The Effect of Cataract Surgery on Ocular
Levels of Topical Moxifloxacin
ROOKAYA MATHER, MD, JAY M. STEWART, MD, TISHA PRABRIPUTALOONG, MD,
JOSHUA WONG, MS, AND STEPHEN D. MCLEOD, MD
● PURPOSE: To investigate the effect of cataract surgery
on the concentration of moxifloxacin in aqueous and
vitreous humor after topical application.
● DESIGN: Prospective laboratory intervention using a
rabbit model.
● METHODS: Following topical administration of 0.5%
moxifloxacin, 60 minutes before surgery and immediately
post cataract surgery, aqueous and vitreous humor were
sampled at 30, 60, and 120 minutes postsurgery. Moxi-
floxacin concentrations were determined by high-pres-
sure liquid chromatography (HPLC). Mean tissue
concentrations obtained in surgical eyes were compared
with concentrations obtained in nonsurgical eyes. The
potential effectiveness of moxifloxacin in providing pro-
phylaxis against intracameral bacterial inoculation was
investigated by comparing antibiotic concentrations to
minimum inhibitory concentration (median MIC90) val-
ues for Staphylococcus aureus and Staphylococcus epi-
dermidis.
● RESULTS: In surgical eyes, mean moxifloxacin concen-
trations in aqueous were 13.9, 16.2, and 12.2 ␮g/ml
versus 25.3, 32.6, and 15.7 ␮g/ml in nonoperated eyes at
30, 60, and 120 minutes, respectively. No statistically
Accepted for publication May 12, 2004.
From the Department of Ophthalmology, University of California, San
Francisco, California; and the Francis I. Proctor Foundation for Research
in Ophthalmology.
Dr. Mather is now affiliated with the University of Western Ontario,
Department of Ophthalmology, London, Ontario, Canada.
From the Department of Ophthalmology (R.M.), University of West-
ern Ontario, London, Ontario, Canada; and the Francis I. Proctor
Foundation for Research in Ophthalmology (J.M.S., T.P., J.W., S.D.M.)
and Cornea Service of the Department of Ophthalmology (T.P., S.D.M.),
University of California, San Francisco, California.
Supported by an unrestricted research grant from Alcon Pharmaceu-
tical, Fort Worth, Texas.
This study was also supported by an unrestricted grant from Research
to Prevent Blindness Inc., New York New York.
Data from this article were presented in part at the Ocular Microbiol-
ogy and Immunology Group meeting, in Anaheim, California, November
2003.
Drs. McLeod and Mather have received consulting fees from Alcon
Pharmaceutical, Fort Worth, Texas.
Inquiries to Stephen D. McLeod, MD, Department of Ophthalmology,
University of California, San Francisco, K-301, Box 0730, 10 Kirkham
St., San Francisco, CA, 94143, Phone: 415-502-5195, Fax: 415-476-
2896, e-mail: smcleod@itsa.ucsf.edu
554 © 2004 BY ELSEVIER INC. ALL
significant differences were found between surgical and
nonsurgical eyes. In surgical eyes, mean moxifloxacin
concentrations in vitreous were 66.8, 66.6, and 400.2
ng/ml versus 43.1, 199.8, and 54.4 ng/ml in nonoperated
eyes at 30, 60, and 120 minutes, respectively. These
differences were not statistically significant.
● CONCLUSIONS: There were no statistically significant
differences in the penetration of topical moxifloxacin in
eyes undergoing cataract surgery compared with unoper-
ated eyes. A multiple-drop schedule of moxifloxacin
produced aqueous concentrations that were well above
the MICs of even resistant strains of the most common
organisms implicated in postcataract surgery endoph-
thalmitis. (Am J Ophthalmol 2004;138:554 –559. ©
2004 by Elsevier Inc. All rights reserved.)
