Safety and efficacy of MicroPulse transscleral laser therapy with the revised P3 delivery device: A randomized controlled trial

Abstract

Objective

To evaluate the safety and efficacy of MicroPulse Transscleral Laser Therapy (MicroPulse TLT) with the Revised P3^® Delivery Device.

Design

Prospective, single-surgeon, interventional study in a tertiary hospital setting.

Participants

Sixty-two eyes of 40 patients with refractory glaucoma.

Methods

All subjects received 360-degree MicroPulse TLT treatment (2500 mW, 31.33% duty cycle) over a total of 240 s (8 sweeps; n = 20), 300 s (10 sweeps; n = 22), or 200 s (10 sweeps; n = 20). Participants were followed up for 6 months to assess changes in intraocular pressure (IOP), glaucoma medication burden, and best-corrected visual acuity (BCVA). Surgical success was defined as a reduction of IOP ≥ 30% from baseline and between 6–18 mmHg at last follow-up with no additional anti-glaucoma medications or secondary reinterventions.

Results

Surgical success was achieved in 72.7% (300 s group), 75.0% (240 s group), and 80.0% (200 s group) of eyes. Mean IOP was significantly reduced (p < 0.001) by 49.0% (300 s group), 45.66% (240 s group), and 39.8% (200 s group) at 6 months. With all groups combined, the mean number of glaucoma medications was significantly reduced by 17.8% (p = 0.005), and no significant changes in BCVA were observed at 6 months. Complications were minimal, including four eyes with IOP spikes, one eye with hyphema, and one eye with cystoid macular edema (CME), all of which resolved. Two eyes of the total sample (3.2%) required secondary glaucoma surgery before 6 months.

Conclusions

Second-generation MicroPulse TLT at fluence values of 154–229 J/cm² appears to be a safe and effective option for IOP reduction in refractory glaucoma.

Keywords

Laser surgery < GLAUCOMA open angle glaucoma < GLAUCOMA angle closure < GLAUCOMA aqueous humor dynamics < GLAUCOMA GLAUCOMA

Introduction

Glaucoma is the leading cause of irreversible blindness worldwide, affecting 80 million individuals, with this statistic expected to increase to 111 million by the year 2040.¹ It is primarily managed through a stepwise treatment approach, using anti-glaucoma eyedrops as the first line treatment. However, when pharmacotherapy fails to decrease intraocular pressure (IOP) sufficiently, laser therapy or surgical intervention is indicated.² Trabeculectomy has historically been considered the “gold-standard” procedure but is limited by bleb-related complications such as blebitis, corneal erosion, conjunctival hemorrhage, and high reoperation rates^3–5; therefore, there has been a push towards performing more minimally invasive surgeries to lower the IOP. In addition to subconjunctival bleb-forming procedures, current glaucoma treatment modalities consist of interventions directed at the trabecular meshwork or Schlemm's canal, suprachoroidal shunting procedures, or approaches aimed at diminishing aqueous production.⁶

MicroPulse Transscleral Laser Therapy (MicroPulse TLT) is a tissue-sparing procedure which targets the ciliary body using repetitive pulses of infrared diode Cyclo G6^® Laser (Iridex Corporation, Mountain View, CA, USA), with a wavelength of 810 nm to treat glaucoma by decreasing the production of aqueous humor.⁷ The first-generation 700-micra fiberoptic handheld device was used for the treatment of refractory glaucoma and was shown to have a favorable safety profile to conventional transscleral cyclophotocoagulation (TSCPC).⁷ However, some clinicians were reluctant to utilize this probe due to the risk of complications secondary to the use of 200J of energy per treatment.⁸ Some studies reported no major postoperative complications,^9–12 but most studies reported uncontrolled hypotony,^9,10,12–16 anterior chamber inflammation,^13–18 loss of BCVA greater than 2 lines,^13–23 and even phthisis bulbi.^16,18

In 2020, a second generation MicroPulse probe with a 600-micra diameter was introduced to the market (MicroPulse Revised P3^® Delivery Device, Iridex Corporation, Mountain View, CA, USA). The predominant differences between the revised probe and its previous iteration include: 1) recession of the fiber tip with the addition of a fluid channel to enable consistent fiber immersion in fluid during treatment to improve coupling, hence delivering more energy in a more consistent fashion; 2) integration of concave “scleral-matching” footplate and “limbal-matching” footplate face curvature to improve probe stability; 3) reduction of the footplate size for easier placement for compromised eyes with limited exposure; 4) elongation of the stem to improve visualization of the treatment area; and 5) adjustment of the photon dispersion profile to a more perpendicular orientation than in the first generation, which ensures more focal laser to the target tissue (see Figure 1).²⁴ Overall, these modifications ensure more optimal tissue coupling between the delivery device and tissue, which facilitates a constant consistent pressure delivered from the footplate to the tissue.

Figure 1.

Comparison of photon dispersion profile between first and second generation MicroPulse P3 delivery device. Permission obtained from IRIDEX Corp.

Recent prospective studies have demonstrated a dose-dependent relationship associated with higher energy settings and improved IOP with both the first- and second-generation probe.^25,26 Given the lack of consensus regarding the ideal treatment parameters for MicroPulse TLT, our study utilizes different treatment paradigms to assess the efficacy and safety profile of MicroPulse Revised P3 Delivery Device in the treatment of refractory glaucoma, under the longest durations and highest fluences reported to date. To the knowledge of the authors, this is the first prospective study in literature which reports outcomes of the second-generation MicroPulse probe utilizing these revised settings.

