1: Am J Vet Res 2001 Oct;62(10):1664-9 Related Articles, Links
Effects of antibiotics on morphologic characteristics and migration of canine corneal epithelial cells in tissue culture.
Hendrix DV, Ward DA, Barnhill MA.
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville 37901, USA.

OBJECTIVE: To determine effects of commonly used ophthalmic antibiotics on cellular morphologic characteristics and migration of canine corneal epithelium in cell culture. SAMPLE POPULATION: Corneal epithelial cells harvested from corneas of 12 euthanatized dogs and propagated in cell culture. PROCEDURE: Cells were treated with various antibiotics after a defect was created in the monolayer. Cellular morphologic characteristics and closure of the defect were compared between antibiotic-treated and control cells. RESULTS: Cells treated with ciprofloxacin and cefazolin had the greatest degree of rounding, shrinkage, and detachment from plates. Cells treated with neomycin-polymyxin B-gramicidin and gentamicin sulfate had rounding and shrinkage but with less detachment. Cells treated with tobramycin and chloramphenicol grew similarly to control cells. On the basis of comparisons of defect circumference between control cells and cells exposed to antibiotics, tobramycin affected cellular migration the least. CONCLUSIONS AND CLINICAL RELEVANCE: Effects of ciprofloxacin and cefazolin on morphologic characteristics of canine corneal epithelial cells in vitro should be taken into consideration before using these antibiotics for first-line of treatment for noninfected ulcers. Of the antibiotics tested that have a primarily gram-negative spectrum of coverage, gentamicin inhibited corneal epithelial cell migration and had greater cytopathologic effects than tobramycin did. For antibiotics with a gram-positive coverage, chloramphenicol had no cytopathologic effects on cells in comparison to cefazolin, which caused most of the cells to shrink and detach from the plate. Polymyxin B-neomycin-gramicidin was midrange in its effects on cellular morphologic characteristics and migration.
1: Am J Ophthalmol 2001 Jan;131(1):131-3 Related Articles, Links



2. Increased incidence of corneal perforation after topical fluoroquinolone treatment for microbial keratitis.
Mallari PL, McCarty DJ, Daniell M, Taylor H.
Centre for Eye Research Australia, University of Melbourne, The Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.

PURPOSE: To compare the incidence of corneal perforation in eyes treated with topical fluoroquinolone or fortified antibiotics for microbial keratitis. METHODS: A retrospective medical record review of patients hospitalized for bacterial keratitis from January 1991 through November 1999. RESULTS: Two hundred seventy-seven cases of bacterial keratitis were identified. The incidence of corneal perforations was significantly higher in fluoroquinolone-treated eyes (18 out of 142, 12.7%) compared with eyes treated with fortified antibiotics (1 out of 135, 0.7%) (chi-square = 13.6, degrees of freedom (df) = 2, P <.001). Within the fluoroquinolone-treated group, all corneal perforations occurred in those eyes treated with ofloxacin (18 out of 125, 14.4%). Corneal perforations that occurred in the ofloxacin-treated eyes were not associated with any particular microbial isolate. CONCLUSION: Our data suggest an increased risk of corneal perforation after fluoroquinolone treatment for bacterial keratitis compared with treatment with fortified antibiotics. Further studies are warranted to verify this association and establish possible mechanisms by which topical fluoroquinolones may alter corneal collagen or keratocyte function.
Drugs 2001;61(6):747-61 Related Articles, Links


3. Fluoroquinolones: place in ocular therapy.
Smith A, Pennefather PM, Kaye SB, Hart CA.
St. Paul's Eye Unit, Royal Liverpool University Hospital, England.
The fluoroquinolones have become widely used antibacterial agents in the treatment of ocular infections, with topical, intravitreal and systemic routes of administration being used. In general, fluoroquinolones (such as ciprofloxacin, ofloxacin, lomefloxacin and norfloxacin) have good activity against gram-negative and gram-positive bacteria. Therapeutic concentrations are achieved in the cornea after topical administration so that the fluoroqinolones have largely replaced combination therapy for the treatment of bacterial keratitis. However, a second line agent is needed when resistance is likely, such as in disease caused by streptococcal species. Reversal of resistance to quinolones may not occur with withdrawal of the antibacterial. This stresses the importance of prudent prescribing to reduce the occurrence of resistance to quinolones. When used in therapeutic topical dosages, corneal toxicity does not occur. Similarly, retinal toxicity is not seen when fluoroquinolones are used at therapeutic dosages, systemically or topically. Corneal precipitation occurs, particularly with ciprofloxacin and to a lesser extent norfloxacin, but does not appear to interfere with healing. In the treatment of endophthalmitis there is reasonable penetration of systemic fluoroquinolones into the vitreous but sufficiently high concentrations to reach the minimum inhibitory concentration for 90% of isolates (MIC90) of all important micro-organisms may not be guaranteed. Systemic administration may be useful for prophylaxis after ocular trauma.


4. Am J Ophthalmol 1998 Feb;125(2):258-60 Related Articles, Links
Corneal ulcer associated with deposits of norfloxacin.
Konishi M, Yamada M, Mashima Y.
Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
PURPOSE: To report a case of corneal ulcer associated with deposits of norfloxacin. METHOD: Case report. A 40-year-old man with right trigeminal and facial nerve palsies and decreased tear secretion developed a corneal ulcer with white deposits in the right eye. The deposits were removed and analyzed by high-performance liquid chromatography. RESULTS: High-performance liquid chromatography results disclosed that the deposits on the corneal surface had the same retention time as norfloxacin. The patient discontinued norfloxacin ophthalmic solution and recovered successfully. CONCLUSION: Clinicians should be aware that frequent applications of topical norfloxacin in patients with decreased tear secretion may result in deposition of the drug on the cornea.

