A Randomized Study Comparing the Safety and Efficacy of the InnFocus MicroShunt® Glaucoma Drainage System to Standard Trabeculectomy In Subjects With Primary Open Angle Glaucoma
Phase: NA
Conditions: Primary Open Angle Glaucoma
Sponsor: InnFocus Inc.

 
June 2nd, 2022 
 
Clinicaltrials.gov 
 
To Whom It May Concern, 
Please see attached, the following document: 
 
Official Title: 
Protocol 
Study ID: 
 
INN-005 
Dated: 
 
21Jul2017 
 
NCT No. 
 
NCT01881425 
 
Thank you, 
 
 
Haydee Frost 
Clinical Research Associate 
InnFocus, Inc. a Santen Company 

                                                          Page 1 of 84                        INN-005 Rev. 072117 
 
  
A Randomized Study Comparing the Safety and Efficacy of the 
InnFocus MicroShunt® Glaucoma Drainage System  
to Standard Trabeculectomy In Subjects 
with Primary Open Angle Glaucoma 
 
Protocol INN-005 
 
July 21, 2017 
 
Sponsor: 
InnFocus, Inc. 
12415 S.W. 136 Avenue, Unit #3 
Miami, FL 33186 
Tel: 305-378-2651 
Fax: 305-378-2652 
 
Medical Monitor: 
Paul F. Palmberg, M.D., Ph.D 
Bascom Palmer Eye Institute 
900 N.W., 17th Street 
Miami, FL 33136 
Tel: 305-781-2561 
Email: mitodoc@aol.com
Sponsor Contact:  
Jeannie Cecka 
Regulatory Consultant to 
InnFocus, Inc. 
12415 S.W. 136 Avenue, Unit #3 
Tel: 510.685.6004 
Email: jmcecka@comcast.net 
 

                                                          Page 2 of 84                        INN-005 Rev. 072117 
 
InnFocus, Inc. 
 
Protocol INN-005 
 
A Randomized Study Comparing the Safety and Efficacy of the 
InnFocus MicroShunt® Glaucoma Drainage System  
to Standard Trabeculectomy In Subjects  
with Primary Open Angle Glaucoma 
 
 
Study Synopsis 
 
Study Objective:  The study objective is to assess the safety and effectiveness of the InnFocus 
MicroShunt when used to lower intraocular pressure (IOP) in subjects with primary open angle 
glaucoma where the IOP is not controlled when using maximum tolerated glaucoma 
medications. 
 
Study Design:  This is a prospective, randomized, controlled, single-masked, multicenter trial.  
Two study groups will be included in the study.  The treatment group consists of subjects who 
receive the InnFocus MicroShunt with Mitomycin C (MMC).   The control group consists of 
subjects who receive trabeculectomy with MMC.    
 
The study will consist of two phases.  In the initial phase (Phase I), 102 subjects (68 treatments 
and 34 controls, 2:1 randomization ratio) were randomized.  After 75 initial-phase subjects 
(about 50 treatments and 25 controls) completed the 3-month follow-up examination, all data 
was submitted to the FDA to request approval for expansion (Phase II) to the full study 
population of an additional 412 randomized subjects (approximately 309 treatments and 103 
controls, 3:1 randomization ratio).  Subsequently an expansion of Phase II was granted for 
another 102 patients with the same randomization schedule (3:1) for a total of 514 Phase II 
patients. Phase I patients will be analyzed as a feasibility cohort separately from Phase II. 
   
A total of 514 subjects will be randomized in Phase II at 3:1 ratio. with a drop-out rate of 6% per 
year, approximately 480 randomized subjects in Phase II (360 treatments and 120 controls) are 
expected to have the 12-month examination and 448 randomized subjects (336 treatments and 
112 controls) are expected to have the 24-month follow-up examination. 
 
The randomization will be stratified by investigational site and within-site by lens status with a 
target of at least 60 randomized phakic eyes in the treatment group and 20 randomized phakic 
eyes in the control group at 24 months.   
 
Study Parameters:  The study population will consist of subjects diagnosed with open angle 
glaucoma with IOPs that are not controlled on maximum tolerated glaucoma medications.    All 
subjects will have medicated IOPs of ≥ 15 mmHg and ≤ 40 mmHg.   

                                                          Page 3 of 84                        INN-005 Rev. 072117 
 
 
Subject Population:  For Phase II, each investigational site will be asked to enroll at least 23 
subjects in the study.  Additionally, no study investigator will exceed 25% of the total number of 
randomized investigational device or control subjects. For study sites with more than one 
investigator, the total randomization will not exceed 33% of the total number of randomized 
investigational device or control subjects.  Each investigator should enroll at least 10 
investigational device subjects and each site will be asked to enroll approximately 23 subjects.   
 
Effectiveness Outcomes:   
The primary effectiveness outcome is the proportion of eyes with ≥ 20% decrease in mean 
diurnal intraocular pressure from screening to 12 months post-operative examination.  
 
The proportion of eyes with ≥ 20% decrease in mean diurnal intraocular pressure from screening 
to 24 months follow-up will also be compared between treatment group and control group. 
 
 
 
The secondary effectiveness outcome is the mean diurnal IOP change from screening to 12 
months follow-up. 
 
The mean diurnal IOP change from screening to 24 months post-operative examination will also 
be compared between the treatment group and control group. 
 
 
Analyses of outcomes will consider subjects that fall into a failure category.  Failure is defined as 
a patient with one or more of the following: 
1. No light perception vision confirmed on two consecutive visits 
2. IOP persistently below 6mmHg (defined as an intraocular pressure below 6mm that is 
present on two consecutive follow-up visits after the three month visit)  
3. Requiring a reoperation in the study eye in an operating room consisting of: 
a. Trabeculectomy 
b. Placement of a drainage device 
c. Bleb revision (other than needling) 
d. Explantation or repositioning of the InnFocus MicroShunt 
e. Iridectomy 
f. Resuturing of the scleral flap  
4. Glaucoma laser procedure (e.g., trabeculoplasty, iridotomy) 
5. Other glaucoma surgery to reduce IOP 
6.   Missing 24-month diurnal IOP due to discontinuation from the study prior to the 24-month 
visit 
7.   Post-operative introduction of an oral carbonic anhydrase inhibitor 
 
The procedures shown below will be reported as complications but are not failures: 
1. Needling of the bleb with or without the use of an injected antifibrotic 
2. Laser removal of blockage at the tip of the InnFocus MicroShunt or at the AC entry 
point for a trabeculectomy 
3. Use of a viscoelastic to limit aqueous flow 
 

                                                          Page 4 of 84                        INN-005 Rev. 072117 
 
The following procedures will not be considered as failures or complications but will be 
documented: 
1. Eye massage 
2. Laser suture lysis in a trabeculectomy 
. 
Inclusion Criteria 
 
All criteria apply to the study eye unless otherwise noted: 
 
1) Male or female patient, age 40 to 85 years, inclusive 
2) Early to severe primary open angle glaucoma where the mean diurnal intraocular pressure is 
not controlled on maximum tolerated medical therapy with intraocular pressure ≥ 15 mm Hg 
and ≤ 40 mm Hg while on glaucoma medications.   
Maximum tolerated medical therapy is defined as:  
a. Three or more classes of topical glaucoma medications (prostaglandin analog, beta–
adrenergic antagonist, carbonic anhydrase inhibitor, alpha-adrenergic agonist, 
parasympathomimetic).  Combination glaucoma medications that consist of two or more 
glaucoma drugs will have each glaucoma drug component counted as a separate drug. 
b. fewer than three classes presently in use if a subject’s intolerance to specific glaucoma 
medications and ineffective medications are included. 
3) Primary open angle glaucoma diagnosis based on: 
a.   visual field mean deviation of -3dB or worse and 
b.   glaucomatous optic nerve damage as evidenced by any of the following optic disc or 
retinal nerve fiber layer structural abnormalities documented on slit lamp stereo 
biomicroscopy or in stereo disc photos: 
 Diffuse thinning, focal narrowing, or notching of the optic disc rim, especially at 
the inferior or superior poles 
 Localized abnormalities of the peripapillary retinal nerve fiber layer, especially at 
the inferior or superior poles 
 Optic disc neural rim asymmetry of the two eyes consistent with loss of neural 
tissue 
 Disc rim or peripapillary retinal nerve fiber layer hemorrhages. 
4)     Prior ab interno conjunctival-sparing glaucoma procedures were conducted more than 6 
months prior to enrollment (e.g., iStent, Trabectome, gonioscopy-assisted transluminal 
trabeculectomy [GATT]). 
5) Patient must have signed and dated the Informed Consent form. 
6) Patient is willing to attend follow-up visits for two years postoperatively. 
 
 

                                                          Page 5 of 84                        INN-005 Rev. 072117 
 
Exclusion Criteria 
All criteria apply to the study eye unless otherwise noted  
1) Patient unwilling or unable to give informed consent, unwilling to accept randomization, or 
unable to return for scheduled protocol visits through 2 years. 
2) Patient < 40 years or >85 years of age. 
3) Patient is pregnant or nursing or unable to use appropriate birth control. 
4) Vision level of no light perception. 
5) Active iris neovascularization, active proliferative retinopathy or other ophthalmic disease 
that could confound study results. 
6) Iridocorneal endothelial syndrome. 
7) Epithelial or fibrous downgrowth. 
8) Secondary glaucoma such as post-trauma, pseudoexfoliation or pigment dispersion. 
9) Chronic ocular inflammatory disease. 
10) Subject already enrolled in this or another study (only one eye can participate in this study) 
or completed their participation in another study within 30 calendar days of the screening 
exam. 
11)  Aphakia. 
12) Vitreous in the anterior chamber.  
13) A history of corneal surgery (including Lasik or PRK), corneal opacities or 
disease/pathology if accurate IOP measurement may be affected. (Active corneal infection or 
Fuchs dystrophy are examples.)  
14) Severe anterior or posterior blepharitis. 
15) Unwilling to discontinue contact lens use after surgery for the duration of the study. 
16) Previous incisional ophthalmic surgery involving the conjunctiva.   
17) Prior clear corneal cataract, angle or trabecular meshwork surgery conducted within the past 
6 months (e.g., iStent, Trabectome, gonioscopy-assisted transluminal trabeculotomy)  
18) Presence of an anterior chamber IOL (ACIOL). 
19) Prior laser peripheral iridotomy conducted within three months of enrollment. 
20) Need for glaucoma surgery combined with other ocular procedures or anticipated need for 
additional ocular surgery during the investigational period. 
21) Fellow eye with poorer than 20/80 best-corrected visual acuity (BCVA) or points in both 
hemifields within 5 degrees of fixation with sensitivity less than <0 dB. 
22) Known allergy or other contraindication to mitomycin C (MMC) drug. 
23) Angle closure glaucoma or narrow anatomical chamber angle as identified by gonioscopy 
and classified as Shaffer Grade 0 or 1. 
24) Endothelial cell density at screening for the central reading of the following values: 
  
                             
Phakic 
Pseudophakic
Age 40-45< 2200  cells/mm2 
Age 40-45 < 1980 cells/mm2 
Age 46-55 < 2000  cells/mm2 
Age 46-55 < 1800  cells/mm2 
Age 56-65 < 1800  cells/mm2 
Age 56-65 < 1620  cells/mm2 
Age over 65 < 1600  cells/mm2 
Age over 65 < 1440  cells/mm2 
 

                                                          Page 6 of 84                        INN-005 Rev. 072117 
 
25) Any condition that prevents the investigational device implantation or trabeculectomy in the 
superior region of the study eye (e.g., peripheral anterior synechiae, scleral staphyloma or 
conjunctival scarring). 
26) Diagnosed degenerative visual disorders not associated with existing glaucoma condition 
(e.g., advanced dry or wet macular degeneration or other retinal disorders, central retinal 
artery or vein occlusion) or choroidopathy (e.g., choroidal detachment, effusion, choroiditis, 
or neovascularization). 
27) Central corneal thickness that is less than 450 microns or greater than 620 microns. 
28) Previous cyclodestructive procedure  
29) Prior retinal laser procedure conducted for any purpose other than treatment of retinal tear or 
hole. 
30) Conditions associated with elevated episcleral venous pressure such as active thyroid 
orbitopathy, cavernous sinus fistula, Sturge-Weber syndrome, orbital tumors, orbital 
congestive disease. 
31) Clinically significant sequelae from trauma (e.g., chemical burns, blunt trauma, etc.) 
32) Ocular pathology or medical condition for which, in the investigator's judgment, the 
following factors would either place the subject at increased risk of complications or 
contraindicate device implantation or interfere with compliance to elements of the study 
protocol (e.g., ophthalmic examinations, follow-up visits), 
a. inability to reliably complete visual field testing over the course of the study, 
b. uncontrolled systemic disease (e.g. diabetes, hypertension) that could compromise their 
participation in the study. 
c. Disorders that pose a fall risk, as well as compromise ability to take a visual field exam 
and take glaucoma medications (e.g., Parkinson's disease), 
d.   inability to discontinue use of blood thinners.  
e.   immunodeficiency concerns. 
f.   known corticosteroid responders whose pressure increases would not allow them to 
withstand the postop corticosteroid regimen. 
33) Intraocular silicone oil. 
34) Ocular steroid use in the planned study eye or systemic steroid use anytime within three 
months of the procedure. (This would not include the use of inhaled or dermatologic 
steroids.) 
35) Completion of chemotherapy within six months of the screening visit. 
36) Use of oral hypotensive glaucoma medications for treatment of fellow eye. 
37) A requirement of general anesthesia for the procedure. 
38) ALT/SLT within 90 days of enrollment. 
 
  

                                                          Page 7 of 84                        INN-005 Rev. 072117 
 
                                  Study Visits and Parameters for Study Eyes 
 
 
1 Diurnal  IOP 
 
Examination Schedule: 
1. Screening Evaluation  
 
6.  3 Months     
 
2. Operative Procedure   
 
7.  6 Months    
3. 1   Day  
 
 
 
8.  12 Months    
4. 1   Week  
 
 
 
9.   18 Months  
5. 4 Weeks  
 
 
 
10. 24 Months 
 
 
 
 
 
 
Activities 
Screening  
Op 
Follow-up Evaluation 
 
 
1 D
1W
4W
3 M
6 M 
12M 
18M 
24M
Informed Consent 
X 
 
 
Randomization 
 
X
 
 
Ocular Medical History 
X 
X
 
 
Ocular Medication Assessment 
X 
X
X
X
X
X
X
X 
X 
X
History/Demographics 
X 
 
 
Manifest Refraction 
X 
X
X
X
X 
X 
X
BCVA (Snellen) or Pinhole VA 
 
X
X
 
 
BCVA (ETDRS) 
X 
X
X
X
X 
X 
X
Visual Field 
X 
X 
X
X 
 
X
Slit Lamp Exam 
X 
X
X
X
X
X
X 
X 
X
Lens Status for Phakic Eyes 
X 
X
X
X 
X 
X
IOP 
X1 
X
X
X
X
X
X1 
X 
X1
Pachymetry 
X 
X 
 
X
Endothelial Cell Density 
X 
X
X
X 
 
X
Gonioscopy 
X 
 
 
 
 
 
Dilated Fundus Exam 
X 
 
 
   Vertical C/D Ratio 
X 
X
X 
X
X 
 
X
   Optic Disc Photo  
X 
X
X
X
X 
 
X
Diplopia 
 
X 
 
X
X
X 
 
X
Motility 
X 
 
X
X
X 
 
X
Pregnancy Test (as applicable) 
X 
 
 
Surgical Procedure 
 
X
 
 
Observations Recorded 
X 
X
X
X
X
X
X
X 
X 
X
Adverse Event Assessment 
 
X
X
X
X
X
X
X 
X 
X
Ocular QOL Questionnaire  
X 
X
X
X
X
X 
X 
X
General Health Questionnaire 
X 
X
X
X
X 
X 
X

                                                          Page 8 of 84                        INN-005 Rev. 072117 
 
The fellow eye will be managed according to the items listed and data will be gathered on 
the case report forms. 
 
             Activities Conducted on Fellow Eye During Clinical Study 
Activities 
Screening 
 
Follow-up Evaluation 
 
 
1 D
1W
4W
3 M
6 M 
12M 
18M 
24M
Ophthalmology Exam 
X 
 
Ocular Medical History 
X 
 
Ocular Medication 
Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
History/Demographics 
X 
 
Visual Field 
X 
X 
 
X
Dilated Fundus Exam 
X 
X
X 
 
X
   Vertical C/D Ratio 
X 
X
X 
 
X
   Optic Disc Photo 
X 
X
X 
 
X
Slit Lamp Exam 
X 
X
X 
X 
X
Manifest Refraction 
X 
X
X
X
X 
X 
X
Visual Acuity (Snellen or 
Pinhole) 
 
X 
X 
 
 
 
 
 
 
BCVA (ETDRS) 
X 
X
X
X
X 
X 
X
IOP 
X 
X
X
X
X
X
X 
X 
X
Pachymetry 
X 
X 
 
X
Endothelial Cell Density 
X 
X
X 
 
X
Motility 
X 
 
 
 
 
 
X 
 
X 
Observations Recorded 
X 
X
X
X
X
X
X 
X 
X
Adverse Event Assessment 
 
X
X
X
X
X
X 
X 
X

                                                          Page 9 of 84                        INN-005 Rev. 072117 
 
 
 
Screening
Subject signs
Informed Consent and is 
enrolled in study
End of Study Form
Subject does not
meet screening criteria
Out of Study
Subject Meets Screening 
Criteria
Subject is Randomized on 
Day of Surgery 
Surgery
Follow up 1d, 7d, 4W
Follow up 3, 6, 18 mo
Follow up 12, 24 mo
Subject Terminates
Study Early
Unscheduled 
Visit Form
Adverse 
Event 
Form
UADE 
Form
If UADE 
or SAE
Additional
Follow up
If Adverse
Event
Reoperation 
Form
If Re-op

                                                          Page 10 of 84                        INN-005 Rev. 072117 
 
LIST OF ABBREVIATIONS 
AE 
Adverse Event 
ALT 
BCVA 
CFR 
Argon Laser Trabeculoplasty 
Best Corrected Visual Acuity 
Code of Federal Regulations 
CRF 
Case Report Form 
DSMB 
Data Safety Monitoring Board 
FE 
GCP 
Fellow Eye 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HVF 
ICF 
Humphrey Visual Field 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IOP 
IRB 
Intraocular Pressure 
Institutional Review Board 
LASIK 
MMC 
MR 
NRS 
OD 
OS 
OU 
PI 
POAG 
SE 
Laser in situ keratomileusis 
Mitomycin 
Manifest Refraction 
Numeric Rating Scale 
Oculus Dextrus (Right Eye) 
Oculus Sinister (Left Eye) 
Oculus Uterque (Both Eyes) 
Principal Investigator 
Primary Open Angle Glaucoma 
Study Eye 
SLE 
SLT 
TA 
UADE 
VA 
VF 
YAG 
Slit-lamp Examination 
Selective Laser Trabeculoplasty 
Tonometry by applanation 
Unanticipated adverse device effect 
Visual Acuity 
Visual Field 
Yttrium-aluminum-garnet laser used in posterior capsule 
opacity; also referred to as a neodymium (Nd): YAG laser 
 

                                                          Page 11 of 84                        INN-005 Rev. 072117 
 
 
                                     InnFocus Study INN-005 
                               Table of Contents                         Page 
 
 
 
 
 
                       
1.0    Study Objective  
 
 
 
 
 
 
 
12 
2.0    Study Design 
 
 
 
 
 
 
 
 
12 
3.0    Rationale for the Study 
 
 
 
 
 
 
 
12 
4.0    Potential Risks and Benefits 
 
 
 
 
 
 
14 
5.0    Device Description 
 
 
 
 
 
 
 
16 
6.0    Primary Effectiveness Outcome  
 
 
 
 
 
17 
7.0    Secondary Effectiveness Outcome 
 
 
 
 
 
18 
8.0    Safety Outcome                                                                                                    18 
9.  0  Protocol Parameters 
 
 
 
 
 
 
 
18 
 
9.1  Study Centers  
 
 
                       
 
          18 
 
9.2   Study Population Characteristics                                                          
18 
 
9.3   Study Entry Procedures                                                                       
22 
  
9.3.1  Informed Consent 
 
 
 
 
 
 
22 
 
9.3.2  Screening Evaluation 
 
 
 
 
 
23 
 
9.3.3  Surgery and Subject Randomization 
 
 
 
24 
 
9.3.4  Evaluation Methods  
 
              
 
 
25 
 
9.4   Study Procedures                                                                                    
31 
 
9.4.1  Training 
 
 
 
 
 
 
 
31 
 
9.4.2  Material and Equipment 
 
 
 
 
 
31 
 
9.4.3  InnFocus MicroShunt Surgical Procedure  
 
 
31 
 
9.4.4  Trabeculectomy with MMC Surgical Procedure 
 
 
33 
 
9.4.5  Post Operative Instructions                        
 
 
35 
 
9.5   Follow-up                                                                                              
39 
 
9.6   Withdrawal Criteria                                                                              
41 
 
9.7   Lost to Follow-up Subjects                                                                         41 
 
9.8   Device Return                                                                                       
41 
 
9.9   Protocol Modifications and Deviations                                                
41 
10.0  Data Handling and Recordkeeping 
 
 
 
 
            42 
11.0  Assessment of Safety                                                                                            44 
12.0  Monitoring Plan  
 
 
 
 
 
 
            47 
13.0  Statistical Plan 
 
 
 
 
 
 
                       48 
14.0  Medical Monitor                                                                                                   48 
15.0  Data Safety Monitoring Board                                                                             48 
16.0  Compliance with Protocol 
 
 
 
 
 
            48 
17.0  References                                                                                                            49 
18.0  Supplementary Information – Definitions 
 
 
 
 
50 
          
Attachment 1- Background on POAG, Management, and Rationale for the Study   
Attachment 2 - Prior Pre-clinical and Clinical Testing                                                 

                                                          Page 12 of 84                        INN-005 Rev. 072117 
 
      
1.0 Study Objective 
The study objective is to assess the safety and effectiveness of the InnFocus MicroShunt 
when used to lower intraocular pressure (IOP) in subjects with primary open angle 
glaucoma where the IOP is not controlled when using maximum tolerated glaucoma 
medications. 
 
2.0 Study Design 
This is a prospective, randomized, controlled, single-masked, multicenter trial.  Two study 
groups will be included in the study.  The treatment group consists of subjects who receive 
the InnFocus MicroShunt with Mitomycin C (MMC).   The control group consists of 
subjects who receive trabeculectomy with MMC.    
 
The study will consist of two phases.  In the initial phase (Phase I), 102 subjects (68 
treatments and 34 controls, 2:1 randomization ratio) were randomized.  After 75 initial-
phase subjects (about 50 treatments and 25 controls) completed the 3-month follow-up 
examination, all data was submitted to FDA to request approval for expansion (Phase II) to 
the full study population of an additional 412 randomized subjects (about 309 treatments 
and 103 controls, 3:1 randomization ratio).  Subsequently an expansion of Phase II was 
granted for another 102 patients with the same randomization schedule (3:1) for a total of 
514 Phase II patients. Phase I patients will be analyzed as a feasibility cohort separately 
from Phase II.  
 
A total of 514 subjects will be randomized in Phase II at 3:1 ratio with a drop-out rate of 
6% per year, about 480 randomized subjects (360 treatments and 120 controls) are 
expected to have the 12-month examination and 448 randomized subjects (336 treatments 
and 112 controls) are expected to have the 24-month follow-up examination.. 
 
If a 40% screening failure is considered, at least 170 subjects should be enrolled for Phase I 
and 687 subjects should be enrolled for Phase II.  Therefore, total of at least 857 subjects 
will be enrolled for this study in order to have at least 514 subjects be randomized and at 
least 416 randomized subjects reach the 24-month visit. 
 
The randomization will be stratified by investigational site and within-site by lens type, 
with a target of at least 60 randomized phakic eyes in the treatment group and 20 
randomized phakic eyes in the control group at 24 months.  Each investigator is requested 
to conduct at least 10 InnFocus MicroShunt procedures and each site will be requested to 
enroll approximately 23 subjects. 
 
