spaced over the trabecular meshwork for patients with most open-angle glaucomas. The pressure-lowering effect is improved with 360° treatment. An exception is treating patients with pigmentary glaucoma. In pigmentary glaucoma, the trabecular meshwork surface is covered with pigment, which absorbs the SLT energy, thermally affecting the underlying trabecular meshwork and becoming dispersed into the anterior chamber, both causing pressure spikes. Therefore it is recommended that SLT treatment for patients with pigmentary glaucoma be performed in multiple sessions, treating 90° of the angle at each, and using minimal energy with no bubble formation.
The extent to which the trabecular meshwork should be treated with SLT remains controversial. Though the standard treatment regimen for SLT uses 50 spots at 0.6–1.0 mJ over 180° of trabecular meshwork, Chen and colleagues found that SLT with 25 laser spots on 90° of trabecular meshwork has a similar pressure-lowering effect. More recently, Song and co-workers found failure rates of 68–75% in patients who underwent 180° SLT (with failure defined as IOP decrease of <3 mmHg or IOP decrease of <20%). Nagar, comparing treatment with 90°, 180°, and 360° SLT on 28, 34, and 31 eyes respectively, found significantly greater reduction in IOP in eyes treated with 360° SLT; there was also a significantly greater incidence of adverse effects in this treatment group, including patient discomfort, anterior chamber activity, and pressure spikes.
Postoperative treatment protocols are also in flux. If the biological theory of SLT is correct, mild postoperative cell response is welcome and postoperative steroids are not used. However, most surgeons prefer a modification of the following regimen.
Immediately after completion of the procedure, and after the treated eye has been thoroughly rinsed, 1 drop of prednisolone 1% is instilled. The patient instills 1 drop of prednisolone 1% every 2 hours or q.i.d. on the same day as the procedure. Prednisolone is reduced to q.i.d. 1 day post LTP. The patient may return for a slit-lamp examination and evaluation of IOP response to LTP the day after the procedure. The surgeon evaluates the eye for inflammation and IOP elevation. If IOP response is reasonable, and inflammation mild or non-existent, prednisolone remains at q.i.d. on the second and third day post LTP, and is reduced to b.i.d. the fourth and fifth day post LTP. After 5 days, prednisolone is discontinued. Others use a mild steroid like fluoromethalone 0.1% (FML™) or loteprednol 0.5% (Lotemax™) q.i.d. for 1 week. The patient may be seen 1–2 hours after the treatment to monitor for IOP elevation, and if the eye is quiet and with reasonable IOP, the patient may be seen after several weeks. Many surgeons do not use any anti-inflammatory agents after SLT since the postoperative inflammation is rarely a problem and the authors have noted a less vigorous IOP reduction when anti-inflammatory agents are used.
The patient returns for an evaluation 1 month and 3 months after the procedure to evaluate and monitor IOP. The patient’s preoperative medication regime continues unaltered postoperatively, including in the immediate postoperative period. Maximum effects from ALT may not be seen until 6 weeks whereas maximum response to SLT may take as much as 3 months. Repeat SLT should not be performed until at least 3 months after the initial SLT to be sure that enough time has been given for the response to take place. If the IOP decreases enough, the surgeon may decide to decrease the patient’s medication use.
Kramer and Noecker first studied the effects of ALT and SLT on human eye-bank eyes. Evaluation of the trabecular meshwork of eyes which had undergone ALT revealed crater formation in the uveal meshwork, coagulative damage with disruption of the collagen beams and fibrinous exudates, and lysis of endothelial cells. By comparison, the trabecular meshwork of eyes which had undergone SLT showed no evidence of coagulative damage or disruption of the corneoscleral or uveal trabecular beam structure. Selective laser trabeculoplasty therefore preserves the meshwork for future medical, laser, or surgical intervention, if necessary. Additionally, eyes which had previously undergone failed ALT demonstrated a significantly greater reduction in IOP when treated with SLT than those treated with repeat ALT.
A preliminary clinical trial studying the safety and efficacy of SLT in treating primary open-angle glaucoma demonstrated a mean IOP decrease of 30% at 1 day, 27% at 8 weeks, and 29% at 49 weeks. No serious adverse effects were reported. Melamed and co-workers performed the procedure in 45 eyes of 31 patients, and recorded a decrease in IOP from 25.5 ±2.5 mmHg to 17.9 ± 2.8 mmHg, or 30%. No serious adverse effects were related to SLT. Several multicenter, prospective clinical trials have been conducted which further demonstrate the efficacy and safety of SLT. Pressure reductions ranged from 2.85 to 10.6 mmHg with follow-up periods of 6 weeks to 26 months. Subsequent studies have compared the safety and efficacy of ALT and SLT in treating various types of glaucoma.
