1. Sponsored by the National Eye Institute,
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.

2. 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

3. 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

4. What are Some Pros and Cons of Delivering PRP in 1 Sitting?
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

5. 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)

6. 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

7. 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

8. Prospective, Non-Randomized Study Major Eligibility Criteria Assessed:
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

9. PRP Treatment Regiment
total burns (ETDRS parameters)
Retrobulbar/peribulbar anesthesia optional
Slit lamp delivery systems
1 Sitting and
4 Sitting
Each session 4 weeks apart (+4 days)
300 burns in each of first two sittings
Investigator discretion for # of burns in 3rd and 4th sittings
Total of 4 sittings between 1200 and 1600 burns
4 Sittings

10. 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

11. Outcome Assessment
Visual acuity measured at 3 meters with the Electronic-ETDRS Visual Acuity (EVA) device
Central Subfield Thickness Using Zeiss Stratus OCT
3 Day
4 Week
17 Week
Central Subfield Thickness
Primary Outcome
E-ETDRS Visual Acuity
3-Field Fundus Photographs
34 Week

12. Results

13. 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% 13

14. Baseline Characteristics
Women: 48% 44%
Median Age: 56 yrs 54 yrs
Race:
White 64% 46%
African-American 24% 28%
Hispanic or Latino 11% 18%
Asian 0 6%
More than one race 1% 1%
1 Sitting
4 Sitting

15. Baseline Characteristics
Diabetes Type
Type 1 19% 25%
Type 2 81% 75%
Median Duration of Diab. 18 yrs 20 yrs
Median HbA1c (%)*
1 Sitting
4 Sitting
*HbA1c: Missing 7 in one-sitting group, 13 in 4 sitting group

16. Baseline Characteristics
1 Sitting
4 Sitting
Prior Focal Macular Laser 14% 11%
Median E-ETDRS Letter Score 85 83
(Snellen equivalent) 20/20 20/20
Median OCT CSF Thickness 207µ 198µ
CSF 250 – 299 Microns 3 (4%) 1 (1%)
Median OCT Retinal Volume mm3 7.0 mm3

17. Baseline Retinopathy Severity
1 Sitting
4 Sitting
N 81 66
Mild NPDR 6% 0
Moderate NPDR 9% 3%
Moderately Severe NPDR 30% 38%
Severe NPDR 6% 8%
Mild PDR 23% 15%
Moderate PDR 14% 15%
High Risk PDR 11% 18%
Cannot Grade 1% 3%

18. Scatter Treatment 1 Sitting 4 Sitting N 84 71 Median # of Burns
Median Average Power
Retrobulbar Injection
Incomplete Treatment
Additional PRP
1274
280mW
46% 0% 7%
1 Sitting
1260*
250mW
14%**
15% 0%
4 Sitting
* Total over all 4 sittings.
**At least once

19. Central Subfield Thickness
1-sitting 4-sitting P value
Baseline 207µ 198µ
Change from baseline - median microns 3d
4wks
17wks
34wks

20. Central Subfield Retinal Thickness: 34 Weeks vs. Baseline
Ricks added an 11% line

21. CSF ≥250 Microns and Change from Baseline ≥ 25 Microns

22. Macular Edema on Fundus Photos at 34 weeks8%

23. Treatment of DME
One eye in each group was treated for DME prior to 34 weeks

24. E-ETDRS Visual Acuity 1 Sitting 4 Sitting P Value Baseline 85 83
Change from baseline
3d −3 −
4wks −1 −
17wks −1 −
34wks 0 −
1 Sitting 4 Sitting P Value
Mean Letter Score 24 24

25. E-ETDRS Visual Acuity: 3 Day
N=82
N=66 2%

26. E-ETDRS Visual Acuity: 4 Week
N=78
N=67

27. E-ETDRS Visual Acuity: 17 Week
N=77
N=63

28. E-ETDRS Visual Acuity: 34 Week
N=56
N=72
17% 2%

29. Vitreous Hemorrhage
A vitreous hemorrhage reducing visual acuity by 10 or more letters occurred in 2 eyes in each group.

30. Discussion

31. Summary Treatment groups balanced on baseline factors
Number of total burns similar between treatment groups
Retrobulbar anesthesia more commonly used in 1-sitting group

32. 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

33. 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

34. Study Limitations 1 Sitting vs. 4 Sitting PRP Small Sample Size
Only Large Differences Ruled Out
Non – Randomized Study Design
Uncontrolled Confounding Possible

35. 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 35

36. For further information and all DRCR Network financial disclosures,
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 36 36