1

Developed in collaboration

New Minimally Invasive Glaucoma Surgery Options

Leon W. Herndon Jr., MD

What Is MIGS? • Smart weapons, targeting the enemy, with minimal to no

collateral damage

• Ab interno

• Must have minimal alteration of the tissue– No conjunctival incision

• Must be safe

• At least modestly efficacious

• Rapid recovery

Fingeret M, et al. Optom Vis Sci. 2018;95:155-62.

2

Bleb Complications

Glaucoma Surgery: The New Frontier• MIGS is preeminent in the minds of doctors, patients, industry, and

the ophthalmology media

• With so much churning in the ophthalmic field, how can we find clarity and establish practice patterns?

• Can we practice evidence-based medicine?

• How do we pick the right procedure for any given patient?

• Can we individualize the treatment of glaucoma?

• How many different treatment modalities can one surgeon handle?

3

MIGS—A New Philosophy• Glaucoma surgery was reserved for

patients losing vision despite maximum medical therapy

• Reserving it as a last resort was appropriate because of the high associated risks

• The hallmark of MIGS, however, is safety

Francis BA, et al. Ophthalmology. 2011;118:1466-80.

Patient Profiles: New ProceduresMIGS-Type ProceduresAb Interno Schlemm’s/Suprachoroidal

• Mild-moderate disease

• Open-angle

• Modest IOP target (ie, 15-16 mm Hg)

• Able to tolerate some meds

Trabeculectomy-Type Procedures

• Moderate-advanced disease

• Progressing normal pressure glaucoma

• Open or narrow angle

• Low IOP target (ie, < 13 mm Hg)

• Intolerant to most meds

Saheb H, et al. Curr Opin Ophthalmol. 2012;23:96-104.

4

Implant PlacementAnatomical Placement

External Bypass –subconjuctival space

Inflow

1 Trabecular Micro-Bypass/Schlemm’s Canal

1Trabecular

Outflow2 Suprachoroidal Space

2

Uveoscleral Outflow

Gedde SJ, et al. Am J Ophthalmol. 2012;153:789-803.

33 External Bypass/

Subconjunctival Space

FDA PMA MIGS CLASS

GlaukosiStent 2012 Trabecular Micro-Bypass

GlaukosiStent Inject 2018 Trabecular Micro-Bypass

IvantisHydrus 2018 Trabecular Bypass

AlconCyPass 2016 Suprachoroidal

AllerganXen 2016 Subconjunctival/External

Overview of the MIGS Landscape

Fingeret M, et al. Optom Vis Sci. 2018;95:155-62.

5

CLASS

EllexABiCSight Sciences Visco360; Omni

Canal/Trabecular Dilation

New World MedicalKahook Dual Blade (KDB)Sight SciencesTrab360; Omni

Trabecular Meshwork Removal

NeoMedixTrabectome Trabecular Meshwork Removal

Overview of the MIGS Landscape

Putting MIGS Into Perspective

6

MIGS Approaches:Trabecular Micro-Bypass

Second-Generation Trabecular Micro-Bypass Injector

• Heparin-coated titanium

• Dimensions: 360 x 230 μm with radial symmetry

• Injected through the trabecular meshwork into Schlemm's canal

• Treatment consists of implantation of two stents

Fingeret M, et al. Optom Vis Sci. 2018;95:155-62.

7

Second-Generation Trabecular Micro-Bypass Procedure• Step 1. Approach perpendicular to the tissue• Step 2. Penetrate the tissue with trocar• Step 3. Lightly press on the TM (or dimple), hold

steady, then deploy stent

Package insert.

One, Two, or Three Trabecular Bypass Stents StandaloneDose-Response Study

Note: final numbers in manuscript different than this graph.Katz LJ, et al. Clinical Ophthalmology. 2015;9:2313-20.

Mea

n (

+/-

SD

) IO

P, m

m H

g

Screening(n = 40, 39, 40;

119 overall)

20.420.119.8

6

10

14

18

22

26

Baseline(n = 40, 39, 40;

119 overall)

Day 1(n = 40, 39, 40;

119 overall)

Week 1(n = 40, 39, 40;

119 overall)

Month 1(n = 40, 39, 40;

119 overall)

Month 3(n = 40, 39, 40;

119 overall)

Month 6(n = 40, 39, 40;

119 overall)

Month 12(n = 40, 39, 40;

119 overall)

Month 18(n = 20, 20, 20;

60 overall)

24.925.025.0

Dose Response Seen With 4– to 7–mm Hg IOP Reductions From Screening and 90+% Medication Reductions

One stentTwo stentsThree stents

12.111.811.5

12.012.212.3

12.612.212.0

12.812.012.8

13.413.312.9

14.212.812.2

16.013.812.3

8

12

16

20

24

28

PRE 3M 6M 1Y 1.5Y

25.6 ± 5.5

13.6 ± 2.3

14.2 ± 2.114.6 ± 2.3

13.5 ± 1.9

15.1 ± 2.6

13.0 ± 1.9 13.1 ± 1.4

14.1 ± 2.1

26.3 ± 4.9

Mea

n ±

SD

IO

P, m

m H

g

Naïve Eyes: 12.5–mm Hg IOP decrease (47% reduction)Eyes With Prior Sx: 12.2–mm Hg IOP decrease (45% reduction)

Naïve to surgery (n = 33)Prior glaucoma surgery (n = 32)

Trabecular Bypass Stent Standalone or + Phacoin Naïve or Prior Glaucoma Surgery PatientsCase Series—IOP Through 18M

Hengerer F. Poster presented at AAO 2016; Chicago, IL.

