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3DEVELOPMENT OF LASER TRABECULOPLASTY IN THE TREATMENT OF GLAUCOMA (LITERATURE REVIEW)
1Yusupov A.F., 2Jamalova Sh.A., 3Mukhanov Sh.A., 4Umarova N.O.
1,2,3,4Republican Specialized Scientific and Practical Medical Center for Eye Microsurgery, JV
LLC "SIHAT KO'Z" https://doi.org/10.5281/zenodo.13636782
Abstract. Glaucoma is a chronic, progressive disease that leads to optic neuropathy, characterized by a narrowing of the visual field and often an increase in intraocular pressure. Thus, the main goal of glaucoma treatment is to reduce intraocular pressure. Various treatment methods have been used for many years in the management of primary open-angle glaucoma, with laser methods undergoing several stages of development. Micropulse laser trabeculoplasty is the latest and safest alternative treatment for primary open-angle glaucoma.
Keywords: primary open-angle glaucoma, intraocular pressure, laser trabeculoplasty, treatment.
Glaucoma is a chronic, progressive disease that leads to optic neuropathy, characterized by a narrowing of the visual field and often increased intraocular pressure. Therefore, the main goal of glaucoma treatment is to reduce intraocular pressure [1]. About 30-40 years ago, intraocular pressure reduction was achieved only through pharmacological treatments. However, with the invention of laser devices and large randomized trials, laser treatment for glaucoma became a common practice, particularly for primary open-angle glaucoma [2].
The first use of lasers on the trabecular meshwork was in 1979 with argon laser trabeculoplasty (ALT) [3]. Later, in 1995, selective laser trabeculoplasty (SLT) was introduced [4,5]. Since the introduction of laser trabeculoplasty, laser treatment has become a leading method for managing primary open-angle glaucoma. It offers several advantages, such as enabling patients to achieve target intraocular pressure with fewer medications. However, there are disadvantages as well: scarring at the laser impact sites on the trabecular meshwork was observed with argon laser radiation, reducing the efficacy of the treatment. These disadvantages were absent with selective laser trabeculoplasty, which also allowed for repeated applications [5,7-10]. SLT delivers energy specifically to the pigmented cells of the trabecular meshwork, leading to the selective destruction of pigmented endothelial cells, as evidenced by electron microscopy [7]. This process causes cellular damage and triggers an inflammatory response, thereby increasing the outflow of intraocular fluid.
In 1990, Pankratov and colleagues were the first to use a micropulse laser for retinal photocoagulation [13]. This technique has been particularly useful in treating macular edema in diabetic retinopathy, retinal vein occlusion, and central serous chorioretinopathy [16-18]. These findings marked the beginning of using trabeculoplasty in micropulse mode.
The first large randomized trial of micropulse laser trabeculoplasty (MLT) was conducted by Ingvoldstad et al., with results presented at the annual meeting of the Association for Research in Vision and Ophthalmology in 2005 [20]. The study demonstrated the feasibility of using micropulse diode laser trabeculoplasty on the trabecular meshwork without the thermal damage associated with argon laser trabeculoplasty, effectively reducing intraocular pressure [7]. Histological examinations confirmed the absence of damage to the trabecular meshwork.
Following Ingvoldstad et al.'s findings, numerous researchers began investigating the effects of micropulse diode laser trabeculoplasty on the trabecular meshwork and intraocular pressure using various laser wavelengths and intensities, achieving varying degrees of success [2126].
The laser targeted the intersection of pigmented and non-pigmented trabecular meshwork areas, with bubble formation or blanching observed upon exposure. The treatment area covered 360 degrees with 50 burns, and some practitioners used 100 burns over 180 degrees [33,34]. When treating 360 degrees, intraocular pressure spikes were more common, especially in cases of pseudoexfoliative glaucoma, peripheral anterior synechiae, and, in rare cases, corneal endothelial decompensation [35-39]. Treating only 180 degrees resulted in fewer pressure surges and allowed for repeat argon laser trabeculoplasty sessions.