In their comparison of the long-term success rates of SLT and ALT, Juzych and co-workers found that both techniques are similarly effective in lowering IOP over a 5-year follow-up period. Likewise, in a clinical study of 40 patients, 20 of whom were treated with SLT (180°) and 20 with ALT (180°), Martinez-de-la-Casa and colleagues found that at 6 months following treatment, pressure reduction was similar in both groups. In addition, the energy released during treatment and inflammation in the anterior chamber in the immediate postoperative period was significantly lower for the SLT procedure, as was pain reported by the patients during treatment. Similarly, in a prospective trial with a follow-up period of 36 months, there was no significant difference between IOP reductions in patients who had undergone ALT and those who had undergone SLT.
Contraindications to ALT include inadequate visualization of the trabecular meshwork, hazy media, closure of the iridocorneal angle, corneal edema, uveitic glaucoma, juvenile glaucoma (usually), patient age of 35 years or less, and a need for IOP-lowering greater than 7–10 mmHg.
While inflammatory glaucoma is considered a contraindication for ALT, in a study of 130 eyes of 87 patients with allergic, uveitic, and post-transplantation diagnoses, IOP was reduced by 4 mmHg or more in 56% of eyes treated with SLT.
A heavily pigmented trabecular meshwork, especially combined with previous ALT, may be a contraindication to SLT. In a retrospective, non-comparative case series of 4 eyes which presented with IOP spikes after undergoing SLT, Harasymowycz and colleagues found that all eyes were characterized by heavy trabecular meshwork pigmentation, and 50% had previously undergone ALT. The authors suggest that eyes with heavy pigmentation and a history of previous ALT should be considered at increased risk for IOP spikes post SLT.
AS INITIAL THERAPY
The Glaucoma Laser Trial demonstrated the efficacy of ALT as initial therapy for open-angle glaucoma. Selective laser trabeculoplasty may prove equally effective as initial therapy. To evaluate the potential of SLT as a replacement for medications, Francis and colleagues performed SLT inferiorly on 66 eyes of 66 patients with medically controlled open-angle or exfoliative glaucoma. At 12 months, 87% of patients achieved a significant reduction in medications (mean reduction at 12 months: 1.5), while maintaining a previously determined target IOP. Further study is needed to determine if clinically significant IOP control is possible using SLT as primary treatment.
PREDICTORS OF OUTCOME
While it has been suggested that pigmentation may contribute to determining the outcome of SLT, several studies have shown otherwise. Hodge and associates evaluated whether any characteristics of 72 patients, including age, race, sex, pigmentation, or other risk factors for glaucoma, were predictors of successful SLT at 1 year (successful SLT defined as a reduction in IOP = 20%). Only baseline IOP was a significant predictor of successful SLT.
APHAKIC AND PSEUDOPHAKIC OPEN-ANGLE GLAUCOMA
Laser trabeculoplasty is generally less effective in aphakic eyes, but when it is successful the decrease in IOP in aphakic open-angle glaucoma is similar to that for chronic open-angle glaucoma (average, approximately 7 mmHg). Preliminary data indicate that LTP may be as effective in pseudophakic eyes with posterior chamber lenses as it is in phakic eyes. Cataract surgery after LTP seems not to have a deleterious effect on IOP control. Laser trabeculosplasty performed before cataract surgery may be more effective than that performed afterward.
Intraocular pressure elevation
Few complications are associated with LTP ( Table 31-2 ). Up to 50% of patients, however, experience a transient IOP spike similar to that seen after laser iridotomy (see Ch. 30 ) and respond to the same therapeutic approach. Pretreatment and/or post treatment with most of the antiglaucoma agents have all helped reduce the spike but topical α agonists (apraclonidine, brimonidine) seem to be the preferred agents because of their effectiveness and lack of side effects with short-term use. Intraocular pressure spikes increase with the number of laser applications – which is one argument for treating only 180° of the angle initially. A pressure spike may be delayed for 2 hours but almost always appears within 3 hours. Patients have had loss of central acuity, which might have been related to a pressure spike, and although rare, central vein occlusion has reportedly occurred within 24 hours of LTP.