STUDY DESIGN

Phase 2, prospective, multicenter, randomized, single-masked trial

DURATION

12 months

STUDY SUBJECTS

Major inclusion criteria:

• DME affecting the central fovea
  • ≥3 months after 1 or more laser sessions OR
  • Investigator determination that laser would be unhelpful
• 20/40 to 20/400 vision

Major exclusion criteria:

• Glaucoma requiring >1 medication or uncontrolled
• Other causes of vision loss
• Severe systemic disease or any condition affecting follow-up or documentation

RANDOMIZATION SCHEME AND INTERVENTIONS

Randomized 1:1

(a) Intravitreal bevacizumab 1.25 mg
(b) Intravitreal dexamethasone implant 0.7 mg

Retreatment was considered at subsequent visits if:

• ≥4 weeks since last bevacizumab
• ≥16 weeks since last dexamethasone implant
• Unless CMT <300 µm
• Unless VA was 20/25 or better

RESULTS (52 weeks)

Study population

• 88 eyes were randomized, 42 to bevacizumab, 46 to dexamethasone implant, 81 eyes completed 12 months of follow up

Visual acuity end-points

• Percentage of eyes in which BCVA ≤10 letters at the 12 month visit (primary outcome)
  • 17/42 (40%) eyes treated with bevacizumab
  • 19/46 (41%) eyes treated with dexamethasone implant (p = 0.99)
• Percentage of eyes which gained ≤15 letters
  • 13/42 (31%) eyes treated with bevacizumab
  • 10/46 (33%) eyes treated with dexamethasone
• Mean change in BCVA
  • 8.9 letters for eyes treated with bevacizumab
  • 5.6 letters for eyes treated with dexamethasone (p = 0.24)

Mean Central Macular Thickness change from baseline to 12 months

• Bevacizumab: -122 µm
• Dexamethasone: -187 µm (p = 0.015)

Treatment load, mean number of treatments over 12 months

• Bevacizumab: 8.6 injections
• Dexamethasone: 2.7 injections

Patient reported outcomes, measured using the Impact of Vision Impairment questionnaire to determine person measures (logits, higher score indicates greater increase in vision-related quality of life)

• Entire study: +0.77 logits (p <0.001)
• Single eye enrolled in the study:
  • Bevacizumab: +0.82 logits
  • Dexamethasone: +0.38 logits (p > 0.1)
• Both eyes enrolled and treated with both agents
  • 8/24 (33%) preferred bevacizumab
  • 11/24 (46%) preferred dexamethasone
  • 5/24 (21%) no preference

Adverse Events:

• An increase in intraocular pressure by at least 5 mmHg at any follow up visit
  • 46% (21/46) of dexamethasone treated eyes
  • 19% (8/42) of bevacizumab treated eyes
• A pressure above 25 mmHg at least once
  • 26% (12/46) of dexamethasone treated eyes
  • 0% of the bevacizumab group
• Increase in cataract density by 2 grades and incidence of cataract surgery
  • 13% (6/46) and 6.5% (3/46) of the dexamethasone group
  • 4.8% (2/42) and 2.4% (1/42) of the bevacizumab group
• Vision decreased by more than 10 letters
  • 11% (5/46) of the dexamethasone group
    • cataract progression (4/5) and syphilitic chorioretinitis (1/5)
  • 0% of the bevacizumab treated eyes lost more than 10 letters.
• Systemic adverse events included 2 cerebrovascular accidents and and 1 myocardial infarction in patients receiving both treatments

CONCLUSIONS

• Both the dexamethasone implant and bevacizumab injection resulted in approximately 40% of eyes gaining at least 10 letters over 12 months.
• Mean improvement in visual acuity was non-significantly greater in the bevacizumab group, related to the higher rate of cataract progression in eyes treated with steroids.
• Mean central macular thickness improved significantly more in the dexamethasone implant group, and the number of treatments required was much lower in this group as well.
• Conversely, cataract progression and IOP elevation were more common in eyes treated with dexamethasone.