Clinical trial NCT03875911
Conditions: Glaucoma Open-Angle Primary Glaucoma Open Angle Glaucoma Glaucoma, Open-Angle
Keywords: Trabeculectomy Mitomycin-C Glaucoma
Sponsor: University of California, Los Angeles
Start date: 2019-03-30; Completion date: 2022-12-31
Enrollment: 19 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
In this Pilot explorative study, the investigators are going to estimate and compare the outcomes of three different delivery methods of MMC for Trabeculectomy: a subconjunctival injection of MMC 0.002% at the site of future Trabeculectomy two to four weeks before the surgery, a subconjunctival injection of MMC 0.01% intraoperatively and topical sponge applied MMC 0.02% intraoperatively (typical use) in patients with Primary Open Angle Glaucoma who did not have any filtering surgeries before.

After obtaining informed consent from the patients, the patients are randomly divided into three groups via a block randomization method: Group A receives 0.1 mL MMC 0.002 % (0.1mL MMC 0.02mg/mL) subconjunctival injection preoperatively in superior conjunctiva at the site of future Trabeculectomy surgery. Group B receives 0.1mL MMC 0.01% subconjunctival injection intraoperatively at the site of Trabeculectomy and Group C receives conventional sponge delivery of MMC 0.02% intraoperatively. To avoid observer bias during postoperative evaluation of results, IOP staff obtaining measurements of IOP will be masked to the randomization allocation.

All groups undergo conventional Trabeculectomy surgery (fornix-based) as scheduled, and the same routine follow up and post-op regimen will be scheduled for all three groups. Patients are routinely visited in the clinic at first day postoperatively, one week (+/-2 days), one month (+/-1 week), three months (+/-2 weeks), six months (+/-3 weeks) and finally at one year (+/-(4 weeks)). In each of these visits we will be assessing: Visual acuity, intraocular pressure, number and type of glaucoma medication, slit lamp examination of the anterior segment and fundus examination.

Detailed description:
Purpose:

To obtain estimates of the effect on intraocular pressure and side effects of three delivery methods of Mitomycin C (MMC) compared among each other: preoperative subconjunctival injection of 0.1 mL MMC 0.002%, subconjunctival injection of 0.1 mL MMC 0.01% intraoperatively, and conventional sponge applied MMC (0.02%) during trabeculectomy surgery in patients with Primary Open Angle Glaucoma who did not have any filtering surgeries before.

Objective:

To obtain estimates for intraocular pressure reduction among three delivery methods of MMC compared among each other: preoperative subconjunctival injection, intraoperative subconjunctival injection, and intraoperative topical use during trabeculectomy surgery, and to report any associated adverse effects.

Null hypothesis:

There is no use of hypothesis testing in this pilot study.

Alternative hypothesis:

There is no use of hypothesis testing in this pilot study.

The effect and safety of MMC subconjunctival injection either preoperatively or intraoperatively has been previously investigated in Pterygium surgery (Khakshoor H, Razavi ME, Daneshvar R, Shakeri MT, Ghate MF, Ghooshkhanehi H. Am J Ophthalmol. 2010 Aug;150(2):193-8. Preoperative subpterygeal injection vs intraoperative mitomycin C for pterygium removal: comparison of results and complications).

Previous studies comparing effectiveness of subconjunctival injection of MMC vs sponge-applied MMC have shown inconsistent results. In one retrospective study, Mitomycin-C applied by injection resulted in significantly lower IOP, and the need for fewer glaucoma medications, however description of methods is incomplete. (Lim MC. A comparison of trabeculectomy surgery outcomes with mitomycin-C applied by intra-Tenon injection versus sponge method. American Glaucoma Society 23rd Annual Meeting; 2013, San Francisco, CA). One retrospective study showed similar efficacy and safety of intraoperative MMC injection compare to sponge application in trabeculectomy surgery with overall lower IOP in the injection group and main advantages being a large surface area of exposure and a predictable dose of deliver when the injection was performed. No difference in postoperative complications between groups was observed. A small sample size (30) in each group might prevent finding statistical significant results. (Khouri AS, Huang G, Huang LY. Intraoperative Injection vs Sponge-applied Mitomycin C during Trabeculectomy: One-year Study. J Curr Glaucoma Pract 2017;11(3):101-106). A previous case report on preoperative administration of MMC for Trabeculectomy showed reduction of IOP with short follow-up (6 months) Hung PT, Lin LL, Hsieh JW, Wang TH. Preoperative mitomycin-C subconjunctival injection and glaucoma filtering surgery. J Ocul Pharmacol Ther. 1995;11(3):233-241.

