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We developed a technique that can measure corneal transepithelial electrical resistance (TER) in mice, which was used for evaluating corneal toxicity induced by ophthalmic drugs. We used a tissue culture well and its insert to mount the mouse globe and separated the cornea from the rest of the globe to enable corneal TER measurements to be taken. The explanted mouse eyes were divided into groups, and the corneal epithelia were exposed to different concentrations of BAC. Half of these eyes were fixed for transmission electron microscopy (TEM) examination and the other for ZO-1 immunohistochemical (IHC) evaluation. After exposure to control, 0.1%, 0.2%, and 0.5% BAC, the TER was 100 ± 0%, 91 ± 14%, 83 ± 13%, and 34 ± 12% of the pre-exposure TER at 1 min, respectively, with a statistically significant decrease in the 0.5% group. After 3 min, the TER showed a statistically significant decrease in the 0.2% and 0.5% groups. The TEM examinations showed a loss of epithelial tight junctions between superficial cells in the 0.2% and 0.5% groups. The IHC examination showed decreased ZO-1 staining of the corneal epithelium of the same groups as compared to the control. To the best of our knowledge, we succeeded in developing an innovative technique for corneal TER measurement in mice.
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BACKGROUND: Most cases of microsporidial keratoconjunctivitis are found in the Southern hemisphere. Our purpose was to investigate the first outbreak of microsporidial keratoconjunctivitis in Japan among healthy, immunocompetent soccer players from the same team during a 1-month period. CASE PRESENTATION: This study is an observational case series. The medical records were analyzed for five cases with microsporidial keratoconjunctivitis who presented within September 2022. All five cases were males between 28 and 36 years old. These previously healthy individuals belonged to the same football team. Their eyes were considered susceptible to contaminated water or dirt from the turf at game and practice sites. All cases involved unilateral conjunctivitis, with scattered round white lesions that showed positive fluorescein staining in the corneal epithelium. All cases experienced diminution of vision in the affected eye. In three cases, direct smears showed spores of approximately 2-3 µm in diameter. Polymerase chain reaction (PCR) analysis of corneal scrapes revealed partial amplification of microsporidial 18 S ribosomal RNA gene in four cases. Sequences of PCR products from all four cases showed 100% identity with strains of Vittaforma corneae previously reported from an outbreak in Singapore. All cases were treated with topical therapy, including voriconazole, fluorometholone, and levofloxacin. Four eyes underwent corneal scraping. After treatment, all eyes healed without residual opacities. CONCLUSIONS: Only a few sporadic case reports of this disease have previously been reported in Japan. We detected V. corneae in our case series, representing what appears to be the first outbreak of microsporidial keratoconjunctivitis in Japan. Exposure to contaminated water or soil, in addition to inadequate sanitary facilities, represents a potential source of infection. Further investigations to clarify the characteristics of microsporidia seem warranted.
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Queratoconjuntivitis , Microsporidiosis , Masculino , Humanos , Adulto , Femenino , Microsporidiosis/epidemiología , Japón/epidemiología , Queratoconjuntivitis/epidemiología , Brotes de Enfermedades , AguaRESUMEN
Background and Objectives: To report a case of microbial keratitis complicated by severe corneal melting and whole corneal descemetocele. Methods: A 72-year-old male farmer presented with a right corneal ulcer involving nearly the entire cornea, which was almost completely melted down with the remaining Descemet's membrane (DM). The pupil area was filled with melted necrotic material, with the intraocular lens partially protruding from the pupil and indenting the DM. Corneal optical coherence tomography (OCT) examination revealed a corneal thickness of 37 µm that was attached to its back surface, with the iris and a part of the intraocular lens (IOL) protruding through the pupil. The patient was hospitalized and treated with local and systemic antibiotics until control of the inflammation was achieved. Corneoscleral transplantation plus excision/transplantation of the corneal limbus were performed, and the entire corneal limbus was lamellarly incised. After completely suturing all around the transplanted corneoscleral graft, the anterior chamber was formed. Postoperative treatment included local antibiotics, anti-inflammatory drugs, and cycloplegic drops. Results: There was no recurrence of infection, and the corneal epithelium gradually regenerated and covered the whole graft. Visual acuity was light perception at 6 months after the surgery. The patient was satisfied that the globe was preserved and did not wish to undergo any further treatment. Conclusions: Corneoscleral transplantation is preferred for the treatment of large-sized descemetoceles with active microbial keratitis and extensive infiltrates, especially in cases where the whole cornea has transformed into a large cyst.