 
 
3.0 Rationale for the Study   
 
Trabeculectomy with MMC is one of the established treatment methods and for many years 
has been the gold standard treatment for individuals with glaucoma who are uncontrolled 

                                                          Page 13 of 84                        INN-005 Rev. 072117 
 
on maximum tolerated glaucoma medications, and is generally considered the first 
incisional surgery choice.  The latest poll of U.S. glaucoma specialists done in 2008 9 
indicates that 84% of primary trabeculectomies use MMC and 90% of combined 
phacoemulsification/trabeculectomy procedures use MMC.  The effectiveness and safety 
have been documented in numerous studies.  Data from a recent pilot studies are indicative 
that safety and effectiveness comparable to or better than trabeculectomy with MMC can 
be obtained with the use of the InnFocus MicroShunt.   
 
This prospective, randomized, controlled, open-label, multi-center trial directly comparing 
trabeculectomy with MMC to the InnFocus MicroShunt has been designed to establish the 
comparable safety and effectiveness of the InnFocus MicroShunt and trabeculectomy with 
MMC.  Trabeculectomy with and without MMC has been used previously as the literature 
control to prove comparability to another glaucoma drainage device that was granted FDA 
premarket approval (PMA), i.e., the AquaflowTM Collagen Glaucoma Drainage Device by 
Staar Surgical.  By using a randomized active control in the InnFocus MicroShunt study, a 
better comparison than literature controls can be made because there will be clearly defined 
and comparable subject populations in the two arms of the study. 
 
The MMC concentration of 0.2mg/mL and 2 minutes of exposure were selected based on 
the recent NDA approval of the Mobius Therapeutics MitosolTM Mitomycin C kit for use as 
an adjuvant to glaucoma filtering surgery.  This is the only approved source of MMC for 
this purpose.  Prior pilot studies conducted on the InnFocus MicroShunt used 0.4mg/mL 
and 3 minutes of application and there were no safety issues related to the concentration or 
application time of the MMC.  Review of the literature shows the MMC has been used over 
a wide range of MMC concentrations and application times from 0.1-0.5mg/mL and 1-5 
minutes application times.  Results of the various studies have shown no clear advantage of 
0.4mg/mL versus 0.2mg/mL; therefore, it is appropriate for this study to utilize the only 
approved source of MMC for the specific purpose of providing an adjuvant to glaucoma 
filtering surgery. 
 
The allowance of at least 6 months from the time of IOL placement for the pseudophakic 
subjects in the study was to assure that most of the healing from the surgery had occurred 
and there would be no residual inflammation or rapid endothelial cell configuration 
changes.  
 
Investigational sites for the clinical study have been selected to assure that an appropriate 
balance of gender, minority, and age are obtained during the study.  Many of the sites are in 
metropolitan settings, which assist greatly in providing this balance.  Also, the sites are 
distributed across the country to minimize any geographic differences.  The inclusion and 
exclusion criteria of the study will inherently result in the majority of subjects in the 60-80 
years of age range where the most subjects on maximum tolerated glaucoma medications 
would be expected to be.  Based on not allowing any subject less than 40 years of age in 
the study, there is not expected to be a significant effect on enrollment of women in the 
study because of the one exclusion “subject is pregnant or nursing or unable to use 
appropriate birth control”. 
 

                                                          Page 14 of 84                        INN-005 Rev. 072117 
 
4.0  Potential Risks and Benefits 
 
InnFocus has reviewed the potential risks and benefits associated with the InnFocus 
MicroShunt Glaucoma Drainage System.  The risks have been evaluated and design and 
procedure recommendations implemented to mitigate these risks where applicable. 
 
The following potential risks have been identified: 
a. 
The cornea or iris could be damaged during the implantation procedure or post 
implantation.  Based on prior clinical data, no cornea or iris damage has been observed 
although occasionally the device has made direct contact with the iris.  Additionally, 
surgeons are instructed on the proper insertion method.  This potential contact risk 
with the iris or cornea is similar to presently commercialized aqueous shunts (Ahmed, 
Baerveldt, Molteno) as they require placement of the proximal end of the tube in the 
same location as the InnFocus MicroShunt. 
b. 
The device may not be inserted completely into the anterior chamber.  If this occurs, 
the device may be relocated to a different access tract or another device may be 
implanted.  In either case, this would result in an overall longer procedure.  There has 
only been one case with the present device in which a second insertion location 
adjacent to the original location was required with the same device with a 
corresponding longer procedure time.  No other complications were observed. 
c. 
Tube obstruction is a risk with the InnFocus MicroShunt surgery. The device could 
clog if it remains in contact with the iris with resultant low flow and increased IOP.  
Although contact with the iris has been observed with the present device, flow has 
been maintained.  If the tip does become clogged, the physician can use a standard 
laser to remove the iris material from the tip of the device.  Also, fibrin that develops 
during surgery can occlude the device.  There has been one transient tube obstruction 
from fibrin in a combined InnFocus MicroShunt implantation and cataract surgery in 
an ongoing study that was resolved with a flush of the AC end of the tube during the 
initial surgery.  This risk of clogging is also present with the proximal end of 
commercial aqueous shunts, which can contact the iris, or cornea and lasers are 
routinely used to clear debris from the proximal end. 
d. 
The bleb that is typically created by the aqueous flow into the Tenon/subconjunctival 
pocket may develop excessive scarring (bleb encapsulation or also called “Tenon’s 
cyst”) which can result in lower aqueous flow through the bleb and increased IOP.  
The implantation procedure has been refined to provide for a large pocket that is 
resistant to fibrosis and scarring.  One bleb encapsulation was observed in prior 
InnFocus MicroShunt studies and was successfully needled.  A similar risk of scarring 
is observed with trabeculectomy. 
e. 
Choroidal effusion may occur and lead to an observable choroidal detachment.  This 
has been observed in 2 prior InnFocus MicroShunt cases during combined surgery 
with cataract removal and resolved with the use of cycloplegics.  There was no 
incidence of suprachoroidal hemorrhage in studies to date but this should be 
considered a risk of this surgery, as it is with trabeculectomy. 
f. 
Flat or shallow chambers may occur as the result of low pressure in the anterior 
chamber.  Two cases of shallow chambers were observed in studies to date and 
resolved spontaneously with no observable damage to the cornea or iris. 

                                                          Page 15 of 84                        INN-005 Rev. 072117 
 
g. 
Wound leaks may occur shortly after surgery and may be related to the suturing of the 
conjunctiva to the limbus.  One short-term wound leak was observed but resolved 
spontaneously within the first three weeks after surgery.  No long-term wound leaks 
have been observed in existing studies of this device. 
h. 
No blebitis has been observed in clinical studies to date but is a risk whenever a bleb is 
developed as a result of the surgery. 
i. 
No endophthalmitis has been observed but it is a risk of this type of surgery, especially 
in the event that blebitis develops. 
j. 
Hyphema has been observed in several cases but not at a level of 10% or more of the 
anterior chamber and typically resolves within one week of surgery. 
k. 
Aqueous misdirection is a potential risk of filtering surgery but has not been observed 
in existing studies of the device.  
l. 
Decompression retinopathy has not been observed but remains a risk with this type of 
surgery. 
m. Persistent hypotony is defined as an intraocular pressure below 6mmHg that is present 
on two consecutive follow-ups after three months.  This can lead to hypotony 
maculopathy. No persistent hypotony or hypotony maculopathy have been observed in 
studies to date. 
n. 
Corneal decompensation from MMC exposure could occur if MMC reached the 
corneal endothelium as has been reported in an animal model in the literature and is 
another risk. Avoiding contact of MMC with the cornea endothelium by rinsing MMC 
out of the subconjunctival pocket prior to entry of the needle into the AC should assure 
no entry of MMC and therefore no effect on the endothelium.  Corneal 
decompensation has not been observed in InnFocus MicroShunt clinical studies to 
date. 
o. 
A thin-walled avascular bleb may be associated with low IOP.  This has not been 
observed in the prior InnFocus MicroShunt studies. 
p. 
Tube erosion over time resulting in a break in the conjunctival barrier and potential 
infection is a risk in the InnFocus MicroShunt arm of the study.  There have been no 
tube erosions in the ongoing studies of the InnFocus MicroShunt. 
q. 
Chronic or recurrent iritis is a risk associated with filtering surgery.  No chronic or 
recurrent iritis has been observed in the ongoing InnFocus MicroShunt clinical studies. 
r. 
Migration of device out of anterior chamber.  There have been no clinical cases of 
InnFocus MicroShunt migration out of the anterior chamber, but there has been one 
case where the surgeon inadvertently moved the InnFocus MicroShunt out of the 
anterior chamber during conjunctival closure at time of the original procedure. 
 
The following potential benefits have been identified (please note we do not necessarily 
intend to seek specific claims for all these potential benefits): 
a. The surgical procedure does not require extensive cutting into the sclera, as does the 
trabeculectomy in the creation of a sclera flap and in punching an internal ostium, and 
where if the cut is too deep, there is a risk of hemorrhage and loss of the eye.  In this 
regard, the InnFocus MicroShunt is less invasive. 
b. The aqueous outflow through the InnFocus MicroShunt is controlled by the diameter 
and length of the InnFocus MicroShunt tube and does not rely on subjective tensioning 
of sutures as does trabeculectomy. 

                                                          Page 16 of 84                        INN-005 Rev. 072117 
 
c. If the implanted device is effective and reduces intraocular pressure, the subject may 
reduce or eliminate glaucoma medication therapy.  Reduction of glaucoma medication 
is desirable as more than half of the patients on glaucoma medications do not comply 
with their regimens and vision loss continues.  If the implanted device is effective and 
reduces intraocular pressure, the subject may not require additional glaucoma surgery 
and further vision loss may be avoided. 
d. Based on the minimally invasive procedure and the characteristics of the device, there 
may be fewer complications.  Historical clinical data suggests that the short term 
control of IOP with the InnFocus MicroShunt may be better than trabeculectomy with 
MMC with less inflammation and bleb scarring and less hypotony and associated 
concerns. 
 
5.0  Device Description 
 
This study evaluates the InnFocus MicroShunt Glaucoma Drainage System, which includes 
the InnFocus MicroShunt device and associated components.  There is only one device 
model in the clinical study.  The InnFocus MicroShunt can be stored at room temperature.  
Brief descriptions of each are presented below: 
 
5.1 InnFocus MicroShunt device 
The lumen of the device as shown below is approximately 70 microns in diameter with an 
outer diameter of 350 microns and a length of approximately 8.5mm.  It is designed to 
allow aqueous flow from the anterior chamber to a bleb (blister-like formation below the 
conjunctiva/Tenons).   
 
InnFocus MicroShunt 
(All dimensions in mm) 
                                             
 
 
It is packaged in a thermoform tray that is enclosed in a sealed Tyvek pouch. 
 
5.2   Double Step Incision Knife 
This disposable stainless steel knife has a 1.0mm wide cutting edge and a separate 0.5mm 
wide cutting edge at the distal end of the knife.  This double cutting edge allows a track to 

                                                          Page 17 of 84                        INN-005 Rev. 072117 
 
be completed through the sclera into the anterior chamber while simultaneously creating a 
1mm wide scleral pocket for the fin to be located. 
 
5.3   3mm Scleral Marker 
This disposable component is made from stainless steel.  The gentian violet from the 
marker pen is transferred to the tips of the marker during surgery.  The marker is lined up 
with the limbus and a point on the sclera 3mm from the limbus is marked with the marker.  
The marker is packaged in the InnFocus MicroShunt thermoform tray and enclosed in a 
sealed Tyvek pouch. 
 
5.4   Marker Pen 
The disposable marker pen contains gentian violet to be used with the 3mm marker to 
identify the point of entry for the knife.  It is provided in a separate sealed and sterilized 
package in the InnFocus MicroShunt System Box. 
 
5.5 23 Gauge Thin Wall Cannula 
This stainless steel cannula can be attached to a syringe filled with balanced sterile saline 
(BSS) and placed over the distal end of the InnFocus MicroShunt to flush saline through 
the lumen of the device and aid in initiating flow of aqueous.  The cannula is supplied in a 
separate sterile package in the InnFocus MicroShunt kit.   
 
5.6  Outer Packaging   
The ethylene oxide sterilized InnFocus MicroShunt and 3mm marker are packaged in a unit 
box with the other purchased and separately packaged sterilized components for shipment 
to the clinical site. 
 
6.0  Primary Effectiveness Outcome 
 
The primary effectiveness outcome is the proportion of eyes with ≥ 20% decrease in mean 
diurnal intraocular pressure from screening to 12 months follow-up.  
 
The proportion of eyes with ≥ 20% decrease in mean diurnal intraocular pressure from screening 
to 24 months follow-up will also be compared between treatment group and control group. 
 
Analyses of outcomes will consider subjects that fall into a failure category.  Failure is defined as 
a patient with one or more of the following: 
1.  No light perception vision confirmed on two consecutive visits 
2.  IOP persistently below 6mmHg (defined as an intraocular pressure below 6mm that is 
present on two consecutive follow-up visits after the three month visit)  
3.  Requiring a reoperation in the study eye in an operating room consisting of: 
a. Trabeculectomy 
b. Placement of a drainage device 
c. Bleb revision (other than needling) 
d. Explantation or repositioning of the InnFocus MicroShunt 
e. Iridectomy 
f. Resuturing of the scleral flap  

                                                          Page 18 of 84                        INN-005 Rev. 072117 
 
4.  Glaucoma laser procedure (e.g., trabeculoplasty, iridotomy) 
5.  Other glaucoma surgery to reduce IOP 
6.  Missing 24-month diurnal IOP due to discontinuation from the study prior to the 24-month 
visit 
7.  Post-operative introduction of an oral carbonic anhydrase inhibitor. 
 
The procedures shown below will be reported as complications but are not failures: 
1. Needling of the bleb with or without the use of an injected antifibrotic 
2. Laser removal of blockage at the tip of the InnFocus MicroShunt or at the AC entry 
point for a trabeculectomy 
3. Use of a viscoelastic to limit aqueous flow 
 
The following procedures will not be considered as failures or complications but will be 
documented: 
1. Eye massage 
2. Laser suture lysis in a trabeculectomy 
 
7.0  Secondary Effectiveness Outcome 
 
The secondary effectiveness outcome is mean diurnal IOP change from screening to 12 months 
follow-up post-operative examination.  
 
The mean diurnal IOP change from screening to 24 months post-operative examination will also 
be compared between the treatment group and control group. 
 
8.0  Safety Outcome 
 
Safety will be evaluated at one year follow-up as a comparison of all adverse events between the 
investigational device and control groups and will also be compared at 2 years follow-up. 
     
9.0  Protocol Parameters 
 
9.1  Number of Study Centers 
A total of 30 centers will be recruited to participate in the study to assure enrollment in a 
reasonable timeframe.  Thirteen centers are identified for the Phase I activities and will 
continue into Phase II as part of the total of 30 centers.  A maximum of 6 centers of the 
thirty are planned to be outside of the United States. 
 
9.2  Study Population Characteristics 
All of the following ophthalmic criteria apply to the study eye unless otherwise noted.  The 
study population will consist of subjects diagnosed with open angle glaucoma. Subjects 
will be currently taking ocular hypotensive medications and have IOPs that are not 
controlled.  Pseudophakic participants must have at least 180 days between cataract surgery 
and study enrollment. All subjects must have IOPs that are not controlled on maximum 

                                                          Page 19 of 84                        INN-005 Rev. 072117 
 
tolerated glaucoma medications.  The term “maximum tolerated glaucoma medications” is 
defined for this study as three or more classes of topical glaucoma medications 
(prostaglandin analog, beta blocker, carbonic anhydrase inhibitor, alpha agonist, miotic).   
If a subject is intolerant to specific glaucoma medications or the medications are 
ineffective, “maximum tolerated glaucoma medications” may be fewer than three classes 
presently in use. In cases where one or more of the classes of glaucoma medications have 
been used unsuccessfully because of ineffectiveness or allergic reaction or intolerable side 
effects, this will be noted on the Screening form.  Combination glaucoma medications that 
consist of two or more glaucoma drugs will have each glaucoma drug component counted 
as a separate drug. 
 
The rationale for adopting these criteria is derived from the observed outcomes in the 
Advanced Glaucoma Intervention Study (AGIS)1-3, the Early Manifest Glaucoma 
Treatment study (EMGT) 4-5 and the Collaborative Initial Glaucoma Treatment Study 
(CIGTS)6-8.   These studies taken together have shown that most eyes with primary open-
angle glaucoma will progress to a clinically significant degree without treatment, that 
visual field progression in glaucomatous eyes is intraocular pressure dependent, and that 
visual field loss can be stabilized in a large majority of eyes with optimal pressure 
reduction, which is best obtained with pressures in the low-normal range (11-13 mm Hg) 
for eyes with advanced damage, and no higher than the mid-normal (14-17 mm Hg) range 
for eyes with mild-moderate damage. All subjects will have medicated IOPs of > 15mmHg 
and < 40mmHg at time of screening.  In addition, all subjects will be in compliance with 
the inclusion and exclusion criteria presented below. 
 
9.2.1  Inclusion Criteria  (All criteria apply to the study eye) 
9.2.1.1  Male or female patient, age 40 to 85 years, inclusive 
9.2.1.2 Patient has early to severe primary open angle glaucoma where the mean 
diurnal intraocular pressure is not controlled on maximum tolerated 
medical therapy with the intraocular pressure ≥ 15 mm Hg and ≤ 40 
mm Hg while on glaucoma medications.   
 
Maximum tolerated medical therapy is defined as:  
9.2.1.2.1 Three or more classes of topical glaucoma medications 
(prostaglandin analog, beta–adrenergic antagonist, carbonic 
anhydrase inhibitor, alpha-adrenergic agonist, 
parasympathomimetic).  Combination glaucoma medications 
that consist of two or more glaucoma drugs will have each 
glaucoma drug component counted as a separate drug. 
9.2.1.2.2 Fewer than three classes presently in use if a subject’s 
intolerance to specific glaucoma medications and ineffective 
medications are included. 
9.2.1.3 Primary open angle glaucoma diagnosis based on: 
9.2.1.3.1  visual field mean deviation of -3dB or worse and 
9.2.1.3.2  glaucomatous optic nerve damage as evidenced by any of the 
following optic disc or retinal nerve fiber layer structural 
abnormalities documented on slit lamp stereo biomicrosopy or 
in stereo disc photos: 

                                                          Page 20 of 84                        INN-005 Rev. 072117 
 
 Diffuse thinning, focal narrowing, or notching of the optic 
disc rim, especially at the inferior or superior poles 
 Diffuse or localized abnormalities of the peripapillary retinal 
nerve fiber layer, especially at the inferior or superior poles 
 Optic disc neural rim asymmetry of the two eyes consistent 
with loss of neural tissue 
 Disc rim or peripapillary retinal nerve fiber layer 
hemorrhages 
9.2.1.4   Prior ab interno conjunctival-sparing glaucoma procedures were 
conducted more than 6 months prior to enrollment (e.g., iStent, 
Trabectome, gonioscopy-assisted transluminal trabeculectomy [GATT]). 
9.2.1.5   Patient must have signed and dated the Informed Consent form. 
9.2.1.6   Patient is willing to attend follow-up visits for two years postoperative. 
 
9.2.2  Exclusion Criteria (All criteria apply to the study eye unless otherwise noted) 
9.2.2.1  Patient unwilling or unable to give informed consent, unwilling to accept 
randomization, or unable to return for scheduled protocol visits through 2 
years. 
9.2.2.2  Patient < 40 yr or >85 years of age. 
 
9.2.2.3  Patient is pregnant or nursing or unable to use appropriate birth control. 
 
9.2.2.4  Vision level of no light perception. 
9.2.2.5  Active iris neovascularization or active proliferative retinopathy or other 
ophthalmic disease that could confound study results. 
9.2.2.6  Iridocorneal endothelial syndrome. 
 
9.2.2.7  Epithelial or fibrous downgrowth. 
 
9.2.2.8  Secondary glaucoma such as post-trauma, pseudoexfoliation or pigment  
dispersion. 
 
9.2.2.9  Chronic ocular inflammatory disease. 
9.2.2.10 Subject already enrolled in another study (only one eye can participate) 
or completed their participation in another study within 30 calendar 
days of the screening exam. 
 
9.2.2.11 Aphakia. 
 
9.2.2.12 Vitreous in anterior chamber for which a vitrectomy is anticipated. 
 
9.2.2.13 A history of corneal surgery (including Lasik or PRK), corneal opacities 
or disease/pathology if accurate IOP measurement may be affected. 
(Active corneal infection or Fuch’s dystrophy are examples.) 
 
9.2.2.14 Severe anterior or posterior blepharitis. 
 
9.2.2.15 Unwilling to discontinue contact lens use after surgery for the duration of 
the study. 
9.2.2.16 Previous incisional ophthalmic surgery involving the conjunctiva  
9.2.2.17 Prior clear corneal cataract, angle or trabecular meshwork surgery 
conducted within the past 6 months (e.g., iStent, Trabectome, 
gonioscopy-assisted transluminal trabeculotomy)  
9.2.2.18 Presence of an anterior chamber IOL (ACIOL). 
9.2.2.19 Prior laser peripheral iridotomy conducted within 3 months of 
enrollment.  

                                                          Page 21 of 84                        INN-005 Rev. 072117 
 
9.2.2.20 Need for glaucoma surgery combined with other ocular procedures or 
anticipated need for additional ocular surgery during the investigational 
period. 
9.2.2.21 Fellow eye with poorer than 20/80 best-corrected visual acuity (BCVA) 
or points in both hemifields within 5 degrees of fixation with sensitivity 
<0 dB. 
9.2.2.22 Known allergy or other contraindication to use of mitomycin C (MMC) 
drug. 
9.2.2.23 Angle closure or narrow angle as identified by gonioscopy and classified 
as Shaffer Grade 0 or 1. 
9.2.2.24 Endothelial cell density for the central reading at screening of the 
following values: 
Phakic
Pseudophakic 
Age 40-45< 2200  cells/mm2 
Age 40-45 < 1980 cells/mm2 
Age 46-55 < 2000  cells/mm2 
Age 46-55 < 1800  cells/mm2 
Age 56-65 < 1800  cells/mm2 
Age 56-65 < 1620  cells/mm2 
Age over 65 < 1600  cells/mm2 
Age over 65 < 1440  cells/mm2 
 
9.2.2.25 Any condition that prevents the investigational device implantation or 
trabeculectomy in the superior region of the study eye (e.g., peripheral 
anterior synechiae, scleral staphyloma or conjunctival scarring). 
9.2.2.26 Diagnosed degenerative visual disorders not associated with existing 
glaucoma condition (e.g., advanced dry macular degeneration or other 
retinal disorders, central or branch retinal artery or vein occlusion) or 
choroidopathy (e.g., choroidal detachment, effusion, choroiditis, or 
neovascularization). 
9.2.2.27 Central corneal thickness that is less than 450 microns or greater than 
620 microns. 
9.2.2.28 Previous cyclodestructive procedure  
9.2.2.29 Prior retinal laser procedure conducted for any purpose other than 
treatment of retinal tear or hole. 
9.2.2.30 Conditions associated with elevated episcleral venous pressure such as 
active thyroid orbitopathy, cavernous sinus fistula, Sturge-Weber 
syndrome, orbital tumors, orbital congestive disease. 
9.2.2.31 Clinically significant sequelae from trauma (e.g., chemical burns, blunt 
trauma, etc.) 
9.2.2.32 Ocular pathology or medical condition for which, in the investigator's 
judgment, the following would be either at risk or contraindicate device 
implantation or compliance to elements of the study protocol (e.g., 
ophthalmic examinations, follow-up visits), 
a. inability to reliably complete visual field testing over the course of 
the study, 
b. uncontrolled systemic disease (e.g. diabetes, hypertension) that could 
compromise their participation in the study. 

                                                          Page 22 of 84                        INN-005 Rev. 072117 
 
c. Disorders that pose a fall risk, as well as compromise ability to take 
a visual field exam and take glaucoma medications, (e.g., 
Parkinson's disease) 
d. inability to discontinue use of blood thinners  
e. immunodeficiency concerns. 
f. known corticosteroid responders whose pressure increases would not 
allow them to withstand the postop corticosteroid regimen. 
9.2.2.33 Intraocular silicone oil. 
9.2.2.34 Ocular steroid use in the planned study eye or systemic steroid use 
anytime within three months of the procedure. (This would not include 
the use of inhaled or dermatologic steroids.) 
9.2.2.35 Completion of chemotherapy within six months of the screening visit. 
9.2.2.36 Use of oral hypotensive medications for treatment of fellow eye.  
9.2.2.37 A requirement of general anesthesia for the procedure. 
9.2.2.38 ALT/SLT within 90 days of enrollment. 
 