Methods

Study design

A prospective, interventional study was conducted at a tertiary hospital setting from January 2022 to June 2023. The study was approved by the Mayo Clinic Institutional Review Board (IRB) on November 11, 2019, and adhered to the tenets of the Declaration of Helsinki. The registration number of this study on the National Institute of Health (NIH) website https://clinicaltrials.gov/ is NCT05654493. Participants were followed up for 6 months by a single glaucoma subspecialist at Mayo Clinic in Jacksonville, FL. Informed consent was obtained from all patients.

Participants

Patients of both genders and of any race aged over 18 years, were deemed eligible for the current study if they had been diagnosed with refractory glaucoma (defined by an IOP above the target level or having evidence of disease progression with visual field deterioration despite maximal tolerated medical therapy) and/or were considered poor candidates for secondary incisional glaucoma surgery. The exclusion criteria consisted of patients with significant scleral thinning, concurrent eye infection or inflammation, and a history of intraocular surgery performed ≤2 months prior to enrollment. Significant scleral thinning was diagnosed in patients with >1 clock hours of involvement detected on transillumination and confirmed using Cirrus high-definition optical coherence tomography (HD-OCT) imaging before exclusion. Pregnant women and patients enrolled in other clinical trials were also excluded.

Procedure

Patients were enrolled to receive MicroPulse TLT and were randomly assigned into three groups with differing total treatment times (200, 240, or 300 s) and sweep numbers (8 or 10 sweeps). Participant randomization was performed using an online random number generator.²⁷ Participant enrollment and random assignment was performed by the primary investigator, and all subjects were blinded to the treatment arm to which they were assigned. Treatment parameters are summarized in Table 1. A single glaucoma surgeon (S.D.) carried out all MicroPulse TLT procedures. Patients were placed in a supine position and a lid speculum was placed after monitored anesthesia care with propofol injection. Topical lidocaine gel in conjunction with a viscous artificial tear (Goniosol) was used as a coupling agent. No peri- or retrobulbar blocks were performed. All patients were treated with 2500 mW with a wavelength of 810 nm and duty cycle of 31.3%. A sterile, single-use, revised MicroPulse P3 Probe was applied using steady pressure parallel to the visual axis and the fiber-optic tip was positioned approximately 3 mm posterior to the conjunctival limbus. Three and 9 o'clock hours, previous sites of glaucoma surgery (filtering and drainage implant areas), and places of scleral thinning were avoided. The probe was moved continuously along the limbus and slid back and forth 4 or 5 times per hemisphere, depending on the treatment group. Eyes under MicroPulse TLT for 300 s underwent total of 10 sweeps (300 s group), MicroPulse TLT for 240 s had a total of 8 sweeps (240 s group), and MicroPulse TLT for 200 s underwent a total of 10 sweeps (200 s group). The average arc length spanned was 22 mm. Patients were discharged with topical 1% prednisolone acetate QID followed by a tapering course over an additional 2 weeks. No preoperative glaucoma medication washout was performed.

Table 1.

Micropulse transscleral laser therapy treatment.

	Total Sample	Treatment group
	Total Sample	300 s 10 sweeps	240 s 8 sweeps	200 s 10 sweeps
Time to laser from presentation (days)	8.29 ± 7.73 [1–34]	9.00 ± 9.32 [1–34]	8.25 ± 7.91 [1–33]	7.55 ± 5.68 [1–20]
Power of laser (mW)	2500	2500	2500	2500
Time duration of laser procedure (s)	248.39 ± 41.85 [200–300]	300	240	200
Number of passes of laser	9.35 ± 0.94 [8–10]	10	8	10
Total energy (J)	193.33	235	188	157
Fluence (J/cm²)	203.7	229	229	154

Note: values are presented as Mean ± SD, Median [Range].

Data collection and follow-up

Clinical data was recorded within electronic medical records using a standardized data collection form. Pre-operative data of interest included the following: age, gender, race, laterality, type of glaucoma, severity, procedure date, number of glaucoma medications, prior eye or laser surgery in the treated eye, lens status, IOP, imaging of anterior (ciliary body, angle) and posterior segment structures (optic nerve and fovea), and best-corrected visual acuity (BCVA). Glaucoma severity was classified according to the International Classification of Diseases 10 (ICD-10) definition.²⁸ The following post-operative data was collected: IOP, number of glaucoma medications, changes to anterior segment structures (ciliary body, angle, nerve, and fovea), BCVA, laser settings (power, time superior and inferior, duty cycle), and complications related to the procedure (iritis, corneal edema, hyphema, vitreous hemorrhage, vision loss, cataract progression or hypotony maculopathy). Total energy (J) and fluence (J/cm²) were also recorded for each treatment group. Total energy was calculated from the product of duty cycle, laser power (W), and exposure duration, while fluence was calculated from the product of laser power (W), duty cycle, and dwell time (s) divided by area (cm²). The spot diameter from the revised probe was measured to be 600 μm, corresponding to an area of 0.0028 cm².²⁹

Follow-up visits were set at 1, 3, and 6 months post-MicroPulse TLT laser intervention. Intraocular pressure, glaucoma medications, and BCVA were recorded at every follow-up visit. Intraocular pressure was measured using Goldmann Applanation Tonometry (GAT), and BCVA was assessed using a Snellen eye chart at 20 feet. Changes to the structure of the ciliary body, angle, nerve, and fovea were assessed in an observational manner using Cirrus HD-OCT imaging and ultrasound biomicroscopy (UBM) examination by the study's principal investigator (S.D.) at months 3 and 6.

