Laser Trabeculoplasty: ALT vs SLT
Argon laser trabeculoplasty (ALT) was introduced by Wise and Witter in 1979 for the treatment of medically uncontrolled glaucoma. Soon after its introduction, the efficacy and safety of this new technique was studied in a large multicenter prospective clinical trial funded by NEI, Glaucoma Laser Trial (GLT), in which eyes receiving ALT 360 degrees were compared with timolol monotherapy. From 2.5 to 5.5 years of follow-up, GLT demonstrated that trabeculoplasty was as efficacious as medical therapy in treating early POAG. Despite these favorable results, laser therapy did not replace medications as primary therapy in patients with POAG. This was partly due to attrition seen in efficacy over time and introduction of more effective glaucoma medications, namely prostaglandin analogues. The role of laser trabeculoplasty was limited and it was used either as an adjunctive therapy or as an intermediate step between failed medical therapy and surgical intervention. Interest in laser trabeculoplasty has been re-ignited in the past few years with the introduction of selective laser trabeculoplasty (SLT). A number of studies comparing ALT and SLT have shown similar IOP reduction with the two lasers. Because SLT appears to be less destructive histopathologically, a potential benefit of repeatability has been advocated.
Laser trabeculoplasty, both argon laser trabeculoplasty(ALT) and selective laser trabeculoplasty (SLT) types, is used to increase aqueous outflow facility through the trabecular meshwork (TM) in order to lower intraocular pressure (IOP) in cases of ocular hypertension and glaucoma.
Both ALT and SLT are indicated for the treatment of ocular hypertension, primary open angle and secondary open angle glaucomas, such as pseudoexfoliation and pigment dispersion glaucoma. Steroid induced glaucoma is another possible candidate for the procedure. Narrow angle glaucoma, where the trabecular meshwork is not obstructed by iris apposition or synechiae, may also benefit. If there is synechial closure, trabeculoplasty is not advised. Contraindications are inflammatory, iridocorneal endothelial (ICE) syndrome, developmental, and neovascular glaucoma. Laser trabeculoplasty is also not effective in angle recession glaucoma due to distortion of the angle anatomy and TM scarring. If there is a lack of effect in one eye, then it is relatively contraindicated in the fellow eye.
Elevated intraocular pressure is caused by resistance to aqueous outflow at the trabecular meshwork and Schlemm’s canal (SC) junction. The purpose of both ALT and SLT is to increase outflow facility through the trabecular meshwork in order to lower IOP.
The exact mechanism of action of laser trabeculoplasty is not well established. Various theories have been proposed as explanations for the increased aqueous outflow facility seen following successful trabeculoplasty, including mechanical, cellular, and biochemical theories.
The mechanical theory for ALT suggests that the laser electromagnetic energy is converted to thermal energy when it contracts the TM. Tissue contraction and scar formation result in mechanical stretching of the surrounding untreated regions of the meshwork , facilitating flow into SC with subsequent reduction in IOP. However, there is some evidence that the mechanical theory may be flawed 
The celluar theory for ALT is based on stimulation and increased cell division and repopulation of the trabecular meshwork.An increase in DNA replication and cell division following argon laser treatment have been demonstrated.
The biochemical theory for both ALT and SLT suggests a release of chemical mediators after laser treatment that increase aqueous outflow facility. ALT has been shown to increase macrophage recruitment at the site of treatment, resulting in remodeling of the extracellular matrix and increased outflow facility. ALT has also been shown to increase the release of interleukin-1 and tumor necrosis factor gene expression, which upregulate matrix metalloproteinase expression and remodeling of the extracellular matrix. It has been demonstrated that in cultured human trabecular meshwork irradiated with the SLT laser, interleukins 8, 1-alpha, 1-beta, and tumor necrosis factor alpha are upregulated. When the trabecular meshwork medium was added to Schlemm’s canal endothelial cells, the Schlemm’s canal endothelium underwent a 4-fold increase in fluid permeability. 
Studies conducted by Kramer and Noecker in eyes treated by ALT or SLT using scanning and transmission electron microscopy have shown coagulative damage, trabecular beam disruption, endothelial membrane formation on TM collapsed SC lumen, and intertrabecular debris in ALT-treated eyes, in contrast to eyes treated with SLT, in which minimal change was apparent on imaging. In post SLT eyes, general structure of TM was intact with no endothelial membrane formation and SC lumen was not collapsed. Less histopathological destruction observed with SLT has promoted repeatability of SLT over ALT. It is important to note that some earlier studies of ALT did not show the same crater-like damage seen in the previously mentioned study, but only mild coagulative damage. Less destruction seen with SLT laser system is secondary to its ability to selectively photolyse pigmented TM cells without inducing photocoagulation and collateral damage to non-pigmented cells or structures since its pulse duration is shorter (3 nsec) than the thermal relaxation time of melanin (1msec).
