Effect of Selective Laser Trabeculoplasty in Ocular Hypertension

Abstract

The aim of the study was to compare the results of using eye drops (a beta-blocker) with the results of selective laser trabeculoplasty in ocular hypertension. The retrospective study was conducted among treatment-naïve patients of two clinics in Yerevan, Armenia, during a period from 2019 to 2022. The eligible participants were divided into two groups as follows: group 1 (85 eyes) with patients who received SLT once and group 2 (52 eyes) where the patients have applied a single type of eye drops. The patients were allocated to the groups taking into account their preferences; this corresponded to random sampling. The IOP measures taken after 1, 3, 6, and 12 months showed reduction for more than 20% each time compared to baseline data. The mean IOP reduction was not significantly different in both treatment groups. SLT, as an effective and convenient technique allowing avoidance of the side effects of eye drops and an issue of low compliance, can be recommended as a method of the first choice in primary prevention of glaucoma.

1. Introduction

Use of laser for intraocular pressure (IOP) reduction is dated to 1970s. In 1979, Wise and Witter suggested low-energy argon laser photocoagulation (ALT) and concluded that it was a successful procedure for the short-term IOP decrease [1].

The mechanism of ALT is ambiguous [2]. According to mechanical theory, laser thermal burns to trabecular meshwork (TM) lead to collagen contraction and local scarring, thus enhancing space for nearby tissues. In obedience to biological theory, thermal energy of ALT causes structural changes of TM by means of “altered cytokine secretion, matrix metalloproteinase induction, increased cell division, repopulation of burn sights, and macrophage recruitment”. As a result, extracellular matrix is changed, and intraocular fluid outflow increases [2, 3].

In 1983, Anderson and Parrish found that pigmented cells of tissue could absorb applied radiation energy selectively, resulting in localized damage. This process was called selective photothermolysis (SP) [4].

SP had two main criteria. The first criterion was an intracellular chromophore with a higher optical absorption at the laser wavelength than in neighboring tissues, and the second criterion was that the period of laser radiation could not be longer than it is required for thermal diffusion into the tissue (thermal relaxation time) [5].

The ALT duration (~0.1 s) is longer than the thermal relaxation time of melanin (1 μs); it allows heat generated in pigmented cells to dissipate and damage collateral TM [5].

Selective Laser Trabeculoplasty (SLT) was introduced in 1995 by Latina and Park. They used a 532 nm Q-switched, frequency-doubled Nd:YAG laser that generated a shorter pulse duration (3 ns). It suits the abovementioned requirements of SP, preventing heat dissolution outside of pigmented TM cells and causing less surrounding damage [6].

In 2001, SLT received approval of Food and Drug Administration (FDA). According to Arora et al., 75,647 trabeculoplasties were performed in 2001 in the USA; this number was almost doubled, reaching 142,682 procedures in 2012 [7].

SLT lowers the IOP by increasing the outflow through the TM [8].

Histopathological study showed that SLT causes less damage to TM compared to ALT [9].

It is suggested that TM disruption could depend on energy dosage, as higher power SLT can lead to more severe TM damage than lower power SLT [10].

The mechanical and biological theories, which have been suggested to explain ALT’s mechanism of action, do not entirely suit to SLT, as limited damage of tissues occurs to the TM in SLT, as thermal relaxation time of melanin is approximately 1 millisecond and the pulse duration of SLT laser is 3 nanosecond [5].

SLT lowers intraocular pressure (IOP) by improving aqueous outflow mainly by biological changes in the TM [5].

SLT has demonstrated the regulation of expression of genes responsible for cell motility, extracellular matrix production, membrane repair, and reactive oxygen species production [11].

In vitro studies have shown an increase in pro-inflammatory cytokine expression, including interleukin-1-alpha, interleukin-1-beta, tumor necrosis factor-alpha, and interleukin-8 post SLT [12].

These cytokines enhance stromelysin-1 expression (MMP-3), a matrix metalloproteinase, involved in TM extracellular matrix remodeling to increase aqueous outflow through the juxtacanalicular meshwork [13].

After SLT, increase in TM monocyte recruitment has been registered as a result of increased chemokine production [14].

Several studies demonstrated that local increase in endothelin-1 may lead to acute IOP rise after SLT (IOP spike); meanwhile, increase in lipid peroxide levels and reduction in antioxidant enzyme levels can occur due to the increased inflammatory response precipitated after laser [15, 16].

In vivo, monocytes improve aqueous outflow and, in vitro, facilitate Schlemm’s canal permeability through the secretion of cytokines or directly phagocytosis of the debris within TM [15].

