Novel Micropulse Transscleral Cyclophotocoagulation System for Clinical Treatment of Refractory Glaucoma

Summary

This study introduces a novel protocol for micropulse transscleral cyclophotocoagulation (MP-TSCPC) in the clinical management of refractory glaucoma. The proposed MP-TSCPC system demonstrates significant therapeutic efficacy, including substantial reduction in intraocular pressure, decreased dependence on medication, and minimized incidence of treatment-related complications.

Abstract

Traditional transscleral cyclophotocoagulation has been established as an effective intervention for refractory glaucoma. While demonstrating therapeutic efficacy, conventional TSCPC raises concerns regarding potential complications to ocular structures. In contrast, micropulse transscleral cyclophotocoagulation (MP-TSCPC) represents a significant advancement by selectively targeting pigmented epithelium to modulate aqueous humor production. This innovative approach has emerged as a well-tolerated treatment modality with reduced complication risks, supported by an increasing body of clinical evidence. This protocol details the application of a commercially available MP-TSCPC system for intraocular pressure reduction and complication mitigation in refractory glaucoma management. The procedure requires specific instrumentation, including the laser system equipped with the Micropulse Pars Plana Procedure (MP3) handpiece. Treatment efficacy and safety are governed by four critical parameters: power, duty cycle, treatment duration, and dwell time, which collectively determine the total energy delivered to the ciliary body. This paper systematically reviews the methodological framework for implementing MP-TSCPC in refractory glaucoma treatment.

Introduction

Glaucoma represents the predominant cause of irreversible vision loss globally, characterized by progressive optic neuropathy. The pathogenesis is primarily associated with sustained elevation of intraocular pressure (IOP), which induces structural damage to the optic nerve head, resulting in characteristic visual field defects and potential progression to complete vision loss¹. Epidemiological projections indicate a substantial increase in global glaucoma prevalence, with estimates surpassing 100 million cases by 2040, particularly concentrated in Asian populations. China, bearing the largest glaucoma burden in Asia, reported a significant disease prevalence with approximately 21 million diagnosed cases in 2020. Notably, epidemiological data reveal that 25% of these cases had advanced to blindness, underscoring the substantial public health impact². Reducing IOP remains the cornerstone of glaucoma management and is crucial for controlling disease progression. Treatment strategies typically include medications, laser therapy, and surgical interventions³.

Refractory glaucoma refers to glaucoma that is resistant to control despite maximal treatment with medications or conventional filtering surgeries and is associated with poor prognosis. This complex condition manifests as severe visual impairment and often debilitating ocular pain, substantially impacting patients' quality of life. The spectrum of refractory glaucoma encompasses several distinct subtypes, including neovascular glaucoma, secondary inflammatory glaucoma, traumatic glaucoma, and developmental glaucoma^4,5,6. Laser-based ciliary body treatments reduce intraocular pressure (IOP) by selectively damaging the ciliary body, thereby decreasing aqueous humor production and slowing glaucoma progression. While conventional laser therapies demonstrate effective IOP reduction, their clinical application is limited by significant complication profiles, including postoperative pain, uveitis, pigment dispersion syndrome, and hyphema, among others⁷.

Micropulse transscleral cyclophotocoagulation (MP-TSCPC) has recently emerged as a promising therapeutic modality for refractory glaucoma^8,9. This innovative technique induces subthreshold cell damage to the pigmented epithelium and the nonpigmented epithelium, which both can directly reduce the production of aqueous humor. The procedure utilizes a unique micropulse delivery system characterized by alternating ON and OFF cycles: during the ON phase, thermal energy accumulates in pigmented ciliary body tissues, achieving therapeutic coagulation thresholds, while the subsequent OFF phase allows for tissue cooling, thereby preserving adjacent nonpigmented structures^10,11.

Emerging evidence suggests that MP-TSCPC exerts its hypotensive effects through multiple mechanisms. The observed increase in choroidal thickness may facilitate enhanced uveoscleral outflow⁸. Additionally, recent studies propose that contraction of longitudinal ciliary muscle fibers induces posterior and inward displacement of the scleral spur, subsequently enlarging the trabecular meshwork configuration and promoting conventional aqueous outflow^7,8. These multifaceted mechanisms distinguish MP-TSCPC from conventional TSCPC, offering potentially superior IOP-lowering efficacy with improved safety profiles.