A detailed medical and ocular history is recommended prior to either form of trabeculoplasty.
The preoperative examination must include gonioscopic evaluation of the angle. This is routinely done at the slit lamp with a Zeiss, Posner, or Sussman lens, or with a standard single or triple mirror Goldmann type lens. Take note of whether or not the trabecular meshwork is visible without indentation since this is the structure that must be treated by trabeculoplasty. If the iris approach is somewhat steep, but the trabecular meshwork is revealed by rotating the eye towards the mirror, then there is probably sufficient angle area for treatment. The presence or absence of synechiae should be looked for, as synechiae may be a contraindication to the procedure. The degree of trabecular meshwork pigmentation should be noted, as this may influence the initial energy level chosen for trabeculoplasty.
Complete glaucoma evaluation should be done prior to recommending trabeculoplasty. This evaluation should include gonioscopy, intraocular pressure measurement, central corneal pachymetry, optic nerve examination and evaluation, and visual field testing.
Laser trabeculoplasty can be used as a primary treatment or as an adjunctive treatment to medications. In the U.S., ALT is seldom chosen as the first-line treatment for IOP reduction, while SLT is increasingly gaining popularity as a first-line treatment.
Approximately 30-60 minutes prior to either ALT or SLT, the eye should receive alpha adrenergic agonist, either apraclonidine or brimonidine, to decrease the risk of an immediate IOP spike. Topical anesthetic is used immediately prior to the procedure to anesthetize the eye for the laser contact lens.
In ALT, the argon green laser is typically set at a 50-micron spot size, 0.1-second duration, while the power setting can vary between 300-1000 mW, depending on response. The desired endpoint is blanching of the trabecular meshwork or production of a tiny bubble. If a large bubble appears, the energy should be titrated downward. The laser beam is focused through a goniolens at the junction of the anterior non-pigmented and the posterior pigmented edge of trabecular meshwork. Very posterior application of the laser beam tends to produce more inflammation, pigment dispersion, prolonged elevation of IOP and peripheral anterior synechiae (PAS). Many patients have satisfactory IOP reductions with treatment of 180º of the trabecular meshwork (approximately 40-50 applications). Treating 360º is associated with a higher incidence of pressure spikes, but additional 180 degrees of treatment can be performed later if treatment response is appreciated with initial treatment. The ALT procedure can also be performed with a diode laser. In this case, typical settings are 75-micron spot size, 0.1-second duration, and 600-1000 mW power.
In SLT, the laser is a frequency-doubled (532-nm) Q-switched Nd:YAG laser (Selecta 7000, Coherent Medical Group, Santa Clara, CA). The laser settings are fixed except for the power. Spot size is 400-microns and pulse duration is 3 ns. The large spot size results in low fluences (mJ/cm2). In more lightly pigmented angles, initial energy can be set at 0.8-1.0 mJ. In more heavily pigmented angles, the initial power can start off lower at 0.3-0.6 mJ. The aiming beam is centered over the trabecular meshwork and straddles the entire TM. Because precise placement of the laser beam is not necessary as it is in ALT, SLT is considered technically easier to do. The aiming beam will not be in sharp focus when the surgeon focuses on the trabecular meshwork to deliver treatment. The treatment endpoint is the appearance of small cavitation bubbles adjacent to the TM. Generally, 180 or 360 degrees are treated in a session. Laser spots can be placed contiguously or several spot sizes apart.
Surgical follow up
Similar to other laser procedures, it is routine to place a drop of apraclonidine or brimonidine in the eye after ALT or SLT to decrease the risk of a IOP spike.
Approximately 1 hour after both ALT and SLT, an intraocular pressure check is recommended. If the IOP is elevated beyond what is reasonable for the eye at one hour, the IOP must be treated and the patient should be seen the next day. The treatment required may be mild (i.e.—one hypotensive eyedrop) or aggressive (i.e.—systemic carbonic anhydrase inhibitors) depending on the eye’s circumstances. The follow-up interval will also depend on the severity of IOP spike. If the 1-hour postoperative IOP check is not elevated, the patient can be seen back in 1-2 weeks. The follow-up thereafter will depend on the patient and doctor, but a commonly followed routine is 4-6 weeks later and then every 3-4 months.
After ALT, a topical steroid is prescribed four to six times per day for 4-7 days, as the procedure is inflammatory. In SLT, it is more common not to prescribe any anti-inflammatory medications postoperatively, as it is felt that these agents may blunt the biological effects of the laser. Many surgeons will give a script for a non-steroidal anti-inflammatory to be used as needed if patient suffers ocular discomfort. Of note, a small prospective observer-masked study found that a 1-week course of topical prednisolone acetate 1% did not affect the IOP-lowering effect of SLT at 3 months. Patients are instructed to resume their usual antihypotensive drops immediately after the laser. A decision to discontinue drops can be made based on IOP response after 6-8 weeks.
