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Robert P Wooldridge, OD, FAAO

Speakers Bureau for Aeri, Alcon Surgical, Bausch & Lomb, Glaukos, Ivantis, Novartis, Optovue, Synemed, Telscreen

Bypass trabecular meshwork or use

suprachoroidal approach

Usually performed in conjunction with cataract surgery

More effective in lowering IOP than Phacoalone

Easier for surgeon and patient than trabeculectomy though less effective

May reduce or eliminate dependence on meds

• Intervene earlier in disease and lower IOP to reduce morbidity of progression

• Reduce the need for more aggressive surgical options while preserving that option

• Reduce medication burden

• Some procedures limited to use in conjunction with cataract surgery

• Some are not restricted to use with CE

Ab-interno approach◦ Clear corneal micro-incision (<2.0mm)◦ Conjunctival sparing

Minimally traumatic◦ Negligible disruption of normal

anatomy/physiology

Reduce the need for more aggressive surgical options while preserving that option

• Reduce medication burden

Significant Treatment Opportunity

One in Five Eyes with Cataract on OHT Medication

3.5M US Cataract Procedures

20.5%Cataract +

Minimum of1 OHT Med

79.5%Cataract Only

718K

Centers for Medicare and Medicaid Services. 2002 – 2007. Medicare Standard Analytical File. Baltimore, MD. 2007.

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Current MIGS Solutions

MILD MODERATE ADVANCED

4.5M US Diagnosed Glaucoma Patients*

Gla

uco

ma P

ati

en

t P

op

ula

tio

n

75% Mild / Moderate 25% Moderate / Advanced

CONVENTIONAL

OUTFLOWBYPASS DEVICES

Schlemm’s CanalSuprachoroidal/ Subconjunctival

• iStent®

• iStent inject®

Hydrus®

Microstent

• CyPass

• XEN®

Conventional outflow first-line therapy for implantable MIGS devices due to optimal risk/benefit

* Market Scope 2017 Glaucoma

Surgical Device Report

† CyPass withdrawn from the market

August 29, 2018

iStent and iStent inject are registered trademarks of Glaukos

Corporation. Hydrus is a registered trademark of Ivantis, Inc.,

CyPass is a registered trademark of Alcon Laboratories, Inc.,

XEN is a registered trademark of AqueSys, Inc., an Allergan

Affiliate

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Goniotomy◦ Trabectome

◦ Kahook Dual Blade (KDB)

iStent

iStent Inject

Cypass

Hydrus Stent

Xen

SEM Procedure

Unroof trabecular meshwork and inner wall of Sclemm’s canal

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The iStent Trabecular Micro-Bypass Stent is indicated for use in

conjunction with cataract surgery for the reduction of intraocular

pressure (IOP) in adult patients with mild to moderate open-angle

glaucoma currently treated with ocular hypotensive medication Dimensions are customized for a natural fit within the 270 µm canal space

iStent is the smallest medical device known to be implanted in the human body and weighs just 60 µg

Self-Trephining Tip

Snorkel0.3 mm

Lumen 120 µm

Designed to be used in conjunction with cataract surgery to safely and effectively reduce IOP while facilitating the eye’s natural outflow in mild to moderate OAG patients.

• Lowers IOP while helping to reduce medication burden

• Decrease risk of IOP fluctuations associated with non-adherence to prescription medication regimens

• Avoid serious complications associated with end-stage filtration and shunt procedures

• Spare the conjunctiva and safely preserve future treatment options

• Minimizes risks of hypotony and bleb related complications

16

• Placed in the eye during cataract surgery

• The complete procedure is typically accomplished in 15 to 20 minutes per eye

• iStent has an overall safety profile similar to cataract surgery

• The natural episcleral back pressure of 8 to 11 mm Hg, minimizes the risk of hypotony1,2

1. Rosenquist R, Epstein D, Melamed S, et al. Outflow resistance of enucleated human eyes at two different perfusion pressures and different extents of trabeculotomy. Curr Eye Res 1989;8:1233-40.

2. Samuelson TW, Katz LJ, Wells JM, Duh Y-J, Giamporcaro JE. Randomized evaluation of the trabecular micro-bypass stent with phacoemulsification in patients with glaucoma and cataract. Ophthalmology 2011;118:459-467

Single Use Disposable Pre-loaded

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Snorkel in TM

• Rails are seated against scleral wall of Schlemm’s canal

• Snorkel sits parallel to the iris plane

Surgical Procedure

Single iStent + Cataract Surgery Achieves IOP < 15 mm Hg Through 3 Years

36%

86

Neuhann TH. Trabecular micro-bypass stent implantation during small-incision cataract surgery for open-angle glaucoma or ocular hypertension: Long-term results. J Cataract Refract Surg 2015; 41:2664–2671.

