Cataract Controversy
By Miriam
Karmel
Is the
incidence on the rise?
What’s the best antibiotic to use?
What
about prophylaxis?
Cataract surgeons are struggling with too many
questions—and not enough answers.
Endophthalmitis following
cataract surgery may be on the rise. Or, it may not be. Nobody knows for
sure. What is known is that endophthalmitis is a blinding, devastating
condition. Outside of that, everything from its cause to its prevention is
subject for debate.
Holes in the
Evidence
The dispute was rekindled this past year, with
the introduction of a new generation of fluoroquinolones and a
meta-analysis of the literature. “It truly is an unsettled area,” said
Peter J. McDonnell, MD.
It is unsettled due to what might be
called the only good thing about endophthalmitis: The condition is rare,
with an incidence historically of 1 in 1,000 or less. Given the 2.8
million cataract surgeries in the United States, there are perhaps only
2,800 new cases per year, a number far too small to conduct the kind of
randomized, prospective clinical studies that might put some of the
controversy to rest.
In the absence of such studies,
prevention and treatment strategies have been based on clinical
impressions and personal experience. But Dr. McDonnell argues that we need
to get beyond that. “This is our most common surgical procedure and it
looks like there is a growing body of evidence indicating that
endophthalmitis may be on the increase, particularly over the last
decade.” Dr. McDonnell, who hopes to get funding to conduct a major study,
added, “Out of fairness to our profession and our patients, we need to do
our best to answer this one way or another.”
Until then, noted
David F. Chang, MD, “Without definitive randomized studies, we’re left
with using our best judgment in the area of infection
prophylaxis.”
Samuel Masket, MD, agrees. “The evidence-based
literature may not reflect the best methods for endophthalmitis
prophylaxis because studying endophthalmitis is difficult and the
appropriate studies have not been performed. So unfortunately, looking at
the literature is not always the best way for finding the best
methods.”
Even the question of incidence is up in the air. “There
are certainly publications that suggest endophthalmitis is on the rise,”
said Dr. McDonnell, who was part of the meta-analysis team, which reviewed
the literature to determine the incidence of acute endophthalmitis
following cataract surgery and penetrating keratoplasty.1 “I
happen to believe that it is on the rise,” he said. “But I don’t think
there is consensus.”
If it is on the upswing, said Dr. McDonnell,
“We’d better figure out how to deal with that. Because if the risk is
increased by two to three times, I think most ophthalmologists would say
it truly does represent a public health problem of very significant
dimension.”
What follows is a look at some of the controversy
surrounding endophthalmitis.
Clear
Corneal Surgery
Clear corneal cataract extraction is
often blamed for the perceived rise in endophthalmitis. The procedure,
introduced in the early 1990s, has many advantages, Dr. McDonnell said. It
is efficient to perform, cost-effective and allows for rapid visual
rehabilitation.
But recent studies, reported in the American
Journal of Ophthalmology2 and the Canadian Journal of
Ophthalmology,3 found a threefold and a 2.5-fold increased
risk of infection with clear corneal incisions, respectively.
The
meta-analysis corroborates the risk factor. After examining some 7,000
citations and studies that mentioned endophthalmitis, Dr. McDonnell and
his colleagues found some correlation between clear corneal surgery and a
higher incidence of endophthalmitis. The literature shows that since the
1990s, the incidence of endophthalmitis following clear corneal surgery
was 0.2074 percent, compared with 0.0826 percent for scleral/limbal
incisions.
Not everyone, however, accepts the notion that the
sutureless surgery leads to more infection. Some attribute the rise to the
learning curve, arguing that the numbers are an artifact, reflecting
nothing more than the complications that arise as doctors learn a new
procedure. When sutureless incisions were introduced, said Dr. Masket,
“there was a blip on the screen, an increased number of infections. People
had adapted it to their armamentarium, but had not learned the procedure.”
While the retrospective studies suggest a correlation,
ophthalmologists must not jump to conclusions that incriminate all clear
corneal incisions, Dr. Chang said. As a group, the incisions can vary
significantly in terms of size, location and architecture, he noted. Some
are less than 3 millimeters wide, while others are wider than 4 mm. “In
the cornea, that’s a big difference.” Also, some have greater radial
length than others. Some are temporal, and some are superior in location.
Some surgeons make a groove, while others do not. Some use diamond blades;
others use metal. “Clearly, these incisions are not all equal in terms of
the risk of transient leak.”
As Dr. Masket, who has been
performing clear corneal surgery exclusively since 1993, put it, “I don’t
think that you can condemn the technique. It’s more the technician.” The
creation of the incision involves finesse, he said. “If one doesn’t pay
attention, it can be associated with a greater likelihood of infection.”
Both Drs. Chang and Masket argue that the technique demands that
surgeons pay attention to size and architecture of the incision, because
the cornea is less forgiving than the sclera. “The absence of a
conjunctival barrier makes the construction of a corneal incision much
more important,” Dr. Masket said.
