SELECTIVE LASER TRABECULOPLASTY 

Guest author

GULAFSHAN FATIMA

Ajmal Khan Tibbiya College 

Aligarh-India

INTRODUCTION 

Selective laser trabeculoplasty (SLT) is an effective treatment option for reduction of intra-ocular pressure (IOP) in patients with ocular hypertension.

SLT is at least as effective as Argon Laser Trabeculoplasty at lowering IOP in many forms of Glaucoma. SLT decreases IOP fluctuation and can be successfully used as a primary or adjunctive therapy for management of both early and advanced Glaucoma. Limited evidence suggests that SLT is cost effective as primary therapy for patients with Glaucoma.

[FURTHER READING: https://ourgsc.blogspot.com/search?q=selective]

BASIC PRINCIPLES

SLT is based on the principle of selective laser thermolysis.

According to this concept, radiation energy applied to trabecular meshwork (TM) selectively targets pigmented cells without causing significant collateral thermal damage.

The SLT base is a 532-nm frequency-doubled Q-switched Nd:YAG laser with a fixed spot size of 400-nm and duration of 3 nanoseconds.

The power range for treatment varies from 0.4-1.4 mJ.

These parameters spare surrounding non-pigmented cells as the pulse duration is significantly shorter than thermal relaxation time (1 microsecond) of melanin granules contained in pigmented TM cells.

MECHANISM OF ACTION

The exact mechanism by which IOP is lowered by SLT is unknown and probably multifactorial.

SLT appears to lower IOP by increasing trabecular outflow.

Proposed mechanism of action include: structural alteration inflammatory response with remodeling of extracellular matrix and stimulation of TM cell proliferative changes.

SLT IN SPECIFIC TYPES OF GLAUCOMA

SLT is useful in various types of glaucoma including:

Normal tension glaucoma

Pseudoexfoliative glaucoma

Pigmentary glaucoma

Steroid induced glaucoma

Normal tension glaucoma:

SLT can have a significant IOP lowering effect in patients with NTG, albiet with a smaller absolute reduction in IOP. The use of SLT in NTG has been limited historically because of the fact that the most reliable predictor of success is a higher preoperative IOP. Lee et. al. treated 45 NTG eyes with 360-degree SLT after 1 month of medication washout, the IOP was significantly reduced.

Steroid induced glaucoma:

Although there is limited data available, SLT appears to effectively lower IOP in patients with steroid induced glaucoma and may even help prevent IOP spikes from subsequent steroid treatment.

SLT was found to produce a 35.9% drop in IOP over 12 months of follow up in patients with steroid induced glaucoma.

CONCLUSIONS

SLT is an effective treatment option for the reduction of IOP in patients with ocular hypertension and open angle glaucoma. Based on published data SLT is at least as effective as ALT and medications.

There is evidence that SLT can successfully be repeated to achieve additional or recurrent IOP reduction in eyes that had a modest response to initial treatment.

Adverse effects are uncommon after SLT. The most common complications being mild and transient rise in IOP immediately following the procedure.

SLT can be a useful and effective treatment option when medications are ineffective or are causing unwarranted side-effects.

DIRECT SELECTIVE LASER TRABECULOPLASTY (DSLT)

Selective Laser Trabeculoplasty (SLT) is an effective first-line treatment option for patients with open-angle glaucoma and normal-tension glaucoma.

Alcon has improved the delivery system of SLT machines with the development of the Voyager Direct Selective Laser Trabeculoplasty (DSLT) system.

Voyager™ DSLT is designed to automatically deliver 120 laser pulses directly through the limbus to the trabecular meshwork, thereby improving aqueous outflow and reducing intraocular pressure.

The GLAUrious Study comparing DSLT and SLT did not find inferiority of the DSLT procedure at 6 and 12 months of follow-up.

The study demonstrated that DSLT with the Eagle device is effective in providing a clinically meaningful reduction in IOP at 6 months that is sustained out to 12 months.

The protocol included DSLT: 120 shots, 3 ns, 400 µm spot size, energy 1.4–1.8 mJ delivered at the limbus over 2 s. SLT: approximately 100 shots, 3 ns, 400 µm spot size administered 360 degrees at the limbus using any gonioscopy lens, energy 0.3–2.6 mJ.

