Treatment Outcomes of MicroPulse Trans-scleral Cyclophotocoagulation (mTSCPC) in Uncontrolled Glaucoma at the University of Montreal Hospital Center (CHUM)
Phase: NA
Conditions: Glaucoma, Glaucoma, Open-Angle, Glaucoma, Neovascular, Glaucoma and Ocular Hypertension, Glaucoma Eye, Glaucoma, Uncompensated, Glaucoma Secondary
Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

 
 
 
 
 
 
Research Protocol and Statistical Analysis 
 
 
 
 
 
Treatment Outcomes of MicroPulse Trans-scleral Cyclophotocoagulation in 
Uncontrolled Glaucoma 
NCT03187418 
 
 
 
Investigators: 
Michael Marchand, MD, FRCSC 
Harmanjit Singh, MD, FRCSC 
Younes Agoumi, MD, FRCSC 
 
 
 
 
Protocol Version: 1.0 (2017-02-14) 
 
Funding: Fonds de recherche en ophtalmologie de l’Université de Montréal (FROUM) 
 

Nagano # : 2017-6956 
mTSCPC - HS 
PI : Harmanjit Singh 
Protocol – V01-00 
2017-02-14 
Page 2 of 9 
TABLE OF CONTENTS 
 
Introduction ............................................................................................................................... 3 
Purpose ........................................................................................................................................ 3 
Study Design  .............................................................................................................................. 4 
Population ................................................................................................................................... 4 
Baseline Parameters ............................................................................................................... 4 
Treatment .................................................................................................................................... 5 
Post-Intervention Follow-Up ................................................................................................ 5 
Primary and Secondary Outcomes ..................................................................................... 6 
Statistical Analysis ................................................................................................................... 6 
Benefits, Risks and Disadvantages  .................................................................................... 6 
Confidentiality  .......................................................................................................................... 7 
Information and Consent Form  .......................................................................................... 7 
Scientific and Ethics Committees ........................................................................................ 7 
Budget ........................................................................................................................................... 7 
References ................................................................................................................................... 7 
 
 
 
 

Nagano # : 2017-6956 
mTSCPC - HS 
PI : Harmanjit Singh 
Protocol – V01-00 
2017-02-14 
Page 3 of 9 
Introduction 
Glaucoma is a leading cause of irreversible blindness worldwide.1-2 Adequate control of the 
intraocular pressure (IOP), which is the only well-established modifiable risk factor in glaucoma, 
generally allows to prevent significant loss of visual field.3 Glaucoma treatments are therefore 
intended to either increase the outflow or decrease the production of aqueous humor in order 
to reduce intraocular pressure and maintain good visual function. When IOP is difficult to 
control with medications only, surgical procedures are sometimes required to preserve optic 
nerve function.4-5  
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 IOP. This strategy is effective for all forms of glaucoma.6-11 
Traditional trans-scleral cyclophotocoagulation (TSCPC) achieve its cyclodestructive action by 
using continuous diode laser to target the melanin in the pigmented ciliary body epithelium.12-14 
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 rarely phthisis bulbi and sympathetic ophthalmia.15-18 Due 
to these risks of serious complications and the unpredictability of effect, TSCPC is typically 
reserved for the treatment of refractory glaucoma or palliation of painful eyes with a very poor 
prognosis.19  
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.13 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. This allows energy to build up in the targeted pigmented tissues, eventually reaching the 
coagulative threshold, while the adjacent non-pigmented structures have time to cool off during 
the off cycle without reaching the point of coagulation.20-27 
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.13-14,28 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. 
Purpose 
The goal of this study is to evaluate the efficacy and safety of the novel form of trans-scleral 
cyclophotocoagulation using micropulse diode laser and trans-pars plana treatment (Micropulse 
TSCPC, mTSCPC MP3, IRIDEX CYCLO G6™ Glaucoma Laser System, CA, USA).  
The main outcome will be the efficacy of the mTSCPC MP3 evaluated by the short-term and 
long-term reduction of IOP and number of anti-glaucomatous drops used postoperatively. The 
other outcomes will be the safety of this device by looking at the possible decrease in corrected 
distance visual acuity (CDVA), the progression of the optic nerve cupping and the complications.   
 