9.3  Study Entry Procedures 
 
9.3.1  Informed Consent 
The InnFocus and IRB approved informed consent form (ICF) will be presented and 
explained to each prospective subject by the investigator or a trained clinical 
professional before study-specific tests have been performed.  The investigator or a 
trained clinical professional will explain the elements of the informed consent form, 
including the risks or discomforts, the fact that he or she will be randomized and 
therefore may or may or may not receive a device and he or she will not know their 
randomization treatment until the 2 year visit is completed.   
 
Once the subject has been informed of all aspects of the study, the potential subject 
will be given the opportunity to ask questions, and allowed time to consider the 
information provided. The subject’s willingness and ability to meet follow-up 
requirements will be determined. The subject will be given a choice to voluntarily 
confirm his or her participation in the study as documented by completion of the 
Informed Consent.  After signing and dating the Informed Consent, the HIPAA 
(Health Insurance Portability and Accountability Act) authorization, and other 
applicable local documentation (e.g., California Bill of Rights), the subject can then 
proceed with the screening evaluation.  The subject has the right to withdraw from the 
study at any time without consequences, as indicated in the Informed Consent 
document. 
 
Subjects are enrolled upon signing the informed consent document even if they 
subsequently fail to meet the eligibility criteria. Subjects will be added to the 
enrollment log, and assigned a subject number.  
 
The principal investigator(s) must retain the original, signed and dated Informed 
Consent Form.  A copy of the signed and dated Informed Consent Form must be 
given to the subject. Note: Subjects will remained masked throughout the two year 

                                                          Page 23 of 84                        INN-005 Rev. 072117 
 
follow-up period to the treatment they will received, this will be explained to the 
subject prior to their signing the informed consent document.  
 
9.3.2  Screening Evaluation  
After obtaining an understanding of the purpose of this study, then reviewing and 
signing the informed consent form, all potential subjects will undergo a series of 
standard clinical tests to determine their eligibility for the study.  
 
Subjects who do not meet the screening exam eligibility criteria will be exited from 
the study.  An ocular and non-ocular medication or supplements (including vitamins) 
assessment will be performed at screening visit and collected on CRF for the duration 
of the study. Subjects who are intolerant to maximum tolerated medications should 
have history glaucoma medications recorded on CRF. 
 
The screening examination will consist of the activities included in Table 1. The 
study eye and fellow eye of each subject will undergo the tests as indicated in Table 
1. 
 
                    Table 1.  Activities Conducted During Screening Evaluation 
Activity 
Study eye 
Screening 
Evaluation 
Fellow Eye 
Screening 
Evaluation 
Informed Consent 
X
X 
Demographics 
X
X 
Ocular Medical History 
X
X 
Systemic Disease History 
X
X 
Ocular Medication Assessment
X
X 
Ophthalmology Exam 
X
X 
BCVA (ETDRS) 
X
X 
Lens Evaluation (LOCS III)
X
 
Diurnal Medicated IOP 
X
 
Medicated IOP (during first IOP for study eye)
X 
Gonioscopy 
X
 
Optic Nerve Head Imaging 
X
X 
Vertical C/D Ratio 
X
X 
Pachymetry  
X
X 
Diplopia Evaluation 
X
 
Motility Evaluation 
X
 
Visual Field (only if < 3 mo. is not available) 
X
X 
Pregnancy Test (as applicable) 
X 
 
Endothelial Cell Density 
X 
X 
Ocular QOL Questionnaire 
X 
 
General Health Questionnaire 
X 
 
 

                                                          Page 24 of 84                        INN-005 Rev. 072117 
 
 
If both eyes meet the applicable inclusion and exclusion criteria, the eye that has the 
greater visual field defect will be in the study. If the mean deviations are within 1dB of 
each other, then the eye with the worse BCVA (or PAM result in phakic eyes in which 
the visual acuity is not 20/25 or better) will be selected. 
 
The other eye will be excluded based on the first eye already being included in the 
study.  
 
Note: If a subject does not meet the eligibility criteria, he/she may be re-screened 
after 30 calendar days. Subject should be exited from the study and pertinent clinical 
data to the screening exam will be recorded on the appropriate CRFs. If the subject is 
screened the second time, another subject identification number will be assigned.  
 
During the screening process, the surgeon will prospectively decide at what 
postoperative interventional IOP he/she will want to reinitiate glaucoma medication 
or physically intervene.  In this manner, the decision will be set before randomization, 
such that there will be no bias on the group to which the subject is randomized. 
 
 Default interventional IOP: IOP ˃ 21 mm Hg (or ˃ the preoperative medicated 
IOP if that was lower than 21mm Hg) is the default IOP for reinitiating 
glaucoma medication or physically intervening.  
 
 Alternate interventional IOP: IOP chosen by the surgeon above which he/she 
will reinitiate glaucoma medication or physically intervene.  
 
(If the alternate interventional IOP was chosen and the post-procedure IOP exceeds 
the surgeon’s choice, the subject will be asked to come back for a second visit within 
1 week to confirm the IOP before reinitiating glaucoma medication or physically 
intervening. If the IOP also exceeds the default interventional IOP, such that safety is 
a concern, a second visit is not required before taking any action.)  
 
9.3.3  Surgery and Subject Randomization 
On the day of the surgery, the subject is randomized to participate in the Treatment or 
Control groups using a pseudo-random number generator with subjects enrolled 
according to a predetermined list.  Each investigational site will be provided 
envelopes with randomization assignments.  The Treatment group will receive the 
InnFocus MicroShunt with MMC.  The Control group will receive trabeculectomy 
with MMC.  Note: The subject will not be informed of what procedure he/she will 
receive. Neither the investigator nor the investigational staff will reveal the treatment 
assignment to the study subject for the duration of their participation in the clinical 
study 
 
9.3.4  Evaluation Methods 
The following background information is provided to assist with appropriate 
screening and follow-up for all subjects in this study: 
 

                                                          Page 25 of 84                        INN-005 Rev. 072117 
 
a.  Measurement of intraocular pressure 
Each time IOP is measured, the physician or technician is to utilize a Goldmann 
tonometer; however, the individual operating the tonometer should not view the dial 
during the measurement and another individual who is masked to the treatment 
should read the measurement and then record the measurement to minimize observer 
bias.  At each visit, IOP will be measured prior to gonioscopy or dilation of the pupil. 
 
Each time IOP is measured, two measurements should be taken and the mean 
recorded on the case report form unless they differ by more than 2mmHg in which 
case a third measurement is taken and the median value is recorded.  All 
measurements must be recorded within the source documents. 
 
In order to determine the mean diurnal intraocular pressure (IOP) measurements at 
screening, 12 months and 24 months, values should be taken at 9:00AM + 1.5 hours, 
12:00PM + 1 hour, and 4:00PM + 2 hours. The three IOP measurements should then 
be averaged to determine the mean diurnal IOP. 
 
Standard postoperative IOP measurements (i.e., taken at Day 1, Week 1, Week 4, 
Months 3, 6 and 18), only 1 set of pressure measurements will be needed.  Every 
attempt should be made to have these values taken at the same time interval for each 
visit. 
 
b. Visual Field Examination 
Visual fields must be automated threshold visual fields, 24-2 Humphrey Stimulus III.  
The SITA Standard must be used for the visual field conducted at the pre-operative 
evaluation and all subsequent evaluations, 
 
Visual fields must be reliable at screening for eligibility, defined as ≤ 33% false 
positives, false negatives, and fixation losses.  (These are the acceptance criteria used 
in the previous OHTS study.)  A visual field done within 90 days prior to the subject 
informed consent date and in accordance with the 24-2 SITA Standard requirements 
can be used for the screening evaluation.  For visual fields that do not meet the 
reliability standards, the test should be repeated within two weeks. 
 
Visual fields are to be performed with a non-dilated pupil unless, in the opinion of the 
investigator, the pupil is so miotic that dilation is required (e.g., < 3mm).  If dilation 
was performed at screening, it should be performed at all subsequent visual field 
examinations.  However, dilation should not be performed before the IOP 
measurement on the appropriate visits. 
 
 
Visual field interpretation will be documented on the Screening form and one of the 
choices in the following categories will be marked (Mills GSS criteria were referenced 
to obtain these choices): 
 
 
 

                                                          Page 26 of 84                        INN-005 Rev. 072117 
 
Mean Deviation 
Early defect outside of inclusion range = MD of  > -2.99 dB 
Early defect within inclusion range = MD of -3.00 dB to - 6.00 dB  
Moderate defect = MD of -6.01 to -12.00 dB  
Advanced defect = MD of -12.01 dB to -20.0 dB 
Severe defect = MD of ≤ -20.01 dB 
 
Central Defects <0 dB within 5⁰ of fixation  
None 
1 in one hemifield only 
2 in one hemifield only 
1 in both hemifields 
2 in one hemifield and 1 in the other hemifield 
2 in one hemifield and 2 in the other hemifield 
 
c.  Pachymetry 
Pachymetry is performed to determine central corneal thickness at screening, Months 
12 and 24. For each evaluation, three measurements are taken utilizing an electronic 
pachymeter and annually thereafter. The measurements and the mean value will be 
recorded in the source documents.  
 
Follow-up measurements conducted at the 12 and 24 month visits should be 
performed using the same instrument that acquired the screening data if at all 
possible.  These measurements should be performed on the study eye.  
 
d.  Distance Visual Acuity   
During the screening visit, Best Corrected Visual Acuity (BCVA) should be 
measured (BCVA must be 25 or more letters equivalent to 20/80 or better in the 
fellow eye) using Early Treatment of Diabetic Retinopathy Study (ETDRS) charts at 
4 meters (13 feet and 1.5 inches, or 157.5 inches) in both eyes and reported in 
LogMAR units.  At all subsequent follow-up visits from 1 month and longer where 
BCVA measurements are required, LogMAR measurement (utilizing ETDRS) should 
be documented.  MR must be performed prior to BCVA using the ETDRS charts and 
will be performed at all visits except Operative, Day 1, and Week 1 visits. The 
Snellen or Pinhole visual acuity is used for the 1 day and 1 week post-op values.   
 
Visual acuity testing should precede slit lamp examination, intraocular pressure 
measurement, the administration of topical anesthetic agents, or any examination 
requiring contact with the anterior segment. 
 
The visual acuity chart must be retro-illuminated (“back-lit”).  The standard chart 
requires a distance from subject to chart of 4 meters.  Ideally, the subject should be 
seated.  Sites are directed to refer to the instructions on the commercial ETDRS charts 
and the Visual Acuity Testing Manual. 
 

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The subject should attempt to read each letter, line by line, left to right, beginning 
with line 1 at the top of the chart (20/200 line).  The subjects should be told that the 
chart has letters only, no numbers.  If the subject reads a number, he or she should be 
reminded that the chart contains no numbers, and the examiner should then request a 
letter in lieu of the number.  The subjects should be asked to read slowly, about one 
letter per second, so as to achieve the best identification of each letter.  He/she is not 
to proceed to the next letter until he/she has given a definite response. 
 
In order to provide standardized and well-controlled assessment of visual acuity 
during the study, all visual acuity assessments for a subject must be performed 
consistently (e.g., the same lighting conditions, viewing distance, etc.) during the 
entire study. 
 
The following steps will be used for LogMAR scoring: 
1.  The examiner records each letter identified correctly by circling the corresponding 
letter on the Distance Visual Acuity Worksheet to be provided to the 
investigational sites.   
2.  Letters read incorrectly or not read at all are not marked on the form.   
3.  Each letter read correctly is scored as one point.   
4.  The total score for each eye is recorded on the worksheet after testing is 
completed. 
          
e.  Dilated fundus examination 
A mydriatic should be used to dilate the pupil so that an examination of the fundus can 
be conducted with an indirect ophthalmoscope and slit lamp biomicroscopy (with 
contact lens, Hruby lens or 60-, 66-, 78-, or 90 diopter lens).  The appearance of the 
optic disc, macula, vessels and periphery should be evaluated in support of a glaucoma 
indication as defined in the inclusion criteria and reported on the Screening form.  A 
measurement of the vertical cup-to-disc ratio should be made and reported.  All 
methods used to assess nerve abnormalities at screening must also be used at all 
required postoperative exams.   
 
The optic disc photos should be performed using HRT, OCT, GDx or other method 
(such as stereo disc photography with either true stereo or sideways displacement of the 
camera). Note: Assessment of nerve abnormalities conducted < 6 months of screening 
visit can be used as part of the subject’s evaluation for inclusion in (or exclusion from) 
the study. 
 
The examination will be conducted at the prescribed intervals in the activity list and 
may be used for further investigation at other follow-up periods in cases of hypotony to 
assure there are no choroidal effusions, choroidal detachments or related concerns. 
 

                                                          Page 28 of 84                        INN-005 Rev. 072117 
 
f.  Endothelial Cell Density  
Each subject must have a screening density of the central endothelium in accordance 
with the clinical study inclusion criteria to participate in the study.  Endothelial cell 
densities are to be taken before gonioscopic testing is completed. 
 
A Konan specular microscope is to be used for measurement of endothelial cell density 
at screening and at the defined follow-up periods.  All readings will be conducted by 
the Corneal Image Analysis Reading Center (CIARC) located at the Department of 
Ophthalmology and Visual Sciences, Case Western Reserve University School of 
Medicine, Cleveland, Ohio. 
 
Cornea Image Analysis Reading Center (CIARC) will certify technicians and approve 
specular microscopes for study participation.   Only instruments confirmed as 
calibrated by CIARC may be used.  Only technicians certified by CIARC may conduct 
study imaging.  Calibration of the specular microscope at each investigational site must 
be confirmed by the CIARC prior to conducting the first readings.  CIARC will provide 
sites a detailed site manual. 
 
All technicians at CIARC conducting endothelial cell reading will be masked to 
the treatment group.  Investigational site technicians will be masked to the treatment 
group for imaging as well. 
 
For each subject, central images of the study eye will be collected at screening, 3 
months, 6 months, 12 months and 24 months follow-ups.  Fellow eye central images 
will be collected at screening, 3, 12 and 24 months. 
 
General instructions are as follows: 
1.  Place chin forward on chin rest until it touches the chin stop.  Ask the subject to 
close teeth together and relax their head, which depresses the chin rest. 
2. Forehead should touch forehead bar.  Lower table enough for patient to lean in 
comfortably. 
3. The axis of head should be perpendicular to the forehead bar. 
4. Ask the patient to focus on the green indicator light. 
5. Ensure the patient’s pupil is within the target circle on the monitor in upper right of 
screen. 
6. Once adjusted, tell the patient you are going to record and let them know they can 
blink until told to hold the eye open. 
7. Press the record button. 
8. Allow patient to blink until just before the “rec” sign in upper left of monitor starts 
flashing.  This can be predicted because the beam begins to move toward dead 
center. 
9. Tell patient to open wide and hold as soon as “rec” starts flashing. 
 

                                                          Page 29 of 84                        INN-005 Rev. 072117 
 
Notes:   
a. Use saline drops to moisten the eye if it is dry, photograph is black or photograph 
resembles the moon’s surface. 
b. If a shadow prevents analysis, straighten the head left or right to center in 
camera.  Auto may need to be turned off and camera adjusted manually + 5 
increments to start to photograph in Manual Mode. 
c. If patient’s eyelid interferes with photograph, hold the lid for patient while 
keeping the forehead against the forehead bar, or lightly tape the eyelid up still 
allowing the patient to be able to blink. 
d. IOLs can reflect multiple beams of light into the camera interfering with the 
photograph.  If so, have patient look slightly off (right/left/up/down) from 
indicator light until white reflections coalesce into one or two reflection spots 
and then take picture. 
 
g.   Slit Lamp Examination 
The study eye should include a measurement of aqueous cell and flare using the 
following grading system and then reported. 
 
For anterior chamber cells, in a field size of 1x1-mm slit beam, the following grades are 
standardized as follows: 0 (< 1 cell), 0.5+ (1-5 cells), 1+ (6-15 cells), 2+ (16-25 cells), 
3+ (26-50 cells), and 4+ (>50 cells). The presence of hypopyon is recorded separately.  
The grading for anterior chamber flare is standardized as follows: 0 (none), 1+ (faint), 
2+ (moderate, iris and lens details clear), 3+ (marked, iris and lens details hazy), and 4+ 
(intense, fibrin or plastic aqueous).  
The presence of corneal edema, pupillary irregularities, iris atrophy and pigment 
dispersion should also be evaluated and noted. 
For patients with a phakic study eye, the lens should be evaluated for presence of 
cataract.  A LOCS III classification system is used and the outcome reported on the 
form.  For anterior subcapsular cataracts, the LOCS III posterior subcapsular grading 
system is used to approximate the characteristics of the cataract and the number value 
reported.  If no cataract is present, grade as a 0.0 in the respective categories.  Use the 
visual LOCS III scale for grading each of the categories, i.e., nuclear (color and 
opalescence), cortical, posterior subcapsular and anterior subcapsular. 
h.  Gonioscopy 
Gonioscopy will be conducted as part of the screening process to verify that the subject  
has an open angle and to identify any anterior synechiae as well as determine if there is 
any pigment dispersion.  A Zeiss, Sussman or similar lens should be used and 
gonioscopy conducted in a dark room with a narrow, short slit beam that does not pass 
through the pupil and without a fixation light being used.  The Shaffer method will be 
used as follows: grade 4, wide open (35º-45º): grade 3, moderately open (25º-34º); 
grade 2, moderately narrow (20º); grade 1, very narrow (10º); grade 0, closed (0º).  The 
grade number will be reported for each quadrant of the eye in the appropriate location 
on the form. 
 

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Gonioscopy may also be used post-surgery with a trabeculectomy if an elevated IOP is 
observed to determine if the sclerostomy is filling with iris or fibrin before adding 
glaucoma medications.  
 
i.  Ocular Hypotensive Medications 
Each ocular hypotensive medication will be recorded on the case report form.  If 
subjects are taking combination medications such as Cosopt® this is to be counted as 
two medications even though this is only in 1 bottle. 
 
j.  Pregnancy Testing, Nursing and Contraceptives 
Women of childbearing potential are excluded from participation if they are currently 
pregnant, have a positive urine pregnancy test at screening, or intend to become 
pregnant during the study period; are breast-feeding; or are not in agreement to use 
adequate birth control methods to prevent pregnancy throughout the study ((hormonal – 
oral, implanted, transdermal, or injected contraceptives)(mechanical – spermicide in 
conjunction with a barrier such as a condom or diaphragm or IUD)).  All women are 
considered to be of childbearing potential unless one or more of the following criteria 
are met: 
• 
Postmenopausal for at least 1 year 
• 
Surgically sterile 
 
For non-sexually active females, abstinence may be regarded as an adequate method of 
birth control; however if the patient becomes sexually active during the study, she must 
agree to use adequate birth control methods as define above prior to sexual activity and 
for the remainder of the study. 
 
Females of childbearing potential will be instructed to immediately inform the 
investigator if they become pregnant during the study.  Should this occur, the 
investigator must immediately contact the sponsor. 
 
k.  Ocular Quality of Life (QOL) Questionnaire  
A patient questionnaire is being used in this study to evaluate visual function and local 
eye effects related to the surgeries.  The questionnaire has been derived from the 
Collaborative Initial Glaucoma Treatment Study {CIGTS} (Ophthalmology 
1999;106:653–662)and identified in a draft manuscript (yet to be published) as 
potentially useful for QOL evaluation based on the CIGTS history. The questionnaire 
was provided to InnFocus by one of the authors of the manuscript. 
 
The questionnaire contains 2 subgroups, consisting of 18 separate items: 11 on Visual 
Function and 7 on the Local Eye, that have been extracted from the 43 question QOL 
questionnaire used in CIGTS. The visual function subscale (11 items) includes 
symptoms and health problems deemed by clinical center ophthalmologists to be 
related to glaucoma as a disease process independent from any treatments or side 
effects: difficulties going from light to dark, blurred vision, difficulty seeing in dark 
places, difficulty with near vision, trouble seeing when stepping down, problems with 
distance vision, dimming of vision, problems with depth perception, visual distortion, 

                                                          Page 31 of 84                        INN-005 Rev. 072117 
 
difficulty with bright lights or sunlight, and trouble with color vision. The local eye 
subscale (7 items) includes such problems as eye irritation and burning, excessive 
tearing, and red eyes.  
 
After enrollment during screening, the patient will be initially interviewed using the 
questionnaire.  The statements to be used are at the beginning of the questionnaire and 
should be followed closely to assure consistency of response.  Document the patient 
responses directly on the questionnaire. 
 
The interviewing process will be conducted again at several intervals in accordance 
with the testing schedule. 
 
l. General Health Questionnaire (EQ-5D-5L) 
A second questionnaire will also be used to document the general health of the subject 
before and after surgery.  This questionnaire, in association with the questionnaire in 
item k above will be used to compare the overall health status of the subject as a result 
of the surgery.  Both questionnaires will also be used as part of a health economics 
comparison of the InnFocus MicroShunt surgery and trabeculectomy.  This 
questionnaire was selected based on the well-documented history of its use and the 
relative ease of questionnaire completion.  The subject completes this questionnaire 
without the assistance of an interviewer initially after enrollment and during the 
screening process.  The subject again completes the questionnaire at the defined follow-
up points in the test schedule. 
 
The EQ-5D-5L consists of a cover page and 2 pages to complete – the EQ-5D-5L 
descriptive system (page 2) and the EQ Visual Analogue scale (EQ VAS) (page 3).  
The descriptive system comprises 5 dimensions (mobility, self care, usual activities, 
pain/discomfort, anxiety/depression). Each dimension has 5 levels: no problems, slight 
problems, moderate problems, severe problems, and extreme problems. The patient is 
asked to indicate his/her health state by ticking (or placing a cross) in the box against 
the most appropriate statement in each of the 5 dimensions.  
 
9.4    Study Procedures 
 
9.4.1  Training 
Before any site may begin actual device implantation, all investigators will participate 
in an InnFocus investigator training session.  Investigators will gain familiarity with the 
InnFocus MicroShunt through the use of animal or human cadaver eyes.  Further 
training will be provided to the study coordinators at each site by an InnFocus trained 
designee.  
 
9.4.2  Material and Equipment 
A listing of general equipment and materials required at the investigational site for the 
preoperative, operative, and postoperative steps of the investigational study is provided 
below. 
 

                                                          Page 32 of 84                        INN-005 Rev. 072117 
 
1. 
InnFocus MicroShunt Glaucoma Drainage System 
2. 
Goldmann Applanation Tonometer 
3. 
Humphrey Visual Field Analyzer  
4. 
Goniolens (Zeiss, Sussman or similar, not Goldmann to screen for angle closure) 
5. 
Ultrasound Pachymeter 
6. 
Slit lamp and fundus contact lens, Hruby lens or 90 diopter lens 
7. 
Indirect ophthalmoscope 
8. 
ETDRS Visual Acuity System/Snellen Visual Acuity System 
9. 
Specular Microscope (Konan XL) 
10. Fully equipped surgical suite equipped with operating microscope 
11. Video equipment in operating room 
12. Fundus camera 
13. Mobius Therapeutics Mitosol MMC Kit 
14. Light Meter 
 
The Goldmann tonometer should be calibrated at each investigational site in accordance 
with the manufacturer’s instructions.  Each site is also to follow their own standard 
procedures for equipment maintenance and calibration by outside vendors.  Calibration 
values should be recorded and the documents maintained accordingly. 
 
9.4.3  InnFocus MicroShunt Surgical Procedure 
Mark the location of the implant on the study eye sketch in the source documents.  The 
following provides an overview of the surgical procedure for implantation of the 
InnFocus MicroShunt.  If possible, each surgical procedure should be videotaped. 
 
A.  Anesthesia 
The type of anesthesia will be at the surgeon’s discretion except general anesthesia 
is excluded and the type will be documented on the Operative form. 
 
B.  Preparation of InnFocus MicroShunt 
Carefully examine the package containing the InnFocus MicroShunt for signs of 
damage that could compromise sterility.  If damaged, discard the device.   
Remove InnFocus MicroShunt from sterile packaging onto sterile field.  No more 
than 2 devices should be opened for each case.  Wet the InnFocus MicroShunt using 
a solution of Balanced Salt Solution (BSS).  
 
Note:  No cutting or modification of the InnFocus MicroShunt is allowed. 
 
C.  Preparation of Mitomycin C 
 
Follow the instructions for use of the Mobius Therapeutics Mitosol Kit.   
Prepare a syringe or line that can flush copious amounts of BSS (>20ml). (Training 
on the Mitosol kit will be provided prior to study initiation). 
 
