Infection Control and Injection Safety:
a Work in Progress
surgeons gain experience and anti-infectives gain strength, guideline updates should
NATALONI, CONTRIBUTING EDITOR
ago, retinal specialists used intravitreal injections mainly to combat retina surgery-related
eye infections, such as endophthalmitis. Today, intravitreal injections have become
an increasingly popular therapeutic tool for the treatment of age-related macular
degeneration (AMD). This evolution comes with an ironic twist: the tool that was
mainly used to fight infection is now the center of ongoing debate regarding how
best to use it to avoid infection.
Pegaptanib sodium (Macugen, Eyetech/Pfizer), the most recent
injectable to enter the AMD treatment arena, earned high enough marks from the Food
and Drug Administration to attain the "safe and effective" seal of approval, but
suggested protocol rather than strict mandates and a relatively high endophthalmitis
rate of 1.3% (the risk for 1 year of therapy, or a total of 9 injections) brought
the issue of safe usage and infection control to the forefront.
Eyetech revised its pegaptanib-usage protocol while the clinical
trials were still ongoing in May 2003. An amendment of the injection protocol required
the use of a sterile preparation and drape similar to that used for routine intraocular
surgery, and use of either pre-injection topical ophthalmic antibiotic drops for
3 days prior to the injection or a 10 mL povidone-iodine flush immediately prior
Christopher Ta, MD, of Stanford University, reviewed the available
literature and reported that povidone-iodine be used prior to intravitreous injection
and that topical antibiotics might also be used prior to and after injections. Dr.
Ta also recommended that clinicians follow aseptic guidelines including the use
of an eyelid speculum.1
William F. Mieler, MD, professor and chairman of the Department
of Ophthalmology and Visual Science at the University of Chicago, says the formula
for safer injections and infection control is the use of a sterile technique including
a povidone-iodine lid scrub, use of a speculum, and avoidance of an anterior chamber
"The anterior chamber paracentesis is not necessary and is somewhat
risky," says Dr. Mieler, who also opts for use of a topical fourth-generation fluoroquinolone
antibiotic. "We generally place 1 or 2 drops of a new fourth-generation fluoroquinolone
on the eye 15 to 20 minutes prior to the injection even though the need is still
not fully proven," he says. "After we do the injection, we monitor the IOP and once
we're sure there is no problem, we send the patient home on the same bottle of antibiotic,
and have them use a drop 3 or 4 times a day for about 4 days," explains Dr. Mieler.
"We generally have the patient return for follow-up within 3 to 7 days following
the injection, and instruct them to call us immediately if they encounter any significant
pain, discharge from the eye, or change in their vision," he adds.
Jennifer I. Lim, MD, associate professor of ophthalmology at the
Doheny Retina Institute of the Doheny Eye Institute Los Angeles, uses povidone-iodine
before and after placing the sterile drape to decrease the risk of endophthalmitis
in AMD eyes receiving therapeutic injections.
"In the past, injections were usually done to treat infected eyes,
so we didn't sterilize the eye prior to obtaining the cultures from the aqueous
and vitreous," she says. Her injection technique, too, is geared toward infection
prevention. "I like to inject in the superotemporal quadrant vs. inferotemporal
quadrant because pooling of tears is less superiorly and this may equate to a reduced
risk of infection," says Dr. Lim.
Joel Corwin, MD, founder of Miramer Eye Specialists Group in Ventura
County, Calif, says combining the use of preoperative antibiotics with the use of
a sterile technique dramatically reduces the number of incidents of gram-positive
cultures prior to injection.
"Many physicians argue that the incidence of endophthalmitis
is extremely low, regardless of the technique used to perform the injection. I believe,
however, that the occurrence of endophthalmitis is still too frequent. For this
reason, I believe it is prudent to combine preop and postop antibiotics with sterile
technique, because neglecting these vital steps can result in unsafe injections.
Following this protocol ensures that every action has been taken to prevent the
occurrence of endophthalmitis," says Dr. Corwin.
He uses a fourth-generation fluoroquinolone to further prophylax
and prevent endophthalmitis after pegaptanib injection. "I use gatifloxacin (Zymar,
Allergan) because it contains preservative, rather than moxifloxacin (Vigamox, Alcon),
which is self-preserved," he explains. "This is important, because when patients
are receiving injections every 6 weeks, according to protocol, the bottle of antibiotics
stays open longer than with a 1-time procedure like cataract surgery. Patients might
touch the tip of the bottle to their eyes, lids or foreign surfaces, increasing
the risk for contamination and infection. The preservative in gatifloxacin provides
protection against bottle contamination, while moxifloxacin doesn't. Once moxifloxacin
has been opened it only lasts 1 injection cycle. Gatifloxacin can be used for several
injections," he adds.