One RCT with a follow-up of 3 years compared outcomes of intraoperative injection versus sponge-applied MMC and no significant difference in IOP was found however a more favorable bleb morphology was found in the injection group which is correlated with better function and long-term success of Trabeculectomy ( Esfandiari, Hamed et al. Treatment Outcomes of Mitomycin C-Augmented Trabeculectomy, Sub-Tenon Injection versus Soaked Sponges, after 3 Years of Follow-up Ophthalmology Glaucoma , Volume 1 , Issue 1 , 66 - 74)

In this study the comparison will be the timing and route of delivery of MMC in all three groups, having found inconsistent reports in the literature and very scarce data on the effect of preoperative subconjunctival MMC the investigators would like to further explore in this pilot study the effect of subconjunctival injection on IOP reduction for trabeculectomy at preoperative and intraoperative phases. Since there is no group receiving placebo, the inclusion of a sham injection will not affect the outcomes compared to GROUP C and could increase preoperative risks to patients. The same methodology has been applied in two previous randomized controlled trials. (Pakravan M, Esfandiari H, Yazdani S, et al. Mitomycin C-augmented trabeculectomy: subtenon injection versus soaked sponges: a randomized clinical trial Br J Ophthalmol 2017;101:1275-1280 and Khan F, Niazi S, Awais M et all. Effectiveness of Preoperative Subconjunctival Injection of Mitomycin-C in Primary Pterygium Surgery Journal of the College of Physicians and Surgeons Pakistan 2017, Vol. 27 (2): 88-91)

Glaucoma patients who need glaucoma surgery, such as trabeculectomy, have ongoing damages that cannot be managed only with medication such as drops, and pressure reduction is absolutely crucial in preserving visual function in these patients, hence any possible action that can add to this reduction is valuable.

On the other hand, there are several risks associated with the topical applied MMC usage at the time of surgery mainly due to the inability to precisely quantify the amount of MMC delivered by the sponge application which was shown to be far less with the injection of MMC by delivering a predicted volume either at surgery or before the surgery which are mentioned in the first two paper references.

The selected concentrations for the MMC injection are based on pharmacological studies performed on ocular tissue in which the concentration achieved after subconjunctival injection was established.

STUDY DESIGN This is a multicenter, randomized, controlled pilot study with a main objective of obtaining estimates of differences in IOP reduction among three methods of delivery of mitomycin C for use in trabeculectomy surgery.

The injectors and patients are unmasked in this study while the evaluators are masked.

This study will be performed at the Glaucoma Division of Stein Eye Institute-UCLA Los Angeles, CA.

METHODS

Patients who met inclusion criteria and had signed an informed consent will then be randomized into three groups as follows:

* Group A: Patients will receive a subconjunctival injection of 0.1mL MMC 0.02mg/mL which corresponds to 0.002% (a tenth of the concentration of conventional topical MMC use) at the site of future trabeculectomy surgery two to four weeks in advance. A follow-up phone call 1 week after the MMC injection will assess any side effects of the procedure. If side effects are reported by the patient an appointment will be schedule for a follow up in-office visit and appropriate treatment will be delivered. On the day of conventional trabeculectomy no MMC will be injected. Follow-up will be scheduled for one year.
* Group B: On the day of conventional trabeculectomy patients will receive a subconjunctival injection intraoperatively of 0.1 mL MMC 0.1mg/mL which corresponds to 0.01% (half the concentration of conventional topical MMC use) at the site of trabeculectomy. Surgeon will irrigate the surface of the eye after MMC injection to remove any MMC that might have leaked out. Follow-up will be scheduled for one year.
* Group C: On the day of conventional trabeculectomy patients will receive MMC by applying a sponge soaked in 1mL of MMC 0.2 mg/mL (0.02%) for 1 minute to the site of trabeculectomy surgery followed by irrigation. MMC is standard of care for trabeculectomy surgery at UCLA. This differs from the proposed research because the MMC will be administered as an injection either two to four weeks before the surgery in Group A or intraoperatively in Group B rather than the usual topical administration on the day of surgery (Group C). Follow-up will be scheduled for one year.

The concentration of MMC in each group were chosen according to the delivery method and the timing of exposition of the tissue to the MMC in order to prevent complications from overdose. Based on experimental studies on ocular tissues that evaluated the final amount of MMC delivered to scleral tissue and finding a similar result when using subconjunctival injection of 0.02% with immediate irrigation and 0.002% without irrigation, the investigators chose the latter for group A. Few studies evaluated MMC subconjunctival injection one month before pterygium surgery using 0.02% and 0.015% with a follow-up of 3 years establishing safety of this approach. For group B the investigators chose a similar methodology of a previous RCT comparing subconjunctival injection versus topical administration of MMC for trabeculectomy that used a reduced concentration of 0.01%.

Data collection will be as follows: At preoperative visit, postoperative day one, one week (+/- 2 days), one month (+/- 1 week), three months (+/- 2 weeks), six months (+/- 3 weeks) and one year (+/- 4 weeks). The data will be recorded in the REDCap (Research Electronic Data Capture) software which has free access and allows for easy recording and uploading of imaging (VF, Optic nerve OCT, AS-OCT and bleb photography) for future analysis.

In each of these visits, the following data will be collected: Visual acuity, intraocular pressure, number and type of glaucoma medication, slit lamp examination of the anterior segment, fundus examination and adverse events if present. Visual field and optic nerve OCT will also be included in the preoperative evaluation and at 12 months postoperatively.

For better assessment of the bleb morphology, the investigators will include a clinical grade system, slit lamp photography, and AS-OCT \[Anterior segment module of Spectralis OCT device (Heidelberg Engineering, Inc., Heidelberg, Germany)\] of the bleb.