In 2018, the Steroids after Laser Trabeculoplasty (SALT) trial intended to assess the impact of topical anti-inflammatory drugs after a SLT procedure in inflammation, pain and IOP reduction in 96 eyes. Three subgroup of patients submitted to SLT were studied: a first subgroup with only artificial tears, a second subgroup submitted to steroid therapy (prednisolone 4id 5 days) and a third subgroup submitted to NSAID therapy (ketorolac 0.5% 4id 5 days). 
Regarding IOP reduction and inflammatory outcomes, there was no significant difference between subgroups at 1 week post-SLT. At 6 weeks post-SLT, there was a trend for greater reduction in NSAID (-6.37 mmHg) and steroid (-5.85 mmHg) subgroups than in saline tears (-4.26 mmHg), albeit statistically non-significant (p=0.14). However, at 12 weeks post-SLT, there was a statistically significant greater reduction in IOP in the NSAID (-6.22 vs. -2.96 mmHg, p=0.002) and steroid (-5.21 vs. -2.96 mmHg, p=0.02) subgroups than in the saline tears subgroup. When comparing NSAID and steroid subgroup, there was a trend for greater reduction of IOP in the NSAID, although statistically non-significant (p=0.18).
Then, the SALT trial dispels the theory of an “inflammatory” mechanism of action in SLT with underlying reduction of efficacy when prescribing topical anti-inflammatories after SLT procedures. Furthermore, the SALT trial suggests the use of NSAIDs or steroids post-SLT procedures as auxiliary agents in SLT short-term efficacy.
A transient rise in IOP after laser trabeculoplasty is the complication of greatest significance to glaucoma patients undergoing this treatment. With 180° of ALT in the Glaucoma Laser Treatment Trial, a rise of > 5 mmHg was reported in 34% and a rise >10 mmHg was seen in 12% of patients. Of note, there was no perioperative alpha-adrenergic prophylaxis used in this trial. The frequency of IOP spikes is reduced by two-thirds with the use of prophylactic alpha-adrenergics. Postoperative IOP rise is more severe and frequent with higher energy levels, 360° treatments, posterior placement, heavy angle pigmentation, and a low preoperative outflow facility. Spikes are usually transient, occur within the first hour although they may be delayed, and most resolve with medical treatment by the next day.
In SLT prophylactically treated for a pressure spike, the reported rate of an IOP rise > 5 mmHg is around 10% or less and the rate of an IOP rise > 10 mmHg is around 3%. There are rare cases requiring trabeculectomy for sustained IOP increases after both SLT and ALT, and this possibility should be included in the informed consent process for either procedure.
Other complications seen with either form of trabeculoplasty, but which are popularly believed to occur more often with ALT although the literature does not show this to be true, are low-grade iritis and the formation of PAS. Corneal edema attributable to HSV reactivation has been reported following SLT. The thought is that the inflammatory cascade following laser contributes to virus reactivation. Hyphemas have also been reported.
There is only one randomized, clinical trial comparing SLT (n=89 eyes) and ALT (n=87 eyes) with one year of follow-up. See table for comparative results.
|ALT treatment within 1 year||5.7%||3.4%|
|SLT treatment within 1 year||4.6%||6.7%|
|Trabeculectomy within 1 year||8.0%||9.0%|
Efficacy of ALT and SLT
Selected Studies ALT
|Author||Number of Eyes/Dx||Follow Up (Years)||IOP Reduction(%)|
|Amon et al. 1990
|Lotti et al. 1995
|Sharma et al. 1997
Indian J Ophthal.
|Odberg et al. 1999
Acta Oph. Scand.
