The Dangers of Dropless Cataract Surgery: Dangers of Intravitreal Trimoxi

The Dangers of “Dropless Cataract Surgery:” The Dangers of Intravitreal Trimoxi

Cataract surgery remains the most commonly performed surgery in the world. While we have made great advances in cataract surgery in the last few years (i.e., in particular the advent of using a femtosecond laser to achieve unprecedented accuracy in correcting astigmatis, making our clear cornea incisions, and perfection in the implantation of intraocular lenses, AND the innovations in intraocular lens technologies that allow patients to, for the first time in history, have a chance of not always having to use reading, intermediate, and distance glasses to be able to see after cataract surgery [like the Tecnis Multifocal, Restor Multifocal, Crystalens Accommodating, Trulign Accommodating that corrects for Astigmatism also]), few innovations have been made in the pre-operative and post-operative care of our patients.

In particular, patients have always used multiple drops before and after surgery to prevent infection and achieve the best outcome possible.

Currently, all patients use the following before surgery:
1. Antibiotic: Used to prevent infection 
-Besivance 2-3x/day starting 3 days before surgery
-OR Ciprofloxacin 4x/day starting 3 days before surgery
2. Steroid Drop: 
-usually Durezol 2x/day starting 3 days before surgery 
-OR Prednisolone 4x/day starting 3 days before surgery
3. Non-Steroidal Drop: used to prevent inflammation and cystoid macular edema (CME) after surgery
-Ilevro (nepafenac) OR Prolensa ((bromfenac ophthalmic solution): 1x/day starting 3 days before surgery
-OR Generic Ketorolac 4x/d starting 3 days before surgery
4. Dilating Drop: usually Tropicamide: use 1 drop 2 hrs before surgery

Currently there are 3 options for post operative care after cataract surgery:
1. To use 3-4 drops given by prescription multiple times per day: the antibiotic (currently Besivance® (besifloxacin) 2-4 times per day OR Vigamox 
2. Dropless Cataract Surgery: discussed below
3. Compounded eye drops so all drops are in one bottle

I will talk about option 2 here.
“Dropless Cataract Surgery,” which means the eye surgeon injects two FDA approved medicines into the anterior vitreous (front part of the back chamber of the eye), under the label “Trimoxi” after cataract surgery, has the potential to revolutionize post operative care after cataract surgery.

All patients who have had cataract surgery and their surgeons know that there are multiple drops needed for weeks to months after surgery. Each one of these drops have risk of toxicity to the cornea, not to mention the significant cost, especially if the patient does not have insurance. Additionally there are multiple follow up surgical visits to be sure there is not worsening inflammation in the eye after cataract surgery and no signs of infection. 

If the ophthalmic community can develop a way to reduce the need for drops and reduce the need for follow up visit, this would be a real help to our patients.

The positive key issues with Dropless Cataract Surgery are the following:
1. Studies in Europe noted below have for years suggested that injecting antibiotics into the eye prevents eye infections better than drops.
2. There are many published studies noting the benefit of intracameral (injections in the front chamber of the eye called the anterior chamber) antibiotics.
3. Retina surgeons have been injecting medicines for macular degeneration into the vitreous for years with a low risk of infection or retinal detachment: but there is a risk.

The negative issues with Dropless Catarct Surgery:
1. While the drugs used inside the Trimoxi injection ARE FDA approved, this technique is not FDA approved: this should be in all consent forms for patients so they understand this.
2. We do not have published studies showing the outcomes with Trimoxi. 
3. There have been a couple of large studies with thousands of patients that have had Trimoxi injected into their eye but these studies have not been published yet. Some of them were sponsored by the drug company.
4. The real risks here of Trimoxi are the same as with any intraocular surgery:
a. Risk of infection, loss of vision permanently, loss of the eye
b. Risk of vitreal hemorrhage: none reported to date
c. Risk of retinal detachment: none reported to date.
5. The only other risk of Trimoxi is the fact that a compounding pharmacy puts the drops together. While compounding pharmacies have been doing this for intravitreal injections for macular degeneration for years, it remains a risk for any such injection. The risk is very low but it is not zero.

