Transcript Peribulbar Triamcinilone Acenotide with and without Focal

A Randomized Trial of Peribulbar
Triamcinolone Acetonide with and
without Focal Photocoagulation for
Mild Diabetic Macular Edema: A
Pilot Study
Diabetic Macular Edema (DME)
DME-most common cause of visual
loss in patients with diabetes
ETDRS- focal/grid laser reduced 3year rate of moderate visual loss by
50%
Only 17% of patients with baseline
acuity worse than 20/40 experienced
moderate visual gain
Treatments for DME
Laser-Standard of care
Tight Glycemic Control
Corticosteroids-intravitreal, peribulbar
Anti-VEGF agents
Vitrectomy
Studies with Peribulbar Steroids DME
 Bakri and Kaiser (2005)-63 eyes, 40 mg, VA improved from 20/80 to 20/63 at
12 months
Benefits of Peribulbar
Steroids are Inconclusive
 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
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
Study Design
Phase 2 randomized, multi-center clinical
trial
Major Eligibility Criteria Assessed:
>18 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 < 24 mm Hg with no history of openangle
glaucoma
Laser
Anterior
Anterior
Peribulbar Peribulbar
20 mg
20mg+Laser
Posterior
Posterior
Peribulbar Peribulbar
6
40 mg
40mg+Laser
Protocol Overview
4 Weeks
8 Weeks
17 Weeks
34 Weeks
1 Year
Safety outcomes – elevated IOP, cataract, ptosis,
other complications
IOP measured at each visit
Peribulbar injection repeated at if DME was still
present
 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
2 Year
Safety Follow-up to two years
7
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 Laser
Modified ETDRS
Laser burns-50 microns, gray
intensity
Multiple settings (all completed
in single setting)
Results
Baseline Characteristics
Anterior Anterior
+ laser
Posterior
Posterior
+ laser
Laser
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
Anterior
Anterior
+ laser
-50 ± 49
-49 ± 79
Posterior
Posterior
+ laser
Laser
-29 ± 76
-52 ± 45
-54 ± 62
Mean Central Subfield Thickness
(Microns)
Mean Change in Vision at 34 weeks
from Baseline
Anterior
Anterior
+ laser
-1 ± 5
-1 ± 7
Posterior
Posterior
+ laser
-3 ± 9
-1 ± 9
Laser
-1 ± 6
Results
No significant differences in
primary outcome of central
subfoveal thickness
No differences in visual acuity
outcomes at 34 weeks.
Safety Phase Visit Completion
Visit
Follow-up rates
(not including
deaths)
1 Year
2 Year
92%
76%
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
Visit
Anterior
N=46
Posterior Laser
N=44
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
Anterior
Posterior
Laser
1 Year
IOP Lowering Meds
≥ 10 mmHg increase*
≥ 30 mmHg at F/U*
N = 43
9%
10%
5%
N = 38
0%
8%
5%
N = 41
0%
0%
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 Extraction
1 Year
2 Year
Treatment
Group
Anterior
N
%
N
%
38
0%
31
19%
Posterior
33
3%
25
12%
Laser
38
0%
30
10%
Adverse Effects-Ptosis
Anterior – 4/48 (8%)
Posterior – 3/47 (7%)
focal/grid - none
Discussion
No 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
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
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