Ab Interno Gelatin Stent With Mitomycin C Using Targeted Supra-tenon's Placement
Conditions: Glaucoma
Sponsor: Prism Eye Institute

BRAMPTON 
7700 Hurontario St, Unit 605, L6Y 4M3 
 
MISSISSAUGA 
3200 Erin Mills Pkwy, Unit 1, L5L 1W8 
71 King Street West, Unit 207, L5B 4A2 
 
CONFIDENTIAL 
 
Version 1.0, Dec 14th, 2018 
 
 
 
 
 
Ab interno Gelatin Stent with mitomycin C using targeted 
supra-tenon’s placement 
 
 
 
 
 
 
 
PI: Iqbal Ike K Ahmed MD FRCSC 
Research Staff: Fady Sedarous 
Study Coordinator: Ayda Shahidi 
Version 1.0 
Dec 14th, 2018 
 
 
 

BRAMPTON 
7700 Hurontario St, Unit 605, L6Y 4M3 
 
MISSISSAUGA 
3200 Erin Mills Pkwy, Unit 1, L5L 1W8 
71 King Street West, Unit 207, L5B 4A2 
 
CONFIDENTIAL 
 
Version 1.0, Dec 14th, 2018 
Table of Abbreviations 
 
Any abbreviations that you will be using in your protocol must be defined in this table in 
alphabetical order. If no abbreviations are being used, then this section does not need to be 
included 
 
GVT—Gelatin Stent vs. Trabeculectomy 
MMC—Mitomycin C 
IOP—Intraocular Pressure 
PKP—Penetrating Keratoplasty 
DALK—Deep Anterior Lamellar Keratoplasty 
DSAEK—Descemet's stripping automated endothelial keratoplasty 
DMEK—Descemet's membrane endothelial keratoplasty 
CPC—Cyclophotocoagulation 
AC—Anterior Chamber 
POM—Post-op month 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

BRAMPTON 
7700 Hurontario St, Unit 605, L6Y 4M3 
 
MISSISSAUGA 
3200 Erin Mills Pkwy, Unit 1, L5L 1W8 
71 King Street West, Unit 207, L5B 4A2 
 
CONFIDENTIAL 
 
Version 1.0, Dec 14th, 2018 
Background 
The Xen-45 gelatin microstent (Allergan, Dublin, Ireland) is a novel, bleb-forming 
microinvasive glaucoma surgery (MIGS).1 Creation of a filtering bleb through the gel stent and 
under the conjunctiva lowers intraocular pressure (IOP) by bypassing the natural outflow 
pathway of aqueous. A recent retrospective cohort study showed comparable safety and risk of 
failure to trabeculectomy.2 Amongst the main advantages of this device is the ability to create a 
bleb without dissecting and disrupting tissue, thus decreasing the amount of wound healing 
and potentially limiting bleb failure. However, despite demonstrating similar efficacy and safety 
to trabeculectomy,2 the Xen-45 gelatin microstent continues to suffer from occasional surgical 
failure due to fibrosis of the filtering bleb, and obstruction of the stent.3 Although 
antimetabolites, such as mitomycin C, have decreased reactionary wound healing that can 
result following surgery, fibrosis may still occur, especially when the components of the Xen-45 
gelatin microstent are in close proximity to the fibroblastic structures of tenon’s fascia.4,5  
Tenon’s capsule resembles a sponge-like layer with multiple adhesions to the overlying 
conjunctiva and underlying episclera.6 Implantation of the XEN within this space creates a 
higher risk of obstruction and subsequent failure. To ensure the lowest potential for occlusion, 
bleb scarring, and failure, one must ensure careful placement of the device in the 
subconjunctival space, avoiding intra-tenon’s placement. Placement in the supra-tenon’s space 
is believed to maximize aqueous outflow, while preventing obstruction, limiting fibrosis of the 
bleb, and promoting long-term patency.7 Despite the theoretical merits, long-term data of 
outcomes after targeted supra-tenon’s placement is needed to fully assess its potential in 
improving Xen-45 microstent outcomes. 
 
Research Question/Objective 
Hypothesis 
• Targeted supra-tenon’s placement of the Xen-45 gel microstent results in higher success, less 
needling and lower IOPs than non-targeted placement. 
 
