Intravitreal corticosteroid MWS 2012 Han.ppt (Read-Only)
Intravitreal corticosteroid MWS 2012 Han.ppt (Read-Only)
Intravitreal corticosteroid MWS 2012 Han.ppt (Read-Only)
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12/12/11<br />
Disclosure<br />
<strong>Intravitreal</strong> Corticosteroid<br />
Therapy for Retinal Disease:<br />
How and When<br />
Dennis P. <strong>Han</strong>, M.D.<br />
Ø Investigator or co-investigator in<br />
clinical trials for which my institution<br />
(MCW) receives research funds<br />
Allergan<br />
Genentech<br />
2<br />
Acknowledgements<br />
Objecves <br />
Ø Brian Berger, M.D.<br />
Ø David Callanan, M.D.<br />
Ø Judy Kim, M.D.<br />
Ø Glenn Jaffe, M.D.<br />
Ø Define delivery modalies, indicaons, <br />
and risks of intravitreal corcosteroid <br />
therapy <br />
Ø Perspecve on the problem of glaucoma <br />
Ø Recommendaons <br />
3<br />
1
12/12/11<br />
Case presentation<br />
Ø 54 year old man with non-ischemic<br />
CRVO OD, negative systemic workup<br />
Ø s/p Trental 400 mg; VA worsened<br />
from 20/25 to 20/100 (8/07-11/07)<br />
Ø 11/07: VA 20/100, 4+CME, phakic<br />
5<br />
Ø Elected participation in the SCORE<br />
trial on IVTA for CRVO 6<br />
7/31/08, 4 months after 2 nd IVTA injection (SCORE trial), VA 20/60, IOP 17, lens clear<br />
7<br />
Mechanisms of corcosteroid <br />
acon <br />
Ø Enhances the barrier function of<br />
vascular tight junctions<br />
Ø Prevents leukocyte migration<br />
Ø Inhibits proinflammatory cytokine<br />
synthesis, and VEGF expression<br />
Ø DME and RVO-ME associated ME are<br />
mediated by VEGF induced loss of<br />
tight junctions and inflammation<br />
Kiernan DF, Mieler WF. Expert Opin Pharmacother 2009;10:2511-2525<br />
Leopold IH. In: Surgical Pharmacology of the Eye. New York, NY: Raven<br />
Press; 1985:83-133.<br />
2
12/12/11<br />
<strong>Intravitreal</strong> triamcinolone<br />
acetonide<br />
Ø Treatment effect lasts<br />
3-5 months<br />
Ø Commonly used<br />
dosages 1-4 mg<br />
Ø Preservative-containing<br />
(Kenalog, Bristol-Myers<br />
Squibb) and<br />
preservative-free<br />
(Triescence, Alcon)<br />
Ozurdex (Allergan)<br />
Dexamethasone implant (6<br />
week sustained release, 0.7 mg<br />
total dose : biphasic release<br />
with lower therapeutic levels for<br />
6 months)<br />
10<br />
Retisert (Bausch and<br />
Lomb)<br />
Fluocinolone acetonide: 2.5<br />
year sustained release for 30<br />
months; 0.59 mg (0.6 mcg/day<br />
for 1 month, decreasing to 0.3-.<br />
4 mcg over 30 mo)<br />
Surgically implanted<br />
Iluvien (Alimera Sciences)<br />
11<br />
Fluocinolone acetonide: 2-3 year sustained<br />
release, 0.2 and 0.5 mcg/day dosage; injector<br />
system for delivery<br />
12<br />
3
12/12/11<br />
Glaucoma in perspective:<br />
sustained therapy<br />
Tube vs Trabeculectomy (TVT)<br />
Study (3 year outcomes)<br />
Agent Topical control Surgery<br />
IVTA 20-35% 1% at 2 years<br />
(DRCR.net)<br />
Dexamethasone implant .7 mg 24% 0.7% at 6 months<br />
Retisert fluocinolone implant 70% 37% at 3 years<br />
Iluvien fluocinolone implant 0, 29% (.2 vs .5 mcg/d) 5% at 1 year<br />