Both caution against making an
incision larger than 3.5 mm, because it won’t seal as well, and the larger
the incision, the less watertight it’s going to be. Leakage in the early
postoperative period could allow organisms to enter the eye. “With any
incision, whether it’s corneal or scleral, make sure it’s well apposed and
watertight at the end of the case,” Dr. Chang said. “If it’s not, you
could put in a suture and reinforce it.”
A study conducted by Dr.
McDonnell and his colleagues and published in
Ophthalmology4 lends support to suturing. In the
study, self-sealing clear corneal incisions were created in rabbit eyes.
Then, using an artificial anterior chamber, India ink was applied to the
surface of cadaveric human corneas with clear corneal incisions to detect
possible flow of surface fluid along the incision. Because this study did
not involve in vivo human eyes, the authors did not feel confident making
any firm clinical recommendations, Dr. McDonnell said. “We simply
suggested that this may, if confirmed in patients, cause surgeons to
reconsider use of a stitch or how they use antibiotics postoperatively.”
“The real message,” said Dr. Chang, “is not that clear corneal
incisions are inherently risky, but rather that there’s less margin for
error. They must be properly sized and constructed.”
Antibiotic Selection and Prophylaxis
Although the FDA has not approved topical antibiotics
for surgical prophylaxis to prevent endophthalmitis, and will not allow
them to be marketed as such, they are widely used in this way. Despite the
absence of any scientific study to say that this practice is effective,
physicians administer antibiotic drops pre- and postoperatively to
eradicate any conjunctival contamination.
“All cataract surgeons I
know use them,” Dr. McDonnell said. “It’s the standard of care in our
profession.”
That doesn’t mean their use isn’t controversial.
While some lab studies have found antibiotics protective of
endophthalmitis in rabbit models, there are no human studies, Dr. Masket
noted. “Therein lies the controversy.”
Then there’s the matter of
which antibiotic to use. Last year, a fourth generation of
fluoroquinolones was introduced, raising the questions of which generation
of quinolone to use and whether the newer, more expensive drugs are
necessary. Without the proper studies to say that they are necessary or
even effective, how do physicians know whether moxifloxacin (Vigamox) and
gatifloxacin (Zymar) should become part of their armamentarium?
Deepinder K. Dhaliwal, MD, and her colleagues at the University of
Pittsburgh tested moxifloxacin and found that topical application was able
to effectively eradicate bacteria in the anterior chamber of rabbits. In a
study funded by Alcon, 10 rabbits were injected with bacteria into the
anterior chamber and treated with the antibiotic pre- and postinjection,
and 10 were injected with bacteria and received placebo drops. None of the
moxifloxacin-treated rabbits developed infection; all of the placebo
rabbits did. “This is the first study to show that topical application of
antibiotic drops could prevent the development of endophthalmitis. The
difference in appearance of the eyes in the two groups was very dramatic,”
Dr. Dhaliwal said.
So dramatic, in fact, that the decision to
switch from second- and third-generation fluoroquinolones to the
fourth-generation options is “an obvious choice,” she said. “These
antibiotics penetrate better. They’re more potent. Moxifloxacin is
preservative free, so surface toxicity should be minimal.”
What’s
more, the second- and third-generation drugs, though effective against
gram-negative germs, don’t provide the necessary coverage against the
predominantly gram-positive strains that cause endophthalmitis.
Another issue is the increase in resistance to the earlier
fluoroquinolones. “If we continue to use these less-powerful antibiotics,
we’re going to have more organisms that become resistant,” Dr. Dhaliwal
said.
The ability of the newer antibiotics to penetrate into the
anterior chamber is “something that we have never seen with any ocular
topical antibiotic,” Dr. Dhaliwal said. “We need to get the antibiotics to
where the bacteria are. The bacteria are in the eye. That’s why
intraocular penetration is so critical.”
While she believes
there’s no reason not to use the fourth-generation drugs, Dr. Dhaliwal
acknowledges that in the absence of a convincing prospective study, some
doctors may not want to switch. Cost may be one deterrent, especially as
the second-generation fluoroquinolones become available in generic form.
What’s more, physicians who have not seen a case of endophthalmitis in
1,000 cases might not see a reason to change a practice pattern when the
drug they’ve been prescribing has worked.
Intraoperative Antibiotics
Another
unsettled question is whether to apply antibiotics during surgery and, if
so, by what route. And those who do use intracameral antibiotics at the
end of a case are divided between those who infuse and those who inject
directly into the anterior chamber. Again, there have yet to be
well-designed studies to indicate that such use of antibiotics—typically
vancomycin (Vancocin)—prevents infection.
Survey results suggest
that around 40 percent of physicians use antibiotics at the end of a case,
although the CDC, the Academy and academic medical centers have taken a
position against prophylactic use of vancomycin, arguing that its
systematic use has led to microbial resistance. But Dr. Masket asserts
that using it in the eye, in an outpatient setting, is different and “has
no likelihood whatsoever of contributing to the problem.”
