1) Ozurdex (dexamethasone intravitreal implant) is effective for treating recalcitrant or non-responsive cases of diabetic macular edema (DME) and retinal vein occlusion (RVO). 2) Ensuring patient compliance with regular treatment is a major challenge in managing DME, and Ozurdex's long duration of action can help control disease progression through improved compliance. 3) Case reports demonstrate that Ozurdex can improve vision in DME and RVO patients who were previously non-responsive or partial responders to anti-VEGF therapies like ranibizumab and aflibercept.

1. Messiah of Macula: Ozurdex
Dr Ajay Dudhani

2. Overview
Rebellious Rebels of Diabetic Macular Edema
Startlers of Retinal Vein Occlusion

3. Rebellious Rebels of Diabetic Macular Edema
Surely you would have experienced REBELLIOUS
DME- which just does not respond to any
treatment
A major problem in DME is REBEL Patients-
Who will not come for regular treatment

4. Rebellious Rebels of DME
40% pts gained ≥3line VA@ 24 months with ranibizumab
after monthly injections through 100 weeks*
Is Visual Acuity gains with monthly anti- VEGF injections, reproducible in real world scenario?
In a real world clinical utilization study from USA#
75% of pts receive ≤ 3 anti-VEGF inj in their first year
Compliance and comprehension to treatment is the biggest challenge in developing nations, like India
Ref: *- Korobelnik JF, Do DV, Schmidt-Erfurth U, et al. Intravitreal aflibercept for diabetic macular edema. Ophthalmology. 2014;121(11):2247-2254; #- Kiss S, Liu Y, Brown J, et al. Clinical utilization of anti-vascular endothelial growth-factor agents and patient monitoring in retinal vein
occlusion and diabetic macular edema. Clin Ophthalmol. 2014;8:1611-1621

5. Rebellious Rebels of DME
Ensuring compliance to treatment is key in controlling progression and irreversible visual loss
Progression to PDR in 5 years among NPDR pts
mild (13.0%), moderate(27.2%), severe (45.5%)*
Ref: *- Lee CS, The United Kingdom Diabetic Retinopathy Electronic Medical Record Users Group: Report 3: Baseline Retinopathy and Clinical Features Predict Progression of Diabetic Retinopathy; #-Chang-Lin J-E, et al. Invest Ophthalmol Vis Sci 2011;52:80–6
Ozurdex with long duration of action and help in ensuring
compliance, controlling progression and visual disability#

6. Rebellious Rebels of DME
Non Responders or partial responders is a big problem with Anti-VEGF therapies
VEGF is not the whole story
RISE AND RIDE: Roughly 60% failed to meet primary endpoint after 2 years
VISTA and VIVID: >60% failed to meet secondary endpoint through 100 wks
Protocol T: 33% and 50% did not improve by 15 or more letters at 1 year
Established data shows that : IL-1, RA and
RANTES are key in DME pathogenesis, while
VEGF is pathogenic in PDR
Nguyen QD, Brown DM, Marcus DM, et al. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012;119(4):789-801. 2. Korobelnik JF, Do DV, Schmidt-Erfurth U, et al. Intravitreal aflibercept for diabetic macular edema.
Ophthalmology. 2014;121(11):2247-2254. 3. The Diabetic Retinopathy Clinical Research Network. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Eng J Med. 2015;372(13):1-11.; Sohn HJ et al. Am J Ophthalmol 2011; 152:686–94

7. Rebellious Rebels of DME
Predicting Prognosis on Anti-VEGF; when to switch is the real question?
Early Analysis of Protocol I: < 5 letter gain: 39.7%; 5-9 letter
gain: 23.2%; >10 letter gain: 37.1%; >15 letter gain: 17.6%
VA gain at 12 week can predict VA response at end of 1 year
and and 3rd year
Khan Z’s Metanalysis on Efficacy of the Ozurdex for DME
Refractory to Anti-VEGF
3,859 pts in 15 studies, Ozurdex led to 4 line BCVA gain @ 6
months
 EARLY Analysis in DME, AAO Congress 2015; Khan Z et al. Ophthalmic Surgery, Lasers & Imaging Retina. 2016

8. Case Report
Patient Name: Maria
Diagnosis : DM Uncontrolled , 6/60 OU
AUG 11 -SEVERE NPDR WITH CSME
Therapy :
 BE- Laser + Avastin
 BE Ozurdex AS MAINTENANCE
 Pred Forte + Nevanac
12 MONTHS LATER
 Cataract surgery with Ozurdex INJECTION; PREOP AVASTIN WITH LASER
 FINAL VISION 6/12 N8