Postoperative Adverse Events

Package insert.

Postoperative Events

Cataract Surgery With Trabecular

Bypass StentN = 386 n (%)

Cataract Surgery Only

N = 119n (%)

Ocular surface disease 62 (16.1%) 20 (16.8%)

Stent obstruction, partial or complete, regardless of how long the obstruction is present 24 (6.2%) NA

Any intraocular inflammation (non-preexisting) remaining or arising after the protocol’s specified medication regimen is complete

22 (5.7%) 5 (4.2%)

Secondary surgical intervention 21 (5.4%) 6 (5.0%)

Ocular allergies 11 (2.8%) 4 (3.4%)

Loss of BSCVA of 2 lines or more (10 letters or more on ETDRS chart) at or after 3 months postoperative 10 (2.6%) 5 (4.2%)

Posterior vitreous detachment 10 (2.6%) 5 (4.2%)

Foreign body sensation 9 (2.3%) 0 (0.0%)

Blurred vision/visual disturbance 9 (2.3%) 2 (1.7%)

Extraocular inflammation 9 (2.3%) 2 (1.7%)

Epiretinal membrane 9 (2.3%) 3 (2.5%)

IOP increase ≥ 10 mm Hg vs baseline IOP occurring at ≥ month 1 8 (2.1%) 1 (0.8%)

Perioperative ocular pain within 14 days of surgery 8 (2.1%) 1 (0.8%)

Vitreous floaters 9 (2.1%) 3 (2.5%)

Corneal abrasion 8 (2.1%) 4 (3.4%)

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Schlemm’s Canal Microstent Overview

Evolution of Canal Stenting

BYPASS

iSTENT (2012)

BYPASS + ADDED COVERAGE

iSTENT INJECT (2018)

BYPASS + 90° SPAN + SCAFFOLD

HYDRUS MICROSTENT (2018)

Package insert.

10

Schlemm’s Canal Microstent: Ab Interno Canal-Based MIGS

BYPASS

Courtesy of Jason Jones, MD

24-Months Postoperative

Inlet

SCAFFOLD

Schlemm’s Canal in Natural State

Schlemm’s Canal With Microstent

Gong H, et al. Poster #115.American Glaucoma Society; 2012; NY

Republished with permission from the Association  for Research in Vision and Ophthalmology. Hays CL, et al. Invest OphthalmolVis Sci. 2014;55:1893‐900; permission conveyed through Copyright Clearance Center Inc.

Reprinted from Samuelson TW, et al; HORIZON Investigators. Ophthalmology. In press with permission from Elsevier

90° SPAN

90ºOptimal Outflow

Tri-Modal Mechanism of Action

Brandao L et al. J Opthalmol. 2013; 2013:705915

Schlemm’s Canal Microstent• Flexible, biocompatible, 8 mm–long microstent

• Made out of 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

View From Anterior Chamber

Windows

Package insert.

11

Real-Time Confirmation of Accurate Delivery

Video courtesy of I. Paul Singh, MD.

Visual Confirmation of Proper Placement—No Need

for Targeting

Reliable & Efficient Access to Multiple Collector Channels

Dye Test Verifies Outflow in Stented Quadrant

Video courtesy of Ike Ahmed, MD

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HORIZON Clinical Trial

Overview

Nu

mb

er

of

Ra

nd

om

ize

d P

ati

en

ts

HORIZON: Largest Ever MIGS Pivotal Trial

1. Package insert. 2. Vold S, et al. Ophthalmology. 2016;123:2103-12. 3. Package insert. 4. Samuelson TW, et al. Ophthalmology. In press.

Enrolled US Pivotal Trials(MIGS + Phaco vs Phaco Alone)

239

iStent GLAUKOS1

505

CyPassALCON2

505

iStent Inject

GLAUKOS3

556

HydrusMicrostentIVANTIS4

US ONLY 9 COUNTRIES IN 3 CONTINENTS

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Eligibility • Inclusion: Mild/moderate POAG (VF MD ≥ 12 dB), cataract, 1-4 medications, no prior glaucoma surgery, ± prior SLT

Wash-Out & DIOP • After 4-week wash-out: mean DIOP 22-34 mm Hg

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

12 & 24M Wash-Out

• Primary endpoint: 20% reduction in washed-out DIOP at 24 months

• Secondary endpoint: Change in mean washed-out DIOP at 24 months

• Medications: mean and counts at each visit

• Statistics: > 90% power for primary endpoint; ITT analysis

Kuldev Singh, MD, MPH, Medical Monitor 

MS n = 369

Phaco Only n = 187

2:1 randomization

Cataract SurgeryN = 556

• Treatment: 2:1 randomization in the OR to MS or phaco only after successful PC IOL

HORIZON Trial: Study Design

Samuelson TW, et al; HORIZON Investigators. Ophthalmology. In press.