Lasting Outcomes Through 3 Years (T. Neuhann)

◦ Consecutive series of 62 eyes: decision to implant based on patient desire to reduce topical meds and intent to offer surgical treatment with favorable safety profile

◦ In consistent cohort of 39 eyes followed through 36 months, mean IOP was 14.9 mm Hg, a 36% reduction

◦ Over same period, mean number of topical meds declined from 1.9 to 0.3 or 86%

Prospective, non-comparative, uncontrolled, non-randomized, interventional case series

◦ 19 patients with uncontrolled mild to moderate OAG using 1 or more topical glaucoma medications

Results after mean follow-up of 54 months

◦ 42% of patients were medication free, with mean IOP reduction to 16.1 mm Hg

◦ Mean IOP declined to 16.1 mm Hg versus preoperative medicated IOP of 19.4 mm Hg

◦ Number of topical medications used declined from 1.3 to 0.8

Arriola-Villalobos P et al Br J Ophthalmol

January 2012

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iStent Candidate◦ Mild to moderate open angle glaucoma (no more

severe than a mean deviation of -12dB)

◦ Visually significant cataract is present on examination

◦ Patient desires to reduce dependence on glaucoma medications

Any patient with cataracts being treated for mild to moderate open angle glaucoma with medications may

be a potential candidate for an iStent1

1 See Directions for Use for a complete list of Contraindications and Precautions

Review risks and benefits of possible medical and surgical treatment options

Do NOT promise that the patient will be able to stop some or all of their glaucoma medications

Continue current glaucoma medications through day of surgery

Confirm patient’s VF, ONP and OCT are up to date

Gonioscopy – evaluating for synechia, iris processes, narrow anatomical angles, angle recession or any other abnormalities of the angle structure that may interfere with placement of the iStent

Use normal postoperative medications◦ Antibiotic, steroid, NSAID of choice

Continue current glaucoma medications

Watch for IOP rise related to steroid response

Evaluate IOP in context of target IOP◦ Degree of damage, patient age, likelihood of

progression

If indicated, decrease medical treatment in stepwise fashion

Perform gonioscopy to confirm iStent position

72yo WM treated for COAG Travatan-Z OU

Ran out of Travatan while on vacation in June

Never refilled Rx

IOP R 23 L 18

S/P ½ SLT OS

VA R 20/20 L 20/50

Contrast Sensitivity/Glare 20/100 OU

9 Days post phaco/IOL/iStent OS

VA sc L 20/25

IOP L 18

Still on Travatan-Z OU

One Day Postop

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OD OS

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OD OS

1, 2 or 3 iStents in OAG subjects on drops◦ I stent: 38; 2 stents 41; 3 stents 40

12 month IOP reduction unmedicated IOP </= 15 mmHg◦ 1 stent: 64.9%◦ 2 stents: 85.4% ◦ 3 stents: 92.1%

18 months, mean unmedicated IOP◦ 1 stent:15.9±0.9 mmHg ◦ 2 stents: 14.1±1.0 mmHg◦ 3 stents: 12.2±1.1 mmHg

Month 18 IOP reduction was significantly greater (P<0.001) with implantation of each additional stent, with mean of 1.84 mmHg for three-stent vs two-stent groups and 1.73 mmHg for two-stent vs one-stent groups.

Katz LJ Clinical Oph 11 December 2015iStent in injector

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same potential complications as iStent

TWO stents

• Flexible, 8 mm

• Nitinol (highly biocompatible material used in cardiovascular stents)

• Contoured to match canal curvature

• Three open windows face anterior chamber

• The canal-facing surface is completely open for unobstructed collector channel access

Inlet

Scaffold

VIEW FROM CANAL

Window

s

Hydrus is a registered trademark of Ivantis, Inc.

