Intravitreal corticosteroid MWS 2012 Han.ppt (Read-Only)

12/12/11
Disclosure
Intravitreal Corticosteroid
Therapy for Retinal Disease:
How and When
Dennis P. Han, M.D.
Ø Investigator or co-investigator in
clinical trials for which my institution
(MCW) receives research funds
Allergan
Genentech
2
Acknowledgements
Objecves
Ø Brian Berger, M.D.
Ø David Callanan, M.D.
Ø Judy Kim, M.D.
Ø Glenn Jaffe, M.D.
Ø Define delivery modalies, indicaons,
and risks of intravitreal corcosteroid
therapy
Ø Perspecve on the problem of glaucoma
Ø Recommendaons
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Case presentation
Ø 54 year old man with non-ischemic
CRVO OD, negative systemic workup
Ø s/p Trental 400 mg; VA worsened
from 20/25 to 20/100 (8/07-11/07)
Ø 11/07: VA 20/100, 4+CME, phakic
5
Ø Elected participation in the SCORE
trial on IVTA for CRVO 6
7/31/08, 4 months after 2 nd IVTA injection (SCORE trial), VA 20/60, IOP 17, lens clear
7
Mechanisms of corcosteroid
acon
Ø Enhances the barrier function of
vascular tight junctions
Ø Prevents leukocyte migration
Ø Inhibits proinflammatory cytokine
synthesis, and VEGF expression
Ø DME and RVO-ME associated ME are
mediated by VEGF induced loss of
tight junctions and inflammation
Kiernan DF, Mieler WF. Expert Opin Pharmacother 2009;10:2511-2525
Leopold IH. In: Surgical Pharmacology of the Eye. New York, NY: Raven
Press; 1985:83-133.
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Intravitreal triamcinolone
acetonide
Ø Treatment effect lasts
3-5 months
Ø Commonly used
dosages 1-4 mg
Ø Preservative-containing
(Kenalog, Bristol-Myers
Squibb) and
preservative-free
(Triescence, Alcon)
Ozurdex (Allergan)
Dexamethasone implant (6
week sustained release, 0.7 mg
total dose : biphasic release
with lower therapeutic levels for
6 months)
10
Retisert (Bausch and
Lomb)
Fluocinolone acetonide: 2.5
year sustained release for 30
months; 0.59 mg (0.6 mcg/day
for 1 month, decreasing to 0.3-.
4 mcg over 30 mo)
Surgically implanted
Iluvien (Alimera Sciences)
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Fluocinolone acetonide: 2-3 year sustained
release, 0.2 and 0.5 mcg/day dosage; injector
system for delivery
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Glaucoma in perspective:
sustained therapy
Tube vs Trabeculectomy (TVT)
Study (3 year outcomes)
Agent Topical control Surgery
IVTA 20-35% 1% at 2 years
(DRCR.net)
Dexamethasone implant .7 mg 24% 0.7% at 6 months
Retisert fluocinolone implant 70% 37% at 3 years
Iluvien fluocinolone implant 0, 29% (.2 vs .5 mcg/d) 5% at 1 year
Ranibizumab 9% 0.2% at 2 years
(DRCR.net)
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Ø In POAG patients, compared to
trabeculectomy, aqueous shunts had
Lower failure rate (15 vs 31%)
Lower endophthalmitis rate (1 vs 3%,
N.S.)
Ø Ranibizumab for DME
endophthalmitis rate 1% over 2 yrs
Ø 22% of tube patients lost ≥2 lines VA
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Implications of the Tube vs
Trabeculectomy (TVT) Study
Ø “if intravitreal corticosteroid therapy
is deemed appropriate, the physician
should proceed with the knowledge
that its risks are manageable and
that visual outcome, not IOP, should
be the final arbiter in the decisionmaking
process.”
Evidence-­‐based data on intravitreal
corcosteroids: mulcenter clinical
trials
Ø Diabec macular edema
Ø Renal vein occlusion
Han DP and Heuer DK. Intravitreal corticosteroid therapy: putting the problem of
glaucoma in perspective. Arch Ophth, in press
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Ozurdex for DME (PLACID
trial): one year results
Mean Change From Baseline BCVA in
Patients With Verified DDME (mITT
Population)
P=.002
P

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Iluvien for DME: long term
results
Ø Subgroup analysis of duration of
DME at baseline (0.2µg/d, 3 year
results):
If

