STUDY SUBJECTS

Major Inclusion criteria:

• Age > 18 years old
• Macular edema present from at least 6 weeks - 12 months (BRVO) or 6 weeks - 9 months from initial diagnosis (CRVO)
• BRVO or CRVO
• 1 eye per study patient
• BCVA between 20/50 - 20/200 in study eye AND better than 20/200 in non study eye
• Central subfield thickness of > 300 microns in the study eye

Major exclusion criteria:

• Epiretinal membrane
• Active retinal or optic disc neovascularization
• Active or history of choroidal neovascularization
• Presence of rubeosis irises
• Any active infection
• Aphakia or anterior chamber intraocular lens
• Clinical significant medial opacity
• Glaucoma or current ocular hypertension requiring more than 1 IOP lowering medication
• History of steroid-induced IOP increase in either eye
• Diabetic retinopathy in either eye
• Uncontrolled systemic disease
• Current or anticipated use of systemic steroids or anticoagulants
• Ocular condition that would prevent a 15 letter improvement in visual acuity

RANDOMIZATION SCHEME AND INTERVENTIONS

Randomized 1:1:1

0.35 mg dexamethasone (DEX)

0.7 m dexamethasone (DEX)

Sham injections

Protocol: Patients received each intervention on day 0 with topical antibiotics 3 days before and 3 days after the procedure

Dexamethasone implant: biodegradable copolymer of lactic acid and glycolic acid containing micronized dexamethasone on a 22 gauge needle applicator.

STUDY DURATION: 6 MONTHS

PRIMARY ENDPOINT:

• Proportion of patients achieving at least a 15-letter improvement from baseline BCVA at day 180
• Time to reach 15-letter improvement from baseline BCVA- based on ETDRS

SECONDARY ENDPOINTS:

• Proportion of eyes achieving at least 10-. 11-,12-, 13-, 14- or 15- letter improvement from baseline BCVA
• Proportion of eyes with > 15 letter vision loss from baseline NCVA
• Mean change from baseline NCVA
• Subgroup: stratification based BRVO vs CRVO, duration of ME at baseline
• Central subfield retinal thickness

RESULTS

Study population

• 1267 patients (DEX 0.7 mg n= 427; DEX 0.35 mg n=414; sham n=426).

PRIMARY OUTCOME:

• Eyes receiving the DEX implant 0.7 or 0.35 mg achieved a 15 letter BCVA significantly faster than those receiving sham
• Cumulative response rate of 15 letter BCVA improvement at day 180 was higher in DEX groups: 41% DEX 0.7 mg, 40% 0.35 mg, 23% sham (improvement as early as day 30, peak at 60, maintained through day 90, and then no difference at day 180)
• Greatest response at day 60 (21% with 15 letter improvement)
• No significant differences between DEX 0.7 mg versus 0.35 mg

NOTABLE SECONDARY OUTCOMES

• Proportion of eyes achieving at least 10+ letter in BCVA improvement was significant greater in both DEX groups compared to sham at days 30, 60, and 90 (peak at day 60 with 10+ of ~50% in the DEX groups).
• Proportion of eyes achieving at least 10+ letter improvement was significant greater in DEX 0.7 mg group compared to sham at day 180, but no difference between DEX 0.35 mg and sham.
• Mean decrease in central subfield thickness was statistically greater in the DEX implant groups compared to sham at day 90 but not at day 180
• Subgroup analyses: BRVO vs CRVO response to treatment was similar;
  • Those with a duration of ME < 90 days from diagnosis had a statistically higher rate of achieving > 15 letter or better gain at day 60 (peak response).

Adverse events

Ocular

• Eye pain, ocular hypertension, and anterior chamber cells occurred more significantly in the DEX groups than sham
• Incidence of retinal neovascularization was significantly lower in the DEX 0.7 mg group compared to sham
• No significant difference in rate of cataract formation between DEX groups and sham
• No cases of endophthalmitis were reported
• No difference in rate of vitreous hemorrhages
• Significant higher rate of ocular hypertension in both DEX groups compared to sham (~3.9-4.0% versus 0.7% sham)
• Peak change in IOP occurred at Day 60 with no difference at day 180
• Most eyes were treated topically, but 5 eyes required glaucoma surgery

CONCLUSIONS

• Dexamethasone implants are effective in significantly improving vision in patients with macular edema from branched or central retinal vein occlusions compared to sham treatment