Ranibizumab 9% 0.2% at 2 years<br />
(DRCR.net)<br />
13<br />
Ø In POAG patients, compared to<br />
trabeculectomy, aqueous shunts had<br />
Lower failure rate (15 vs 31%)<br />
Lower endophthalmitis rate (1 vs 3%,<br />
N.S.)<br />
Ø Ranibizumab for DME<br />
endophthalmitis rate 1% over 2 yrs<br />
Ø 22% of tube patients lost ≥2 lines VA<br />
14<br />
Implications of the Tube vs<br />
Trabeculectomy (TVT) Study<br />
Ø “if intravitreal <strong>corticosteroid</strong> therapy<br />
is deemed appropriate, the physician<br />
should proceed with the knowledge<br />
that its risks are manageable and<br />
that visual outcome, not IOP, should<br />
be the final arbiter in the decisionmaking<br />
process.”<br />
Evidence-‐based data on intravitreal <br />
corcosteroids: mulcenter clinical <br />
trials <br />
Ø Diabec macular edema <br />
Ø Renal vein occlusion <br />
<strong>Han</strong> DP and Heuer DK. <strong>Intravitreal</strong> <strong>corticosteroid</strong> therapy: putting the problem of<br />
glaucoma in perspective. Arch Ophth, in press<br />
15<br />
4
12/12/11<br />
Ozurdex for DME (PLACID<br />
trial): one year results<br />
Mean Change From Baseline BCVA in<br />
Patients With Verified DDME (mITT<br />
Population)<br />
P=.002<br />
P
12/12/11<br />
Iluvien for DME: long term<br />
results<br />
Ø Subgroup analysis of duration of<br />
DME at baseline (0.2µg/d, 3 year<br />
results):<br />
If
12/12/11<br />
Mean Change in Visual Acuity*<br />
at Follow-up Visits:<br />
Pseudophakic Eyes at Baseline<br />
Cumulative Probability of<br />
Cataract Surgery Over 2-Years<br />
Change in Visual Acuity from Baseline (letter score)<br />
11<br />
10<br />
9<br />
8<br />
7<br />
6<br />
5<br />
4<br />
3<br />
2<br />
1<br />
0<br />
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<br />
Visit Week<br />
*Truncated ± 30 letters<br />
Sham+Prompt Laser<br />
Ranibizumab+Prompt Laser<br />
Ranibizumab+Deferred Laser<br />
Triamcinolone+Prompt Laser<br />
N = 205 (52 weeks)<br />
N = 199 (68 weeks)<br />
N = 196 (84 weeks)<br />
N = 206 (104 weeks)<br />
25<br />
100%<br />
90%<br />
80%<br />
70%<br />
60%<br />
50%<br />
40%<br />
30%<br />
20%<br />
10%<br />
0%<br />
0 120 4 240 8 360 12 480 16 600 20 720 24<br />
Month<br />
74%<br />
18%<br />
16%<br />
Sham (N = 192)<br />
Ranibizumab (N = 265)<br />
Triamcinolone (N = 124)<br />
26<br />
Iniaon of IOP-‐lowering <br />
medicaons* or glaucoma surgery <br />
(2 year follow-‐up) <br />
IOP meds Glauc surgery<br />
Ø TA + prompt laser (n=93): 50% (2 eyes, 1.1%) <br />
Ø Ranibizumab (n=34): 9% (1 eye, 0.2%) <br />
Ø Sham + prompt laser (n=32): 11% (1 eye, 0.3%) <br />
Ø P
12/12/11<br />
Retinal Vein Occlusion<br />
Ø Benefits of IVTA shown in CRVO but not<br />
BRVO (SCORE trial); 1 mg dose with better<br />
risk profile compared to 4 mg dose*<br />
Ø Benefit of Dexamethasone implant in eyes<br />
with BRVO and CRVO combined w/o<br />
subgroup analysis on outcome**<br />
Ø No direct comparisons exist between<br />
<strong>corticosteroid</strong>s and anti-VEGF agents<br />
*Standard Care vs Corticosteroid for Retinal Vein Occlusion. Report 6. SCORE<br />
