A Randomized Trial of Peribulbar Triamcinolone Acetonide with and without Focal Photocoagulation for

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A Randomized Trial of Peribulbar Triamcinolone
Acetonide with and without Focal Photocoagulation
for Mild Diabetic Macular Edema A Pilot Study
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Diabetic Macular Edema (DME)

• DME-most common cause of visual loss in patients
  with diabetes
• ETDRS- focal/grid laser reduced 3-year rate of
  moderate visual loss by 50
• Only 17 of patients with baseline acuity worse
  than 20/40 experienced moderate visual gain

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Treatments for DME

• Laser-Standard of care
• Tight Glycemic Control
• Corticosteroids-intravitreal, peribulbar
• Anti-VEGF agents
• Vitrectomy

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Studies with Peribulbar Steroids DME

• Bakri and Kaiser (2005)-63 eyes, 40 mg, VA
  improved from 20/80 to 20/63 at 12 months
• Entezari et. al. (2005)-randomized trial, 64
  eyes, 40 mg vs placebo injection, no benefit VA
  or OCT thick
• Tunc et. al. (2005)-randomized trial, 60 pts,
  focal laser vs laser plus 20 mg, mild benefit in
  VA (2.5 lines in combined group vs 1.5 lines in
  laser group)
• Cardillo et. al. (2005)-randomized trial, 24 eyes
  in 12 pts, 40 mg vs IVK (4 mg), short term impt
  greater in IVK grp (VA impt and decrease OCT
  thick
• Bonini-Filho et. al. (2005)-randomized trial, 36
  eyes, 40 mg vs IVK (4 mg), IVK has sign greater
  impt VA and decrease OCT thick
• Ozdek et. al. (2006)-retrospective study, 126
  eyes in 95 pts, 20 mg vs IVK (4 mg), both grps
  had sign impt in VA and decrease OCT thick with
  greater impt in IVK group

Benefits of Peribulbar Steroids are Inconclusive
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Potential Advantages of Peribulbar Steroids

• Lower incidence of adverse effects compared with
  intravitreal steroids
• Particular interest in eyes with good VA and mild
  DME
• Combination with focal/grid laser may be
  beneficial

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Study Design
Phase 2 randomized, multi-center clinical trial

• Major Eligibility Criteria Assessed
• gt18 years old
• Best corrected electronic-ETDRS letter score
  69 (20/40 or
  better)
• Retinal thickening due to DME on clinical exam
• OCT CST 250 microns
• IOP lt 24 mm Hg with no history of open-angle
  glaucoma

Anterior Peribulbar 20 mg
Posterior Peribulbar 40 mg
Anterior Peribulbar 20mgLaser
Laser
Posterior Peribulbar 40mgLaser
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Protocol Overview

• Safety outcomes elevated IOP, cataract, ptosis,
  other complications
• IOP measured at each visit

4 Weeks
8 Weeks

• Peribulbar injection repeated at if DME was still
  present

17 Weeks
34 Weeks

• Primary Outcome change in OCT- Measured central
  subfield thickening
• After the primary outcome treatment was at the
  investigators discretion
• Secondary outcome frequency of retreatment and
  change in VA

1 Year
2 Year
Safety Follow-up to two years
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Study Design

• One study eye-equal probability of randomization
  to one of 5 groups
• Two study eyes-focal laser in one eye other eye
  to one of 4 other treatment groups
• Subjects masked to injection type not to focal
  laser
• VA testers, OCT techs/readers masked
  Investigators not masked

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Treatment Protocol-Steroid Injection

• Standard injection technique
• Anesthesia at investigators discretion
• 27-g 5/8 inch needle
• Anterior (20 mg)-bulbar conj, lower lid
• Posterior (40 mg)-subtenons space, ST quad, 10
  mm post to limbus

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Examination Procedures

• BCVA with electronic ETDRS-all visits with
  standard refraction at baseline and 34 weeks
• Clinical exam at each visit
• Lens assessment, HbA1c-baseline, 17 wks, 34 weeks
• OCT-all visits, University of Wisconsi-Madison
  Reading Center for grading
• EDTRS fundus photos 7-fields baseline, 8 mo, 24
  mo, 3-fields 4 mo, 12 mo
• FA-baseline and 4 mo (if part of standard care)

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Treatment Protocol-Focal Laser

• Modified ETDRS
• Laser burns-50 microns, gray intensity
• Multiple settings (all completed in single
  setting)

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Results
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Baseline Characteristics
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Mean Change in Central Subfield at 34 weeks From
Baseline
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Mean Central Subfield Thickness (Microns)
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Mean Change in Vision at 34 weeks from Baseline
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Results

• No significant differences in primary outcome of
  central subfoveal thickness
• No differences in visual acuity outcomes at 34
  weeks.

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Safety Phase Visit Completion
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Treatments for DME Post 34 Weeks
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Subjects on IOP Lowering Medication or with IOP
increase 10 mmHg
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Intraocular Pressure Elevation
Subjects not on IOP lowering medication at the
visit
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Cataract Extraction
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Adverse Effects-Ptosis

• Anterior 4/48 (8)
• Posterior 3/47 (7)
• focal/grid - none

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Discussion

• No significant effect on central retinal
  thickness or VA from peribulbar triamcinolone
  laser compared with laser alone
• Anterior and posterior subtenons injections were
  similar
• Need for retreatment reduced in peribulbar with
  focal/grid laser
• Investigators not masked to treatment group

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Discussion

• Significant complication rate (elevated IOP,
  cataract, ptosis) in peribulbar steroid group
• Worse for Anterior vs. Posterior
• Important to follow-up patients for at least 2
  years for adverse side effects

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Conclusion

• No benefit from peribulbar steroids as a therapy
  for mild DME
• No justification to warrant phase 3 trial
• Demonstrates the need for long term studies (2
  years) to evaluate potential adverse effects