For the clinical description of the bleb and a more standardized comparison of the morphological changes over time, the investigators included at every postoperative visit the description of the bleb using the Moorfields Bleb Grading System (MBGS) which captures more morphological features and regional vascularity compared to other systems. (Wells AP, Ashraff N, HalL RC et all Comparison of Two Clinical Bleb Grading Systems Ophthalmology 2006;113:77-83).

The bleb photography will be included at the Month 3 and Month 12 postoperative visits and AS-OCT at 1,3,6 and 12 Month follow-ups. The inclusion of AS-OCT allows for evaluation of the internal structure of the bleb that has been shown to have prognostic implications for outcomes of surgery. Kokubun T, Tsuda S, Kunikata H et all. Anterior-Segment Optical Coherence Tomography for Predicting Postoperative Outcomes After Trabeculectomy, Current Eye Research, DOI: 10.1080/02713683.2018.1446535

Block randomization:

To ensure the balance of sample size between three treatment groups, block randomization is used for treatment assignment. Specifically, each block consists of 6 patients, including 2 patients in each of three treatment groups, and all possible permutations of a sequence of treatment assignment for these 6 patients are generated, such as AABBCC, ABCABC, etc. A random number is then generated to select a block of treatment assignment for 6 patients among all possible blocks, and a sequence of such random blocks will form the sequence of treatment assignment for all patients after their enrollment.

Arms: arm 1: Subconjunctival injection of 0.1 ml of Mitomycin-C 0.002% at the site of future trabeculectomy surgery (2 - 4 weeks preoperatively). arm 2: Intraoperative subjconjunctival injection of 0.1 mL of Mitomycin-C 0.01% (0.1mg/mL) to the site of trabeculectomy arm 3: Topical application of Mitomycin-C intraoperatively by applying a sponge soaked in 1mL of Mitomycin-C 0.02 mg/mL for 1 minute to the site of trabeculectomy
Interventions: intervention 1: Mitomycin C
Intervention descriptions: intervention 1: Three delivery methods of Mitomycin-C in Trabeculectomy

Protocol documents:
Prot_SAP_002.pdf: 
Official Title: A Prospective Randomized Clinical Trial Comparing Three Delivery Methods of Mitomycin-
C for Trabeculectomy Surgery: Preoperative Subconjunctival Injection, Intraoperative Subconjunctival 
Injection, and Topical Application (Conventional Use) During Trabeculectomy Surgery   
NCT Number: 03875911 
Date of Document: 01-19-2018 
 


Mitomycin-C Injection for Trabeculectomy: Pilot study 
 
Title 
Comparison of three delivery methods of Mitomycin C for trabeculectomy surgery: Preoperative 
subconjunctival injection, intraoperative subconjunctival injection and topical application during 
trabeculectomy surgery: A pilot study 
 
Purpose:   
To obtain estimates of the effect on intraocular pressure and side effects of three delivery methods of 
Mitomycin C (MMC) compared among each other: preoperative subconjunctival injection of 0.1 mL MMC 
0.002%, subconjunctival injection of 0.1 mL MMC 0.01% intraoperatively and conventional sponge 
applied MMC (0.02%) during trabeculectomy surgery in patients with Primary Open Angle Glaucoma who 
did not have any filtering surgeries before. 
 
Objective:  
To obtain estimates for intraocular pressure reduction among three delivery methods of MMC compared 
among each other: preoperative subconjunctival injection, intraoperative subconjunctival injection and 
intraoperative topical use during trabeculectomy surgery and to report any associated adverse effects. 
 
Null hypothesis: 
There is no use of hypothesis testing in this pilot study 
 
Alternative hypothesis: 
There is no use of hypothesis testing in this pilot study 
 
BRIEF SUMMARY 
 
In this Pilot explorative study, we are going to estimate and compare the outcomes of three different 
delivery methods of MMC for Trabeculectomy: a subconjunctival injection of MMC 0.002% at the site of 
future Trabeculectomy two to four weeks before the surgery, a subconjunctival injection of MMC 0.01% 
intraoperatively and topical sponge applied MMC 0.02% intraoperatively (typical use) in patients with 
Primary Open Angle Glaucoma who did not have any filtering surgeries before. 
 
After obtaining informed consent from the patients, the patients are randomly divided into three 
groups via a block randomization method: Group A receives 0.1 mL MMC 0.002 % (0.1mL MMC 
0.02mg/mL) subconjunctival injection preoperatively in superior conjunctiva at the site of future 
Trabeculectomy surgery. Group B receives 0.1mL MMC 0.01% subconjunctival injection intraoperatively 
at the site of Trabeculectomy and Group C receives conventional sponge delivery of MMC 0.02% 
intraoperatively. To avoid observer bias during postoperative evaluation of results, IOP staff obtaining 
measurements of IOP will be masked to the randomization allocation. 
 
All groups undergo conventional Trabeculectomy surgery (fornix-based) as scheduled, and the same 
routine follow up and post-op regimen will be scheduled for all three groups. Patients are routinely visited 
in the clinic at first day postoperatively, one week (+/-2 days), one month (+/-1 week), three months (+/-
2 weeks), six months (+/-3 weeks) and finally at one year (+/-(4 weeks)). In each of these visits we will be 
assessing: Visual acuity, intraocular pressure, number and type of glaucoma medication, slit lamp 
examination of the anterior segment and fundus examination.  