What should a patient do?

There is a risk/benefit trade off each surgeon and patient will need to choose.

I have seen at least 15 patients in my career, not always my post-op patient, who “forgot,” “lost,” or completely got mixed up on which drops they had to use and ended up not using any antibiotic drops at all after their cataract surgery. The first time this happened when I was at Harvard Medical School’s Massachusetts Eye and Ear Infirmary as a young attending surgeon, I was scared: how could this patient not have developed an infection. Thus, if I know a patient will return after cataract surgery if there is any worsening vision or pain (a sign of an infection), worsening flashing lights (a sign of retinal detachment), or contact me if anything does not seem right, then Dropless Cataract Surgery in my opinion is a valid option despite its risks.

If I had to choose myself today which option to take: taking multiple drops for weeks versus Dropless Cataract surgery, I would choose to have Trimoxi Dropless Cataract Surgery.

We are currently submitting an IRB proposal to evaluate the long term effects of Trimoxi. I do not have any stock in this company and am not paid in any way by this company, but I want to know what is best for our patients.

To Summarize:

The FDA approved drops which we have used for years after cataract surgery have been combined to into an injectable solution called Trimoxi (intravitreal triamcinolone/moxifloxacin, Imprimis Pharmaceuticals). Though Trimoxi has not been FDA approved yet, it does contain FDA approved drugs. Trimoxi has the potential to prevent postoperative inflammation, cystoid macular edema (CME), and endophthalmitis. Even more so, studies from Europe, where they have been injecting antibiotics into the eye after cataract surgery for years, have shown that injecting antibiotics into the eye is more effective than antibiotic eye drops in preventing endophthalmitis which is a devastating eye infection, I pray none of my patients will ever have.

This recent publication below published in the prestigious Ophthalmology Journal notes that patients receiving intracameral (injected into the eye) antibiotics was 100% effective against endophthalmitis.

 2015 Dec 15. pii: S0161-6420(15)00844-1. doi: 10.1016/j.ophtha.2015.08.023. [Epub ahead of print]

Endophthalmitis Occurring after Cataract Surgery: Outcomes of More Than 480 000 Cataract Surgeries, Epidemiologic Features, and Risk Factors.

  • 1Department of Ophthalmology, Ophthalmology Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.
  • 2Department of Ophthalmology, Ophthalmology Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:
  • 3Department of Ophthalmology, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.

AbstractPURPOSE:To report the incidence of endophthalmitis after senile cataract surgery and to describe the epidemiology and main risk factors.DESIGN:Retrospective, single-center, cross-sectional descriptive study.PARTICIPANTS:Patients who underwent cataract surgery in Farabi Eye Hospital from 2006 through 2014.METHODS:All patients were evaluated retrospectively to compare risk factors, epidemiologic factors, and prophylaxis methods related to endophthalmitis. Patient records were used to gather the data.MAIN OUTCOME MEASURES:Epidemiologic factors, systemic diseases, other ocular pathologic characteristics, complications during the surgery, technique of cataract surgery, intraocular lens type, method of antibiotic prophylaxis, surgeon experience, vitreous culture, and vision outcome were evaluated in these patients.RESULTS:One hundred twelve endophthalmitis cases among 480 104 operations reported, equaling an incidence of 0.023%. Patients with diabetes mellitus (14.3%) and of older age (mean age, 81 years), perioperative communication with the vitreous (17.9%), extracapsular cataract surgery procedure (11%), and surgery on the left eye (58.9% vs. 41.1% for right eye; P = 0.03) showed a statistically significant association with endophthalmitis. Short-term treatment with topical or systemic preoperative antibiotics or postoperative subconjunctival injection was associated with a 40% to 50% reduced odds of endophthalmitis compared with no prophylaxis (P = 0.2). No cases of endophthalmitis were observed among the 25 920 patients who received intracameral cefuroxime, suggesting that this approach to antibiotic prophylaxis may be far more effective than traditional topical or subconjunctival approaches.CONCLUSIONS:The incidence of endophthalmitis after cataract surgery in our center was 0.023%, comparable with that of other previously published international studies. Older rural patients with immune suppressive diseases, such as diabetes mellitus, are particularly more prone to endophthalmitis. Vitreous loss at the time of surgery was associated with a significantly increased risk. Whereas antibiotic prophylaxis overall showed a 40% to 50% reduction in risk, intracameral cefuroxime was 100% effective in preventing endophthalmitis in this series.