90° SPAN

90ºOptimal

Outflow

SCAFFOLD

Schlemm’s Canal in Natural State

Schlemm’s Canal with Hydrus

BYPASS

Courtesy of Ike Ahmed, MD

Hydrus 30 Days Postoperative

Inlet

Source: Gong H, Johnstone M, et al. Poster #115

American Glaucoma Society, New York 2012

Source: Hays CL, Toris CB, et al. Invest

Ophthalmol Vis Sci. 2014;55:1893-1900

HORIZON Trial: Study Design1

Eligibility • Inclusion: Mild/moderate POAG (VF MD

>-12dB), cataract, 1-4 medications, no prior

glaucoma surgery, ±prior SLTWash Out & DIOP

• After 4 week wash out: Mean diurnal IOP

22-34 mmHg

1, 3, 6, & 12, 18, 24 M visits

12 & 24M Wash Out

• Primary Endpoint: 20% reduction in washed

out diurnal IOP at 24 months

• Secondary endpoint: Change in mean

washed out diurnal IOP at 24 months

• Medications: mean and counts at each visit

• Statistics: >90% power for primary endpoint;

Intention-to-treat analysis

Kuldev Singh, MD, MPH Medical Monitor

Hydrus

MicrostentN=369

Cataract

Surgery Only N=187

2:1 randomization

Cataract Surgery

(CS)

N=556• Treatment: 2:1 randomization in the OR to

Hydrus or phaco only after successful PC IOL

1. Samuelson TW, Chang DF, Marquis R, et al. A Schlemm canal microstent for intraocular pressure reduction in primary open-angleglaucoma and cataract: The HORIZON Study. Ophthalmology 2019;126:29-37.

ITT Analysis

I Bars are 95% Confidence Intervals

85.9%77.3%

70.0%

57.8%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

12 Months 24 Months

Δ = 15.9%

P < 0.001

Δ = 19.5%

P < 0.001

N=369 N=187N=369 N=187

Increasing treatment effect through 24 Months

48

1. Samuelson TW, Chang DF, Marquis R, et al. A Schlemm canal microstent for intraocular pressure reduction in primary open-angle glaucoma and cataract: The HORIZON Study. Ophthalmology 2019;126:29-37..

Hydrus Microstent + CS

CS Only

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-8.4-7.6

-6.3

-5.3

-10.0

-9.0

-8.0

-7.0

-6.0

-5.0

-4.0

-3.0

-2.0

-1.0

0.0

Me

an

Ch

an

ge

in

DIO

P -

mm

Hg

12 Months 24 Months

Δ = -2.1 mmHg

P < 0.001

Δ = -2.3 mmHg

P < 0.001

ITT Analysis

I Bars are 95% Confidence Intervals

N=369 N=187N=369 N=187

Largest IOP reduction of all MIGS pivotal trials to date1-4

49

1. Samuelson TW, Chang DF, Marquis R, et al. A Schlemm canal microstent for intraocular pressure reduction in primary open-angle glaucoma and cataract: The HORIZON Study. Ophthalmology 2019;126:29-37. 2. Vold S,

Ahmed II, Craven ER, et al; CyPass Study Group. Two-Year COMPASS Trial Results: Supraciliary Microstenting with Phacoemulsification in Patients with Open-Angle Glaucoma and Cataracts. Ophthalmology. 2016;123(10):2103-2112. 3. US Food and Drug Administration. Summary of Safety and Effectiveness Data (SSED): Glaukos iStent® Trabecular Micro-Bypass Stent. US Food and Drug Administration website.

https://www.accessdata.fda.gov/cdrh_docs/pdf8/P080030B.pdf. Published June 25, 2012. 4. US Food and Drug Administration. Summary of Safety and Effectiveness Data (SSED): iStent inject Trabecular Micro-Bypass System.

US Food and Drug Administration website. https://www.accessdata.fda.gov/cdrh_docs/pdf17/P170043b.pdf. Published June 21, 2018.

Hydrus Microstent + CS

CS Only 81% 78%

51% 48%

30%

40%

50%

60%

70%

80%

90%

100%

% U

nm

ed

icate

d a

t V

iist

24 Months

Δ = 30%

P<0.001

N=369 Hydrus and 187 phaco

Largest treatment effect of all MIGS pivotal trials to date1-5

1. Samuelson TW, Chang DF, Marquis R, et al. A Schlemm canal microstent for intraocular pressure reduction in primary open-angle glaucoma and cataract: The HORIZON Study. Ophthalmology 2019;126:29-37. 2. Vold S,

Ahmed II, Craven ER, et al; CyPass Study Group. Two-Year COMPASS Trial Results: Supraciliary Microstenting with Phacoemulsification in Patients with Open-Angle Glaucoma and Cataracts. Ophthalmology. 2016;123(10):2103-2112.

