Steroids and DME
Scott E. Pautler, M.D.
Associate Clinical Professor of Ophthalmology
University of South Florida
Tampa, FL
Case Presentation
• 71 year old woman with type 2 diabetes for 12
years with gradually decreasing vision OU
• Visual acuity: R-20/50, L-20/125
• Slit lamp: 2+ nuclear sclerosis
• IOP 18 OU
• Fundus: DME OU; moderate NPDR OU
3/23/2009
Right Eye
Treatments:
Focal – 2
IVK – 10
CE/IOL
Left Eye
Treatments:
Focal – 3
IVK – 13
CE/IOL
VTX/ILM peel
PRP -2
2/5/2014
Visual Acuity and OCT Outcomes
Date
Eye
CSMT (µ)
VA
3/23/2009
Right
398
20/50
Left
397
20/125
Right
267
20/20
Left
490
20/100
2/5/2014
Steroid Mechanism of Action
• Decrease VEGF production
• Widespread anti-inflammatory effects
• More rapid onset and more profound initial
effect on edema than anti-VEGF agents
• Adverse effects: cataract, glaucoma
Pre-injection IVTA
1 month later
Steroid Agents
Triamcinolone vs Focal/Grid Laser
• DRCR Protocol B: 840 eyes
• Three-year results
• Problems: 79% of eyes were phakic and IVTA
dosing interval was ≥ 4 months
Treatment
Mean
BCVA
gains
Δ CSMT
In microns
Cataract
Surgery
Glaucoma
Surgery
Glaucoma
Drops
Focal/Grid
+5 letters
-158
0
0
3%
IVTA 1 mg
0 letters
-103
46%
0
2%
IVTA 4 mg
0 letters
-114
83%
4 (1.6%)
12%
Combination IVTA + Focal/Grid Laser
(FGL)
• DRCR Protocol I: Pseudophakic eyes (206)
– Two-year results
Treatment
Mean
Δ BCVA
(letters)
Mean
Δ CSMT
(μ)
IVTA 4 mg + FGL
+8
-128
Sham + FGL
+5
-145
IVR + Prompt FGL
+5
-126
IVR + Deferred FGL
+9
-148
Triamcinolone Options
Triamcinolone
FDA
approve
d
Crystal
Size
Dissolution Cost
Profile
Pseudo
Endophth
Preserved
No
18.86 μ
Faster
$9.32
≤7%
PreservativeFree
Yes
11.51 μ
Slower
$157.58
≤1%
Dexamethasone Implant
• Recently approved by FDA for DME
Bio-erodible
Duration ≤6 months
• Ozurdex MEAD Study Group 2014:
– 1048 eyes; 20/50-20/200; CRT ≥300μ; 3-year
Mean CRT
(μ)
Cataract
Glaucoma
Surgery
Sham injection 12%
-42
20%
0%
Dex 0.35 mg
18.4%
-108
64%
0.3%
Dex 0.70 mg
22.2%
-112
68%
0.6%
Treatment
≥15 letter
improvement
Dexamethasone Implant
• BEVORDEX Study (AAO subspecialty meeting)
– 1-year result of RCT
– bevacizumab vs dexamethasone
– Dexamethasone superior functional and anatomic
outcomes in pseudophakic eyes
– Mean number of injections:
• 3.7 Dexamethasone injections
• 8.6 bevacizumab injections
Fluocinolone Implant
• Recently approved by FDA for DME
Non-responders; Duration ≤3 years
• FAME Study 2012:
– 953 eyes; failed FLT; 20/50-20/400; CRT ≥250μ;
3-year study
Mean CRT (μ) Cataract
Glaucoma
Surgery
Sham injection* 21%
NG
51%
0.5%
Fluo 0.2 μg/d
33%
NG
82%
4.8%
Fluo 0.5 μg/d
32%
NG
89%
8.1%
Treatment
≥15 letter
improvement
*Rescue treatment with focal laser and/or anti-VEGF occurred more often in Sham
Steroids and IOP
• Risk Factors: Glaucoma, OHT, steroid
response, young age, higher loading dose
Steroid Agent
≥10mm
(values adjusted over
by control group) baseline
≥25mm
at any
exam
Any
IOP
meds
Surgery
For
IOP
Attrition
by
3 years
Triamcinolone
1 mg
18% (14%) -
2% (0%)
0% (0%)
64%
Triamcinolone
4 mg
33% (29%) -
12% (9%)
4% (4%)
64%
Dexamethasone
Impl 0.70 mg
28% (24%) 32% (28%)
42% (33%)
1% (1%)
42%
Fluocinolone
Impl 0.19 mg
34% (24%) 20% (16%)
38% (24%)
5% (4%)
30%
Case Selection
• Pseudophakic, Non-Glaucoma/Suspect Eyes
– AC IOL: consider avoiding an implant
– Post vitrectomy: consider avoiding IVTA (storm)
– Prior glaucoma surgery offers
limited protection against
steroid-IOP response
Case Selection
• DME resistant to anti-VEGF/laser*
• Macula-threatening exudates (BEVORDEX)
• One-time use for DME prior to surgery:
– PRP laser
– cataract surgery
* Fluocinolone implant relatively more effective in chronic edema (>3yrs)
Steroid Selection
• Triamcinolone
– Less expensive (Kenalog®)
– More frequent injection
– Greater peak/trough effect
• Steroid implant
– More expensive
– Fewer injections
– Better pharmacokinetics (Iluvien®>Ozurdex®)
Thank you
Scott E. Pautler, M.D.
Tampa, FL