Dropless cataract surgery offers ‘significant benefit’

Using an intravitreal transzonular injection improves patient compliance while maintaining good outcomes

Examining how utilizing an intravitreal transzonular injection can help patient compliance.
Crossville, TN—Intravitreal transzonular antiobiotic/steroid combination concurrent with cataract surgery can provide a “significant benefit with minimum risk,” said M. Stewart Galloway, MD, Cumberland Eye Care, Crossville, TN.
Trimoxi (intravitreal triamcinolone/moxifloxacin, Imprimis Pharmaceuticals) following phacoemulsification with IOL implantation “is able to prevent postoperative inflammation, cystoid macular edema (CME), and endophthalmitis,” said Dr. Galloway, Cumberland Eye Care (Tenn.).
It is common practice to deliver antibiotics topically, but with Trimoxi, the delivery is transzonular. Trimoxi is compounded, preservative-free triamcinolone acetonide and moxifloxacin delivered 15 mg/1mg/ml, with 0.2 ml injected transzonularly into the anterior vitreous, Dr. Galloway said, resulting in a total drug delivery of 3 mg triamcinolone and 0.2 mg of moxifloxacin.
“After the lens implant is in place, and prior to removing viscoelastic, you pass a cannula through the incision, over the anterior capsule, underneath the iris, and then penetrate the zonules into the anterior vitreous so the drug is delivered into the vitreous itself,” Dr. Galloway said.
Unlike intracameral injections, which go into the anterior chamber, Trimoxi is designed to be delivered to the posterior chamber, directly into the vitreous, he said.
In his retrospective chart review of 2,300 consecutive eyes that underwent phaco/IOL implantation with the use of Trimoxi instead of topical antibiotic/steroids postoperatively, not one eye has developed endophthalmitis.
“There have been more than 14,000 eyes injected with Trimoxi—not all at our center, of course—and while we can’t say we have a zero rate of endophthalmitis, we can say it’s zero thus far,” he said.
Dr. Galloway said he believes the reason Trimoxi has yet to result in a single case of endophthalmitis is because when bacteria do enter the eye, it colonized in the vitreous.
“It’s a nutrient-rich place, and that’s where the bacteria grow and cause the problems,” he said. “We put the antibiotic where the bacteria want to grow. We’re not putting drops on the cornea and hoping they diffuse into the eye, we’re not delivering them intracamerally and hoping some of it gets through to the vitreous.”
He noted that a problem with intracameral injections is that “the drug is washed out of the eye in a fairly short time frame,” he said. In rabbit eyes, conversely, “the moxifloxacin stays at therapeutic concentrations for at least eight hours. The anti-inflammatory portion is detectable there for months afterwards.”
Study details
In Dr. Galloway’s study, all patients were seen day of surgery (4-7 hours postoperatively). All patients were then seen between 3 and 4 weeks postoperatively, and then again at 6 months.
Of the original 2,300 patients, only 10 were lost to follow-up. The average age was 73 years (ranging from 34 to 95 years old). Almost one-fifth of the eyes/patients had diabetes, and 5% presented with epiretinal membrane (ERM).
Dr. Galloway said 19% of the patients received supplemental topical nonsteroidal anti-inflammatory drugs (NSAIDs) because of diabetes, ERM, or premium IOL implantation.
The rate of breakthrough inflammation requiring the addition of topical steroids during the postop period was 2% but was “slightly higher at 3.5% in those with ERM, and 6.3% in those who developed CME,” Dr. Galloway said. Mean intraocular pressure fell from 21.1 mm Hg on day of surgery to 14.1 mm Hg at weeks 3-4 postop, he added.
The overall CME rate in the study was 1.4% (see Figure 1).  The rate of CME in the diabetic subgroup was slightly higher at 1.9% and not significantly altered with the addition of topical NSAIDs.  In the ERM subgroup however, the CME rate was very significantly affected by the topical NSAID, decreasing from 8.5% without to 2.2 % with topical NSAIDs.  Dr. Galloway added he now routinely uses NSAIDs only on patients with ERMs and no longer uses them on diabetic patients without pre-existing maculopathy.
With the diabetic patient population, “if there’s no maculopathy, then there’s no reason to treat them differently than someone without diabetes,” he said.
There are some disadvantages to the procedure, he said—primarily that patients experience decreased immediate postop vision and floaters, due to the opaque nature of the drug. There also may be an increased incidence of patients who experience foreign body sensation, “presumably due to a lack of topical anti-inflammatory drugs at the wound itself,” he said.
Patient compliance
By not relying on postoperative drops to control potential inflammation, Dr. Galloway said there’s also no issue with patient compliance.
Calling the use of Trimoxi “truly a dropless surgery, there’s decreased patient cost as well, and a decrease in postop care,” he said, explaining the lack of postop drops eliminates numerous call backs related to pharmacy and drop regimen.
“There’s enormous potential for this in Third World countries, where follow-up care is less than ideal,” he said.
M. Stewart Galloway, MD