3. US Food and Drug Administration. Summary of Safety and Effectiveness Data (SSED): Glaukos iStent® Trabecular Micro-Bypass Stent. US Food and Drug Administration website.

https://www.accessdata.fda.gov/cdrh_docs/pdf8/P080030B.pdf. Published June 25, 2012. 4. US Food and Drug Administration. Summary of Safety and Effectiveness Data (SSED): iStent inject Trabecular Micro-Bypass System. US Food and Drug Administration website. https://www.accessdata.fda.gov/cdrh_docs/pdf17/P170043b.pdf. Published June 21, 2018.

Hydrus Microstent + CS

CS Only

73%

48%

0%

20%

40%

60%

80%

100%

1 Day 12 months 24 Months 36 Months

% U

nm

ed

icate

d a

t V

isit

36 Months

Δ = 25%

P<0.001

Durable effect through 3 Years

Hydrus Microstent + CS

CS Only

*Data on File – Ivantis, Inc.

Intraoperative EventsHydrus MS + CS

N=369

CS Only

N=187

Device malposition 1.6% 0

Hyphema 1.1% 0

Post Operative EventsHydrus MS + CS

N=369

CS Only

N=187

Incisional glaucoma surgery (Trab/GDD) 0 2.1%

IOP elevation (> 10 mmHg over baseline >30 day follow up) 0.5% 2.7%

Hypotony ≤ 6 mmHg ≥ 1 day 0 0

Uveitis/Iritis requiring steroids 5.6% 3.7%

Layered Hyphema, >2 mm > 1 day 0.5% 0.5%

Laser synechialysis 0.8% 0%

Tissue obstruction/obstructive PAS 3.8% 0%

1. Samuelson TW, Chang DF, Marquis R, et al. A Schlemm canal microstent for intraocular pressure reduction in primary open-angle glaucoma and

cataract: The HORIZON Study. Ophthalmology 2019;126:29-37.

HORIZON: Stable Central ECD*

400

600

800

1000

1200

1400

1600

1800

2000

2200

2400

2600

2800

3000

Preop 3M 6M 12M 18M 24M 36M 48M

HORIZON Trial: Average Central Endothelial Cell Count

Hydrus + CS CS Only

N (CS) 185 180 179 173 170 167 150 137 N (H) 365 352 355 358 354 345 324 301

3M△= 2%p=ns

24M△=4%p=ns

48M△=5%p=ns

*Data on File – Ivantis, Inc.

-2%

-3% -3%

-4% -4%

-5% -5%

-1%-1%

-1%

-3%-3%

-11%-10%

-12%

-10%

-8%

-6%

-4%

-2%

0%

Between Group Difference in Central %ECL through 5 Years

Hydrus - Control Cypass - Control

Hydrus1 vs. CyPass2: Difference in ECL

3M 6M 12M 24M 36M 48M 60M

HORIZON:

79% complete

HORIZON:

31% complete

1. Data on file – Ivantis, Inc.

2. Lane S. Overview of the results from the 5 yr follow up study of the CyPass ® MicroStent. https://drive.google.com/file/d/1jl1JhJjHXNnYXwJ8BCPb4xNlIsZDtxJ5/view.

ESCRS. September 2018.

54

N=203COMPASS

N=174HORIZON

N=149COMPASS

N=438HORIZON

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Safety – Stable from Year 2 to 3

Post Operative EventsCumulative – 2 Years1 Cumulative – 3 Years2

HYDRUS MS

(N=369)

CS Only

(N=187)

HYDRUS MS

(N=369)

CS Only

(N=187)

IOP related events –IOP elevation (≥ 10 mmHg, >30 days)Hypotony ≤ 6 mmHg ≥ 1 month

0.5%0

2.7%0

0.8%0

2.7%0

Loss of BCVA ≥ 2 lines after 3 months 1.4% 1.6% 1.4% 2.7%

Loss of HVF – MD ≥ 2.5 dB 4.3% 5.3% 5.9% 7.4%

Uveitis/Iritis requiring steroids 5.6% 3.7% 5.6% 3.7%

Nickel/allergic reaction 0 - 0 -

Device Obstruction/PASObstructive Non – obstructive

3.8%14.9%

02.1%

3.8%16.3%

02.1%

Laser procedures (tissue ablation/SLT) 0.8% 0.5% 1.6% 2.1%

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1. Samuelson TW, Chang DF, Marquis R, et al. A Schlemm canal microstent for intraocular pressure reduction in primary open-angle glaucoma

and cataract: The HORIZON Study. Ophthalmology 2019;126:29-37.