B
ACTERIAL ENDOPHTHALMITIS IS A POTENTIALLY
devastating ocular infection that has been reported
to occur following approximately 0.1% of routine
cataract procedures. Recently there has been great concern
regarding an apparent increase in the rate of endoph-
thalmitis associated with a number of changes in surgical
technique including sutureless clear corneal wounds and
infection prophylaxis strategies.1 At present, many cata-
ract surgeons advocate using a prophylactic antibiotic
regimen both pre- and postoperatively as a means of
reducing the risk of endophthalmitis. Ideally the antibiotic
chosen for endophthalmitis prophylaxis should be potent,
nontoxic, bacteriocidal, and have a broad spectrum of
activity. Particularly in the postoperative period, this agent
should also display rapid and high levels of penetration
into the anterior chamber to achieve a sufficient concen-
tration in the aqueous humor to minimize the likelihood of
clinical infection by organisms that have potentially been
inoculated at the time of surgery.1–3 Furthermore, adequate
levels of antibiotic should persist in the intracameral space
following surgery to suppress bacterial proliferation.
Effective anti-infective prophylaxis for cataract surgery
has two components. The first is preoperative administra-
tion of topical agents to eliminate surface organisms that
may seed the anterior chamber during surgery. The second
involves postoperative administration of topical antibiot-
RIGHTS RESERVED. 0002-9394/04/$30.00
doi:10.1016/j.ajo.2004.05.011
ics not only to maintain surface sterility in the event of
surface fluids entering the eye via the corneal wound, but
also to penetrate into the anterior chamber and suppress
the proliferation of an intracameral inoculum. Ideally,
therefore, anterior chamber penetration should be high
enough to achieve concentrations that exceed the mini-
mum inhibitory concentration (MIC) values for the or-
ganisms most commonly responsible for postoperative
endophthalmitis.
Studies to evaluate the penetration of antibiotics into
the anterior chamber in the setting of cataract surgery have
typically been designed such that aqueous samples are
withdrawn at the beginning of the cataract procedure.4,5
At this stage, topically applied antibiotic must penetrate
an intact epithelium because there is no alternative route
of ingress. The process of cataract surgery is unavoidably
traumatic to the ocular surface, however, and may reduce
the barrier function of the epithelium. Moreover, the
creation of limbal wounds with potential incontinence and
backflow establishes an alternative route for antibiotic
influx if concentrations in the tear film are adequately
high.6 Alternatively, corneal and anterior chamber irriga-
tion and an accompanying increase in the effective volume
of the anterior chamber following removal of the crystal-
line lens may cause dilution of drug and lower antibiotic
concentrations. Until now, differences in antibiotic levels
as a result of cataract surgery have not been formally
investigated. Such differences might produce higher levels
(based on enhanced penetration) or lower, potentially
ineffective levels (based on dilution) than those suggested
by studies that measure antibiotic levels in the aqueous
humor at the beginning of surgery. It is important to
establish whether topical antibiotic administered at the
conclusion of surgery will achieve an effective, supra-MIC
concentration in the anterior chamber in the early post-
operative period and whether an effective bacteriocidal
concentration is sustained during the time interval be-
tween surgery and the time when the patient initiates their
own postoperative antibiotic application.
The purpose of this study was to investigate the ocular
concentration of topically applied moxifloxacin in a rabbit
model of cataract surgery and to evaluate the effect that
surgery might have on these dynamics. The study design also
allowed us to evaluate the potential effectiveness of moxi-
floxacin in providing prophylaxis against intracameral bacte-
rial inoculation by comparing antibiotic concentrations
measured over the first 2 hours after surgery to MIC values for
Staphylococcus aureus and Staphylococcus epidermidis.
DESIGN
A PROSPECTIVE LABORATORY INTERVENTION DESIGN US-
ing a rabbit model to study the effect of cataract surgery on
the aqueous and vitreous concentrations of topically ad-
ministered moxifloxacin.
VOL. 138, NO. 4 EFFECT OF CATARACT SURGERY ON
METHODS
● SAMPLE SIZE: Based on previously reported studies of
aqueous penetration of ofloxacin in eyes with intact
epithelium and in eyes with epithelial compromise from
bullous keratopathy, we predicted a difference in magni-
tude of moxifloxacin concentration of approximately 75%
in surgical eyes compared with eyes that did not undergo
cataract surgery.4,5,7
Assigning an ␣ of 0.05 and ␤ of 0.20 (power of 0.8), a
paired t test yielded a sample size of 17 eyes per arm (17
surgical and 17 nonsurgical eyes). To facilitate aqueous
and vitreous humor sampling at three time points, each
arm was divided into three groups of six eyes. Thus, 18 eyes
per arm were required to detect a 75% difference in
antibiotic concentration between surgical and nonsurgical
eyes. To sacrifice the fewest animals possible, the fellow
eye served as the nonsurgical control arm. An additional
30 eyes (15 rabbits) were enrolled in the study to establish
standards for high-pressure liquid chromatography
(HPLC) analysis.