 

Nagano # : 2017-6956 
mTSCPC - HS 
PI : Harmanjit Singh 
Protocol – V01-00 
2017-02-14 
Page 4 of 9 
Study Design  
This will be a prospective, interventional and monocentric study based in a university hospital 
setting. 
Based on the established inclusion and exclusion criteria, the study investigators will enrol 
patients followed in their own clinic or new patients referred by other ophthalmologists. After 
learning and asking questions about the risks and benefits of participating in this study, patients 
will be requested to sign the appropriate information and consent form. They will then have a 
complete pre-interventional ophthalmologic evaluation including corrected distance visual 
acuity (CDVA), a complete slit-lamp biomicroscopy examination, an IOP measurement with the 
Goldmann applanation tonometer, a measurement of the central corneal thickness with a 
handheld pachymeter (IOPac Advanced, Heidelberg Engineering, Franklin, MA, USA), and a 
dilated fundus examination with a particular attention to the cup-to-disk ratio (CDR) of the optic 
nerve. 
Population 
A total of fifty (50) glaucoma patients will be included in this prospective study. They will be 
recruited by two (2) glaucoma specialists at the Notre-Dame Hospital department of 
ophthalmology (University of Montreal Hospital Center, CHUM). Patients will meet the inclusion 
and exclusion criteria listed below (Tables 1-2). Participants will undergo a micropulse trans-
scleral cyclophotocoagulation (mTSCPC MP3) treatment session in the affected eye. 
Table 1: 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. 
IOP above target and unresponsive to maximal tolerated medical therapy with or without 
previous surgical intervention. 
a. mild glaucoma: IOP > 18 mmHg 
b. moderate glaucoma: IOP > 15 mmHg 
c. advanced glaucoma: IOP > 12 mmHg 
Considered poor candidates for additional filtering surgery or implantation of glaucoma 
drainage devices. 
 
Table 2: 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. 
Baseline Parameters 
The following baseline parameters will be recorded for each patient: age, gender, race/ethnicity, 
type of glaucoma diagnosis, ocular history (previous surgery and laser therapy), preoperative 
IOP, number of glaucoma medications prior to intervention, preoperative corrected distance 
visual acuity (CDVA), preoperative cup-to-disc ratio (CDR), pain level (using a verbal analog scale, 
see Table 3). 
 

Nagano # : 2017-6956 
mTSCPC - HS 
PI : Harmanjit Singh 
Protocol – V01-00 
2017-02-14 
Page 5 of 9 
Table 3: Verbal analog scale for pain level 
Pain grade 
Description of pain during laser, after subconjunctival anesthesia 
None 
No subjective feeling of pain. 
Mild  
Pain easily tolerable. 
Moderate  
Pain tolerable with difficulty. 
Severe  
Pain intolerable. 
Treatment 
The intervention will have to take place within thirty days following the screening appointment 
and will be executed by one of the two glaucoma specialists listed as the investigators of this 
study. The procedure will be done under local subconjunctival or rarely retrobulbar anesthesia. 
All participants will have a treatment session of micropulse trans-scleral cyclophotocoagulation 
in the affected eye, using the MicroPulse® P3 Glaucoma Device (MP3) powered by the CYCLO 
G6™ Glaucoma Laser System (Iridex, Mountain View, CA, USA). 
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 3 and 9 o’clock positions will be bypassed to avoid damage to ciliary 
neurovascular structures, as is standard technique with traditional continuous wave TSCPC. 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). 
Post-Intervention Follow-Up 
The patients will be seen by their attending ophthalmologist one (1) week, one (1) month, three 
(3) months, six (6) months, twelve (12) months and eighteen (18) months after the intervention. 
They will be seen more often if any complication occurs, in which case the frequency of their 
visits will be decided by their glaucoma specialist. 
The following follow-up parameters will be recorded at each visit: postoperative IOP, number of 
glaucoma medications, corrected distance visual acuity (CDVA), cup-to-disc ratio (CDR), and 
presence of complications detected by a complete slit-lamp biomicroscopy examination. The 
pain level (using a verbal analog scale, see Table 3) will be assessed while performing the laser 
treatment. 
A less than 25% reduction in IOP from baseline after 1 month on two consecutive visits 
separated by an interval of 1 week will be the basis for a second treatment. The same criteria 
will apply for third treatment if necessary. Repeat treatments will be done in the same 
conditions and settings as the primary treatment. 
 

