Evaluation of the Corneal Effects of Topical Ophthalmic Fluoroquinolones Using In Vivo Confocal Microscopy

Kovoor, Timmy A.; Kim, Andrea S.; McCulley, James P.; Cavanagh, Harrison D; Jester, James V.; Bugde, Abhijit; Petroll, Walter M

doi:10.1097/01.icl.00000117255.97190.98

Cited by 72 publications

(39 citation statements)

References 9 publications

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“…Burka et al 21 compared the epithelial wound healing after the treatment of photorefractive keratectomy with moxifloxacin (Vigamox) or with gatifloxacin (Zymar), and found that the eye treated with moxifloxacin healed faster. Kovoor et al, 22 using confocal microscopy to evaluate corneal epithelium and stromal thickness after treating rabbits with different FQs, found that moxifloxacin induced less damage than other FQs. However, the ofloxacin and levofloxacin they tested contained 0.005% BAC, which was different from the commercial solutions we tested.…”

Section: Discussionmentioning

confidence: 99%

“…13 Although the superiority of clinical efficacy between different FQs is still under evaluation, [14][15][16][17][18][19][20] controversial results exist that compare the toxicity of FQs towards the corneal epithelial cells. 19,[21][22][23] The ocular and systemic safety profile of newer FQs is generally considered comparable with those of other FQ antimicrobial agents, with a low recognized risk of quinolone-related toxicity. [24][25][26][27] However, Walter et al 28 reported two cases of severe sterile corneal ulcers after the topical application of moxifloxacin, and the drug was suspected of interfering with corneal healing.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of fluoroquinolones: cytotoxicity on human corneal epithelial cells

Tsai

Chen

2009

Eye

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Purpose To compare the cytotoxicity of different fluoroquinolones (FQs) towards human corneal epithelial cells (HCECs). Methods HCECs were incubated with FQs (norfloxacin, ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, and gatifloxacin), both as commercial ophthalmic formulations and as unpreserved solutions. Cells incubated in different formulations of gentamicin, cefazolin, and benzalkonium chloride (BAC) were also compared. A cell viability assay, using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, was used to evaluate the drug effects on cell viability after five incubation times (30 min, 1 h, 4 h, 8 h, and 24 h). Transepithelial electrical resistance (TEER) was measured with a voltohmmeter to help understand changes in paracellular permeability at five time points (4 h, 8 h, 12 h, 24 h, and 48 h). Cell morphology was observed with an inverted fluorescence microscope, with multiple stage position and in time-lapse mode. Results The preserving solutions and BAC at concentrations above 0.005% significantly decreased cell viability, when assayed by MTS. Increased paracellular permeability and decreased membrane integrity were also observed by TEER measurements and inverted fluorescence microscopy. Ofloxacin and levofloxacin were both free of preservatives and showed the least cytotoxicity towards HCECs in commercial FQ eye drops. Conclusions The cytotoxicity observed with FQ eye drops seems to be caused mainly by the preservative, which induced a significant decrease in membrane integrity and increased paracellular permeability. We found the new generation of FQs (moxifloxacin and gatifloxacin) no less cytotoxic towards HCECs than the old generation ones.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparison of fluoroquinolones: cytotoxicity on human corneal epithelial cells

Tsai

Chen

2009

Eye

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“…4. Данные количественной оценки состояния клеток эпителия роговицы до и после закапывания антибактериального препарата (Левофлоксацин дженерик) у пациентов 3-й группы по данным конфокальной микроскопии Если антибиотик или консервант, входящий в состав капель, обладает токсичностью по от-ношению к эпителию роговицы, проницаемость также может повышаться [12].…”

Section: пациентunclassified

“…Проведённые Таблица 4 Данные качественной оценки состояния клеток эпителия роговицы у пациентов 2-й группы (Моксифлоксацин) по дан-ным конфокальной микроскопии ранее зарубежные исследования показали, что фторхинолоны в различной степени способны подавлять пролиферацию кератоцитов [14] и при высоких концентрациях оказывать цитотоксиче-ский эффект на эпителий и эндотелий роговицы [12]. В ранних работах по оценке цитотоксично-сти фторхинолонов было установлено, что ци-профлоксацин обладал наименьшей цитотоксич-ностью по отношению к роговичному эпителию в сравнении с норфлоксацином и офлоксацином, а также гентамицином и тобрамицином [9].…”