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Trasplante de Córnea , Queratitis , Masculino , Humanos , Anciano , Trasplante de Córnea/métodos , Córnea , Tomografía de Coherencia Óptica , Antibacterianos/uso terapéuticoRESUMEN
A previous study suggested that the airlift condition is superior to the Optisol-GS condition for preserving the limbal tissue of the human cornea. The purpose of this research is to investigate a new preservation device that preserves the cornea while separating epithelial and endothelial areas. The differences after preserving the corneal epithelium under different conditions were compared. A total of 24 corneas of New Zealand rabbits were divided into four groups in which the corneal epithelia were submersed in Optisol-GS or under airlift conditions for 1 and 2 weeks at 4 [Formula: see text]C. Transparency, optical coherence tomography (OCT), hematoxylin and eosin (H &E) staining, and epithelial migration tests were used to assess corneal status. The epithelial migration examination showed significantly greater migration ability after the airlift condition. Corneas in the 1-week Optisol-GS group were the most transparent, followed by the 1-week airlift group. OCT showed a progressive increase in corneal thickness to the end of the study. H &E staining showed that the epithelial cells retained intact cellular structure and morphology of the cells for both 1-week-preserved groups. However, there was disruption of the corneal epithelial cell structure for both 2-week-preserved groups. Corneal epithelium preserved under the hypothermic airlift condition was comparable to that under the Optisol-GS condition.
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Epitelio Corneal , Preservación de Órganos , Conejos , Humanos , Animales , Preservación de Órganos/métodos , Córnea , Sulfatos de Condroitina , Dextranos , Gentamicinas , Mezclas Complejas , Medio de Cultivo Libre de Suero , Endotelio CornealRESUMEN
Inverted internal limiting membrane (ILM) flap technique was developed to achieve macular hole (MH) closure in large MH and refractory cases. In this study, we evaluate the effect of the technique for small-medium size MH. We recruited patients who underwent vitrectomy for small-medium size (< 400 µm) MH with either inverted ILM flap technique (flap group) or with conventional ILM peeling (peeling group). Using propensity score, 21 eyes of 21 patients in the peeling group were matched against 21 eyes of 21 patients in the flap group. We compared MH closure rate, postoperative visual acuity, and recovery of the external limiting membrane (ELM) and ellipsoid zone (EZ). The MH closure rate was not different between the two groups (flap vs peeling: 90% vs 100%, P = 0.49). Whereas there was no significant difference in visual acuity improvement between the two groups, the flap group showed more disruption of the ELM 3 months after surgery and of the EZ at 3 and 6 months after surgery (P = 0.02, P = 0.03, and P = 0.04, respectively). The result suggested that inverted ILM flap technique does not have additional benefits for small-medium size MHs and may delay recovery of retinal integrity.
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Membrana Basal/cirugía , Perforaciones de la Retina/cirugía , Colgajos Quirúrgicos , Vitrectomía/métodos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Recuperación de la Función , Perforaciones de la Retina/patología , Perforaciones de la Retina/fisiopatología , Resultado del Tratamiento , Agudeza VisualRESUMEN
RATIONALE: Rifabutin is a broad-spectrum antibiotic known to cause deposits on the corneal endothelium and lens. We report a patient in whom cataracts developed and progressive pigment deposits were seen on the corneal endothelium, lens, and iridocorneal angle. PATIENT CONCERNS: The patient was a 45-year-old woman who had been received long-term treatment with a combination of various anti-mycobacterial drugs for multidrug-resistant tuberculosis starting in 2004. Rifabutin was started in 2009, and she was referred to our department in 2017 for detailed ophthalmological examination. DIAGNOSES: Both eyes showed pigmented deposits over the entire corneal endothelium, the entire periphery of the iridocorneal angle, and the anterior surface of the lens. Mild cataracts were also diagnosed bilaterally. Pigment deposits on the anterior surface of the lens and the cataracts in both eyes gradually progressed. These lesions were assumed to be associated with long term rifabutin intake. INTERVENTIONS: Rifabutin intake was discontinued after progression of intraocular deposits, cataracts, and ERG deterioration. OUTCOMES: Visual acuity improved, although cataracts, deposits, and ERG deterioration remained. LESSONS: Rifabutin may induce not only corneal endothelial deposits, but also cataracts and iridocorneal angle deposits.