Kramer et al. conducted a study, which compared changes after SLT and ALT in the uveal meshwork part of the TM in autopsy eyes. After ALT, TM structures detected to be damaged with coagulative destruction, (ablation craters), while in SLT, minimal mechanical damage of tissues occurred. At the same time, cracking of intracytoplasmic pigment granules and the disruption of TM endothelial cells were observed [4]. Signs of destruction and scrolling of trabecular beams at the edges of laser burns appeared on tissues treated with energy of 2 mJ [7].

Alvarado JA et al. showed that SLT and prostaglandin (PGA) analogues may have a common pathway of action by causing intercellular junction disassembly in Schlemm’s canal and TM cells in this way increasing aqueous permeability [17, 18].

SLT was evaluated as the first-line therapy by Melamed et al. and McIlraith et al. in prospective studies and demonstrated reduction of IOP by approximately 30% compared to baseline levels, which is comparable with prostaglandin efficacy [19, 20, 21].

According to Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial, SLT was found to be a clinically safe and cost-effective procedure as an initial treatment of open-angle glaucoma (OAG) and ocular hypertension (OHT) at 3 years [22].

SLT is performed using topical anesthetic. The patient sits at the slit lamp; a single mirror gonioscopic lens (Latina lens) with coupling medium is used. Laser beam is focused on the pigmented part of TM [18].

A frequency doubled, Q-switched Nd:YAG laser is used during SLT. The wavelength is 532 nm. Pulse duration is 3 ns, and laser spot size is 400 μm. Pulse energy ranges from 0.4 to 1.4 mJ [5, 23].

The laser energy is initially set at 0.6 mJ. If cavitation bubbles (“champagne bubbles”) appear, the energy is reduced by 0.1 mJ increments until the formation of bubbles is minimal, and treatment is continued at this energy level [5, 23].

Several studies compared treating different degrees of the TM with SLT to see how it influences IOP lowering [18].

Chen et al. had discovered that there is no difference between the application of SLT over 90° and 180° using 25 nonoverlapping laser spots per quadrant [24].

Other studies have shown that 180° and 360° laser is more effective than 90° laser. And the success rate is the highest over 360° SLT [25, 26].

In current practice, typical treatment parameters are 50–100 shots applied over 180°–360° with energy adjusted to 0.6–1.4 mJ and the end point of visible tissue reaction in the form of microbubbles [18, 23].

The indications for SLT include as follows:

1. Newly diagnosed open-angle glaucoma (OAG) patients,

2. OHT,

3. OAG patients uncontrolled on medical treatment,

4. OAG patients with likely or actual poor compliance or poor tolerance to medical treatment,

5. patients with pseudoexfoliation or pigmentary glaucomas,

6. patients who cannot afford glaucoma medications,

7. patients who would like to reduce the number of glaucoma medications they are taking,

8. patients who do not tolerate glaucoma medications [27, 28].

Current contraindications are as follows:

1. Inflammatory/uveitic glaucoma;

2. congenital glaucoma;

3. poor visualization of the TM;

4. active uveitis or history of uveitis (relative contraindication);

5. traumatic glaucoma (relative contraindication);

6. congenital or early childhood glaucoma (relative contraindication);

7. primary or secondary angle-closure glaucoma (relative contraindication) [27, 28].

Contrary to the past theories, Ho et al. have reported that IOP is successfully decreased by SLT in eyes with primary angle closure and a patent iridotomy in case when there was a sufficient extent area of visible TM [29].

Some studies have shown that long-term use of topical medication can lead to conjunctival fibrosis and postoperative bleb dysfunction [30, 31].

Complications of SLT include elevated IOP, iritis, hyphema, macular edema, foveolar burn. and corneal haze [32].

2. Materials and methods

The aim of the study was to compare the results of using eye drops (a beta-blocker) with the results of selective laser trabeculoplasty in ocular hypertension.

The retrospective study was conducted among patients who visited Zilfyan Eye Care Clinic, Yerevan, Armenia, or Shengavit Medical Center, Yerevan, Armenia, during a period from 2019 to 2022. The clinical records of the patients were reviewed, and those that met the inclusion criteria were included into the study. Totally, 1473 records were reviewed.

The eligible records were divided into two groups as follows: group 1 (85 eyes) with treatment-naïve patients with ocular hypertension, who received SLT once and group 2 (52 eyes) where the patients with ocular hypertension have applied a single type of eye drops for the first time (Timolol 0.5%). The patients were allocated to the groups taking into account their preferences; this approached random sampling. The two groups were not significantly different by age and gender characteristics, which allowed minimizing the confounding factors.

Inclusion criteria were treatment-naïve patients with newly diagnosed ocular hypertension whose intraocular pressure exceeds 21 mmHg, no evidence of glaucomatous optic neuropathy and no glaucoma changes on Humphrey field analyzer (by the “SITA” standart algorithm), and who visited the clinic after treatment starting in 1, 3, 6 months, and a year.

