Diabetic Retinopathy Clinical Research Network
The Importance of Using Povidone-Iodine
and Elimination of Topical Antibiotics for
Intravitreous Injections: Update from the
DRCR.net
Supported through a cooperative agreement from the National Eye Institute and the National
Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health,
Department of Health and Human Services; EY14231 and EY018817
1
Financial Disclosure
 DRCR.net: Principle Investigator, research funds
 Allergan: Advisory Board
 No relevant financial relationships for this presentation.
Background
 DRCR.net has previously reported low rates of
endophthalmitis via a protocol requiring topical
povidone-iodine, a sterile lid speculum, and topical
anesthetic, but not requiring topical antibiotics, sterile
gloves, or a sterile drape1,2
 A total of 24,065 intravitreous injections have now been
administered to 2,598 eyes across DRCR.net trials.
1.
2.
Bhavsar AR, Googe JM, Jr., Stockdale CR, et al. Risk of endophthalmitis after intravitreal drug
injection when topical antibiotics are not required: the diabetic retinopathy clinical research
network laser-ranibizumab-triamcinolone clinical trials. Arch Ophthalmol. 2009;127(12):1581-3.
Bhavsar AR, Stockdale CR, Ferris FL III, et al. Update on Risk of Endophthalmitis After
Intravitreal Drug Injections and Potential Impact of Elimination of Topical Antibiotics. Arch
Ophthalmol. 2012;130(6):809-810.
Purpose
 Update of a non-randomized comparison of
endophthalmitis rates after intravitreal injection with and
without use of topical antibiotics in six DRCR.net Trials:
•
•
•
•
•
•
•
Phase II Bevacizumab for DME (Protocol H)
Laser-Ranibizumab-Triamcinolone for DME (Protocol I)
Laser-Ranibizumab-Triamcinolone for DME + PRP (Protocol J)
Intravitreal Ranibizumab vs Saline for VH from PDR (Protocol N)
Prompt PRP vs Ranibizumab+Deferred PRP for PDR (Protocol S)
Aflibercept, Bevacizumab and Ranibizumab for DME (Protocol T)
Treatment for CI-DME with Very Good VA Study (Protocol V)
 A new look at development of endophthalmitis without use
of povidone-iodine
4
Standardized DRCR.net Injection
Procedure






Requires application of topical anesthetic drops or gel
(sub-conjunctival injection discouraged)
Requires use of a sterile eyelid speculum
Requires application of topical povidone-iodine to
conjunctiva
Does not require topical antibiotics prior to, on day of,
or after injection
Does not require sterile gloves, sterile drape, or face
mask
Product was required to be drawn up by investigator
from single-use vial at time of injection (bevacizumab,
ranibizumab, aflibercept, saline)
5
Pre- and Post-Injection
Antibiotic Use
Number of
Injections (%)
No Pre-Injection
and No PostInjection
Antibiotics
Number of Injections
(%)
13608 (57%)
Pre-Injection OR
Post-Injection
Antibiotics
10,444 (43%)
No Povidone
Iodine
13
Total
24,065
6
Evolution of Antibiotic Use
in DRCR.net Over Time
100%
Yes (Pre- or Post-)
No
80%
60%
40%
20%
0%
2006
2007
2008
2009
2010
2011
2012
2013
2014
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Use of Povidone Iodine
 Use of pre-injection povidone-iodine is strictly
required
 The procedure requires topical povidone-iodine
allowed to be present for at least 30 seconds
over the injection site, use of a sterile lid
speculum, and topical anesthetic
 Omission of povidone-iodine is a protocol
violation
 For eyes in which povidone-iodine cannot be
used (e.g. allergy), study injections should not
be given per protocol
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Povidone-Iodine Use
24,065
Intravitreal Injections
(2,598 eyes)
13 injections (2 eyes)
without Povidone-Iodine
(protocol violation)
15% of injections without
Povidone-iodine
developed
endophthalmitis
9
Povidone-Iodine Use
24,065
Intravitreal Injections
(2,598 eyes)
13 injections (2 eyes)
without Povidone-Iodine
(protocol violation)
100% of eyes developed
endophthalmitis
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Rates by Antibiotic Use
24,052*
Intravitreal Injections
(2,596 eyes)
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Cases of
Endophthalmitis
3 (0.02%)
Without
Topical Antibiotics
6 (0.06%)
p = 0.19
With
Topical Antibiotics
*Excluding injections given without povidone iodine (13 injections in 2 eyes)
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Cases of Endophthalmitis
Case
1
2
3
4
Intravitreal
Product
Injected
Culture Results
Coagulase
Bevacizumab
negative
staphylococcus
Coagulase
Ranibizumab
negative
staphylococcus
Culture
Ranibizumab
negative
Coagulase
Ranibizumab
negative
staphylococcus
Povidone
Pre-op
-Iodine
Antibiotic
Use
s
Post-op
Antibiotic
s
Yes
No
No
Yes
Yes
Yes
Yes
No
Yes
No*
Yes
Yes
* Since this event, the DRCR.net has clarified to participating investigators that no study injections may be performed without use
of povidone-iodine over the injection site, even as a protocol deviation.