 
BACKGROUND INFORMATION 
 
The effect and safety of MMC subconjunctival injection either preoperatively or intraoperatively has been 
previously investigated in Pterygium surgery (Khakshoor H, Razavi ME, Daneshvar R, Shakeri MT, Ghate 
MF, Ghooshkhanehi H. Am J Ophthalmol. 2010 Aug;150(2):193-8. Preoperative subpterygeal injection vs 
intraoperative mitomycin C for pterygium removal: comparison of results and complications).  
 
Previous studies comparing effectiveness of subconjunctival injection of MMC vs sponge-applied MMC 
have shown inconsistent results. In one retrospective study, Mitomycin-C applied by injection resulted in 
significantly lower IOP, and the need for fewer glaucoma medications, however description of methods 
is incomplete. (Lim MC. A comparison of trabeculectomy surgery outcomes with mitomycin-C applied by 
intra-Tenon injection versus sponge method. American Glaucoma Society 23rd Annual Meeting; 2013, 
San Francisco, CA). One retrospective study showed similar efficacy and safety of intraoperative MMC 
injection compare to sponge application in trabeculectomy surgery with overall lower IOP in the injection 
group and main advantages being a large surface area of exposure and a predictable dose of deliver when 
the injection was performed. No difference in postoperative complications between groups was 
observed. A small sample size (30) in each group might prevent finding statistical significant results. 
(Khouri AS, Huang G, Huang LY. Intraoperative Injection vs Sponge-applied Mitomycin C during 
Trabeculectomy: One-year Study. J Curr Glaucoma Pract 2017;11(3):101-106). A previous case report on 
preoperative administration of MMC for Trabeculectomy showed reduction of IOP with short follow-up 
(6 months) Hung PT, Lin LL, Hsieh JW, Wang TH. Preoperative mitomycin-C subconjunctival injection and 
glaucoma filtering surgery. J Ocul Pharmacol Ther. 1995;11(3):233-241. 
One RCT with a follow-up of 3 years compared outcomes of intraoperative injection versus sponge-
applied MMC and no significant difference in IOP was found however a more favorable bleb 
morphology was found in the injection group which is correlated with better function and long-term 
success of Trabeculectomy ( Esfandiari, Hamed et al. Treatment Outcomes of Mitomycin C-Augmented 
Trabeculectomy, Sub-Tenon Injection versus Soaked Sponges, after 3 Years of Follow-up 
(Ophthalmology Glaucoma , Volume 1 , Issue 1 , 66 – 74) 
 
In this study the comparison will be the timing and route of delivery of MMC in all three groups, having 
found inconsistent reports in the literature and very scarce data on the effect of preoperative 
subconjunctival MMC we like to further explore in this pilot study the effect of subconjunctival injection 
on IOP reduction for trabeculectomy at preoperative and intraoperative phases. Since there is no group 
receiving placebo, the inclusion of a sham injection will not affect the outcomes compared to GROUP C 
and could increase preoperative risks to patients. The same methodology has been applied in two 
previous randomized controlled trials. (Pakravan M, Esfandiari H, Yazdani S, et al. Mitomycin C-
augmented trabeculectomy: subtenon injection versus soaked sponges: a randomized clinical trial Br J 
Ophthalmol 2017;101:1275–1280 and Khan F, Niazi S, Awais M et all. Effectiveness of Preoperative 
Subconjunctival Injection of Mitomycin-C in Primary Pterygium Surgery Journal of the College of 
Physicians and Surgeons Pakistan 2017, Vol. 27 (2): 88-91) 
 
Glaucoma patients who need glaucoma surgery, such as trabeculectomy, have ongoing damages that 
cannot be managed only with medication such as drops, and pressure reduction is absolutely crucial in 
preserving visual function in these patients, hence any possible action that can add to this reduction is 
valuable. 


On the other hand, there are several risks associated with the topical applied MMC usage at the time of 
surgery mainly due to the inability to precisely quantify the amount of MMC delivered by the sponge 
application which was shown to be far less with the injection of MMC by delivering a predicted volume 
either at surgery or before the surgery which are mentioned in the first two paper references. 
The selected concentrations for the MMC injection are based on pharmacological studies performed on 
ocular tissue in which the concentration achieved after subconjunctival injection was established 
 
STUDY DESIGN 
This is a multicenter randomized controlled pilot study with a main objective of obtaining estimates of 
differences in IOP reduction among three methods of delivery of mitomycin C for use in trabeculectomy 
surgery. 
The injectors and patients are unmasked in this study while the evaluators are masked. 
 
Inclusion Criteria  
1. 
Age: 20-85 years 
2. 
Willingness to participate in the study by signing informed consent 
3. 
Primary open angle glaucoma (including pigmentary glaucoma and pseudoexfoliation glaucoma) 
indicated with open angles upon previous gonioscopy and demonstrative optic nerve and visual field 
damage 
4. 
Trabeculectomy needed as treatment as determined by the care provider 
 
Exclusion criteria  
1. Patient unwilling or unable to give informed consent, unwilling to accept randomization, or unable to 
return for scheduled study visits throughout the duration of the study (1 year) 
2. Any secondary cause of glaucoma, or angle closure shown on gonioscopy 
3. Any ocular or neurological problems with optic nerve or visual field defect (ie. retinal disease, post 
trauma, corneal scar) that may confound the interpretation of glaucoma such as visual field or optic nerve 
interpretation 
4. Pregnant women, nursing women, and/or anyone with a history of allergy to MMC 
5. Previous glaucoma surgery or ocular surgery that included manipulation of the conjunctiva. 
 