Outcome measures

The primary outcome measure of this study was surgical success at the final follow-up visit (6 months). Surgical success was defined as a reduction of IOP ≥ 30% from baseline and between 6–18 mmHg, with no additional anti-glaucoma medications or secondary glaucoma surgical reinterventions required.³⁰ All eyes which did not meet surgical success were considered failures. Secondary outcome measures of success included changes from baseline in the number of glaucoma medications taken, BCVA, anterior (ciliary body, angle) and posterior segment structures (optic nerve, fovea), and visual fields at 6 months. The frequency of MicroPulse TLT-related complications and number of secondary glaucoma surgical reinterventions required throughout the follow-up period were also assessed.

Statistical analysis

Statistical analysis was performed using the software SPSS v25.0 software (IBM Corporation, NY). Descriptive statistics were expressed as the mean ± standard deviation for continuous variables, and frequency (percentage) for categorical variables. A paired sample t-test was performed for the primary analysis to compare mean IOP reduction from baseline to all the three time points (1, 3, 6 months). Within groups comparison of reduction of topical medications was performed and p-values were derived using Wilcoxon Signed-Ranks tests for each follow-up time point (1, 3, 6 months). A paired sample t-test was also performed to compare change in BCVA (logMAR) from baseline to all three time points (1, 3, 6 months). Intergroup comparisons were performed using the Kruskal-Wallis test.

Results

Patient demographics are reported in Table 2, and a diagram depicting the flow of eyes through each stage of the study can be found in Figure 2. A total of 62 eyes from 40 patients met inclusion criteria and were enrolled in this study. The 300 s, 240 s, and 200 s groups consisted of 22, 20, and 20 eyes, respectively. Most eyes were Caucasian (51 eyes, 82.3%) with 33 eyes from female subjects (53.2%). Primary open angle glaucoma (POAG) was the most common diagnosis, affecting 57 eyes (91.9%), and the majority of eyes had severe-stage glaucoma (39 eyes, 62.9%). The mean number of prior glaucoma laser procedures for all eyes was 1.27 ± 1.22 and was similar across all groups. Cataract surgery was the most common prior ocular procedure, having been performed in 50 eyes (80.6%). Differences in baseline values for IOP, topical medications, and LogMAR were found to be statistically significant between groups.

Figure 2.

CONSORT flow diagram showing flow of eyes (n) through each stage of the clinical trial.

Table 2.

Baseline patient demographic and clinical factors.

	Total Sample	Treatment group
	Total Sample	300 s 10 sweeps	240 s 8 sweeps	200 s 10 sweeps
Patient Demographics
Number of eyes, n	62	22	20	20
Left eye	33 (53.2%)	14 (63.6%)	7 (35.0%)	12 (60.0%)
Age	72.69 ± 9.53 [54–88]	71.73 ± 11.47 [54–88]	73.10 ± 8.87 [57–88]	73.35 ± 8.13 [58–87]	p = 0.14
Female	33 (53.2%)	9 (40.9%)	14 (70.0%)	10 (50.0%)
Ethnicity
Asian	2 (3.2%)	0 (0%)	0 (0%)	2 (10.0%)
African	3 (4.8%)	3 (13.6%)	0 (0%)	0 (0%)
Caucasian	51 (82.3%)	17 (77.3%)	17 (85.0%)	17 (85.0%)
Not reported	6 (9.7%)	2 (9.1%)	3 (15.0%)	1 (5.0%)
Co-morbidities
NIDDM	12 (19.4%)	5 (22.7%)	3 (15.0%)	4 (20.0%)
HTN	38 (61.3%)	10 (45.5%)	12 (60.0%)	16 (80.0%)
Type of glaucoma diagnosis
POAG	56 (90.3%)	19 (86.3%)	19 (95.0%)	18 (90.0%)
ACG	1 (1.6%)	0 (0%)	0 (0%)	1 (5.0%)
Neovascular	3 (4.8%)	1 (4.5%)	1 (5.0%)	1 (5.0%)
Uveitic/inflammatory	2 (3.2%)	2 (9.1%)	0 (0%)	0 (0%)
Glaucoma severity
Mild	3 (4.8%)	1 (4.5%)	1 (5.0%)	1 (5.0%)
Moderate	19 (30.6%)	2 (9.1%)	9 (45.0%)	8 (40.0%)
Severe	39 (62.9%)	19 (86.4%)	10 (50.0%)	10 (50.0%)
Indeterminate	1 (1.6%)	0 (0%)	0 (0%)	1 (5.0%)
Number of prior glaucoma procedures performed	1.27 ± 1.22 [0–5]	1.14 ± 1.39 [0–5]	1.55 ± 1.28 [0–4]	1.15 ± 0.93 [0–3]
Number of types of prior glaucoma procedures performed	1.21 ± 1.12 [0–4]	1.09 ± 1.27 [0–4]	1.45 ± 1.10 [0–3]	1.10 ± 0.97 [0–3]
Laser Peripheral Iridotomy
Selective Laser	4 (6.5%)	0 (0%)	3 (15.0%)	1 (5.0%)
Trabeculoplasty	23 (37.1%)	7 (31.8%)	7 (35.0%)	9 (45.0%)
Other prior ocular procedures
Cataract surgery	50 (80.6%)	17 (77.3%)	18 (90.0%)	15 (75.0%)
Anti-VEGF injections	7 (11.3%)	4 (18.2%)	2 (10.0%)	1 (5.0%)
Panretinal Photocoagulation	1 (1.6%)	1 (4.5%)	0 (0%)	0 (0%)
Other ocular surgeries or laser for retinal or corneal pathologies	12 (19.4%)	5 (22.7%)	5 (25.0%)	2 (10.0%)

