A summary of prominent RVO studies

1. Retinal Vein Occlusion
Studies
Dr. Riyad Banayot

2. Prevalence
Retinal vein occlusions (RVOs) are the 2nd most common retinal
vascular diseases after diabetic retinopathy.
 The Beaver Dam Study reported a prevalence of 0.1% in patients
older than 43 years.
 A cross-sectional study from 6 US communities reported that the
prevalence of CRVO was 0.2%. (the prevalence was similar
across different ethnic and racial groups).
 The Blue Mountains Eye Study, the 10-year cumulative incidence
of CRVO in a population older than 48 years was 0.4%.
 The Singapore Malay Eye Study reported a 0.2% prevalence of
CRVO in the Malay population 40 to 80 years old.
 The Beijing Eye Study reported that the prevalence of CRVO in a
Chinese population of people 40 years and older was 0.1%.(No
racial or gender predilection for the disease is apparent).

3. Associated systemic factors
 Diabetes
 Hypertension
 Hyperlipidaemia
 Hyperhomocysteinaemia
 Blood coagulation disorders:
 high plasma viscosity such as due to leukaemia, myeloma,
Waldenstrom’s macroglobulinaemia, myelofibrosis, changes
in protein C pathway, Factor V Leiden.
 Systemic inflammatory disorders
 (Behçets disease, polyarteritis nodosa, sarcoidoisis,
Wegener’s Granulomatosis and Goodpasture’s Syndrome)
 Glaucoma
 Shorter axial length
 Retrobulbar external compression

4. CRVO
 Disc edema
 Increased dilatation and
tortuosity of all retinal
veins
 Widespread deep and
superficial hemorrhages
 Cotton wool spots
 Retinal edema
 Capillary non-perfusion
in all four quadrants of
the retina

5. HRVO & BRVO

6. Complications

7. Classical Treatment
 Branch Vein Occlusion Study, 1984, showed that
macular photocoagulation for the treatment of
macular edema was superior in improving visual acuity
compared with observation.
 Central Vein Occlusion Study, 1995, showed that grid
laser treatment of macular edema was of no visual
benefit despite the elimination of macular edema in
treated eyes. Observation for macular edema
secondary to CRVO was the standard of care set by
this study.

8. Pharmacologic Rx options for
Macular edema
Dexamethasone
intravitreal implant
(Ozurdex)
Ranibizumab
(Lucentis)
Aflibercept
(Eylea)
Bevacizumab
(Avastin)
CRVO FDA FDA FDA Off label
BRVO FDA FDA Off label

9. RVO studies
 SCORE-C/B 2009 IV Triamcinolone Vs. Observe/Grid
 GENEVA-C/B 2010 evaluate IV Dexamethasone
 extended to 1 year
 SHASTA-C/B 2014 evaluate IV Dexamethasone
 CRUISE-C 2010 evaluate IV Ranibizumab
 extension HORIZON
 BRAVO-B 2010 evaluate IV Ranibizumab
 extension RETAIN
 COPERNICUS-C 2014 evaluate IV Aflibercept
 GALILEO-C 2014 evaluate IV Aflibercept
 VIBRANT-B 2013 evaluate IV Aflibercept

10. SCORE study 2009
 Compared the use of 1-mg, 4-mg
intravitreal triamcinolone (Trivaris*) to
standard care:
 Observation for CRVO
 Grid laser for BRVO
• unpreserved triamcinolone
• Triesence

11. Results: SCORE-BRVO
Trivaris 1mg Trivaris 4mg Grid Laser
Year 1
VA gain ≥ 3 lines
26% 27% 29%
Year 2 & 3
VA
Sustained Sustained Sustained
Patients who were randomized to grid laser underwent a
mean 1.5 treatments in year 1, and those who received
IVTA had an average of 2 injections
• The rates of cataract formation and IOP elevation were
higher in the steroid groups
• The recommendation was that laser remain the
standard of care for BRVO

12. Results: SCORE-CRVO
Trivaris 1mg Trivaris 4mg Observation
Year 1
VA gain ≥ 3 lines
27% 26% 7%
Year 2
VA
Sustained Sustained
Patients received an average of 2 injections of IVTA over
the course of 1 year