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Antibacterianos/efectos adversos , Catarata/inducido químicamente , Enfermedades de la Córnea/inducido químicamente , Rifabutina/efectos adversos , Antibacterianos/administración & dosificación , Femenino , Humanos , Persona de Mediana Edad , Rifabutina/administración & dosificación , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológicoRESUMEN
PURPOSE: To report the possible complications of intravitreal injection of tissue plasminogen activator (t-PA) for the treatment of submacular hemorrhage associated with retinal arterial macroaneurysm (RAM). OBSERVATIONS: A 75-year-old man complained of a sudden diminution of visual acuity in his left eye. Fundus examination of this eye revealed rupture of a RAM (0.5 disc diameters (DD) in size), submacular hemorrhage and hemorrhage under the internal limiting membrane (ILM). The patient had untreated hypertension and his systolic blood pressure was over 200â¯mmHg. Intravitreal injection of t-PA (42,000 units/0.07 ml) was given 1 day before undergoing vitrectomy. On the following day, the fundus was no longer visible because of a dense vitreous hemorrhage. After performing vitrectomy to remove the dense vitreous hemorrhage, we confirmed a marked increase in subretinal hemorrhage, and seemed to have markedly enlarged the macroaneurysm (6 DD). In addition, macular hole was found to have occurred. One week after surgery, the macular hole closed. Four months after surgery, best-corrected visual acuity improved from 20/400 to 20/40. CONCLUSIONS AND IMPORTANCE: Untreated hypertension and the use of t-PA can cause re-ruptured RAM and deterioration of subretinal hemorrhage. In this case, a macular hole was also occurred. Since there are risks of various complications, it is necessary to be careful in the use of t-PA for RAM.
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PURPOSE: We investigated succinate metabolism in cells undergoing clinically relevant cyclic stretch and in spontaneously hypertensive rat (SHR) retina. METHODS: We seeded ARPE-19 cells on 6-well BioFlex collagen I-coated, silicone elastomer-bottomed culture plates. Cells then were subjected to pulsatile stretch using a computer-controlled vacuum stretch apparatus. A physiologic stretch frequency of 60 cycles per minute and 5% to 15% prolongation of the elastomer-bottomed plates were used. Succinate concentration was assessed by enzymatic analysis and high-performance liquid chromatography-mass spectrometry. The VEGF was measured using enzyme-linked immunosorbent assays. The 12-week-old male SHRs and weight-matched Wistar-Kyoto (WKY) control rats were treated with or without 100 mg·kg(-1)·day(-1) captopril for 1 week. The vitreous body and retina of each rat were extracted after 1 week of therapy, and the vitreoretinal succinate concentration was measured. RESULTS: Cells exposed to cyclic stretch accumulated intracellular succinate in a time- and magnitude-dependent manner, and also accumulated VEGF protein levels. Moreover, BAPTA/AM, an intracellular calcium chelate reagent, significantly inhibited the stretch-induced succinate increase. After cyclic stretch, levels of intracellular fumarate, a citric acid cycle intermediate, also were significantly increased compared to controls. The BAPTA/AM inhibited this increase. For the in vivo experiments, hypertension increased vitreoretinal succinate and fumarate in SHRs compared to the normotensive WKY controls. When hypertension was reduced using captopril, vitreoretinal succinate returned to baseline levels. CONCLUSIONS: These findings suggest that cyclic stretch and hypertension increased intracellular succinate in cultured retinal pigment epithelial cells and the vitreoretinal succinate of SHRs through a calcium-dependent pathway.
