Can Intraocular Lenses DeliverAntibiotics Intracamerally?

Jeremy Shaw,1,2 Edward F. Smith,1,2 Rajen U. Desai,1,2 Brian Enriquez,1,2 and Amilia Schrier3

Abstract

Purpose: To determine the therapeutic concentrations of moxifloxacin achieved in an artificial anterior chamberby soaking the hydrophobic acrylic AcrySof� SA60 (Alcon Inc.) intraocular lens (IOL) and the hydrophiliccollamer Afinity� CQ2015 (Staar Inc.) IOL in commercially available moxifloxacin 0.5% (Vigamox�; AlconInc.).Methods: Forty IOLs (20 Acrysof SA60 and 20 Afinity CQ2015) were soaked in 1 mL of commercially availablemoxifloxacin 0.5%: 10 of each IOL for 1 min, and another 10 of each IOL for 10 min. The IOLs were placed onabsorbent pads for 10 s on each side to dry excess liquid, and then placed in vials of 10 mL balanced salt solution(BSS�) for 30 min. Five milliliters of the balanced salt solution was removed and analyzed by high-pressureliquid chromatography to determine antibiotic levels.Results: The moxifloxacin levels achieved after soaking the hydrophobic SA60 lens were 0.238 and 0.342 mg/mLfor 1 and 10-min soaks, respectively. The moxifloxacin levels achieved after soaking the hydrophilic CQ2015 lenswere 0.283 and 0.717 mg/mL for 1 and 10-min soaks, respectively.Conclusions: Both lenses were capable of delivering clinically significant antibiotic levels after a 1-min soak.Moxifloxacin concentrations reached at both 1 and 10-min soak times exceed the MIC90 of the most commonpathogens responsible for postoperative endophthalmitis. The antibiotic-soaked IOL has potential to become aclinically significant technique in the prevention of postoperative endophthalmitis.

Introduction

Endophthalmitis after cataract extraction is a dreadedcomplication with poor visual outcomes. Current pro-

phylactic practice includes preoperative sterile preparation,including isolation of the eyelids and lashes, topical betadine,along with pre- and postoperative topical antibiotics. Suchmeasures help prevent intraoperative microbial seeding andpostoperative bacterial growth.1–3

Recent studies have demonstrated the ability of the in-traocular lens (IOL) to produce antimicrobial activityin vitro as well as to serve as a vehicle to deliver antibioticsinto the eye.4–7 Hydrophilic acrylic IOLs (C-Flex�) soakedin commercially available moxifloxacin or gatifloxacin for24 h, and implanted into the capsular bag of rabbits, pro-duced concentrations in the aqueous humor above theminimum inhibitory concentration (MIC90) for Staphylo-coccus epidermidis, and other common pathogens causingendophthalmitis.4,5

Antibiotic-soaked IOLs, compared with topical antibioticsregimens, increase the chance of attaining MIC90-levels andmutation-preventing doses of antibiotic intraocularly, as wellas reduce the variance of antibiotic corneal penetrance andpatient compliance. Clinically significant antibiotic protec-tion is most crucial in the immediate postoperative period,before topical dosing achieves adequate levels of antibioticconcentration.

The goal of this study was to determine the concentrationsof antibiotic achieved in vitro by soaking the hydrophobicacrylic AcrySof� SA60 (Alcon, Inc.) and the hydrophiliccollamer Afinity� CQ2015 (Staar, Inc.) IOLs in commerciallyavailable moxifloxacin 0.5% (Vigamox�; Alcon, Inc.) withshort presoaking times.

Methods

AcrySof SA60 and Afinity CQ2015 IOLs were obtainedfrom Alcon Laboratories, Inc., and Staar Surgical Co., respectively.

Poster Presentation at the Association for Research in Vision and Ophthalmology 2009 Annual Meeting, Ft. Lauderdale, FL, May 2009.1Department of Ophthalmology, SUNY Downstate Medical Center, Brooklyn, New York.2Department of Veterans Affairs, New York Harbor Healthcare System—Brooklyn Campus, Brooklyn, New York.3Harkness Eye Institute, Columbia University, New York, New York.

JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICSVolume 26, Number 6, 2010ª Mary Ann Liebert, Inc.DOI: 10.1089/jop.2010.0021

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The IOLs were removed from their packaging with sterileforceps and placed in vials containing commercially availablemoxifloxacin 0.5% (Vigamox; moxifloxacin hydrochlorideophthalmic solution 0.5%; Alcon, Inc.). Ten SA60 and 10CQ2015 IOLs were soaked for 1 min. Another 10 SA60 and 10CQ2015 IOLs were soaked for 10 min. All IOLs were soakedundisturbed at room temperature. After the soak period, theIOLs were removed with sterile forceps and placed on ab-sorbent pads (BD Bioscience) for 10 s on each side to dry ex-cess liquid. Subsequently, the IOLs were placed in vialscontaining 10 mL of balanced salt solution (BSS�; Alcon, Inc.).After 30 min, 5 mL of the solution was sampled and frozen.High-performance liquid chromatography analysis for anti-biotic levels was performed. Microsoft Excel (Microsoft Inc.)calculated P values using a 2-tailed Student’s t-test.

Results

1-min soak

There was no significant difference between the moxi-floxacin levels attained for the SA60 compared with theCQ2015 (0.24� 0.21 vs. 0.28� 0.10 mg/mL, P> 0.5).

10-min soak

The longer soak times resulted in higher moxifloxacinlevels for both lenses. The increase was statistically significantfor the CQ2015 (0.72� 0.43mg/mL, P< 0.02), whereas it wasnot statistically significant for the SA60 (0.34� 0.39mg/mL,P> 0.4). The moxifloxacin level for CQ2015 was not signifi-cantly higher than that for SA60 (P> 0.05). Although theCQ2015 demonstrated a trend toward higher levels of mox-ifloxacin than did the SA60, the difference was not statisti-cally significant for either the 1-min or 10-min soaks (Fig. 1).

Discussion

Both lenses demonstrated measurable levels of moxi-floxacin release from both 1-min and 10-min soaks. More-over, levels from both lenses at both soak times exceed theMIC90 of the most common pathogens responsible for post-operative endophthalmitis, S. epidermidis (0.13 mg/mL), Sta-

phylococcus aureus (0.06 mg/mL), and Haemophilus influenzae(0.06 mg/mL).4 Levels from the 10-min soak of SA60 and bothtimes for CQ2015 also exceeded the MIC90 for Streptococcusspp. (0.25 mg/mL) and Proteus mirabilis (0.25 mg/mL).4

Longer soaking time for the SA60 did not show a significantincrease in moxifloxacin levels. This is consistent with aprevious study by Smith et al. demonstrating that the SA60soaked in moxifloxacin for 1 min produced a larger kill zoneof plated S. aureus compared with a 60-min soak.4 Anotherrecent study confirmed significant time release moxifloxacinlevels achieved after soaking the hydrophilic acrylic lens.5

The amphipathic nature of moxifloxacin has been used toexplain these findings. The combination of hydrophobicityand hydrophilicity of the moxifloxacin molecule may explainthe surprising interaction with the hydrophobic SA60.8

While the exact cause is unclear, theories include that theshort soak allows easier antibiotic release or that the initialaffinity may be higher while longer soaks yields a lower,steady-state concentration. Comparing the results to previ-ous studies using longer soak times of 60 min up to 24 h, thepositive results from the 1-min soak time are noteworthy.4,5

Our study investigated moxifloxacin levels available30 min after placing the IOL in balanced salt solution. Thistime period is crucial for initial inoculation and proliferationof microbes. However, this and previous studies have notaccounted for aqueous turnover, which could cause a steadydecline in aqueous antibiotic levels. It has not been studiedwhether the soaked hydrophobic IOL can serve as a depotfor a longer periods of time. In either case, initial levels of

FIG. 1. Moxifloxacin concentrations for CQ2015 and SA60IOLs for 1-min versus 10-min soak. Bars represent the meanconcentrations, with 95% confidence intervals presented bythe black lines. Abbreviation: IOL, intraocular lens.

FIG. 2. Proposed device that combines a modified IOLcartridge (A) fitted with a port for the insertion of a single-use vial (B) of 1 mL moxifloxacin solution.

588 SHAW ET AL.

antibiotic, direct delivery of antibiotic into the anterior cham-ber, and tissue uptake of antibiotic will each contribute to theefficacy against microbes.9 In addition, the initial highest an-tibiotic levels will be achieved within the capsular bag, likelywhere it is needed most. Moreover, moxifloxacin has beenproven to be safe and effective when injected intracamerally,and its delivery into the capsular bag would be easily ac-complished by presoaking lenses before implantation.10

A 1-min IOL antibiotic soak can easily be incorporated intothe current cataract extraction protocol. However, a potentialsource of variability would be surgical technique during thedrying phase. Another source of variability would be volumeof antibiotic solution in which the IOL is soaked. To stan-dardize this soaking phase, we propose a unique drug de-livery system that allows the insertion of a single-use vial oftopical antibiotic into a modified IOL manufacturer cartridge(Fig. 2). After cataract extraction, the surgeon would join thevial and cartridge, and instill the 1 mL moxifloxacin solution(0.5%), allowing the IOL to soak in the cartridge for 1 min. Theroutine insertion of the IOL would follow. Even if 50mL of themoxifloxacin was retained within the capsule and anteriorchamber, there would be no expected intraocular toxicity.10,11

