Ozurdex Versus Ranibizumab Versus Combination for Central Retinal Vein Occlusion

This is a 52 week, single masked, 1:1:1, randomized, phase IV, multicenter injection
controlled clinical study with a 24 week treatment phase followed by a 24 week follow up
phase. Subjects will be randomly assigned to Ozurdex every 16 weeks, Ranibizumab monthly, or
combination Ozurdex every 16 weeks with Ranibizumab. Patients assigned to IV Ozurdex arm
will receive a total of 2 intravitreal Ozurdex injections (in combination with monthly
Ranibizumab sham) administered at 16 week intervals beginning on Day 1 and ending at Week
16. Patients assigned to IV Ranibizumab arm will receive injections administered at monthly
intervals (in combination with Ozurdex sham beginning on Day 1 and Week 16). Patients
assigned to IV Ozurdex with IV Ranibizumab will receive a total of 2 intravitreal Ozurdex
injections administered at Week 16 intervals beginning on Day 1 and ending at Week 16 with
an initial IV Ranibizumab injection administered on Day 1, then treated with Ranibizumab
according to reinjection parameters assessed monthly through Week 20 (in combination with
Ranibizumab sham if Ranibizumab reinjection parameters are not met). Treatment at end of
study treatment phase Week 24 will be standard of care for all arms at the Investigator's
discretion.

Inclusion Criteria:

- Adults greater than or equal to 18 years of age with foveal center involved macular
edema secondary to CRVO diagnosed within 12 months before the screening visit (CRVO
is defined as an eye with retinal hemorrhage or other biomicroscopic evidence of RVO
[eg telangiectatic capillary bed] and a dilated [or previously dilated] venous system
in at least 3 quadrants of the retina drained by the affected vein.

- Best corrected visual acuity (ETDRS) letter score of 73 to 24 inclusive (20/40 to
20/320) in the study eye at Screening and at Day 1

- Mean central subfield thickness greater than or equal to 310 µm from 2 OCT
measurements (Spectralis HRA + OCT) at Screening and Day 1

- Willing and able to comply with clinic visits and study-related procedures

- Ability to provide signed informed consent form

Exclusion Criteria:

- History of vitreoretinal surgery in the study eye or anticipated within 12 months of
Day 1

- Current bilateral manifestation of CRVO

- Decrease in VA due to causes other than CRVO in the study eye

- Prior episode of RVO in study eye

- Afferent pupillary defect, obvious and unequivocal

- Greater than 10 letter improvement in BCVA between Screening and Day 1

- History or presence of exudative or dry macular degeneration

- Panretinal scatter photocoagulation or sector laser photocoagulation within 3 months
prior to Day 1 or anticipated within 4 months after Day 1

- Anticipated laser photocoagulation for macular edema within 4 months after Day 1

- History of or evidence on examination of any diabetic retinopathy in the study eye

- CVA or MI within 3 months prior to Day 1

- Prior anti-VEGF treatment in study or fellow eye within 3 months before day 1 or
systemic anti-VEGF or pro-VEGF treatment within 6 months prior to Day 1

- Ocular or periocular infections including active or suspected viral diseases of the
cornea and conjunctiva, active epithelial herpes simples keratitis (dendritic
keratitis), vaccinia, varicella, mycobacterial infections, and fungal diseases

- Glaucoma or current ocular hypertension requiring more than 1 medication to control
IOP in the study eye or a history of steroid induced IOP increase in either eye

- Prior Ozurdex treatment in study eye within 4 months prior to Day 1

- Aphakic eyes with rupture of posterior lens capsule

- Anterior chamber IOL and rupture of posterior lens capsule

- Hypersensitivity to any components of Ozurdex or Ranibizumab in either eye

- History of other disease, metabolic dysfunction, physical exam finding, including
renal failure on dialysis which renders the patient at high risk from treatment
complications based on the judgment of the Investigator's at his/her discretion.

- Sexually active men or women of childbearing potential who are unwilling to practice
adequate contraception during the study (adequate contraceptive measures include
stable use of oral contraceptives or other prescription pharmaceutical contraceptives
for 2 or more menstrual cycles prior to screening; intrauterine device; bilateral
tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or
diaphragm plus contraceptive sponge, foam, or jelly).