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Hipertensión/complicaciones , Retina/química , Neovascularización Retiniana/etiología , Estrés Mecánico , Ácido Succínico/metabolismo , Animales , Células Cultivadas , Cromatografía Líquida de Alta Presión , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Hipertensión/metabolismo , Líquido Intracelular/química , Masculino , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Retina/metabolismo , Retina/patología , Neovascularización Retiniana/metabolismo , Neovascularización Retiniana/patología , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
PURPOSE: The aim of this study was to examine the ophthalmic additives responsible for modulating acute corneal epithelial toxicity induced by benzalkonium chloride (BAC) and investigate the ability of polyoxyethylene hydrogenated castor oil 40 (HCO-40) and polysorbate 80 (PS-80) to reduce the corneal toxicity and antimicrobial effects of BAC. METHODS: Cytotoxicity of the additives, which included glycerin, polyvinyl alcohol, propylene glycol, polyethylene glycol, and PS-80, on rabbit corneal epithelial cells was examined using the cell proliferation assay in the presence and absence of 0.02% BAC. The corneal transepithelial electrical resistance change after a 60-second exposure to HCO-40 or PS-80 mixed with 0.02% BAC was measured in living rabbits. Corneal damage was examined using scanning electron microscopy. The antimicrobial activities of HCO-40 and PS-80 with 0.02% BAC against Staphylococcus aureus, Propionibacterium acnes, Pseudomonas aeruginosa, Escherichia coli, and Streptococcus pneumoniae were assessed. RESULTS: Of all the tested additives, only PS-80 could prevent the BAC-induced cytotoxicity. Corneal epithelial barrier function disorder caused by 0.02% BAC was significantly alleviated by either PS-80 or HCO-40 in a concentration-dependent manner. Scanning electron microscopy images showed an improvement of BAC-induced corneal epithelial toxicity after the addition of HCO-40 or PS-80. The antimicrobial effect of the BAC against P. aeruginosa, E. coli, and S. pneumoniae was reduced after adding HCO-40 or PS-80. CONCLUSIONS: HCO-40 and PS-80 reduce acute corneal toxicity and the antimicrobial effect of BAC. Possible interactions between BAC and other additives should be taken into consideration when evaluating the toxicity and antibacterial properties of BAC.
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Antiinfecciosos Locales/toxicidad , Compuestos de Benzalconio/toxicidad , Aceite de Ricino/análogos & derivados , Epitelio Corneal/efectos de los fármacos , Soluciones Oftálmicas/toxicidad , Polisorbatos/farmacología , Conservadores Farmacéuticos/toxicidad , Animales , Aceite de Ricino/farmacología , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Córnea/efectos de los fármacos , Córnea/ultraestructura , Impedancia Eléctrica , Epitelio Corneal/ultraestructura , Escherichia coli/efectos de los fármacos , Escherichia coli/fisiología , Glicerol/toxicidad , Masculino , Pruebas de Sensibilidad Microbiana , Microscopía Electrónica de Rastreo , Polietilenglicoles/toxicidad , Alcohol Polivinílico/toxicidad , Propilenglicol/toxicidad , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/fisiología , Conejos , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/fisiologíaRESUMEN
PURPOSE: The benzalkonium chloride (BAK) content of tafluprost ophthalmic solution (Tapros(®): tafluprost) has been reduced to balance corneal safety and preservative effectiveness (old formulation: 0.01%; new formulation: 0.001%). However, no reports have been published on its clinical effect. Therefore, we conducted a clinical research study to compare the safety of BAK-reduced tafluprost on the ocular surface with other prostaglandin ophthalmic solutions. METHODS: This clinical study included 28 glaucoma patients (28 eyes) with a treatment history of latanoprost ophthalmic solution (Xalatan(®)) or travoprost ophthalmic solution (Travatan Z(®)), who presented with corneal epithelial disorders. The subjects were switched to BAK-reduced tafluprost, and its effect on the ocular surface was examined after 1 and 2 months of treatment [using fluorescein staining score, hyperemia, tear film breakup time, and intraocular pressure (IOP) lowering]. RESULTS: In all analyzed subjects (N=27), the fluorescein staining score was significantly improved after switching to BAK-reduced tafluprost (P<0.0001). Conversely, the IOP-lowering effect was not notably changed. The subjects switched from latanoprost (n=10) showed significant improvement in fluorescein staining score (P<0.05) as well as in IOP lowering (P<0.01). The subjects switched from travoprost (n=17) also showed significant improvement in fluorescein staining score (P<0.001), but without a significant change in IOP lowering. CONCLUSIONS: Tafluprost with reduced BAK has potential as a superior antiglaucoma drug, not only for its IOP-lowering effect, but also for its good corneal safety profile.
