A Randomized Trial of Peribulbar Triamcinolone Acetonide with and without Focal Photocoagulation for
Mild Diabetic Macular Edema: A Pilot Study
A Randomized Trial of Peribulbar Triamcinolone Acetonide with and without Focal Photocoagulation for
Mild Diabetic Macular Edema: A Pilot Study
Diabetic Macular Edema (DME)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
Treatments for DMETreatments for DMELaser-Standard of care
Tight Glycemic Control
Corticosteroids-intravitreal, peribulbar
Anti-VEGF agents
Vitrectomy
Studies with Peribulbar Steroids DMEStudies 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
Potential Advantages of Peribulbar Steroids
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 DesignStudy Design
Anterior Peribulbar
20 mg
Posterior Peribulbar
40 mg
Phase 2 randomized, multi-center clinical trial
Major Eligibility Criteria Assessed:
>18 years oldBest corrected electronic-ETDRS letter score ≥ 69 (20/40 or better) Retinal thickening due to DME on clinical exam OCT CST≥ 250 micronsIOP < 24 mm Hg with no history of open-angle glaucoma
Anterior Peribulbar
20mg+LaserLaser
PosteriorPeribulbar
40mg+Laser
Protocol OverviewProtocol Overview
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4 Weeks
8 Weeks
17 Weeks
34 Weeks
2 Year
1 Year
Safety Follow-up to two years
Primary Outcome: change in OCT- Measured central subfield thickening
After the primary outcome treatment was at the investigator’s discretion
Secondary outcome: frequency of retreatment and change in VA
Safety outcomes – elevated IOP, cataract, ptosis, other complications
IOP measured at each visit
Peribulbar injection repeated at if DME was still present
Treatment Protocol-Steroid Injection
Treatment Protocol-Steroid Injection
Standard injection technique Anesthesia at investigator’s
discretion 27-g 5/8 inch needle Anterior (20 mg)-bulbar conj,
lower lid Posterior (40 mg)-
subtenon’s space, ST quad, 10 mm post to limbus
Treatment Protocol-Focal LaserTreatment Protocol-Focal Laser
Modified ETDRS
Laser burns-50 microns, gray intensity
Multiple settings (all completed in single setting)
ResultsResults
Baseline CharacteristicsAnterior Anterior
+ laserPosterior Posterior
+ laserLaser
N=23 N=25 N=21 N=22 N=28
Women 22% 32% 62% 18% 45%
Age 60±8 63±13 58±12 64±7 58±11
White 91% 76% 76% 86% 82%
VA <20/30 26% 44% 57% 45% 66%
OCT 342
±79
336 ±58
321 ±53
319 ±59
324 ±70
Mean Change in Central Subfield at 34 weeks From Baseline
Mean Change in Central Subfield at 34 weeks From Baseline
Anterior
Anterior + laser
Posterior Posterior + laser
Laser
-50 ± 49 -49 ± 79 -29 ± 76 -52 ± 45 -54 ± 62
Mean Central Subfield Thickness (Microns)
Mean Central Subfield Thickness (Microns)
Mean Change in Vision at 34 weeks from Baseline
Mean Change in Vision at 34 weeks from Baseline
Anterior
Anterior + laser
Posterior Posterior + laser
Laser
-1 ± 5 -1 ± 7 -3 ± 9 -1 ± 9 -1 ± 6
ResultsResults
No significant differences in primary outcome of central subfoveal thickness
No differences in visual acuity outcomes at 34 weeks.
Safety Phase Visit CompletionSafety Phase Visit Completion
Visit 1 Year 2 Year
Follow-up rates (not including deaths)
92% 76%
Treatments for DME Post 34 Weeks Treatments for DME Post 34 Weeks
Anterior Posterior Laser
focal/grid Laser 23% 25% 4%
Posterior Peribulbar 2% 0% 8%
Anterior Peribulbar 0% 0% 0%
Intravitreal Steroid 9% 5% 7%
Intravitreal Anti-VEGF 4% 3% 5%
Subjects on IOP Lowering Medication or with IOP increase ≥
10 mmHg
Subjects on IOP Lowering Medication or with IOP increase ≥
10 mmHg
Visit Anterior
N=46
Posterior
N=44
Laser
N=42
17 Week 9% 2% 0%
34 Week 14% 5% 2%
1 Year 19% 8% 0%
2 Year 20% 10% 3%
Intraocular Pressure Elevation Intraocular Pressure Elevation
Anterior Posterior Laser
1 Year N = 43 N = 38 N = 41
IOP Lowering Meds 9% 0% 0%
≥ 10 mmHg increase* 10% 8% 0%
≥ 30 mmHg at F/U* 5% 5% 0%
2 Year N = 35 N = 30 N = 33
IOP Lowering Meds 17% 10% 3%
≥ 10 mmHg increase* 3% 0% 0%
≥ 30 mmHg at F/U* 3% 0% 0%
*Subjects not on IOP lowering medication at the visit
Cataract ExtractionCataract Extraction
1 Year 2 Year
Treatment Group
N % N %
Anterior 38 0% 31 19%
Posterior 33 3% 25 12%
Laser 38 0% 30 10%
Adverse Effects-PtosisAdverse Effects-Ptosis
Anterior – 4/48 (8%)
Posterior – 3/47 (7%)
focal/grid - none
DiscussionDiscussionNo significant effect on central retinal
thickness or VA from peribulbar triamcinolone ± laser compared with laser alone
Anterior and posterior subtenon’s injections were similar
Need for retreatment reduced in peribulbar with focal/grid laser
Investigators not masked to treatment group
DiscussionDiscussion
Significant complication rate (elevated IOP, cataract, ptosis) in peribulbar steroid group
Worse for Anterior vs. PosteriorImportant to follow-up patients
for at least 2 years for adverse side effects
ConclusionConclusionNo 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