D.  Corneal Traction and Conjunctival Flap 
Perform corneal traction with 7-0 Vicryl suture at surgeon’s discretion. 

                                                          Page 33 of 84                        INN-005 Rev. 072117 
 
In the planned surgical area, dissect a fornix-based subconjunctival//subTenon 
pouch over a circumference of 90o-120o at least 8mm deep. 
 
E.  Application of MMC 
Apply the MMC in accordance with the Mobius Therapeutics Mitosol Kit 
instructions for use.  Use only 4 half-moon sponges in the kit to prepare with MMC 
and place under the subconjunctival/subTenon’s flap.  Rinse with generous amounts 
of BSS (>20mL).  Note: Assure that the conjunctival wound edge does not come 
into contact with antimetabolite. 
 
F.  Preparation of Anterior Chamber Entrance Site 
Mark a point 3mm from the limbus, utilizing 3mm scleral marker and marker pen. 
At the marked point, use a 1mm double step knife in one motion to create both a 
scleral track into the anterior chamber (AC) so as to enter the angle just above the iris 
plane and a shallow scleral pocket at the mark just big enough to tuck the fin portion 
of the InnFocus MicroShunt. 
 
G.  Insertion of InnFocus MicroShunt into Anterior Chamber 
Gently insert the InnFocus MicroShunt tube with the bevel facing toward the cornea 
through sclera track using forceps and holding close to the track entrance while 
keeping the fin face parallel to the scleral surface and tuck the fin into the scleral 
pocket.  If there is resistance to the placement of the InnFocus MicroShunt after 
multiple attempts to position it, use a 25G blunt tip cannula to re-enter the sclera 
track and assure it is open. Then attempt placement of the InnFocus MicroShunt 
again. 
 
 
 
If the InnFocus MicroShunt is damaged during the procedure, use a new InnFocus 
MicroShunt and repeat the insertion step using the same tract.   If not accessible, 
another track can be made. After successful insertion of the InnFocus MicroShunt, 
check that the InnFocus MicroShunt tube position in the AC is not in contact with 
the cornea or iris and that there is flow of aqueous.  If flow is not visible, place the 
23G cannula over the distal end of InnFocus MicroShunt up to the fin while 
applying slight pressure and inject BSS to prime the tube.  Confirm flow, tuck the 
distal end of the InnFocus MicroShunt tube under the subconjunctival/Tenon’s flap 
on scleral surface making sure it is not caught in Tenons. 
 
H.  Conjunctival Closure 
Reposition the Tenon’s and conjunctiva to the limbus and suture using  sutures with 
a long history of successful use by glaucoma specialists (i.e., nylon, vicryl).   A 
moistened fluorescein strip is used to check for a conjunctival leak, which may be 
closed with additional sutures. 
 
Verify the presence of the proximal end of the InnFocus MicroShunt in the anterior 
chamber. 
 
 

                                                          Page 34 of 84                        INN-005 Rev. 072117 
 
Pull corneal traction suture out if it was used.  
 
Apply antibiotic and steroidal medication post-op per clinical protocol requirements. 
 
After use, dispose of product and packaging in accordance with hospital, 
administrative, and/or local government policy. 
 
Follow the Mobius Therapeutics Mitosol Kit instructions for use for proper disposal 
of the MMC and kit components. 
 
Warnings and Precautions: 
- 
For one-time use only.  Do not reuse or re-sterilize. 
- 
Long term effects of MMC with the use of this device have not been 
evaluated.  Necessary precautions on the use of MMC are highly 
recommended. 
- 
All types of Viscoelastics have not been tested with this device.  However, in 
an emergency when all other therapies have failed, the use of hydroxyl 
methyl-cellulose (HPMC) may be an option. Use of HPMC should be a last 
resort to correct a flat chamber with the InnFocus MicroShunt and may risk 
loss of flow through the device for one or more weeks after use necessitating 
close or more frequent observation of IOP. 
- 
Should the InnFocus MicroShunt appear deformed, folded and/or distorted, do 
not use.  Avoid use of toothed forceps to handle device. McPherson type 
forceps are recommended.  
- 
Do not use knife if it has been hit against or in contact with other parts than 
the eyeball. Such knife may be damaged and lose sharpness. 
- 
Do not resterilize the device. 
 
9.4.4  Trabeculectomy with MMC Surgical Procedure 
 
1. Investigators should use the following procedure for conducting the trabeculectomy 
procedure with the use of MMC: Anesthesia type is at the surgeon’s discretion 
except general anesthesia is excluded. 
 
2. Conjunctival flap – the trabeculectomy is performed in a superior quadrant.  A 
fornix-based conjunctival flap is used.  A corneal traction suture or superior rectus 
traction suture may be used to rotate the globe inferiorly and improve exposure. 
 
3. Mitomycin C application –The MMC is prepared and used in accordance with the 
Mobius Therapeutics Mitosol Kit instructions for use, again using 4 half-moon 
sponges for delivery of the MMC under the subconjunctival flap.  The mitomycin 
may be applied before or after the scleral flap creation dependent on the 
investigator’s standard practice (Training on the Mitosol Kit will be conducted prior 
to study initiation). 
 
4. Scleral flap – A corneal-based scleral flap is dissected approximately one-half 
scleral thickness.  The shape and size of the scleral flap is determined by the 

                                                          Page 35 of 84                        INN-005 Rev. 072117 
 
surgeon in keeping with his or her usual practice and should be kept consistent 
throughout the study. 
 
5. Paracentesis tract – A peripheral clear cornea paracentesis tract is made. 
 
6. Excision of Limbal tissue – A block of limbal tissue is excised from underneath the 
trabeculectomy flap using a sharp blade and Vannas scissors or a Kelly punch.  The 
amount of limbal tissue excised is at the surgeon’s discretion. 
 
7. Peripheral iridectomy – A peripheral iridectomy is performed unless a specific 
rationale is provided as to why it is not required.  The sclerostomy opening is 
inspected for entrapped iris tissue, and a cellulose sponge is used to test for the 
presence of vitreous.  Vitreous presenting to the surgical wound is excised.  The 
method used to remove the vitreous present at the surgical site is at the surgeon’s 
discretion.  Document any presence of vitreous observed. 
 
8. Scleral flap closure – The scleral flap is reapproximated to the scleral bed with 
interrupted or releasable 10-0 nylon suture.  The number and tension of the scleral 
flap sutures is determined by the surgeon.  Following injection of balanced salt 
solution into the anterior chamber through the paracentesis tract, the anterior 
chamber should remain formed with a visible leak present around the scleral flap at 
equilibrium. 
 
9. Conjunctival flap closure – The type of suture material and needle used for the 
conjunctival flap closure is of the surgeon’s choice.  Either a double layered closure 
(conjunctiva and Tenon’s closed separately) or single layered closure (conjunctiva 
and Tenon’s together) may be performed. 
 
10. Reformation of the Anterior Chamber and Bleb Elevation – Balanced salt solution 
is injected through the paracentesis tract to deepen the anterior chamber and elevate 
the bleb.  A moistened fluorescein strip is used to check for a conjunctival leak or 
leakage from the paracentesis tract, which may be closed with additional sutures. 
 
11. Intraoperative medications – The use of intraoperative medications is at the 
surgeon’s discretion.  
 
9.4.5  Post-operative Instructions 
A.  Following surgery, the subjects will be instructed to adhere to the following 
antibiotic/anti-inflammatory regiment and the frequency will be documented on the 
Concomitant Medication form: 
 Topical polymyxin B sulfate and trimethoprim ophthalmic solution 
combination (e.g., Polytrim) antibiotic or fourth generation fluoroquinolone 
(e.g., gatifloxacin [Zymar], or moxafloxacin [Vigamox], for one week 
postoperatively by instilling one drop in the operated eye four (4) times per 
day distributed during the waking hours. All subjects at a given investigational 
site must use the same antibiotic regimen unless contraindicated by allergy.  
 Anti-inflammatory medication (prednisolone acetate 1% ophthalmic 
suspension): 

                                                          Page 36 of 84                        INN-005 Rev. 072117 
 
o Weeks 1-4: at least four (4) times per day for the first 4 weeks. .   
o Weeks 5-8: two (2) times per day for the next 4 weeks  
o Weeks 9-12: one time per day for the next 4 weeks.   
NOTE: 
1. Anti-inflammatory medications may be increased to ≥ 4 times a day for the first 
month. If frequency is increased during the first month, consideration should be 
given to the appropriate tapering schedule at follow-up visits.  
2. In the event of an adverse event during post-operative medication regimen, 
consideration should be given to the appropriate tapering schedule.  
At the 3 months follow-up, the investigator will determine if further treatment is 
needed.  Alternate antibiotic and anti-inflammatory medication regimens are 
allowed when the patient does not respond well to the initial regimen.  Cycloplegics 
may also be used for patients as needed during the initial healing phase or in phakic 
eyes. 
 
B.  At follow-up visits, there are some fairly routine practices that are done by the 
investigator to assure a diffuse bleb and lower IOP.   These are not considered as 
adverse events in the study.   They are as follows: 
1.  Eye massage done by the investigator will be documented on the follow-up 
form.  Eye massage should only be done by investigators and not by 
subjects. 
 
2.  Laser suture lysis is commonly used to lyse one or more sutures in the first 
week or later after surgery to bring the IOP down.  Tensioning of the sutures 
used to close the scleral flap may set the pressure higher than desired, but tight 
suturing is done purposely in many cases to limit acute hypotony.   The suture 
lysis is also documented on the follow-up form. 
 
3. Depending on the surgeon’s method of tightening the scleral flap during 
trabeculectomy procedures, the surgeon may choose to temporarily use 
glaucoma medications rather than lyse a suture too early and cause hypotony.  
Therefore, the use of temporary glaucoma medications for post trabeculectomy 
subjects will be allowed and will be documented on the appropriate case report 
form as needed.  The use of a topical CAI or alpha-2 adrenergic agonist is 
typically used for this purpose because of the short washout periods (5 days for 
CAI and 14 days for alpha-2 adrenergic agonist), and if any other glaucoma 
medication is used, a rationale should be provided on the follow-up form. 
 
 
 
C.  Interventional techniques are employed if the IOP increases to the default 
interventional IOP value of greater than 21mmHg or greater than the pre-surgery 
medicated IOP if lower than 21mmHg for any subject.    
 
As described in the Screening section earlier in the protocol, the investigator may 
have established an alternate interventional IOP for the subject on the screening 

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form prior to randomization, and in this case, the investigator will use this value 
as the maximum value before considering intervention.   
 
All investigators will intervene in a consistent manner per the pre-established 
interventional IOP point for each subject in the treatment and control groups and 
only when necessary to control IOP.  (If the alternate interventional IOP was 
chosen and the post-procedure IOP exceeds the surgeon’s choice, the subject will 
be asked to come back for a second visit within 1 week to confirm the IOP before 
reinitiating glaucoma medication or physically intervening. If the IOP also 
exceeds the default interventional IOP, such that safety is a concern, a second 
visit is not required before taking any action.)  
 
 
There may be cases where the investigator needs to bring the IOP down when the 
subject has not exceeded the interventional IOP.  In these cases, the Medical 
Monitor will consult with the physician to understand the rationale for the 
intervention and it will be documented by the investigator on the source 
document.  For the intervention, the reason for the decision will be noted on the 
case report form as one or more of the following:  IOP> default interventional 
IOP or alternate interventional IOP, visual field change, optic nerve change or 
temporary glaucoma med use pending suture lysis.   A field for “Other” will be 
used to document any other reason for the intervention. 
 
 
      Physical intervention should be considered prior to employing glaucoma 
medications to bring the IOP down.  The reasons for the IOP increase are multiple 
but there are two commonly observed methods for reducing the IOP:  
1)     “Needling the bleb” to overcome partial or complete closure of the 
subconjunctival pocket.  In these cases, The InnFocus MicroShunt or 
trabeculectomy path to the anterior chamber is open and can allow flow, but 
the lack of an adequate subconjunctival drainage field is preventing this.  To 
improve the flow, a needle is inserted into the sub-Tenons/conjunctival area, 
any fibrous attachment separated, and the pocket re-established (this is not a 
failure criterion but is documented as a complication on the Adverse Event 
form).    
a. Needling with an injected antifibrotic may be preferred.  Both MMC 
and 5FU are used to accomplish this.  If either antifibrotic is injected 
subconjunctivally, the type of antifibrotic, dosage, and method of 
introduction by the investigator should remain consistent with both 
arms of the study.  Dosages of MMC and 5FU vary by investigator and 
are in the 10-100 microgram range for MMC and 5-10 milligram range 
for 5FU.  The dosage may be delivered as a mixture with an 
anesthetic, e.g., Lidocaine.  The total dosage volume is in the 0.1-
0.3ml range.  The name of the antifibrotic, injection volume, dosage 
and mixed anesthetic or other agents are documented in the 
concomitant medications log and needling with an antifibrotic is 
indicated on the adverse event form. 
 

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2)  Laser removal of blockage at the tip of the InnFocus MicroShunt or at the AC 
entry point for a trabeculectomy is another possibility and is documented as a 
complication on the Adverse Event form. 
                       
D. Glaucoma medications are added if common physical interventional techniques 
have been employed, but do not decrease the IOP below the target IOP for any 
subject, or if physical intervention is not attempted at all to reduce the IOP.    
  
E.  If glaucoma medications need to be re-introduced, glaucoma medications to 
which the subject is naïve should be deferred until after previously used 
medications have been introduced.   Barring interfering factors regarding the 
method of re-introduction of glaucoma medications post-surgery, the 
recommended sequence is to first add a beta blocker, then a prostaglandin, and 
either an alpha adrenergic agonist or a carbonic anhydrase inhibitor as a third 
medication.  As routine practice, medications should be added one at a time and 
the IOP lowering effect determined before introducing the next medication.  
Based on the IOP level, the physician should decide on which medications, 
dosage and order of re-introduction to choose.   The rationale for the re-
introduction or discontinuation should be documented in the follow-up form field 
identified as “Investigator rationale for medication re-introduction or 
discontinuation” and the Medical Monitor will discuss the rationale with the 
investigator as needed to assure consistency.  
 
 
Based on the sequence of drug re-introduction, there should not be a case 
where an oral carbonic anhydrase inhibitor will be required, but if it is, it 
will be counted as a failure.   It is unlikely that any subject will be on oral 
carbonic anhydrase inhibitors at the effectiveness determination, since they would 
be the last drug added.  
 
Medications which have been re-started by the investigator may be discontinued 
if the investigator’s judgment is that the target intraocular pressure has been 
reached and the continued use of some or all of the therapy may not be required. 
Discontinuation of medications after re-introduction is recommended to be in the 
reverse order of re-introduction.  The rationale for discontinuation will also be 
documented on the follow-up form by the investigator and the Medical Monitor 
will follow up with the investigator as needed to assure consistency within the 
study parameters.  For medication discontinuation, the reason for the decision will 
be noted on the case report form as IOP controlled or allergy to medication.  A 
field for “Other” will be used to document any other reason for glaucoma 
medication discontinuation. 
 
F. Another potential reason for intervention is an IOP below 6mmHg (hypotony).  
Interventions such as those indicated below should only be considered if the 
hypotony has caused or is likely to cause sequelae such as a flat chamber. No 
intervention is indicated when the vision is unchanged from screening, there is no 
persistent choroidal detachment, the anterior chamber is not flat with lens corneal 

                                                          Page 39 of 84                        INN-005 Rev. 072117 
 
touch, or the patient is asymptomatic.  No intervention should be undertaken for 
hypotony which is not causing, or threatening to cause, a reduction in vision, as 
the intervention might cause procedure failure.  These interventions should be 
documented as adverse events.  Otherwise, the hypotony should be monitored 
with additional follow-ups as necessary.   
 
1) Too loose or not enough sutures can result in hypotony that may be treated by 
adding more sutures in a separate surgical intervention (this action will be 
considered a failure).  
 
2)   Introduction of viscoelastic into the anterior chamber for the purpose of 
slowing aqueous flow and eliminating hypotony that is causing a reduction of 
best corrected visual acuity (two or more lines) or causing the presence of 
persistent choroidal detachment (3 or more months if peripheral, up to one 
month if kissing), or causing hypotony maculopathy (also documented as a 
complication on the Adverse Event form.) 
 
G.  A secondary procedure that is performed including a trabeculectomy, 
repositioning of a InnFocus MicroShunt, Tenon’s resection, glaucoma laser, 
glaucoma drainage device or other incisional treatment to establish a new aqueous 
flow path from the anterior chamber in order to maintain acceptable IOPs will be 
considered a failure of the original procedure. 
 
H.  If the InnFocus MicroShunt is repositioned, removed and/or replaced with 
another type of device based on the device performance, the conjunctiva should 
be cut at the limbus in a similar manner to the original procedure.  The device 
should be exposed and the repositioning or removal conducted.  If the device is 
removed, verify that there is no aqueous leakage from the track.  If there is, use a 
Vicryl suture to seal the track.  The limbus should then be resutured in a similar 
manner as the original surgery.  The removed InnFocus MicroShunt should be 
returned to InnFocus, Inc. for analysis in accordance with the explanted device 
procedure. 
 
 
If the InnFocus MicroShunt is removed, another InnFocus MicroShunt should not 
be implanted in the same subject.  Use an alternate procedure. 
 
If repositioning, removal, replacement or removal with another glaucoma 
procedure occurs, the event will result in the subject being followed according to 
standard of care until the adverse event resolves and the follow-up visits over the 
two years period under the protocol schedule will be part of the safety analyses.  
Any extra visits to evaluate the patient due to the secondary procedure will be 
considered “Unscheduled Visits” if performed outside of the standard visit 
windows in the protocol and the Unscheduled Visit form will be used to 
document the visit. 
 
I.  For any surgery or interventions not directly related to the subject’s glaucoma that 
occur during the study, e.g., cataract surgery, the standard of care for the 
particular type of intervention will be followed until the subject has recovered.  

                                                          Page 40 of 84                        INN-005 Rev. 072117 
 
Unless a post-surgery visit coincides with the standard protocol follow-up visit, 
the visits will be handled as “Unscheduled Visits” and the Unscheduled Visit 
form will be used to document the visit. 
 
9.5  Follow-up 
All subjects will participate in defined follow-up visits throughout two years.  A follow-up 
case report form shall be completed from source data gathered at the time the subject is 
examined.  Unscheduled or interim visits should also be recorded using the appropriate 
forms.  Table 5 provides an overview of all activities to be conducted during the clinical 
study.  Table 5a indicates the testing that should be conducted on the fellow eye during the 
study.  All attempts should be made to conduct each follow-up evaluation within the 
specified time intervals shown in Table 6.  Evaluations conducted outside the prescribed 
time period will be considered protocol deviations.  Visits conducted outside scheduled 
timeframes will be considered an additional visit and must be documented using the 
Unscheduled Visit form. 
 
Table 5.  Study Visits and Parameters for Study Eyes 
 
    1Diurnal IOP 
Activities 
Screening  
Op 
Follow-up Evaluation 
 
 
1 D
1W
4W
3 M
6 M 
12M 
18M 
24M
Informed Consent 
X 
 
 
Randomization 
 
X
 
 
Ocular Medical History 
X 
X
 
 
Ocular Medication Assessment 
X 
X
X
X
X
X
X
X 
X 
X
History/Demographics 
X 
 
 
Manifest Refraction 
X 
X
X
X
X 
X 
X
BCVA (Snellen) or Pinhole VA 
 
X
X
 
 
BCVA (ETDRS) 
X 
X
X
X
X 
X 
X
Visual Field 
X 
 
X
X 
 
X
Slit Lamp Exam 
X 
X
X
X
X
X
X 
X 
X
Lens Status for Phakic Eyes 
X 
X
X
X 
X 
X
IOP 
X1 
X
X
X
X
X
X1 
X 
X1
Pachymetry 
X 
X 
 
X
Endothelial Cell Density 
X 
X
X
X 
 
X
Gonioscopy 
X 
 
 
 
 
 
Dilated Fundus Exam 
X 
 
 
   Vertical C/D Ratio 
X 
X
X 
X
X 
 
X
   Optic Disc Photo  
X 
X
X
X
X 
 
X
Diplopia 
 
X 
 
X
X
X 
 
X
Motility 
X 
 
X
X
X 
 
X
Pregnancy Test (as applicable) 
X 
 
 
Surgical Procedure 
 
X
 
 
Observations Recorded 
X 
X
X
X
X
X
X
X 
X 
X
Adverse Event Assessment 
 
X
X
X
X
X
X
X 
X 
X
Ocular QOL Questionnaire  
X 
X
X
X
X
X 
X 
X
General Health Questionnaire 
X 
X
X
X
X 
X 
X

                                                          Page 41 of 84                        INN-005 Rev. 072117 
 
Testing of the fellow eye will be conducted as per the table below and data will be gathered on 
the case report forms. 
 
          Table 5a.  Activities Conducted on Fellow Eye During Clinical Study 
     
 
Follow-up Examination Schedule 
 
Table 6.  Examination Schedule 
Activity 
Acceptable Time Interval in Days 
Post Surgery Evaluations
1 Day  
1 
7 Days  
5-9 
4 Weeks  
21-35 
3 Months 
70-98 
6 Months 
168-196 
12 Months 
330-420 
18 Months 
510-600 
24 Months 
690-780 
 
 
 
Activities 
Screening 
 
Follow-up Evaluation 
 
1 D
1W
4W
3 M
6 M 
12M 
18M 
24M
Ophthalmology Exam 
X
 
 
Ocular Medical History 
X
 
 
Ocular Medication 
Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
History/Demographics 
X
 
 
Visual Field 
X
X 
 
X
Dilated Fundus Exam 
X
X
X 
 
X
   Vertical C/D Ratio 
X
X
X 
 
X
   Optic Disc Photo  
X
X
X 
 
X
Slit Lamp Exam 
X
X
X 
X 
X
Manifest Refraction 
X
X
X
X
X 
X 
X
Visual Acuity (Snellen or 
Pinhole) 
 
X 
X 
 
 
 
 
 
 
BCVA (ETDRS) 
X
X
X
X
X 
X 
X
IOP 
X
X
X
X
X
X
X 
X 
X
Pachymetry 
X
X 
 
X
Endothelial Cell Density 
X
X
X 
 
X
Motility 
X 
 
 
 
 
 
X 
 
X 
Observations Recorded 
X
X
X
X
X
X
X 
X 
X
Adverse Event Assessment 
X
X
X
X
X
X 
X 
X

                                                          Page 42 of 84                        INN-005 Rev. 072117 
 
9.6  Withdrawal Criteria 
All subjects have the right to withdraw at any point during the treatment without prejudice.  
The investigator can discontinue any subject at any time if continued participation in the 
study would result in harm to the subject.  All efforts should be made by the investigator to 
retain the patient in the study.  If a subject withdraws prematurely from the study, a 
genuine effort must be made to determine the reason(s) the subject discontinued the study.  
The reason must be recorded in the subject’s file and on the End of Study Form. The site 
will then notify InnFocus, Inc. 
 
9.7  Lost-to-Follow-up Subjects 
Subjects who do not show up for a follow-up must be contacted to attempt to have them 
come for the follow-up.  For those subjects who cannot be reached, at least 3 phone call 
attempts should be made and documented.  If still no response, a registered letter shall be 
sent to the address on file for the subject in an attempt to make contact.  If there is still no 
response, the subject will be considered lost-to-follow-up unless there is a further 
communication by the subject. 
 
9.8  Device Return 
If an InnFocus device needs to be returned, the Device Return Form must be completed and 
returned with the product as instructed by the Device Return Procedure (located in the 
Regulatory Binder).  Prior to explantation or return, please contact InnFocus as soon as 
possible. Reasons for return could include any of the following: 
1. Device has exceeded the labeled expiration date. 
2. Implant was not present or damaged in packaging. 
3. Implant was damaged or contaminated before or during surgical procedure. 
4. Implant could not be inserted during surgical procedure. 
5. Flow was never observed prior to closing the flap (implying an obstruction in the 
device) 
6. Implant was removed during post-operative/secondary surgical intervention. 
7. Unused inventory upon completion of the study or site exiting from the study. 
 
 
For any device to be returned that has been exposed to blood or tissue, a special package 
will be provided by InnFocus, Inc. for return of the device. 
 
9.9   Protocol Modifications and Deviations 
Protocol modifications may occur during the study.   Each will be approved by the 
sponsor before implementation. Each will undergo Institutional Review Board (IRB) 
review and approval as necessary. 
 
Any deviations from this protocol intended to protect the life or physical well-being of a 
subject in an emergency are to be reported to InnFocus, Inc. as well as the IRB as soon as 
possible, and no later than 5 working days after the emergency occurred. 
 
All protocol deviations will be documented using Protocol Deviation form. 
 