LogMAR Visual Acuity	0.459 ± 0.753 [0–2.7]	0.827 ± 1.009 [0–2.7]	0.194 ± 0.233 [0–0.88]	0.320 ± 0.626 [0–2.10]
IOP	27.74 ± 6.42 [16–56]	32.32 ± 7.05 [21–56]	26.60 ± 4.48 [22–42]	23.85 ± 3.98 [16–32]	p = 0.033
# of Topical Glaucoma Medications taken [median]	1.79 ± 1.16, [2]	2.27 ± 1.08, [2]	1.60 ± 1.19, [1.5]	1.45 ± 1.10, [1]	p = 0.008
# of Drug Classes of Topical Glaucoma Medications	1.42 ± 0.90 [0–4]	1.77 ± 0.87 [1–4]	1.35 ± 0.99 [0–4]	1.10 ± 0.72 [0–3]	p = 0.004

Notes: values are presented as Mean ± SD [range], n (%); NIDDM = Non-insulin dependent diabetes mellitus; HTN = Hypertension; POAG = Primary Open-Angle Glaucoma; ACG = Angle-Closure Glaucoma; YAG = Yttrium Aluminum Garnet; VEGF = Vascular Endothelial Growth Factor; CME = Cystoid Macular Edema.

Intergroup comparisons were analyzed using Kruskal-Wallis tests.

Mean time from MicroPulse TLT to last follow-up visit for each group is displayed in Supplementary Table 1, and changes from baseline in IOP at each post-operative timepoint can be found in Figure 3 and Supplementary Table 2. IOP reductions from baseline were between 36.1 to 49.8% with the highest reductions seen in the 300 s group at all timepoints. Furthermore, statistically significant reductions from baseline in mean IOP (in absolute units and percentages) were seen within and between all three groups at all three timepoints (1, 3, 6 months). Surgical success was achieved in 72.7% (300 s group), 75.0% (240 s group), and 80.0% (200 s group) of eyes.

Figure 3.

Line graph showing the percentage decrease in intraocular pressure at 1-, 3-, and 6-month follow-up timepoints for each group. IOP – Intraocular pressure.

Changes from baseline in BCVA (in logMAR) at each postoperative timepoint can be found in Figure 4 and Supplementary Table 3. Overall, there were no significant changes in visual acuity in the total sample at any of the three time points (1, 3, 6 months). Transient reductions in visual acuity prior to 6 months were linked to cystoid macular edema, IOP spikes, and hyphema; however, all these cases resolved by the 6-month mark. Nine of 42 eyes (21.4%) assessed at 6 months showed a decrease in visual acuity by ≤2 Snellen lines. At 6 months, only 2 of 37 eyes demonstrated a reduction in visual acuity >2 Snellen lines. In one case, the decline was attributed to lens subluxation associated with aging, while the other involved a patient with limited visual potential (baseline visual acuity of 20/300). Both instances were deemed unrelated to the MicroPulse TLT procedure. One eye in the 240 s group experienced significant improvement in visual acuity at 6 months (p = 0.025).

Figure 4.

Line graph showing the change in LogMAR best corrected visual acuity at baseline, 1-, 3-, and 6-month follow-up timepoints for each group. BCVA – Best corrected visual acuity.

Changes from baseline in the number of glaucoma medications at each postoperative timepoint can be found in Figure 5 and Supplemental Table 4. Overall, a statistically significant reduction in the number of topical medications from baseline was found at each follow-up point (1, 3, 6 months) for the total sample. Within groups, significant medication reduction was reported for the 300 s group at 6 months (p = 0.049) and for the 200 s group at 1 month (p = 0.015). All groups showed a decrease in the number of medications at all other time points but did not reach statistical significance. No statistical difference was found in medication reduction when comparing between groups at any timepoint.

Figure 5.

Line graph showing the change in anti-glaucoma medications used at baseline, 1-, 3-, and 6-month follow-up timepoints for each group.

Postoperative complications are listed in Table 3. No adverse events were reported intraoperatively while performing the MicroPulse TLT. Following the procedure, adverse events were minimal. IOP spikes (defined as an increase in IOP by 25% greater than baseline) that were suggestive of steroid response occurred in three eyes in the 300 s group within 1 month and in one eye of the 200 s group at 3 months post-operatively. In the 300 s group, one eye developed hyphema and one eye developed cystoid macular edema. Secondary glaucoma surgical interventions before the 6-month post-operative timepoint included implantation of an Ahmed glaucoma valve FP7 (New World Medical, Rancho Cucamonga, CA, USA) in one eye in the 300 s group and a Xen gel stent (Allergan Inc., CA, USA) in one eye in the 200 s group. Both eyes had a history of multiple glaucoma procedures and IOPs continued to be uncontrolled following MicroPulse TLT. Additionally, no structural changes, including ciliary body thinning or damage, peripheral anterior synechiae, cyclodialysis, hypotony maculopathy or other posterior findings, for any eye were visualized on the Cirrus HD-OCT or UBM scans at months 3 and 6 post-operatively.

