Updates from AMD clinical trials

Updates from AMD Clinical trials
Yasuo Yanagi
Associate Professor, Duke-NUS Medical School
Singapore National Eye Centre, Singapore Eye Research Institute

2
• The presentation is for scientific exchange purpose only
and may include presenter’s own treatment experiences.
• Details of product please refer to local package insert
Disclaimer

Clinical Trials Update
• Anti PDGF-B Pegylated aptamer
• Visual Cycle Modulators
• Anti-inflammatory agents
• Radiation therapy
• Stem cell therapy
• RPE protection agents
• Drugs that increase choroidal blood flow
• Other clinical trials

Anti PDGF-B Pegylated aptamer
FovistaTM: Anti PDGF-B Pegylated aptamer which strips the
pericytes making the CNV susceptible to anti VEGF drugs.
Phase 2b
Fovista® and Lucentis ®
10.6letters
Lucentis® monotherapy
6.5letters (p=0.019).
No significant safety issues
Phase 3 ongoing
 2 trials
in combination with Lucentis®
 1 trial
in combination with each of
Avastin® or Eylea®

5
Visual Cycle Modulators
Lipofuscin accumulation: a hallmark of aging RPE cells
Toxic properties of A2E may interfere with RPE function via various mechanisms.
Emixustat Hydrochloride (ACU-4429),
(NCT01802866) Acucela Inc, Phase II/III finished
- failed to demonstrate a significant
difference in lesion growth rate from
placebo.
Fenretinide, (NCT00429936) Sirion Therapeutics, Inc.
(Acquired by Alcon (NYSE: NVS) and Bausch + Lomb)
Phase II completed
ALK-001, NCT02230228 Alkeus Pharmaceuticals, Inc.
Phase I Completed
1.6
1.7
1.8
1.9
Lesion growth rate (24months)

6
Anti-inflammatory agents
Polymorphisms in the complement pathway have been shown to be associated with AMD.
Inhibition of the alternative complement pathways represents a viable therapeutic approach for halting
AMD and GA.
MAHALO phase II study suggested that the treatment effect with lampalizumab (Fab of a humanised,
monoclonal antibody directed against complement factor D) might be stronger in patients positive for the
CFI genetic biomarker.
Terminal complement
components (MAC)
C5b-9
C3b
C3b
Bb C3 convertase
C3b
C3b
Bb
C3b
C5 convertase
bloodstream
Host
cell
Non-ac ve
surface
FactorH
iC3b
Factor I
FactorH
C3bFactorB
C3
C3a
C3
FactorB
Precursor
Proinflammatory
fragments
C5
LiverLampalizumab (NCT02745119)
Roche initiated Phase III extension trial for Geographic atrophy
Eculizaumab (NCT00935883), Alexion Pharmaceuticals completed Phase II
Sirolimus (NCT00766649) National Eye Institute Completed Phase I/II
ARC-1905 (NCT00950638) Ophthtech Completed Phase I
Glatiramer acetate (NCT00541333) the New York Eye & Ear Infirmary Phase I
suspended participiant recruitment.

7
Stem cell therapy
• Replacement of the
degenerating RPE cells
with stem cell derived
RPE cells before the
photoreceptors are
damaged.
• Delivery of trophic factor
by stem cell
transplantationAMD (GA)
Stem cells
Transplantation
MA-09-hRPE, hESC derived RPE (NCT01344993)
Ocata phase I/II currently recruiting
cf. Intravitreal autologous Bone Marrow CD34+ cells in patients with advance retinopathy
In AMD/DR/RVO/RP/HMD where VA <20/100 for more than 3 months
Phase I showed safe and subtle improvement in AO-OCT, ERG, FA.

8
Drugs that increase choroidal blood flow
Improving choroidal blood flow could facilitate the removal of
metabolic wastes for RPE, Bruch’s membrane and photoreceptor cells to halt AMD disease
progression.
MC-1101 (NCT02127463) Topical ophthalmic solution
MacuCLEAR Inc, Phase II/III currently recruiting.
MC-1101 was shown to increase choroidal blood flow by 55% in 60min.