Advantages plentiful with dropless cataract surgery

The technique is effective, saves time and money, and has good results.
Ophthalmic surgeons can expect their cataract patients to complain about the high cost of postop medications. Staff time is lost on brand vs. generic discussions, insurance coverage concerns, frequency and duration of treatment questions, and renewals. Tech resources are devoured in determining exactly which drugs were received and how they are being used because these rarely coincide with the scripts written.
Once Jeff Liegner, MD, of Sparta, N.J., described his technique and special formulation of triamcinolone, moxifloxacin and vancomycin (TriMoxiVanc), I gave it a try. I will never go back to the time sink of postop poly-pharmacopoeia.
Approximately 3 months and 500 patients later, the patients, staff and surgeon are happier with dropless cataract surgery. No more emergency pages for medication clarification, no more requests for a suitable generic, no more time wasted looking through a patient’s possessions to determine the actual name of the drops they are using, and no more explaining that we do not have free samples to give.
James S. Lewis, MD

James S. Lewis
I have put video of my first cases on the Internet, and while it has not gone viral, there is considerable interest. I believe it is only a matter of time before patients insist on dropless cataract surgery in the same way they demand custom or bladeless LASIK. In fact, Imprimis Pharmaceuticals, the company that acquired the intellectual property in August 2013 for the special patent-pending blend of antibiotics and steroids, has launched a “GoDropless” campaign.