 

                                                          Page 43 of 84                        INN-005 Rev. 072117 
 
10.0  Data Handling and Recordkeeping 
 
10.1  Subject Identification 
The subjects will be identified by a five digit subject number composed of a one-digit study 
identification number, a two digit center identification number followed by a two digit 
sequential subject number.  The subject identification will be assigned when ICF is 
obtained.  The initials for each subject will also be included on CRFs.  In this way, 
information contained in the study records will be kept as confidential as possible. 
 
10.2   Subject Accountability 
All subjects randomized in this clinical investigation shall be monitored for the duration of 
the investigation. The clinical investigation shall be considered completed when all 
subjects that have been enrolled in the investigation, including subjects whose device was 
removed or replaced, have reached the final reporting period.   
 
10.3   Confidentiality 
All medical records associated with the clinical investigation will be made available for 
review by InnFocus personnel, its contract research organization (CRO) and 
governmental/regulatory agencies involved.  The results of the study may be published in 
the future for scientific and marketing purposes, but the identity (name) of each subject will 
not be revealed.  All records will be stored in a secure area at the investigator’s facility, the 
CRO, and at InnFocus, Inc. 
 
10.4    Source Data and Electronic Case Report Forms 
  All sites will be given instructions by a trained InnFocus designee on source data 
completion at site initiation visit and/or interim monitoring visits.  
 
Source data forms are to be maintained at the site in the subject records.  All entries must 
be made in black or blue ink and changes must be made by strike-through only with date 
and initials or signature.  All source documents must be completed and signed by the 
authorized study personnel (e.g., study coordinator).    No correction fluid or correction 
tape is to be used on the source documents. The source document will be used by the 
Sponsor to verify data submitted on the CRFs. 
 
The source data will be entered into a validated electronic Case Report Form system at 
each site by trained study personnel in accordance with 21CFR Part 11 requirements.  The 
following forms will be utilized to collect source data during this clinical investigation 
 
Source Data Forms 
Screening  
Operative  
1 Day  
7 Day  
1M  
3M 
6M 

                                                          Page 44 of 84                        INN-005 Rev. 072117 
 
12M 
18M 
24M 
Unscheduled Visit 
Adverse Event/ Unanticipated Adverse Device Effect (UADE) 
Protocol Deviation  
Re-operation  
End of Study Form 
Glaucoma Medication 
Concomitant Medication 
Ocular QOL Questionnaire 
EQ-5D-5L Health Questionnaire 
 
10.5  Device Accountability 
With each shipment of investigational devices, InnFocus will include a Packing List that 
will give the amount shipped and the lot numbers. This packing list must be reconciled by 
the investigational site with the contents of the shipment and then complete the Inventory 
Logs for the InnFocus MicroShunt and the Mobius Mitosol (these logs are contained within 
the regulatory binder at the site).  All investigational products (IMS) at the site must be 
stored in a secured/locked area.  The InnFocus MicroShunt and Mobius Mitosol Kits may 
be stored at room temperature. Device reconciliation activities will also be conducted 
periodically in conjunction with site monitoring visits. 
 
The investigator must maintain accurate records of the receipt of all devices shipped by 
InnFocus, including the date and lot numbers received with the use of the device inventory 
tracking log. The use of devices will also be recorded.  An extra label provided with the 
device may be placed in the patient records.  Any unused inventory will be returned to the 
Sponsor upon completion of a given procedure, expiration, or Sponsor’s request. 
 
10.6  Record Retention 
Clinical sites are to retain any and all clinical trial material (documentation, photographs, 
etc.) for a period of two years from the date the marketing application is approved or two 
years after the investigation has been discontinued and the FDA notified, or as directed by 
their institutional document retention requirements, whichever is the longest.  After that 
time, the items may be returned to InnFocus for archiving.  Unused medical devices are to 
be returned to the sponsor at the conclusion of the enrollment period. 
 
10.7  Database Management 
The database will be designed to be compliant with 21 CFR Part 11 and relevant guidance 
documents.  The electronic database will be developed and maintained by an independent 
Contract Research Organization, Promedica International. 
 
The database will incorporate time-stamped audit trails, protection of human subjects, 
restricted access, and data security at the component level.  Each database module, 
including each individual CRF, will be validated by conducting a series of standard tests 
that demonstrate usability and correctness of the database system.  The database will be 

                                                          Page 45 of 84                        INN-005 Rev. 072117 
 
maintained on an ongoing basis and will be routinely backed up with both onsite and offsite 
storage.  
 
11.0  Assessment of Safety 
 
11.1  Adverse Events 
Adverse Events are defined below.  Adverse events that occur in the study eye during the 
trial as well as other non-ocular events whether they are considered to be device related or 
not must be documented in the subject’s records.  Date of the event, its severity, treatment 
(if any) and the assessed relationship of the event to the study device will be recorded on 
the Adverse Event Form.  Conditions which exist at the time the subject is enrolled do not 
need to be recorded on the Adverse Event Form as adverse events unless they increase in 
severity during the study. 
 
Anticipated Adverse Events 
Anticipated adverse events include those that might reasonably be expected to occur in this 
study because they are associated with glaucoma, glaucoma surgery, and/or prior cataract 
surgical procedures.   
 
Specific examples of anticipated adverse events include hypotony, increased intraocular 
pressure requiring medical or surgical intervention and decrease of BCVA. Increased 
intraocular pressure will be considered an adverse event if a subject has an IOP higher than 
the preoperative medicated screening pressure or 21mmHg, whichever is lower.  At this 
IOP level, the investigator will intervene either physically or with the addition of glaucoma 
medication.  There may also be cases where intervention for increased IOP is done at a 
lower IOP level than stated above because of other patient-related factors; these will also 
be adverse events. BCVA decreases of 2 lines or more should not be reported as adverse 
events until two consecutive standard visits after the 3-month follow-up visits unless 
surgical or medical intervention is required.  (Note:  a loss of BCVA in conjunction with 
posterior capsular opacification, followed by Nd:YAG capsulotomy and improvement of 
BCVA, is not considered an adverse event.) 
 
 
Intraoperative adverse events: 
  Hyphema (>10% of anterior chamber) 
  Choroidal effusion/detachment 
 Choroidal hemorrhage  
  Corneal abrasion during surgery 
 Failure to implant the device  
  Tube touching iris  
  Tube touching cornea 
  Iris abrasion during surgery 
 Globe perforation during the implantation or anesthesia 
 Flat anterior chamber  
 Needle damaged corneal endothelium 
 

                                                          Page 46 of 84                        INN-005 Rev. 072117 
 
Post-operative adverse events: 
 Anesthesia-related complications  
 Anterior chamber puncture 
 Aqueous humor misdirection (malignant glaucoma) 
 Blebitis 
 Bleb leak based on Seidel positive test 
 Choroidal effusion/detachment  
 Choroidal hemorrhage  
 Chronic pain 
 Clinically significant corneal damage 
 Clinically significant iris damage 
 Conjunctival dehiscence 
 Conjunctival dissection 
 Corneal edema 
 Diplopia 
 Encapsulated bleb causing increased IOP 
 Endophthalmitis 
 Erosion of the device through the conjunctiva  
 Flat anterior chamber 
 Hypotony (IOP<6mmHg at any time) 
 Hypotony maculopathy 
 
Implant migration 
 Inadequate pain control following surgery 
 Increased IOP requiring Needling 
 Increased IOP requiring Needling with 5FU/MMC post-surgical injection of bleb area. 
 Increased IOP requiring addition of glaucoma medications 
 Increased IOP requiring treatment with oral or intravenous medications 
 Prolonged inflammation resulting from surgery defined as requiring anti-inflammatory 
medication with duration and dosage in excess of protocol post-op instructions 
 Loss of 2 lines or more of BCVA on 2 consecutive standard follow-ups 90 days or more 
 after implantation  
(Note: a loss of BCVA in conjunction with posterior capsule opacification, followed by  
Nd:YAG capsulotomy and improvement of BCVA, is not considered an adverse event) 
 Loss of light perception 
 Macular edema  
 Posterior capsule opacification 
 Proptosis 
 Pupillary block 
 Re-suture scleral flap 
 Retinal complication (dialysis, flap tears, detachment, decompression or proliferative 
retinopathy) 
 Shallow anterior chamber 
 
Subconjunctival bleeding or hyphema at any time (including microhyphema) 
 

                                                          Page 47 of 84                        INN-005 Rev. 072117 
 
 
Event requiring unplanned surgical intervention for reason other than glaucoma  
 
 Tube obstruction, partial or complete, regardless of how long the obstruction is present 
 Tube touching iris  
 Tube touching cornea 
 Vitreous hemorrhage 
 Leakage of wound site based on Seidel test 
 Suture abscess or other local infection 
 Significant increase in IOP vs. screening ≥10 mmHg occurring at any visit  
 Strabismus 
 Event requiring unplanned glaucoma-related ocular surgical intervention 
 Device malfunction 
 Increase in C/D ratio of ≥0.3 units on slit lamp biomicroscopic examination 
 Confirmed worsening in the visual field of mean deviation (MD) of ≥2.5 dB compared to 
the MD used to determine subject eligibility (confirmed on at least 2 out of 3 visual field 
tests performed after 3 months post procedure) 
 Laser removal of blockage at the tip of MicroShunt or at the AC entry point for 
trabeculectomy 
 
Use of a viscoelastic to limit aqueous flow 
 Other – complete AE description  
 
Sight-Threatening Adverse Events 
 Sight-threatening AEs included but are not limited to events such as endophthalmitis and 
corneal decompensation, globe perforation during the implantation or anesthesia, severe 
retinal detachment, severe choroidal hemorrhage, severe choroidal detachment and aqueous 
misdirection. 
 
Sight-threatening AEs will be reported to InnFocus and to the investigator’s IRB as soon as 
possible, but no later than 10 working days after the investigator first learns of the event.  
Subjects who are terminated from the study due to the adverse experiences will be followed 
until their medical outcome is determined; written reports will be provided to the sponsor 
by the investigator. 
 
Unanticipated Adverse Device Effect 
Unanticipated adverse device effect (UADE) is defined as any serious adverse effect on the 
health or safety or any life-threatening problem or death caused by, or associated with, a 
device, if that effect, problem, or death was not previously identified in nature, severity, or 
degree of incidence in the investigational plan or application (including a supplementary 
plan or application), or any other unanticipated serious problem associated with a device 
that relates to the rights, safety, or welfare of subjects.  Date of event, its severity, treatment 
if any, and the assessed relationship of the event to the study device will be recorded on the 
AE form. 
 
11.2  Reporting Adverse Events and Unanticipated Adverse Device Effects 
All unanticipated adverse device effects (UADE) will be reported to the study sponsor, 
InnFocus, Inc., (Fax   305-378-2652) or by e-mail and to the reviewing IRB as soon as 
possible but no later than 10 working days after the investigator first learns of the event.  A 

                                                          Page 48 of 84                        INN-005 Rev. 072117 
 
UADE should be documented as an adverse event using the Adverse Event form and then 
also documented on the UADE form.   All adverse events should be documented by 
completing the Adverse Event form and, if applicable, a specific IRB AE form. 
 
Identification and collection of adverse event information will be the joint responsibility of 
the study sponsor, the CRO, and the study investigators.  The sponsor, the investigator, and 
the CRO will all follow the Declaration of Helsinki in order to ensure the safety of all 
subjects. 
 
The sponsor will conduct an evaluation of unanticipated adverse device effects.  If the 
sponsor determines that an unanticipated adverse device effect presents an unreasonable 
risk to subjects, parts of the investigation presenting risks will be terminated.  Termination 
will occur not later than 5 working days after the sponsor makes such a determination and 
not later than 15 working days after the sponsor first received notice of the effect. 
 
11.3  Type and Duration of Follow-up after Adverse Events 
The investigator is responsible for recommending the type and duration of follow-up for 
each subject who experiences an adverse event.  All events must be followed until 
complete resolution, resolution with sequelae, or the subject exits from the study.  All 
details must be documented on the Adverse Event Form. 
 
If a subject in either study arm requires an additional glaucoma surgery, the subject shall 
continue to be seen for the required follow-up visits so that safety and effectiveness can 
continue to be monitored. 
 
12.0  Monitoring Plan 
 
InnFocus or its designee(s) will monitor the study in a manner consistent with applicable 
health authority regulations and the clinical research standards adopted by InnFocus.  Study 
monitoring will involve the following elements: 
 
12.1 InnFocus or its designee(s) will meet with investigators prior to the initiation of the 
study in order to review the adequacy of the subject population, facilities, and equipment 
with respect to the needs of the study, and to familiarize the investigator with the study 
protocol and Good Clinical Practices 
 
12.2 InnFocus or its designee(s) may meet with the investigator(s) at the time the site 
begins to enroll in order to ensure that subjects are being properly selected and that study 
data are being correctly recorded. 
 
12.3 InnFocus or its designee(s) will visit the clinical site at any time during the study to 
review and/or collect the Case Report Forms. 
 
12.4 Interim monitoring visits and telephone consultation will occur as necessary during 
the course of the study to ensure the proper progress and documentation of the study 
findings. 

                                                          Page 49 of 84                        INN-005 Rev. 072117 
 
 
12.5 A close-out monitoring visit will be conducted at the completion of the study or study 
termination. 
 
13.0  Statistical Plan 
 
 
The statistical analysis plan has been detailed in a separate document. 
 
14.0  Medical Monitor 
 
An independent Medical Monitor will be used in the study.  The Medical Monitor will 
not be an investigator in the study.  The Medical Monitor will be a certified 
ophthalmologist with a glaucoma specialization.  The Medical Monitor will review 
adverse events and determine if the appropriate action have or are being taken.  In cases 
where there was an IOP increase and intervention or glaucoma medication was initiated 
or in cases where medication was discontinued, the Monitor will assure that the actions of 
the investigator met the intent of the protocol and were appropriate for the specific 
subject involved.   
 
15.0   Data Safety Monitoring Board 
 
A clinical trial DSMB will be used for this clinical study with pertinent expertise and will 
review on a regular basis accumulating data from this clinical study. The DSMB will 
advise the sponsor regarding the continuing safety of trial subjects and those yet to be 
recruited to the trial, as well as the continuing validity and scientific merit of the trial. 
 
The DSMB will review the Phase I study results and provide their recommendations 
directly to FDA for continuing the study into Phase II.  The Phase I interim report will be 
provided to them in a masked fashion for review.  Only in the event of unexpected safety 
findings will the data be unmasked for further study. 
 
DSMB meetings will be scheduled to review the status of the study.  After review of the 
first 75 subjects at 3 months follow-up in the Phase I study, DSMB meetings will be 
scheduled at least every six months to review interim results including 1 year Phase II 
results.  All data reviews by the DSMB will be masked to the treatment group. 
 
A charter and operational procedures will be established for the DSMB.  The DSMB will 
consist of at least three members and will be established by the sponsor.  No DSMB 
member will have a conflict of interest in maintaining objectivity in study evaluation. 
 
16.0  Compliance with Protocol 
 
An investigator shall conduct this investigation in accordance with the signed agreement 
with the sponsor, the investigational plan, the IDE regulation and other applicable FDA 
regulations, and any conditions of approval imposed by an IRB or FDA. 

                                                          Page 50 of 84                        INN-005 Rev. 072117 
 
 
 
 
 
 
17.0  References 
 
1. The Advanced Glaucoma Intervention Study Investigators: The Advanced Glaucoma 
Intervention Study (AGIS): 1. Study design and methods, and baseline characteristics of 
study patients. Controlled Clinical Trials 1994;15:299-325. 
2. The AGIS Investigators.  The Advanced Glaucoma Intervention Study (AGIS) 14.  
Distinguishing progression of glaucoma from visual field fluctuations.  Ophthalmology 
2004; 111:2109-2116. 
3. The AGIS Investigators.  The Advanced Glaucoma Intervention Study (AGIS) 7. The 
relationship between control of intraocular pressure and visual field deterioration. Am J 
Ophthalmol 2000;130:429-440. 
4. Heijl A, Leske MC, Bengtsson B, Hyman L, Bengstsson B, Hussein M; Reduction of 
intraocular pressure and glaucoma progression: results from the Early Manifest 
Glaucoma Trial.  Arch Ophthalmology. 2002;120:1268-1279. 
5. Heijl A, Bengtsson B, Hyman L, Leske MC; Early Manifest Trial Group.  Natural 
history of open-angle glaucoma.  Ophthalmology 2009;116:):2271-2276. 
6. Lichter PR, Musch DC, Gillespie BW, Guire KE, Janz NK, Wren PA, Mills RP; CIGTS 
Study Group.  Interim clinical outcomes in the Collaborative Initial Glaucoma 
Treatment Study comparing initial treatment randomized to medications or surgery.  
Ophthalmology 2001;108:1943-1953. 
7. Musch DC, Gillespie BW, Lichter PR, Niziol LM, Janz NK; CIGTS Study Investigators. 
Visual field progression in the Collaborative Initial Glaucoma Treatment Study.  The 
impact of treatment and other baseline factors.  Ophthalmol: 2009;116:200-7.  
8. Musch DC, Niziol LM, Gillespie BW.  A critical evaluation of the evidence for visual 
field improvement in the CIGTS.  ARVO 2012 Abstracts #4479, p-283.  (The paper in 
preparation will include Palmberg P who suggested the analysis.) 
9   Desai, Practice Preferences for Glaucoma Surgery: A Survey of the American Glaucoma 
Society in 2008, Ophthalmic Surg Lasers Imaging 2011;42:202-208 
10  Wilkins, Intraoperative Mitomycin C for glaucoma surgery (Review), Cochrane 
Collaboration, Wiley and Sons, 2010 
11   Alwrity, Primary low-risk trabeculectomy augmented with low-dose mitomycin-C, Eur J 
Ophthalmol 2009; 19:971-6 
12    Maris, Comparison of Trabeculectomy With Ex-PRESS Miniature Glaucoma Device 
Implanted Under Scleral Flap, J Glaucoma 2007;16:14–19 
13  Johnson, CA. Keltner JL, Cello KE,  Edwards M, Kass MA, Gordon MO, Budenz DL, 
Gaasterland DE, Werner E, and the Ocular Hypertension Study Group, Baseline Visual 
Field Characteristics in the Ocular Hypertension Treatment Study, Ophthalmology 
2002;109:432–437  

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18.0  Supplementary Information – Ophthalmic Definitions 
 
Anterior Chamber:  The fluid filled space filled with aqueous fluid between the iris and back 
surface of the cornea. 
 
Aqueous Flare:  A clinical sign occurring when there is increased protein content at the aqueous.  
It occurs when there is increased protein content in the aqueous fluid indicating a breakdown of 
the blood/aqueous barrier. 
 
Aqueous Humor:  Clear, watery fluid that fills the space between the back corneal surface and 
the front vitreous surface, bathing the lens.  Produced by ciliary processes: nourishes the cornea, 
iris, and lens and maintains the ocular pressure. 
 
Best Corrected Visual Acuity (BCVA):  Measurement of vision obtained with the best possible 
lens correction. 
 
Choroid:  The layer of major blood vessels (vascular layer) of the eye, which lies between the 
retina and sclera and provides nourishment to the outer layers of the retina. 
 
Ciliary Body:  The circumferential tissue inside the eye composed of ciliary muscle and ciliary 
processes that produce aqueous fluid.   
 
Ciliary Processes:  The innermost, epithelial portion of the ciliary body that secretes aqueous 
fluid and serves as attachment site of suspensory ligaments of the lens (zonules). 
 
Collagen:  Protein fibrils within the corneal tissue that help sustain its shape. 
 
Conjunctivitis:  An inflammation of the conjunctiva (mucus membranes that cover the white 
portion of the eye and inner surfaces of the eyelids).  Characterized by discharge, grittiness, 
redness and swelling.  Contagious, usually viral in origin. 
 
Cornea:  The outer, transparent, front segment of the cornea often having specific signs and 
symptoms with a known cause. 
 
Corneal Ulcer:  Area of epithelial tissue loss from the corneal surface: associated with 
inflammatory cells in the cornea and anterior chamber and usually caused by bacterial, fungal or 
viral infection. 
 
Cystic Bleb – thin, avascular blister under the conjunctiva 
 
Encapsulated Bleb - dome-shaped, elevated, tense, thick-walled, demarcated area centered over 
the trabeculectomy or other subconjunctival wound site 
 
Epithelium:  Tissue covering the outer surfaces of the cornea, conjunctiva, and eyelid surfaces. 
 

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Filtering Bleb:  A surgical procedure causing a bubble-like blister of the conjunctiva overlying a 
tunnel that leads to inside of the eye: formed by a surgical drainage procedure.  The most 
common form of filtering surgery is trabeculectomy. 
 
Glaucoma:  Damage to the optic nerve and to retinal nerve fiber diagnosed by excavation of the 
optic nerve head and documented by typical visual field defects.  A common cause of 
preventable vision loss. Elevated intraocular pressure is the only modifiable risk factor. 
 
Goldmann Applanation Tonometer:  Instrument device that measures intraocular pressure and 
usually attaches to a slit lamp. 
 
Gonioprism:  A special type of contact lens with prism that permits examination of the periphery 
of the anterior chamber or the peripheral retina. 
 
Intraocular Pressure (IOP):  Pressure of the fluid inside the eye, which varies among individuals. 
 
Iritis:  An inflammation of the colored part of the eye (iris) that can cause pain, tearing, blurred 
vision, a small pupil and a red, congested eye, which is sensitive to light. 
 
Keratitis:  Corneal inflammation, characterized by the loss of luster and transparency, and 
cellular infiltration. 
 
Lens:  The natural crystalline lens of the eye: transparent, bioconvex intraocular tissue that helps 
bring rays of light to focus on the retina.  Suspended by fine ligaments (zonules) attached 
between the ciliary processes.   
 
Limbus:  The transitional zone, about 1-2 millimeters wide, where the cornea joins the sclera and 
the bulbar conjunctiva attaches to the eyeball. 
 
Low Vision:  Visual loss, which cannot be corrected with eyewear or contact lenses and 
interferes with daily living activities.  
 
Lumen:  The space within the inside of any tubular structure, e.g., the inside walls of the arteries 
ore veins or tubular medical device. 
 
Open-angle glaucoma (OAG):  Glaucoma not associated with mechanical coverage of the 
trabecular meshwork by iris. 
 
Optic cup:  The white depression in the center of the optic disc; usually occupies about one-third 
or less of the total disc diameter.   
 
Optic Disc/Optic Nerve Head:  The exit site of the retinal nerve fibers from the eye. 
 
Persistent Hypotony - intraocular pressure below 6mm that is present on two consecutive follow-
ups after three months post-surgery. 
 

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Posterior Chamber:  The space between the back of the iris and the front face of the vitreous; 
filled with aqueous fluid. 
 
Pupil:  The variable-size, circular opening in the center of the iris; regulating the amount of light 
that enters the eye. 
 
Retina:  The part of the eye, that converts images (from the eye’s optical system) into electrical 
impulses sent along the optic nerve for transmission back to the brain.  It consists of many named 
layers that include cones, rods, bipolar cells, amacrine cells, ganglion cells, horizontal cells, 
Mueller cells, and all interconnecting nerve fibers. 
 
Schlemm’s Canal:  The circular channel deep in the corneo-sclera junction (limbus); collecting 
aqueous fluid from the anterior chamber of the eye and delivering it through a series of veins into 
the blood stream.  Passageway in which aqueous fluid leaves the eye. 
 
Sclera:  The opaque, fibrous, protective outer layer of the eye; contains collagen and elastic 
fibers.  This is directly continuous with the cornea (interiorly) and with the sheath covering the 
optic nerve (posteriorly).  
 
Stroma (Iris):  The primary substance of the iris and contains pigment cells that determine eye 
color, and two non-striated muscles: the ring-shaped sphincter and the radially-fibered dilator. 
 
Tonometry:  The procedure that measures intraocular pressure in the eye.  The various types of 
devices measure the pressure by indenting the cornea and are as follows:  applanation, 
indentation, pneumotonometer, and pneumatic tonometer. 
 
Trabecular Meshwork:  The mesh-like structure inside the eye bridging the anterior chamber 
angle between the cornea and the sclera. The trabecular meshwork, associated 
glycosaminoglucans, and the endothelium of Schlemms canal comprise the outflow resistance 
for aqueous leaving the anterior chamber and entering into the canal of Schlemm. 
 
Trabeculectomy:  Type of filtering procedure used in the treatment of glaucoma.  Involves the 
formation of an opening or hole under the conjunctiva and scleral flap into the anterior chamber, 
such that aqueous humor is drained onto the outer surface of the sclera.  
 