RPE protection agents
Amyloid-b was observed in druse and correlated with
the location of degenerating photoreceptor and RPE
cells.
MRZ-99030 (NCT01714969) Merz Pharmaceuticals GmbH Phase I completed
RN6G (NCT01003691) Pfizer Phase I completed
GSK933776 (NCT01342926) GlaxxoSmithKline Phase II ongoing

Radiation therapy
Selectively targets proliferating endothelial cells by inhibiting cytokines.
24Gy in two 12 Gy (Sr-90) radiation resulted in less number of RBZ injections
compared to early clinical trials where RBZ was used as PRN.
The study of Sr-90 bera radiation with RBZ to treat AMD (VARBERNET) failed to
demonstrate a visual benefit.
IRAY Radiotherapy system (Oraya Therapeutics Inc,) delivers low-voltage X-rays
for the treatment of wet AMD (investigational system devise and not available
for sale)
The INTERPID study
– To confirm the safety and effectiveness of low voltage SRT using the IRAY system for
subjects with recurrent leakage to neovascular AMD as determined by decreasing the
number of RBZ inejctions required during the first 12 months.
– A single dose of SRT significantly reduces intravitreal injections over 2 years.
– The best response occurs when active AMD lesions fit within the treatment zone.

DARPin: Designed ankyrin repeat proteins
Other clinical trials
• Abicipar Pegol (anti-VEGF DARPin®; Allergan)
Phase 2at 16weeks
Abicipar Pegar (2.0mg)
8.2letters
8.2letters
5.3letters
Phase 3 ongoing
Phase 2at 20weeks
9.0letters
7.1letters
4.7letters

12
Update on clinical studies: Outline
1. Anti-VEGF therapy is a major long-term therapeutic advance for neovascular AMD;
however, VA decreases progressively in the long-term
due to macular atrophy and increased CNV size.
2. It may not be imperative to resolve all fluid to achieve good VA.
Subretinal fluid may be associated with better VA.
3. Aflibercept more effectively induces polyp regression for PCV than Ranibizumab,
but we still do not know the best treatment option.
4. “Treat and extend” might be better than “PRN”, but there remains issues in real world
practice

13
Laser
photocoagulation
SMDS
1982 1993 1999 2000 2004 2005 2006 2009 2011
MPS TAP VISION
VIEW
PIER
Verteporfin
(Visudyne)
Japan: 2004-
Bevacizumab
(Avastin)
Off-label use
Pegaptanib
(Macugen )
Ranibizumab
(Lucentis)
Japan: 2008-
20121975 1994
IVAN
2013
HARBOR
Aflibercept
(EYLEA)
Japan: 2012-
CATT
ANCHOR
MARINA
Maintenance therapy: evolution of concept
7 year outcome
5 year
outcome

7 year Vision Outcomes in Subjects from the MARINA, ANCHOR
and HORIZON studies
Initial study
(MARINA,ANCHOR) HORIZON SEVEN-UP
Monthly Real world treatment
-10
-5
0
5
10
15
+11.2
+1.7
-8.6
+9.0
+4.1
+2.0
1 2 3 4 5 6 7.3 year
-15
-20
**
***
Ranibizumab treated: SEVEN-UP
Ranibizumab treated: HORIZON
ETDRSletters
(n=65)
(n=50)
(n=65)
(n=388)
Rofagha S et al; SEVEN-UP Study Group. Ophthalmology. 2013
Bhiaitkul et al; SEVEN-UP Study Group. Ophthalmology. 2015
6.8 injection
*
* p＜0.005
** p＜0.0001
***p＜0.001
(vs. SEVEN-UP 7.3y)
SEVEN-UP study
Primary end point
>20/70: n=24(36%)
Macular atrophy: 2.22mm2, a growth rate of 0.28mm2/year [present in 98%]
Further loss in visual acuity was observed in the follow-up for about 7 years.