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Presión Intraocular/efectos de los fármacos , Soluciones Oftálmicas/uso terapéutico , Prostaglandinas F/uso terapéutico , Prostaglandinas/uso terapéutico , Anciano , Compuestos de Benzalconio/efectos adversos , Cloprostenol/análogos & derivados , Cloprostenol/uso terapéutico , Córnea/efectos de los fármacos , Enfermedades de la Córnea/tratamiento farmacológico , Femenino , Humanos , Latanoprost , Masculino , Conservadores Farmacéuticos/efectos adversos , Prostaglandinas F Sintéticas/uso terapéutico , TravoprostRESUMEN
PURPOSE: To determine the element that modulates benzalkonium chloride (BAC) toxicity by using a new electrophysiological method to evaluate acute corneal barrier dysfunction induced by travoprost Z with sofZia (Travatan Z(®)), travoprost with 0.015% BAC (Travatan(®)), and its additives. METHODS: Corneal transepithelial electrical resistance (TER) was measured in live white Japanese rabbits by 2 Ag/AgCl electrodes placed in the anterior aqueous chamber and on the cornea. We evaluated corneal TER changes after a 60-s exposure to travoprost Z, travoprost, and 0.015% BAC. Similarly, TER changes were evaluated after corneas were exposed for 60 s to the travoprost additives ethylenediaminetetraacetic acid disodium salt, boric acid, mannitol, trometamol, and polyoxyethylene hydrogenated castor oil 40 (HCO-40) with or without BAC. Corneal damage was examined after exposure to BAC with or without travoprost additives using scanning electron microscopy (SEM) and a cytotoxicity assay. RESULTS: Although no decreases of TER were noted after exposure to travoprost Z with sofZia and travoprost with 0.015% BAC, a significant decrease of corneal TER was observed after 0.015% BAC exposure. With the exception of BAC, no corneal TER decreases were observed for any travoprost additives. After corneal exposure to travoprost additives with BAC, HCO-40 was able to prevent the BAC-induced TER decrease. SEM observations and the cytotoxicity assay confirmed that there was a remarkable improvement of BAC-induced corneal epithelial toxicity after addition of HCO-40 to the BAC. CONCLUSIONS: Travoprost Z with sofZia and travoprost with BAC do not induce acute corneal barrier dysfunction. HCO-40 provides protection against BAC-induced corneal toxicity.
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Compuestos de Benzalconio/toxicidad , Aceite de Ricino/análogos & derivados , Cloprostenol/análogos & derivados , Córnea/efectos de los fármacos , Animales , Aceite de Ricino/farmacología , Cloprostenol/administración & dosificación , Cloprostenol/toxicidad , Córnea/metabolismo , Impedancia Eléctrica , Electrofisiología , Excipientes/toxicidad , Masculino , Microscopía Electrónica de Rastreo , Conservadores Farmacéuticos/toxicidad , Conejos , TravoprostRESUMEN
PURPOSE: To evaluate acute corneal epithelial toxicity induced by benzalkonium chloride (BAC) homologs with different alkyl chain lengths using an in vivo electrophysiological method. METHODS: BAC homologs with C12, C14, and C16 alkyl chain lengths were used at concentrations of 0.0025%, 0.005%, and 0.01%, respectively. Cytotoxicity of BAC homologs on the normal rabbit corneal epithelial cells was examined by using a WST-1 assay. Corneal transepithelial electrical resistance (TER) was measured in living Japanese white rabbits by 2 Ag/AgCl electrodes placed in the anterior aqueous chamber and on the cornea. TER changes were then evaluated after a 60-second exposure to these BAC homologs. Morphological changes in corneal epithelium after exposure to the BAC homologs were examined using scanning electron microscopy. The antimicrobial activity of BAC homologs against Escherichia coli was also assessed. RESULTS: All BAC homologs caused cytotoxicity and corneal barrier dysfunction in a concentration-dependent manner. However, the degree of corneal toxicity differed among the BAC homologs. Based on cytotoxicity and TER measurement, C14-BAC caused the greatest corneal impairment followed in order of severity by mixed BAC/C16-BAC and C12-BAC. Scanning electron microscopy images indicated an intact corneal epithelium after exposure to 0.005% C12-BAC, whereas 0.005% C14-BAC damaged the epithelium. There were no remarkable differences noted in the antimicrobial activity among the BAC homologs. CONCLUSIONS: Acute corneal epithelial toxicity induced by BAC homologs depends on the alkyl chain length. Thus, the use of C12-BAC instead of commercially available BAC is potentially safer for patients undergoing ophthalmological pharmacotherapy.