METHODS 
 
Patients who met inclusion criteria and had signed an informed consent will then be randomized into 
three groups as follows: 
 
 
Group A: Patients will receive a subconjunctival injection of 0.1mL MMC 0.02mg/mL which 
corresponds to 0.002% (a tenth of the concentration of conventional topical MMC use) at the 
site of future trabeculectomy surgery two to four weeks in advance. A follow-up phone call 1 
week after the MMC injection will assess any side effects of the procedure. If side effects are 
reported by the patient an appointment will be schedule for a follow up in-office visit and 
appropriate treatment will be delivered. On the day of conventional trabeculectomy no MMC 
will be injected. Follow-up will be scheduled for one year. 
 
 
Group B: On the day of conventional trabeculectomy patients will receive a subconjunctival 
injection intraoperatively of 0.1 mL MMC 0.1mg/mL which corresponds to 0.01% (half the 


concentration of conventional topical MMC use) at the site of trabeculectomy.  Surgeon will 
irrigate the surface of the eye after MMC injection to remove any MMC that might have leaked 
out. Follow-up will be scheduled for one year. 
 
 
Group C: On the day of conventional trabeculectomy patients will receive MMC by applying a 
sponge soaked in 1mL of MMC 0.2 mg/mL (0.02%) for 1 minute to the site of trabeculectomy 
surgery followed by irrigation.  MMC is standard of care for trabeculectomy surgery at UCLA. This 
differs from the proposed research because the MMC will be administered as an injection either 
two to four weeks before the surgery in Group A or intraoperatively in Group B rather than the 
usual topical administration on the day of surgery (Group C). Follow-up will be scheduled for one 
year. 
 
The concentration of MMC in each group were chosen according to the delivery method and the timing 
of exposition of the tissue to the MMC in order to prevent complications from overdose. Based on 
experimental studies on ocular tissues that evaluated the final amount of MMC delivered to scleral tissue 
and finding a similar result when using subconjunctival injection of 0.02% with immediate irrigation and  
0.002% without irrigation, we chose the latter for group A. Few studies evaluated MMC subconjunctival 
injection one month before pterygium surgery using 0.02% and 0.015% with a follow-up of 3 years 
establishing safety of this approach. For group B we chose a similar methodology of a previous RCT 
comparing subconjunctival injection versus topical administration of MMC for trabeculectomy that used 
a reduced concentration of 0.01%. 
 
Data collection will be as follows: At preoperative visit, first day postoperatively, one week (+/- 2 days), 
one month (+/- 1 week), three months (+/- 2 weeks), six months (+/- 3 weeks) and one year (+/- (4 
weeks)). The data will be recorded trough the Redcap (Research Electronic Data Capture) software 
which has free access and allows for easy recording and uploading of imaging (VF, Optic nerve OCT, AS-
OCT and bleb photography) for future analysis. 
In each of these visits the following data will be collected: Visual acuity, intraocular pressure, number 
and type of glaucoma medication, slit lamp examination of the anterior segment, fundus examination 
and adverse events if present. Visual field and optic nerve OCT will also be included in the preoperative 
evaluation and at 12 months postoperatively.  
For better assessment of the bleb morphology we will include a clinical grade system, slitlamp 
photography and AS-OCT ( Anterior segment module of Spectralis OCT device (Heidelberg Engineering, 
Inc., Heidelberg, Germany) of the bleb. 
For the clinical description of the bleb and a more standardized comparison of the morphological 
changes over time we included at every postoperative visit the description of the bleb using the 
Moorfields Bleb Grading System (MBGS) which captures more morphological features and regional 
vascularity compared to other systems.  (Wells AP, Ashraff N, HalL RC et all Comparison of Two Clinical 
Bleb Grading Systems Ophthalmology 2006;113:77–83). 
The bleb photography will be included at the 3 and 12 months postoperatively and AS-OCT at 1,3,6 and 
12 months follow-ups. The inclusion of AS-OCT allows for evaluation of the internal structure of the 
bleb that has been shown to have prognostic implications for outcomes of surgery. Kokubun T, Tsuda S, 
Kunikata H et all. Anterior-Segment Optical Coherence Tomography for Predicting Postoperative 
Outcomes After Trabeculectomy, Current Eye Research, DOI: 10.1080/02713683.2018.1446535 
 
 


Block randomization: 
To ensure the balance of sample size between three treatment groups, block randomization is used for 
treatment assignment. Specifically, each block consists of 6 patients, including 2 patients in each of three 
treatment groups, and all possible permutations of a sequence of treatment assignment for these 6 
patients are generated, such as AABBCC, ABCABC, etc. A random number is then generated to select a 
block of treatment assignment for 6 patients among all possible blocks, and a sequence of such random 
blocks will form the sequence of treatment assignment for all patients after their enrollment. 
 