Due to increased complications with ALT, Latina and Park developed a selective laser trabeculoplasty (SLT) technique in 1995 that targeted only pigmented cells [4]. SLT utilized a frequency-doubled Nd:YAG laser system at 532 nm [5], with energy levels ranging from 0.4 to 1.2 mJ, a spot diameter of 400 p,m, and a pulse duration of 3 nanoseconds. When the trabecular meshwork undergoes SLT, cavitation bubbles, or "champagne bubbles," form, indicating a therapeutic effect. The power is reduced for more pigmented areas. Around 100 laser spots (25 per quadrant) are applied, primarily over a 180-degree area, leaving the rest for subsequent treatments [40,41]. Adverse reactions post-SLT included transient mild redness, acute iritis, and elevated intraocular pressure within the first week. Less common complications included transient corneal thinning, endothelial decompensation, peripheral anterior synechiae, corneal opacification, and cystoid macular edema [42-44].
A large-scale controlled study, the LIGHT study, compared SLT with eye drops in patients with elevated intraocular pressure. It showed that target pressure was achieved in % of the patients who had not previously undergone treatment, and results were maintained over three years. However, in studies by Lai et al., the success rate dropped from 71% after one year to 25% after five years, prompting the use of laser trabeculoplasty in sub-threshold mode, which also demonstrated effectiveness in reducing intraocular pressure.
MLT technique and its advantages: Micropulse laser trabeculoplasty (MLT) is a laser trabeculoplasty method utilizing low-impact energy. The safety of the micropulse laser is based on the period between pulses, which allows the temperature of the pigmented cells to return to baseline before the next pulse. This prevents cell damage due to cumulative thermal effects, scarring, and morphological changes in trabecular meshwork tissue. This mechanism of action helps avoid intraocular pressure spikes post-treatment, even in highly pigmented trabecular tissues [21,46]. However, the molecular effects of the micropulse laser remain unclear, with only hypotheses proposed. Researchers suggest that ALT, SLT, and MDLT (micropulse diode laser trabeculoplasty) may operate through different mechanisms but achieve similar cellular responses [21,46]. The principle of modern laser trabeculoplasty is to enhance aqueous humor outflow while minimizing tissue damage by stimulating a cellular biochemical cascade via cytokine release [55,56]. Low energy levels used in MDLT are sufficient to initiate this therapeutic process in living trabecular cells without the severe coagulative and cellular damage seen at higher energy levels used in ALT and SLT [7,47].
The initial MLT study was conducted by Ingvoldstad and Willoughby using the IRIS Medical OcuLight SLx 810 nm diode laser system (IRIDEX Corporation, Mountain View, CA,
USA). For the procedure, the power was set to 2000 mW, with a spot diameter of 300 p,m and a duration of 200 milliseconds, operating at a duty cycle of 15% over the entire 360-degree trabecular meshwork. A 3-month follow-up showed an 18.3% reduction in intraocular pressure. Subsequent studies involved laser trabeculoplasty at 532 and 577 nm wavelengths with varying powers and duty cycles. The table is shown below (Table 1).
Table 1.
Study Wavel ength( nm) Power (mW) Spot diameter (l^m) Cycle duration (ms) Duty cycle Impact area Duration of the study Succes s rate
Fea at al. (2008) 810 2000 200 200 15% Lower than 180 12 months 60%
Detry-Morel et al. (2008) 810 2000 300 200 15% Lower than 180 5 months 36%
Rantala et al. (2012) 810 2000 300 200 15% Lower than 180 12 months 7.5%
Babalola (2015) 810 1000 Between 75, 125, 200 200 15% Lower than 180 160 days -
Lee at al. (2015) 577 1000 300 300 15% 360 6 months 73%
Abouhussei n (2016) 577 1000 300 300 15% 360 6 months -
De Leon et al. (2017) 577 1000 300 300 15% 360 3 months 48%
Abramowitz et al. (2018) 577 1000 300 300 15% 360 12 months 37%
Kakihara et al. (2010) 577 7001000 300 300 15% 360 6 months 44%
MLT for POAG. Micropulse laser trabeculoplasty (MLT) studies have primarily focused on patients with primary open-angle glaucoma (POAG), excluding other types of primary glaucoma. These studies paid special attention to patients who had not previously received drug treatment.
One of the pioneering studies in this area was conducted by Babalola et al. on Nigerian patients. The wavelength used was 810 nm, with spot sizes varying from 75, 125, to 200 p,m. Greater success in reducing intraocular pressure (IOP) was achieved in the group with a spot size of 200 p,m. MLT resulted in a statistically significant reduction in IOP over several months [23].