5. Kawazu K, Midori Y, Shiono H, Ota A. Related Articles, Links
Characterization of the carrier-mediated transport of levofloxacin, a fluoroquinolone antimicrobial agent, in rabbit cornea.
J Pharm Pharmacol. 1999 Jul;51(7):797-801.
PMID: 10467954 [PubMed - indexed for MEDLINE]

6. Kang F, Serdarevic ON, Kuang K, Li J, Zhu Z, Fischbarg J. Related Articles, Links
Effects of ciprofloxacin, streptomycin, and gentamicin on rabbit corneal transendothelial electrical potential difference.
Cornea. 1998 Mar;17(2):185-90.
PMID: 9520196 [PubMed - indexed for MEDLINE]
Nippon Ganka Gakkai Zasshi 1999 Aug;103(8):576-9

7. Madhavan HN, Rao SK. Related Articles, Links
Ciprofloxacin precipitates in the corneal epithelium.
J Cataract Refract Surg. 2002 Jun;28(6):909; author reply 909. No abstract available.
PMID: 12036608 [PubMed - indexed for MEDLINE]


8. [The uptake of fluoroquinolone agent drugs by cultured human conjunctival epithelial cells and cultured SIRC rabbit corneal cells]
[Article in Japanese]
Fukuda M, Yoshitake Y, Sasaki K.
Department of Ophthalmology, Kanazawa Medical University, Ishikawa, Japan
J Cataract Refract Surg 2001 Oct;27(10):1701-2 Related Articles, Links


9. Ciprofloxacin microprecipitates and macroprecipitates in the human corneal epithelium.
Eiferman RA, Snyder JP, Nordquist RE.
Research Service, Veterans Administration Medical Center, Louisville, Kentucky, USA. reiferman@cs.com
In 4 corneal transplantation patients treated preoperatively with ciprofloxacin ophthalmic drops, microprecipitates associated with damaged corneal epithelium were noted in 2 patients. Another patient developed a large macroprecipitate in a corneal ulcer. All specimens were examined by electron microscopy and high-pressure liquid chromatography. The crystalline precipitates were pure ciprofloxacin. The macroprecipitate demonstrated a large zone of inhibition on agar plates seeded with a susceptible organism at 24 and 48 hours. It was bioactive and bioavailable in vitro.

10. Kim HS, Sah WJ, Kim YJ, Kim JC, Hahn TW. Related Articles, Links
Amniotic membrane, tear film, corneal, and aqueous levels of ofloxacin in rabbit eyes after amniotic membrane transplantation.
Cornea. 2001 Aug;20(6):628-34.
PMID: 11473165 [PubMed - indexed for MEDLINE]

11. Ann Ophthalmol 1979 Mar;11(3):341-6 Related Articles, Links
Nonfamilial anterior corneal dystrophy.
Kielar RA, Wallace GR.
A 31-year-old woman with subepithelial corneal opacification and numerous clear round or oval areas of epithelial edema confined to the palpebral fissure underwent a penetrating keratoplasty. The clinical appearance was similar to that of a severe Meesmann or Stocker-Holt dystrophy. The prominent histopathologic features were thickening and excrescences of the epithelial basement membrane, intense basal cell edema, but no intraepithelial cysts. The basement membrane changes are compatible with those seen in Meesmann, Stocker-Holt, and map-dot-fingerprint dystrophy, but the lack of intraepithelial cysts is not characteristic of these dystrophies. This case represents a variant of the known anterior corneal dystrophies which have an overproduction of epithelial basement membrane.


12. The effect of ofloxacin on the human corneal endothelium.
McDermott ML, Hazlett LD, Barrett R.
Department of Opthalmology, Kresge Eye Institute, Wayne State University, Detroit, Michigan 48201, USA.
PURPOSE: Possible toxic effects of ofloxacin on human corneal endothelia were assessed by using electron microscopy and in vitro specular perfusion. METHODS: Five pairs of corneas [with one cornea of each pair receiving balanced salt solution (Endosol; Allergan, Irvine, CA, U.S.A.) and the other receiving Endosol with 10 micrograms/ml of ofloxacin] underwent perfusion for 3 h with corneal pachymetry every 15 min followed by tissue fixation. A mean corneal swelling rate was calculated from a first-order regression line fit for each of the five experiments. The swelling rates between groups was compared by-using a paired t test. Scanning and transmission electron micrographs were examined for cellular architecture. Another group of five pairs of corneas was perfused the same way with the only difference being a test dose of 30 micrograms/ml. RESULTS: The mean swelling rate for corneas perfused with 10 micrograms/ml of ofloxacin of -3.5 microns/h was not significantly different from that of the Endosol-alone corneas at -3.0 microns/h (p = 0.71). The mean swelling rate for corneas perfused at 30 micrograms/ml of ofloxacin was -4.1 microns/h, not significantly different from Endosol-alone perfused corneas at -6.5 microns/h (p = 0.08). No consistent ultrastructural changes could be attributed to exposure to 10 or 30 micrograms/ml of ofloxacin. CONCLUSION: Human corneal endothelium can be exposed to ofloxacin at a dose of 30 micrograms/ml for a period of 3 h without adverse ultrastructural or physiologic side effects