● RABBITS: Pigmented, Dutch-belted rabbits (2 to 3 kg)
were maintained in strict accordance with the institutional
guidelines and maintained in animal care facilities fully
accredited by the American Association of Laboratory
Standards. All experimental studies were conducted in
accordance with the Association for Research in Vision
and Ophthalmology Resolution on the Use of Animals in
Research and were approved by the Committee on Animal
Research and the Office of Environmental Health and
Safety of the University of California, San Francisco
(UCSF). Rabbits were anesthetized by intramuscular in-
jections of ketamine (35 to 50 mg/kg) and xylazine (5 to 10
mg/kg). During all steps of the study, rabbits were carefully
monitored for pain, discomfort, and adverse reactions.
Additional ketamine and xylazine were administered to
ensure adequate anesthesia during the procedure as well as
to ensure deep anesthesia at the time of euthanasia.
Animals were euthanized with an intracardiac injection of
pentobarbital (250 mg/kg) 6 mg/ml, followed by bilateral
thoracotomy.
● MOXIFLOXACIN: Commercially available 0.5% moxi-
floxacin (Vigamox) self-preserved was provided by Alcon
(Forth Worth, Texas).
● MOXIFLOXACIN DOSING: A dosing regimen considered
comparable to one employed routinely in surgicenter
practice was applied. Topical 0.5% moxifloxacin was
administered to all eyes, 60 minutes preoperatively and
immediately postcataract surgery, as three single-drop (30
␮l/drop) applications separated by 5 minutes. The same
regimen of three drops (each separated by 5 minutes) was
applied at the end of surgery.
OCULAR LEVELS OF MOXIFLOXACIN 555
● CATARACT SURGERY: One hour preoperatively, all
eyes received one drop of flurbiprofen (0.03%) followed by
three drops of moxifloxacin 0.5% (Alcon) as described
earlier. Thirty minutes later, eyes in the surgical arm
received one drop each of proparacaine, phenylephrine
hydrochloride (10%), and cyclopentolate (1%). After 30
minutes, eyes in the surgical arm underwent cataract
extraction by phacoemulsification via a 3-mm clear cor-
neal incision. Two 10-0 nylon sutures were placed to close
the incision at the conclusion of the surgery. The fellow
eyes received all antibiotic drops but did not undergo
cataract surgery. Immediately following surgery, all eyes
(surgical eyes and nonsurgical fellow eyes) received three
drops of moxifloxacin separated by 5 minutes each.
● AQUEOUS HUMOR AND VITREOUS HUMOR SAM-
PLING: The concentration of moxifloxacin in ocular tis-
sues in both operated and unoperated eyes was evaluated at
three time points after surgery. Eighteen rabbits (36 eyes)
were divided into three groups. Eyes in groups 1, 2, and 3
underwent aqueous and vitreous sampling at 30, 60, and
120 minutes, respectively, postsurgery.
A volume of 0.2 ml of aqueous humor was withdrawn
from the anterior chamber using a 27-gauge needle on a
tuberculin syringe. Vitreous humor was aspirated using a
25-gauge needle and 1-ml syringe. All samples were im-
mediately placed on dry ice and stored at ⫺70 C for
subsequent HPLC analysis of moxifloxacin levels.
● AQUEOUS AND VITREOUS HUMOR SAMPLES: Tissue
preparation and HPLC were performed in the Bioanalyti-
cal Department of Alcon Research (Fort Worth, Texas).
Samples were submitted in a masked fashion, with only the
UCSF investigators being aware of the sample identity.