Fellow eye comparisons of SEVEN-UP study
• Within-patient comparisons at year 7
(For the 35% of subjects with exudative AMD in both eyes at baseline)
 Better vision in the study eye in 82%
 Better mean final vision in study eyes
(54.7 vs. 27.3 letters in fellow eyes).
 Less severe MA in study eye than the fellow eye in 88%
of patients.
(mean area 2.8 mm2 vs. 5.8 mm2 in the fellow eyes).
• MA severity
– Significantly correlated with final fellow eye vision outcome
– Intereye vision difference corresponded to the degree of MA asymmetry
Bhisitkul et al., Ophthalmology 2016;123:1269-1277
Fellow eyes: Preclusion of anti-VEGF treatment for at least the first 2 yrs,
and physician-discretion treatment thereafter
Fellow eye -> Severe MA despite less intensive treatment
“MA occurs secondary to exudative episodes.”

CATT Follow up study
• Patients were assigned randomly to ranibizumab or bevacizumab and to 1 of 3 dosing regimens.
• After 2 years, patients were released from the clinical trial protocol.
• At 5 years, patients were recalled for examination.

17
Maguire MG et al., Ophthalmology, 2016
overall and by drug assigned in the clinical trial
Vision gains during the first 2 years were not maintained at 5 years.
-3.0 letters
14.8 injections
+8.0 letters
Mean total lesion area
12.9 mm2, a mean of 4.8 mm2 largerthan at 2 years.
SD-OCT
83% had fluid (61% intraretinal, 38% subretinal, and 36% subRPE).
Geographic atrophy
41 %(213) [subfoveal in 85 eyes (17%)]
Mean foveal total thickness
278 mm, a decrease of 182 mm from baseline and 20 mm from 2 years.
The retina was abnormally thin(<120 mm) in 36%of eyes.
Expansion of the size of the total neovascular complex
Persistence of fluid
Increased macular atrophy

18
Distribution of visual acuity over time
Maguire MG et al., Ophthalmology, 2016
20/40 or better: 50%
20/20 or better: nearly 10%
“These results would have been unimaginablein the era before the
availability of anti-VEGF therapy”
However, the results highlight the need for agents that can prevent or
minimize macular atrophy and expansion of the total
neovascular lesion.

19
Outline
practice

Baseline
RV=(0.7p)
RV=(0.8)
RV=(0.7)
RV=(0.7p)
RV=(0.7p)
RV=(0.7)
RV=(0.7)
4w
4w
4w
4w
6w (10w from previous dosing)
6w (10w from previous dosing)
+2w (6w from previous dosing)
4w
1+PRN dosing is adopted due to old age
“Real world practice”
79 y.o. Male 1+PRN

RV=(0.7)
RV=(0.6p)
RV=(0.6)
RV=(0.6)
RV=(0.6p)
RV=(0.6p)
RV=(0.6p)
4w
6w
4w (20w from previous dosoing
6w
4w
6w
4w
Subretinal Fluid
may be associated with
better VA.2
Stringent retreatment
criteria
=“no tolerance” protocol
“If fluid is detected, additional doses
must be administered as soon as
possible even if there is no change in
visual acuity.”1
1. CATT, IVAN, HARBOUR
2: Ophthalmology, Volume 123, 2016,

Macular morphology & Visual acuity in the 2nd year of CATT
Ophthalmology, Volume 123, 2016, 865-875
Participants: CATT participants*
Eyes with SRF in the foveal center
had better mean VA than eyes with
no SRF.
Eyes with IRF in the foveal center
had worse mean VA than eyes
without IRF.
Ongoing study (FLUID study) will determine whether less aggressive anti-VEGF therapy is
appropriate in eyes with persistent SRF or smaller amounts of fluid.
*: Eyes with even a small amount of fluid received anti-VEGF therapy per the treatment protocol.