Table 3.

Adverse events after MicroPulse transscleral Laser therapy.

	Follow-up time point (months)
	1 (n = 60)	3 (n = 38)	6 (n = 42)
Total sample
IOP spike	3 (5.0%)	1 (2.6%)	0 (0%)
Hypotony	0 (0%)	0 (0%)	0 (0%)
Hyphema	1 (1.7%)	0 (0%)	0 (0%)
Corneal edema	0 (0%)	0 (0%)	0 (0%)
Cystoid macular edema	1 (1.7%)	0 (0%)	0 (0%)
Serous choroidal detachment	0 (0%)	0 (0%)	0 (0%)
Persistent inflammation of iritis	0 (0%)	0 (0%)	0 (0%)
Phthisis bulbi or sympathetic ophthalmia	0 (0%)	0 (0%)	0 (0%)
Cataract	0 (0%)	0 (0%)	0 (0%)
Mydriasis	0 (0%)	0 (0%)	0 (0%)
Vitreous Hemorrhage	0 (0%)	0 (0%)	0 (0%)
300 s 10 sweeps
IOP spike	3 (13.6%)	0 (0%)	0 (0%)
Hypotony	0 (0%)	0 (0%)	0 (0%)
Hyphema	1 (4.5%)	0 (0%)	0 (0%)
Corneal edema	0 (0%)	0 (0%)	0 (0%)
Cystoid macular edema	1 (4.5%)	0 (0%)	0 (0%)
Serous choroidal detachment	0 (0%)	0 (0%)	0 (0%)
Persistent inflammation of iritis	0 (0%)	0 (0%)	0 (0%)
Phthisis bulbi or sympathetic ophthalmia	0 (0%)	0 (0%)	0 (0%)
Cataract	0 (0%)	0 (0%)	0 (0%)
Mydriasis	0 (0%)	0 (0%)	0 (0%)
Vitreous Hemorrhage	0 (0%)	0 (0%)	0 (0%)
240 s 8 sweeps
IOP spike	0 (0%)	0 (0%)	0 (0%)
Hypotony	0 (0%)	0 (0%)	0 (0%)
Hyphema	0 (0%)	0 (0%)	0 (0%)
Corneal edema	0 (0%)	0 (0%)	0 (0%)
Cystoid macular edema	0 (0%)	0 (0%)	0 (0%)
Serous choroidal detachment	0 (0%)	0 (0%)	0 (0%)
Persistent inflammation of iritis	0 (0%)	0 (0%)	0 (0%)
Phthisis bulbi or sympathetic ophthalmia	0 (0%)	0 (0%)	0 (0%)
Cataract	0 (0%)	0 (0%)	0 (0%)
Mydriasis	0 (0%)	0 (0%)	0 (0%)
Vitreous Hemorrhage	0 (0%)	0 (0%)	0 (0%)
200 s 10 sweeps
IOP spike	0 (0%)	1 (10.0%)	0 (0%)
Hypotony	0 (0%)	0 (0%)	0 (0%)
Hyphema	0 (0%)	0 (0%)	0 (0%)
Corneal edema	0 (0%)	0 (0%)	0 (0%)
Cystoid macular edema	0 (0%)	0 (0%)	0 (0%)
Serous choroidal detachment	0 (0%)	0 (0%)	0 (0%)
Persistent inflammation of iritis	0 (0%)	0 (0%)	0 (0%)
Phthisis bulbi or sympathetic ophthalmia	0 (0%)	0 (0%)	0 (0%)
Cataract	0 (0%)	0 (0%)	0 (0%)
Mydriasis	0 (0%)	0 (0%)	0 (0%)
Vitreous Hemorrhage	0 (0%)	0 (0%)	0 (0%)

Note: values are presented as n (%); IOP = Intraocular Pressure.

Discussion

This study reports safety and efficacy outcomes of the second-generation MicroPulse TLT, up to 6 months post-operatively. To our knowledge, this is only the second prospective study on the MicroPulse Revised P3 Delivery Device and the first which evaluates MicroPulse TLT outcomes with 300-, 240-, and 200-s treatment durations. Additionally, outcomes following 3 differing MicroPulse TLT treatment times have not previously been reported. In this study, all three treatment times resulted in surgical success in over 70% eyes in all three groups at 6 months post-operatively, with the highest success rate being 80% in the 240 s group. Significant reductions in IOP were seen at all three timepoints in all three groups, with the 300 s group experiencing the largest reduction in IOP at 6 months (−16.06 mmHg; −49.0%); however, this may possibly be due to the significantly higher baseline mean IOP within this group (32.32 mmHg). Likewise, the 300 s group had the only statistically significant reduction in anti-glaucoma medications at 6 months (−0.41; p = 0.049), although it should be noted that this group consisted of 19 (86.4%) severe glaucoma patients compared to 10 (50%) in the other two groups.

Overall, the second-generation Micropulse TLT demonstrated an excellent safety profile across all three groups as all adverse events were temporary, and no vision-threatening complications occurred, despite the use of longer fluence and treatment durations. The 300 s treatment group did experience more transient postoperative complications (including hyphema, IOP spikes, and cystoid macular edema) compared with the other groups but these events were largely associated with patients diagnosed with secondary glaucomas (including pseudoexfoliative, neovascular, and uveitic types) or those undergoing treatment changes, such as alterations in antiglaucoma medication use. Similarly, although a trend suggested that patients with longer treatment durations and energy levels were more likely to require secondary glaucoma surgery, this was mainly attributed to the presence of secondary glaucomas and more severe glaucoma in these individuals.

