Editorial

A New Complication Associated with the Use of Prophylactic Intracameral

Antibiotics: Hemorrhagic Occlusive Retinal Vasculitis
Stephen G. Schwartz, MD, MBA - Naples, Florida
Nidhi Relhan, MD - Miami, Florida
Terrence P. OBrien, MD - Palm Beach Gardens, Florida
Harry W. Flynn, Jr., MD - Miami, Florida

Given the substantial increase in antimicrobial resistance Centers for Disease Control and Prevention reported that
among ocular pathogens worldwide, evidence-based strate- more than half of antibiotics used are either unnecessary
gies are needed to carefully analyze the risks and benets of or inappropriate and reiterated the recommendation that
routine prophylactic intracameral antibiotics for prevention vancomycin should be reserved for treatment of life- or
of infection in cataract surgery. In ophthalmology, 2 basic organ-threatening infections. These concerns illustrate the
issues are debated frequently: (1) the effectiveness of need for antibiotic stewardship programs.4
intracameral antibiotics in lowering rates of endophthalmitis The rate of acute-onset postoperative endophthalmitis after
in association with cataract surgery and (2) the use of cataract surgery generally is reported between approximately
vancomycin as a prophylactic antibiotic. 0.03% and 0.2%.5 Some big data retrospective series have
Intracameral antibiotics during cataract surgery, although reported lower rates associated with the use of intracameral
used in some parts of the world, remain controversial.1 antibiotics, but these studies are limited and likely awed
Prophylactic antibiotics are associated with increased costs, relating to their study designs in which, generally, an earlier
risks to the individual patient, and risks to the population at cohort of patients who underwent surgery without
large, by contributing to the emergence of drug-resistant or- intracameral antibiotics is compared with a later cohort of
ganisms. In the current issue of patients who underwent surgery
Ophthalmology, Witkin et al2 (see Prophylactic antibiotics are associated with intracameral antibiotics.
http://www.aaojournal.org/article/ with increased costs, risks to the Endophthalmitis rates may
S0161-6420(16)31231-3/fulltext) decline over time for many
illustrate a striking example of risk
individual patient, and risks to the reasons other than the use of
to the individual patient: they population at large, by contributing to intracameral antibiotics, including
report 36 eyes of 23 patients that the emergence of drug-resistant improvements in surgical
demonstrated hemorrhagic organisms. technique, equipment and other
occlusive retinal vasculitis factors.6
associated with intracameral or intravitreal vancomycin used A single randomized clinical trial (RCT) conducted by
during or shortly after cataract surgery. the European Society of Cataract & Refractive Surgeons
In this series, visual outcomes generally were poor in 2007 reported that intracameral cefuroxime was asso-
despite treatment, with 61% of eyes (22/36) attaining nal ciated with an approximate 5-fold reduction in endoph-
visual acuity of 20/200 or worse, including 22% (8/36) thalmitis rates.7 This study has been criticized on multiple
attaining no light perception. Of note, 7 eyes initially were grounds, including the limited spectrum of activity of
diagnosed with endophthalmitis and were treated with cefuroxime, the high rate of endophthalmitis in eyes not
additional intravitreal vancomycin; of these eyes, 71% (5/7) randomized to receive intracameral cefuroxime
showed a nal visual acuity of no light perception. The (approximately 0.2%), the use of topical levooxacin
subgroup of eyes treated with additional intravitreal 0.5% beginning 24 hours after surgery (as opposed to
vancomycin therefore comprises most (63% [5/8]) of the the same day), and the use of multiple surgical
eyes with no light perception outcomes. techniques.8,9 Yet, it remains the only published RCT to
Alternatively, 3 eyes were treated with intravitreal date on intracameral antibiotics in cataract surgery. We
corticosteroids and 2 of these 3 achieved nal visual acuities suspect that based on this RCT, the use of intracameral
of 20/40 and 20/70. Although the sample size is small, the antibiotics has become more common, especially in those
ndings that additional vancomycin is associated with nations in which a packaged, approved intracameral
poorer outcomes and that intravitreal corticosteroids are cefuroxime preparation (Aprokam; Thea Pharmaceuticals,
associated with better outcomes collectively support the Clermont-Ferrand, France) is available.
hypothesis that hemorrhagic occlusive retinal vasculitis Intracameral cefuroxime currently is not approved in the
represents a delayed-onset hypersensitivity to vancomycin. United States and is unlikely to become approved without a
Of note, the Centers for Disease Control and Prevention second RCT to support the European Society of Cataract &
published guidelines that explicitly discouraged the use of Refractive Surgeons trial, which is now a decade old. There
vancomycin for surgical prophylaxis in 1995.3 In 2013, the seems to be a preference among United States cataract

2017 by the American Academy of Ophthalmology http://dx.doi.org/10.1016/j.ophtha.2017.01.038 1

