ABSTRACT
PURPOSE: The purpose of this study was to compare the cytotoxicity and antiinflammatory effect of preserved and unpreserved 0.1% fluorometholone (FML). METHODS: Drug-induced morphological changes and cytotoxicity were examined in human corneal epithelial cells. Dry eye was induced in mice by treatment with 0.2% benzalkonium chloride (BAC) for the first 2 weeks, and then, the eyes (4 groups; Normal saline, BAC, preserved FML, and unpreserved FML) were treated thrice daily with each formulation for the next 2 weeks. Corneal tissues were embedded in paraffin and stained with hematoxylin and eosin for histopathological examination. Immunofluorescence staining was performed for tumor necrosis factor-α, interleukin-6, and human leukocyte antigen-DR. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay was performed to evaluate drug-induced cytotoxicity. RESULTS: BAC and preserved FML caused cell shrinkage and detachment from the plate in a dose-dependent manner, and cell viability decreased significantly. However, cytotoxicity was reduced on treatment with unpreserved FML. Hematoxylin-eosin staining revealed surface desquamation, irregular surface, loss of cell borders, and stromal shrinkage in the group treated with BAC. On BAC exposure, tumor necrosis factor-α, interleukin-6, and human leukocyte antigen-DR were strongly detected, and cytotoxicity was markedly increased, as evidenced by a positive result in the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Ocular surface damage and inflammation were slightly reduced on treatment with preserved FML. In comparison, unpreserved FML did not induce morphological changes; moreover, decreased cell cytotoxicity and ocular surface inflammation were observed. CONCLUSIONS: The cytotoxicity of antiinflammatory eye drops evaluated in this study was induced by the preservative BAC. Accordingly, unpreserved FML is more effective than preserved eye drops in decreasing ocular inflammation.
Subject(s)
Benzalkonium Compounds/toxicity , Dry Eye Syndromes/drug therapy , Epithelium, Corneal/drug effects , Fluorometholone/toxicity , Glucocorticoids/toxicity , Preservatives, Pharmaceutical/toxicity , Administration, Topical , Animals , Cell Line , Cell Survival , Dose-Response Relationship, Drug , Dry Eye Syndromes/metabolism , Epithelium, Corneal/metabolism , Female , Fluorescent Antibody Technique, Indirect , HLA-DR Antigens/metabolism , In Situ Nick-End Labeling , Interleukin-6/metabolism , Mice , Mice, Inbred C57BL , Ophthalmic Solutions , Treatment Outcome , Tumor Necrosis Factor-alpha/metabolismABSTRACT
This study investigated the toxicity of commercial non-steroid anti-inflammatory drug (NSAID) eye solutions against corneal epithelial cells in vitro. The biologic effects of 1/100-, 1/50-, and 1/10-diluted bromfenac sodium, pranoprofen, diclofenac sodium, and the fluorometholone on corneal epithelial cells were evaluated after 1-, 4-, 12-, and 24-hr of exposure compared to corneal epithelial cell treated with balanced salt solution as control. Cellular metabolic activity, cellular damage, and morphology were assessed. Corneal epithelial cell migration was quantified by the scratch-wound assay. Compared to bromfenac and pranoprofen, the cellular metabolic activity of diclofenac and fluorometholone significantly decreased after 12-hr exposure, which was maintained for 24-hr compared to control. Especially, at 1/10-diluted eye solution for 24-hr exposure, the LDH titers of fluorometholone and diclofenac sodium markedly increased more than those of bromfenac and pranoprofen. In diclofenac sodium, the Na(+) concentration was lower and amount of preservatives was higher than other NSAIDs eye solutions tested. However, the K(+) and Cl(-) concentration, pH, and osmolarity were similar for all NSAIDs eye solutions. Bromfenac and pranoprofen significantly promoted cell migration, and restored wound gap after 48-hr exposure, compared with that of diclofenac or fluorometholone. At 1/50-diluted eye solution for 48-hr exposure, the corneal epithelial cellular morphology of diclofenac and fluorometholone induced more damage than that of bromfenac or pranoprofen. Overall, the corneal epithelial cells in bromfenac and pranoprofen NSAID eye solutions are less damaged compared to those in diclofenac, included fluorometholone as steroid eye solution.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/toxicity , Epithelium, Corneal/drug effects , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Benzophenones/administration & dosage , Benzophenones/toxicity , Benzopyrans/administration & dosage , Benzopyrans/toxicity , Bromobenzenes/administration & dosage , Bromobenzenes/toxicity , Cell Movement/drug effects , Cells, Cultured , Diclofenac/administration & dosage , Diclofenac/toxicity , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Epithelial Cells/ultrastructure , Epithelium, Corneal/cytology , Epithelium, Corneal/metabolism , Fluorometholone/administration & dosage , Fluorometholone/toxicity , Humans , L-Lactate Dehydrogenase/metabolism , Microscopy, Electron, Transmission , Ophthalmic Solutions , Propionates/administration & dosage , Propionates/toxicityABSTRACT
OBJECTIVE: To investigate the ocular hypertensive response to topical dexamethasone (DEX), rimexolone (RIM), loteprednol etabonate (LOT) and fluorometholone (FML) in rabbits of different ages. METHODS: Seventy-five rabbits of three age groups (7 weeks, 6 months and 1-year old) received topical administration of 0.1% DEX, 1% RIM, 0.5% LOT, 0.1% FML or balanced salt solution four times daily for 1 month. Intraocular pressure (IOP) was monitored at regular time intervals. After a month, eyes were harvested for histological study with haematoxylin and eosin (H&E), periodic acid Schiff and Masson trichrome staining. Trabecular meshwork changes were graded by masked ocular pathologists. RESULTS: Topical DEX caused the greatest increase in IOP, followed by RIM and FML. LOT caused the least IOP increase. Similar pattern of IOP response to the four corticosteroids was observed in the three studied age groups. Young rabbits (7 week) were the most responsive to corticosteroids among the age groups. Extracellular matrix thickening in the trabecular meshwork region and loss of trabecular meshwork cells were observed after DEX, FML or RIM treatments. CONCLUSION: Young rabbits are more susceptible to steroid induced increase in IOP, even for milder steroids such as fluorometholone and rimexolone.
