Anti-VEGF Treatment and Glaucoma€¦ · Bausch & Lomb, Glaukos, Ivantis, Novartis, Optovue,...
Transcript of Anti-VEGF Treatment and Glaucoma€¦ · Bausch & Lomb, Glaukos, Ivantis, Novartis, Optovue,...
10/12/2019
1
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.
10/12/2019
2
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† CyPass withdrawn from the market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
7
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
10/12/2019
3
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
10/12/2019
4
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
10/12/2019
5
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
10/12/2019
6
OD OS
10/12/2019
7
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
10/12/2019
8
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
10/12/2019
9
-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
10/12/2019
10
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%
55
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.
10/12/2019
11
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.
10/12/2019
12
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
10/12/2019
13
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
10/12/2019
14
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
10/12/2019
15
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)
10/12/2019
16
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.
10/12/2019
17
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
10/12/2019
18
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
10/12/2019
19
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