Nagano # : 2017-6956 
mTSCPC - HS 
PI : Harmanjit Singh 
Protocol – V01-00 
2017-02-14 
Page 6 of 9 
Primary and Secondary Outcomes 
The primary outcome measure of success of this study will be defined as an IOP between 6 and 
21 mmHg at final follow-up (18 months) with or without IOP lowering medications, at least 25% 
reduction in IOP at final follow-up compared to baseline, and no need for incisional glaucoma 
surgery during follow-up period. The need for a repeat micropulse TSCPC will not be considered 
a failure. 
The secondary outcome measure of success will include the number of repeat treatments, the 
number of IOP lowering medications at 18 months, changes in CDVA (number of lines reduction 
or improvement from baseline), the progression of CDR compared to baseline, and the 
frequency of complications associated with the laser therapy (e.g., prolonged AC inflammation 
[cells 1+ or higher for more than 2 weeks with topical steroid eye drops], sympathetic 
ophthalmia, chronic hypotony, phthisis bulbi, scleral thinning). 
The outcome of the therapy will ultimately be defined in terms of success rate, hypotony rates, 
response rates (success and hypotony rates considered together) and retreatment rates. 
Statistical Analysis 
Paired 2-tailed Student t-tests will be used to compare changes in IOP, number of glaucoma 
medications, CDVA and CDR between each time point. For each of these measures, a single 
factor analysis of variance will be realized. Snellen visual acuities will be converted to logarithm 
of the minimum angle of resolution (logMAR) values for statistical analysis. Bonferroni 
correction will be used to control the multiplicity of t-tests. Frequency distribution and 
percentage will be used for categorical data. Demographic analysis will use Wilcoxon rank-sum 
test for age and chi-square test for gender. Fisher’s exact test will evaluate equivalence of 
glaucoma types. A level of p≤0.05 will be considered statistically significant. Analysis will be done 
with the SPSS version 20.0 software (SPSS Inc., Chicago, IL, USA). 
Benefits, Risks and Disadvantages  
Benefits 
Micropulse trans-scleral CPC is thought to be an effective strategy to reduce the intraocular 
pressure in patients who are poor candidates for additional filtering surgery or implantation of 
glaucoma drainage devices. This therapy is considered less invasive and associated with fewer 
side effects than the traditional trans-scleral CPC procedure. 
By participating in this study, patients will contribute to the research community in the 
ophthalmology field. The results already published on the micropulse trans-scleral CPC are 
encouraging, but additional results regarding the efficacy and safety of this procedure will 
further support its beneficial use. 
Risks 
Participants are exposed to all conventional complications that may be associated with CPC:  
prolonged anterior chamber inflammation, sympathetic ophthalmia, chronic hypotony, phthisis 
bulbi, scleral thinning, decrease in visual acuity, pain. However, the side effect profile of 
micropulse CPC is thought to be better than conventional glaucoma surgeries and conventional 
CPC, which has been used for many years in the treatment of advanced glaucoma. In case of 
failure of micropulse CPC to control adequately the IOP, there is always a possibility to add 
topical or systemic medication, or to undergo another surgery if needed. 

Nagano # : 2017-6956 
mTSCPC - HS 
PI : Harmanjit Singh 
Protocol – V01-00 
2017-02-14 
Page 7 of 9 
Disadvantages 
The only disadvantage in participating in this study will be to come to the requested follow-up 
appointments, which do not imply any risky or painful procedure. 
Confidentiality  
Collected information will only be accessible by the investigators of this study, and only relevant 
data needed to achieve the scientific objectives of this project will be collected. No identifiable 
information will be stored in the documents of this study, as patients will be identified solely by 
a code number. The key of the code linking the identity of the participant to his research file will 
be retained exclusively by the principal investigator of this project. No nominative information 
will appear in the final results of this study. Research data may be published or scientifically 
discussed, but it will not be possible to identify participants. 
Data will be stored in the research office of the principal investigator at the CHUM 
Ophthalmology Department, Notre-Dame hospital, Montreal (Quebec, Canada) on a single 
password-protected computer device (Removable HDD) for a period of 10 years, and then 
erased from the device. 
Information and Consent Form   
An information and consent form will be signed by all participants. Patients who refuse to 
participate in this study will have no prejudice and will receive the best standard of care from 
their attending ophthalmologist. 
Scientific and Ethics Committees 
This research project will be reviewed and approved by the CHUM local research ethics 
committee (CER).  
Budget 
MicroPulse® P3 (MP3) laser probes reusable for 5 patients each: 
395$/probe x 10 (primary treatment for 50 patients) = 3,950$ 
395$/probe x 5 (for estimated repeat treatments) = 1,975$ 
Total……………………………………………………………………………………………………...... 
 