Demographics and Preoperative Status

Patient CharacteristicMS

n = 369No Stentn = 187

Age, years 71.1 ± 7.9 71.2 ± 7.6

OD study eye, % 48.2% 49.2%

EthnicityAsianBlack or AfricanCaucasianOther

5.7%12.2%78.9%3.3%

5.9%8.0%

81.8%4.3%

Glaucoma medications1234

52.6%27.1%17.6%2.7%

54.0%25.7%15.0%5.3%

Ocular and Glaucoma Status

MSn = 369

No Stentn = 187

BCVA, mean 20/40 20/40

VF, MD -3.6 ± 2.5 -3.6 ± 2.6

Corneal thickness, 548 ± 32 549 ± 35

Prior SLT 15.7% 15.0%

Medicated IOP, mm Hg(mean medications)

17.9 ± 3.1(1.7)

18.1 ± 3.1(1.7)

Washed-out DIOP, mm Hg

25.5 ± 3.0 25.4 ± 2.9

Samuelson TW, et al; HORIZON Investigators. Ophthalmology. In press.

14

85.9%77.2%70.1%

57.8%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

12 Months 24 Months

ITT analysisI-bars represent 95% confidence intervals

Δ = 15.9% P < .001

Δ = 19.5% P < .001

Increasing Treatment Effect Through 24 Months

HORIZON: Primary Endpoint20% Reduction in Washed-Out DIOP

Reprinted from Samuelson TW, et al; HORIZON Investigators. Ophthalmology. In press with permission from Elsevier

n = 369 n = 187n = 369 n = 187

Microstent (HM)No stent

-8.5-7.6

-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

12 Months 24 Months

Δ = -2.1 mm Hg P < .001

Δ = -2.3 mm HgP < .001

ITT analysisI-bars represent 95% confidence intervals

Largest IOP Reduction of All MIGS Pivotal Trials to Date

HORIZON: Secondary EndpointChange in Washed-Out DIOP

Reprinted from Samuelson TW, et al; HORIZON Investigators. Ophthalmology. In press with permission from Elsevier; Vold S, et al. Ophthalmology. 2016;123:2103-12; Package inserts

Microstent (HM)No stent

n = 369 n = 187n = 369 n = 187

Mea

n C

han

ge

in D

IOP,

m

m H

g

15

81% 78%

51% 48%

30%

40%

50%

60%

70%

80%

90%

100%

% U

nm

edic

ated

at

Vis

it

24 MonthsΔ = 30%P < .001

n = 187 phaco

Largest Treatment Effect of All MIGS Pivotal Trials to Date

HORIZON: Medication-FreeMedication-Free 0-24 Months

Reprinted from Samuelson TW, et al; HORIZON Investigators. Ophthalmology. In press with permission from Elsevier; Vold S, et al. Ophthalmology. 2016;123:2103-12; Package inserts

Microstent (HM)No stent

24M18M12M6M3M1MPreoperativeWash-Out n = 369 HM

n = 187 phaco

Cumulative Adverse Events Through 24 Months

Intraoperative EventsMS

n = 369No Stentn = 187

Device malposition 1.6% 0

Hyphema 1.1% 0

Postoperative eventsMS

n = 369No Stentn = 187

IOP-related events Trabeculectomy/GDDIOP spike (> 10 mm Hg over baseline > 30 days)Paracentesis > 7 daysHypotony 6 mm Hg 1 day

0.8%a

00.5%0.3%

0

5.8%2.1%2.7%0.5%

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

aP < .05 vs control.Samuelson TW, et al; HORIZON Investigators. Ophthalmology. In press.

16

Q&A

© 2018

Unless otherwise indicated, photographed subjects who appear within the content of this activity or on artwork associated with this activity are models;

they are not actual patients or doctors.

MIGS: Abbreviations and Acronyms BSCVA = best spectacle-corrected visual acuity DIOP = diurnal intraocular pressure ETDRS = Early Treatment Diabetic Retinopathy Study GDD = glaucoma drainage device HM = Hydrus microstent IOP = intraocular pressure ITT = intention-to-treat MD = mean deviation MIGS = minimally invasive glaucoma surgery MS = microstent OD = oculus dexter (right eye) OR = operating room PAS = peripheral anterior synechiae PC IOL = posterior chamber intraocular lens PMA = premarket approval POAG = primary open-angle glaucoma SD = standard deviation SLT = selective laser trabeculoplasty TM = trabecular meshwork VF = visual field