Whether
it contributes to the resistance problem or not, Eric D. Donnenfeld, MD,
said that vancomycin is associated with other problems. It can be toxic,
and it has been associated with the development of cystoid macular edema.
It doesn’t provide gram-negative coverage, and has a very slow kill curve
so that the drug drains out of the eye through the trabecular meshwork
before it has a chance to be effective.
In a search of a better
treatment, Dr. Donnenfeld has been conducting a prospective study of
intracameral gatifloxacin injected directly into the anterior chamber at
the conclusion of surgery. Injection of gatifloxacin (100 micrograms in
0.1 cc) achieves a 50 times higher level of protection in the aqueous than
does topical application, he said. What’s more, treatment may be
supplemented with topical gatifloxacin, unlike with vancomycin, which has
no topical equivalent.
Although Dr. Donnenfeld uses this treatment
in his own practice, he said that for safety reasons he prefers waiting
for more data—expected by early summer—before advocating this treatment.
______________________________
1 Taban, M. et al. Presented at
the Academy’s Annual Meeting, Nov. 18, 2003, Anaheim, Calif.
2 Cooper,
B. A. et al. Am J Ophthalmol 2003:136(2):200–305.
3 Colleaux,
K. M. and W. K. Hamilton. Can J Ophthalmol 2000;35:373–378.
4
Ophthalmology 2003;110(12):2342–2348.
______________________________
Points of Discussion
Proper Draping
Dr.
Masket: “[Proper draping] is of utmost importance. It prevents
microbes on the patient’s lids, lashes and lid margins from getting into
the eye and potentiating infection. If that is the source of infection, it
behooves us to prevent contamination by isolating lashes and lid margins
as well as possible.
“I fashion the drape to curl under the lid
margin. And I isolate the ocular margin as much as possible from the lids.
Both the lid margins and drape are covered with steristrips. I always
double glove and remove the first set of gloves after applying the
steristrips, because those gloves may have touched the skin during
application.”
The
Incision
Dr. Masket: “The architecture
must be nearly square in its surface anatomy. The incision must never
exceed 3.2 mm in width and the length of the tunnel should be at least 2.5
mm. A 3-mm by 2.5-mm incision is going to be physically very stable, and
will not be subjected to deformation by external pressure.
“Do not
assume that a smaller incision is a better incision. If it’s too small,
the emulsification equipment or the lens can stretch and distort the
tissue. A well-constructed 3-mm incision is far better than a stretched
2.5-mm incision.
“It is important to avoid hypotony. If the
pressure is low, the incision won’t seal and it will leak. I test IOP with
an applanating tonometer [Kratz-Terry, made by Ocular Instruments of
Bellevue, Wash.], and perform an intraoperative Seidel test on all
incisions. I routinely perform stromal hydration, including the roof of
the tunnel, in addition to the sides. If the wound leaks, I rehydrate. If
there is leakage after a second Seidel test, I add a
suture.”
Which
Antibiotic?
Dr. Chang: “It makes sense to use the
fourth-generation fluoroquinolones, moxifloxacin and gatifloxacin. I’m
using them. There is less bacterial resistance, good penetration and broad
spectrum of activity.”
Dr. Dhaliwal: “I start
antibiotic prophylaxis an hour before the case [every 15 minutes for four
doses], instill a drop immediately after the surgery, and then four times
a day for a week.”
Dr. Masket: “I start them the
day before surgery, four times a day, and continue for five days after
surgery. Postsurgery every two hours, then four times a day for another
five days.”
Administration of the
Antibiotic
Dr. Chang: “If you’ve made a decision that
you want to administer some antibiotic at the time of surgery, what makes
the most sense to me is to inject it directly into the eye. You know the
exact dose that reaches the anterior chamber. With addition to the
infusion bottle, you can’t be sure how much is actually getting into the
eye at the end of the case.”
Dr. Masket: “I put 20
mg of vancomycin in 500 cc of balanced salt solution. My sense is that
injection at the end of surgery is likely to be more efficacious, but I
operate in more than one location, and I have concerns that there could be
a dilutional error. Because I have to rely on someone else to dilute it,
putting 1 mg in 0.1 cc directly into the chamber takes a greater leap of
faith [for me].”
_______________________________
Meet the
Experts
David F. Chang, MD
Clinical professor of ophthalmology at the University of California, San
Francisco. Financial interests: None.
Deepinder K.
Dhaliwal, MD Director of refractive surgery, director of cornea
and external disease and associate professor of ophthalmology at the
University of Pittsburgh. Financial interests: Serves on the speakers’
bureau of Alcon.
Eric D. Donnenfeld, MD
Cochairman of external disease and cornea at Manhattan Eye Ear and Throat
Hospital and in private practice in New York. Financial interests: Is
a consultant for Allergan and Alcon.
Samuel Masket,
MD In private practice in Los Angeles and clinical professor of
ophthalmology at the University of California, Los Angeles. Financial
interests: No related interests.
Peter J. McDonnell,
MD Professor of ophthalmology and director of the Wilmer
Ophthalmological Institute. Financial interests: No related
interests.