This protocol aims to systematically review the treatment methodology for refractory glaucoma using MP-TSCPC. It is imperative to emphasize that this advanced procedure should only be performed by trained, licensed ophthalmic professionals with specialized expertise in laser glaucoma surgery.

Protocol

This protocol has been developed in strict accordance with the ethical guidelines established by the local institutional human research ethics committee, the Clinical Research Ethics Committee at Nanjing Medical University Eye Hospital. Informed consent was obtained from all participants. Ensuring compliance with all applicable regulatory standards and ethical principles governing clinical research.

1. Preparation before the treatment

NOTE: Patients with albinism are strongly advised against using MP-TSCPC. Caution should be exercised in patients with congenital/pediatric glaucoma or for those at high risk of postoperative inflammation, such as patients with uveitis.

1. Patient's preparation
   1. Use the following inclusion criteria: 1) Positive diagnosis of refractory glaucoma treatment; 2) Age ≥ 18 years; 3) Signed informed consent; 4) Intraocular pressure ≥ 21 mmHg with maximal topical and/ or systemic IOP-lowering medication or standard glaucoma filtration surgery.
   2. Use the following exclusion criteria: 1) Eye surgery performed over the last 3 months; 2) Eye inflammation; 3) albinism; 4) congenital glaucoma, and childhood glaucoma; 5) active uveitis; 6) scleral thinning > 1 clock hour.
      NOTE: Scleral thinning > 1 clock hour indicates that the area of thinning extends over more than one clock hour, not the actual thickness of the sclera.
   3. Review the patient's medical history to be aware of any relevant information and maintain appropriate documentation in the patient's medical record.
   4. Conduct a consultation with the patient, allowing them to ask any questions they may have regarding the treatment. Following the discussion, ensure they sign an informed consent document in preparation for the procedure.
   5. Prior to surgery, perform a comprehensive baseline ophthalmic examination for all patients. This includes a review of medical history, slit-lamp biomicroscopy, gonioscopy, assessment of best-corrected visual acuity (BCVA), fundus photography, intraocular pressure (IOP) measurement, optical coherence tomography, axial length (AL) measurement using IOL-Master, evaluation of anterior chamber depth (ACD), and corneal thickness measurement. The required surgical tools and equipment are detailed in Table of Materials.
2. Equipment preparation
   1. Ensure that all necessary equipment is available, including the laser system with the original handpiece and the laser foot pedal.

2. Treatment design

1. Configure the laser to MicroPulse mode and set the following parameters:
   Power: Set between 1.5 W and 2.5 W, with 2 W being the most commonly used value.
   Duty cycle: Set at 31.3%.
   Treatment duration: The total laser treatment time usually ranges from 100 s to 360 s.
   Dwell time: the time (s) that the probe remains in the same location.
   ​Total Energy = Power x Duration x 31.3% Duty Cycle.
2. Laser application
   1. Apply treatment in a circular distribution around the entire ciliary body. Localized intensification may be implemented based on specific clinical requirements, like in cases requiring avoidance of prior glaucoma surgical sites or areas with scleral thinning.

3. Pre-operative procedure

1. Ask patients to lie down in a supine position and administer retrobulbar anesthesia with lidocaine hydrochloride injection, combined with topical anesthesia using proparacaine hydrochloride eye drops Figure 1.
   NOTE: For patients unable to tolerate local anesthesia, general anesthesia should be induced through intravenous infusion. Tracheal intubation can be performed under general anesthesia using a laryngeal mask airway.
2. Perform skin disinfection using 5% povidone-iodine with some sterilized gauze or cotton balls. Demarcate the disinfection field as follows: centered on the operative eye, extending superiorly to 2 cm above the supraorbital ridge, inferiorly to the nasolabial fold, medially beyond the nasal midline, and laterally to the anterior border of the temporal hairline. Apply a disposable surgical adhesive film to maintain a sterile field.
3. Position the eyelid speculum to fully expose the eyeball, then disinfect the conjunctival sac with 0.5% povidone-iodine solution (diluted from 10% stock with balanced saline) using a sterile syringe for 3 min. For iodine-sensitive patients, substitute with 0.05% chlorhexidine. Avoid corneal contact during instillation.
4. Mark the 3 o'clock and 9 o'clock positions of the operated eye using a fluorescent marker pen to avoid damage to the long posterior ciliary arteries Figure 2.