Uvea, Uveal Tract:  The pigmented layers of the eye (iris, ciliary body and choroid) that contain 
the majority of the blood vessel supply. 
 
Visual Acuity (VA):  The measurement of the eye’s ability to distinguish objects, details and 
shapes.  This is assessed by the smallest identifiable letters that can be discerned at a specified 
distance (usually 20 feet or 14 inches). 
 
Visual Field:  The vertical and horizontal extent of visual perception of specific targets, 
measured in degrees in each direction from fixation.  
 

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Vitrectomy:  Surgical procedure for the removal of vitreous fluid, blood, or membranes from the 
vitreous cavity in the posterior of the eye, usually performed by entering through the pars plana 
with a needle-like rotary cutter that has fluid injection and suction capabilities. 
 
Vitreous:  The transparent, colorless gelatinous mass of fine collagen fibrils and hyaluronic acid 
filling the rear two-thirds of the interior of the eyeball, between the lens and the retina. 
 
Zonules:  Radially arranged fibers that suspend the lens from the ciliary body and hold it in 
position. 
 

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APPENDIX 1 
1.0 Background on POAG, Management, and Rationale for the 
Study 
 
1.1 Background on Primary Open Angle Glaucoma 
 
The following summary in this section has been excerpted from the American Academy of 
Ophthalmology Preferred Practice Patterns for Primary Open Angle Glaucoma, October, 
2010.  Additional information and specific literature references can be obtained by going to 
the following website: 
http://one.aao.org/ce/practiceguidelines/ppp_content.aspx?cid=93019a87-4649-4130-8f94-
b6a9b19144d2 
EPIDEMIOLOGY 
Primary open-angle glaucoma is a significant public health problem. It is estimated that 45 
million people in the world have open-angle glaucoma (OAG).  Glaucoma (both open-
angle and angle-closure) is the second leading cause of blindness worldwide, with 
approximately 8.4 million people blind from glaucoma.  Overall in 2004, the prevalence of 
POAG for adults 40 and older in the United States was estimated to be about 2%.  Open-
angle glaucoma affects an estimated 2.2 million people in the United States, and that 
number is likely to increase to 3.3 million in 2020 as the population ages. However, large 
differences exist in the prevalence of glaucoma among different ethnic groups. Overall, 
there appears to be a threefold higher prevalence of OAG in African Americans relative to 
non-Hispanic Whites in the United States.  It is also the leading cause of blindness in 
African Americans. Further, the prevalence of OAG is even higher in Afro-Caribbeans 
relative to African Americans. Recent evidence on Hispanics/Latinos suggests that they 
have high prevalence rates of OAG that are comparable to African Americans.  There are 
no data on the prevalence of OAG in Asians in the United States. 
RISK FACTORS 
The findings of epidemiological investigations and clinical trials provide a framework for 
assessing the risk factors associated with POAG. The important risk factors associated with 
POAG are as follows: 
 Intraocular pressure level 
 Older age 
 Family history of glaucoma 
 African ancestry or Latino/Hispanic ethnicity 
 Thinner central cornea 
 Low ocular perfusion pressures 
 Type 2 diabetes mellitus 
 Myopia 
 Genetic mutations  

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Intraocular Pressure  
Several population-based studies have demonstrated that the prevalence of POAG increases 
as the level of IOP increases.  These studies provide strong evidence that IOP plays an 
important role in the neuropathy of POAG. Furthermore, studies have demonstrated that 
reduction in the level of IOP lessens the risk of visual field progression in OAG.  In 
addition, treated eyes that have a greater IOP fluctuation may be at increased risk of 
progression, although this has not been shown consistently.  
In spite of the relationship between the level of IOP and POAG, there is great inter-
individual variation in the susceptibility of the optic nerve to IOP-related damage. 
Population-based studies indicate that a variable proportion of patients with IOP greater 
than 21 mmHg (Northern Italy [13%], Los Angeles [18%], Arizona [20%], Blue Mountains 
[25%], Melbourne [39%], Baltimore [45%], Rotterdam [61%], Barbados [71%]) have 
glaucomatous optic nerve damage.  This suggests that an IOP level of greater than 21 
mmHg is an arbitrarily defined level and highlights the poor value of utilizing a specific 
IOP cutoff as a measure for screening and diagnosing POAG. 
Age 
Older age is another important risk factor for the presence of POAG.   A number of 
epidemiological studies demonstrate that the prevalence of glaucoma increases 
dramatically with age, particularly among individuals of Latino/Hispanic and African 
descent (see Table 1, Figures 1 and 4). African Americans 73 to 74 years old and 75 and 
older had a prevalence of 5.7% and 23.2%, respectively. Similarly, the prevalence of OAG 
was 3.4% for white individuals 73 and 74 years old and 9.4% for those 75 and older.  
Family History 
Family history is a risk factor for glaucoma. In the Rotterdam Eye Study, where all siblings 
of glaucoma cases and controls were examined, the odds of having POAG was 9.2-fold 
higher for individuals who have a first-degree relative (sibling or parent) with medically 
confirmed POAG.  Other studies in which family members were not physically examined 
depend on patient reports of the status of family members, and these are known to be 
subject to several biases. Nonetheless, they support the concept that first degree relatives of 
those with OAG are at greater risk. For example, in the Baltimore Eye Survey and the Los 
Angeles Latino Eye Study (LALES), for individuals with POAG the odds were twice as 
high (1.92 and 2.85, respectively) of reporting a first-degree relative (parent, child, or 
sibling) with glaucoma compared with individuals who did not have glaucoma. However, 
the odds increased to over three times as high if they reported that they had a sibling with 
glaucoma (LALES 3.47, Baltimore 3.7). Interestingly, the odds rose to fivefold higher if 
there were two or more siblings who were reported to have a history of glaucoma. 
Race or Ethnicity 
For POAG, ethnicity is an important risk factor. The prevalence of POAG is higher in 
individuals of West African, Afro-Caribbean, or Latino/Hispanic origin than of other 
groups. The prevalence is three times higher in African Americans and Hispanics of 
Mexican ancestry compared with non-Hispanic Whites. Blindness from glaucoma is at 
least six times more prevalent in African Americans than in Caucasian Americans.  

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Central Corneal Thickness  
Because applanation tonometry measurements are derived from resistance to corneal 
indentation and corneal stiffness, differences in central corneal thickness (CCT) may 
introduce artifacts in IOP measurement. The mean CCT in healthy human eyes varies by 
race/ethnicity. The average CCT measured ultrasonically in Caucasian Americans is 556 
μm, in Latinos it is 546 μm and in African Americans it is 534 μm. If IOP is 
underestimated in those with thinner CCT, the relationship between IOP level and OAG 
damage may be underestimated, since the IOP is actually higher than measured. 
Conversely, if IOP is overestimated in those with a non-edematous thicker CCT, the 
relationship between IOP level and OAG damage may be overestimated, since the IOP is 
actually lower than measured. Although several tables and figures have been published, no 
standard nomogram correcting applanation IOP measurements for CCT has yet been fully 
validated.  
A thinner central cornea has been reported as an independent risk factor (independent of 
IOP) associated with POAG, though not in all studies. In LALES, the risk of having OAG 
was higher in persons with thinner CCT compared with those with normal or thicker CCT 
even after adjusting the IOP.  Studies show that differences in corneal biomechanics across 
individuals may have a greater impact on IOP measurement errors than CCT.  
Low Ocular Perfusion Pressure  
Ocular perfusion pressure is the difference between blood pressure (at systole or diastole) 
and the IOP. It has been hypothesized that low ocular perfusion pressures lead to alterations 
in blood flow at the optic nerve head and contribute to progressive glaucomatous optic 
nerve damage. Population-based studies in African Americans, Hispanics, and non-
Hispanic Whites have provided evidence that low diastolic perfusion pressure (<50 mmHg) 
is associated with a higher prevalence of POAG.  In addition, in the Early Manifest 
Glaucoma Treatment Study, low systolic perfusion pressure (≤125 mmHg) was associated 
with a higher risk of glaucoma progression (relative risk of 1.42) over an 8-year period.  
Type 2 Diabetes Mellitus 
While there are some conflicting data on the association between type 2 diabetes mellitus 
(type 2 DM) and POAG, there is increasing evidence from population-based studies 
suggesting that type 2 DM is an important risk factor for POAG.  Population-based 
assessments of Hispanics (in Los Angeles, California), non-Hispanic Whites (in Beaver 
Dam, Wisconsin and Blue Mountains, Australia), and a large cohort enrolled in the Nurses 
Health Study have shown that persons with type 2 DM are more likely (40% higher odds in 
Hispanics, twofold higher odds in non-Hispanic Whites) to have POAG. Further, in the 
LALES, longer duration of type 2 DM was associated with a higher risk of having POAG. 
One explanation for this observation is that microvascular changes in the optic nerve may 
contribute to the greater susceptibility of optic nerve damage in persons with type 2 DM.  
Myopia 
Large cross-sectional epidemiologic studies in Afro-Caribbeans, Hispanics, non-Hispanic 
Whites, Chinese, Asian Indians, and Japanese suggest that persons with myopia have a 
higher prevalence of OAG than those without myopia. More recently, data from the 

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LALES have provided evidence of an independent relationship between longer axial length 
(axial myopia) and a higher prevalence of OAG.  The underlying hypothesis is that 
individuals with axial myopia have weaker scleral support at the optic nerve, and this 
contributes to a greater susceptibility of the optic nerve to glaucomatous damage. 
Genetic Factors  
The first gene to be linked to POAG was the myocilin gene (MYOC) on chromosome 1.  In 
one study, 3% to 4% of cases with POAG were found to have mutations in the myocilin 
gene.  Several chromosomal regions have now been linked to POAG and additional genes 
identified.  However, a majority of the cases with POAG do not have an identified genetic 
abnormality, suggesting that glaucomatous optic nerve damage may be multifactorial in its 
development, with different genes modifying the impact of various factors such as age, 
IOP, and blood flow. 
Other Factors 
In addition, migraine headache and peripheral vasospasm have been identified as risk 
factors for glaucomatous optic nerve damage.  The association between POAG and factors 
such as concurrent cardiovascular disease and systemic hypertension has not been 
demonstrated consistently.  
1.2. Management of Primary Open Angle Glaucoma 
 
Goals 
The goals of managing patients with POAG are to achieve the following: 
 Controlled IOP in the target range 
 Stable optic nerve/retinal nerve fiber layer status 
 Stable visual fields 
 
Because elevated IOP is a treatable cause of POAG damage, one can expect to reduce the 
risk of disease progression in many patients by lowering the IOP by means of medication, 
laser therapy, or incisional glaucoma surgery. Results from randomized controlled trials 
and other studies reinforce this expectation and provide evidence that the more the IOP is 
lowered, the more likely is it to slow the rate of progression of POAG. 
 
 Management is a challenge for the patient and the doctor, because POAG is a chronic, 
often asymptomatic, condition that may require frequent use of multiple and expensive 
medications181 that may cause side effects or may require laser or incisional surgery. The 
effects of treatment, the patient's quality of life, and the patient's life expectancy are 
important to consider when choosing therapy. The diagnosis, severity of the disease, 
prognosis and management plan, and likelihood of long-term therapy should be discussed 
with the patient.  Substantial field loss in glaucoma is associated with a decrease in quality 
of life measures. 
 
Target Intraocular Pressure for Patients with POAG 
The goal of glaucoma treatment is to maintain the IOP in a range at which a patient is 
likely to remain stable or at which worsening of glaucoma will be slow enough that the risk 

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of additional intervention is not justified.  The estimated upper limit of this range is 
considered the "target pressure." The initial target pressure is an estimate and a means 
toward the ultimate goal of protecting the patient's vision. The target pressure should be 
individualized and may need adjustment during the course of the disease. 
  
When initiating therapy, the ophthalmologist assumes that the measured pretreatment 
pressure range contributed to optic nerve damage and is likely to cause additional damage 
in the future. Lowering the pretreatment IOP by 25% or more has been shown to inhibit 
progression of POAG.  It is reasonable to select an initial target pressure at least 25% lower 
than pretreatment levels. Choosing an even lower target IOP can be justified if there is 
more severe optic nerve damage, if the damage is progressing rapidly, or if other risk 
factors such as family history, age, or disc hemorrhages are present  
 
Choosing a less aggressive target IOP may be reasonable if the risks of aggressive 
treatment outweigh the benefits (e.g., if a patient does not tolerate medical therapy well and 
surgical intervention would be difficult or if the patient's life expectancy is short). In a 
study of newly diagnosed patients with moderate to advanced glaucoma, a subset of 
patients randomized to initial lowering of IOP by surgery did better than those assigned to 
medical treatment over an 8-year period, and this could be due to the lower mean post-
treatment IOP in the surgery group. 
 
 The adequacy and validity of the target pressure are periodically reassessed by comparing 
optic nerve status (by optic disc appearance, quantitative assessments of the disc and nerve 
fiber layer, and visual field tests) with previous examinations. If progression occurs at the 
target pressure, undetected IOP fluctuations and adherence to therapy can be re-evaluated 
before adjusting the target IOP. However, target pressure is an estimate, and all treatment 
decisions must be individualized according to the needs of the patient. 
 
Therapeutic Choices 
The IOP can be lowered by medical treatment, laser therapy, or incisional glaucoma 
surgery (alone or in combination). The choice of initial therapy depends on numerous 
considerations, and discussion of treatment with the patient should include the relative risks 
and benefits of the three options. 
 
Medical treatment 
Unless contraindicated, medical therapy is presently the most common initial intervention 
to lower IOP. There are many drugs available for initial therapy, and medication choice 
may be influenced by potential cost, side effects, and dosing schedules Patient adherence to 
therapy is enhanced by using eyedrops with the fewest side effects as infrequently as 
necessary to achieve the target IOP. If target IOP is not achieved by one medication, then 
additional separate medications, combination therapies, or switching of treatments may be 
considered to reach the target IOP.  
 
Prostaglandin analogs and beta-blockers are the most frequently used initial eye drops for 
lowering IOP in patients with glaucoma. Prostaglandin analogs are the most effective drugs 
at lowering IOP and can be considered as initial medical therapy unless other 

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considerations such as cost, side effects, intolerance, or patient refusal preclude this. Other 
agents in addition to prostaglandin analogs and beta-blockers include alpha2 adrenergic 
agonists, parasympathomimetics, and topical and oral carbonic anhydrase inhibitors. 
 
The ophthalmologist should consider the balance between side effects and effectiveness in 
choosing a regimen of maximal effectiveness and tolerance to achieve the desired IOP 
reduction for each patient. Frequent dosing and side effects (such as depression, exercise 
intolerance, and impotence with topical beta-blockers) may affect adherence to therapy. 
 
Adequate treatment of glaucoma requires a high level of adherence to therapy. Frequently 
this is not achieved; studies indicate relatively poor adherence to therapy.  Even with 
instruction, free medication, once-daily administration, use of a dosing aid, and electronic 
monitoring of adherence, nearly 45% of patients in one study took fewer than 75% of their 
prescribed doses.  Instilling eyedrops correctly is difficult for patients, and their ability to 
do so may worsen as glaucoma progresses. Repeated instruction and counseling in proper 
techniques for using medication as well as a clearly written medication regimen and 
follow-up telephone calls may improve adherence to therapy.  
 
Laser trabeculoplasty 
Laser trabeculoplasty can be considered as initial therapy in selected patients or an 
alternative for patients who cannot or will not use medications reliably due to cost, memory 
problems, difficulty with instillation, or intolerance to the medication. Laser 
trabeculoplasty lowers IOP by improving aqueous outflow and can be performed using 
argon, diode, and frequency-doubled YAG lasers. 
 
Argon and diode laser trabeculoplasty 
Studies using continuous-wave argon laser with a wavelength spectrum that peaks at 488 
nm (argon laser trabeculoplasty [ALT]) found that treatment increases aqueous outflow and 
provides a clinically significant reduction of IOP in more than 75% of initial treatments of 
previously unoperated eyes.  Since these initial studies, more compact solid-state diode 
lasers have mostly replaced the original argon laser with equal IOP lowering efficacy. 
For patients initially treated with ALT, the amount of medical treatment required for 
glaucoma control is reduced.  Results from long-term studies of patients receiving 
maximum medical therapy who subsequently had laser and incisional surgery indicate that 
30% to more than 50% of eyes require additional surgical treatment within 5 years after 
ALT.  For eyes that have failed to maintain a previously adequate response, repeat ALT has 
a low long-term rate of success, with failure occurring in nearly 90% of these eyes by 2 
years. After previous applications to the full circumference of the anterior chamber angle, 
repeat ALT has a lower success rate than initial therapy in eyes that have not had a 
reduction in IOP for at least a year following the first laser surgery. Compared with initial 
laser trabeculoplasty, there is an increased risk of problems and complications such as IOP 
spikes after repeat laser trabeculoplasty. 
 
Selective laser trabeculoplasty 
The introduction of selective laser trabeculoplasty (SLT) is most likely responsible for the 
increase in use of laser trabeculoplasty in 2001 after a previous decline. Selective laser 

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trabeculoplasty uses a Q-switched, frequency doubled, 532 nm Nd:YAG laser that delivers 
less energy and is purported to be selectively absorbed by pigmented cells in the trabecular 
meshwork. These attributes appear purportedly to produce less thermal damage to the 
trabecular meshwork compared with ALT.  However, several prospective and retrospective 
studies indicate that SLT appears comparable to but not better than ALT in lowering IOP. 
Selective laser trabeculoplasty also appears to be comparable in efficacy to medical therapy 
with prostaglandin analogs, although in one prospective study, SLT was only comparable 
to latanoprost when 360 degrees of the trabecular meshwork was treated.  In this study, 
latanoprost had a better IOP-lowering effect compared with 90 and 180 degrees of 
treatment. 
 
It has been claimed that SLT has greater success than ALT with repeated treatments, but no 
controlled, randomized clinical trial has shown that this is true. Only one study with a 
significant sample size has studied the results of SLT repeated after prior SLT treatment. 
This was a retrospective study of repeat 360 degree SLT after prior successful 360-degree 
SLT.  In the postoperative period, repeat SLT treatment lowered IOP, but the effect was 
less than that with initial SLT treatment at 1 to 3 months and 5 to 8 months. These results 
suggest that repeat SLT may be less efficacious compared with primary treatment, but 
further studies are needed to clarify this issue. The safety profile of SLT appears to be 
good, with mild anterior chamber inflammation after treatment and less ocular discomfort 
compared with ALT. Intraocular pressure spikes have been noted after SLT in 4.5% to 27% 
of eyes in various studies. 
 
Incisional glaucoma surgery 
Trabeculectomy 
Filtering surgery is effective in lowering IOP; it is generally indicated when medicine or 
laser therapy is insufficient to control disease and can be considered in selected cases as 
initial therapy. 
  
Filtering surgery provides an alternative path for the escape of aqueous humor, and it often 
reduces IOP and the need for medical treatment. Estimates of success rates over time range 
from 31% to 56% in different populations. The failure rate of filtering surgery, without the 
use of adjunctive antifibrotic medications, alone or combined with medical therapy in a 
previously unoperated eye in the Advanced Glaucoma Intervention Study reached 
approximately 30% in African American patients and 20% in Caucasian American patients 
over a 10-year period. While long-term control is often achieved, many patients may 
require further therapy or a reoperation, which carries a higher failure rate. Furthermore, 
filtering surgery increases the likelihood that phakic eyes may undergo cataract surgery. In 
eyes that have undergone previous cataract surgery involving the conjunctiva, the success 
rate of initial glaucoma surgery is reduced.  
 
Antifibrotic agents may be used intraoperatively and postoperatively to reduce the 
subconjunctival scarring after filtration surgery that can result in failure of the operation. 
The use of intraoperative mitomycin-C reduces the risk of surgical failure both in eyes at 
high risk of surgical failure and in eyes that have not undergone previous surgery. Some 
studies have demonstrated a benefit of intraoperative 5-fluorouracil and others have not. 

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The use of postoperative injections of 5-fluorouracil also reduces the likelihood of surgical 
failure in both high-risk eyes and eyes that have not undergone previous surgery. 
 
The use of an antifibrotic agent carries with it an increased likelihood of bleb-related 
complications such as hypotony, hypotony maculopathy, late-onset bleb leak, and late-
onset infection that must be weighed against the benefits when deciding whether or not to 
use these agents. These complications may be even more common in primary filtering 
surgery of phakic patients. 
  
Aqueous shunts 
All commercialized aqueous shunts (also known as tube shunts, glaucoma drainage 
devices, and setons) consist of a tube that diverts aqueous humor to an end plate located in 
the equatorial region of the eye. The primary resistance to flow through these devices 
occurs across the fibrous capsule that develops around the end plate. Aqueous shunts differ 
in their design with respect to the size, shape, and material from which the end plate is 
made. They may be further subdivided into valved and non-valved shunts, depending on 
whether or not a valve mechanism is present to limit flow through the shunt if the IOP 
becomes too low. Examples of non-valved implants are the Baerveldt glaucoma implant 
(Abbott Medical Optics, Santa Ana, CA) and the Molteno implant (Molteno Ophthalmic 
Ltd., Dunedin, New Zealand). Examples of the valved implants are the Ahmed glaucoma 
valve (New World Medical, Inc., Rancho Cucamonga, CA) and the Krupin implant (Eagle 
Vision, Inc., Memphis, TN). 
 
Aqueous shunts have traditionally been used to manage medically uncontrolled glaucoma 
when trabeculectomy has failed to control IOP or is deemed unlikely to succeed. This 
includes eyes with neovascular glaucoma, uveitic glaucoma, extensive conjunctival 
scarring from previous ocular surgery or cicatrizing diseases of the conjunctiva, and 
congenital glaucoma in which angle surgery has failed. However, the indications for using 
aqueous shunts have been broadening, and these devices are being increasingly utilized in 
the surgical management of glaucoma. Medicare data show a steady rise in the number of 
shunts placed from 1995 to 2004, while there has been a concurrent decline in the number 
of trabeculectomies performed.  Recent surveys of the American Glaucoma Society 
membership have also demonstrated a progressive increase in the number of surgeons 
using tube shunts. 
  
A systematic review concluded that aqueous shunts are comparable with trabeculectomy 
for IOP control and duration of benefit, that larger end-plate surface area provides better 
IOP control, and that there appears to be no advantage to the use of antifibrotic agents or 
systemic corticosteroids as adjuncts to aqueous shunt procedures. The need for comparative 
studies and long-term follow-up was identified by the authors. 
 
Several studies have compared aqueous shunts with trabeculectomy. A retrospective study 
evaluating surgical results in matched patient groups reported similar IOP reduction with 
the single-plate Molteno implant and trabeculectomy with 5-fluorouracil. However, another 
retrospective case-control study observed a higher 5-year success rate after trabeculectomy 
with mitomycin-C than with Ahmed glaucoma valve implantation. A randomized clinical 

                                                          Page 63 of 84                        INN-005 Rev. 072117 
 
trial in Sri Lanka comparing the Ahmed implant and trabeculectomy in patients with 
primary open-angle and angle-closure glaucoma found comparable IOP reduction and 
success rates with a mean follow-up of 31 months. The Tube Versus Trabeculectomy 
(TVT) Study is a multicenter, prospective, randomized clinical trial that compared the 
safety and efficacy of tube-shunt surgery using the 350-mm2 Baerveldt glaucoma implant 
and trabeculectomy with mitomycin-C in patients with previous cataract extraction and/or 
failed trabeculectomy. Tube-shunt surgery had a higher success rate than trabeculectomy 
(85% vs. 69%) after 3 years of follow-up as defined by loss of vision, and/or IOP less than 
or equal to 5 mmHg or greater than or equal to 21 mmHg. Both surgical procedures were 
associated with similar IOP reduction and use of supplemental medical therapy at 3 years.  
Postoperative complications occurred more frequently after trabeculectomy compared with 
tube-shunt surgery, but the rate of serious complications associated with vision loss and/or 
reoperation to manage the complication was similar with both procedures. 
 
Aqueous shunts are associated with intraoperative and postoperative complications that are 
similar to those that occur with trabeculectomy. In addition, they have unique 
complications related to implantation of a foreign body. Erosion of the tube may occur 
through the conjunctiva, and this typically develops a few millimeters behind the limbus 
following anterior chamber insertion. Diplopia may result from extraocular muscle fibrosis 
or a mass effect of the bleb overlying the end plate. Tube-cornea touch can lead to 
progressive endothelial cell loss and persistent corneal edema. The risk of postoperative 
infection appears to be less with aqueous shunts than after trabeculectomy with an 
antifibrotic agent. 
 
