Treatment Outcomes of MicroPulse Trans-scleral Cyclophotocoagulation in Uncontrolled Glaucoma

Cyclophotocoagulation (CPC) is a type of cycloablation using laser to treat glaucoma. It involves ciliary body destruction by targeting the ciliary epithelium and stroma, resulting in a reduction in aqueous secretion and hence intraocular pressure. This strategy is effective for all forms of glaucoma.

Traditional trans-scleral cyclophotocoagulation (TSCPC) achieve its cyclodestructive action by using continuous diode laser to target the melanin in the pigmented ciliary body epithelium. However, the continuous mode has been shown to cause significant collateral tissue damage to adjacent non-pigmented structures including the ciliary stroma and ciliary muscle. Traditional TSCPC may therefore be associated with serious complications including uveitis, visual deterioration, chronic hypotony, and others.

More recently, a micropulse delivery mode of diode laser (Micropulse TSCPC, mTSCPC) has been used to treat glaucoma by ablating the ciliary processes and reduce aqueous humor production with more selective targeting and less collateral damage. In contrast to conventional laser delivery where a continuous flow of high intensity energy is delivered, micropulse laser application delivers a series of repetitive short pulses of energy with rest periods in between pulses. Only a few studies have described the outcomes of this novel glaucoma therapy, showing mTSCPC to have comparable efficacy with fewer side effects when compared with traditional continuous wave mode diode laser delivery.This improved side effect profile has the potential to make mTSCPC an earlier therapeutic option instead of reserving it exclusively for end-stage refractory eyes.

• MicroPulse® P3 Glaucoma Device (MP3) (Device), also known as CYCLO G6 Glaucoma Laser System (Iridex, Mountain View, CA): Laser settings will be programmed as follows: power-2000mW-2500mW (average 2000mW) of 810nm infrared diode laser set on micropulse delivery mode; micropulse "on" time-0.5ms; micropulse "off" time-1.1ms; and duty cycle (proportion of each cycle during which the laser is on)-31.33 %. The laser probe will be applied in a continuous sliding or painting motion from 9:30 to 2:30 and from 3:30 to 8:30. The probe will be applied perpendicular to the limbus with the edge directly on the limbus at all times (fiberoptic tip at 3 mm posterior to the limbus). The laser will be delivered over 360° for 160-320s. Treatment duration will be adjusted based on iris color and glaucoma severity (mild glaucoma: 160s, moderate glaucoma: 240s, advanced glaucoma: 240-320s).

Primary outcomes

• Intraocular Pressure (IOP) [18 months]: In millimeters of mercury (mmHg), measured with the Goldmann applanation tonometer

Secondary outcomes

• Intraocular Pressure (IOP) [1 week, 1 month, 3 months, 6 months, 12 months]: In millimeters of mercury (mmHg), measured with the Goldmann applanation tonometer
• Number of Participants With Repeat Treatments [18 months]: Number of participants needing a repeat laser treatment during the study
• Number of Intraocular Pressure Lowering Medications [1 week, 1 month, 3 months, 6 months, 12 months, 18 months]: Number of drops and oral medications used by the patient compared to baseline
• Corrected Distance Visual Acuity (CDVA) [1 week, 1 month, 3 months, 6 months, 12 months, 18 months]: Number of lines reduction or improvement from baseline on Snellen acuity chart at 6 meters
• Cup-to-disc Ratio (CDR) [18 months]: Progression of CDR compared to baseline, assessed by an ophthalmologist on dilated fundus examination
• Visual Field Index (VFI) [18 months]: Determined by Humphrey automated perimetry Sita 24-2 visual field testing
• Mean Deviation (MD) [18 months]: Determined by Humphrey automated perimetry Sita 24-2 visual field testing
• Pattern Standard Deviation (PSD) [18 months]: Determined by Humphrey automated perimetry Sita 24-2 visual field testing
• Average Retinal Nerve Fiber Layer (RNFL) Thickness [18 months]: In micrometer, determined by optical coherence tomography (OCT)
• Average Ganglion Cell Layer (GCL) Thickness [18 months]: In micrometer, determined by optical coherence tomography (OCT)
• Cup-to-disc Ratio (CDR) Assessed by Optical Coherence Tomography (OCT) [18 months]: Progression of vertical CDR compared to baseline, assessed by optical coherence tomography (OCT) parameters
• Pain Level During Laser Treatment [1 day]: Using a verbal analog scale for pain level (none = no subjective feeling of pain, mild = pain easily tolerable, moderate = pain tolerable with difficulty, severe = pain intolerable)