According to the authors, a sample size of 164 is sufficient to detect a non- inferiority margin of 1.95 mm Hg for change from baseline IOP.

REFERENCE:

Congdon N, Azuara-Blanco A, Solberg Y, Traverso CE, Iester M, Cutolo CA, Bagnis A, Aung T, Fudemberg SJ, Lindstrom R, Samuelson T, Singh K, Blumenthal EZ, Gazzard G; GLAUrious study group. Direct selective laser trabeculoplasty in open angle glaucoma study design: a multicentre, randomised, controlled, investigator-masked trial (GLAUrious). Br J Ophthalmol. 2023 Jan;107(1):62-65. doi: 10.1136/bjophthalmol-2021-319379. Epub 2021 Aug 25. PMID: 34433548; PMCID: PMC9763163.

LASER TRABECULOPLASTY

INTRODUCTION:

A number of lasers have been used to target the anterior chamber angle and achieve reduction in IOP. This laser induced modification of the angle is known as Laser Trabeculoplasty (LTP). Some of the lasers which have been used for LTP include: the argon (peaks at 488 nm and 514 nm); krypton (647.1 or 568.2 nm); diode (810 nm); and the continuous wave, frequency doubled Nd:YAG (532 nm) laser. The Glaucoma Laser Trial and the Glaucoma Laser Trial-Follow-up Study showed that eyes initially treated with argon laser trabeculoplasty (ALT) had lower IOP and better visual field and optic disc status than their fellow eyes treated initially with topical treatment.

ARGON LASER TRABECULOPLASTY (ALT):

ALT was first described by Wise and Witter in 1979. Usually 50 spots over 180⁰ of 50 micron spot size, 0.1 second duration and an average power ranging from 400-600 mW are given.

The precise mechanism by which LTP works is not known. It has been suggested that the ALT scars induce tightening of the trabecular beams around the scar with widening of the spaces between them, thus enhancing outflow. In ALT, light energy enters the tissue faster than it can dissipate, resulting in a rise of temperature and thermal energy which spreads from the beam focus. ALT also destroys a viable area of the trabecular meshwork (TM), creates a crater in this tissue and causes depopulation of all normal structures. Studies have shown that ALT causes increased division of trabecular cells and remodeling of the juxtacanalicular extracellular matrix. However, over time the biological changes lead to the formation of a fibrocellular membrane over the trabecular meshwork, resulting in decreased aqueous outflow and failure of LTP. 

Previous LTP also increases the probability of bleb encapsulation following subsequent trabeculectomy. ALT produces significant tissue disruption and coagulative damage to the TM. This limits the reapplication of LTP again in an effective manner. Complications reported with ALT include: transient IOP spikes (6.3-54%), peripheral anterior synechiae (12-47%) and uveitis. 

SELECTIVE LASER TRABECULOPLASTY:

In 1995 Latina and Park reported that a 532 nm, frequency-doubled Q-switched Nd:YAG laser could selectively cause cytotoxicity and cell death of TM cells without any apparent changes in the adjacent non-pigmented cells. This came to be known as Selective Laser Trabeculoplasty (SLT).

SLT is based on the principle of “selective thermolysis”, whereby only pigmented trabecular cells are targeted by the laser. There is no associated structural or coagulative damage to the TM. Selective thermolysis is effective as it targets intracellular chromophore (melanin) sparing the nonpigmented cells. Transmission electron microscopy following SLT demonstrated fracture of melanin granules, rupture of lysosomal membranes in pigmented cells and absence of ultrastructural damage in neighboring nonpigmented cells. In the areas where the SLT laser had struck, beams of TM were intact except for rare crack-like defects between preserved beams. There was total absence of coagulative damage. The endothelium was intact, with a few vacuolated cells. Many pigmented trabecular cells contained disrupted, fragmented intracytoplasmic pigment granules and others also had intact granules in their cytoplasm.