2. Data on file

IOVS March 2014

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

C (

µL/m

in/m

mH

g)

1 HYDRUS 2 ISTENTS

Pre

Im

pla

nt

OUTFLOW FACILITY

12 Eye Bank Pairs

Pre

Im

pla

nt

Po

st

Imp

lan

t

Po

st

Imp

lan

t

↑72%

P<0.0

5

↑34%

P<0.05

Lumen*

11,300

𝝁𝒎2

ISTENTHYDRUS

MICROSTENT

Lumen†

53,066

𝝁𝒎2

Outflow Comparison: Hydrus Microstent and Two iStents

56

*Lumen area calculated based on published data ref. Directions for Use - US Food and Drug Administration. Summary of Safety and Effectiveness Data

(SSED): Glaukos iStent® Trabecular Micro-Bypass Stent. US Food and Drug Administration website.

https://www.accessdata.fda.gov/cdrh_docs/pdf8/P080030B.pdf. Published June 25, 2012)

†Lumen area calculated based on published data ref. Directions for Use - US Food and Drug Administration. Summary of Safety and Effectiveness Data

(SSED): Ivantis Hydrus® Microstent. US Food and Drug Administration website. https://www.accessdata.fda.gov/cdrh_docs/pdf17/P170034B.pdf. Published

August 10, 2018.

Difference = 38% (P=0.027)

Lumen§

11,300

𝝁𝒎2

ISTENT

Lumen*

5,024

𝝁𝒎2

ISTENT INJECT

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

C (

µL/m

in/m

mH

g)

Pre

Im

pla

nt

OUTFLOW FACILITY

10 Eye Bank Pairs

Pre

Im

pla

nt

Po

st

Imp

lan

t

Po

st

Imp

lan

t

↑10%

P=0.5

3

↑55%

P<0.00

1

Difference = 44% (P=0.001)

AGS 2018 Poster

2 ISTENTS 2 INJECTS

Outflow Comparison: Two iStents and Two iStent injects

§ Lumen area calculated based on published data – (Ref. Directions for Use - US Food and Drug Administration. Summary of Safety and Effectiveness

Data (SSED): Glaukos iStent® Trabecular Micro-Bypass Stent. US Food and Drug Administration website.

https://www.accessdata.fda.gov/cdrh_docs/pdf8/P080030B.pdf. Published June 25, 2012

*Directions for Use - US Food and Drug Administration. Summary of Safety and Effectiveness Data (SSED): iStent inject Trabecular Micro-Bypass System.

US Food and Drug Administration website. https://www.accessdata.fda.gov/cdrh_docs/pdf17/P170043b.pdf. Published June 21, 2018)

* COMPASS allowed 0 medications at baseline (n=87). Average IOP and meds for medicated patients shown (Ref #2). † Mean medication count derived from data in inject SSED (Ref

#3).

§ Included DIOP range was slightly different: 22-34 (HORIZON), 21-33 (COMPASS), 21-36 (INJECT).

HORIZON1 COMPASS2 iSTENT INJECT3

HYDRUS CS Only CYPASS CS Only INJECT CS Only

N 369 187 374 131 387 118

Age 71 ± 8 71 ± 8 70 ± 8 70 ± 8 69 ± 8 70 ± 8

Female - % 56% 56% 53% 55% 58% 54%

Caucasian - % 79% 82% 84% 82% 73% 73%

Visual Field -

MD-3.6 ± 2.5 -3.6 ± 2.6 -3.4 ± 2.9 -3.7 ± 3.0 -3.4 ± 3.3 -3.4 ± 3.1

Mean IOP - mm

Hg (screening)17.9 ± 3.1 18.1 ± 3.1 17.4 ± 2.9 17.6 ± 3.0 17.5 ± 3.0 17.5 ± 2.8

Mean

Medications1.7 1.7 1.7* 2.2* 1.6† 1.5†

Washed out

DIOP§ - mm Hg25.5 ± 3.0 25.4 ± 2.9 24.4 ± 2.8 24.5 ± 3.0 24.8 ± 3.3 24.5 ± 3.1

1. Samuelson TW, Chang DF, Marquis R, et al. A Schlemm canal microstent for intraocular pressure reduction in primary open-angle

glaucoma and cataract: The HORIZON Study. Ophthalmology 2019;126:29-37.