Currently, there are two studies in prior literature which have reported the outcomes of MicroPulse TLT with the Revised P3 Delivery Device. In their single-blinded randomized controlled trial (RCT), Balendiran et al.,²⁵ reported 6-month outcomes of the second-generation MicroPulse TLT under total treatment durations of 120 s (6 sweeps) and 100 s (6 sweeps). The authors observed a significantly greater reduction in the 120 s group at month 3 (32.2% vs 4.1% decrease; p = 0.007) and month 6 (37.8% vs 3.6% decrease; p = 0.021) when compared to the 100 s group, with no vision-threatening complications or changes in BCVA reported throughout the follow-up period.²⁶ The comparably higher percentage IOP reduction observed in our total sample at month 3 (36.1–49.8% decrease) and month 6 (39.8–49.0% decrease) may suggest longer treatment times to be more efficacious. However, comparison is limited by differing study designs (single-blinded RCT vs non-blinded RCT) and the patient inclusion criteria for both studies (POAG patients only vs various glaucoma types). In a second study, Akiyama et al retrospectively assessed 40 patients with varying glaucoma types receiving second-generation MicroPulse TLT over a total treatment duration of 100 s and reported a comparably lower mean percentage IOP reduction of 26% at 3 months post-operatively.³¹ However, these authors did not report the total number of sweeps applied during the treatment procedure.

Prior prospective MicroPulse TLT studies using the first-generation P3 probe reported mean IOP reductions of 34.6%-49.9% at 6 months.^7,32,33 In their retrospective study, Akiyama et al compared clinical outcomes between the original and revised MicroPulse P3 probes and did not find significant differences in IOP reduction, glaucoma medication reduction, or BCVA changes between both devices, through 3 months.³¹ However, the study reported significantly lower pain levels for the procedure, compared to patients receiving MicroPulse TLT with the original P3 probe in another study by Tan et al (No pain: 68.4% vs 94.1%; Mild pain: 5.9% vs 26.3%; Moderate pain: 0% vs 5.3%).^31,32 It was hypothesized that the revised probe may cause less patient discomfort due to an additional fluid channel at the device tip, thereby preventing the protrusion from making contact with the conjunctiva.³¹

From a surgeon's perspective, the Revised P3 Delivery Device possesses numerous advantages over the first-generation probe. This second-generation probe was designed to address the ergonomic flaws of the original probe, with the aim of increasing energy delivery without compromising safety and efficacy outcomes. Unlike the protruding, rounded tip of the original probe, the revised probe has a recessed tip to allow for smoother gliding across the conjunctiva, minimizing any resultant trauma. The revised probe is also angled to direct laser delivery away from the limbal tissues and is positioned 3 mm posterior to the subconjunctival limbus, leading to better visualization of the treatment area and more consistent energy delivery. The footplate surface is concave to enhance stabilization, keeping the probe angled to the scleral surface. The original probe faced difficulties with maintaining a perpendicular position to the globe which led to less consistent laser delivery and treatment outcomes.²⁴ The enhancements of the Revised P3 Delivery Device are expected to improve surgical dexterity and reduce the significant complications seen with the first-generation probe, thereby positioning the device as a promising option for the treatment of refractory glaucoma. Furthermore, Agnifili et al. investigated the mechanisms of action of MicroPulse TLT with the first-generation probe, focusing on its beneficial modifications in the sclera that enhance uveoscleral aqueous humor outflow. Their study showed a significant increase in intra-scleral hypo-reflective space, with the superior, inferior, and total areas (S-MISHA, I-MISHA, and T-MISHA) increasing by 50% (p < 0.001), and a reduction in scleral reflectivity (S-SR, I-SR, and T-SR), particularly in successful treatments. These changes were associated with a median IOP reduction of 21% in failures and 38% in successes.³⁴ Building on the enhancements of the second-generation probe, it could be hypothesized that the refined 600-micra design would allow for more accurate scleral targeting, potentially resulting in more consistent and significant improvements in uveoscleral outflow and a greater overall reduction in IOP.

Despite its prospective design, this study possesses several limitations. Changes in anterior segment structures were measured subjectively rather than quantitatively; therefore, the precision and accuracy of these findings is limited. This study is also a relatively short-term one, with a few eyes having incomplete follow-up. The significant loss to follow-up observed over 6 months can be attributed to several factors, including patient non-compliance leading to reduced communication with physicians, difficulty attending follow-up visits, and the occurrence of adverse events or difficulties related to the COVID-19 pandemic leading to the delay of follow-up visits. Two patients also underwent secondary glaucoma surgeries prior to 6 months, which impacted their participation in the study. However, although a similar number of eyes from each group were analyzed at each timepoint and the sample size remained large enough at each timepoint to reach statistical significance for IOP reduction outcomes. Another significant limitation was the imbalance in baseline IOP, LogMAR, and glaucoma medication use between the three groups. As a result, intergroup comparisons of IOP and medication outcomes are limited. Despite this, we believe that reporting clinical outcomes from the longest treatment durations and highest fluence values to date adds valuable insights to the literature, enhancing the understanding of the efficacy of MicroPulse TLT when applied at higher energy levels. Regardless of the lack of clinically meaningful intergroup comparison, our study demonstrates that MicroPulse TLT with the Revised P3 Delivery Device can be safely performed at a fluence as high as 229 J/cm² without causing significant long-term vision-affecting complications, through 6 months. Larger scale and longer-term prospective studies on the second generation MicroPulse TLT are currently ongoing.