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Mean Change in Visual Acuity*
at Follow-up Visits:
Pseudophakic Eyes at Baseline
Cumulative Probability of
Cataract Surgery Over 2-Years
Change in Visual Acuity from Baseline (letter score)
11
10
9
8
7
6
5
4
3
2
1
0
0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100104
Visit Week
*Truncated ± 30 letters
Sham+Prompt Laser
Ranibizumab+Prompt Laser
Ranibizumab+Deferred Laser
Triamcinolone+Prompt Laser
N = 205 (52 weeks)
N = 199 (68 weeks)
N = 196 (84 weeks)
N = 206 (104 weeks)
25
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
0 120 4 240 8 360 12 480 16 600 20 720 24
Month
74%
18%
16%
Sham (N = 192)
Ranibizumab (N = 265)
Triamcinolone (N = 124)
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Iniaon of IOP-­‐lowering
medicaons* or glaucoma surgery
(2 year follow-­‐up)
IOP meds Glauc surgery
Ø TA + prompt laser (n=93): 50% (2 eyes, 1.1%)
Ø Ranibizumab (n=34): 9% (1 eye, 0.2%)
Ø Sham + prompt laser (n=32): 11% (1 eye, 0.3%)
Ø P

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Retinal Vein Occlusion
Ø Benefits of IVTA shown in CRVO but not
BRVO (SCORE trial); 1 mg dose with better
risk profile compared to 4 mg dose*
Ø Benefit of Dexamethasone implant in eyes
with BRVO and CRVO combined w/o
subgroup analysis on outcome**
Ø No direct comparisons exist between
corticosteroids and anti-VEGF agents
*Standard Care vs Corticosteroid for Retinal Vein Occlusion. Report 6. SCORE
Study Research Group. Arch Ophthamol 2009;127:1115-1128
**Haller JA, et al. Dexamethasone Intravitreal Implant in Patients with Macular
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Edema Due to Retinal Vein Occlusion. Ophthalmology 2010;117:1134-1146
Mean Change from Baseline in
VA Letter Score
Mean change from baseline
in visual acuity letter score
5
0
-5
-10
-15
Obs 1mg 4mg
SCORE CRVO Trial
M4 M8 M12 M16 M20 M24
RVO and ranibizumab: CRUISE
and BRAVO studies
Ø Ranibizumab beneficial for CRVO
and BRVO associated ME given
monthly for 6 months
Ø No significant increase in risk of
cataract or IOP elevation
Ø Open label extension study with
lower dosing frequency after 6
months (HORIZON) showed
sustained benefit in BRVO eyes, but
deterioration in CRVO eyes 31
Mean Change from Baseline in
VA Letter Score
Mean change from baseline
in visual acuity letter score
20
16
12
8
4
0
D7 M1 M2 M3 M4 M5 M6
Sham 0.3mg 0.5mg
9.3 letters
BRAVO Trial
11 letters
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CRUISE Trial
Mean Change from Baseline in
VA Letter Score
Case Presentation
D7 M1 M2 M3 M4 M5 M6
Mean change from baseline
in visual acuity letter score
20
16
12
8
4
0
-4
Sham 0.3mg 0.5mg
11.9 letters
14.1 letters
7/31/08, 4 months after 2 nd IVTA injection (SCORE trial), VA 20/60, IOP 17, lens clear
Patient underwent 3 rd injection of IVTA on 7/31/08; 9/2/08 (5 weeks later)
VA was 20/100, residual IVTA in vitreous cavity; observation elected
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12/21/10 OCT OD; VA 20/150
11/17/08, 3.5 months after IVTA (SCORE); VA 20/160
From 11/17/08 to 11/16/10 Patient received Avastin 1.25 mg every
month for a total of 19 injections
VA 11/6/10 (after 2 years of Avastin) was 20/150
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Administered intravitreal Lucentis q 1 month x 7, from 1/11/11 to 7/12/11
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1 month after 6 Lucentis
injections, VA 20/125
7/12/11 OCT OD
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Intravitreal corticosteroid
therapy
Ø IOP and cataract are downsides
Ø Probably second line to ranibizumab
for DME and RVO
Ø A viable option for DME in
pseudophakes: less frequent
injections, IOP control easier with
some modalities vs. others
Ø Sustained release devices show
promise 38
RVO and ranibizumab: CRUISE
and BRAVO studies
(references)
Ranibizumab for macular edema following branch retinal vein occlusion: six-month primary
end point results of a phase III study.
Campochiaro PA.,et al.Ophthalmology. 117(6):1102-1112, 2010.
Ranibizumab for macular edema following central retinal vein occlusion: six-month primary
end point results of a phase III study.
Brown DM, et al. Ophthalmology. 117(6):1124-1133.e1, 2010.
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