ways to treat diabetic macular edema, in brief

1. The Current Treatment
Options for
DME
,in Brief
Nawat watanachai
CMU
01, 2014

2. treatment options for DME
laser
laser+antiVEGF
antiVEGF
new comers

3. Laser treatment
80’s
ETDRS
focal/ grid laser to microaneurysms or area of DME

4. laser + antiVEGF
DRCRnet
prospective trial
comparing standard laser to combination with
Lucentis or steroid
VA : laser + Lucentis > laser alone

5. laser + antiVEGF
RESTORE trial
randomized control
VA : Lucentis/ Lucentis+laser > laser
1 yr : Lucentis(7inj) = Lucentis + laser
2 yrs : Lucentis(3.9inj) = Lucentis(3.5inj) +
laser

6. laser + antiVEGF
at 1 yr
Lucentis
Lucentis
+laser
laser
REVEAL
Asian population
similar to RESTORE
VA
(ETDRS
letter)
no of
injection
+5.9
+5.7
+1.4
7.8
7.4
-

7. antiVEGF mono therapy
Lucentis
RISE and RIDE trials
double masked, sham-controlled, multicenter
Lecentis monthly 0.3mg, 0.5mg, sham
24 mths duration + additional Rx through 36 mths
after 3 mtgs : rescue laser could apply

8. antiVEGF mono therapy
Lucentis
24mths
sham
0.3mg
0.5mg
>15 letters
gain (%)
18.1
44.8
39.2
required PRP
(%)
11
0
0.8
RISE

9. antiVEGF mono therapy
Lucentis
24mths
RIDE
sham
0.3mg
0.5mg
>15 letters
gain (%)
12.3
33.6
45.7
required PRP
(%)
12.3
1.6
1.6

10. antiVEGF mono therapy
Lucentis
RISE and RIDE
24 mths : macular laser procedures needed
sham 1.8, 1.6
lucentis 0.3, 0.8
RISE and RIDE
august 2012 : USFDA approved 0.3mg Lucentis for DME Rx

11. antiVEGF mono therapy
Avastin
BOLT trials
1.25mg Avastin VS laser
non-ischemic center-involving CSME
12 mths : median VA (ETDRS letters)
Avastin : +8
laser : -0.5

12. New Comers
Ozurdex
sustain-released dexamethasone intravitreal implant
22G needle
last 6 mths
FDA approved for
BRVO/CRVO associated ME
non-infectious uveitis

13. New Comers
Dexa implant
Ozurdex
Haller J, Kuppermann B, Blumenkranz M.
Randomized Controlled Trial of an Intravitreous Dexamethasone Drug Delivery System in
Patients With Diabetic Macular Edema. Arch Ophthalmol 2010
persistent DME > 90d, 171 eyes
observation VS Ozurdex 350mcg, 700mcg
6 mths : BCVA improved > 10 letter
observe
23%
Ozurdex 350 mcg
19%
Ozurdex 700 mcg
30%
6 mths : CRT, FA leakage also better in the 700 mcg groups

14. New Comers
Dexa implant
Ozurdex
Boyer D, Faber D, Gupta S, et al. Dexamethasone
Intravitreal Implant for Treatment of Diabetic Macula
r Edema in Vitrectomized Patients. Retina 2011
improved VA and CRT with the 700 mcg implant

15. New Comers
fluocinolone implant
Iluvein
sustained-release fluocinolone intravitreal implant
25G needle
last 2.5-3 yrs

16. New Comers
fluocinolone implant
iluvein
FAME study
prospective randomized trial
3 yrs data
0.2mcg/d, 0.5mcg/d, sham

17. New Comers
fluocinolone implant
iluvein
FAME study
3 yrs : >15 letters gain
0.2mcg/d
28.7%
0.5mcg/d
27.8%
sham
18.9%
all phakic developed cataract
glaucoma Sx 4.8 and 8.1%
approved for treating DME in Europe
not in the USA

18. New Comer
Eylea
Eylea (Aflibercept)
FDA-approved for AMD
recombinant fusion protein comprising the key
VEGF-binding domains of human VEGF receptors 1
and 2
higher binding affinity versus Lucentis/ Avastin

19. New Comer
Eylea
Eylea (Aflibercept)
Da Vinci trial : phase II
center-involving DME : 5 groups
eylea 0.5mg q 4 wks
eylea 2 mg q 4 wks
eylea 2 mg mthly for 3X, then q 8 wks
eylea 2 mg mthly for 3X, then as needed
laser

20. New Comer
Eylea
Da Vinci trial : phase II
0.5mg
2mg
2mg for
2mg for
3X, then q 3x, then pr
8 wks
n
laser
+9.7
+12.0
+1.3
q4
wks
q4
wks
mean
BCVA (lett
ers)
+11.0
+13.1
gain>15
letters (%)
40.9
45.5
23.8
42.2
11.4
Mean CRT
(mcn)
-165.4
-227.4
-187.8
-180.3
-58.4
1 yr

21. the time to evolve is NOW!!
- after >20 yrs, macular focal/grid laser monotherapy is now called into question as the best
clinical practice
- evidences to change the standard of care for treating center-involving DME to anti-VEGF
therapy, particularly ranibizumab with or without laser treatment
- adding laser to anti-VEGF therapy doesn’t provide better visual outcomes, it may decrease total
injections
- The exact best injection treatment protocol has yet to be established
- monthly injection
- as-needed
- “treat and extend”
- An interesting result from the RISE and RIDE studies is the suggestion that ranibizumab
monotherapy had a lower progression to proliferative retinopathy than the sham arm
- Bevacizumab remain readily available alternatives to ranibizumab.
- The role of aflibercept has yet to be established but its Phase II data demonstrates promising
efficacy and safety
- The extended-release steroid devices are intriguing for post-vitrectomized eyes or potentially for
resistant cases of DME