A Randomized Trial Comparing Intravitreal Triamcinolone to Focal/Grid Photocoagulation for Diabetic Macular Edema

1

• A Randomized Trial Comparing Intravitreal
  Triamcinolone to Focal/Grid Photocoagulation for
  Diabetic Macular Edema

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 (N371)
  would use IVT for persistent DME3
• Community equipoise present Randomized,
  controlled comparison with standard care
  (focal/grid photocoagulation) needed

1- Jonas JB, et al. Am J Ophthalmol
2001132425-7 2- Martidis A, et al.
Ophthalmology 2002109920-7 3- American Society
of Retina Specialists Preferences and Trends
Survey 2005
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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 gt15
• Secondary measure Retinal thickening on OCT

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Major Eligibility Criteria

• At least 18 years old
• Type 1 or type 2 diabetes
• Center-involved DME confirmed on OCT
• (central subfield thickness gt250 microns)
• Best-corrected VA letter score 73 to 24
• (Snellen equivalent 20/40 to 20/320)

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Results
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Study Enrollment and Completion

• 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

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Primary OutcomeMean Change in Visual Acuity at
2 Years
Mean Change in VA (letter score) Laser N330 1 mg N256 4 mg N254
Mean Change in VA (letter score) 1 -2 -3
Pairwise Comparisons Mean Difference P value
Laser vs. 1 mg 3.5 letters 0.02
Laser vs. 4 mg 4.6 letters 0.002
1 mg vs. 4 mg 1.1 letters 0.49
Adjusted for baseline VA and prior focal/grid
laser
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Median Visual Acuity in Laser and IVT Treated Eyes
20/32 -
20/40 -




20/50 -
20/63 -
20/80 -
P lt 0.005
Laser vs. 1mg Laser vs. 4mg 1mg vs. 4mg
Months
10
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Increased gt10 Letters in Laser and IVT Treated
Eyes
Months
11
12
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 N178 N136 N159
Pseudophakic at 2 Yrs or Minimal or No Cataract at 2 Yrs 3 0 0
Pseudophakic at Baseline N54 N48 N43
Pseudophakic at Baseline 2 2 -1
Includes only subjects with a 2 year visit
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Mean Visual Acuity Over 3 Years in All Eyes
20/32
20/40
20/50
20/63
20/80
20
36
0
16
24
8
28
12
32
4
Months
13
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OCT Central Subfield (CSF) Thickening at 2 Years
Change in OCT CSF Laser N220 1 mg N178 4 mg N162
Mean -139 -86 -77
Thickening Decreased gt50 67 46 48
Thickness lt250 microns 53 34 38
Pairwise Comparisons P value
Laser v 1 mg lt0.001
Laser v 4 mg lt0.001
1 mg v 4 mg 0.91
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Median OCT Central Subfield Thickness in Laser
and IVT Treated Eyes
Central Subfield Thickness (microns)
Months
15
16
Change in CSFfrom 2 Years to 3 Years
2 year CSF gt250 2 year CSF gt250 2 year CSF gt250
Laser N50 1mg N59 4mg N54
Mean change (microns) -79 -44 -84
lt250 microns at 3 years 36 31 39
Decreased gt20 and gt50 microns 54 34 46
Increased gt20 and gt50 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
Laser N330 1 mg N256 4 mg N254
Endophthalmitis 0 0 0
Pseudoendophthalmitis 0 0 0
Retinal detachment 2 2 3
Retinal vein occlusion 3 1 2
Retinal 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
Laser N115 1 mg N93 4 mg N98
Increase gt10 mmHg any time 3 17 31
Mean IOP at 3 yr visit (mmHg) 16 17 16
IOP gt21 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
18
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Cataract Surgery Prior to 2 Years
Laser 1 mg 4 mg
Phakic at Baseline N262 N203 N197
Cataract Surgery 13 23 51
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Cumulative Probability of Cataract Surgery Over
3 Years
83
46
31
4
8
12
16
20
24
36
28
32
Months
Among phakic eyes at baseline
20
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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