12
Cases of Endophthalmitis
Case
Intravitreal
Product
Injected
Culture Results
5
Ranibizumab
Streptococcus
viridans†
6
Coagulase
Ranibizumab
negative
staphylococcus
7
8
Pre-op
PovidoneAntibiotic
Iodine Use
s
Post-op
Antibiotic
s
Yes
No
Yes
Yes
No
Yes
Culture negative
Yes
No
Yes
Ranibizumab Culture negative
Yes
Yes
Yes
Saline
† Scant growth of methicillin resistant staphylococcus aureus also was reported.
13
Cases of Endophthalmitis
Case
9
Intravitreal
Product
Injected
Culture Results
Coagulase
Ranibizumab
negative
staphylococcus
Pre-op
PovidoneAntibiotic
Iodine Use
s
Post-op
Antibiotic
s
No*
No
No
10
Aflibercept
Culture Negative
Yes
No
No
11
Bevacizumab
Staphylococcus
epidermis
Yes
No
No
* Against DRCR.net policy, an injection was performed without povidone-iodine due to severe betadine allergic reaction
experienced with prior injections (Shur-Clens was used for prep).
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Discussion
 The standardized intravitreal injection protocol
in the DRCR.net trials offers an opportunity to
evaluate the role of topical antibiotics and
povidone-iodine use on the risk of
endophthalmitis following intravitreal injection
 As reported in multiple previous studies, a low
rate of post-injection endophthalmitis has
occurred in the DRCR.net trials
 Topical antibiotic use no longer is standard in a
majority of injections given as part of Network
protocol
15
Conclusions
Not including topical povidone-iodine
substantially increases the risk of
endophthalmitis
Current data suggest that it is extremely
unlikely that omitting topical antibiotics
prior to, on the day of, or after injection has
a moderate or large increase on the risk of
endophthalmitis
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Thank You!
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References
1. Bhavsar AR, Googe JM, Jr., Stockdale CR, et al. Risk of endophthalmitis
after intravitreal drug injection when topical antibiotics are not required: the
diabetic retinopathy clinical research network laser-ranibizumabtriamcinolone clinical trials. Arch Ophthalmol. 2009;127(12):1581-3.
2. Diabetic Retinopathy Clinical Research Network, Scott IU, Edwards A, et al.
A phase II randomized clinical trial of intravitreal bevacizumab for diabetic
macular edema. Ophthalmal. 2007;114(10):1860-7.
3. The Diabetic Retinopathy Clinical Research Network. Randomized trial
evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus
prompt laser for diabetic macular edema. Ophthalmology. 2010;117(6):106477 e35.
4. Googe J, Brucker AJ, Bressler NM, et al. Randomized trial evaluating shortterm effects of intravitreal ranibizumab or triamcinolone acetonide on
macular edema after focal/grid laser for diabetic macular edema in eyes also
receiving panretinal photocoagulation. Retina. 2011;31(6):1009-27.
5. Diabetic Retinopathy Clinical Research Network. An Evaluation of
Intravitreal Ranibizumab for Vitreous Hemorrhage Due to Proliferative
Diabetic Retinopathy. http://drcrnet.jaeb.org/Studies.aspx?RecID=186.
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Accessed October 25, 2011.