Transcript Funding Mechanism

An Observational Study of the
Development of Diabetic Macular
Edema Following Panretinal
(Scatter) Photocoagulation (PRP)
Given in 1 or 4 Sittings
Sponsored by the National Eye Institute,
National Institutes of Health, U.S. Department of Health and Human Services.
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Background:
Panretinal Photocoagulation (PRP) for PDR
PRP is the standard treatment of PDR
Usually performed over 1 or more sittings
(ETDRS 2 or more sittings)
2004 survey of DRCR.net investigators:
one-quarter routinely use one sitting for
PRP
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PRP and Macular Edema
PRP associated complications include
macular edema
• ETDRS - 18% developed macular edema 4
months after full PRP (1200 – 1600 spots)
 Theories:
 Oncotic fluid accumulation related to tissue
destruction
 PRP induced inflammation leading to cytokine
release and increased permeability of the
retinal capillaries
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What are Some Pros and Cons of
Delivering PRP in 1 Sitting?
Pros
 Convenience
 Completion before complications occur [e.g.,
vitreous hemorrhage (VH)]
Cons (theoretical):
 May cause macular edema with VA loss
 Greater patient discomfort
 Need for retrobulbar or peribulbar anesthetic
 Higher risk of acute pressure rise, angle
closure, or choroidal effusion
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What are Some Pros and Cons of
Delivering PRP in More Than One Sitting?
Pros (theoretical):
 Allows edema and associated VA loss to
subside before next PRP sitting
Cons:
 Inconvenient
 Potential for failure to complete intended
treatment plan (VH)
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Primary Study Objective
Determine the incidence of new macular
edema on OCT, following PRP in diabetic
eyes without center edema at 34 weeks
To compare the incidence of macular
edema with a 1-sitting versus 4-sitting
regimen
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Non-Randomized Study:
Rational
Investigators who complete PRP in one
sitting were unwilling to perform PRP in
multiple sittings and vice versa
Therefore, prospective nonrandomized
study conducted
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Study Design
Prospective, Non-Randomized Study
Major Eligibility Criteria Assessed:
>18 years old
Type 1 or type 2 diabetes
Early-PDR or Severe-NPDR (high risk PDR not eligible)
Retinal thickness on OCT < 300 microns in the central subfield
Visual Acuity letter score > 73 (20/32 or better)
No clinical DME requiring treatment
Investigator declared, prior to study initiation, if PRP
planned for 1 or 4 sittings for all subjects
participating in protocol
1 Sitting
4 Sittings
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PRP Treatment Regiment
• 1200-1600 total burns (ETDRS parameters)
1 Sitting and
4 Sitting
• Retrobulbar/peribulbar anesthesia optional
• Slit lamp delivery systems
• Each session 4 weeks apart (+4 days)
• 300 burns in each of first two sittings
4 Sittings
• Investigator discretion for # of burns in 3rd
and 4th sittings
• Total of 4 sittings between 1200 and 1600
burns
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PRP Burn Characteristics
Laser Parameters:
Burn Size
200 microns with Rodenstock lens (or equivalent)
500 microns with three mirror contact lens
Burn Duration
0.05 – 0.2 seconds (0.1 recommended)
Wavelength
Green to yellow (red if vitreous hemorrhage present)
Intensity
Standard mild white burns
Distribution
Edges at least 1 burn width apart, no closer than one
row within the arcades and two disc diameters
temporal to the fovea
Extent
Arcades to at least the equator
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Outcome Assessment
3 Day
4 Week
17 Week
• Visual acuity measured at 3 meters
with the Electronic-ETDRS Visual
Acuity (EVA) device
• Central Subfield Thickness Using
Zeiss Stratus OCT
• Central Subfield Thickness
• Primary Outcome
34 Week
• E-ETDRS Visual Acuity
• 3-Field Fundus Photographs
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Results
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Study Enrollment
155 subjects enrolled at 27 sites
1 sitting
84 subjects
4 sittings
71 subjects
34-week Visit Completion (Primary Outcome)
1 sitting
88%
4 sittings
82%
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Baseline Characteristics
Women:
Median Age:
Race:
White
African-American
Hispanic or Latino
Asian
More than one race
1 Sitting
48%
56 yrs
4 Sitting
44%
54 yrs
64%
24%
11%
0
1%
46%
28%
18%
6%
1%
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Baseline Characteristics
1 Sitting
4 Sitting
19%
81%
18 yrs
7.7
25%
75%
20 yrs
8.2
*HbA1c: Missing 7 in one-sitting group, 13 in 4 sitting group
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Diabetes Type
Type 1
Type 2
Median Duration of Diab.
Median HbA1c (%)*
Baseline Characteristics
1 Sitting
Prior Focal Macular Laser
14%
Median E-ETDRS Letter Score 85
4 Sitting
11%
83
(Snellen equivalent)
20/20
20/20
Median OCT CSF Thickness
207µ
198µ
3 (4%)
1 (1%)
CSF 250 – 299 Microns
Median OCT Retinal Volume 6.9 mm3
7.0 mm3
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Baseline Retinopathy Severity
1 Sitting
N
81
Mild NPDR
6%
Moderate NPDR
9%
Moderately Severe NPDR 30%
Severe NPDR
6%
Mild PDR
23%
Moderate PDR
14%
High Risk PDR
11%
Cannot Grade
1%
4 Sitting
66
0
3%
38%
8%
15%
15%
18%
3%
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Scatter Treatment
N
Median # of Burns
1 Sitting
84
1 Sitting
1274
Median Average Power 280mW
4 Sitting
71
4 Sitting
1260*
250mW
Retrobulbar Injection
46%
14%**
Incomplete Treatment
0%
15%
Additional PRP
7%
0%
* Total over all 4 sittings.
**At least once
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Central Subfield Thickness
Baseline
1-sitting
4-sitting
207µ
198µ
Change from baseline - median microns
3d
+9
+5
4wks
+13
+5
17wks
+14
+15
34wks
+14
+22
P value
0.01
0.003
0.08
0.06
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Central Subfield Retinal Thickness:
34 Weeks vs. Baseline
OCT Central Subfield
(Microns)
500
400
300
200
100
100
1-sitting
4-sittings
150
200
250
300
Baseline OCT Central Subfield (Microns)
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CSF ≥250 Microns and Change
from Baseline ≥ 25 Microns
100%
80%
60%
40%
20%
0%
1%
3%
3-Day
10%
17%
5%
4-Week
1-sitting
6%
17-Week
24%
13%
34-Week
4-sitting
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Macular Edema on Fundus Photos at
34 weeks
8%
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Treatment of DME
One eye in each group was treated for
DME prior to 34 weeks
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E-ETDRS Visual Acuity
1 Sitting
4 Sitting
P Value
Mean Letter Score
Baseline
85
83
3d
−3
−1
0.005
4wks
−1
−1
0.37
17wks
−1
−1
0.66
34wks
0
−2
0.006
Change from baseline
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E-ETDRS Visual Acuity: 3 Day
N=82
N=66
2%
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E-ETDRS Visual Acuity: 4 Week
N=78
N=67
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E-ETDRS Visual Acuity: 17 Week
N=77
N=63
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E-ETDRS Visual Acuity: 34 Week
N=56
17%
N=72
2%
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Vitreous Hemorrhage
A vitreous hemorrhage reducing
visual acuity by 10 or more letters
occurred in 2 eyes in each group.
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Discussion
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Summary
Treatment groups balanced on baseline
factors
Number of total burns similar between
treatment groups
Retrobulbar anesthesia more commonly
used in 1-sitting group