2. US Food and Drug Administration. Summary of Safety and Effectiveness Data (SSED): CyPass® System (Model 241-S) . US Food and Drug Administration website https://www.accessdata.fda.gov/cdrh_docs/pdf15/P150037B.pdf. Published July 29, 2016..

3. US Food and Drug Administration. Summary of Safety and Effectiveness Data (SSED): iStent inject Trabecular Micro-Bypass System.

US Food and Drug Administration website. https://www.accessdata.fda.gov/cdrh_docs/pdf17/P170043b.pdf. Published June 21, 2018.

THREE PIVOTAL TRIALS – MIGS + CSDemographics & Pre Op Status

58

Primary Endpoint ComparisonIOP REDUCTION ≥ 20% AFTER MEDICATION WASH OUT

72.5% 58…

0%

20%

40%

60%

80%

100%

Cypass CS Only

COMPASS: 24 Months2

77.3%

57.8%

0%

20%

40%

60%

80%

100%

Hydrus CS Only

HORIZON: 24 Months1

Intention-to-Treat analysis

N=369 N=187 N=374

Intention to Treat Analysis

N=131

75.8% 61.9

%

0%

20%

40%

60%

80%

100%

Inject CS Only

INJECT IDE: 24 Months3

N=380 N=118

Δ = 14.4% P=0.003

Δ = 13.9% P=0.003

Δ = 19.5% p<0.001

↑34% vs. Phaco

↑25% vs. Phaco

↑22% vs. Phaco

Per Protocol Analysis

1. Samuelson TW, Chang DF, Marquis R, et al. A Schlemm canal microstent for intraocular pressure reduction in primary open-angle glaucoma

and cataract: The HORIZON Study. Ophthalmology 2019;126:29-37.

2. US Food and Drug Administration. Summary of Safety and Effectiveness Data (SSED): CyPass® System (Model 241-S) . US Food and Drug

Administration website https://www.accessdata.fda.gov/cdrh_docs/pdf15/P150037B.pdf. Published July 29, 2016..

3. US Food and Drug Administration. Summary of Safety and Effectiveness Data (SSED): iStent inject Trabecular Micro-Bypass System. US Food

and Drug Administration website. https://www.accessdata.fda.gov/cdrh_docs/pdf17/P170043b.pdf. Published June 21, 2018.

7.6

-5.3

-10.0

-9.0

-8.0

-7.0

-6.0

-5.0

-4.0

-3.0

-2.0

-1.0

0.0HORIZON: 24

Months1

Hydrus CS Only

N = 369 N = 187 N=369 N=166

-7.0

-5.3

-10.0

-9.0

-8.0

-7.0

-6.0

-5.0

-4.0

-3.0

-2.0

-1.0

0.0

COMPASS: 24 Months2

Cypass CS Only

N = 374 N = 131

Intention-to-Treat analysis Intention to Treat Analysis

-7.0

-5.4

-10.0

-9.0

-8.0

-7.0

-6.0

-5.0

-4.0

-3.0

-2.0

-1.0

0.0INJECT: 24

Months3

Inject CS Only

N = 380 N = 118

Δ = 2.3 mm HgP < 0.001

Δ = 1.7 mm HgP < 0.001

Δ = 1.6 mm HgP < 0.001

↑43% vs. Phaco

↑32% vs. Phaco

↑30% vs. Phaco

Per Protocol Analysis

Secondary Endpoint ComparisonDIOP REDUCTION AFTER MEDICATION WASH OUT

60

1. Samuelson TW, Chang DF, Marquis R, et al. A Schlemm canal microstent for intraocular pressure reduction in primary open-angle glaucoma and cataract: The

HORIZON Study. Ophthalmology 2019;126:29-37.

2. US Food and Drug Administration. Summary of Safety and Effectiveness Data (SSED): CyPass® System (Model 241-S) . US Food and Drug Administration

website https://www.accessdata.fda.gov/cdrh_docs/pdf15/P150037B.pdf. Published July 29, 2016..

3. US Food and Drug Administration. Summary of Safety and Effectiveness Data (SSED): iStent inject Trabecular Micro-Bypass System. US Food and Drug

Administration website. https://www.accessdata.fda.gov/cdrh_docs/pdf17/P170043b.pdf. Published June 21, 2018.

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Supra-ciliary SpaceApproved for use in conjunction with cataract surgery Cypass in position Aqueous Flow

Stent placement

Early hypotony Decrease glaucoma meds as necessary

Monitor weekly?

