The Diabetic Retinopathy Clinical

Research Network

Management of DME in Eyes with

PDR

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What Has Been Learned?

Diabetic Retinopathy Treatment

Protocol F: Results suggest that clinically meaningful

differences are unlikely in OCT thickness or visual

acuity following application of PRP in 1 sitting compared

with 4 sittings in absence of DME. These results suggest

PRP costs to some patients in terms of travel and lost

productivity as well as to eye care providers could be

reduced. Diabetic Retinopathy Clinical Research Network. Observational study of the

development of diabetic macular edema following panretinal (scatter)

photocoagulation given in 1 or 4 sittings. Arch Ophthalmol.2009

Feb;127(2):132-40

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Diabetic Retinopathy Clinical Research Network. Randomized Trial Evaluating Short-Term

Effects of Intravitreal Ranibizumab or Triamcinolone Acetonide on Macular Edema Following

Focal/Grid Laser for Diabetic Macular Edema in Eyes Also Receiving Panretinal

Photocoagulation. Retina. 2011 June;31(6):1009-27

Randomized Trial Evaluating Short-Term Effects of

Intravitreal Ranibizumab or Triamcinolone Acetonide

on Macular Edema Following Focal/Grid Laser for

Diabetic Macular Edema in Eyes Also Receiving

Panretinal Photocoagulation. (Protocol J)

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*Adjusted for baseline visual acuity, number of planned PRP sittings, and correlation between 2 study eyes.

** Missing (or un-gradeable) data as follows for the sham+focal/grid/PRP laser group, ranibizumab+focal/grid/PRP laser group,

and triamcinolone+focal/grid/PRP laser groups, respectively: 3, 3, 2 † Adjusted for baseline OCT retinal thickness and visual acuity, number of planned PRP sittings, and correlation between 2

study eyes. Confidence intervals are adjusted for multiple comparisons.

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Results

Mean Change from baseline to 14 Weeks

Sham+

Focal/Grid/P

RP Laser

N = 123

Ranibizumab+

Focal/Grid/PR

P Laser

N = 113

Triamcinolo

ne+

Focal/Grid/P

RP Laser

N = 109

Visual Acuity -4 +1 +2

Difference in mean change

from Sham

+Focal/Grid/PRP Laser [P

Value]*

+5.6

[P < 0.001]

+6.7

[P < 0.001]

OCT central subfield

thickening (µm)** -5 -39 -92

Difference in mean change

from Sham+

Focal/Grid/PRP Laser

[P Value] †

-35

[P = 0.007]

-100

[P < 0.001]

000 444 141414 343434 565656

Me

an

Ch

an

ge

in

Vis

ua

l A

cu

ity

fro

m B

as

elin

e (

lett

er

sc

ore

)

-5

-4

-3

-2

-1

0

1

2

3

4

5

Sham+Focal/Grid/PRP Laser

Ranibizumab+Focal/Grid/PRP Laser

Triamcinolone+Focal/Grid/PRP Laser

Mean Change in Visual Acuity* from

Baseline

5

Safety Phase (DME treatment at investigator discretion)

Randomized Phase (DME treatment according to protocol)

* Values that were ±30 letters were assigned a value of 30

000 444 141414 343434 565656

Mean

Ch

an

ge in

OC

T C

en

tral S

ub

field

Th

ickn

ess f

rom

Baselin

e (

mic

ron

s)

-120

-100

-80

-60

-40

-20

0

20

40

60

80

100

120 Sham+Focal/Grid/PRP Laser

Ranibizumab+Focal/Grid/PRP Laser

Triamcinolone+Focal/Grid/PRP Laser

Mean Change in Retinal Thickness

from Baseline

6 Randomized Phase

(DME treatment according to protocol)

Safety Phase (DME discretion)

Safety Phase (DME treatment at investigator discretion)

Summary Randomized Phase

14 week primary outcome visit: • On average, both ranibizumab and triamcinolone statistically

significantly improve visual acuity and retinal thickness compared to

sham injection in eyes with central DME receiving focal/grid laser and

requiring prompt PRP

• Focal/grid given with PRP does not, on average, reduce edema in short-

term (in contrast to focal/grid in absence of PRP which does reduce

edema)

Safety Phase

14 week to 56 week visits:

• Differences in visual acuity and retinal thickness outcomes above no

longer identified

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Conclusion

The addition of 1 intravitreal triamcinolone or

2 ranibizumab injections in eyes receiving

focal/grid laser for DME and PRP is associated

with better visual acuity and decreased

macular edema by 14 weeks, but these effects

are not maintained by 56 weeks in absence of

continued injections for persistent or

recurrent DME.

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Coexisting PDR and DME

49 yo BM NIDDM x 20 yrs VA 20/50 RE 20/200 LE

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Coexisting PDR and DME

Irregular FAZ, temporal

capillary non-perfusion, NVE

Capillary nonperfusion

adjacent to FAZ; fluorescein in

cystoid spaces

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No DME RE

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But substantial DME LE

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Coexisting PDR and DME LE

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NVE nasally

Capillary nonperfusion

adjacent to FAZ; fluorescein in

cystoid spaces

Coexisting PDR and DME

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Treatment OS

One week later VA 20/25

RE

PRP OD 2331 spots

Pascal laser (complete)

200 microns, 20 msec,

343 mW, Mainster 165

lens

No anti-VEGF or

steroids given

Treatment OD

One week later VA

20/200 LE and RZB 0.3

mg IVT given

2 weeks after RZB, PRP

OS 1683 spots Pascal

laser (incomplete), 200

microns, 20 msec, 275

mW, Mainster 165 lens

2 weeks post PRP RE, no new DME,

VA 20/25

15

2 weeks post ranibizumab LE, DME

persists but better, VA 20/200, PRP done

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4 weeks post RZB, 2 weeks post PRP LE,

DME reduced, VA 20/200

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Conclusions and Opinions

Management of coexisting DME and PDR is challenging but pharmacologic

treatment of the DME component reduces the risk of exacerbation of the DME

post-PRP in the short term

In eyes without DME that receive PRP for PDR or severe NPDR, the risk of

developing DME post-PRP is low, even if the PRP is completed in one sitting

Extrapolating current knowledge of anti-VEGF treatment of center involved

DME from multiple trials, treatment of DME with anti-VEGF therapy prior to

PRP should be continued post laser until the DME is stabilized or resolved to

achieve the best visual outcomes

Additionally, focal/grid laser plus anti-VEGF injection prior to PRP may not be

necessary since no additional benefit of laser has been found when treating

center involved DME alone

Protocol S will give additional data on the effect of ranibizumab on DME in

the setting of PDR treated with PRP

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