Aqueous and vitreous humor samples were evaporated to
dryness under a stream of nitrogen at 42 C using a
TurboVap apparatus. The dried residue was dissolved in
100 ␮l of mobile phase and assayed by reverse-phase
HPLC, (mobile phase: 50 mmol/l sodium phosphate, 15
mmol/l tetrabutyl ammonium hydroxide; pH 3.0; acetoni-
trile:methanol (80:15:5); flow rate 1.5 ml/min). Detection
was by fluorescence (excitation and emission wavelengths:
275 and 500 nm, respectively). High-pressure liquid chro-
matography column was a Waters Symmetry C18, 5
␮mol/l, 3.9 ⫻ 150 mm; run time was 5 to 6 minutes.
Calibration curve and quality control samples were pre-
pared by spiking cornea homogenates with authentic
moxifloxacin standards at appropriate concentrations for
the desired concentration range. Concentrations of moxi-
floxacin were determined by linear regression from peak
height ratios of the moxifloxacin peak to the internal
standard peak (lomefloxacin). Calibration curves, gener-
ated by Waters Millennium Chromatography Manager
software, were used.
556 AMERICAN JOURNAL
● MINIMUM INHIBITORY CONCENTRATIONS: Aqueous
humor and vitreous humor concentrations of moxifloxacin
were compared with MIC values for moxifloxacin against
S. aureus and S. epidermidis clinical endophthalmitis iso-
lates as reported by Mather and associates.8 In that study,
the MICs (␮g/ml) of bacterial endophthalmitis isolates
were determined using E-tests (AB Biodisk, Piscataway,
New Jersey), and the median MIC for different isolates of
a given species used as the reference MIC.
● STATISTICAL ANALYSIS: Differences in moxifloxacin
concentration between surgical and nonsurgical eyes were
compared using a Wilcoxon signed rank test. An ␣ of .05
was used to determine statistical significance.
RESULTS
● AQUEOUS HUMOR: Relatively high concentrations of
moxifloxacin were detected in the aqueous humor of both
operated and nonoperated eyes at all time points. No
statistically significant differences were found between
operated and nonoperated eyes at any time point. At 30
minutes, the mean (geometric mean) concentration of
moxifloxacin in aqueous humor was 25.3 ␮g/ml (95%
confidence interval [CI] ⫾ 16.8) in nonsurgical eyes and
13.9 ␮g/ml (95% CI ⫾ 7.2) in surgical eyes (P ⫽ .68). At
60 minutes, the mean moxifloxacin concentration was
32.6 ␮g/ml (95% CI ⫾ 20.1) in nonsurgical eyes and 16.2
␮g/ml (95% CI ⫾ 3.12) in surgical eyes (P ⫽ .69). At 120
minutes, the mean moxifloxacin concentration was 15.7
␮g/ml (95% CI ⫾ 15.0) in nonsurgical eyes and 12.2
␮g/ml (95% CI ⫾ 5.1) in surgical eyes (P ⫽ 1.00). At all
time points, the mean moxifloxacin concentrations are at
least 200-fold greater than the median MIC values for
fluoroquinolone-susceptible isolates of S. aureus and coag-
ulase negative Staphylococcus and are at least fourfold
higher than the median MIC values for fluoroquinolone-
resistant isolates of S. aureus and coagulase-negative
Staphylococcus.
● VITREOUS HUMOR: At 30 minutes, the mean moxi-
floxacin concentrations in vitreous aqueous humor was
43.1 ng/ml (95% CI ⫾ 122.7) in nonsurgical eyes and 66.8
ng/ml (95% CI ⫾ 59.2) in surgical eyes (P ⫽ .38). At 60
minutes, the mean moxifloxacin concentration was 200
ng/ml (95% CI ⫾ 631.2) in nonsurgical eyes and 66.6
ng/ml (95% CI ⫾ 86.3) in surgical eyes (P ⫽ .45). At 120
minutes, the mean moxifloxacin concentration 54.4 ng/ml
(95% CI ⫾ 49.7) in nonsurgical eyes and 400 ng/ml (95%
CI ⫾ 1083.3 in surgical eyes (P ⫽ .12). Vitreous concen-
trations of moxifloxacin did not reach therapeutic levels at
any time point, particularly with respect to fluoroquinolo-
ne-resistant isolates of S. aureus and coagulase-negative
Staphylococcus.