Subretinal hyperreflective material (SHRM) in
predicting treatment outcomes
–76.6% (908) at baseline
–54% persisted at 2 years
Mean VA (letters)
• SHRM (-) 73.5
• Foveal center 63.9
–More frequent incident of GA or Scar in eyes with SHRM †
Ophthalmology, Volume 122, 2015, 1846–1853
†: Scar was present in 45.3% at 2 years.
SHRM is likely composed of
many elements, including
fluid, fibrin, blood,
scar, and CNV,with the
composition changing over time.
Participants: The 1185 CATT participants.

Macular morphology and VA
Summary of recent findings
Factors associated with poor VA
 Intraretinal fluid
(Persistent or primary PED who developed secondary intraretinal cyst when
switching to PRN1)
 Cystoid macular edema (FA)
 Abnormally Thin retina (<120μm)
 Macular atrophy involving the foveal center
 Subretinal tissue complex
(SHRM, RPE, and RPE elevation)
Factors associated with good VA
Subretinal fluid (foveal)
1: Schmidt-Erfurth et al., VIEW 2 study group Ophthalmology 2015.

25
Outline
practice

27
0.5q4 2q82q4
Overall Population
Asian*
Demographics and baseline patient characteristics:
Asian patients ≈ 10%
n 60 70 66 73
Age, mean (SD), years 67.6 (8.6) 68.9 (8.3) 72.0 (9.9) 68.9 (8.4)
Male, n (%) 45 (75) 51 (72.9) 47 (70.1) 47 (64.4)
Baseline VA, mean (SD), ETDRS letter 53.0 (13.7) 52.6 (14.3) 48.5 (13.5) 52.9 (13.9)
Baseline CRT, mean (SD), μm 344 (147) 329 (120) 327 (138) 318 (142)
*Asian patients, including Indians, entering 2nd year; ETDRS, early treatment
diabetic retinopathy study; CRT, choroidal retinal thickness; VA, visual acuity;
Rq4, ranibizumab 0.5 mg every 4 weeks; 2q4, Aflibercept 2 mg every 4
weeks; 0.5q4, Aflibercept 0.5 mg every 4 weeks; 2q8, Aflibercept 2 mg every
8 weeks
Schmidt-Erfurth et al. Ophthalmology 2013; ePub ahead of print.
n 595 613 597 607
Age, mean (SD), years 75.6 (8.7) 75.9 (8.4) 76.5 (8.5) 75.8 (8.8)
Male, n (%) 254 (42.7) 243 (39.6) 283 (47.4) 254 (41.8)
Baseline VA, mean (SD), ETDRS letter 53.9 (13.4) 54.0 (13.6) 53.6 (13.8) 53.6 (13.5)
Baseline CRT, mean (SD), μm 321 (110) 325 (113) 320 (112) 334 (118)
Rq4
0.5q4 2q82q4Rq4

28
Efficacy in Asian patients at Week 52
*Including Indians. †Change from baseline; Rq4, ranibizumab 0.5 mg every 4
weeks; 2q4, Aflibercept 2 mg every 4 weeks; 0.5q4, Aflibercept 0.5 mg every
4 weeks; 2q8, Aflibercept 2 mg every 8 weeks
Schmidt-Erfurth et al. Ophthalmology 2013
• Effects in Asian patients were consistent with the overall
population
Asian* All
Number of patients 60 595 70 613 67 597 73 607
Patients gaining ≥15 letters, n (%) 25 (41.7) 193 (32.4) 24 (34.3) 205 (33.4) 28 (42.4) 178 (29.8) 25 (34.2) 188 (31.0)
Change in CRT,† mean (SD), μm -151 (164) -128 (116) -165 (127) -138 (113) -143 (117) -123 (111) -139 (141) -139 (117)
Asian* All Asian* All Asian* All
Rq4 2q4 0.5q4 2q8
11.0
9.6
12.2
9.48.7 9.3
8.3 8.4
0
2
4
6
8
10
12
14
Rq4 2q4 0.5q4 2q8
MeanchangeinVAfrom
baseline(letters)
Asian* All