Our standardized method helps deliver a therapeutic antibi-otic concentration into the anterior chamber, while avoidingthe highly variable results of direct intracameral delivery.12

One may consider a situation where the IOL would besoaked in moxifloxacin intraoperatively without causing anysignificant delays in the surgery. Although further studies willneed to be conducted, this step may add to the armamentar-ium for the surgeon to combat postoperative endophthalmitis.

Conclusion

SA60 and CQ2015 lenses soaked in commercially availablemoxifloxacin 0.5% may be used by the surgeon to deliverantibiotic into the eye. Future studies will be needed to see ifthis will decrease rates of postoperative endophthalmitis.

Acknowledgment

The study was supported by an unrestricted grant fromAlcon, Inc.

Author Disclosure Statement

The authors, J. Shaw, E.F. Smith, R.U. Desai, B. Enriquez,and A. Schrier, have no proprietary or competing financialinterests in the materials presented.

References

1. Ciulla, T.A., Starr, M.B., and Masket, S. Bacterial en-dophthalmitis prophylaxis for cataract surgery: an evidence-based update. Ophthalmology 109:13–24, 2002.

2. Speaker, M.G., and Menikoff, J.A. Prophylaxis of en-dophthalmitis with topical povidone-iodine. Ophthalmology98:1769–1775, 1991.

3. Mather, R., Stewart, J.M., Prabriputallong, T., Wong, J., andMcLeod, S.D. The effect of cataract surgery on ocular levelsof topical moxifloxacin. Am. J. Ophthalmol. 138:554–559, 2004.

4. Smith, E.F., Elbash, A.R., Schrier, A., Berg, P.D., and Eid, I.Antimicrobial activity of acrylic intraocular lenses soaked infourth generation fluoroquinolones. J. Ocul. Pharmacol. Ther.24:495–500, 2008.

5. Kleinmann, G., Apple, D.J., Chew, J., Hunter, B., Stevens, S.,Larson, S., Mamalis, N., and Olson, R.J. Hydrophilic acrylicintraocular lens as a drug-delivery system for fourth-generation fluoroquinolones. J Cataract Refract. Surg. 32:1717–1721, 2006.

6. Pershing, S., Charalel, R., Banaei, N., Liao, Y., and Shrivas-tava, A. In vitro activity of antibiotic-permeated intraocularlenses. Invest. Ophthalmol. Vis. Sci. 50:E-Abstract 5981, 2009.

7. Ulanski, L.J., II, Nijm, L., Winkler, S., Fiscella, R., Trager, L.,and Tu, E. In vitro drug delivery characteristics of theSTARR, Akreos, and hydrophobic lenses. Invest. Ophthalmol.Vis. Sci. 50:E-Abstract 1154, 2009.

8. Bauernfeind, A. Comparison of the antibacterial activitiesof the quinolone Bay 12–8039, gatifloxacin (AM 1155), tro-vafloxacin, clinafloxacin, levofloxacin and ciprofloxacin.J. Antimicrob. Chemother. 40:639–5, 1997.

9. Mather, R., Karenchak, L.M., Romanowski, E.G., and Ko-walski, R.P. Fourth generation fluoroquinolones: new weap-ons in the arsenal of ophthalmic antibiotics. Am. J. Ophthalmol.133:463–466, 2002.

10. Lane, S., Osher, R., Masket, S., and Belani, S. Evaluation ofsafety of prophylactic intracameral moxifloxacin in cataractsurgery. J. Cataract Refract. Surg. 34:1451–1459, 2008.

11. Choi, J.A., and Chung, S.K. Safety of intracameral injectionof gatifloxacin, levofloxacin on corneal endothelial structureand viability. J. Ocul. Pharmacol. Ther. 25:425–431, 2009.

12. Lockington, D., Flowers, H., Young, D., and Yorston, D.Assessing the accuracy of intracameral antibiotic prepara-tion for use in cataract surgery. J. Cataract Refract. Surg.36:286–289, 2010.

Received: February 7, 2010Accepted: August 24, 2010

Address correspondence to:Dr. Edward F. Smith

Department of OphthalmologySUNY Downstate Medical Center

Downstate Ophthalmology Associates11 Plaza St. West

Brooklyn, NY 11217

E-mail: esmith6960@aol.com

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