Section: пациентunclassified

Comparison of cytotoxicity of fluoroquinolone antimicrobial eye drops and its effect on their bioavailability

Hintuba

Takhtaev

Околов

et al. 2017

Ophthalmology Reports

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In addition to the breadth of activity of antibacterial medications as well as to their pharmacokinetic and pharmacodynamic properties, their safety and bioavailability represent an important aspect. Currently, there is no consensus on fluoroquinolone toxicity. The aim of the present study was to compare the total cytotoxic effect on corneal epithelium and bioavailability of three antibacterial fluoroquinolone eye drops, registered in the Russian Federation: 1) Oftaquix™ (levofloxacin 5 mg/ml; preservative benzalkonium chloride (BAC) 0.05 mg/ml; produced by Santen Oy, Finland), hereafter “levofloxacin (original)”; 2) Signicef® (levofloxacin 5 mg/ml; preservative BAC 0.1 mg/ml; produced by Sentiss Pharma Pvt. Ltd., India), hereafter “levofloxacin (generic)”; 3) Vigamox® (moxifloxacin® 5 mg/ml; preservative-free; produced by Alcon Laboratories, Inc., USA) hereafter “moxifloxacin” - using in vivo methods and determining the possible effect of preservative presence (in different concentration) or of its absence on reaching the minimal threshold concentrations of the antibiotic in the anterior chamber fluid, using the high-yield liquid chromatography combined with mass-spectrometric detection. The study showed that tested antibacterial medications could exert a cytostatic effect on the corneal epithelium at in vivo conditions and differ in their cytotoxic potential. Benzalkonium chloride presence in Signicef in a concentration twice as high than that of the main medication (Oftaquix) causes a proven by confocal microscopy effect on the corneal epithelium, and this may influence the bioavailability of the medication.

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“…Thus, the fourth-generation fluoroquinolones are extensively used clinically in the ocular field with time. However, fluoroquinolones may delay the healing process of the corneal epithelium and particularly the development of haze and scarring in corneal tissue, and these may have a negative effect on the visual outcome [11]. …”

Section: Discussionmentioning

confidence: 99%

Effects of Fluoroquinolone Eye Solutions without Preservatives on Human Corneal Epithelial Cells in vitro

et al. 2014

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Aims: To evaluate the biologic effects of fluoroquinolone eye solutions without preservatives on cultured human corneal epithelial cells in vitro. Methods: We studied the effect of diverse generations of topical fluoroquinolones such as ofloxacin 0.3%, levofloxacin 0.5%, tosufloxacin 0.3%, moxifloxacin 0.5% and gatifloxacin 0.3% on cultured human corneal epithelial cells. MTT-based calorimetric assay, lactate dehydrogenase leakage (LDH) assay and scratch wound test were performed. Corneal epithelial cell morphologies were examined by performing inverted light microscopy and transmission electron microscopy. Results: In all topical fluoroquinolones, the metabolic activity of the corneal epithelial cells decreased in a time-dependent fashion and the LDH titer increased with longer exposure times. Especially, the LDH titers significantly increased after exposure to moxifloxacin 0.5% and gatifloxacin 0.3% compared with controls. The migration rates of the corneal epithelial cells were faster in ofloxacin 0.3% or levofloxacin 0.5% than other fluoroquinolones. Severe cellular morphological damage was observed after exposure to moxifloxacin 0.5% and gatifloxacin 0.3%. Conclusions: As moxifloxacin 0.5% and gatifloxacin 0.3% induced the toxic effect to the corneal epithelial cells, compared with other fluoroquinolones, the 4th fluoroquinolone eye solutions should be carefully used in case of the corneal epithelium is damaged by long duration of treatment or overdosage.

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Evaluation of the Corneal Effects of Topical Ophthalmic Fluoroquinolones Using In Vivo Confocal Microscopy

Cited by 72 publications

References 9 publications

Comparison of fluoroquinolones: cytotoxicity on human corneal epithelial cells

Comparison of fluoroquinolones: cytotoxicity on human corneal epithelial cells

Comparison of cytotoxicity of fluoroquinolone antimicrobial eye drops and its effect on their bioavailability

Effects of Fluoroquinolone Eye Solutions without Preservatives on Human Corneal Epithelial Cells in vitro

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