4. Laser therapy

1. Use the diode laser photocoagulation system, operating at 810 nm wavelength, in micropulse mode.
2. Position the laser probe perpendicular to the scleral surface, aligned along the posterior 1.0 mm of the corneal limbus. Direct the indentation toward the limbus and press the probe against the bulbar conjunctiva. Apply viscoelastic agents to the surface for lubrication and coupling (Figure 3).
   NOTE: During treatment, avoid the previous filtering operation site, as well as the 3 o'clock and 9 o'clock positions, to prevent injury to the long ciliary nerve.
3. Perform continuous arc scanning with the laser probe on the upper half of the eyeball from 9:30 to 2:30, repeat 8x for 10 s each, totaling 80 s. Perform the same procedure on the lower half of the eyeball from 3:30 to 8:30, matching the duration used for the upper half. Set the scanning speed at a 150° arc of one ocular hemisphere in 15 s. (Figure 4).
   NOTE: The scanning speed of the laser probe should not be too fast to ensure therapeutic efficacy. Additionally, the laser should not remain stationary at any single position during emission.
4. Press the appropriate foot pedal to stop the laser emission. Document the treatment-related parameters, such as power, duty cycle, treatment duration, and the size of the treated area.
5. Withdraw the probe from the operated eyeball, followed by the removal of the eyelid speculum.
6. Apply tobramycin and dexamethasone eye ointment to the conjunctival sac, bandage the eye with sterile gauze, and assist the patient in leaving the treatment room.
7. Turn off the laser photocoagulation system using the power switch before unplugging it from the wall power source.
8. Disconnect the connectors from the laser photocoagulation system and dispose of them according to institutional policy.

5. Postoperative treatment

1. Medical treatment
   1. Administer anti-inflammatory drugs such as tobramycin and dexamethasone eye drops (0.3% tobramycin + 0.1% dexamethasone) for 1-2 weeks postoperatively.
      NOTE: These drugs help reduce ocular inflammation, alleviate symptoms such as eye redness and pain, prevent tissue adhesion and excessive scar formation, suppress immune responses, and minimize the risk of postoperative complications.
   2. Administer non-steroidal anti-inflammatory drugs (NSAIDs) such as pranoprofen eye drops (0.1%) for 1-2 weeks.
      NOTE: These drugs serve as adjuncts to glucocorticoid eye drops (0.1% fluorometholone), helping to reduce the dosage and duration of glucocorticoid use, thereby lowering the risk of associated side effects.
   3. Use intraocular pressure-lowering medications such as beta-blockers (1% Carteolol eye drops), carbonic anhydrase inhibitors (1% dorzolamide), and prostaglandin analogs (0.005% latanoprost) if needed. Depending on intraocular pressure fluctuations observed during follow-up, prescribe these medications alone or in combination, for either short-term control or long-term management. Early postoperative use of prostaglandin analogs necessitates concurrent anti-inflammatory therapy (glucocorticoids/NSAIDs) and vigilant OCT assessment for macular edema.
   4. Administer antibiotic eye drops such as levofloxacin eye drops (0.5%) for 3-7 days postoperatively to prevent ocular infections and protect the surgical site from bacterial invasion and subsequent inflammation.
2. Complications treatment
   1. Elevated intraocular pressure: If postoperative intraocular pressure is significantly elevated and unresponsive to medication, carry out additional measures such as anterior chamber puncture and drainage to rapidly reduce intraocular pressure and protect the optic nerve.
   2. Low intraocular pressure: If low intraocular pressure results from excessive inhibition of ciliary body function, leading to reduced aqueous humor production, administer neurotrophic drugs such as mecobalamin to promote ciliary body recovery, increase aqueous humor production, and improve intraocular pressure.
   3. Severe inflammation: In cases of severe inflammation, such as endophthalmitis, begin administration of systemic antibiotics or glucocorticoids. Administer intravitreal injections, if necessary.
   4. Corneal edema: Manage mild corneal edema with topical hypertonic agents, such as 50% glucose eye drops, to promote corneal hydration and reduce swelling. For severe corneal edema that affects vision, use adjunctive treatments such as corneal bandage lenses to facilitate corneal recovery.