Learning the technique

Jim Gills, Doug Koch, Stewart Galloway and others pioneered the trail, and I am very happy to follow. There is a very short learning curve to this technique. Liegner suggests walking the cannula out beyond the capsule, tapping it gently as you proceed. I find it best to visualize the anatomy while the eye is oriented orthogonally. One caveat is that aiming too far out will generate some mild patient discomfort and some annoying but self-limited bleeding. I find it helpful to make certain the patient is cooperative before this maneuver. It is important to make sure the cannula is well secured, there are no bubbles in the syringe and you have more than 0.2 cc of medication. In fact, I prefer to use the same amount in the syringe each time.
The surgeon must be comfortable watching a perfect red reflex become obscured. This cloud dissipates quickly; few patients will notice it and even fewer will complain. There were only a few reports of floaters or clouds postoperatively, and most patients were comforted to know that it was “just the medicine.” The first thing you notice on postoperative day 1 is that there is an unexpected pause at the end of the examination. In the same way LASIK patients reach for their glasses for the first few weeks after surgery, you will have an instinctual 
desire to remind the patient to use drops. This awkwardness passes easily.
My staff and I made absolutely no effort to avoid adding a steroid if needed. Any patient who had cystoid macular edema in the other eye or those with any degree of corneal edema got a steroid on day 1. Any patients with even modest complaints of photophobia, redness or foreign body sensation, as well as those with ciliary flush, were treated. I added steroids to an uncomplicated post-graft cataract but did not use steroids in a few cases with planned vitrectomies and sutured posterior chamber IOLs.
After IOL implantation, while dispersive viscoelastic fills the anterior chamber, a 27-gauge Knolle cannula on a 1 cc tuberculin syringe is inserted behind the iris and above the peripheral anterior capsule.
Once the cannula is advanced through the zonules, 0.2 cc of TriMoxiVanc is injected into the retrozonular space of Petit.
A slow but steady motion of 2 to 4 seconds is required.
During this time, most of the viscoelastic exits the eye.
Residual viscoelastic is removed through irrigation and aspiration, followed by stromal hydration and limbal relaxing incisions as needed.
Residual viscoelastic is removed through irrigation and aspiration, followed by stromal hydration and limbal relaxing incisions as needed.
After IOL implantation, while dispersive viscoelastic fills the anterior chamber, a 27-gauge Knolle cannula on a 1 cc tuberculin syringe is inserted behind the iris and above the peripheral anterior capsule. Once the cannula is advanced through the zonules, 0.2 cc of TriMoxiVanc is injected into the retrozonular space of Petit. A slow but steady motion of 2 to 4 seconds is required. During this time, most of the viscoelastic exits the eye. Residual viscoelastic is removed through irrigation and aspiration, followed by stromal hydration and limbal relaxing incisions as needed. This technique is applicable to femtosecond laser-assisted cataract surgery as well as conventional phacoemulsification. The antibiotic-steroid combination is seen behind the implant, obscuring the red reflex. Eighty-six percent of my first 500 patients required no postoperative drops. Pressure spikes, vitreous loss, bleeding and visual complaints are rare,
transient or entirely absent.
Images: Lewis JS

 Antibiotics: Ophthalmic

Clinical Notes

Drug Generic Name

Drug Brand Name


Average cost per claim ($)

azithromycin ophthalmic solution Azasite PA   $128.67  
bacitracin ophthalmic ointment $65.69  
besifloxacin ophthalmic suspension Besivance * PA   $144.20  
ciprofloxacin ophthalmic ointment Ciloxan PA   $150.21  
ciprofloxacin ophthalmic suspension Ciloxan # $9.56 (#)  
erythromycin ophthalmic ointment Ilotycin # $17.50 (#)  
gatifloxacin 0.5% ophthalmic solution Zymaxid PA   $113.04 (#)  
gentamicin ophthalmic ointment, solution Gentak # $10.75 (#)  
levofloxacin 0.5% ophthalmic solution PA   $69.93  
moxifloxacin ophthalmic solution-moxeza Moxeza PA   $137.13  
moxifloxacin ophthalmic solution-Vigamox Vigamox PA   $153.97  
natamycin Natacyn $295.95  
ofloxacin ophthalmic solution Ocuflox # $27.23 (#)  
sulfacetamide ophthalmic ointment, solution Bleph-10 # $27.85 (#)  
tobramycin ophthalmic solution Tobrex # $7.53 (#)  
tobramycin ophthalmic ointment Tobrex PA   $113.19
 2011 Jun;37(6):1082-9. doi: 10.1016/j.jcrs.2010.12.046.

Human aqueous humor concentrations of besifloxacinmoxifloxacin, and gatifloxacin after topical ocular application.