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Summary
 CSF Thickness Remained Normal in Most Eyes
 3 Days –
• CSF Greater in 1 than 4 Sitting Group
 34 Weeks –
•
CSF Greater in 4 than 1 Sitting Group
 Differences Unlikely to be Clinically Relevant

VA and OCT Results Consistent
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Conclusion
Eyes Without Edema
Single Sitting PRP –
• Safe
• Little Change in VA or Edema
 1 Sitting vs. 4 Sitting PRP –
• Clinically Meaningful Differences Unlikely
• VA and OCT Changes Similar
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Study Limitations
1 Sitting vs. 4 Sitting PRP
 Small Sample Size
• Only Large Differences Ruled Out
 Non – Randomized Study Design
• Uncontrolled Confounding Possible
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Conclusion
1 Sitting vs. 4 Sitting PRP
 Results Apply Only to Eyes Without
Edema
 Impact if 1 & 4 Sittings Clinically
Equivalent
 One Sitting Benefits and Risks
• Increased Patient Convenience
• Decreased Patient Cost – Travel & Productivity
• Possible Risk of Retrobulbar Anesthesia
 Unknown if results apply to eyes with DME
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Thank You
 Subjects who volunteered to participate in this trial
 27 clinical study sites investigators, coordinators, and
other staff
 DRCR Network Data and Safety Monitoring Committee
 DRCR Network General Steering Committee
 Other DRCR Network investigators and staff
 Sponsor: National Eye Institute of the National
Institutes of Health (U.S. Department of Health and
Human Services
For further information and all DRCR Network financial disclosures,
go to www.drcr.net
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