Exclusion criteria were any type of glaucoma, any concomitant eye diseases, previous treatment for ocular hypertension (OHT), any previous eye surgery, and patients who missed a visit to the clinics after 1, 3, 6 months, or 1 year (incomplete results). In addition, those patients from SLT group, who had to use eye drops because of not reaching lower IOP level, were not included into the study.

In the first group, the SLT was done with Q-switched Nd:YAG laser wavelength 532 nm, with a spot size of 400 μm. The laser system was coupled to a slit lamp delivery system with a helium-neon laser (HeNe) aiming beam. The eye was anesthetized with topical eye drops (tetracaine hydrochloride 1%). The patient was seated in front of slit lamp. Latina goniolens with coupling medium (artificial tear gel) was used, and laser beam was focused on pigmented part of trabecular meshwork. Laser spot size was 400 μm. Hundred nonoverlapping shots (25 per quadrant) with pulse duration of 3 nanosecond were applied.

The laser energy varies within 0.8–1.3 mJ range. If cavitation bubbles formed, the energy was decreased by 0.1 mJ, and laser was done at that energy level. If no cavitation bubbles appeared, the pulse energy was increased by 0.1 mJ steps until “champagne bubbles” formation was observed, then decreased again by 0.1 mJ.

After the procedure, anti-inflammatory steroidal eye drops (dexamethasone 0.1%) were prescribed 4 times a day during 5 days. The patients were examined the next day afterSLT, in order not to miss the surge of IOP spike, which can occur after SLT.

The participants of the second group were using a B-blocker 2 times a day (every 12 hours).

In order to prevent poor compliance, the explanation of how and when to use eye drops was provided to the patients at each visit.

At baseline, visual acuity testing, IOP measurement (I-care manual rebound tonometer), slit-lamp examination, automated visual field (VF) testing (Humphrey Field Analyzer, the Swedish Interactive Threshold Algorithm 24-2 program), gonioscopy, CCT measurement, evaluation of optic disc, macula, and fundus were performed to all patients.

The IOP was measured with I-care manual rebound tonometer before and after eye drops or SLT at next day, 1 month later, 3 months later, 6 months later, and 1 year later.

In cases when target IOP was more than 10 mmHg on the next day after SLT (IOP spike), a 7-day course of a topical aqueous inhibitor was prescribed.

Two-sample T-test (Welch’s T-test) was used to compare the clinical effect of one-time SLT and single type of eye drops. A p value of <0.05 was considered statistically significant.

3. Results

The results were calculated using online statistics calculators: www.calculator.net and https://www.statskingdom.com/

The baseline characteristics of the study participants include age, gender, and laterality.

Participant baseline characteristics are shown in Table 1. In the group of SLT, the average age of the patients was 64.43 years (± 10.46 years), with more female patients than male (21.15% male vs. 78.85% female).

Characteristics	SLT group	Eye drops group
Age (years), Mean (SD)	64.43 ± 10.46	58.55 ± 16.24
Gender (patients), (%); Male; Female	11 (21.15%); 41 (78.85%)	11 (32.35%); 23 (67.65%)
Laterality (patients), (%); Both eyes; Right eye; Left eye	33 (63.46%); 7 (13.46%); 12 (23.08%)	18 (52.94%); 8 (23.53%); 8 (23.53%)

Table 1.

Baseline characteristics of SLT and eye drops groups.

Thirty-three patients out of 52 (63.46%) had bilateral OHT, and 19 patients (36.54%) had unilateral OHT.

In the eye drops group, the average age of the patients was 58.55 years (± 16.24 years), and again, the number of female patients was higher than male (32.35% male vs. 67.65% female). Eighteen patients out of total 34 (52.94%) had bilateral OHT, while 16 patients (47.06%) had unilateral OHT (Table 1).

The initial mean IOP was 25 mmHg ±2.89 (SD) in the group treated with SLT and 24.38 mmHg ±2.46 (SD) in the group treated with eye drops. High P-value (0.1833) indicates that the difference between the sample average of initial IOP in 2 groups was not big enough to be statistically significant (CI = 95%).

The median value was 24 in both groups, and mode was 23 and 22 in SLT group versus 22 in the group using eye drops (Table 2).

Initial IOP	SLT	Eye drops
Number of eyes	85	52
Mean (average)	25	24.38
Median	24	24
Mode	23, 22 (each appeared 17 times)	22 (appeared14 times)
Largest	34	33
Smallest	22	22
Range	12	11
Standard Deviation	2.89	2.46
Variance	8.35	6.04
Sample Standard Deviation	2.90	2.48
Sample Variance	8.45	6.16

Table 2.

Results of IOP evaluation before SLT and eye drops usage.