Sex: All, ages: 18 Years to any, accepts healthy volunteers

Inclusion Criteria:

* Patients of either sex and any race aged 18 years old and above.
* Followed by a glaucoma subspecialist at University of Montreal Hospital Center.
* Intraocular pressure (IOP) above target and unresponsive to maximal tolerated medical therapy with or without previous surgical intervention.

  1. mild glaucoma: IOP > 18 mmHg
  2. moderate glaucoma: IOP > 15 mmHg
  3. advanced glaucoma: IOP > 12 mmHg
* Considered poor candidates for additional filtering surgery or implantation of glaucoma drainage devices.

Exclusion Criteria:

* Patients unable to give informed consent.
* Patients with significant scleral thinning, defined as thinning of more than one clock hour noticed on scleral transillumination.
* Ocular infection or inflammation in the study eye in the 2 months prior to enrolment.
* Intraocular surgery in the study eye in the 2 months prior to enrolment.

Participant flow

Outcome results

• Intraocular Pressure (IOP) (Primary), Mean, millimeters of mercury (mm Hg): Micropulse Trans-scleral CPC 15.2 +/- 4.1
• Intraocular Pressure (IOP) (Secondary), Mean, millimeters of mercury (mm Hg): Micropulse Trans-scleral CPC 18.2 +/- 6.3
• Number of Participants With Repeat Treatments (Secondary), Count of participants, Participants: Micropulse Trans-scleral CPC 10
• Number of Intraocular Pressure Lowering Medications (Secondary), Mean, glaucoma medication classes: Micropulse Trans-scleral CPC 3.5 +/- 0.7
• Corrected Distance Visual Acuity (CDVA) (Secondary), Mean, LogMAR: Micropulse Trans-scleral CPC 0.81 +/- 0.86
• Cup-to-disc Ratio (CDR) (Secondary), Mean, ratio: Micropulse Trans-scleral CPC 0.82 +/- 0.13
• Visual Field Index (VFI) (Secondary), Mean, percents: Micropulse Trans-scleral CPC 57 +/- 27
• Mean Deviation (MD) (Secondary), Mean, decibel (dB): Micropulse Trans-scleral CPC -15.16 +/- 7.72
• Pattern Standard Deviation (PSD) (Secondary), Mean, decibel (dB): Micropulse Trans-scleral CPC 7.87 +/- 3.18
• Average Retinal Nerve Fiber Layer (RNFL) Thickness (Secondary), Mean, micrometers: Micropulse Trans-scleral CPC 62 +/- 12
• Average Ganglion Cell Layer (GCL) Thickness (Secondary), Mean, micrometers: Micropulse Trans-scleral CPC 53 +/- 14
• Cup-to-disc Ratio (CDR) Assessed by Optical Coherence Tomography (OCT) (Secondary), Mean, ratio: Micropulse Trans-scleral CPC 0.82 +/- 0.13
• Pain Level During Laser Treatment (Secondary), Count of participants, Participants: Micropulse Trans-scleral CPC 34

Adverse events

Time frame: 18 months

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• Results publication: Marchand M, Singh H, Agoumi Y. Micropulse trans-scleral laser therapy outcomes for uncontrolled glaucoma: a prospective 18-month study. Can J Ophthalmol. 2021 Dec;56(6):371-378. doi: 10.1016/j.jcjo.2021.01.015. Epub 2021 Feb 10. PMID 33577756

• Study Protocol and Statistical Analysis Plan (PDF, 2017-02-14)

• Harmanjit Singh, MD, Principal investigator, Centre hospitalier de l'Université de Montréal (CHUM)
• Michael Marchand, MD, Principal investigator, Centre hospitalier de l'Université de Montréal (CHUM)