6. Postoperative observation

NOTE: Postoperative follow-ups were conducted regularly by professional optometrists and ophthalmologists. Modifications to the follow-up schedule or treatment plan may be required based on individual patient needs and clinical conditions.

1. Follow-up schedule: Schedule follow-up visits with a certified optometrist or ophthalmologist on the 1^st day, at 1 week, 1 month, 3 months, 6 months, and 1 year post-surgery.
2. Primary outcome measures: During follow-up visits, record the following primary outcome measures:
   Postoperative intraocular pressure (IOP): Measure at each visit using a non-contact tonometer.
   Visual acuity: Assess using a logarithmic visual acuity chart.
   Use of anti-glaucoma medications: Document the medications by a professional optometrist or ophthalmologist.
   Postoperative adverse events: Monitor and record to ensure timely intervention if needed.

Results

Data from the above clinical trial evaluating a novel MP-TSCPC was recently presented and is summarized in Table 1. This study included 10 patients (10 eyes) with refractory glaucoma, comprising 2 male patients (2 eyes) and 8 female patients (8 eyes). The cohort comprised 4 eyes (40%) with neovascular glaucoma, 4 eyes (40%) with chronic angle-closure glaucoma, 1 eye (10%) with open-angle glaucoma, and 1 eye (10%) with secondary glaucoma.

The mean preoperative IOP was 37.4 ± 11...

Discussion

This protocol establishes methodology for MP-TSCPC application in medically refractory glaucoma management, detailing perioperative workflow from preoperative preparation through initial intervention execution. The parameters for a typical treatment session are also introduced. It is important throughout the course of the parameter's determination and subsequent treatment sessions to take care that all steps of this protocol are being followed correctly, and that the patient is communicative with the operator to ensu...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Eyelid Retractor	Nanjing Beden Medical Co .	NA	fully expose the eyeball
Gonioscope	Volk Optical Inc	CS002	Evaluates the anterior chamber angle.
IOL-Master	Carl Zeiss Meditec	Model 700	Precise measurement of axial length, anterior chamber depth, and corneal curvature.
Laser Probe	Iridex	LP-3001	Delivers laser energy to the target tissue.
Levofloxacin Eye Drops	Santen	NA	Antibiotic eye drops to prevent postoperative infection.
Lid Speculum	Katena	SPC-3001	Holds the eyelids open to expose the surgical area.
Lidocaine Injection	Otsuka Pharmaceutical Co.	NA	used to administer retrobulbar anesthesia
MicroPulse Laser System	Iridex	MP3-1001	Example: Iridex MicroPulse P3, used for cyclophotocoagulation.
Non-Contact Tonometer	Topcon	CT-800A	Measures preoperative intraocular pressure (IOP).
Ophthalmic A/B Ultrasonic Scanner	Suowei Electronic Technology Co.	SW-2100	diagnosing eye conditions by providing precise measurements of ocular structures and detailed imaging of the eye and orbit.
Optical Coherence Tomography (OCT)	Carl Zeiss Meditec	CIRRUS5000	Non-invasive imaging for detailed retinal layer analysis.
Povidone-Iodine Solution	JumpCan	NA	Used for preoperative ocular disinfection (typically 5% concentration).
Proparacaine Eye Drops	Alcon	NA	Topical anesthetic for preoperative anesthesia.
Slit Lamp Microscope	KANGHUA	SLM-2ER	Used for preoperative ocular examination.
Specular Microscope	Tomey	EM-3000	Evaluation of corneal endothelial cell density and morphology.
Sterile Cotton Swabs	Medline	SW-8001	Used for disinfection and cleaning.
Sterile Gloves	Halyard Health	GLV-7001	Worn by the surgical team to ensure aseptic technique.
Sterile Surgical Drape	3M	DRN-5001	Maintains a sterile surgical field.
Surgical Tape	3M	TAP-5001	Used to secure the eye drape.
Tobramycin and Dexamethasone Eye Drops	NOVARTIS	NA	Steroid eye drops to reduce postoperative inflammation.
Topcon Non-Mydriatic Retinal Camera	Topcon	NW-400	Laser scanning ophthalmoscope with multi-modal imaging capabilities.
Ultrasound Biomicroscopy (UBM)	Ellex	UBM-5001	Provides detailed imaging of the ciliary body region.
Visual Acuity Chart	Reichert	VT-1001	Used to assess preoperative visual acuity.