To determine the concentrations of besifloxacinmoxifloxacin, and gatifloxacin in human aqueous humor after topical instillation of commercially available besifloxacin ophthalmic suspension 0.6%, moxifloxacin ophthalmic solution 0.5%, and gatifloxacin ophthalmic solution 0.3%, and to assess these concentrations relative to the minimum inhibitory concentration for 90% of strains (MIC(90)) for each drug against bacterial pathogens identified in recent cases of postoperative endophthalmitis.


Six clinical sites, United States.


Randomized open-label controlled clinical trial.


The aqueous humor drug concentrations were compared 60 minutes ± 5 minutes after instillation of 1 topical drop to patients aged 18 years or older having uncomplicated cataract surgery. Concentrations of besifloxacinmoxifloxacin, and gatifloxacin were determined using a validated liquid chromatography with tandem mass spectrometry method.


A total of 105 patients were randomized, and aqueous humor samples were analyzed for 103 patients. Mean aqueous humor concentrations were 0.13 μg/mL ± 0.58 (SD), 0.67 ± 0.50 μg/mL, and 0.13 ± 0.08 μg/mL for besifloxacinmoxifloxacin, and gatifloxacin, respectively. Both besifloxacin and moxifloxacin achieved aqueous humor concentrations equal to or slightly higher than their respective MIC(90) for methicillin-resistant and methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis; none of the fluoroquinolones achieved concentrations above their MIC(90) for ciprofloxacin-resistant strains of S aureus and S epidermidis.


Based on the aqueous humor drug concentrations measured in this study, it is unlikely that any of the fluoroquinolones tested would be therapeutically effective in the aqueous humor against the most frequently identified drug-resistant staphylococcal isolates from recent cases of postoperative endophthalmitis.


No author has a financial or proprietary interest in any material or method mentioned. Additional disclosures are found in the footnotes.

2. These 2 Articles Below show Besifloxacin to be “more effective” than Moxifloxacin. But both studies were paid for by the Drug company

Someone has to start a Journal where only articles that have 
NO drug funding are published.

The issue is that few groups are able to do such research without funds from drug companies. 

These projects can be very expensive and require a great deal of time.

 2015 May 13;9:843-52. doi: 10.2147/OPTH.S83162. eCollection 2015.

Antibacterial efficacy of prophylactic besifloxacin 0.6% and moxifloxacin 0.5% in patients undergoing cataract surgery.



The purpose of this study was to investigate the ocular bacterial flora in patients scheduled to undergo cataract surgery and compare the antibacterial effects of besifloxacin ophthalmic suspension 0.6% and moxifloxacin ophthalmic solution 0.5% in these patients.


This was a prospective, randomized, laboratory-masked clinical trial. Patients received besifloxacin or moxifloxacin “quater in die” or QID (four times a day) for 3 days before cataract surgery in the surgical eye and 1 hour before surgery in the nonsurgical fellow eye. Conjunctival and eyelid swabs were obtained from both eyes at baseline and after treatment, on the day of surgery (Visit 2). Swabs were processed for bacterial colony counts (in terms of colony-forming units) and species identification. In vitro antibiotic susceptibilities of isolates were determined using Clinical and Laboratory Standards Institute breakpoints.


Fifty-nine patients (n=28 besifloxacin, n=31 moxifloxacin) completed the study. The majority (73%) of conjunctival samples were culture negative at baseline. The most frequent isolates were coagulase-negative staphylococci (CoNS, 89%), specifically Staphylococcus epidermidis (72%). Both fluoroquinolones reduced the lid CFU values when administered QID for 3 days (P≤0.019), but only besifloxacin reduced the lid CFU estimate 1 hour following instillation of a single drop (P=0.039). Fewer besifloxacin-treated eyes had lids that were culture positive for CoNS at Visit 2 compared with moxifloxacin-treated eyes regardless of dosing regimen (P≤0.03). The minimum inhibitory concentration (MIC90) of besifloxacinagainst methicillin-resistant S. epidermidis (MRSE) was eightfold lower than that of moxifloxacin.