Conclusion

Second-generation MicroPulse TLT, performed under fluence values ranging from 154–229 J/cm², appears to be a safe and effective treatment option for patients with refractory glaucoma up to 6 months post-operatively. Both significant IOP reduction and reduced medication burden are observed, with an excellent intra- and post-operative safety profile.

Supplemental Material

sj-docx-1-ejo-10.1177_11206721251340102 - Supplemental material for Safety and efficacy of MicroPulse transscleral laser therapy with the revised P3 delivery device: A randomized controlled trial

Supplemental material, sj-docx-1-ejo-10.1177_11206721251340102 for Safety and efficacy of MicroPulse transscleral laser therapy with the revised P3 delivery device: A randomized controlled trial by P. Connor Lentz, Isabella V. Wagner, Devesh Kumar, Nithya Boopathiraj, Bryan C. H. Ang, Abhimanyu Ahuja, Leticia Checo, Darby D. Miller and Syril Dorairaj in European Journal of Ophthalmology

Footnotes

Acknowledgments

We would like to thank Ms. Joyce Baker for her generous contributions to the Department of Ophthalmology, Mayo Clinic, Florida, United States.

Data sharing statement

The author's institution does not permit data sharing. Any queries should be directed to the corresponding author (S.D.).

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Patient consent

Informed consent was obtained from all participants. All patient data and images have been deidentified and there is no personal identifying information within this report.

ORCID iDs

P. Connor Lentz

Isabella V. Wagner

Devesh Kumar

Abhimanyu Ahuja

Leticia Checo

Darby D. Miller

Syril Dorairaj

Supplemental material

Supplemental material for this article is available online.

References

Tham

Wong

, et al. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology 2014; 121: 2081–2090. DOI:https://doi.org/10.1016/j.ophtha.2014.05.013

Wagner

Stewart

Dorairaj

. Updates on the diagnosis and management of glaucoma. Mayo Clin Proc Innov Qual Outcomes 2022; 6: 618–635. DOI:https://doi.org/10.1016/j.mayocpiqo.2022.09.007

Craven

Singh

, et al. Reoperation rates and disease costs for primary open-angle glaucoma patients in the United States treated with incisional glaucoma surgery. Ophthalmol Glaucoma 2022; 5: 297–305. DOI:https://doi.org/10.1016/j.ogla.2021.10.011

Jampel

Solus

Tracey

, et al. Outcomes and bleb-related complications of trabeculectomy. Ophthalmology 2012; 119: 712–722. DOI:https://doi.org/10.1016/j.ophtha.2011.09.049

Pantalon

Feraru

Tarcoveanu

, et al. Success of primary trabeculectomy in advanced open angle glaucoma. Clin Ophthalmol 2021; 15: 2219–2229. DOI:https://doi.org/10.2147/opth.S308228

Gurnani

Tripathy

Tan

Chockalingam

Aquino

, et al. Micropulse transscleral diode laser cyclophotocoagulation in the treatment of refractory glaucoma. Clin Exp Ophthalmol 2010; 38: 266–272. DOI:https://doi.org/10.1111/j.1442-9071.2010.02238.x

Souissi

Le Mer

Metge

, et al. An update on continuous-wave cyclophotocoagulation (CW-CPC) and micropulse transscleral laser treatment (MP-TLT) for adult and paediatric refractory glaucoma. Acta Ophthalmol 2021; 99: e621–e653. DOI:https://doi.org/10.1111/aos.14661

Kaba

Somani

Tam

, et al. The effectiveness and safety of micropulse cyclophotocoagulation in the treatment of ocular hypertension and glaucoma. Ophthalmol Glaucoma 2020; 3: 181–189. DOI:https://doi.org/10.1016/j.ogla.2020.02.005

10.

Magacho

Lima

Ávila

. Double-session micropulse transscleral Laser (CYCLO G6) as a primary surgical procedure for glaucoma. J Glaucoma 2020; 29: 205–210. DOI:https://doi.org/10.1097/ijg.0000000000001426

11.

Preda

Karancsi

Munteanu

, et al. Clinical outcomes of micropulse transscleral cyclophotocoagulation in refractory glaucoma-18 months follow-up. Lasers Med Sci 2020; 35: 1487–1491. DOI:https://doi.org/10.1007/s10103-019-02934-x

12.

Wong

KYT

Aquino

Macasaet

, et al. MP3 Plus: a modified micropulse transscleral cyclophototherapy technique for the treatment of refractory glaucoma. J Glaucoma 2020; 29: 264–270. DOI:https://doi.org/10.1097/ijg.0000000000001443

13.

de Crom

Slangen

Kujovic-Aleksov

, et al. Micropulse trans-scleral cyclophotocoagulation in patients with glaucoma: 1- and 2-year treatment outcomes. J Glaucoma 2020; 29: 794–798. DOI:https://doi.org/10.1097/ijg.0000000000001552

14.

Emanuel

Grover

Fellman

, et al. Micropulse cyclophotocoagulation: initial results in refractory glaucoma. J Glaucoma 2017; 26: 726–729. DOI:https://doi.org/10.1097/ijg.0000000000000715

15.