OF OPHTHALMOLOGY OCTOBER 2004
 TABLE 1. Minimum Aqueous and Vitreous Humor Concentrations of Moxifloxacin Versus Median MIC Values for Staphylococcus
aureus and coagulase-negative Staphylococcus

MIC12 Bacterial MAC (␮g/ml), MAC (␮g/ml), MVC (ng/ml), MVC (ng/ml),
† † † †
(ng/ml) Isolate Time Surgical Eyes Ratio Control Eyes Ratio Surgical Eyes Ratio Control Eyes Ratio

1750 FR-SA 30 2.59 1.48 14.9 8.51 28.1 0.02 17.7 0.01
60 FS-SA 30 2.59 43.17 14.9 248.33 28.1 0.47 17.7 0.29
2500 FR-CNS 30 2.59 1.04 14.9 5.96 28.1 0.01 17.7 0.01
50 FS-CNS 30 2.59 51.80 14.9 298.00 28.1 0.56 17.7 0.35
1750 FR-SA 60 11.5 6.57 8.58 1.90 22.4 0.01 25.1 0.01
60 FS-SA 60 11.5 191.67 8.58 143.00 22.4 0.37 25.1 0.42
2500 FR-CNS 60 11.5 4.60 8.58 3.43 22.4 0.01 25.1 0.01
50 FS-CNS 60 11.5 230.00 8.58 171.60 22.4 0.45 25.1 0.50
1750 FR-SA 120 8.4 4.80 8.18 4.67 49.0 0.03 23.5 0.01
60 FS-SA 120 8.4 140.00 8.18 125.33 49.0 0.82 23.5 0.39
2500 FR-CNS 120 8.4 3.36 8.18 3.27 49.0 0.02 23.5 0.01
50 FS-CNS 120 8.4 168.00 8.18 163.60 49.0 0.98 23.5 0.47

MIC ⫽ minimum inhibitory concentration; MAC ⫽ minimum aqueous concentration; MVC, minimum vitreous concentration; FR-SA ⫽
fluoroquinolone-resistant S. aureus (Staphylococcus aureus resistant to ciprofloxacin and ofloxacin as determined by disk diffusion); FS-SA
⫽ fluoroquinolone-susceptible S. aureus (Staphylococcus aureus susceptible to ciprofloxacin and ofloxacin as determined by disk diffusion);
FR-CNS ⫽ fluoroquinolone-resistant coagulase-negative Staphylococcus (coagulase-negative Staphylococcus resistant to ciprofloxacin and
ofloxacin as determined by disk diffusion); FS-CNS ⫽ fluoroquinolone-susceptible coagulase-negative Staphylococcus (coagulase-negative
(Staphylococcus susceptible to ciprofloxacin and ofloxacin as determined by disk diffusion).
Tissue concentration expresses the lowest concentration measured of moxifloxacin in aqueous humor and vitreous humor.
†
Concentration: MIC.

The ratios of the lowest measured moxifloxacin con-
centrations to MIC values are listed in Table 1.
DISCUSSION
ALTHOUGH THE SPECIFIC ROLE OF ANTIBIOTIC PROPHY-
laxis in the setting of cataract surgery remains a study of
investigation and debate, recent evidence suggests that
perioperative antibiotic prophylaxis might reduce the risk
for postoperative endophthalmitis.9 For prophylaxis to be
effective in both the preoperative and early postoperative
phases of the procedure, penetration into the anterior
chamber must produce antibiotic levels that are sufficiently
high to inhibit the bacterial colony count of organisms
introduced during or following surgery.