Japanese case series summary:
Treatment-naive PCV
Author Institution Design Duration N (eyes)
IVA
No. of
inj.
VA (logMAR)
Pre-IVA Post-IVA
Ijiri S, 20151
Kanazawa University
Graduate
School of Medical
Science
Prospective,
consecutive
3 33 3 0.40 ± 0.34
0.22 ± 0.20
(P<0.001)
Koizumi H,
20152
Tokyo Women’s
Medical
University
Retrospective,
consecutive
3 56 3
0.40 ±
0.37†
0.28 ± 0.33†
(P<0.0001)
Inoue M,
20144
Yokohama City
University Medical
Center
Prospective,
consecutive
6 16 >3 0.36 ± 0.33
0.26 ± 0.35
(P<0.05)
Hosokawa M,
20155
Okayama
University Graduate
School of
Medicine
Prospective,
consecutive
6 18 4 0.41 ± 0.38
0.297 ±
0.334
(P=0.016)
Oishi A, 20156
Kyoto University
Graduate School of
Medicine
Prospective, non-
randomized
12 39 7 0.29 0.08 ± 0.04
Yamamoto A,
20157
Kyorin University
School of Medicine
Retrospective,
multicenter,
consecutive
12 83 7 0.31 ± 0.32
0.17 ± 0.28
(P<0.001)
*PCV investigated as part of a larger AMD study; †Full data set comprising patients with PCV and typical AMD. AMD, age-related macular degeneration; Inj., injection; IVA, intravitreal aflibercept;
PCV, polypoidal choroidal vasculopathy; VA, visual acuity. 1. Ijiri S et al. Graefes Arch Clin Exp Ophthalmol 2015; 253: 351–357. 2. Koizumi H et al. Am J Ophthalmol 2015; 159 (4): 627–633 3.
Koizumi H et al. Br J Ophthalmol 2015; Mar 16 [Epub ahead of print]. 4. Inoue M et al. Retina 2014; 34: 2178–2184. 5. Hosokawa M et al. Br J Ophthalmol 2015; Feb 23 [Epub ahead of print]. 6.
Oishi A et al. Am J Ophthalmol 2015; 159 (5): 853–860. 7. Yamamoto A et al. Ophthalmology 2015; Jun 15 [Epub ahead of print].

33 29
48 47.8
75 77.7
69.2
55.4
0
10
20
30
40
50
60
70
80
90
100
Proportionofeyeswithcompletepolyp
regressionatprimaryendpoint(%)
Ijiri et al
20152
(N=33)
Koizumi
et al 20153
(N=91)
Japanese case series summary:
Polyp regression in treatment-naive PCV
• A total of 336 Japanese PCV patients in 7 case
series received 2 mg aflibercept monotherapy†
• Treatment duration: 3 to 12 months
30
EVEREST I Japanese Case Series
Study Inoue
et al. 20144
(N=16)
Hosokawa
et al. 20155
(N=18)
Oishi et al.
20156
(N=39)
Yamamoto
et al. 20157
(N=83)
RBZ 0.5 mg
(n=21)*1
†One study, Koizumi 2015 (N=56) did not report polyp regression
*Ranibizumab monotherapy arm from EVEREST I; patients were treatment naïve.
PCV, polypoidal choroidal vasculopathy; RBZ, ranibizumab.
1. Koh A et al. Retina 2012; 32: 1453–1464. 2 Ijiri S et al. Graefes Arch Clin Exp Ophthalmol 2015; 253: 351–357. 3. Koizumi H et al. Br J Ophthalmol 2015; Mar 16 [Epub
ahead of print]. 4. Inoue M et al. Retina 2014; 34: 2178–2184. 5. Hosokawa M et al. Br J Ophthalmol 2015; Feb 23 [Epub ahead of print]. 6. Oishi A et al. Am J Ophthalmol
2015; 159 (5): 853–860. 7. Yamamoto A et al. Ophthalmology 2015; Jun 15 [Epub ahead of print].
Month 3 Month 6
Month 3 Month 6 Month 12