 
Statistical analysis 
Since the literature on the effect of preoperative subconjunctival injection and intraoperative 
subconjunctival injections for trabeculectomy shows inconsistent results and there are no estimates 
available for the IOP reduction among all three methods, the primary objective is to obtain such estimates 
in this pilot study. Hence, we want to perform pairwise comparisons among three groups and obtain the 
mean IOP estimates at each time point up to 1 year. The sample size for each randomized will be 50 
patients (total 150 patients) taking in consideration the patient flow and recruitment for trabeculectomy 
surgery at the Glaucoma Division. 
 
 
 
 
 
 
 
 
SCHEDULE 
VA IOP 
Glaucoma 
medications 
Ant. segment 
exam 
Fundus 
exam 
Bleb 
photo 
AS-
OCT 
Optic nerve 
-OCT 
Visual 
field 
Preoperative exam 
✓ 
✓ 
✓ 
✓ 
✓ 
 
 
✓ 
✓ 
Postoperative exam day 1 
✓ 
✓ 
✓ 
✓ 
 
 
 
 
 
Postoperative exam week 1 
✓ 
✓ 
✓ 
✓ 
 
 
 
 
 
Postoperative exam month 1 
✓ 
✓ 
✓ 
✓ 
 
 
✓ 
 
 
Postoperative exam month 3 
✓ 
✓ 
✓ 
✓ 
 
✓ 
✓ 
 
 
Postoperative exam month 6 
✓ 
✓ 
✓ 
✓ 
 
 
✓ 
 
✓ 
Postoperative exam month 12 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 


 
         
 
 

ICF_003.pdf: 
Version 11Mar2019 
 
Official Title: A Prospective Randomized Clinical Trial Comparing Three Delivery Methods of 
Mitomycin-C for Trabeculectomy Surgery: Preoperative Subconjunctival Injection, 
Intraoperative Subconjunctival Injection, and Topical Application (Conventional Use) During 
Trabeculectomy Surgery   
 
NCT Number: 03875911 
 
Date of Document: 04-11-2019 
 
 
 
 
 


Page 2 of 8 
 
UNIVERSITY OF CALIFORNIA LOS ANGELES 
CONSENT TO PARTICIPATE IN RESEARCH 
 
A Prospective Randomized Clinical Trial Comparing Three Delivery Methods of 
Mitomycin-C for Trabeculectomy Surgery: Preoperative Subconjunctival Injection, 
Intraoperative Subconjunctival Injection, and Topical Application (Conventional Use) 
During Trabeculectomy Surgery 
 
Comparing Preoperative Injection of Mitomycin-C vs. Intraoperative Injection of 
Mitomycin C. vs. Topical Application of Mitomycin-C (Conventional Use) in 
Trabeculectomy 
 
INTRODUCTION  
 
Joseph Caprioli MD and associates from the Glaucoma Division, Jules Stein Eye 
Institute at the University of California, Los Angeles are conducting a research study. 
 
The researchers will explain this study to you. Research studies are voluntary and 
include only people who choose to take part. Please take your time about deciding 
whether to participate in this study. Before deciding: 
 You can discuss this study with friends and family. 
 You can also discuss it with your health care doctor or request a second opinion. 
 If you have any questions, you can ask the researchers for more information before 
deciding to participate. 
 
The research team is asking you to be in this study because you have been diagnosed 
with primary open angle glaucoma and require glaucoma surgery to lower your 
intraocular pressure.  
 
 
WHY IS THIS STUDY BEING DONE?  
 
The purpose of this research study is to evaluate the effects of injection of an 
antimetabolite (Mitomycin C) two to four weeks before the glaucoma surgery 
(Trabeculectomy) or injection during the surgery and its outcome. Mitomycin C (MMC) is 
an antimetabolite commonly used at the time of glaucoma surgery, either by using a 
soaked sponge in the 0.02 mg/mL solution or injecting the same solution underneath 
the conjunctiva, which is the most superficial part of the eye. MMC will decrease the 
number of fibroblasts, which are the cells responsible for scarring, a common cause of 
failure of the surgery. 
 
The following definitions may help you understand how this research study is designed: 
Patients who are eligible for the study will be randomly divided (like a flip of a coin) into 
three groups. In all groups, eyes will be numbed with topical anesthetic drops for at 
least 2 minutes before any injection, to allow the eye to be numbed and decrease eye 
discomfort.  Group A will receive a 0.1ml injection of MMC 0.002% (which is ten times 
more diluted than the concentration usually used at the time of surgery) beneath the 


Page 3 of 8 
 
conjunctiva, two to four weeks before the surgery. To avoid any loss of MMC from the 
surface, a cotton-tip applicator will be used to put pressure on the injection site. Thirty 
seconds after the injection, the eye will be washed with at least 30 milliliters of balanced 
salt saline. Group B will receive a 0.1 mL injection of MMC 0.01% to the trabeculectomy 
site during surgery day. Group C will receive topical administration of MMC during 
surgery day by applying a sponge soaked in 1 mL of 0.02 mg/mL for one minute to the 
site of trabeculectomy surgery. Please note that all three groups will receive MMC, but 
the only difference is the different times and delivery method at which they are applied. 
Group A will receive MMC two to four weeks before the surgery while Group B and C 
will receive the MMC at the time of surgery. 
 