IOP spike It happens

Manage aggressively-Diamox if necessary

Corneal endothelial loss

Voluntary recall August 29, 2018 by Alcon

5-year FU, 27.2 % (44/162) of patients had > 30% loss in ECD.

Related to the amount the device extends into the AC, assessed by the number of visible retention rings

Of the patients that had ECD data at both 2 and 5 years after implantation, mean loss in ECD over the 3-year period was 3.1% when no rings were visible (55 patients), 8.4% with one ring visible (65 patients), 21.0% with two rings visible (26 patients), and 31.4% with three rings visible (eight patients).

Inadequate data on surgical intervention to trim CyPassdevices ◦ no conclusions could be made regarding the impact of

trimming on endothelial cell loss progression.

5-year data suggest that the general rate of cell loss does not plateau at 5 years post-implant.

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FDA advises that all Cypass patients be evaluated periodically for ECD using specular microscopy until the rate of loss stabilizes.

Further advise that all eye care providers evaluate all patients with CyPass to assess device positioning by visualization of the number of retention rings visible on the proximal end of the device. Patients with two or more rings visible upon examination should be evaluated for endothelial cell loss as soon as possible.

Based on the ECD levels and other factors such as age and time post-implantation, the surgeon should determine if additional surgical interventions (that is, trimming, repositioning, removal) are appropriate

Gel stent design

6-mm length, 45-micron lumen diameter1 —about the length of an eyelash3

Gelatin, cross-linked with glutaraldehyde1

Hydrates and minimally swells, softens, and becomes flexible after implantation1

Preloaded, disposable injector1 with a 27-gauge, double-beveled needle2,4,5

Innovative approach

• Requires a small corneal incision1

• The first ab-interno approach to create a new pathway for aqueous flow from the anterior chamber to the subconjunctival space in refractory glaucoma patients1

• XEN® is the first procedure that creates a low-lying, ab-interno bleb in refractory glaucoma2

Minimally Invasive

Inserted using the XEN® Injector via an ab-interno approach, through a small corneal incision.1

In the clinical investigation, standard ophthalmic surgery techniques, viscoelastic, and mitomycin C (0.2 mg/mL) were used before injection.1

Controlled flow throughlumen restriction2

Tenon capsuleadhesions intact2

Undisturbed, low-lying drainage space2

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Study population1

65 patients with refractory glaucoma1

Mean age: 70.0 years1

Prior cataract surgery: 45 (69.2%)1

Prior incisional glaucoma procedure: 41 (63.1%) (eg, trabeculectomy, tube shunt, canaloplasy, trabeculotomy, AquaFlow)1,6

No prior glaucoma procedure and unresponsive to maximally tolerated medical therapy: 10 (15.4%)1,6

Mean cup-to-disc ratio: 0.81

Mean visual field mean deviation (MD) score: -15 dB1

Mean medicated IOP at baseline: 25.1 (± 3.7) mm Hg1

Mean IOP-lowering medications at baseline: 3.5 (± 1.0)1

Primary effectiveness measures6

Proportion of subjects at 12 months achieving ≥ 20% IOP reduction from baseline on the same or fewer number of medications than at baseline

Mean decrease in IOP from baseline to 12 months

Primary safety measures6

• Procedure-related complications

• Biomicroscopic slit lamp and ophthalmoscopy findings

• Ocular adverse events

Established in a phase 3, prospective, multicenter, single-arm, open-label, 12-month, US clinical trial1

XEN® reduced mean IOP by ≥ 25% in

80.8% of eyes.6

15.4% (n = 10/65) of patients had no prior glaucoma procedures.1

• Refractory patients unresponsive to maximally

tolerated medical therapy1

Reduced IOP and medication use at month 121

Results of a prospective, multicenter, single arm, open-label, US clinical trial to evaluate the safety and effectiveness of the XEN® Gel Stent in refractory glaucoma subjects

(N = 65) where previous filtering or cilioablative procedures failed, or IOP was unresponsive to maximally tolerated medication.