EPIC study: 6 month results
Prospective clinical trial of AFL for PCV*
baseline At month 6
Visual acuity 65.7 68.4
Present Resolution
Subretinal fluid 18 eyes 13/18 (72%)
Subretinal hemorrhage 8 eyes 6/8 (75%)
PED 15 eyes 13/15 (87%)
Polypoidal lesion 21 eyes 14/21 (87%)
Bimonthly treatment† 15/21 (71%)
*:Kokame G et al., BMC Ophthalmology 2016
†: Treated bimonthly if there was no fluid at month 3 and 5AFL can stabilize vision, resolve exudative and hemorrhagic complications in the
macula, and promote polyp regression.

1 year results of the VAULT study
(efficacy of fixed-dosing aflibercept for PCV)*
Baselin
e
Month 12
Mean change in
BCVA
Overall 55.1 64.2 (+9.0 letters)
Maintained (n=27) 68.3 (+14.1 letters)
Recurred (n=14) 55.5 (-1.5 letters)
Macular Thickness (mm) 365 253
Polyp regression Complete 61.9%
Partial 23.8%
Phase IV, prospective, single-arm, interventional case series
to prospectively evaluated the effect of AFL on PCV
Three monthly doses were followed by a maintenance injection every 2 months.
Joo Eun Lee et al., Graefes 2016
Fluid recurrence was observed in one-third of patients after
extending the treatment interval to 2 months.
“Because final outcomes in these patients were poor, a more flexible
treatment strategy should be used.“
*: South Korea

Other recent studies of AFL for PCV
Author Design N (eyes)
VA (logMAR) Regressionrate of
polypoidal lesions (%)Pre-IVA Post-IVA
Han Joo Cho,
20161
AFL
RBZ
AFL 38
RBZ 60
0.63 ± 0.49
0.66 ±
0.43
0.44 ± 0.37
0.49 ± 0.36
39.5%
21.6%
Kikushima W,
20162
AFL (3monthly)
Combined PDT
AFL 33
Combined 33
0.52 ± 0.4
0.55 ± 0.3
0.28 ± 0.32
0.25 ± 0.21
60.0%
68.8%
Inoue M,
20163
AFL bimonthly
AFL PRN
25
17
0.31
0.33
- 0.16 ±
0.17
- 0.10 ±
0.19
52.9%
48.0%
RBZ
PEARL4
RBZ 0.5mg 13 0.68 ± 0.40 0.50 ± 0.38 38%
PEARL25
RNB 2.0mg 19 55.7 (letters)
66.1
(Letters) 79% (6m)1. AJO 2016, 2. Graefes 2016, 3. Retina 2016 4. Ophthalmologica 2014 5. Trans Am Ophthalmol Soc 2014

34
Outline
practice

35
0 1 2 3 4 5 6 7 8 9 10 11 12
PRN (as needed)
Bi-monthly*
*Treat and Extend
Dry retina :
*Treat and Extend (T&E):
Injection is given regardless of
dry retina or persistent fluid
(Mo)
Reactive dosing:
Proactive dosing:
Dry Retina: Absence of fluid on OCT
Extension of the next injection interval
Persistent fluid: Presence of fluid on OCT
Shortening of the next injection interval
Can extend the next
injection interval
*Treat and Extend
Persistent fluid:Can not extend the
next injection interval
Injection based on assessment
results
Injection at pre-planned
intervals
Treatment regimens for AMD