9. 01/08/2011
OD

10. 23/08/2011
OD

11. 02/09/2011
OD

12. 16/09/2011
OD

13. ONE YEAR LATER

14. 06/09/2012 OD OS

15. 25/09/2012 OD OD

16. Case Report
Patient Name: Sridhar, 65 year, Male
Diabetic History : Diabetic for 25 years
Diagnosis: proliferative diabetic retinopathy with 6/12 VA
Past Treatment history: PRP done, multiple Avastin
Evaluation: Resistant cyst (giant) and not improving to Avastin
Treatment : Ozurdex switch
End result: Foveal Contour recovery with 6/6 vision

17. 18/02/2012
OS

18. 01/02/2013
OS

19. 07/05/2013
OS

20. 04/02/2014
OS

21. 03/05/2014
OS

22. 19/01/2015
OS

23. 29/01/2016
OS

24. Startlers of Retinal Vein Occlusion
Retinal Vein Occlusion is a complex disease
• Retinal barrier breakdown
• Oxidative stress
• Intracellular edema
1.Ramchandran RS, Shuler RK, Fekrat S. Treatment of retinal vein occlusions. In: Holz FG, Spaide RF, eds. Medical Retina. Berlin, Germany: Springer-Verlag; 2007:147-163.

25. Startlers of Retinal Vein Occlusion
Factors Statistics Implication Ref
Age > 65 years of age High association of multiple systemic risk factors Branch Vein
Occlusion
Study
Group. Am J
Ophthalmol.
1984;98(3):271-
282.
Younger patients High association with hypercoagulable states such as Factor V Leiden
mutations or systemic inflammatory diseases such as lupus
Hypertension ͌60% patients >65 years of age are
hypertensive
6 of 10 patients of RVO are hypertensive R Gupta, Journal
of Human
Hypertension
(2004) 18, 73–7
Arterioscleros
is
85% of patients aged >50 years have
associated atherosclerosis
8 of 10 patients of RVO are at risk of myocardial infarction and stroke Tuzcu EM, et al..
Circulation.
2001;103:2705-
2710.
Diabetes
Mellitus
India is the diabetes capital of the
world with 70 million diabetics
Increased glucose in blood adds to the oxidative and inflammatory
stress to the ischemic retina
Niral Karia. Clin
Ophthalmol.
2010; 4: 809–816.
Glaucoma >4% prevalence of Glaucoma in
patients aged >60 years
1 in 25 RVO patient can have associated glaucoma Chandrima Paul
et al. Hooghly
River Glaucoma
Study. IJO.
2016;64:578-583
Lamellar Hole 0.17% prevalence with mean age of 67
years
Reports of increasing macular hole with anti-VEGF therapy makes
effective management a challenge
Manish Nagpal et
al. Case Reports
in
Ophthalmological
Medicine.
2011;679751:3
Recalcitrant
ME of RVO
<6 letter gain – 30% pts on antiVEGF
therapy after 3 injections and 1 year
Two-thirds of patients that were low-responders after the loading
phase remained low-responders after 1 year
Marcel N.
Menke. J
Ophthalmol.
2016; 2016:
9875741

26. Case Report
Patient Name: Manohar
Diagnosis : 1 Eyed
DM + HT WELL CONTROLLED
BLOOD AND THUNDER CRVO WITH CME 6/60 N36 -FEB 2011
Therapy :
1. Laser DONE BEFORE FOR NPDR
2. Two Macugen (H/O MI ) + 1 OZURDEX
3. 3 Lucentis
4. Nevanac Only (as Steroid Responder)
5 POAG ON XALATAN +2 DRUGS

27. 14/02/2011
OS

28. 21/03/2011
OS

29. 19/06/2011
OS

30. 23/07/2011
OD

31. 06/06/2011
OS

32. 22/06/2011
OS

33. 16/09/2011
OS

34. 07/10/2011
OS

35. 16/11/2011
OS

36. 10 MONTHS LATER
5 MORE LUCENTIS INJECTIONS PRN
CARARACT UNDER LUCENTIS COVER
VISION 6/18 N18
LAST ONE YEAR SWITCHED BACK TO
OZURDEX
STAYS FLAT FOR 4 MONTHS

37. 05/09/2012
OS

38. 06/11/2012
OS

39. 28/11/2012
OS

40. 09/01/2013
OS

41. 13/10/2015
OS

42. 07/11/2015
OS

43. Case Report
Patient Name: Kamruddin Vastani.
Age : 75 Years
Diagnosis : Post Operative CME
Therapy :
1. Ozurdex
2. Pred Forte+ Nevanac

48. 3 years later with single ozurdex