The mean IOP measured 1 month after intervention was 18.4 mmHg ± 3.85(SD) in the first group and 17.94 mmHg±3.97(SD) in the second group. The difference in treatment effect between the two groups 1 month after the treatment was not significant (p = 0.5071) (CI = 95%).

The median value was 19 and 18 and, and the mode was 16 and 15 in first and second groups, respectively (Table 3).

IOP – after 1 month	SLT	Eye drops
Number of eyes	85	52
Mean (average)	18.49	17.94
Median	19	18
Mode	16 (appeared 12 times)	15 (appeared 7 times)
Largest	28	26
Smallest	10	10
Range	18	16
Standard Deviation	3.85	3.97
Variance	14.85	15.79
Sample Standard Deviation	3.88	4.01
Sample Variance	15.03	16.09

Table 3.

Results of IOP evaluation after 1 month of SLT and eye drops usage.

Three months after the intervention, the mean average slightly decreased to 18.19 mmHg±3.23 (SD) in the first group and 17.48 mmHg ± 3.82 (SD) in the second group. The treatment effect 3 months after intervention again was close in both groups (p = 0.2664, CI = 95%). The median was 18 and 17, respectively, and the mode was 18 in the first group and 17 and 14 in the second group (Table 4).

IOP – after 3 months	SLT	Eye drops
Number of eyes	85	52
Mean (average)	18.19	17.48
Median	18	17
Mode	18 (appeared 15 times)	17, 14 (each appeared 7 times)
Largest	27	27
Smallest	10	8
Range	17	19
Standard Deviation	3.23	3.82
Variance	10.44	14.6
Sample Standard Deviation	3.24	3.86
Sample Variance	10.55	14.88

Table 4.

Results of IOP evaluation after 3 months of SLT and eye drops usage.

The IOP evaluation after 6 months showed approximately similar mean in the first and second groups, 18.49 mmHg±3.64 (SD) and 18.6 mmHg ±4.15 (SD), respectively (p = 0.1151, CI = 95%). The median IOP was 18 and the mode 17 in the first group and 19 and 23, respectively, in the second group (Table 5).

IOP – after 6 months	SLT	Eye drops
Number of eyes	85	52
Mean (average)	18.49	18.6
Median	18	19
Mode	17 (appeared 12 times)	23 (appeared 7 times)
Largest	30	26
Smallest	11	10
Range	19	16
Standard Deviation	3.62	4.15
Variance	13.07	17.20
Sample Standard Deviation	3.64	4.19
Sample Variance	13.23	17.54

Table 5.

Results of IOP evaluation after 6 months of SLT and eye drops usage.

The mean IOP measured 1 year after the intervention was 19 mmHg ±3.4(SD) in the SLT group and 19.08 mmHg±4.17(SD) in the group using eye drops. No difference between the sample averages of 2 groups was found (p = 0.9068, CI = 95%). The medians were 19 and 20 and modes were 20 and 23, respectively (Table 6).

IOP – after 12 months	SLT	Eye drops
Number of eyes	85	52
Mean (average)	19	19.08
Median	19	20
Mode	20 (appeared 12 times)	23 (appeared 9 times)
Largest	29	28
Smallest	11	10
Range	18	18
Standard Deviation	3.406	4.13
Variance	11.6	17.04
Sample Standard Deviation	3.426	4.17
Sample Variance	11.74	17.39

Table 6.

Results of IOP evaluation after 12 months of SLT and eye drops usage.

Treatment effect is more visible when expressed in percentage comparing the initial results with follow up at certain points. Thus, 1 month after the intervention, the IOP evaluation showed 26.38 and 26.2% decrease in the first and second groups, respectively. Three months later, the IOP fell down by 27.21% in the SLT group and by 28.1% in the group using eye drops. Further, after 6 months, the IOP reduction was 26.01 and 24.06% in the first and second groups, respectively. Finally, the decrease in IOP 1 year later was 23.97% in the SLT group and 21.51% in the group using SLT.

4. Conclusion

The results of the study have shown that both SLT and eye drops are effective methods of ocular hypertension treatment. In both groups, the IOP measures taken after 1, 3, 6, and 12 months showed reduction for more than 20%.

Comparison of two methods demonstrated no statistically significant difference in treatment effects. Yet further research with larger sample sizes and longer follow-up time is advisable.

This study, in difference with other similar studies, focuses on treatment of OHP cases only, whereas other studies include also glaucoma cases. The value added of the study therefore is the exploration of effectiveness of glaucoma primary prevention.

SLT is proven to be an effective and convenient IOP reduction method [18]. It helps to solve a problem of poor compliance and side effects of eye drops [33]. Therefore, SLT can be offered as a method of the first choice in treatment of ocular hypertension.