|168 POAG and PXF||8||32|
|Agarwal et al. 2002||40 POAG||5||30|
|BJO||39 POAG (on glaucoma medications)||5||13|
Selected Studies SLT
|Author||Number of Eyes||Follow Up||Mean IOP Reduction||% IOP Reduction|
|Gracner 2001||50 OAG||6 months||5.1||22.5|
|Melamed et al. 2003||45 OAG||6 -18 months||7.7||30|
|Lai et al. 2004||58 OAG/OHT||5 years||8.7||32|
|Clin Exp Oph.|
|Cvenkel 2004||44 OAG||1 year||7.1||27.6|
|McIlraith et al. 2006||74 OAG/OHT||1 year||8.3||31|
|Weinand et al. 2006||52 OAG||1 year||6||24.3|
|Eur J Glauc.||4 years||6.3||29.3|
Selected Studies Comparing ALT and SLT
|Author||Number of Eyes||Mean Follow Up||Mean IOP Reduction||P Value|
|Damji et al. 1999||36||6 Months||4.8 4.7||0.97|
|Damji et al. 2006||176||12 Months||5.9 6.04||0.84|
|Popiela et al. 2000||27||3 Months||2.85 2.63||0.84|
|Juzych et al. 2004||154 ALT||5 Years||% IOP Reduction||___|
|Ophthalmology||41 SLT||32% 31%|
The effect of either form of laser trabeculoplasty diminishes over time. In a retrospective analysis of longer term outcomes of SLT (n=41) compared to ALT (n=154), success was defined as an IOP decrease of at least 3 mmHg without additional medication or surgery. Success rate in the SLT group at 1, 3, and 5 year follow-up time points was 68%, 46%, and 32%, respectively, while in the ALT group it was 54%, 30%, and 31%. There was no statistically significant difference at any time point.
A prospective study that randomized patients to 180° of SLT versus ALT, found no statistically significant difference in IOP reduction between the two procedures. At 6 months, IOP decreased by 4.8±3.4 mmHg in the SLT group, and 4.7±3.3 mmHg in the ALT group. An extension of the previously mentioned study to 12 months showed no difference between IOP results, and this extension allowed additional medications, laser and surgery, as would occur in clinical practice.
ALT has been studied in a NEI-sponsored randomized multi-center trial, called the Glaucoma Laser Trial (GLT), which was published in the 1990s. The study compared 360° ALT to medical therapy with timolol 0.5% in newly diagnosed patients with primary open angle glaucoma. The GLT found that ALT lowered IOP by 9 mmHg compared to 7 mmHg with timolol alone. At two years, no further intervention was required in 44% of ALT eyes and in 30% of medication eyes. After seven years of follow-up, the ALT eyes had lower IOPs and less subjective field loss than medication eyes.
A study of prospectively enrolled SLT treated eyes (n=29) has been reported in a study from Hong Kong that had a similar design to the GLT in that one eye was randomized to 360° SLT while the other eye was given topical medication. The patients were recently diagnosed with POAG or OHTN with no previous treatment and were followed for 5 years after treatment intervention. After 5 years, 27.6% of the SLT eyes required additional treatment. No difference in IOP reduction was found between treatments. Mean IOP reduction was 32.1% in SLT eyes and 33.2% in medically treated eyes. Both this study and the GLT can be criticized for overestimating the effect of trabeculoplasty as a result of cross-over effect of the medications in the contralateral eye. In another study comparing 180° degrees of SLT treatment to latanoprost as initial treatment for newly diagnosed OAG and OHTN, in which the treatment was chosen by the patient, IOP percent decrease (~30%) was similar between groups with average starting pressures in the mid-20s. 
The LiGHT trial compared SLT to eye drops as first-line treatment for ocular hypertension and glaucoma and enrolled 718 patients. At 36 months, eyes randomized to SLT were within target IOP at a higher percentage of visits compared to the eye drops group (93% vs. 91.3%, respectively) and were less likely to require glaucoma surgery. SLT was found to be more cost-effective than an eye-drop first approach. Follow-up analyses from the LiGHT trial found that patients treated with medications first were more likely to experience rapid visual field deterioration.
After 360° of angle is treated by ALT, it is recommended that no further ALT is performed. Repeat ALT 1-year success rates vary from 21% to 73%.    With SLT it has been suggested that since there is minimal tissue alteration that the procedure can be repeated with good efficacy. In a study of 360° SLT after prior 360° SLT that was successful for at least 6 months (n=44 eyes), IOP reduction was seen with the second SLT treatment although the magnitude of IOP decrease was smaller, average decrease 5 mmHg after first SLT and 2.9 mmHg after second SLT. 
SLT performed in eyes with previous ALT is comparatively effective.   In one study, IOP was reduced by 5 mmHg or more in 40% of eyes without prior ALT and in 57% of eyes with prior ALT.
In different subgroups of patients, both ALT and SLT have been found efficacious when compared to treatment for POAG. In pseudoexfoliation SLT has not been found to be less efficacious in pseudophakic eyes compared to phakic ones. Whereas it is generally thought that ALT is better performed while an eye is phakic. 
One study compared the cost-effectiveness of generic topical prostaglandin analogues (PGAs) versus laser trabeculoplasty in patients with newly diagnosed mild POAG and found that PGAs provide marginally better value compared to laser trabeculoplasty when utilizing a 25 year time horizon. However, when assuming more realistic levels of medication adherence (25% less effective), laser trabeculoplasty became a more cost effective alternative.
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