The fluoroquinolones are a group of antibiotics that are
widely used for topical antibiotic prophylaxis of bacterial
endophthalmitis following cataract extraction. Fluoro-
quinolones are rapidly bacteriocidal in action and exert
their effects by variably inhibiting the action of bacterial
DNA gyrase, an enzyme essential for bacterial DNA
synthesis. The currently available second- and third-gen-
eration fluoroquinolones for topical ophthalmic use (cip-
rofloxacin, ofloxacin, and levofloxacin) have similar
antimicrobial spectra, including most aerobic gram-nega-
tive and some gram-positive bacteria. Currently, there is
considerable concern regarding the emerging resistance in
Staphylococcus strains, particularly S. aureus and S. epider-
midis.10 –12 However, recent modifications in fluoroquino-
lone chemistry have produced agents with an expanded
spectrum of activity against gram-positive bacteria and
anaerobes. Of particular interest are the fourth-generation
fluoroquinolones adapted for ophthalmic use, including
moxifloxacin (Vigamox) and gatifloxacin (Zymar, Aller-
gan, Irvine, California).
Compared with earlier fluoroquinolones, moxifloxacin
has been shown in vitro to have a wider spectrum of
action, as well as having activity against some Staphylococ-
cus and Streptococcus species that are resistant to the
current second-generation fluoroquinolones.13 Moxifloxa-
cin may thus offer an advantage over these earlier fluoro-
quinolones as an effective agent in endophthalmitis
prophylaxis. Ideally, antibiotics applied prophylactically
should be active in two categories. The load of bacteria on
the ocular surface should be effectively reduced before
surgery to minimize the probability of intracameral con-
tamination from the introduction of bacteria from the
ocular surface. Furthermore, adequate levels should persist
in the intracameral space following surgery to suppress
proliferation of any bacteria that might have been intro-
duced.
Previous studies have examined the effect of the appli-
cation of preoperative antibiotics on ocular surface flora, as
well as aqueous obtained at the beginning of surgery.4,5,14
With regard to the latter, aqueous levels of antibiotic
achieved by topical administration measured at the begin-
ning of surgery are not necessarily indicative of the levels

VOL. 138, NO. 4 EFFECT OF CATARACT SURGERY ON OCULAR LEVELS OF MOXIFLOXACIN 557
that will be available at the end of surgery. Furthermore,
the level of penetration in the unoperated eye might differ
substantially from that in an eye subjected to surgical
trauma immediately before topical administration. The
creation of an entry into the eye for the introduction of
instruments, combined with the inevitable epitheliopathy
that occurs because of surface irrigation, may serve to
enhance antibiotic penetration, leading to higher drug
levels. Conversely, irrigation might reduce the depot effect
of preoperative antibiotic administration, reducing the
postoperative levels of antibiotic compared with an unop-
erated eye. Moreover, the increased aqueous volume cre-
ated by removal of the crystalline lens and replacement
with the smaller intraocular lens is expected to have a
diluting effect on aqueous antibiotic concentration.
The purpose of this study was therefore to investigate
the effect of cataract surgery on intraocular penetration
and on aqueous and vitreous levels of moxifloxacin, an
antibiotic that is considered potentially effective in pro-
phylaxis against postoperative endophthalmitis. We estab-
lished a rigid protocol for dosage, surgical technique, and
sampling times, in comparing operated with unoperated
eyes, and used a sensitive technique (HPLC) for the
assessment of antibiotic concentrations. Despite the highly
controlled nature of this protocol, the standard deviations
of antibiotic concentrations derived from tissue samples in
both the operated and nonoperated groups were found to
be wide and on average suggested no substantial difference
between the groups. This would indicate that a much
larger sample size might be required to identify an effect,
either positive or negative, of cataract surgery on corneal
and aqueous levels of antibiotic following topical admin-
istration. It is noteworthy that despite the wide range of
concentrations measured in the aqueous humor, the min-
imum concentrations recorded were found to be high
enough to be considered effective against the most com-
mon organisms implicated in postcataract endophthalmitis
(see Table 1). In fact, none of the rabbits had aqueous
concentrations below the MIC values.