Besifloxacin appeared more effective in reducing bacterial counts on eyelids of patients undergoing cataract surgery, with significant reductions as early as 1 hour postdose, compared with moxifloxacinBesifloxacin was more active in vitro against MRSE.


besifloxacin; cataract patients; coagulase-negative staphylococci; moxifloxacin; prophylaxis

Journal of Ocular Pharmacology and Therapeutics

Ocular Pharmacokinetics/Pharmacodynamics of Besifloxacin, Moxifloxacin, and Gatifloxacin Following Topical Administration to Pigmented Rabbits

To cite this article:
Joel W. Proksch and Keith W. Ward. Journal of Ocular Pharmacology and Therapeutics. October 2010, 26(5): 449-458. doi:10.1089/jop.2010.0054.
Published in Volume: 26 Issue 5: October 6, 2010
Online Ahead of Print: September 29, 2010

Author information

Joel W. Proksch and Keith W. Ward
Global Pharmaceutical Research & Development, Bausch & Lomb, Incorporated, Rochester, New York.
Address correspondence to:
Dr. Joel W. Proksch

Global Pharmaceutical Research & Development

Bausch & Lomb, Incorporated
1400 N. Goodman Street
Rochester, NY 14609


Received: April 16, 2010
Accepted: July 7, 2010


Purpose: The purpose of this investigation was to evaluate the ocular pharmacokinetic/pharmacodynamic (PK/PD) relationship for besifloxacin, moxifloxacin, and gatifloxacin using rabbit ocular PK data, along with in vitro minimum inhibitory concentration (MIC90) values against methicillin- and ciprofloxacin-resistant Staphylococcus aureus(MRSA-CR) and Staphylococcus epidermidis (MRSE-CR).
Methods: Rabbits received a topical instillation of Besivance™ (besifloxacin ophthalmic suspension, 0.6%), Vigamox® (moxifloxacin hydrochloride ophthalmic solution, 0.5% as base), or Zymar® (gatifloxacin ophthalmic solution, 0.3%), and ocular tissues and plasma were collected from 4 animals/treatment/collection time at 8 predetermined time intervals during the 24 h after dosing. Ocular levels of each agent were measured by LC/MS/MS, and PK parameters (CmaxTmax, and AUC0–24) were determined. AUC0–24/MIC90 ratios were calculated for tears, conjunctiva, cornea, and aqueous humor using previously reported MIC90 values for MRSA-CR and MRSE-CR.
Results: All of the fluoroquinolones tested demonstrated rapid penetration into ocular tissues after a single instillation. Besifloxacin demonstrated the highest exposure in tear fluid, while exposure in conjunctiva was comparable for all 3 compounds. Peak concentrations of all fluoroquinolones in aqueous humor were at or below ∼1 μg/mL. In comparison with their MIC90 values against MRSE-CR and MRSA-CR, besifloxacin achieved an AUC0–24/MIC90 ratio of ∼800 in tears, compared with values of ≤10 for moxifloxacin and gatifloxacin. In cornea, conjunctiva, and aqueous humor, the AUC0–24/MIC90 ratios were <10 for all compounds. However, in these tissues AUC0–24/MIC90 ratios for besifloxacin were 1.5- to 38-fold higher than moxifloxacin and gatifloxacin.
Conclusions: In rabbits, besifloxacin demonstrates a nonclinical ocular PK profile characterized by high and sustained concentrations in tear fluid, resulting in AUC0–24/MIC90 ratios of ∼800 for ciprofloxacin-resistant MRSE and MRSA after a single administration. Although besifloxacin had the highest AUC0–24/MIC90 ratios for intraocular tissues, the ratios for all of the drugs were below the target values needed for effective bacterial killing of ciprofloxacin-resistant MRSE and MRSA. Taken together, these nonclinical data indicate that besifloxacin has a favorable ocular PK/PD profile, consistent with the reported clinical efficacy of besifloxacin in the treatment of bacterial conjunctivitis, and consistent with the profile needed for ocular surface sterilization.
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