ARE ANTIBIOTICS NECESSARY?
On the other side of the debate sits Minneapolis retinal surgeon
David F. Williams, MD, MBA, who says a careful sterile technique and use of topical
povidone-iodine are the single most important factors to decrease the risk of endophthalmitis
associated with invasive ophthalmic procedures.
Dr. Williams does not use antibiotics in association with intravitreal
injections for 2 reasons. "The incidence of endophthalmitis following properly done
intravitreal injections is extremely low at about 1/1000 and there is no evidence
that use of pre-or post-injection topical antibiotics decreases this risk," he says.
Dr. Williams says he would make an exception if the patient showed evidence of significant
ocular surface disease and/or severe blepharitis. "In these cases, I ask the patient
to go through a regimen of lid hygiene, and I would strongly consider both pre-
and post-injection antibiotics."
Dr. Williams points out that antibiotics, such as the fourth-generation
fluoroquinolones, are also expensive, costing about $50 wholesale, and $75 or more
retail. "Just to theoretically decrease the risk of the 1/1000 cases of endophthalmitis
would therefore cost somewhere between $50,000 and $75,000 per case of endophthalmitis,
with no assurance that using the antibiotics would even be effective," says Dr.
"NEW" PROTOCOL NEEDS UPDATE
Terrence P. O'Brien, MD, the Charlotte Breyer Rodgers distinguished
professor of Ophthalmology at Bascom Palmer Eye Institute in Miami and former director
of ocular infectious diseases and ocular microbiology laboratory at The Wilmer Eye
Institute at Johns Hopkins University School of Medicine in Baltimore, notes that
patients desperate with sight-threatening diseases of the posterior segment tend
to view these therapeutic intravitreal injections as a "magic bullet," sometimes
failing to fully appreciate that the route of delivery carries with it the risk
of introducing a microorganism into the eye.
"We have some valuable surrogate evidence from cataract surgery,
and I think retinal surgeons may be able to adopt some of the lessons learned from
cataract surgeons, particularly with respect to proper utilization of antiseptics
and antibiotic agents, including the fourth-generation fluoroquinolones, in an effort
to better prepare the ocular surface for injections," says Dr. O'Brien. "The best
way to reduce ocular surface contamination is through a 2-pronged strategy. The
first prong is represented by the use of an antiseptic such as povidone-iodine that
has a direct contact mechanism and rapid onset of action. The use of povidone-iodine
5% directly onto the field without irrigation will help keep it in contact with
the conjunctival and ocular surface to help reduce contamination. The second prong
is the use of a fourth-generation fluoroquinolone in a brief perioperative pulse."
Dr. O'Brien says fourth-generation fluoroquinolones are more effective
against a broader spectrum of gram-positive bacteria than earlier antibiotics were.
"With the newer generation we have better coverage against Staphylococcus epidermis,
Staphylococcus aureus, and even streptococci," he said. "Moreover, with the
fourth-generation fluoroquinolones, we have compelling pharmacodynamic kill curve
data that says that using gatifloxacin or moxifloxacin the day of [treatment] is
perhaps as good as beginning it 2 or 3 days prior," says Dr. O'Brien.
While the updated pegaptanib protocol calls for either pre-injection
topical ophthalmic antibiotic drops for 3 days prior to the injection or a 10 mL
povidone-iodine flush immediately prior to injection, Dr. O'Brien thinks the combination
of both is better than just 1 or the other because those guidelines were based on
studies using ofloxacin, an earlier generation of antibiotic. "This is why we have
to update those recommendations to be consistent with data achievable with the new
generation of fluoroquinolones gatifloxacin and moxifloxacin," he explains.
How long after treatment the fluoroquinolone should be used remains
to be seen, and whether a topically administered drop achieves sufficiently high
concentrations in vitreous humor to be protective is still in question, he points
out. "We may be fooling ourselves thinking that we can achieve levels in the vitreous
that are therapeutic," says Dr. O'Brien. "We're doing studies right now to find
out just how many drops are needed to achieve a level that might be protective if
there were organisms that were introduced at the time of the injection," he adds.
Findings may be reportable by the annual fall meeting of the American Academy of
Ophthalmology, according to Dr. O'Brien.
1. Ta C. Minimizing the risk of endophthalmitis following intravitreous
injections. Retina. 2004;24(5):699-705.
Retinal Physician, Issue: September 2005