Our results suggest that in this rabbit model, topical
moxifloxacin, when administered as three drops adminis-
tered 5 minutes apart at 60 minutes preoperatively and
then immediately after cataract extraction, achieves an
aqueous humor concentration at 2 hours postsurgery that is
in the order of at least 100-fold higher than the reported
MIC values for fluoroquinolone-susceptible S. aureus and
coagulase-negative Staphylococcus and at least threefold
greater than the MIC values for fluoroquinolone-resistant
S. aureus and coagulase-negative Staphylococcus.
Vitreous concentrations obtained were substantially
lower but remained almost equivalent to the MIC values
for fluoroquinolone-susceptible S. aureus and coagulase-
negative Staphylococcus but cannot be considered adequate
for resistant strains. In the absence of posterior capsular
rupture, it is not surprising that vitreous penetration was
relatively low following topical administration, indicating
558 AMERICAN JOURNAL
that despite the relatively high levels of ocular surface
penetration observed in this study following topical appli-
cation, topical fourth-generation fluoroquinolones cannot
be considered adequate for the treatment of bacterial
vitritis. More effective vitreous levels of moxifloxacin
might be achieved with oral administration, as has been
demonstrated with both moxifloxacin and gatifloxacin.14,15
The aqueous levels of moxifloxacin reported here are
higher than those previously reported in a rabbit model
(Robertson SM, Association for Research in Vision and
Ophthalmology [ARVO] Meeting, 2003, Abstract 1454).
In that study of moxifloxacin penetration and distribution,
30 minutes after a single drop of 0.3% moxifloxacin was
administered, the concentration of moxifloxacin was found
to be 1.8 ␮g/ml in aqueous humor by reverse-phase HPLC.
In our current study, a higher concentration of moxifloxa-
cin was applied (0.5% as opposed to 0.3%), and three
drops were applied 5 minutes apart at two time points
separated by approximately 1 hour, for a total of six drops.
A comparison of the results of these studies, both of which
utilized pigmented rabbits, would support the established
principle that multiple-drop dosing of a higher concentra-
tion of antibiotic is expected to substantially increase
tissue levels of antibiotic. Another potentially significant
difference in the protocol followed in this study compared
with studies reflecting relatively lower aqueous concentra-
tions is the use of general anesthesia. General anesthesia
might lead to enhanced ocular penetration through a
reduction in blink rate, allowing extended antibiotic sur-
face contact time; increased epithelial desiccation and
disruption, allowing higher penetration; reduced tear pro-
duction and thus reduced antibiotic dilution and spill;
reduced blink and lacrimal pump drainage; and increased
cul-de-sac volume for antibiotic retention from periorbital
muscular laxity.16,17
The ocular tissue concentrations achieved by topical
0.5% moxifloxacin using the dosing regimen reported in
this study were also higher than those reported for topical
gatifloxacin. Batoosingh and associates (ARVO Meeting,
2003, Abstract 2117) recently studied the ocular penetra-
tion of topical 0.3% gatifloxacin in a rabbit model.
Gatifloxacin achieved a maximum concentration in the
aqueous humor of 0.271 ␮g/ml after a single-dose applica-
tion and 0.536 ␮g/ml after a multiple-dose regimen (four
times a day for 3 days) measured at 1 hour and 30 minutes
postapplication, respectively. In our study, the mean aque-
ous concentrations of moxifloxacin were 13.88, 16.18, and
12.18 ␮g/ml at 30, 60, and 120 minutes postdosing,
respectively. Given the difference in the dosing regimen,
direct comparisons of these antibiotic levels cannot be
made.
The results of this study indicate that cataract surgery
does not produce a statistically significant alteration in
antibiotic concentration in the eye, thereby validating
previous studies that have estimated ocular penetration
based on preoperative aqueous levels. Furthermore, the
OF OPHTHALMOLOGY OCTOBER 2004
results demonstrate that anterior segment antibiotic con-
centrations might vary widely despite a controlled regimen
of administration. In the case of moxifloxacin, as indicated
by this model, a multiple-drop dosing schedule produced
aqueous concentrations such that the lowest levels re-
corded were well above the MICs of even resistant strains
of the most common organisms implicated in postcataract
endophthalmitis. This would suggest that moxifloxacin
may be an attractive choice for antibiotic prophylaxis
following cataract surgery. Further clinical studies will be
necessary to confirm this in practice and to better define
optimal dosing regimens.
ACKNOWLEDGMENTS
The authors greatly appreciate the assistance provided by
Thomas Lietman, MD, MPH, and Zhaoxia Zhou, BS (F.I.
Proctor Foundation for Research in Ophthalmology, San
Francisco, CA) in the statistical analysis.
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