Varikuti

VNV

Shah

Rai

, et al. Outcomes of micropulse transscleral cyclophotocoagulation in eyes with good central vision. J Glaucoma 2019; 28: 901–905. DOI:https://doi.org/10.1097/ijg.0000000000001339

16.

Williams

Moster

Rahmatnejad

, et al. Clinical efficacy and safety profile of micropulse transscleral cyclophotocoagulation in refractory glaucoma. J Glaucoma 2018; 27: 445–449. DOI:https://doi.org/10.1097/ijg.0000000000000934

17.

Jammal

Costa

Vasconcellos

JPC

, et al. Prospective evaluation of micropulse transscleral diode cyclophotocoagulation in refractory glaucoma: 1 year results. Arq Bras Oftalmol 2019; 82: 381–388. DOI:https://doi.org/10.5935/0004-2749.20190076

18.

Magacho

Lima

Ávila

. Double-session micropulse transscleral laser (CYCLO G6) for the treatment of glaucoma. Lasers Med Sci 2020; 35: 1469–1475. DOI:https://doi.org/10.1007/s10103-019-02922-1

19.

Garcia

Nguyen

Yelenskiy

, et al. Micropulse transscleral diode laser cyclophotocoagulation in refractory glaucoma: short-term efficacy, safety, and impact of surgical history on outcomes. Ophthalmol Glaucoma 2019; 2: 402–412. DOI:https://doi.org/10.1016/j.ogla.2019.08.009

20.

Radhakrishnan

Wan

Tran

, et al. Micropulse cyclophotocoagulation: a multicenter study of efficacy, safety, and factors associated with increased risk of complications. J Glaucoma 2020; 29: 1126–1131. DOI:https://doi.org/10.1097/ijg.0000000000001644

21.

Sarrafpour

Saleh

Ayoub

, et al. Micropulse transscleral cyclophotocoagulation: a look at long-term effectiveness and outcomes. Ophthalmol Glaucoma 2019; 2: 167–171. DOI:https://doi.org/10.1016/j.ogla.2019.02.002

22.

Tekeli

Köse

. Outcomes of micropulse transscleral cyclophotocoagulation in primary open-angle glaucoma, pseudoexfoliation glaucoma, and secondary glaucoma. Eur J Ophthalmol 2021; 31: 1113–1121. DOI:https://doi.org/10.1177/1120672120914231

23.

Yelenskiy

Gillette

Arosemena

, et al. Patient outcomes following micropulse transscleral cyclophotocoagulation: intermediate-term results. J Glaucoma 2018; 27: 920–925. DOI:https://doi.org/10.1097/ijg.0000000000001023

24.

Grippo

Töteberg-Harms

Giovingo

, et al. Evidence-Based consensus guidelines series for MicroPulse transscleral Laser therapy – surgical technique, post-operative care, expected outcomes and retreatment/enhancements. Clin Ophthalmol 2023; 17: 71–83. DOI:https://doi.org/10.2147/opth.S389198

25.

Balendiran

Landreneau

. Micropulse transscleral Laser therapy dosimetry utilizing the revised P3 delivery device: a randomized controlled trial. Ophthalmol Glaucoma 2023; 6: 283–290. DOI:https://doi.org/10.1016/j.ogla.2022.09.004

26.

Marchand

Singh

Agoumi

. Micropulse trans-scleral laser therapy outcomes for uncontrolled glaucoma: a prospective 18-month study. Can J Ophthalmol 2021; 56: 371–378. DOI:https://doi.org/10.1016/j.jcjo.2021.01.015

27.

Number Picker Wheel, https://pickerwheel.com/tools/random-number-generator/.

28.

Glaucoma ICD-10-CM Quick Reference Guide.

29.

Grippo

Sanchez

Stauffer

, et al. Micropulse(®) transscleral laser therapy – fluence may explain variability in clinical outcomes: a literature review and analysis. Clin Ophthalmol 2021; 15: 2411–2419. DOI:https://doi.org/10.2147/opth.S313875

30.

Shaarawy

Sherwood

Grehn

. WGA Guidelines on Design and Reporting of Glaucoma Surgical Trials. Amsterdam, The Netherlands: Kugler Publications, 2009.

31.

Akiyama

Fujishiro

Sugimoto

, et al. Short-term outcomes of micropulse transscleral laser therapy using the revised delivery probe in refractory glaucoma. Jpn J Ophthalmol 2022; 66: 549–558. DOI:https://doi.org/10.1007/s10384-022-00938-9

32.

Aquino

Barton

Tan

, et al. Micropulse versus continuous wave transscleral diode cyclophotocoagulation in refractory glaucoma: a randomized exploratory study. Clin Exp Ophthalmol 2015; 43: 40–46. DOI:https://doi.org/10.1111/ceo.12360

33.

Issiaka

Zrikem

McHachi

, et al. Micropulse diode laser therapy in refractory glaucoma. Adv Ophthalmol Pract Res 2023; 3: 23–28. DOI:https://doi.org/10.1016/j.aopr.2022.10.003

34.

Agnifili

Palamini

Brescia

, et al. Uveoscleral outflow routes after MicroPulse laser therapy for refractory glaucoma: an optical coherence tomography study of the sclera. Int J Mol Sci 2024; 25: 20240529. DOI:https://doi.org/10.3390/ijms25115913

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