Study Research Group. Arch Ophthamol 2009;127:1115-1128<br />
**Haller JA, et al. Dexamethasone <strong>Intravitreal</strong> Implant in Patients with Macular<br />
29<br />
Edema Due to Retinal Vein Occlusion. Ophthalmology 2010;117:1134-1146<br />
Mean Change from Baseline in<br />
VA Letter Score<br />
Mean change from baseline<br />
in visual acuity letter score<br />
5<br />
0<br />
-5<br />
-10<br />
-15<br />
Obs 1mg 4mg<br />
SCORE CRVO Trial<br />
M4 M8 M12 M16 M20 M24<br />
RVO and ranibizumab: CRUISE<br />
and BRAVO studies<br />
Ø Ranibizumab beneficial for CRVO<br />
and BRVO associated ME given<br />
monthly for 6 months<br />
Ø No significant increase in risk of<br />
cataract or IOP elevation<br />
Ø Open label extension study with<br />
lower dosing frequency after 6<br />
months (HORIZON) showed<br />
sustained benefit in BRVO eyes, but<br />
deterioration in CRVO eyes 31<br />
Mean Change from Baseline in<br />
VA Letter Score<br />
Mean change from baseline<br />
in visual acuity letter score<br />
20<br />
16<br />
12<br />
8<br />
4<br />
0<br />
D7 M1 M2 M3 M4 M5 M6<br />
Sham 0.3mg 0.5mg<br />
9.3 letters<br />
BRAVO Trial<br />
11 letters<br />
8
12/12/11<br />
CRUISE Trial<br />
Mean Change from Baseline in<br />
VA Letter Score<br />
Case Presentation<br />
D7 M1 M2 M3 M4 M5 M6<br />
Mean change from baseline<br />
in visual acuity letter score<br />
20<br />
16<br />
12<br />
8<br />
4<br />
0<br />
-4<br />
Sham 0.3mg 0.5mg<br />
11.9 letters<br />
14.1 letters<br />
7/31/08, 4 months after 2 nd IVTA injection (SCORE trial), VA 20/60, IOP 17, lens clear<br />
Patient underwent 3 rd injection of IVTA on 7/31/08; 9/2/08 (5 weeks later)<br />
VA was 20/100, residual IVTA in vitreous cavity; observation elected<br />
34<br />
12/21/10 OCT OD; VA 20/150<br />
11/17/08, 3.5 months after IVTA (SCORE); VA 20/160<br />
From 11/17/08 to 11/16/10 Patient received Avastin 1.25 mg every<br />
month for a total of 19 injections<br />
VA 11/6/10 (after 2 years of Avastin) was 20/150<br />
35<br />
Administered intravitreal Lucentis q 1 month x 7, from 1/11/11 to 7/12/11<br />
36<br />
9
12/12/11<br />
1 month after 6 Lucentis<br />
injections, VA 20/125<br />
7/12/11 OCT OD<br />
37<br />
<strong>Intravitreal</strong> <strong>corticosteroid</strong><br />
therapy<br />
Ø IOP and cataract are downsides<br />
Ø Probably second line to ranibizumab<br />
for DME and RVO<br />
Ø A viable option for DME in<br />
pseudophakes: less frequent<br />
injections, IOP control easier with<br />
some modalities vs. others<br />
Ø Sustained release devices show<br />
promise 38<br />
RVO and ranibizumab: CRUISE<br />
and BRAVO studies<br />
(references)<br />
Ranibizumab for macular edema following branch retinal vein occlusion: six-month primary<br />
end point results of a phase III study.<br />
Campochiaro PA.,et al.Ophthalmology. 117(6):1102-1112, 2010.<br />
Ranibizumab for macular edema following central retinal vein occlusion: six-month primary<br />
end point results of a phase III study.<br />
Brown DM, et al. Ophthalmology. 117(6):1124-1133.e1, 2010.<br />
39<br />
40<br />
10