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%)
9
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
12
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
13
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