SLT delivers light energy in extremely short nanosecond pulses, 8 orders of magnitude shorter than that of ALT. Cooling from dissipation does not occur and temperature rise is very rapid. This causes disintegration of a small volume of tissue into a collection of ions and electrons called "plasma". Vaporization of water around melanosomes at temperatures around 150⁰C causes formation of small, short duration microbubbles which disintegrate cellular structures by micro-explosions in the region of pigmented TM cells.

SLT also causes increased secretion of cytokines by TM endothelial cells. This could theoretically be linked to the IOP lowering effect of SLT. Other mechanisms suggested for SLT include: proliferation of trabecular endothelial cells, release of cytokines, inflammation (recruitment of macrophages) and phagocytosis. SLT causes nuclear translocation of transcription factors and an induction of vasoactive agents (e.g. cytokines) followed by macrophage recruitment. IOP then decreases even as the repair process begins.

Following SLT there is also significant elevation in the aqueous concentration of lipid peroxide. Such free oxygen radicals can cause inflammation and prove to be a double edged sword during SLT.

SLT uses a 532 nm, frequency-doubled, Q-switched Nd:YAG laser with a 3 nanosecond pulse and 400µ  beam diameter. The size of the aiming beam is much larger than the typical 50µ size ALT beam. This allows the SLT beam to cover the entire width of the TM, thus accurate aiming is less critical. The TM is a strip of tissue approximately 44 mm long and 0.3 mm wide. The larger spot size is less harmful to ocular tissue because the energy is not concentrated in a small area. The low fluency of energy safely and effectively diffuses over a large area.

The energy density of a typical ALT pulse of 800 mW, 0.1 second and 50 micron spot size is roughly 4 million mJ/cm2. Contrarily, an SLT pulse of 0.8 mJ and 400 microns spot size delivers energy of 637 mJ/cm2. This shows that each SLT pulse delivers less than 0.1% total energy compared to ALT.

The procedure with the diode laser is similar: a 50–75-µm laser beam is focused through a goniolens with a power setting of 600–1000 mW and duration of 0.1 second.

The patient is pre-treated with an alpha-agonist to prevent post-laser spike in IOP. Topical anesthesia and a Goldmann 3-mirror or Latina SLT Lens is used. A low power beam is focused at the pigmented TM. Power is usually set at 0.8 mJ per pulse initially. In heavily pigmented eyes, it can be lowered further. About 50 non-overlapping spots are applied to 180 degrees of the angle circumference. Unlike ALT where blanching or large vaporization bubbles are produced, the endpoints of SLT are more subtle. Some authors increase the energy to obtain small “champagne bubbles” and then decrease power by 0.1 mJ without any subsequent visible changes. Others strive to achieve these tiny bubbles during 50% or more of applications. 

Post-laser anti-Glaucoma medications are continued until the IOP becomes stable. Topical steroids/NSAIDs are also added to control inflammation. However, some suggest that postlaser inflammation might help in lowering of IOP.

Some practitioners apply 100 shots over 360⁰. However, studies have shown that success rates do not differ significantly between 180⁰ and 360⁰ SLT. However, 90⁰ of SLT is not as effective as 180⁰. Studies report latanoprost to be more effective than 180⁰ SLT.

Compared to ALT, SLT is better tolerated with less discomfort and post-laser inflammation.

However, Samples et al performed a meta analysis of 145 papers and concluded there is no evidence of superiority of any particular form of LTP.

Indications for SLT include:

1. In medically non-compliant patients.

2. Those who cannot tolerate medications.

3. As an adjuvant treatment to reduce the number of anti-Glaucoma medications.

4. Those with uncontrolled IOP despite previous ALT.

5. As a primary modality to treat OAG, pxg, pigmentary Glaucoma, NTG, OHT, juvenile glaucoma, aphakic/pseudophakic Glaucoma.

Side effects of SLT:

1. Post-laser IOP spike (0-27%)

2. Hyphema

3. Upto 50% pts show mild-moderate uveitis lasting for about 24 hours and managed with steroid/NSAID topically

4. Corneal edema (resolved with topical anti-inflammatory agents)

5. Transient corneal endothelial changes.

Results:

IOP reductions following SLT ranged from 2.1-10.6 mmHg with follow-up ranging from 4 weeks to 72 months. Reductions in IOPs ranging from 18-40% over a 6 to 12 month follow-up have been reported. Most of the IOP lowering effect has been reported in the first week with some additional effect during the next 4-6 weeks.