All groups will have routine preoperative preparation, then undergo routine conventional 
trabeculectomy, and will receive the routine postoperative medication and care.  
 
This study is being funded by the Glaucoma Division. 
 
 
HOW MANY PEOPLE WILL TAKE PART IN THIS STUDY?  
 
150 people will take part in this study at UCLA.   
 
 
WHAT WILL HAPPEN IF I TAKE PART IN THIS STUDY?  
 
Before you begin the study: 
Before you begin the study, you will need to be seen by your Glaucoma specialist, who 
will determine your eligibility to be included in this study during a routine scheduled visit. 
No additional tests, visits, or imaging is needed. 
 
During the study: 
If you take part in this study, you will be randomly placed into one of three groups. 
Group A will receive a 0.1mL injection of MMC 0.002% (which is ten times more diluted 
than the concentration usually used at the time of surgery) beneath the conjunctiva, two 
to four weeks before the surgery. Thirty seconds after the injection, the eye will be 
washed with large amounts of sterile saline solution. After this procedure, you will 
continue your routine before surgery with the standard medication and preparation. You 
will receive a phone call from one of the research team members one week after your 
injection to assess any side effects of the procedure. If any are reported, a follow-up 
may be scheduled in the clinic. Group B will receive a 0.1 mL injection of MMC 0.01% to 
the trabeculectomy site during surgery day. Group C will receive topical administration 
of MMC during surgery day by applying a sponge soaked in 1 mL of 0.02 mg/mL for one 
minute to the site of trabeculectomy surgery. The type of surgery planned for you is the 
same as any other glaucoma surgery of the same kind (Trabeculectomy). You will also 
receive the routine postoperative medication and care. Routine follow up visits after the 
surgery will be planned for you.  
 


Page 4 of 8 
 
Routine visits after the surgery are planned for all three groups and data from these 
standard of care visits will be collected for the study for one year after your operation. 
Data will be collected from your pre-operative visit and from your standard of care visits 
that are done at one day, one week, one month, three months, six months, and one 
year after your operation.  
 
 
HOW LONG WILL I BE IN THIS STUDY?  
 
This study will last one year after the date of the surgery and all visits are part of 
standard of care. 
 
 
WHAT KINDS OF RISKS OR DISCOMFORTS COULD I EXPECT?  
 
Known risks and discomforts: 
The possible risks and/or discomforts associated with the procedures described in this 
consent form include: (these side effects are based on previous studies) 
 Scleral whitening  
 Scleral hypo vascularity (lack of blood vessels in the underlying wall of the eye)  
 Scleral melting 
 Endophthalmitis (inflammation of the interior of the eye caused by infection) 
 Hyperemia (excess of blood in vessels to the eye) 
 Corneal damage 
 Cataract (clouding of the eye) 
 Scleral thinning or ulceration 
 Hypotony (low pressure in the eye) 
 Late infection (years after MMC administration) in the eye 
 
The risks and/or discomforts listed above are the same for all study arms but might be 
higher with the group that receives the MMC injection one month before the surgery. 
The possible risks and/or discomforts listed above can result in loss of vision and the 
need for an additional surgery. 
 
 
 
Unknown risks and discomforts: 
The experimental treatments may have side effects that no one knows about yet. The 
MMC injection before surgery might have more adverse effects or be less effective than 
the standard of care procedure. The researchers will let you know if they learn anything 
that might make you change your mind about participating in the study.  
 
 
 
 
ARE THERE ANY BENEFITS IF I PARTICIPATE? 
 


Page 5 of 8 
 
Possible benefits to me: 
The possible benefits you may experience from being in this study include a better 
outcome from the glaucoma surgery and less scarring (which usually causes failure of 
the surgery).  
 
Possible benefits to others or society: 
There will be no direct benefit to you from participating in this study.  This study will help 
the researchers learn more about Trabeculectomy and MMC usage in this surgery. We 
hope that this information will help in the treatment of future patients with Glaucoma like 
yours.  
 
 
WHAT OTHER CHOICES DO I HAVE IF I DON’T WANT TO PARTICIPATE? 
 
If you decide not to take part in this study, or if you withdraw from this study before it is 
completed, the following alternative procedures or courses of treatment are available:  
Routine care and surgeries will be available for you, and you will not be withheld from 
any type of treatment due to your withdrawal from study. If you choose not to 
participate, you will continue with routine care. 
 
 
CAN THE RESEARCHERS REMOVE ME FROM THIS STUDY?  
 
The researchers may end your participation in this study for a number of reasons, such 
as if your safety and welfare are at risk, if you do not follow instructions or if you miss 
scheduled visits. The researchers or the study sponsor might also decide to stop the 
study at any time. 
 
If you decide to stop being in the study, or are removed from the study, or the study is 
stopped the researcher will ask you to return for a final close-out visit and then routine 
follow up will be scheduled for you.    
 
 
HOW WILL INFORMATION ABOUT ME AND MY PARTICIPATION BE KEPT 
CONFIDENTIAL? 
 
The researchers will do their best to make sure that your private information is kept 
confidential. Information about you will be handled as confidentially as possible, but 
participating in research may involve a loss of privacy and the potential for a breach in 
confidentiality. Study data will be physically and electronically secured.  As with any use 
of electronic means to store data, there is a risk of breach of data security.  Data will be 
used for future research.  
 
