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