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Transcript of Sponsored by the National Eye Institute,
A Randomized Trial Comparing Intravitreal A Randomized Trial Comparing Intravitreal Triamcinolone Triamcinolone to Focal/Grid Photocoagulation to Focal/Grid Photocoagulation
for Diabetic Macular Edemafor Diabetic Macular Edema
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Sponsored by the National Eye Institute, National Institutes of Health, U.S. Department of Health and Human Services.
2
Intravitreal Triamcinolone for DME 2001-2002: potential benefit first reported1,2
Short term improvement in visual acuity Rapid decrease in retinal thickening on OCT 2005: 91% of retina specialists surveyed (N=371)
would use IVT for persistent DME3
Community equipoise present: Randomized, controlled comparison with standard care (focal/grid photocoagulation) needed1- Jonas JB, et al. Am J Ophthalmol 2001;132:425-72- Martidis A, et al. Ophthalmology 2002;109:920-73- American Society of Retina Specialists Preferences and Trends Survey 2005
3
DRCR.net Study Design Multicenter, randomized clinical trial Three treatment groups
• Focal/grid laser• 1 mg IVT• 4 mg IVT
Duration of follow-up: 3 years Follow-up visits and re-treatment as often as
every 4 months
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Primary Study Objective
To compare the efficacy and safety of preservative-free IVT (1 mg or 4 mg) with focal/grid laser
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Efficacy Outcomes
Primary outcome assessment at 2 years Primary outcome measure: visual acuity
• Scientific objective: mean change in VA• Regulatory objective for FDA: proportion with
decrease in VA letter score >15Secondary measure: Retinal thickening on OCT
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At least 18 years old Type 1 or type 2 diabetes Center-involved DME confirmed on OCT
• (central subfield thickness >250 microns) Best-corrected VA letter score 73 to 24
• (Snellen equivalent 20/40 to 20/320)
Major Eligibility Criteria
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ResultsResults
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840 eyes (693 subjects) enrolled at 88 clinical sites (2004-2006)
Treatment Groups• Laser: N = 330• 1 mg: N = 256• 4 mg: N = 254
2-year visit completion rate • 88% excluding deaths
Study Enrollment and Completion
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Primary Outcome:Mean Change in Visual Acuity at 2 Years
Mean Change in VA (letter score)
LaserN=330
1 mgN=256
4 mgN=254
+1 -2 -3 Pairwise
Comparisons Mean Difference* P value*
Laser vs. 1 mg +3.5 letters 0.02Laser vs. 4 mg +4.6 letters 0.0021 mg vs. 4 mg +1.1 letters 0.49
* Adjusted for baseline VA and prior focal/grid laser
0 4 8 12 16 20 24
Laser1 mg4 mg
10Months
VisualAcuityScore
20/80 -
20/50 -
20/32 -
Median Visual Acuity inLaser and IVT Treated Eyes
P < 0.005* Laser vs. 1mg# Laser vs. 4mg+ 1mg vs. 4mg
20/40 -
20/63 -
*
# + * # * #
0%
10%
20%
30%
40%
4 8 12 16 20 24
Laser1 mg4 mg
11Months
% Increased >10 Letters inLaser and IVT Treated Eyes
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Visual Acuity at 2 YearsAccording to Lens Status
Mean Change in VA (letter score) Laser 1 mg 4 mg
Pseudophakic at 2 Yrs or Minimal or No
Cataract at 2 Yrs
N=178 N=136 N=159
+3 0 0
Includes only subjects with a 2 year visit
Pseudophakic at Baseline
N=54 N=48 N=43
+2 +2 -1
Laser (All eyes)
1 mg (All eyes)
4 mg (All eyes)
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Mean Visual Acuity Over 3 Years in All Eyes
Months
VisualAcuityScore
20/80
20/50
20/32
20/40
20/63
0 12 16 20 244 8 28 32 36
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OCT Central Subfield (CSF) Thickening at 2 Years
Change in OCT CSF LaserN=220
1 mgN=178
4 mgN=162
Mean* -139 -86 -77
Thickening Decreased >50% 67% 46% 48%
Thickness <250 microns 53% 34% 38%
*Pairwise Comparisons P valueLaser v 1 mg <0.001Laser v 4 mg <0.0011 mg v 4 mg 0.91
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Median OCT Central Subfield Thickness in Laser and IVT Treated Eyes
200
250
300
350
400
450
0 4 8 12 16 20 24
Laser1 mg4 mg
Months
Central Subfield
Thickness(microns)
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Change in CSFfrom 2 Years to 3 Years*
2 year CSF >=250LaserN=50
1mgN=59
4mgN=54
Mean change (microns) -79 -44 -84<250 microns at 3 years 36% 31% 39%Decreased >=20% and >=50 microns 54% 34% 46%
Increased >=20% and >=50 microns 10% 12% 13%
* Among completers of both the 2 year and 3 year visit
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Major Ocular Adverse EventsDuring 2 Years of Follow-up
LaserN=330
1 mgN=256
4 mgN=254
Endophthalmitis* 0 0 0Pseudoendophthalmitis 0 0 0Retinal detachment† 2 2 3Retinal vein occlusion† 3 1 2Retinal artery occlusion† 1 0 0
Glaucoma procedure 0 0 4
Vitrectomy‡ 31 26 19
* 1 case of endophthalmitis occurred after vitrectomy, not related to study drug injection† Judged not necessarily related to treatment‡ Includes vitrectomy for diabetic macular edema, vitreous hemorrhage or other cause
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Intraocular Pressure During 3 Years of Follow-up*
LaserN=115
1 mgN=93
4 mgN=98
Increase >10 mmHg any time 3% 17% 31%Mean IOP at 3 yr visit (mmHg) 16 17 16IOP >21 mmHg at 3 yr visit 5% 15% 10%On IOP-lowering meds at 3 yr visit 8% 12% 30%
* Among completers of the 3 year visit
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Cataract Surgery Prior to 2 Years
Laser 1 mg 4 mg
Phakic at Baseline N=262 N=203 N=197
Cataract Surgery 13% 23% 51%
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Cumulative Probability of Cataract Surgery* Over 3 Years
* Among phakic eyes at baseline
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Laser (N=262)
1 mg (N=203)
4 mg (N=197)
4 8 12 16 20 24 28 32 36Months
83%
46%
31%
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Conclusion VA benefit in 4 mg IVT group at 4 months
consistent with published case series However, no difference in VA between IVT
groups and laser group by 1 year By 2 years, there was a greater VA benefit and
fewer side effects (IOP and cataract) in laser group compared with the IVT groups 3 year results similar to the 2 year results
OCT results mirrored VA results
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Conclusion
Results re-affirm importance of laser in management of DME
Focal/grid currently most effective treatment for patients with DME (with characteristics similar to those enrolled in this trial)
Focal/grid currently benchmark against which other new treatments for DME should be compared in clinical trials for DME