Use of personal information that can identify you: 
All identifiers will be deleted from stored information and each patient will be given a 
unique number (patient ID) which is only used for the study and will not be linked to any 
identifying data. 


Page 6 of 8 
 
 
How information about you will be stored: 
All the information will be stored in an encrypted Excel sheet that only research team 
members have access to. 
 
People and agencies that will have access to your information: 
Only the research team will have access to stored information, and these stored 
information, as mentioned above, does not have any identifying data. 
 
The research team, authorized UCLA personnel and regulatory agencies such as the 
Food and Drug Administration (FDA), may have access to study data and records to 
monitor the study.  Research records provided to authorized, non-UCLA personnel will 
not contain identifiable information about you. Publications and/or presentations that 
result from this study will not identify you by name. 
 
How long information from the study will be kept: 
Information will be held in the database for 3 years after completion of the study. 
 
 
ARE THERE ANY COSTS FOR TAKING PART IN THIS STUDY?  
 
The study will pay for research-related items and/or services that are provided only 
because you are participating in the study. These research-related items and/or 
services are explained in other areas of this consent form. 
 
You or your health plan may be responsible to pay for all the types of items listed below: 
 
Items and services that would have been provided to you even if you were not in 
the study 
 
Health care given during the study as part of your regular care  
 
Items or services needed to give you study drugs or devices 
 
Monitoring for side effects or other problems 
 
Deductibles or co-pays for these items and/or services. 
WILL I BE PAID FOR MY PARTICIPATION?  
 
You will not be paid for your participation in this research study.  
 
WHAT OTHER THINGS SHOULD I CONSIDER BEFORE PARTICIPATION? 
 
Researcher Financial Interests in this Study 
 
There are no financial interests in this study. 
  
 
WHO CAN I CONTACT IF I HAVE QUESTIONS ABOUT THIS STUDY? 
 


Page 7 of 8 
 
The Research Team: 
You may contact Dr. Joseph Caprioli at 310-794-9442 with any questions or concerns 
about the research or your participation in this study. You can also call the UCLA Page 
Operator at (310) 825-6301 to reach Dr. Joseph Caprioli 24 hours a day, 7 days a week. 
 
UCLA Office of the Human Research Protection Program (OHRPP): 
If you have questions about your rights while taking part in this study, or you have 
concerns or suggestions and you want to talk to someone other than the researchers 
about the study, you may contact the UCLA OHRPP by phone: (310) 825-5344; by 
email: mirb@research.ucla.edu or U.S. mail: UCLA OHRPP, 11000 Kinross Ave., Suite 
211, Box 951694, Los Angeles, CA 90095-1694. 
 
Public Information about this Study: 
ClinicalTrials.gov is a website that provides information about federally and privately 
supported clinical trials. A description of this clinical trial will be available on 
http://www.ClinicalTrials.gov, as required by U.S. Law. This website will not include 
information that can identify you. At most, the website will include a summary of the 
results. You can search this website at any time.  
 
 
WHAT HAPPENS IF I BELIEVE I AM INJURED BECAUSE I TOOK PART IN THIS 
STUDY?  
 
It is important that you promptly tell the researchers if you believe that you have been 
injured because of taking part in this study. You can tell the researcher in person or call 
him/her at the number(s) listed above. 
 
If you are injured as a result of being in this study, UCLA will provide necessary medical 
treatment. The costs of the treatment may be covered by the University of California or 
the study, or billed to you or your insurer just like other medical costs, depending on a 
number of factors. The University and the study sponsor do not normally provide any 
other form of compensation for injury.  For more information about this, you may call the 
UCLA Office of the Human Research Protection Program at 310-825-5344 or send an 
email to mirb@research.ucla.edu. 
 
 
WHAT ARE MY RIGHTS IF I TAKE PART IN THIS STUDY?  
 
Taking part in this study is your choice. You can choose whether or not you want to 
participate. Whatever decision you make, there will be no penalty to you and you will not 
lose any of your regular benefits. 
 You have a right to have all of your questions answered before deciding whether to 
take part. 
 Your decision will not affect the medical care you receive from UCLA. 
 If you decide to take part, you can leave the study at anytime.  


Page 8 of 8 
 
 If you decide to stop being in this study you should notify the research team right 
away. The researchers may ask you to complete some procedures in order to 
protect your safety.  
 If you decide not to take part, you can still get medical care from UCLA. 
 
 
HOW DO I INDICATE MY AGREEMENT TO PARTICIPATE?  
 
 
If you agree to participate in this study you should sign and date below. You have been 
given a copy of this consent form and the Research Participant’s Bill of Rights to keep.  
You will be asked to sign a separate form authorizing access, use, creation, or 
disclosure of health information about you. 
 
 
SIGNATURE OF THE PARTICIPANT  
 
______________________________________ 
Name of Participant 
 
______________________________________ 
______________________ 
Signature of Participant 
 
 
 
 
Date 
 
 
SIGNATURE OF PERSON OBTAINING CONSENT 
 
______________________________________ 
______________________ 
Name of Person Obtaining Consent 
 
 
Contact Number 
 
______________________________________ 
______________________ 
Signature of Person Obtaining Consent  
 
Date