 
5,925$ 
Patient recruitment and follow-up require the help of a research assistant for 
18 months (part-time)…………………………………………………………………………………… 
 
1,500$ 
Didactic material (posters, publications, presentations)………………………………… 
1,000$ 
Statistical consultation…………………………………………………………………………………… 
1,000$ 
Other sources of funding……………………………………………………………………………….. 
0$ 
 
 
Total…………………………………………………………………………………………………………….... 9,425$ 
References 
1. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 
2020. Br J Ophthalmol 2006; 90(3):262–267. 
2. Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global prevalence of glaucoma 
and projections of glaucoma burden through 2040: a systematic review and meta-
analysis. Ophthalmology 2014; 121(11):2081–2090. 

Nagano # : 2017-6956 
mTSCPC - HS 
PI : Harmanjit Singh 
Protocol – V01-00 
2017-02-14 
Page 8 of 9 
3. Chang P, Hodapp EA. Risk Factors in Glaucomatous Progression. Glaucoma Today 2015;  
13(5):24–25. 
4. Lai JS, Tham CC, Lam DS. Surgical management of chronic closed angle glaucoma. Asian 
Pac J Ophthalmol 2003; 15:5–10. 
5. Nguyen QH. Primary surgical management refractory glaucoma: tubes as initial surgery. 
Curr Opin Ophthalmol 2009; 20:122–5. 
6. Schlote T, Derse M, Rassman K et al. Efficacy and safety of contact trans-scleral diode 
laser cyclophotocoagulation for advanced glaucoma. J Glaucoma 2001; 10:294–301. 
7. Agarwal HC, Gupta V, Sihota R. Evaluation of contact versus non-contact diode laser 
cyclophotocoagulation for refractory glaucomas using similar energy settings. Clin 
Experiment Ophthalmol 2004; 32:33–8. 
8. Schlote T, Derse M, ZIerhut M. Trans-scleral diode laser cyclophotocoagulation for the 
treatment of refractory glaucoma secondary to inflammatory eye diseases. Br J 
Ophthalmol 2000; 84:999–1003. 
9. Egbert PR, Fladoyor S, Budenz DL et al. Diode laser trans-scleral cyclophotocoagulation 
as a primary surgical treatment for primary open angle glaucoma. Arch Ophthalmol 
2001; 119:345–50. 
10. Leszczynski 
R, 
Gierek-Lapinska 
A, 
Forminska-Kapuscik 
M. 
Trans-scleral 
cyclophotocoagulation inthe treatment of secondary glaucoma. Med Sci Monit 2004; 
10:CR542–8. 
11. Rotchford AP, Jayasawal R, Madhusudhan S, et al. Transscleral diode laser cycloablation 
in patients with good vision. Br J Ophthalmol 2010; 94:1180–1183. 
12. Pantcheva MB, Kahook MY, Schuman JS, Rubin MW, Noecker RJ. Comparison of acute 
structural and histopathological changes of the porcine ciliary processes after 
endoscopic cyclophotocoagulation and transscleral cyclophotocoagulation. Clin Exp 
Ophthalmol 2007; 35(3):270–274. 
13. Tan AM, Aquino MCD, Chew PTK et al. Micropulse trans-scleral cyclophotocoagulation in 
the treatment of refractory glaucoma. Clin Experiment Ophthalmol 2010; 38:266–72. 
14. Aquino MCD, Barton K, Tan AM, Sng C, Li X et al. Micropulse versus continuous wave 
transscleral diode cyclophotocoagulation in refractory glaucoma: a randomized 
exploratory study. Clin Experiment Ophthalmol 2015; 43:40–46. 
15. Bloom PA, Tsai JC, Sharma K, Miller MH, Rice NS, Hitchings RA, Khaw PT. Trans-scleral 
diode laser cyclophotocoagulation in the treatment of advanced refractory glaucoma. 
Ophthalmology 1997; 104(9):1508–1519. 
16. Kosoko O, Gaasterland DE, Pollack IP, Enger CL. Longterm outcome of initial ciliary 
ablation with contact diode laser transscleral cyclophotocoagulation for severe 
glaucoma. The Diode Laser Ciliary Ablation Study Group. Ophthalmology 1996; 
103(8):1294–1302. 
17. Mistlberger A, Liebmann JM, Tschiderer H, Ritch R, Ruckhofer J, Grabner G. Diode laser 
transscleral cyclophotocoagulation for refractory glaucoma. J Glaucoma 2001; 
10(4):288–293. 
18. Oguri A, Takahashi E, Tomita G, Yamamoto T, Jikihara S, Kitazawa Y. Transscleral 
cyclophotocoagulation with the diode laser for neovascular glaucoma. Ophthalmic Surg 
Lasers 1998; 29(9):722–727. 
19. Ness PJ, Khaimi MA, Feldman RM, Tabet R, Sarkisian SR Jr, Skuta GL, Chuang AZ, 
Mankiewicz 
KA. 
Intermediate 
term 
safety 
and 
efficacy 
of 
transscleral 
cyclophotocoagulation after tube shunt failure. J Glaucoma 2012; 21(2):83–88. 
20. Sivaprasad S, Sandhu R, Tandon A, Sayed-Ahmed K, McHugh DA. Subthreshold 
micropulse diode laser photocoagulation for clinically significant diabetic macular 
oedema: a three-year follow up. Clin Experiment Ophthalmol 2007; 35:640–4. 