Success rates in African-American and white subjects were similar.

Baseline IOP was positively associated with better IOP reduction following SLT.

Patients with thinner corneas (<555m) also demonstrated better IOP control atleast for the first 30 months after SLT.

Pigmentation of the angle, type of Glaucoma, age, sex, past history of ocular surgery, phakic status, diabetes were not associated with effectiveness of the procedure.

Chen did report an early better reduction of IOP associated with pigmentation and pseudoexfoliation.

Cross-over effect of SLT:

SLT appears to have a statistically significant IOP lowering effect in the contralateral untreated eye. An, as yet known, biologic effect could be responsible.

In case IOP is lowered in the treated eye, it gives a probability of SLT being effective in the other eye too. However, these effects have not been studied well.

Retreatment of SLT:

Retreatment is defined as treatment over a previously treated area of TM. As the SLT laser beam bypasses surrounding tissue (since it targets pigmented cells only) leaving it undamaged, theoretically SLT can be repeated several times in eyes in which the IOP has risen to pretreatment levels or has not met the target IOP goal. Studies have found that repeat SLT treatment is associated with further IOP lowering and is safe and effective.

The "SLT/MED study" was conducted to compare SLT with medications.IOP reduction was similar in both arms after 9 to 12-months follow-up. More treatment steps were necessary to maintain target IOP in the medication group, although there was not a statistically significant difference between groups. These results support the option of SLT as a safe and effective initial therapy in open-angle glaucoma or ocular hypertension.

MICROPULSE DIODE LASER TRABECULOPLASTY:

In this technique, 200 ms long bursts comprising of 100 micropulses are applied to 200 µm spots on the TM. There is an interval of 1.7 ms between each micropulse. About 70 spots are applied over 180⁰. With this procedure, an IOP lowering of more than 20% was achieved in 60% eyes after 1 year of follow up.

PATTERNED LASER TRABECULOPLASTY:

PLT is based on the PASCAL technology for retinal photocoagulation. The PASCAL system has an aiming beam of 633 nm and therapeutic laser of 532 nm. Continuous wave light laser is directed to the TM by the Latina gonio-lens. 10 ms pulses are used to produce blanching of the TM. The procedure is started from the inferior quadrant which has the maximum pigment. Subsequently the power is maintained but the pulse duration is reduced to half (5 ms from 10 ms). Ophthalmoscopically invisible spots are achieved at the TM with this reduced pulse energy. The pattern consists of several arcs composed of multiple laser spots. Each arc contains 3 rows of 22 spots (total:66 spots). Each arc covers around 22.5⁰ so that 8 applications for 180⁰ or 16 applications for 360⁰ are used. Thus, more than 1000 spots of 100 micron diameter are applied over 360⁰. The IOP was lowered by an average of 24% over 6 months of follow up in 60% eyes.

The PASCAL Streamline 577 uses yellow wavelength of 577 nm. A study by Nozaki showed a 31% IOP reduction over 6 months of follow up.

Looking at almost similar results with PSLT and SLT, the only advantage of PSLT appears to be a faster delivery time.

LiGHT Trial: Selective Laser Trabeculoplasty vs. eyedrops

 

The Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial is a multicenter randomized controlled trial comparing initial treatment using selective laser trabeculoplasty (SLT) with initial treatment with IOP-lowering eye drops.

The study was performed on treatment-naïve patients with open-angle glaucoma (OAG) or ocular hypertension (OHT), assessing health-related quality of life (HRQoL), cost-effectiveness, and clinical efficacy after 3 years.

The initial results of the LiGHT Trial were reported in 2019. The study found that initial treatment of OHT or OAG with SLT is more cost-effective than initial treatment with contemporary IOP-lowering eye drops after 3 years,

It also reported freedom from drops to 74.2% of patients, a reduced number of glaucoma surgeries, and very low rates of adverse events.