In an interventional study, Abouhussein et al. used a 577 nm laser [45], compared to the diode laser used by Ingvoldstad, allowing for an increased spot size of 300 p,m. The study included 30 eyes and achieved IOP stabilization by 21.6% compared to baseline.
Subsequently, researchers began studying the effect of MLT on the trabecular meshwork for all types of open-angle glaucoma using wavelengths of 532, 577, and 810 nm. Detry-Morel et al. conducted a study on patients with phakic open-angle glaucoma, involving 31 eyes and 26 patients [20]. This was the first randomized trial comparing MLT with argon laser trabeculoplasty (ALT). The laser settings were similar to those used by Ingvoldstad, but the treatment area was limited to 180 degrees. Results showed that in the MLT group, the reduction in IOP was up to 12.2%, whereas in the ALT group, it was 21.8% at the 3-month follow-up [22].
In two studies by Fea et al. and Rantaka and Valimaki, the focus was on treating POAG over a 180-degree area rather than 360 degrees. Both studies used an 810 nm wavelength, but unlike Ingvoldstad, a spot size of 200 p,m, power of 2000 mW, and duration of 200 ms were employed. In Fea's study, 15 eyes showed a decrease in IOP by 22.1%, while in 5 eyes, there was no improvement in IOP at the 12-month follow-up. In the study by Rantala and Valimaki, only 2.5% of cases showed a reduction of at least 20% over a 3-month follow-up, and only 7.5% of patients achieved a reduction of at least 3 mmHg, despite using a larger spot diameter of 300 p,m with similar parameters. These disappointing results may have been due to the targeting of the trabecular meshwork only over a 180-degree area, with nearly half of the patients requiring repeat laser trabeculoplasty [21,24].
The lack of significant results with MLT using an 810 nm wavelength prompted the exploration of MLT with a 577 nm wavelength, which was initially applied to the macula. Chudoba et al. were pioneers in applying MLT with a 577 nm wavelength over 180 degrees in 2014. However, they only achieved a reduction in IOP of 1.7 mmHg, whereas patients in the drug treatment group showed a reduction of 1.8 mmHg [25].
In 2015, Lee et al. conducted a prospective study on 48 eyes with POAG. The laser settings were as follows: 577 nm wavelength, treatment over 360 degrees, 1000 mW power, 15% duty cycle, 300 ms duration, and 300 p,m spot size. After a 6-month follow-up, an average IOP reduction of 19.5% was observed, along with a reduction in the number of medications used. In 73% of cases, no additional laser treatment was required [26].
In recent years, the use of MLT with a green laser at a 532 nm wavelength (Iridex Corporation, Mountain View, California, USA) has been explored. Gossage and colleagues studied 18 eyes with POAG over a 2-year follow-up period. Laser power levels of 300, 700, and 1000 mW were tested, with the 1000 mW power group showing a 24% reduction in IOP, indicating that higher power settings may be more effective [48].
Complications. MLT offers an optimal safety profile due to the low incidence of side effects following the procedure.
This safety is attributed to the fact that the micropulse laser does not cause morphological changes in the trabecular meshwork, thus reducing the inflammatory response, which was common in ALT. While ALT causes coagulation and damage to the trabecular meshwork, and SLT leads to the destruction of pigmented trabecular cells, MLT allows for cooling periods between pulses, preventing cellular or morphological changes in the trabeculae [12,19].
No MLT studies have documented vision-threatening complications, such as changes in visual acuity, visible laser flashes, anterior segment inflammation, or anterior synechiae, which have been associated with SLT and ALT. Only a few studies have reported transient increases in IOP of more than 5 mmHg within the first few hours after the procedure, which resolved spontaneously. However, the frequency of IOP spikes was not as significant as those observed with SLT [26,27,28,59,65].
Conclusions. MLT has significant advantages over SLT and ALT, particularly in cases where there is a risk of postoperative side effects and IOP spikes. It is hypothesized that MLT will have a similar therapeutic effect as SLT while being a safer method.
Additionally, if the hypotensive effect of MLT is insufficient, the procedure can be repeated. Ultimately, MLT may improve the management of open-angle glaucoma and reduce the reliance on topical antihypertensive medications.
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