Nagano # : 2017-6956 
mTSCPC - HS 
PI : Harmanjit Singh 
Protocol – V01-00 
2017-02-14 
Page 9 of 9 
21. Parodi MB, Spasse S, Iacono P, Di Stefano G, Canziani T, Ravalico G. Subthreshold grid 
laser treatment of macular edema secondary to branch retinal vein occlusion with 
micropulse infrared (810 nanometer) diode laser. Ophthalmology 2006; 113:2237–42. 
22. Desmettre TJ, Mordon SR, Buzawa DM, Mainster MA. Micropulse and continuous wave 
diode retinal photocoagulation: visible and subvisible lesion parameters. Br J 
Ophthalmol 2006; 90:709–12. 
23. Laursen ML, Moeller F, Sander B, Sjeolie AK. Subthreshold micropulse diode laser 
treatment in diabetic macular oedema. Br J Ophthalmol 2004; 88:1173–9. 
24. Chong LP, Kelsoe W, Donovan D. Selective RPE damage by micropulsed diode laser 
photocoagulation. Invest Ophthalmol Vis Sci 1992; 33:722. 
25. Moorman CM, Hamilton AM. Clinical applications of the micropulse diode laser. Eye 
1999; 13:145–50. 
26. Pollack JS, Kim JE, Pulido JS, Burke JM. Tissue effects of subclinical diode laser treatment 
of the retina. Arch Ophthalmol 1998; 116:1633–9. 
27. Berger JW. Thermal modeling of micropulsed diode laser retinal photocoagulation. 
Lasers Surg Med 1997; 20:409–15. 
28. Kuchar S, Moster MR, Reamer CB, Waisbourd M. Treatment outcomes of micropulse 
transscleral cyclophotocoagulation in advanced glaucoma. Lasers Med Sci 2016; 31:393–
396. 
29. Ho CL. Micropulse diode trans-scleral cyclophotocoagulation. Asian J Ophthalmol 2001; 
3 (Suppl.):3–4. 
30. Hauber FA, Scherer WJ. Influence of total energy delivery on success rate after contact 
diode laser trans-scleral cyclophotocoagulation: a retrospective case review and meta-
analysis. J Glaucoma 2002; 11:329–33. 
31. Vernon SA, Koppens JM, Menon J et al. Diode laser cycloablation in adult glaucoma: 
long-term results of a standard protocol and review of current literature. Clin 
Experiment Ophthalmol 2006; 34: 411–20. 
32. Murphy CC, Burnett CAM, Spry PGD et al. A two centre study of the dose-response 
relation for transscleral diode laser cyclophotocoagulation in refractory glaucoma. Br J 
Ophthalmol 2003; 87:1252–7. 
33. Meyer JJ, Lawrence SD. What’s new in laser treatment for glaucoma? Curr Opin 
Ophthalmol 2012; 23:111–117.