Published by Elsevier Inc. ISSN 0161-6420/17

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 Ophthalmology Volume -, Number -, Month 2017

surgeons for this agent: a member survey conducted by the Intraocular vancomycin should be reserved for the treat-
American Society of Cataract and Refractive Surgery in ment of patients with clinically suspected endophthalmitis.
2014 reported that 69% of members based in nations
without access to intracameral cefuroxime would use it if it References
were available and reasonably priced.10 Thus, cataract
surgeons wishing to use intracameral antibiotics in these
1. Grzybowski A, Schwartz SG, Matsuura K, et al. Endoph-
nations, including the United States, must use off-label
thalmitis prophylaxis in cataract surgery: overview of current
compounded medications. Compounded antibiotics are practice patterns around the world. Curr Pharm Des. 2016 Dec
associated with dilution errors, contaminants, and other 16 [Epub ahead of print].
risks, as well as regulatory barriers. For example, one series 2. Witkin A, Chang D, Jumper JM, et al. Vancomycin-associated
reported Fusarium endophthalmitis in 8 consecutive patients hemorrhagic occlusive retinal vasculitis: clinical characteristics
operated with extemporaneously compounded cefuroxime of 36 eyes. Ophthalmology. 2017 Jan 19. pii:
formulated for intracameral use from a single bottle of S0161e6420(16)31231-3. doi:10.1016/j.ophtha.2016.11.042.
balanced salt solution.11 [Epub ahead of print].
If United States surgeons wish to use intracameral 3. [No authors listed]. CDC issues recommendations for pre-
antibiotics, then vancomycin has some advantages, including a venting spread of vancomycin resistance. Am J Health Syst
Pharm. 1995;52:1272-1274.
broad spectrum of activity against organisms likely to cause
4. Centers for Disease Control and Prevention. Antibiotic resis-
acute-onset postoperative endophthalmitis. However, vanco- tance threats in the United States, 2013. Bethesda, MD:
mycin has many disadvantages for prophylaxis, including its Centers for Disease Control and Prevention, US Department of
effects on antibiotic stewardship. Vancomycin, a rst-line Health and Human Services; 2013.
intravitreal therapy for coverage of gram-positive organisms, 5. Vaziri K, Schwartz SG, Kishor K, Flynn Jr HW. Endoph-
is a mainstay in the treatment of endophthalmitis. The thalmitis: state of the art. Clin Ophthalmol. 2015;9:95-108.
Endophthalmitis Vitrectomy Study12 in 1996 reported that 6. Schwartz SG, Flynn Jr HW, Grzybowski A, et al. Intracameral
100% of gram-positive isolates were sensitive to vancomycin. antibiotics and cataract surgery: endophthalmitis rates, costs,
Similarly, the Antibiotic Resistance Monitoring in Ocular and stewardship. Ophthalmology. 2016;123:1411-1413.
Microrganisms13 study in 2011 reported that 100% of 7. Endophthalmitis Study Group, European Society of Cataract &
Refractive Surgeons. Prophylaxis of postoperative endoph-
Staphylococcus aureus and coagulase-negative staphylo- thalmitis following cataract surgery: results of the ESCRS
coccal isolates were sensitive to vancomycin. Unfortunately, the multicenter study and identication of risk factors. J Cataract
incidence of endophthalmitis resulting from gram-positive or- Refract Surg. 2007;33:978-988.
ganisms with reduced vancomycin susceptibility or vancomy- 8. Liesegang TJ. Intracameral antibiotics: questions for the
cin resistance seems to be increasing. A recent review reported United States based on prospective studies. J Cataract Refract
27 cases of endophthalmitis resulting from organisms with Surg. 2008;34:505-509.
reduced vancomycin susceptibility or vancomycin resistance, 9. OBrien TP, Arshinoff SA, Mah FS. Perspectives on antibiotics
including 11 after cataract surgery, and the visual outcomes for postoperative endophthalmitis prophylaxis: potential role of
typically were poor.14 Hemorrhagic occlusive retinal vasculitis moxioxacin. J Cataract Refract Surg. 2007;33:1790-1800.
represents a major disadvantage for vancomycin specically. 10. Chang DF, Braga-Mele R, Henderson BA, et al. Antibiotic
prophylaxis of postoperative endophthalmitis after cataract
In summary, the routine use of prophylactic intra- surgery: results of the 2014 ASCRS member survey.
cameral antibiotics during cataract surgery, although J Cataract Refract Surg. 2015;41:1300-1305.
enticing as a strategy to reduce infection rates, has 11. Cakir M, Imamoglu S, Cekic O, et al. An outbreak of early-
incompletely proven efcacy, increased costs, possible onset endophthalmitis caused by Fusarium species following
serious risks to the individual patient, and larger risks to cataract surgery. Curr Eye Res. 2009;34:988-995.
the population as a whole by potentially contributing to 12. Han DP, Wisniewski SR, Wilson LA, et al. Spectrum and
antibiotic resistance. Additionally, the recent report herein susceptibilities of microbiologic isolates in the Endoph-
should alert cataract surgeons to the possibility of thalmitis Vitrectomy Study. Am J Ophthalmol. 1996;122:1-17.
introducing a devastating, bilateral, sight-threatening 13. Haas W, Pillar CM, Torres M, et al. Monitoring antibiotic
consequence with routine intracameral antibiotics. This resistance in ocular microorganisms: results from the Anti-
biotic Resistance Monitoring in Ocular micRorganisms (AR-
well-documented case series also has increased our MOR) 2009 surveillance study. Am J Ophthalmol. 2011;152:
fundamental understanding of hemorrhagic occlusive 567-574.
retinal vasculitis.2 Based on currently available safety and 14. Relhan N, Albini TA, Pathengay A, et al. Endophthalmitis
efcacy data, as well as cost-effectiveness data, we believe caused by gram-positive organisms with reduced vancomycin
that vancomycin should not be used as a routine via susceptibility: literature review and options for treatment. Br J
intracameral administration with cataract surgery. Ophthalmol. 2016;100:446-452.

Footnotes and Financial Disclosures

Financial Disclosure(s): The author(s) have made the following disclo- Correspondence:
sure(s): S.G.S.: Consultant e Alimera Sciences Stephen G. Schwartz, MD, MBA, Bascom Palmer Eye Institute, University
of Miami Miller School of Medicine, 3880 Tamiami Trail North, Naples,
FL 34103. E-mail: [email protected].

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