1. Diabetic Retinopathy Clinical Research Network
PRP vs intravitreous ranibizumab for PDR: Comparison of the peripapillary RNFL in a Randomized Clinical Trial
Glenn J. Jaffe, M.D.
Supported through a cooperative agreement from the
National Eye Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health, Department of Health and Human Services EY14231, EY14229, EY018817 1

2. Protocol S primary results
Eyes treated with intravitreous ranibizumab for PDR had a mean visual acuity that was not worse than eyes treated with PRP at 2 years
Eyes randomly assigned to 0.5 mg intravitreous ranibizumab had less visual field loss and less frequent DME development
JAMA. 2015;314(20)

3. Literature RNFL thinning associated with VF loss
Thinning of RNFL with PRP and anti-VEGF
DME: thicker RNFL, inner retinal edema

4. Literature cont’d Diabetic RNFL +/- DR thinner than normal
Normal RNFL thickness could be edematous
ME resolution: thinner than normal RNFL

5. Objectives Pre-planned
To compare changes in the peripapillary RNFL at 2 years between the ranibizumab and PRP groups

6. Objectives Pre-planned
To compare changes in the peripapillary RNFL at 2 years between the ranibizumab and PRP groups
Post-Hoc
To correlate changes in RNFL with changes in VF sensitivities at 2 yrs
60-4 HFV Mean deviation
30-2 HVF Mean deviation
To correlate changes in RNFL with changes in CST at 2 yrs

7. Imaging of the RNFL Spectralis or Zeiss Cirrus OCT RNFL
Images readjusted by DRC if automated measurement inaccurate b/c:
Decentration
Artifacts
Segmentation algorithm failure

8. Baseline characteristics
Participants Included
Ranibizumab
Group
(N = 77)
PRP
(N = 69)
Age (yrs) – Median 52 50
Women
43%
Race
White
64%
58%
Visual Acuity (letter score)
Median
80 (20/25)
81 (20/25)
Central Subfield Thickness (µm)- Median
219
227

9. Pre-Planned Objective
TREATMENT GROUP COMPARISON OF CHANGES IN THE RNFL at 2 yrs

10. Average RNFL Measurements of the 2-Year Cohort
Ranibizumab
Group
(N = 68)
PRP
(N = 57)
Heidelberg Spectralis
N=35
N=32
Baseline
96 ± 19
97 ± 20
At 2 years
85 ± 15
95 ± 19
Zeiss Cirrus
N=33
N=25
94 ± 21
97 ± 23
83 ± 16
89 ± 12

11. Average RNFL: At Baseline
Lower than normal
Cirrus: < 76.9 µm
Heidelberg OCT: < 80.4 µm
Normal
Cirrus: µm Heidelberg OCT: µm
Above normal
Cirrus: > µm
Heidelberg OCT: >131.6 µm
Percentage of Eyes

12. Average RNFL: At 2 Years Lower than normal Cirrus: < 76.9 µm
Heidelberg OCT: < 80.4 µm
Normal
Cirrus: µm Heidelberg OCT: µm
Above normal
Cirrus: > µm
Heidelberg OCT: >131.6 µm
Percentage of Eyes

13. Eyes with Normal Average RNFL at Baseline
Percentage of Eyes

14. Mean change in Average RNFL
Missing 2-Year Outcome was imputed using last observation carried forward
Adjusted Mean Difference at 2 years : -4.9 µm (P-value<0.001)
95% CI: (-7.2 µm, -2.6 µm)
At 2 years
N = 74
N = 66

15. Mean change in Average RNFL: No Baseline DME
Adjusted Mean Difference at 2 years : -5.0 µm (P-value<0.001)
95% CI: (-7.8 µm, -2.3 µm)
At 2 years
N=56
N=48

16. Mean change in Average RNFL: With Baseline DME
Adjusted Mean Difference at 2 years : -2.3 µm (P-value=0.32)
95% CI: (-6.7 µm, +2.2 µm)
At 2 years
N=18
N=18

17. Post-Hoc Objectives
Correlate changes in the RNFL with changes in visual field sensitivities at 2 years
Correlate changes in the RNFL with changes in the central subfield thickness (CST) at 2 years

18. 2-Year correlation of RNFL changes with Change in Mean Deviation (60-4 Test)
Ranibizumab Group N = 45
PRP Group N = 40
r= +0.33
P-value=0.035
r=-0.27
P-value=0.07

19. 2-Year correlation of RNFL changes with CSF changes
Ranibizumab Group N = 74
PRP Group N = 66
r= +0.63
Pvalue <0.001
r= +0.34
Pvalue=0.005

20. 2-Year correlation of RNFL changes with CSF changes: No Baseline DME
Ranibizumab Group N = 56
PRP Group N = 48
r= +0.59
P-value <0.001
r= +0.05
P-value=0.75

21. Example Eye has no DME at baseline
Weighted mean deviation of the 60-4 test for this eye was at baseline and at 2 years
No history of glaucoma
Baseline
2 Years

22. Conclusions RNFL thinning with RBZ and PRP at 2 years
Significantly greater RNFL reduction with RBZ
Most RNFL differences in yr. 1
RNFL thinning in yr. 2 similar
RNFL thinning mechanism in 2 groups may differ

23. Discussion
VF sensitivity and RNFL changes: minimal in both groups; however sample size was relatively small
In RBZ group RNFL thinning may be from decreased retinal edema

24. Clinical Implication
OCT-derived RNFL thickness measurements are used to provide objective means to assess glaucoma progression in non-PDR eyes
Due to fluid changes in the inner retina during ranibizumab therapy, RNFL measurements would be a poor means to diagnose and monitor the progression of glaucoma in these eyes.

25. Thank You on Behalf of the Diabetic Retinopathy Clinical Research Network (DRCR.net)25