Diabetic Retinopathy Clinical Research NetworkDiabetic Retinopathy Clinical Research Network

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

The Importance of Using Povidone-Iodine and Elimination of Topical Antibiotics for Intravitreous Injections: Update from the

DRCR.net

Financial DisclosureFinancial Disclosure

DRCR.net: Principle Investigator, research funds Allergan: Advisory Board

No relevant financial relationships for this presentation.

BackgroundBackground 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. 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.

2. 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.

4

Purpose 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

5

Standardized DRCR.net Injection Procedure

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)

6

Pre- and Post-Injection Antibiotic Use

Pre- and Post-Injection Antibiotic Use

Number of Injections (%)

Number of Injections (%)

No Pre-Injection and No Post-

Injection Antibiotics

13608 (57%)

Pre-Injection OR Post-Injection

Antibiotics 10,444 (43%)

No Povidone Iodine 13

Total 24,065

7

Evolution of Antibiotic Usein DRCR.net Over Time

Evolution of Antibiotic Usein DRCR.net Over Time

2006 2007 2008 2009 2010 2011 2012 2013 20140%

20%

40%

60%

80%

100%Yes (Pre- or Post-)

No

Use of Povidone IodineUse 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

8

9

Povidone-Iodine UsePovidone-Iodine Use

24,065Intravitreal Injections

(2,598 eyes)

13 injections (2 eyes)without Povidone-Iodine

(protocol violation)

15% of injections without Povidone-iodine

developedendophthalmitis

10

Povidone-Iodine UsePovidone-Iodine Use

24,065Intravitreal Injections

(2,598 eyes)

13 injections (2 eyes)without Povidone-Iodine

(protocol violation)

100% of eyes developedendophthalmitis

11

Rates by Antibiotic UseRates by Antibiotic Use

24,052*Intravitreal Injections

(2,596 eyes)

9Cases of

Endophthalmitis

3 (0.02%)Without

Topical Antibiotics

6 (0.06%)With

Topical Antibiotics

*Excluding injections given without povidone iodine (13 injections in 2 eyes)

p = 0.19

Cases of EndophthalmitisCases of Endophthalmitis

12

Case Intravitreal Product Injected

Culture Results Povidone-Iodine

Use

Pre-op Antibiotic

s

Post-op Antibiotic

s

1 BevacizumabCoagulase negative

staphylococcusYes No No

2 RanibizumabCoagulase negative

staphylococcusYes Yes Yes

3 RanibizumabCulture

negative Yes No Yes

4 RanibizumabCoagulase negative

staphylococcusNo* 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.

Cases of EndophthalmitisCases of Endophthalmitis

13

CaseIntravitreal

Product Injected

Culture Results Povidone-Iodine Use

Pre-op Antibiotic

s

Post-op Antibiotic

s

5 Ranibizumab Streptococcus viridans† Yes No Yes

6 RanibizumabCoagulase negative

staphylococcusYes No Yes

7 Saline Culture negative Yes No Yes

8 Ranibizumab Culture negative Yes Yes Yes

† Scant growth of methicillin resistant staphylococcus aureus also was reported.

Cases of EndophthalmitisCases of Endophthalmitis

14

CaseIntravitreal

Product Injected

Culture Results Povidone-Iodine Use

Pre-op Antibiotic

s

Post-op Antibiotic

s

9 RanibizumabCoagulase negative

staphylococcusNo* No No

10 Aflibercept Culture Negative Yes No No

11 BevacizumabStaphylococcus

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).

15

DiscussionDiscussion

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

16

Conclusions 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

17

Thank You!Thank You!

18

ReferencesReferences1. 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.

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):1064-77 e35.

4. Googe J, Brucker AJ, Bressler NM, et al. Randomized trial evaluating short-term 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. Accessed October 25, 2011.