Subject(s)
Disease Models, Animal , Glucocorticoids/toxicity , Intraocular Pressure/drug effects , Ocular Hypertension/chemically induced , Administration, Topical , Age Factors , Androstadienes/toxicity , Animals , Dexamethasone/toxicity , Extracellular Matrix Proteins/metabolism , Fluorometholone/toxicity , Loteprednol Etabonate , Male , Ocular Hypertension/metabolism , Ocular Hypertension/pathology , Ophthalmic Solutions/toxicity , Pregnadienes/toxicity , Rabbits , Tonometry, Ocular , Trabecular Meshwork/drug effects , Trabecular Meshwork/metabolism , Trabecular Meshwork/pathologyABSTRACT
OBJECTIVE: To examine the effects of intravitreal fluorometholone acetate (FMT) on the morphology and function of the retina and to investigate its possible use for vitreous surgery. METHODS: Brown Norway rat eyes (n = 6, 12 groups) were injected with 0.05 ml of SF6 gas for vitrectomization. Four weeks later, FMT solution was injected into the vitreous cavity/subretinal space of the vitrectomized eyes at doses of 10, 20, and 40 mg/ml (0.05 ml/eye, n = 12 for each group). The retinal function was evaluated by electroretinography (ERG) at 4 and 8 weeks after FMT injection. Retinal toxicity was also assessed histologically by a light microscopy. Sham-operated eyes (0.05 ml of irrigating solution, n = 12) were used as control animals. FMT-assisted pars plana vitrectomy with internal limiting membrane (ILM) peeling was performed in primate eyes (n = 2). Retinal toxicity was assessed by ophthalmoscope, fluorescein angiography and electron microscopy three months after the vitreous surgery. RESULTS: There was no remarkable reduction in any ERG waves at either time interval at 4 and 8 weeks after the intravitreal/subretinal injection of FMT. No obvious histological change was observed in any of the rat eyes either. Using ophthalmoscope, fluorescein angiography and electron microscopy, the appearance of the primate retinas remained to be in a non-pathological condition. CONCLUSION: FMT appears to be a potentially useful tool in assisting vitreous surgery including safe ILM peeling.
Subject(s)
Fluorometholone/toxicity , Glucocorticoids/toxicity , Vitrectomy/methods , Animals , Basement Membrane/surgery , Basement Membrane/ultrastructure , Electroretinography/drug effects , Epiretinal Membrane/surgery , Fluorescein Angiography , In Situ Nick-End Labeling , Intraocular Pressure/drug effects , Macaca fascicularis , Male , Microscopy, Electron, Transmission , Ophthalmoscopy , Rats , Rats, Inbred BN , Retina/drug effects , Retina/ultrastructure , Sulfur Hexafluoride/administration & dosageABSTRACT
The retinal toxicity of intravitreally injected steroids, fluorometholone and tetrahydrocortisol, was examined. The concentration of the steroids was 20 mg/ml, and 0.05 ml of each solution were injected into the rabbit vitreous cavity. An equal volume of saline solution was injected as a control. In addition to ophthalmoscopy, intraocular pressure was measured and electroretinography, light microscopy and electron microscopy were performed. The results showed no remarkable changes in all eyes. Fluorometholone and tetrahydrocortisol seem to have neither toxicity to the retina nor adverse effect of elevating intraocular pressure when intravitreally injected with this amount.
Subject(s)
Fluorometholone/toxicity , Retina/drug effects , Tetrahydrocortisol/toxicity , Animals , Fluorometholone/administration & dosage , Injections/methods , Intraocular Pressure/drug effects , Male , Rabbits , Tetrahydrocortisol/administration & dosage , Vitreous BodyABSTRACT
The effectiveness of fluorometholone was compared to dexamethasone phosphate and prednisolone acetate in preventing the immune corneal graft reaction in rabbits. Clear corneal grafts were obtained. Rejection was induced after skin from the corneal donor animal was grafted subcutaneously in the host animal and the animals were randomized into four treatment groups. Rejection occurred in eight of nine rabbits in the control group; one of eight in the dexamethasone phosphate group; one of eight in the fluorometholone group; and one of ten in the prednisolone acetate group. Histologic examination confirmed the above findings. In this animal study fluorometholone prevented immune graft rejection in a percentage similar to that of prednisolone acetate and dexamethasone phosphate.