SLT was performed according to a predefined protocol at 360-degrees of the trabecular meshwork with 100 nonoverlapping shots (25 per quadrant; energy, 0.3-1.4 mJ).

For the first 36 months (3 years) of the trial, 1 additional SLT retreatment was allowed (total of 2 SLT treatments), and thereafter, the next escalation was medical treatment.

Single-drug eye drops were prescribed initially after randomization for patients in the drops arm and for patients whose IOP remained uncontrolled after SLT.

Different or additional eye drops were prescribed in the event of a treatment switch (e.g., adverse reaction) or treatment escalation (e.g., IOP above target).

Drug classes for first-line, second-line, or third-line treatment were defined according to NICE and the European Glaucoma Society guidance: first line, prostaglandin analogs; second line, bblockers; and third or fourth line, topical carbonic anhydrase inhibitors or a-agonists.

Fixed combination drops were allowed; systemic carbonic anhydrase inhibitors were permitted only as a temporary measure while awaiting surgery and were not considered a treatment escalation for the purposes of the analysis.

For the first 36 months (3 years) of the trial, patients initially randomized to receive IOP-lowering eye drops were not permitted SLT; failure to control IOP or OAG with eye drops resulted in surgical treatment (trabeculectomy).

After the first 3 years, patients were allowed a crossover, whereby they could opt to undergo SLT as a treatment switch, that is, to reduce medication load, or as a treatment escalation, that is, to avoid increasing medication load or to delay surgery.

Of the 692 patients who completed 3 years of the LiGHT Trial, 633 patients (91.5%) entered the 3-year extension (from 36 to 72 months); 313 patients (547 treated eyes) initially received SLT, and 320 patients (549 eyes) initially commenced treatment with IOP-lowering eye drops.

Of the 320 patients allocated to medication, 112 patients (176 eyes; 35% of patients) decided to undergo SLT immediately or shortly after the end of the 3-year monitoring period.

Drop-free IOP control at 72 months, was achieved in 69.8% of eyes initially treated with SLT compared with 18.0% of eyes initially treated with IOP-lowering eye drops.

At 72 months, 61.2% of eyes initially treated with eye drops were using 1 or 2 medications compared with 18.5% of eyes initially treated with SLT.

Data published previously have indicated that initial treatment with SLT may delay progression of OHT and OAG. VF analysis suggests more eyes initially treated with IOP-lowering eye drops undergo rapid VF progression compared with eyes first treated with SLT.

After 6 years of treatment, eyes initially treated with SLT demonstrated reduced objectively defined progression compared with IOP-lowering eye drops; this was achieved despite eyes initially treated with IOP-lowering eye drops achieving lower IOP at 6 years, possibly suggesting other protective roles of SLT.

Eyes initially treated with SLT needed fewer trabeculectomies. For the first 3 years after initial treatment, no trabeculectomies were needed in eyes receiving initial SLT. At 6 years, 3 times fewer eyes initially treated with SLT required a trabeculectomy, compared with eyes initially treated with eye drops.

Selective laser trabeculoplasty also leads to a reduced need for cataract surgery. 50% more eyes initially treated with eye drops needed cataract surgery during the 6- year course of the LiGHT Trial compared with eyes initially treated with SLT.

For the first 3 years of the LiGHT Trial, patients using drops experienced comparable HRQoL to those who received initial SLT, and these findings are supported further by the LiGHT Trial extension to 6 years.

The safety profile of SLT remains very good, with no sight-threatening complications. Intraocular pressure rose > 5 mmHg from IOP before treatment in only 1% of treated eyes, and of these, only 1 eye needed treatment.