13. GENEVA study 2010
 Evaluated dexamethasone intravitreal dexamethasone
implant (Ozurdex) for the treatment of macular edema 2ry to
BRVO or CRVO
 Entry criteria:
 VA: 20/50 to 20/200
 CMT ≥300 μm
0.7 mg
Dexamethasone
0.35 mg
Dexamethasone
Sham
Single treatment Single treatment Single treatment

14. Results: GENEVA study
3 month FU 0.7 mg
Ozurdex
0.35 mg
Ozurdex
Sham
VA
improvement
≥15 letters
22% 23% 13%
CMT
improved by
208
±201 μm
177
±197 μm
85
±173 μm
After 3 months, there were significant improvements in visual acuity
Patients with greater than 90 days’ duration of macular edema associated
with BRVO observed a significantly greater response rate

15. Results: GENEVA study
6 month FU 0.7 mg
Ozurdex
0.35 mg
Ozurdex
Sham
VA
improvement
15 or more
letters
22% 19% 18%
CMT
improved by
119
±203 μm
123
±212 μm
119
±188 μm
Changes in VA nor CMT for treatment groups were NOT significant when
compared with the sham group at the 6-month interval

16. Extension of GENEVA study
 After 6 months, study was extended to 12 months
 Patients received the open-label 0.7 mg Dexamethasone
intravitreal implant
 Criteria:
 VA: <84 ETDRS letters or
 CMT: >250 um
12 month 0.7 mg Ozurdex Sham
BCVA improvement 32% 30%

17. Results: Extension of
GENEVA study
12 month 0.7 mg Ozurdex Sham
BCVA improvement 32% 30%
12 month X2 0.7 mg Ozurdex Sham
Cataract 29.8% 5.7%
12 month 0.7 mg Ozurdex
IOP increase ≥10 mm Hg (1st injection) 12.6%
IOP increase ≥10 mm Hg (2nd injection) 15.4%

18. SHASTA Study 2014
 The effects of multiple dexamethasone implants for
macular edema secondary to CRVO or BRVO
 Patients received a mean 3.2 dexamethasone implants
with mean injection interval between implants was 5.6
months
After 6 implants BRVO CRVO
BCVA gain ≥2 lines 59.7% 66.7%
CMT significant reduction significant reduction
IOP increase ≥10 mm Hg 32.6%
Medical treatment for high IOP 29.1%
Surgical treatment for high IOP 1.7%
Laser treatment for high IOP 1.4%

19. CRUISE study 2010
 12-month clinical trial
 Evaluated the efficacy and safety of anti-VEGF injections
in the treatment of macular edema secondary to CRVO
 Criteria:
 visual acuity of 20/40 to 20/320
 CMT≥ 250 μm
 Injections
0.3 mg
ranibizumab
0.5 mg
ranibizumab
Observation
Monthly for 6 M Monthly for 6 M Monthly for 6 M
“as needed” basis
from months 6-12
“as needed”
basis from
months 6-12
0.5 mg ranibizumab,
followed by “as
needed” basis

20. Results: CRUISE study
initial effects of ranibizumab therapy within 7days after the first injections
6 month FU 0.3 mg
ranibizumab
0.5 mg
ranibizumab
Observation
VA
improvement
≥3 lines
46.2% 47.7% 16.9%
Letters from
baseline
BCVA
12.7 14.9 0.8
CMT
improved by
433.7
±51.2 μm
452.3
±44.7 μm
167.7
±53.7 μm
These improvements were maintained in both treated groups at 12 months

21. HORIZON study
extension of CRUISE study
 HORIZON extension trial, patients continue to receive 0.5mg
ranibizumab on a PRN basis
 FU on a mandatory quarterly basis for the next year
 A total of 151 patients with CRVO received ranibizumab therapy
and the mean number of injections was 3.9 (range 0 – 12).
Ranibizumab 0.5mg SHAM
VA improvement from
CRUISE baseline
- 4.1
Letters gained from
CRUISE baseline
12 7.6