Other glaucoma surgeries 
Nonpenetrating glaucoma surgery is an alternative to trabeculectomy. The precise role of 
nonpenetrating surgery in the surgical management of glaucoma remains to be determined. 
The two main types of nonpenetrating glaucoma surgery are viscocanalostomy and 
nonpenetrating deep sclerectomy. The rationale for nonpenetrating glaucoma surgery is that 
by avoiding a continuous passageway from the anterior chamber to the subconjunctival 
space, the incidence of complications such as bleb-related problems and hypotony can be 
reduced. The nonpenetrating procedures have a higher degree of surgical difficulty 
compared with trabeculectomy and require special instrumentation. Randomized clinical 
trials comparing viscocanalostomy with trabeculectomy generally suggest greater IOP 
reduction with trabeculectomy, but more complications with viscocanalostomy.  
One randomized clinical trial found that trabeculectomy was more effective than 
nonpenetrating deep sclerectomy at lowering IOP, and several others found that the two 
surgeries were equally effective. 
  
Other glaucoma surgical procedures currently in use are canaloplasty with a tensioning 
suture (Prolene [Ethicon Inc., Somerville, NJ]), ab interno trabeculotomy using the 
Trabectome (NeoMedix, Tustin, CA), trabecular meshwork bypass stent (i-Stent, Glaukos 
Corp., Laguna Hills, CA) and the Ex-PRESS mini glaucoma shunt (Alcon Laboratories, 
Inc., Ft. Worth, TX). 
 

                                                          Page 64 of 84                        INN-005 Rev. 072117 
 
Cyclodestructive surgery 
Cyclodestructive procedures reduce the rate of aqueous production. There are several ways 
to reduce ciliary body function, such as cyclocryotherapy, transscleral and noncontact 
Nd:YAG laser, and transscleral and noncontact endodiode laser cyclophotocoagulation. 
 
Cyclodestructive procedures have traditionally been used for refractory glaucomas, and 
success rates have been reported in the range of 34% to 94%. They have been associated 
with a subsequent decrease of visual acuity and, rarely, cases of sympathetic ophthalmia.  
Disadvantages of cyclodestructive procedures include postoperative inflammation, IOP 
spike, and the frequent need for repeat treatment weeks or months later.  Compared with 
cyclocryotherapy, laser cyclophotocoagulation causes less postoperative pain and 
inflammation. Therefore, cyclocryotherapy is now rarely used. Laser cyclodestructive 
procedures have advantages over filtration surgery that include technical ease and reduced 
postoperative care. 
 
In 2005, 47% of all Medicare cyclophotocoagulation procedures were performed 
endoscopically; in 2006, 58%; and in 2007, 65%. Endoscopic cyclophotocoagulation (ECP) 
consists of a solid-state 810-nm laser, a video camera, aiming beam, and a xenon light 
source housed together in a fiberoptic cable that can be introduced inside the eye for direct 
visualization and treatment of the ciliary processes. Theoretically, this allows better 
titration of laser treatment. The efficacy of ECP appears to be good, with IOP reduction 
reported in the range of 34% to 57%.  It appears that treating 270 to 360 degrees of the 
ciliary body is necessary to achieve significant IOP lowering.  Fibrin exudates, hyphema, 
cystoid macular edema, vision loss, hypotony, choroidal detachment, and phthisis have 
been noted after ECP in eyes with advanced glaucoma, but more recent studies involving 
eyes with less advanced glaucomatous damage seem to report fewer of these complications. 

                                                          Page 65 of 84                        INN-005 Rev. 072117 
 
APPENDIX 2 
2.0 Prior Pre-clinical and Clinical Testing 
 
2.1  Pre-clinical Studies 
The studies were designed and implemented by InnFocus or independent contractors to 
ensure that all reasonable concerns regarding human implantation were mitigated.  These 
tests evaluated not only the basic safety of the device and the feasibility of performing the 
surgery with the associated surgical instruments, but also the fit and expected performance 
to assure the highest likelihood of success in reducing intraocular pressure in glaucomatous 
eyes.  
 
2.1.1 Physical Stability 
 
 
Accelerated Hydrolysis Testing  
The testing was conducted on three lots of InnFocus MicroShunt facsimiles.   
The test was conducted for a 5 year equivalent timeframe at two temperatures, 
85±2°C and 100±2°C, for 20 and 57 days, respectively.  No significant weight 
loss was observed.  The bond strength of the tube to the fins of the device did not 
change from the hydrolysis.   After incubation, each recovered sample group was 
evaluated for changes in appearance relative to un-aged samples. SEM at 500x 
magnification and optical microscopy at magnifications of 20x and 30x were 
both applied and no significant changes were detected with either imaging 
method.  No significant analytes were detected in the hydrolysates from either 
incubation. These methods consistently demonstrated the chemical hydrolytic 
stability of the poly(styrene-b-isobutylene-b-styrene) thermoplastic hydrophobic 
elastomer (SIBS) from which the device is made. 
 
2.1.2 Pressure/Flow Characteristics 
Studies were conducted to verify that the 70 micron internal diameter and 8.5mm 
length of the InnFocus MicroShunt tube provide adequate aqueous flow to 
reduce intraocular pressure.  The study of three lots of sterilized InnFocus 
MicroShunts demonstrated that the internal diameter and length will provide at 
least 2 microliters/minute of flow at 6mmHg pressure. 
 
2.1.3 Structural Integrity 
 
The fins on the InnFocus MicroShunt are heat fused to the tube.  Testing was 
conducted on three lots pre and post sterilization to verify the fusion was 
adequate. All bonds met the specification of >50grams or >0.5Newtons.  An 
overall average increase in bond strength of 11.2% was observed after 
sterilization. 
 
2.1.4 Chemical Testing 
 

                                                          Page 66 of 84                        INN-005 Rev. 072117 
 
Exhaustive Extraction of InnFocus MicroShunt in Isopropyl Alcohol  
InnFocus MicroShunt facsimiles were exhaustively extracted in isopropyl 
alcohol, a strong but non-dissolving solvent for the SIBS thermoplastic material.  
The test facsimiles, over three lots tested, displayed an average weight loss of 
approximately 0.2%.  The overall sensitivity level of the chromatographic and 
spectroscopic methods applied in this study was approximately 1 ppm or less for 
relevant compounds used in the manufacture of the device.  The study provides 
documented evidence at baseline levels showing only dimethylsiloxanes which 
are related to the packaging materials, and 2-phenylphenol and benzophenone at 
trace levels. None of these was considered to be significant and do not impact the 
biocompatibility of the device.  No other compounds were detected.  There were 
no significant differences in the extractable fractions of the three different lots 
tested. 
 
Leachable Testing 
This study quantified and identified the aqueous and lipophilic leachable 
fractions for the InnFocus MicroShunt.  Samples were incubated at a temperature 
of 35+2oC for 72+2h in both aqueous and lipophilic solvents. Extractions in 
these two solvents cover the possible polarity range that the implant could be 
exposed to in the intraocular environment. HPLC-grade isopropyl alcohol (IPA) 
was used as the lipophilic solvent and HPLC-grade water was used as the 
aqueous solvent.  The leachates from test and control extractions were analyzed 
spectroscopically using UV/VIS spectrophotometry and chromatographically 
using HPLC/PDA (photodiode array UV detection), GC/FID (flame ionization 
detection), and GC/MS techniques.  
 
Low molecular weight siloxanes, ethylene glycol, benzophenone, 2-
phenylphenol, and a low molecular weight alkyl polyol were detected in the 
lipophilic leachates at very low concentrations. These are related to the 
packaging materials and the sterilization process.  Glycerin, which is applied to 
the device to improve handling, was in the leachate at a concentration of 0.5-0.6 
weight%.  Only the water-soluble compounds, glycerin, ethylene glycol, and the 
alkyl polyol, were detected in the aqueous leachates.  None of these was 
considered to be significant and do not impact the biocompatibility of the device. 
 
Insoluble Inorganics Analysis of InnFocus MicroShunt product 
Because the processes used to manufacture the InnFocus MicroShunt involve 
contact with metallic equipment, three lots of the sterilized InnFocus MicroShunt 
were sent for inductive coupled plasma/mass spectrophotometry analysis for 
metallic content.  The data indicated that there is a low level of metallic 
contaminants from the manufacturing processes.  None of the levels of the 
contaminants is near or above any known toxic levels for the particular 
inorganics observed.  Additionally, the biocompatibility tests separately 
conducted by InnFocus used samples that had been prepared with the same 
equipment.  Those samples passed all of the biocompatibility tests as will be 
discussed later in this document.  

                                                          Page 67 of 84                        INN-005 Rev. 072117 
 
 
2.1.5 Dimensional and Surface Quality 
Pre and post sterilization dimensional and visual testing was conducted on three 
separate manufacturing lots of InnFocus MicroShunts.  The testing included 
length, outside diameter, inside diameter, and surface characteristics.  All 
InnFocus MicroShunts met the specifications pre and post sterilization. 
Insignificant shrinkage of post sterilization samples was observed.  
 
2.1.6 Evaluation of the Effect of Viscoelastics in Anterior Chamber 
Studies were conducted with implanted InnFocus MicroShunts in rabbits to 
determine if viscoelastics will flow through the lumen.  One Healon version and 
methyl cellulose were the only types studied.  The studies determined that it 
requires over one week for these viscoelastics to degrade adequately so that flow 
is initiated.  Based on this data, warnings were included in the study protocol 
regarding the use of viscoelastics. 
 
2.1.7 Aging and Transport testing 
Transport Testing 
 
Standard packaged InnFocus MicroShunt units were sent to a contract lab for 
transport testing to assure there is no damage to the product or packaging during 
shipment.  The packaged units met the test requirements.   
 
Accelerated Aging Study 
Units were aged at 60oC for 11.1 weeks to simulate 3 years of real time aging 
and subsequent testing confirmed that the product met specifications supporting 
a 3 year expiration date.   
 
2.1.8 EO Sterilization residuals 
Testing of sterilized InnFocus MicroShunts was conducted to assure ethylene 
oxide residuals met specifications.  The devices passed the test requirements. 
 
2.1.9  Pyrogen Testing 
Testing of sterilized InnFocus MicroShunts was conducted to assure that levels of 
pyrogenic material were below acceptable levels.  All the devices passed the test 
requirements. 
 
 
 
2.1.10  Biocompatibility (ISO 10993) 
Biocompatibility tests were conducted on SIBS polymer samples that had been 
processed through simulated InnFocus MicroShunt manufacturing steps.  The 
SIBS used for the testing included an additive to aid in manufacturing processing. 
After EtO sterilization, the samples were sent to an outside laboratory for a series 
of ISO 10993 GLP biocompatibility studies as shown below.  The processed and 
2x EtO sterilized samples passed all of these tests.   
 
1.   Cytotoxicity – ISO Elution Method 
2.   In Vitro Inhibition of Cell Growth – L-929 Mouse Fibroblast 

                                                          Page 68 of 84                        INN-005 Rev. 072117 
 
3.   ASTM Hemolysis 
4.   ASTM Partial Thromboplastin Time 
5.   ISO Maximization Sensitization Study – Saline 
6.   ISO Maximization Sensitization Study – Sesame Oil  
7.   ISO Muscle Implantation Study – 2 weeks 
8.   Genotoxicity – Bacterial Reverse Mutation Study – DMSO Extract 
9.   Genotoxicity – Bacterial Reverse Mutation Study – Saline Extract 
10. USP Pyrogen Study – Material Mediated 
11. USP and ISO Systemic Toxicity Study – Saline 
12. USP and ISO Systemic Toxicity Study – Sesame Oil 
13. ISO Intracutaneous Study – Saline 
14. ISO Intracutaneous Study - Sesame Oil 
 
2.1.11 Animal and clinical studies on prior InnFocus MicroShunt prototypes 
 
A series of chronic ocular implantation rabbit studies were conducted to evaluate 
the safety of InnFocus glaucoma drainage device prototypes.  These studies were 
conducted on various internal diameter and external diameter tubes.  In some 
prototypes, a tab located on one side of the tube was present.  In one study, a 
small SIBS plate was attached to the distal end of the device.  
 
The chronic ocular implantation studies consisted of device implantation and 
follow-ups at 1 and 7 days, 4 weeks, and 3 and 6 months during which the 
rabbits were examined by slit lamp for healing characteristics and IOP was 
measured.  At the end of each study, histology was conducted on explanted 
devices and surrounding tissue to evaluate the healing response.   In all of these 
studies, the prototypes demonstrated excellent biocompatibility.   
 
Clinical feasibility studies were conducted in France and Dominican Republic.  
Each of these studies had one year follow-up.  Based on the outcome of these 
studies on prior prototypes which identified specific safety and functional 
improvements as well as providing confirmation of many design components, 
the final InnFocus MicroShunt Glaucoma Drainage System design was 
established and additional clinical studies initiated that are described below.   
 
2.1.12  Ongoing InnFocus MicroShunt Clinical Studies 
 
 
  Dominican Republic Study (Protocol INN-003) 
The first study which utilizes the present design of the InnFocus MicroShunt 
(formerly called the MIDI Arrow) study was initiated in Santo Domingo, 
Dominican Republic in 2010.  Twenty-three (23) subjects were enrolled.  The 
patients averaged 59.8+15.3 years of age, IOP of 24.0+5.4 mmHg and 2.2+0.9 
glaucoma meds at baseline.  The subjects had no prior incisional glaucoma 
surgery and 1 of 23 had prior glaucoma laser surgery.  A total of 14 InnFocus 
MicroShunt only cases and 9 combined InnFocus MicroShunt and cataract 
surgery cases were performed. The study will continue through 3 years of 

                                                          Page 69 of 84                        INN-005 Rev. 072117 
 
follow-up for each subject.  As of December 2012, 2 year data are available for 
15 subjects with 1 year data available for all other subjects.  This study used the 
present version of the device except that the length was trimmed to 8-9mm at 
time of implantation versus the pre-cut length of 8.5mm planned for the U.S. 
study.   
 
The data from the InnFocus MicroShunt study provided below are based on 15 
subjects at 24 months follow-up, 7 subjects at 12 months follow-up and one lost 
to follow-up after 12 months follow-up.  The definition of success in the study 
was based on >20% drop in IOP and IOP < 21mmHg with or without glaucoma 
medication usage.  At 12 months follow-up, the success rate was 100% with an 
average IOP decrease of 55.4%.  The mean IOP for the InnFocus MicroShunt 
only cases at 12 months was 11.3 ± 2.9 mmHg, and 9.7 ± 2.4 mmHg for the 
combined InnFocus MicroShunt and cataract cases.  Glaucoma meds usage for 
the total group at 12 months was an average of 0.3 meds/patient with only 3 
patients requiring any glaucoma medications. At two years, the success rate was 
87% with an average IOP drop of 49.1%.  The mean IOP at 2 years was 12.2 ± 
3.9 mmHg for the InnFocus MicroShunt only cases (9) and 12.1 ± 4.4 mmHg for 
the combined group (6).  Glaucoma meds usage for the total group at 24 months 
was an average of 0.5 meds/patient with only 3 patients on any glaucoma 
medications.  Of the three failures at 24 months, 2 failures were due the subjects 
only having an IOP decrease of 19% and 1%.  The third failure was due to 
increased IOP, which resulted in the need for another glaucoma surgery. 
 
Complications of specific interest in the study are summarized below and a table 
presenting all complications is on the following page. 
 
Intra-operative adverse events:  There was one intra-operative adverse event that 
occurred when the tip of the InnFocus MicroShunt tube in the anterior chamber was 
observed to have blood and fibrin on it.  A paracentesis was made and the tip was flushed 
with balanced sterile saline to successfully clear the tip of blood.  A bleb was not present 
at 1 and 7 days post-surgery, but the bleb was present from 21 days post-surgery forward. 
 
Post-operative Adverse Events:  There were a total of 58 mostly mild, post-operative 
ocular adverse events to date in the study.  The most common event was transient acute 
hypotony where all cases cleared up spontaneously without intervention.  Hypotony was 
defined as <6mmHg in the study.  The historical data from the literature has used either 
<6mmHg or <5mmHg as a limit. Also the historical data is variable on when to start 
reporting hypotony, i.e., at Day 1, Day 7 or later.  Because of these reporting differences 
and the fact that any associated adverse events from hypotony tend to increase as the 
pressure moves downward from <6mmHg, special mention is given to the data as to the 
extent of lower pressure. 

                                                          Page 70 of 84                        INN-005 Rev. 072117 
 
 
Hypotony Resolution  
No. of Subjects 
Transient Hypotony                  
< 7 Days
                                 < 90 Days 
                               < 180 Days 
4 (17% 
5 (22%) 
1 (4%)
Chronic Hypotony > 180 Days
0
 
Hypotony resolved in 4 subjects by day 7, in 5 subjects by day 90 and in 1 subject by day 
180.  When patients with IOP values at exactly 5 or with hypotony at 1 day postop only 
are excluded, there were only 3 cases or 13% transient hypotony.  All the patients with 
transient hypotony < 5 mmHg (excluding Day 1) were combined MIDI Arrow procedures 
with cataract surgery.  
  
No chronic hypotony, defined as two consecutive visits after 90 days follow-up with IOP 
< 6 mmHg has been observed to date.  Shallow or flat anterior chambers were observed 
in 13% (3/23) subjects with all cases resolved within 14 days with no associated adverse 
events.  The tube in contact with the iris was observed in 13% (3/23) of the cases, but has 
not led to any occlusion of the tube or other adverse event.   
 
In the combined surgery group, there were 2 choroidal effusions, 4 cases of acute corneal 
edema, 2 cases of posterior capsule opacification, 2 cases of Descemet striae, 1 case of 
fibrin strands, 2 cases of posterior synechiae, 1 case of vitreous hemorrhage and 2 cases 
of IOL pupillary capture.  All are likely related to the cataract surgery or the added IOP 
drop from the cataract surgery.  All of these resolved spontaneously or were treated 
successfully.  
 
There were two cases of elevated IOP that required physical intervention.  In one 
combined surgery case with elevated IOP, the anterior chamber was “burped” with the 
use of a 27G needle on Day 1 post surgery to alleviate the high pressure.  The pressure 
immediately dropped below 5 mmHg and was back above 6 mmHg on Day 7.  The 
pressure increase at Day 1 was thought to be due to fibrin in the anterior chamber from 
the cataract surgery that may have blocked the InnFocus MicroShunt tube temporarily 
until the fibrin resorbed.  The second elevated IOP case resulted in needling of a cystic 
bleb at the slit lamp on Day 90, wherein the pressure returned to the prior reduced level. 
Both of these adverse events are considered severe and are denoted with an “S” in Table 
6. 
 
There were 3 cases of increased IOP that were treated with glaucoma medication. 
  
One exposed Tenon’s capsule was observed at Day 1 post surgery in a patient with thin 
conjunctiva and was resolved by Day 21 without intervention.  A second potential 
exposed Tenon’s capsule was reported in a subject approximately 9 months post-surgery 
with no Seidel positive.  The subject was prescribed lubricant drops, and intact 

                                                          Page 71 of 84                        INN-005 Rev. 072117 
 
conjunctiva was clearly observed over the Tenon’s capsule within the next 3 months with 
no other issues or action taken. 
 
There was one bleb leak not related to the device that resolved within 2 weeks.   
 
Additional visual field loss of >2.5dB in mean deviation (MD) was classified as an 
adverse event and was based on the latest follow-up of subjects with measurable visual 
fields.  At 12 months for 6 patients, 0 of the 6 had additional VF loss of >2.5dB.  At the 
latest follow-up of 24 months for 10 patients, 2 of 10 had additional VF loss of >2.5dB. 
 
One patient with a baseline MD of -19.2dB had additional loss of 12.2dB at 2 years 
follow-up with no bleb and an IOP of 19mmHg.  Based on the excavation of the optic 
nerve (C:D=0.9) and the continuing excellent visual acuity of 20/20, the subject was 
scheduled for surgery to minimize further optic nerve damage and was put on 3 glaucoma 
medications until surgery.  The contralateral eye had been on 3 glaucoma medications for 
12 months. 
 
The second patient with a baseline of -25.0dB had additional loss of 7.1dB at 2 years 
follow-up.  The subject had an IOP of 11.5mmHg with a bleb present and visual acuity of 
20/25.  The contralateral eye had been on 3 glaucoma medications for 2 years.  No further 
action was indicated. 
 

                                                          Page 72 of 84                        INN-005 Rev. 072117 
 
 Adverse Events in Dominican Republic Study 
Non-Ocular Adverse Events 
Number of events 
Angina pectoralis
1
 
Adverse events in study eye 
MIDI Arrow 
Only Surgery 
 
 
N=14 
Combined 
Cataract and 
MIDI Arrow 
Surgery 
N=9 
Overall
% of 
Eyes 
 
N=23 
Corneal edema 
0
4 
4
17.4
BCVA loss of at least 2 lines at or after the three 
month visit 
1 
0 
1 
4.3 
Tube in contact with iris 
3
0 
3
13.0
Transient Hypotony resolved by D7
3
1 
4
17.4
Transient Hypotony resolved by D90
4
1 
5
21.7
Transient Hypotony resolved by D180
0
1 
1
4.3
Chronic hypotony >180 Days 
0
0 
0
0.0
Shallow or flat AC 
1
2 
3
13.0
Posterior capsule opacification 
0
2 
2
8.7
Hyphema 
1
1 
2
8.7
Elevated IOP requiring needling of bleb or AC
1
1 
2
8.7
Descemet striae 
0
2 
2
8.7
Tube obstruction by iris, blood, fibrin, etc.
1
0 
1
4.3
Elevated IOP requiring treatment with glaucoma 
medication 
3 
0 
3 
13.0 
Vitreous hemorrhage 
0
1 
1
4.3
Dry eye 
1
0 
1
4.3
Flat bleb 
1
1 
2
8.7
Tearing 
1
0 
1
4.3
Exposed Tenon’s capsule 
2
0 
2
8.7
Cystic bleb 
2
0 
2
8.7
Bleb leak 
1
0 
1
4.3
Pain 
2
1 
3
13.0
Fibrin strand 
0
1 
1
4.3
Choroidal effusion or detachment 
0
2 
2
8.7
Posterior synechiae 
0
2 
2
8.7
IOL pupillary capture 
0
2 
2
8.7
Endophthalmitis 
0
0 
0
0.0
New cataract or progression 
0
0 
0
0.0
Allergic conjunctivitis 
1
0 
1
4.3
Corrective Surgery 
1
0 
1
4.3
Visual field loss > 2.5dB at 1 yr 
0
0 
0
NA1
Visual field loss > 2.5dB at 2 yr 
2
0 
2
NA1
Totals
32 
27 
59 
 
 
1Not all subjects had visual fields that could be measured

                                                          Page 73 of 84                        INN-005 Rev. 072117 
 
Clinical Study of InnFocus MicroShunt in Bordeaux, France 
 
INN-004 Clinical Study of the Safety and Performance of the Miami InnFocus 
Drainage Implant (MIDI Arrow) to Relieve Glaucoma Symptoms   
 (REP-INF-0152-00 is in Volume 8; Briefcase summaries are in REP-INF-0153-00) 
 
An additional clinical trial of the InnFocus MicroShunt implant is being conducted in 
Bordeaux, France under the direction of Professor Isabelle Riss.  The subjects for the 
study are inadequately controlled on maximum tolerated medical therapy with intraocular 
pressures >18mmHg to < 40mmHg.  The subjects had no prior incisional ophthalmic 
surgery other than uncomplicated cataract surgery.  There are 37 eyes in the study of a 
total of 20 males and 16 females; one patient had both eyes treated with the InnFocus 
MicroShunt.  As shown in the second table below, 32 of 37 eyes had prior non-incisional 
glaucoma procedures.  The study is planned for two years of follow-up.  To date, a total 
of 41 eyes of 36 subjects have received InnFocus MicroShunt devices (Four of these 
InnFocus MicroShunts were implanted outside of the study protocol in fellow eyes of 
subjects in the study for which the surgeon believed the InnFocus MicroShunt to be the 
best choice).  The data below summarizes the 37 eyes of 36 subjects that are in the 
clinical study.  The exceptions to this are the adverse event summary and tables that 
include all 41 eyes implanted.  A total of 19 eyes are phakic and 18 eyes in the study are 
pseudophakic.  The mean age of the subjects is 62.6 years (SD 13.0).  All patients are 
Caucasian.   
 