Medication washout was not performed; all IOP lowering medications were discontinued on the day of surgery.1

*Baseline 25.1 (± 3.7) mm Hg; 12-month 15.9 (± 5.2) mm Hg.1

Baseline 3.5 (± 1.0); 12-month average 1.7 (± 1.5) medications.1

Mean IOP reduced to

15.9 mm Hg(N = 52) from 25.1

mm Hgat medicated

baseline1,*

Mean IOP- lowering medications reduced

to

1.7(N = 52) from 3.5 at

at medicated baseline1,

Primary Effectiveness Analyses1,a n/N (%)(95% CI)*

Mean ± SE(95% CI)

Proportion of Subjects with 12-Month Mean Diurnal IOP Reduction of ≥ 20% from Baseline on Same or Fewer Medications (N=65)b

76.3%(65.8%, 86.8%)

Mean Diurnal IOP Reduction from Baseline at the 12-Month Visit (N=65)c

-6.4 ± 1.1 mmHg

(-8.7, -4.2)

a Study eyes undergoing glaucoma-related secondary surgical intervention and/or removal of XEN® 45 Gel Stent prior to the 12-month evaluation were considered to be nonresponders.1

Seven subjects in the study underwent needling procedures with mitomycin C; 4 of these subjects were considered responders.1

b Primary effectiveness analysis using observed data and failure for subjects with glaucoma-related secondary surgical intervention and multiple imputations for missing data.1

c Primary effectiveness analysis using observed data & worst within-eye IOP for subjects with glaucoma-related secondary surgical intervention and multiple imputations for missing data. 1

* Exact confidence limits per Clopper-Pearson method.1

Based on t-distribution.1

0 of 65 subjects experiencedintraoperative complications1

◦ 0% surgical complications◦ 0% hyphema◦ 0% conjunctival

perforation◦ 0% iris/lens damage

0 of 65 subjects experiencedpersistent hypotony (IOP < 6 mm Hg at 2 visits > 30 days apart)1,*◦ Hypotony (IOP < 6 mm Hg

at any time): 24.6% (16/65)1

In the Pivotal Clinical Trial

*No clinically significant consequences were associated with hypotony, such as choroidal effusions, suprachoroidal hemorrhage, or hypotony maculopathy. IOP < 6 mm Hg was defined as an adverse event, regardless of whether there were any associated complications or sequelae related to the low pressure. Thirteen cases occurred at the 1-day visit; there were no cases of persistent hypotony, and no surgical intervention was required for any case of hypotony.1

Hypotony

Bleb scarring Needling of bleb

5-FU injection

Bleb failure

Endophthalmitis

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VA OD cc 20/20

IOP R 07 on no meds

Bleb flat, quiet

AC Very shallow

Early PSC

Video

Numerous new procedures available

FAR less invasive than trabeculectomy/tube◦ Faster recovery

◦ More comfortable

◦ Less surgical risks, side effects

◦ Safer

◦ Less effective?

IOP not at target level despite less invasive treatments

Need for very low IOP

Progressive damage despite topical meds and/or SLT when appropriate

Appropriate for most types of glaucoma◦ NVG possible exception

Always consider risks v. benefits◦ Risk of symptomatic LOV affecting QOL v life

expectancy

Document current level of damage

Maintain all glaucoma medications up to day of surgery

Treat blepharitis, dry eyes

Advise patient of surgical goals◦ Decrease IOP-NOT to improve VA!

◦ Trying to prevent additional LOV

◦ No guarantee of no drops needed after surgery

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Filtering too much!◦ Leaking incision

◦ Button hole leak

◦ Bleb dissection

Filtering too little!◦ Scleral flap tied too tight

◦ Scleral flap scarred down

◦ Conj. bleb scarring down

◦ Internal sclerostomy closed

Shallow/flat Anterior Chamber

Corneal folds

Choroidal detachments (late sign)

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Leaking bleb

Excessive filtering

Ciliary body “shutdown”

Chronically leaky bleb

IOP 12-20 despite leak

Treated with ◦ BCL

◦ Prokera amniotic membrane

◦ BCL with dry A. M.

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IOP OD 07 IOP OS 12

Filtering too little!

Early postop period◦ Scleral flap tied too tight

◦ Internal sclerostomy closed

Later postop period◦ Conj. bleb scarring down

◦ Scleral flap scarred down

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Check bleb◦ Flat, shallow?

◦ Encysted?

AC◦ Deep?

◦ Hemorrhage?

◦ Internal sclerostomy open?

◦ Iris to internal sclerostomy?

VA 20/80 IOP 42

VA 20/80 IOP 42

VA sc 20/50 IOP 16

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Trabeculectomy still standard glaucoma procedure◦ BUT MIGS becoming more common

Higher risks than MIGS procedures

Higher potential reward than MIGS◦ i.e. lower IOP

Tube shunts another option with trabeculectomy failure or contraindication