22. BRAVO study 2010
 12-month clinical trial
 Evaluated the efficacy and safety of anti-VEGF
injections in the treatment of macular edema secondary
to BRVO
 Injections
0.3 mg
ranibizumab
0.5 mg
ranibizumab
Sham
Monthly for 6 M Monthly for 6 M Monthly for 6 M
“as needed” basis
from months 6-12
“as needed” basis
from months 6-12
0.5 mg ranibizumab,
followed by “as
needed” basis
subjects were eligible to receive rescue laser treatment during the clinical trial

23. Results: BRAVO study
6 month FU 0.3 mg
ranibizumab
0.5 mg
ranibizumab
Sham
VA
improvement
≥3 lines
55.2% 61.1% 28.8%
Letters from
baseline
BCVA
16.6 18.3 7.3
CMT
improved by
337.3
±38.3 μm
345.2
±41.2 μm
157.7
±38.6 μm
Effects were not permanent and the patients might require several re-injections

24. RETAIN study
extension of CRUISE study
 The RETAIN study was an extension study for patients who completed the
HORIZON study.
 Only 34 patients from the BRAVO study were enrolled in the RETAIN
study. On average, patients had a follow-up of 4 years.
 Patients were followed monthly during the first year of the study and at
least every 3 months during the second year of the study.
 Reinjections were performed if intraretinal fluid was identified.
 Results demonstrate the excellent long-term outcomes of eyes with
macular edema secondary to BRVO.
Ranibizumab
Resolution of macular edema 44%
VA improvement ≥3 lines 53%
BCVA of 6/12 or better 80%

25. COPERNICUS study 2014
 Evaluating the efficacy of aflibercept in CRVO
 Entry criteria:
 VA: 20/40 to 20/320
 CMT >250 μm
2 mg aflibercept Sham
Monthly for 6 M Monthly for 6 M
“as needed” basis from
months 6-12
Allowed to receive aflibercept
after week 24

26. Results: COPERNICUS study
6 month FU 2 mg aflibercept Sham
VA improvement
≥15 letters
57.9% 12.3%
CMT improved by 457.2 μm 144.8 μm
Benefits were maintained at 52 weeks

27. GALILEO study 2014
 Evaluating the efficacy of aflibercept in CRVO
 Entry criteria:
 VA: 20/40 to 20/320
 CMT >250 μm
2 mg aflibercept Sham
Monthly for 6 M Monthly for 6 M
“as needed” basis from
months 6-12
“as needed” basis from
months 6-12

28. Results: GALILEO study
6 month FU 2 mg aflibercept Sham
VA improvement
≥15 letters
60% 22%
CMT improved by 448.6 μm 169.3 μm
Benefits were maintained at 52 weeks

29. VIBRANT Study 2013
 Double-masked, randomized, active-controlled study of
183 patients with macular edema following BRVO
 Treatment:
 2 mg intravitreal aflibercept every 4 weeks OR
 laser treatment, up to week 24
Week 24 2 mg aflibercept Laser
BCVA improvement ≥15 letters 53% 27%

30. RVO studies Recommendation
SCORE-C/B
IV Triamcinolone Vs.
Grid/Observation
Laser remain the standard of care for
BRVO
IV Beneficial for CRVO
GENEVA-C/B
evaluate IV
Dexamethasone
3M: Changes significant
6M: Changes NOT significant
extension
12M: Changes NOT significant
Cataract 30%, IOP 15%
SHASTA-C/B
evaluate IV
Dexamethasone
Changes significant
IOP 33%
CRUISE-C evaluate IV Ranibizumab VA, letters, CMT improvement
HORIZON Changes NOT significant
BRAVO-B evaluate IV Ranibizumab
improvement NOT permanent need
re-inject
RETAIN improved CMT & VA
COPERNICUS-C evaluate IV Aflibercept improvement maintained
GALLILEO-C evaluate IV Aflibercept improvement maintained
VIBRANS-B evaluate IV Aflibercept improvement better with IV vs. laser
Summary