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Compuestos de Benzalconio/química , Compuestos de Benzalconio/toxicidad , Epitelio Corneal/efectos de los fármacos , Animales , Impedancia Eléctrica , Fenómenos Electrofisiológicos , Células Epiteliales/efectos de los fármacos , Epitelio Corneal/patología , Epitelio Corneal/fisiopatología , Masculino , Pruebas de Sensibilidad Microbiana , Microscopía Electrónica de Rastreo , ConejosRESUMEN
PURPOSE: We evaluated acute changes in corneal barrier function after instillation with preservatives using corneal transepithelial electric resistance (TER) in vivo and cytotoxicity tests in vitro. METHODS: The corneal TER of live rabbits was measured using a volt-ohm meter and silver/silver chloride electrodes. The cornea was exposed to the preservatives benzalkonium chloride (BAC; 0.001%, 0.002%, 0.005%, 0.01%, and 0.02%), 0.04% paraben, 0.5% chlorobutanol, 0.005% chlorhexidine digluconate, 2% boric acid, and 0.01% ethylenediaminetetraacetic acid, and then changes in the TER were monitored for 60 seconds. Cultured normal rabbit corneal epithelial cells were exposed to the same preservatives for 60 seconds in vitro, and cell viability was evaluated using the WST-1 assay. RESULTS: The TER instantly decreased and became significantly lower than the control within 10 seconds after instillation with 0.01% and 0.02% BAC (P < 0.01) and within 60 seconds after that with 0.005% BAC (P < 0.01). The TER decreased concomitantly with increasing BAC concentration. Cell viability after instillation with 0.005%, 0.01%, and 0.02% BAC for 60 seconds was significantly lower than that of the control (P < 0.0001). None of the other preservatives significantly altered the TER or cell viability. Decreases in the TER correlated with cell viability (r = 0.94, P < 0.0001). CONCLUSIONS: Instillation with BAC immediately disrupted the corneal epithelium. Corneal epithelial cell death is supposed to be associated with a decline in barrier function; thus, corneal TER measurement in vivo can assess the acute toxicity of preservatives added to ophthalmic drugs.
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Epitelio Corneal/efectos de los fármacos , Conservadores Farmacéuticos/toxicidad , Uniones Estrechas/efectos de los fármacos , Administración Tópica , Animales , Permeabilidad de la Membrana Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Impedancia Eléctrica , Epitelio Corneal/patología , Masculino , ConejosRESUMEN
OBJECTIVE: Acute corneal permeability change after instillation of benzalkonium chloride (BAC) was evaluated using a newly developed in vivo corneal transepithelial electric resistance (TER) measurement method. METHOD: Corneal TER was measured by Ag/AgCl electrodes placed in the anterior aqueous chamber and on the cornea of live rabbit eyes. TER was measured and TER change after instillation of 0.05% BAC solution was monitored. After TER measurement, cornea was excised and fixed for transmission and scanning electron microscopy. For the control study, physiologic saline was used instead of BAC. RESULTS: The TER of normal rabbit cornea was 602.3 +/- 195.0 Omega cm(2). TER decreased instantly after instillation of 0.05% BAC. In 5 s, TER decreased to 58.3 +/- 5.2%. In 60 s, TER decreased to 18.5 +/- 3.2%. At all time points, TER after instillation of 0.05% BAC was significantly lower than that of the control (p < 0.0001). Dissociation of tight junctions and the destruction of superficial cell membranes were observed under electron microscopy. CONCLUSION: Corneal epithelial change with increased permeability is rapid and intense after the instillation of highly concentrated BAC solution, accompanied by disorder of tight junctions and cell membranes of superficial cells. The newly developed in vivo corneal TER measurement method is suitable for assessing acute corneal change after drug instillation.