Primary objective  
• Evaluate outcomes of patients receiving an ab interno gelatin stent with mitomycin C (MMC) 
using targeted supra-tenon’s placement to patients receiving an ab interno gelatin stent with 
non-targeted placement. 

BRAMPTON 
7700 Hurontario St, Unit 605, L6Y 4M3 
 
MISSISSAUGA 
3200 Erin Mills Pkwy, Unit 1, L5L 1W8 
71 King Street West, Unit 207, L5B 4A2 
 
CONFIDENTIAL 
 
Version 1.0, Dec 14th, 2018 
 
Secondary objectives 
• Intraoperative complications: corneal abrasion or perforation, hyphema, subconjunctival 
bleeding, gelatin stent fracture or need for re-implanation, iris prolapse, suprachoroidal 
hemorrhage, vitreous loss or posterior capsule rupture. 
• Management interventions (not considered complications): bleb needling, AC reformation, 
suture release, digital ocular compression, use of glaucoma medications, or laser/tpa to blocked 
ostomy or lumen. 
• IOP: mean IOP, mean decrease in IOP from baseline, IOP thresholds of ≥6 and ≤17, ≥6 and ≤14, 
and ≥6 and ≤21 (mmHg). 
• Vision: number of patients who lose more than two lines of best corrected visual acuity, post-
operative cataract surgery rates, auto-refraction. 
• Glaucoma medications: number of topical glaucoma medications and percentage of patients 
on glaucoma medications. 
• Visual recovery: percentage of patients who achieve baseline best corrected visual acuity at 1 
week, 1 month, 3 months, and annually thereafter. 
• Non-protocol visits: number of non-scheduled non-protocol visits. 
 
 
Aim of the project 
• Retrospectively obtain data through a chart review for exploratory purposes. 
 
Study Design 
 
Population + Recruitment Strategies 
• Patients aged 30-90 with primary or pigmentary/pseudoexfolliative open angle, primary 
closed angle, or combined mechanism glaucoma with IOP of 18-40 mmHg on maximum tolerated 
medical therapy who received a gelatin stent with MMC at Prism Eye Institute from June 2012 to 
August 2019. 
• Exclusions: other forms of glaucoma, prior incisional glaucoma surgery, CPC, prior corneal graft 
(PKP, DALK, DSAEK, DMEK). 
 
Sample Size 

BRAMPTON 
7700 Hurontario St, Unit 605, L6Y 4M3 
 
MISSISSAUGA 
3200 Erin Mills Pkwy, Unit 1, L5L 1W8 
71 King Street West, Unit 207, L5B 4A2 
 
CONFIDENTIAL 
 
Version 1.0, Dec 14th, 2018 
• Assuming an alpha of 0.05, a clinically significant IOP difference of 3 mmHg and a standard 
deviation of 5 mmHg, the estimated sample size is 88 eyes (44 eyes per group). 
 
Tools for Data Collection  
• Data will be collected from the Electronic Medical Record. 
 
Methodology 
 
Outcome:  
 
      Survival analysis will be determined by the following success/failure criteria: 
1. Complete success: 
a. IOP: 6-17 mmHg and on no glaucoma medications (starting after POM1[3]) at least 
1 month after surgery with no reoperation. 
b. Absence of the following complications: 
i. Starting after POM1[3]: shallow AC w/ iridocorneal touch, any hyphema, 
corneal edema, wound leak/dehiscience, choroidal effusion, malignant 
glaucoma, dellen/non-healing epithelial defect, ptosis, diplopia. 
ii. At any point: additional glaucoma surgery, loss of light perception vision, 
vitreous hemorrhage, ≥2mm hyphema, hypotony maculopathy, implant 
migration/blockage/exposure/extrusion, 
macular 
edema, 
choroidal 
effusion/hemorrhage requiring drainage, suprachoroidal hemorrhage, 
retinal detachment, suture abscess/blebitis/endophthalmitis 
c. Stable functional testing 
i. After POM1[3] no decrease in best corrected visual acuity of more than 2 
lines from baseline on 2 consecutive visits (unless deemed to be due to 
corneal or retinal disease—e.g., retinal vein occlusion) 
2. Qualified success:  
a. ‘Complete success’ criteria except that IOP can be above IOP thresholds, and then 
reduced to within the ‘Complete criteria’ by medications or laser in 3 visits or less. 
 