FURTHER DETAILS ON SLT AVAILABLE HERE:

SELECTIVE LASER TRABECULOPLASTY

OPTICAL COHERENCE TOMOGRAPHY

GENERAL CONSIDERATIONS

• Structural changes in glaucoma may precede functional changes seen on visual field (VF) examinations.
• Upto 20% of the retinal ganglion cells (RGC) could be damaged before any changes occur in VFs.
• Structural changes in glaucoma have been observed in the retinal nerve fiber layer (RNFL), optic nerve head (ONH) and other layers of the macula.
• A number of investigations are available to study these structural changes. These include:

1. Optical coherence tomography (OCT)
2. Confocal scanning laser ophthalmoscopy (e.g. Heidelberg Retinal Tomography)
3. Scanning laser Polarimetry (e.g. GDx, Nerve Fiber Analyzer)

• OCT remains the most commonly used technique.
• It is more efficient compared to HRT and GDx in the detection of localized RNFL defects and changes occurring in the peripapillary area.
• OCT provides real-time qualitative (morphology & reflectivity) and quantitative (thickness, mapping and volume) analyses of the examined tissues.
• OCT can be used for evaluation of the corneal thickness, anterior segment (angle) as well as the posterior segment.
• OCT uses low coherence infrared light (830nm) and is based on the principle of Michelson Interferometry. The long wavelength of the light used permits it to penetrate deep to the target tissue.
• Light in the OCT is broken into 2 arms. A sample arm (which has the item of interest) and a reference arm (usually a mirror). The combination of reflected light from the sample arm and reference light from the reference arm gives rise to an interference pattern, but only if light from both arms has traveled the “same” optical distance. (Same meaning a difference of less than a coherence length.)

Spectral discrimination by fourier-domain OCT. Components include: low coherence source (LCS), beamsplitter (BS), reference mirror (REF), sample (SMP), diffraction grating (DG) and full-field detector (CAM) acting as a spectrometer, and digital signal processing (DSP)

• OCT has evolved from time-domain (TD-OCT) to spectral-domain (SD-OCT).
• In TD-OCT the path length of the reference arm is varied in time (the reference mirror is translated longitudinally). The repeated movement of the mirror permits repeated scans at different depths. A single coherent measurement focused at a single structure at a given depth is called an “A-scan”. The maximum scan rate can be 17,000 A-scans/second. This provides a 1-dimensional measurement, which is converted to a 2-dimensional image (“B-scan”). Thus, different tissue layers can be acquired in the point of focus. The section of tissue thus obtained is called a “Tomogram”.( The word tomography is derived from ancient Greek τόμος tomos, "slice, section" and γράφω graphō, "to write"). The image is viewed in real time using a scale of false colors representing the degree of backscattering of the light by the tissues at different depths. A collection of parallel B-scans help to form a “3-D” data set.
• In FD-OCT the broadband interference (also called the “interference spectrum”) is acquired with spectrally separated detectors. Due to the Fourier relation, the depth scan can be immediately calculated by the Fourier transform from the acquired spectra, without movement of the reference arm. This feature reduces image acquisition time by simultaneous analysis at different tissue depths (27,000 A-scans per second), reducing any errors due to movement and more accurate (upto 2µ). The disadvantage is that light cannot reach the retina in the presence of lens opacities and fixation must be extremely steady.
• “OCT IMAGES ARE NOT IMAGES OF A STRUCTURE BUT A MATHEMATICAL RECONSTRUCTION BUILT ON A PHOTOGRAPH OF THE FUNDUS”
• The structures visualized are the result of selective absorption and selective reflection by the structure or interface illuminated by the light.
• The strength of the signal reflected by a specific tissue depends on properties like tissue reflectivity, the amount of light absorbed by the overlying tissues and the amount of reflected light which reaches the sensor after it has been further attenuated by the interposed tissue. (When the strength of the reflected signal is strong, the scanned tissue has high reflectivity and vice versa)  [When the structures are perpendicular to the ray, reflectivity is greatest and produces red images on OCT].
• Reflectivity of tissues:

1. The most reflective structures on OCT are: RNFL, internal limiting membrane, junction between inner and outer segments of photoreceptors, retinal pigment epithelium [RPE]-Bruch’s membrane-choriocapillaries complex. These appear “red” on OCT.
2. The least reflective structures are: Inner- and outer-nuclear layers, ganglion cell layer and photoreceptors. They appear “black” on OCT images.
3. Intermediate reflective structures are: Inner- and outer-plexiform layers and external limiting membrane. These appear “green” on OCT.