36
Treatment in the maintenance phase of AMD
Monthly fixed
dosing
Fixed dosing of
once every 3
months
PRN dosing
dependent on
physician’s
discretion
Strict PRN
dosing using
qualitative OCT
assessment
Fixed
intervals
PRN dosing
Maintenance of good visual acuity while
minimizing the dosing frequency.
Monthly follow-up and strict additional dosing are required.
When compared to monthly dosing
Visual acuity and anatomical results are inferior.
Increased burden of patient management
Fixed-interval dosing
= monthly or bimontly
Treat and extend dosing
Dosing extended 2 to 4
weeks and treated if
recurs.
Fixed dosing

Benefits of Treat and Extend
• A proactive therapy, which can be administered without
waiting for pathological exacerbations
• Optimum dosing interval for individual patients can be
explored.
• The patients have no mental anxiety that the physician may
inform the exacerbation and the additional injection based on
the test result.
• Easy to plan dosing schedule since dosing dates are fixed
(including caretakers’ convenience).
• The number of visits may be decreased since dosing and
monitoring are performed on the same date.
• Dosing preparation is easy to plan at medical institutions (the
daily number of dosed patients is obvious in advance).

38
Treatment of AMD (anti-VEGF therapy)
•
PAT survey (ASRS) 2015

Many With Wet AMD Need anti-VEGF
Retreatment Even After Year-Long Pause
Treatment-
free interval
Time to retreatment
after a pause in therapy (Months)
Proportion of eyes
requiring retreatment (%)
20th centile 50th centile At 6 Months At 12 Months
3 Months
(n=8184) 0.58 2.54 68 77
6 Months
(n=5134) 2.07 9.62 44 56
9 Months
(n=3522) 3.69 15.84 31 43
12 Months
(n=2452) 5.90 22.49 21 34
Do not discharge AMD patients from review
after 12 months without treatment.
Multicentre national nAMD database study involving 12,951
eyes receiving 92,976 ranibizumab injections (UK)
Madhusudhana KC, et al. Br J Ophthalmol 2016;0:1–6. doi:10.1136/bjophthalmol-2015-308077
All received three fixed monthly injections, followed by a maintenance phase with PRN.

Treatment Patterns and Visual Outcomes during the
Maintenance Phase of Treat-and-Extend
Time to first reactivation
Ophthalmology 2016 123, 2393-2400
Previous report
Sustained improvements in mean visual acuity to 24 months
+5.3 letters, 11.3 injections
To deactivate the lesions during the induction phase, the authors needed
3 injections or fewer in 63% of eyes (a "short" induction),
> 3 injections in 37% (a "long" induction).
Aim:to comparethe maintenance phase behavior of
eyes with a shorter induction phase vs those with a longer induction phase.

Treatment Patterns and Visual Outcomes during the
Maintenance Phase of Treat-and-Extend
Median days between injections
Long induction phases
43 days (start), 65 days (at 36 months)
Short induction phases
30 days (start), 58 days (at 36 months)
Long induction phases
-> longer treatment intervals
Long induction phases :239 days,
Short induction phases: 405 days
Ophthalmology 2016 123, 2393-2400

42
Figure 6
Ophthalmology 2016 123, 2393-2400
Longer induction-phase group
Greater proportion of eyes had treatment interval longer than ideal.
Clinicians do not necessarily adhere strictly to the
principles of treat and extend and may accept a certain degree of lesion
activity rather than shorten the treatment intervals.
Treatment Patterns and Visual Outcomes during
the Maintenance Phase of Treat-and-Extend

43
Outline
practice

Treatment of AMD: my recommendation
• Induction phase
– Morphological assessment with OCT
• SHRM, IRF - intensive treatment
• SRF only - less intensive treatment
– Consider anti-VEGF + PDT for initial treatment of PCV
• Maintenance phase
– Treat & extend for frequently recurrent cases
– PRN for less frequently recurrent cases
– Regularly check signs of macular atrophy
• Real world patients tend to do worse because they receive
far fewer injections than the participants in clinical trials
– Do not accept even a small degree of lesion activity
– Never discharge patients

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