    Table 1: Demographics and Baseline Characteristics for INN-004 Population 
Number of Eyes
Overall
37
Age (Years) 
Mean
62.6
Std. Dev.
13.0
Minimum
38
Maximum
86
Race 
Caucasian
36
Status of Test Eye 
Phakic
19
Pseudophakic
18
Base line IOP 
Mean 
22.8
Std. Dev.
4.3
Minimum
18
Maximum
35
Visual Acuity in Test Eye 
Mean 
7.3
Min, Max
1-10
Glaucoma Diagnosis 
 
POAG
23
Number of Glaucoma Meds 
Mean
3.4

                                                          Page 74 of 84                        INN-005 Rev. 072117 
 
Std. Dev
1.2
Min, Max
1 - 6
Systemic Diseases 
Hypertension
10
Diabetes
0
Hypertension and Diabetes
1
HTN + Other
3
Other
13
 
 
 
                 Prior Non-Incisional Glaucoma Procedures 
Procedure 
Number of Eyes 
Selective laser trabeculoplasty (SLT)
15 
Laser peripheral iridotomy (LPI)
6 
SLT and LPI 
7 
SLT and unspecified non-incisional procedure (NIP)
2 
SLT, LPI and NIP 
1 
NIP 
1 
Total
32 
 
Follow-ups are shown below: 
 
Length of Follow-up 
No. of Eyes 
1 Year
12
9 Months
9
6 Months
10
<  6 Months
6
 
For eyes with baseline IOP >18 to < 21 mmHg, success is defined as an IOP reduction of 
20% or greater with no reoperation for glaucoma or loss of light perception vision. For 
eyes with baseline IOP >21 mmHG, success is defined as IOP<21 mmHg and IOP 
reduction from baseline of 20% or greater with no reoperation for glaucoma or loss of 
light perception vision.  
  
For the 12 eyes that have reached 12 months follow-up, the surgical success rate is 75%. 
 
The baseline medicated IOP for the 37 eyes is 22.8+4.3mmHg.  The mean decreases in 
IOP are shown below at 6 and 12 months follow-up. 
 
Measurement 
Timepoint 
N 
IOP 
Mean 
SD 
% Decrease 
Baseline 
37
22.8
4.3
NA 
6 Months 
31
15.3
3.4
33 
12 Months 
12
15.5
5.2
32 
 

                                                          Page 75 of 84                        INN-005 Rev. 072117 
 
 
As shown below, the glaucoma medication reduction from an average of 3.4 meds per 
patient is 82% for those subjects at 12 months follow-up and 79% overall. 
  
 
 
 
  Glaucoma Medication Usage 
 
 
 
 
 
 
 
 
 
 
Adverse events related to the treated eye in the study as well as those outside the study 
are summarized below for the 41 eyes: 
 
There was one case of corrective surgery due to the InnFocus MicroShunt being 
dislodged during closure of the conjunctiva without being noticed by the surgeon.  Upon 
observing an IOP of 26mmHg, the next day the surgeon observed that the tip of the 
device was not in the anterior chamber.  Review of the video showed that the device was 
dislodged by the forceps as the conjunctiva was pulled forward to suture.  Because of the 
presence of blood, the surgeon did not observe this.  One week after the original 
procedure, a new procedure was successfully performed to place the same device back 
into the anterior chamber with flow observed through the device prior to conjunctival 
closure.  The patient responded well initially and at 12 months follow-up, the IOP was 
19mmHg with one glaucoma medication. 
 
Hypotony was observed infrequently with a total of 3 eyes with transient hypotony for an 
overall rate of 7.3%, and all were resolved by the 3 week follow-up. 
 
Increased IOP was observed in a total of 17 eyes with 12 of these having one or more 
needling procedures with glaucoma medication and the remaining 5 eyes having 
glaucoma medications only.  Needling was conducted in all cases except one with the use 
of MMC; the one exception was with the use of Healaflow (viscoelastic).  Three eyes had 
over 3 needlings performed (7, 4, 4); the IOP in two of these eyes was brought back into 
control with IOPs at one year of 7mmHg and 13mmHg and the third remained high at 
one year with an IOP of 27mmHg. 
 
Keratitis was observed in 6 eyes and a corneal ulcer in 1 patient with resolution in all 7 
patients. Five of the corneal edema cases and the corneal ulcer were resolved by the 3 
months follow-up, and one corneal edema case was resolved by the 6 months follow-up.   
 
Hyphema was observed in 10 eyes and resolved within the first week after surgery.  In 
one eye, the anterior chamber was flushed to remove the blood. 
 
N 
No. Eyes on 
Meds 
Avg. 
Meds/Eye 
% Reduction 
All Eyes Post 
Surgery 
37 
11 
0.7 
79 
Subjects at 12 
months follow-
up 
12 
5 
0.7 
82 

                                                          Page 76 of 84                        INN-005 Rev. 072117 
 
 
Conjunctival bleeding was noted in 3 eyes.  In one of these eyes, the bleeding was 
considered significant and it occurred approximately 2 weeks after surgery.  It was 
resolved the same day and was attributed to the procedure and not the device. 
 
There were transient irritation issues in 5 patients, which resolved. 
 
There were 5 cases of posterior capsule opacification in the study eye of pseudophakic 
patients not believed to be related to the InnFocus MicroShunt that were treated with 
YAG laser and resolved. 
 
Other notable events included a temporary loss of 2 lines of visual acuity in 1 patient 
which resolved by 12 months, and a bleb leak caused by cutting a suture within a week of 
surgery to eliminate irritation that was quickly resolved. 
 
There were 7 non-ocular adverse events that are listed in the second table below. 

                                                          Page 77 of 84                        INN-005 Rev. 072117 
 
                             Adverse Events for Study Eye in Protocol INN-004 
(Includes 4 eyes implanted outside of study protocol) 
Anticipated adverse event in test eye 
IMS Only 
Surgery 
 
N=38 
Combined 
Cataract and 
IMS Surgery 
N=3 
Overall 
% of 
Eyes 
(n=41) 
Keratitis (Corneal edema) 
5
1
6 
14.6
Corneal ulcer 
1
0
1 
2.4
BCVA loss of at least 2 lines at or after 
the three month visit 
1 
(temporary) 
0 
1 
2.4 
Tube in contact with iris 
0
0
0 
0
Transient Hypotony (< 7 Days)
1
0
1 
2.4
Transient Hypotony (7-180 Days)
2
0
2 
4.9
Chronic hypotony (Post 180 Days)
0
0
0 
0.0
Shallow or flat AC 
1
0
1 
2.4
Posterior capsule opacification
5
0
5 
12.2
Hyphema 
9
1
10 
24.4
Intraoperative AC washout of blood
1
0
1 
2.4
Elevated IOP requiring needling of bleb 
with with MMC or Healaflow 
32 
(11 eyes)
1 
(1 eye)
33 
(12 eyes) 
29.3 
Descemet striae 
0
0
0 
0.0
Tube obstruction by iris, blood, fibrin, 
etc. 
0 
0 
0 
0.0 
Elevated IOP requiring treatment with 
glaucoma medication only 
5 
(5 eyes)
0 
5 
(5 eyes) 
12.2 
Elevated IOP (Other) 
2
0
2 
4.9
Vitreous hemorrhage 
0
0
0 
0.0
Dry eye 
0
0
0 
0.0
Flat bleb 
1
0
1 
2.4
Tearing  
0
0
0 
0.0
Exposed Tenon’s capsule 
0
0
0 
0.0
Resuturing of conjunctiva 
2
0
2 
4.9
Cystic bleb 
0
0
0 
0.0
Bleb leak 
1
0
1 
2.4
Irritation 
4
1
5 
12.2
Conjunctival bleeding 
3
0
3 
7.3
Dislocation of Device During Procedure
1
0
1 
2.4
Fibrin strand 
0
0
0 
0.0
Choroidal effusion or detachment
1
0
1 
2.4
Posterior synechiae 
0
0
0 
0.0
IOL pupillary capture 
0
0
0 
0.0
Endophthalmitis 
0
0
0 
0.0
New cataract or progression 
0
0
0 
0.0
Corrective Surgery 
1
0
1 
2.4
Conjunctivitis 
1
0
1 
2.4
Sinusitis 
1
0
1 
2.4
Age-related Macular Degeneration
1
0
1 
2.4
Totals
82 
4 
86 
 

                                                          Page 78 of 84                        INN-005 Rev. 072117 
 
Non-Ocular Adverse Events in Protocol INN-004 
 
Adverse Event 
Number 
% of 
Subjects 
N=37 
Abnormal Hemogram during follow-up 
of Hyperlymphocytosis
1 
2.7 
Pneumopathy 
1
2.7 
Psychiatric internment 
1
2.7 
Emergency cardiac operation
1
2.7 
Blood pressure increase during surgery
1
2.7 
Hospitalization for alcoholic withdrawal
1
2.7 
Headache 
1
2.7 
Total
7 
 
 
 
Effectiveness Comparison to Historical Trabeculectomy/Glaucoma Drainage Device 
Studies 
 
Literature evaluation was used to study the historical data on glaucoma drainage devices and 
trabeculectomy with or without the use of MMC.  The data collected from these analyses were 
used to compare the performance and safety versus the InnFocus MicroShunt in the most recent 
clinical studies in the Dominican Republic (DR) and Bordeaux, and is presented in the tables 
below.  Based on the data from the 23 eyes in the Dominican Republic study and 37 eyes in the 
Bordeaux study, the performance of the InnFocus MicroShunt is comparable to or exceeds the 
expected success rate at one year for trabeculectomy with MMC and drainage devices. This is 
evidenced by the mean IOP, the use of glaucoma medications, and the InnFocus MicroShunt 
effectiveness at 12 months follow-up as compared to the success rates at one year shown below 
for trabeculectomy with or without MMC and glaucoma drainage devices. 
 
Further comparison of the InnFocus MicroShunt 2-year data can be made to the trabeculectomy 
data by adjusting the one-year trabeculectomy success rates downward by 10%, which is 
generally considered the rate of failure of trabeculectomy per year.  The InnFocus MicroShunt 
results continue to compare favorably at the 2-year timeframe with each of the historical 
trabeculectomy groups at 12 months follow-up in the table that follows. 

                                                          Page 79 of 84                        INN-005 Rev. 072117 
 
Effectiveness Comparison of One Year Follow-up Data Summaries 
 from Literature Search of  Trabeculectomies at One Year Follow-up  
with InnFocus MicroShunt Data at 12 months follow-up 
Effectiveness 
Parameter 
Type of 
Value 
Traba 
(Cochrane data 
@12mo follow-up) 
Trab w/MMCa 
(Cochrane Data 
@12mo follow-up) 
Trab w/MMC 
(12mo follow-up in 
historical studies 
from REP-INF-0117-00) 
Table 4 
IMS at 12 
months 
(n=23) 
DR 
 
IMS at 12 
months 
(n=12) 
Bordeaux 
 
Highb 
Risk 
Primaryc 
High 
Risk 
Primary 
Surgical 
Success  
(% of N) 
Mean 
49.5 
72.0
84.4
92.2
78.6 
100
75
Range 
26-71 
29-78 
71-90 
86-100 
64-89 
 
 
IOP  
 
Mean 
20.7 
17.4
13.8
12.0
13.0 
10.7
15.5
Range 
18.6-
23.9 
16.4-
18.4
12.5-
14.6
11.1-
12.8
9.9-16.0 
 
 
Reduction 
in IOP (%) 
Mean 
40.7 
35.3
59.5
55.4
51.2 
55.6
30
Range 
40-42 
28-42
55-64
50-61
28-63 
Glaucoma 
Meds 
Reduction 
(%) 
Mean 
NR
NR
85.8 
91
79
Range 
NR 
NR 
48-96 
 
 
                     aThe values in this column do not include any combined glaucoma and cataract surgery. 
bHigh risk = previous glaucoma drainage surgery or previous surgery involving anything more than 
trivial conjunctival incision, including cataract surgery; patients with one or more of 
the following forms of glaucoma: glaucoma secondary to intraocular inflammation, 
congenital glaucoma and neovascular glaucoma. 
 
   cPrimary =  people who have received no previous surgical intervention. This group may include people who have  
                     had previous medical therapy, laser procedures or both. 
 

                                                          Page 80 of 84                        INN-005 Rev. 072117 
 
    Effectiveness Comparison of One Year Follow-up Data Summaries from Literature  
              Search of Various Aqueous Shunt Studies with InnFocus MicroShunt Data  
                                                    at 12 months follow-up 
Effectiveness 
parameter 
Type of 
Value 
Aqueous 
shunts 
w/reservoir 
Optonol 
Ex-Press 
Shunt 
Staar 
Aquaflow 
IMS 
DR 
IMS 
Bordeaux
IOP at one year 
(mmHg) 
 
Mean 
15.7 
12.7 
13.4 
10.7 
15.3 
Range 
12.1-18.9 
11.8-13.5 
10.4-16.5 
 
 
Surgical success 
(with or without 
glaucoma meds) 
(% of N)                
Mean 
78.8 
91.3 
65.3 
100 
75 
Range 
53.7-100 
85.6-96.9 
44-75 
 
 
Glaucoma meds  
per patient                Mean 
0.9 
0.6 
0.4 
0.3 
0.7 
 
 
 
                      Extrapolated Surgical Success of Trabeculectomy at 2 years Follow-up  
                                              vs. 2 year InnFocus MicroShunt Data 
 
Effectiveness 
Parameter 
Type 
of 
Value 
Traba 
(Cochrane data) 
Trab w/MMCa 
(Cochrane Data) 
Trab 
w/MMC 
(12mo follow-
up in historical 
studies from 
REP-INF-0117-00) 
Table 4 
IMS at 24 
months 
(n=23) DR 
 
Highb 
Risk 
Primaryc 
High 
Risk 
Primary 
Surgical 
Success  
(% of N) 
Mean 
39.5 
62.0 
74.4 
82.2 
68.6 
87 
                     aThe values in this column do not include any combined glaucoma and cataract surgery. 
bHigh risk = previous glaucoma drainage surgery or previous surgery involving anything more
trivial conjunctival incision, including cataract surgery; patients with one or 
more of the following forms of glaucoma: glaucoma secondary to intraocular 
inflammation, congenital glaucoma and neovascular glaucoma. 
 
 
   cPrimary =  people who have received no previous surgical intervention. This group may include people who have  
                     had previous medical therapy, laser procedures or both. 
 
 

                                                          Page 81 of 84                        INN-005 Rev. 072117 
 
 
Safety Comparisons to Historic Trabeculectomy and Glaucoma Drainage Device Studies 
 
A similar analysis of trabeculectomy with or without MMC and glaucoma drainage devices 
historic studies was done for safety as compared to the InnFocus MicroShunt in the Dominican 
Republic and Bordeaux studies, and the two tables below show the complications breakdown.  
The analysis is based on the data from the 23 eyes in the Dominican Republic study and the 
41eyes in the Bordeaux study.  The analysis includes adverse events through the latest follow-up 
including two-year follow-up on 15 eyes in the Dominican Republic and 12 eyes in the Bordeaux 
study.   
 
The rate of cataract development or progression was noticeably less in InnFocus MicroShunt 
treated eyes with 0% of eyes at one year follow-up versus trabeculectomy with MMC meta 
analysis means of 15.6% and 20.1% and aqueous shunt means ranging from 2.5-11.9%. 
 
Visual acuity decreases were less in the InnFocus MicroShunt groups with 2.4% and 4.3% versus 
a mean of 14.6% in the one trabeculectomy with MMC meta analysis that reported the decreases.  
The InnFocus MicroShunt groups were also less than the reported aqueous shunt visual acuity 
decreases ranging from 10.8-21.8%. 
 
Acute hypotony and related adverse events were similar for the trabeculectomy and InnFocus 
MicroShunt groups, with no chronic hypotony in the InnFocus MicroShunt groups. 
 
Corneal edema was greater in both InnFocus MicroShunt studies with 17.4% and 14.6% as 
compared to the glaucoma drainage device studies mean values of 7.3% and 3.6%.  There was no 
meta analysis data available for trabeculectomy with or without MMC.  The corneal edema value 
of 17.4% was in the Dominican Republic study and was observed only in combined InnFocus 
MicroShunt and cataract cases where corneal edema is expected.  One of the six cases observed 
in the Bordeaux study was also a combined surgery case.  Four of these cases resolved within the 
first 3 months with the final one by the six months follow-up. 
   
There were no other notable differences in the comparisons between the two procedures. 
 
Based on this analysis of the relative safety of the InnFocus MicroShunt as compared to 
commercialized glaucoma drainage devices and trabeculectomy with MMC, the InnFocus 
MicroShunt has comparable or better safety characteristics.  

                                                          Page 82 of 84                        INN-005 Rev. 072117 
 
                                     Safety Comparison of InnFocus MicroShunt to  
                                              Historic Trabeculectomy Studies 
  
 
 
                      Complications (% of Patient Population)
Complication 
Type of 
Value 
Traba 
(Cochrane data 
@12mo follow-
up)
Trab w/MMCa 
(Cochrane Data 
@12mo follow-up) 
Trab 
w/MMC  
(12mo follow-
up in historical 
studies from 
REP-INF-0117-00 
Table 5) 
InnFocus 
MicroShunt 
Combined High 
Risk and 
Primary 
Combined High 
Risk and 
Primary 
23 eyes 
DR 
41 eyes 
BORD 
Wound leak 
Mean 
1.0
1.2
5.6 
5.0
2.4
Range 
0.0-12.5
0.0-19.5
1.9-11.0 
 
Chronic 
Hypotony 
Mean 
2.9b 
0.0-10.0 
3.7b 
0.0-10.0 
8.3 
0.0
0.0
Range 
0-24.3 
 
Acute Hypotony 
Mean 
13.3 
13.0c
7.3
Range 
0-47.9 
 
Shallow or flat 
AC 
Mean 
9.3
7.6
6.2 
8.7
2.4
Range 
0.0-26.7
0.0-35.7
0.2-18.1 
 
Endophthalmitis 
Mean 
0.0
0.0
1.5 
0.0
0.0
Range 
0.0-0.0
0.0-0.0
0.3-3.0 
 
Suprachoroidal 
Hemorrhage 
Mean 
0.0
0.0
3.0 
0.0
0.0
Range 
0.0-0.0
0.0-0.0
3.0-3.0 
 
Cataract Surgery 
Mean 
6.9
15.6
20.1 
0.0
0.0
Range 
0.0-18.2
0.0-26.0
1.0-40.2 
 
Blebitis 
Mean 
NR
NR
3.5 
0.0
0.0
Range 
NR
NR
1.1-10.8 
 
        Hyphema 
Mean 
NR
NR
7.8 
8.7
24.4
Range 
NR 
NR 
0.0-24.6 
 
 
Bleb Leak 
Mean 
NR
NR
9.1 
4.3
2.4
Range 
NR
NR
1.9-27.0 
 
Choroidal 
Effusion 
or Detachment 
Mean 
NR
NR
10.4 
8.7
2.4
Range 
NR 
NR 
0.8-28.0 
 
 
Encapsulated 
Bleb 
Mean 
NR
NR 
10.3 
8.7
0.0
Range 
NR
NR
1.2-37.0 
 
 

                                                          Page 83 of 84                        INN-005 Rev. 072117 
 
Complications (% of Patient Population) (continued) 
Complication 
Type of 
Value 
Traba 
(Cochrane data 
@12mo follow-
up)
Trab w/MMCa 
(Cochrane Data 
@12mo follow-up) 
Trab 
w/MMC  
(12mo follow-
up in historical 
studies from 
REP-INF-0117-00 
Table 5) 
InnFocus 
MicroShunt 
Combined 
High Risk and 
Primary 
Combined High 
Risk and 
Primary 
23 eyes 
DR 
41 eyes 
BORD 
Tenon’s Cyst 
Mean 
NR
NR
50.4 
0.0
0.0
Range 
NR
NR
40.9-62.8 
Visual Acuity 
Decreased 
Mean 
NR
NR
14.6 
4.3e
2.4f
Range 
NR
NR
6.0-28.6 
aThe values in this column do not include any combined glaucoma and cataract surgery. 
bThese values were not defined as acute or chronic hypotony in the individual studies and therefore have been 
grouped. 
cThis value excludes patients with IOP values at exactly 5 or hypotony at 1 day postop only.  
dDefined as > 2 lines of vision loss 
eOccurred in 1 patient and considered unreliable because of patient mental state 
fOne temporary VA decrease was observed but was not present at 12 months follow-up 
NR = Not reported in study 
 
          
                  
   Complications Comparison of InnFocus MicroShunt Data 
  
 
 
                     to Historic Aqueous Shunt Studies  
 
                         Complications (% of patient population) 
Complication 
Type of 
Value 
Aqueous 
shunts with 
reservoir 
Optonol 
Ex-Press 
Shunt 
Staar 
Aquaflow 
InnFocus MicroShunt 
23 eyes 
DR 
41 eyes 
BORD 
Acute hypotony 
Mean 
5.3 
9.8 
8.9b 
0-32b 
13.0a 
7.3
 
 
Range 
2-18.8
4-15.6
Chronic hypotony 
 
Mean 
8.4
2
0.0 
0.0 
Range 
1-23
0-4
 
 
Shallow or Flat AC 
 
Mean 
9.9
3.0
3.8 
8.7 
2.4 
Range 
3-20
2-4.1
0-18 
 
 
Hyphema 
Mean 
9.5
6.7
5.9 
8.7 
24.4 
Range 
0.8-20
2.8-11.5
0-10.3 
 
 
Erosions 
Mean 
6.4
0.0
0 
0.0 
0.0 
Range 
2-12
0-0
0-0 
 
 
Goniopuncture 
Mean 
0
0
38.5
0.0 
0.0 
Range 
0-0
0-0
21-50
 
 
MMC injections 
Mean 
NR
NR
23.7
4.3 
26.8 
Range 
NR
NR
20-31
 
 
 

                                                          Page 84 of 84                        INN-005 Rev. 072117 
 
 
                               Complications (% of patient population) 
 
 
 
 
 
     (continued) 
Complication 
Type of 
Value 
Aqueous 
shunts 
with 
reservoir 
Optonol 
Ex-Press
Shunt 
Staar 
Aquaflow 
InnFocus 
MicroShunt 
23 eyes 
DR 
41 eyes 
BORD 
Strabismus and 
diplopia 
Mean 
3.0 
NR 
NR 
0.0 
2.4 
Range 
0.0-5.0
NR
NR
 
 
Choroidal detachment     
        (effusion) 
Mean 
17.5
4
3.2
8.7 
2.4 
Range 
3.8-52.0
0.0-8.0
0.0-5.0
 
 
Suprachoroidal 
hemorrhage 
Mean 
3.3
NR
NR
0.0 
0.0
Range 
0.8-7.0
MR
NR
 
Retinal detachment 
Mean 
3.2
NR
NR
0.0 
0.0
Range 
1-6.4
NR
NR
 
Corneal edema or 
decomposition 
Mean 
7.3
NR
3.6
17.4d 
14.6
Range 
0.0-27.0
NR
3.6-3.6
 
Cataract formation or 
progression 
Mean 
2.5
NR
11.9
0.0 
0.0 
Range 
2.5-2.5
NR
0.0-31.0
 
 
Bleb problems (leaks, 
Tenon’s cyst, blebitis) 
Mean 
3.6
5.6
23.2
8.7 
2.4
Range 
1.0-8.2
5.2-6.0
7.7-40.0
 
Endophthalmitis 
Mean 
3.3
2.0
0.0c
0.0 
0.0
Range 
1.6-5.0
2.0-2.0
0.0-0.0c
 
Visual acuity decreasee 
Mean 
21.8
NR
10.8c
4.3f 
2.4g
Range 
0.0-33.0
NR
10.8-10.8c
 
aThis value excludes patients with IOP values at exactly 5 or hypotony at 1 day postop only.   
bNo differentiation between acute and chronic. 
cOnly the PMA study of the Aquaflow included data in these areas. 
dCorneal edema observed was the result of cataract surgery done at the same time; no decomposition was 
observed. 
eDefined as > 2 lines of vision loss 
fOccurred in 1 patient and considered unreliable because of patient mental state 
gTemporary decrease in VA but resolved by 1 year follow-up 
 
 
                   Overall Summary of Ongoing InnFocus MicroShunt Clinical Studies 
 
InnFocus has studied the implantation results of the present device design of the InnFocus 
Glaucoma Drainage System in the ongoing studies summarized above.  The summary of the 
preliminary findings is as follows: 
 
 No biocompatibility issues have been observed with the device. 
 
 In all cases, the InnFocus MicroShunt was successfully placed through the needle tract without 
damage to the device.