Statistical Analysis:  Analysis of variance (ANOVA) and Wilcoxon signed-rank test will be used to 
compare univariate normal and non-normal continuous baseline characteristics and outcomes.  
Fisher exact tests will be used to compare univariate categorical baseline characteristics and 
outcomes.  Time to failure will be defined as the time from surgery to the patient no longer 
meeting the ‘success’ criteria. Multivariate analysis will be performed with Cox proportional 
hazard regression analysis. A p-value of 0.05 or less will be considered statistically significant. 
 

BRAMPTON 
7700 Hurontario St, Unit 605, L6Y 4M3 
 
MISSISSAUGA 
3200 Erin Mills Pkwy, Unit 1, L5L 1W8 
71 King Street West, Unit 207, L5B 4A2 
 
CONFIDENTIAL 
 
Version 1.0, Dec 14th, 2018 
 
Safety Considerations 
• Given the nature of this project (retrospective chart review) there are no safety 
considerations. 
 
Data Analysis 
• Data analysis will follow the plan outlined above and use SAS Studio (Cary, NC). 
 
Perceptions of Bias  
• Information bias: Neither the patients nor clinicians are masked, thus in theory reporting can 
be influenced by performance bias and clinician beliefs. This is an inherent limitation of a 
retrospective study. The use of objective clinical measures to quantify success minimizes this 
bias.  
• There may be differential loss to follow-up in the study. Patients can be lost to follow-up for a 
variety of reasons: because they are doing well (sent back to the referring physician), not doing 
well (had a complication and have sought a second opinion), or lost to follow-up for other reasons 
not influenced by outcomes. 
  
Follow-up 
• The follow-up will be according to the patient’s electronic health record.  
 
 
Project Feasibility  
Ethical considerations 
• Given the retrospective nature of this project the main concern is the protection of the 
personal health information of the patients studied.  The data will be collected without personal 
identifying information (instead using a unique identifier), and published will be in aggregate as 
to not reveal personal information about any patient in an identifiable manner. 
 
 
 
 
 
 

BRAMPTON 
7700 Hurontario St, Unit 605, L6Y 4M3 
 
MISSISSAUGA 
3200 Erin Mills Pkwy, Unit 1, L5L 1W8 
71 King Street West, Unit 207, L5B 4A2 
 
CONFIDENTIAL 
 
Version 1.0, Dec 14th, 2018 
 
 
References 
1.  
Conlon R, Saheb H, Ahmed IIK. Glaucoma treatment trends: a review. Can J Ophthalmol. 
2017;52(1):114-124. doi:10.1016/j.jcjo.2016.07.013. 
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Schlenker MB, Gulamhusein H, Conrad-Hengerer I, et al. Efficacy, Safety, and Risk 
Factors for Failure of Standalone Ab Interno Gelatin Microstent Implantation versus 
Standalone Trabeculectomy. In: Ophthalmology. ; 2017. 
doi:10.1016/j.ophtha.2017.05.004. 
3.  
Fea AM, Spinetta R, Cannizzo PML, et al. Evaluation of Bleb Morphology and Reduction 
in IOP and Glaucoma Medication following Implantation of a Novel Gel Stent. J 
Ophthalmol. 2017. doi:10.1155/2017/9364910. 
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Ca C, Wang J, Hau S, Htoon HM, Barton K. Original Article XEN-45 collagen implant for 
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Crowston JG, Akbar AN, Constable PH, Occleston NL, Daniels JT, Khaw PT. 
Antimetabolite-induced apoptosis in Tenon’s capsule fibroblasts. Investig Ophthalmol 
Vis Sci. 1998. 
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Kakizaki H, Takahashi Y, Nakano T, et al. Anatomy of Tenons capsule. Clin Exp 
Ophthalmol. 2012. doi:10.1111/j.1442-9071.2011.02745.x. 
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Lewis RA. Ab interno approach to the subconjunctival space using a collagen glaucoma 
stent. J Cataract Refract Surg. 2014;40(8):1301-1306. doi:10.1016/j.jcrs.2014.01.032.