Quantitative Characterization of Acid- and Alkali-Induced Corneal Injury in the Low-Volume Eye Test

Jester, James V.; Molai, AL; Petroll, Walter M; Parker, Ronald D.; Carr, Gregory J.; Cavanagh, Harrison D; Maurer, James K.

doi:10.1177/019262330002800506

Cited by 17 publications

(22 citation statements)

References 22 publications

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“…For the CM study, the untreated right eyes of a separate set of animals were used as the controls. Opposite eyes of treated animals were not used as controls because of the potential for corneal damage due to desiccation during the in vivo CM examinations interfering with the normal surface integrity (21,22).…”

Section: Methodsmentioning

confidence: 99%

“…In Vivo Confocal Microscopy. Rabbits were anesthetized and evaluated according to techniques previously described (22,25,(41)(42)(43). Brie y, in vivo CM was performed on the central, inferior, nasal and temporal regions of each cornea using a modi ed tandem scanning confocal microscope (Tandem Scanning Corp, Reston, VA).…”

Section: Methodsmentioning

confidence: 99%

“…In ammation, brosis and neovascularization of the cornea have been shown to increase scattering of light within the cornea that can be measured by changes in the CMTF AUC , thus providing a means to evaluate collectively the corneal changes occurring in one animal over time (23,24,37). This technique has been used previously to measure depth of corneal injury and temporal responses to surfactants (20,21,24,26,31) and acetic acid and sodium hydroxide (22) as well as to characterize corneal changes following contact lens wear (17,19,(44)(45)(46)(47), refractive surgery (34)(35)(36), and corneal injury (5,16,18,38).…”

Section: Methodsmentioning

confidence: 99%

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Pathology of Ocular Irritation with Acetone, Cyclohexanol, Parafl uoroaniline, and Formaldehyde in the Rabbit Low-Volume Eye Test

et al. 2001

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The ocular irritation responses to 11 different surfactants and two concentration s of acetic acid and sodium hydroxide have been shown to depend on the extent of initial injury, despite marked differences in the processes leading to tissue damage. The purpose of these studies was to determine the extent to which this fundamenta l relationship applies to other nonsurfactants . Ten l l of acetone (ACT), cyclohexano l (CY), para uoroaniline (PF), or 37% formaldehyd e (FA) was directly applied to the cornea of the right eye of each rabbit. Eyes and eyelids were macroscopicall y scored for signs of irritation beginning 3 hours after dosing and periodically until recovery or 35 days. Tissues were obtained for light microscopic examination after 3 hours and on days 1, 3, and 35. Initial corneal injury was characterized quantitatively at 3 hours and 1 day using in vivo confocal microscopy (CM) and by postmortem quantitation of dead corneal epithelial cells and keratocytes using a Live-Dead Assay (L/D, Molecular Probes) and scanning laser CM. Corneal changes over time were characterized quantitatively using in vivo CM performed at 3 hours and 1, 3, 7, 14, and 35 days. The changes with ACT were consistent with mild irritation. Corneal injury was limited to the epithelium and super cial stroma, with the mean normalized depth of injury (NDI) being less than 10% with the majority of regions showing no stromal injury. Changes with CY and PF were consistent with moderate to severe irritation, and FA caused severe irritation. Speci cally, corneal injury by CY and PF tended to involve the epithelium and anterior stroma, with the mean NDI being 10.4% to 23.8%, while injury with FA involved the epithelium, deep stroma, and at times the endothelium. Interestingly, with FA signi cantly less injury was observed at 3 hours with a dramatic increase in injury observed at 1 day and thereafter. In conclusion, these results continue to support and extend our hypothesis that ocular irritation is principally de ned by the extent of initial injury despite clear differences in the means by which irritants cause tissue damage. We believe this approach can be applied to developing alternative assays based on injury to ex vivo eyes or injury to an in vitro corneal equivalent system.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Pathology of Ocular Irritation with Acetone, Cyclohexanol, Parafl uoroaniline, and Formaldehyde in the Rabbit Low-Volume Eye Test

et al. 2001

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“…For the CM study, a separate set of control animals was used. Opposite eyes of treated animals were not used as controls because of the potential for corneal damage due to desiccation during the in vivo CM examinations interfering with the normal surface integrity (28,29).…”

Section: Methodsmentioning

confidence: 99%

“…Areas having denudation were not included when determining mean epithelial cell size but were included when determining mean epithelial thickness. All of these techniques have been used previously to measure depth of corneal injury and temporal response of the cornea to surfactants (27,28,32,35,42) and nonsurfactants (29,36) as well as to characterize corneal changes following contact lens wear (22,24,(58)(59)(60)(61), refractive surgery (45)(46)(47)(48), and corneal injury (10,21,23,49). Postmortem Live/Dead Examination.…”

Section: Methodsmentioning

confidence: 99%

Pathology of Ocular Irritation with Bleaching Agents in the Rabbit Low-Volume Eye Test

et al. 2001

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Despite differences in the processes leading to tissue damage, the ocular irritation response to various surfactants, two concentration s of an acid and an alkali, and an acetone, alcohol, aromatic amine, and aldehyde has been shown to depend on the extent of initial injury. The purpose of this study was to assess the extent to which this fundamenta l relationship exists for bleaching agents in the rabbit low-volume eye test. Ten l l of sodium perborate monohydrat e (NaBO 3 ), sodium hypochlorite (NaOCl), 10% hydrogen peroxide (H 2 O 2 ), and 15% H 2 O 2 was applied directly to the cornea of the right eye of each rabbit. Macroscopic assessments for irritation were made 3 hours after dosing and periodically until 35 days. Light microscopic examinations were conducted on tissues obtained at 3 hr and on 1, 3, and 35 days. In vivo confocal microscopy (CM) and measurements of dead corneal epithelial cells and keratocytes at 3 hours and 1 day were used to characterize quantitatively initial corneal injury, while in vivo CM performed at 3 hours and 1, 3, 7, 14, and 35 days was used to characterize quantitatively the corneal changes over time. The changes with NaBO 3 and NaOCl were consistent with mild irritancy. For both, corneal injury was limited to the epithelium and super cial stroma. The changes with 10% H 2 O 2 and 15% H 2 O 2 were consistent with severe irritation. Both concentrations affected the epithelium and deep stroma, with 15% H 2 O 2 also at times affecting the endothelium. However, unlike other irritants previously studied, with 10% H 2 O 2 and 15% H 2 O 2 there was an incongruit y between the extent of epithelial and stromal injury, with stromal injury being more extensive than epithelial injury. A similar, although less dramatic, effect was observed with NaBO 3 . Additionally, there was still signi cant keratocyte loss at 35 days with 10% H 2 O 2 and 15% H 2 O 2 even though the eyes at times were considered to be macroscopicall y normal. These observations highlight the need to include both epithelial and stromal component s in an ex vivo or in vitro alternative assay. In conclusion, these results continue to support and extend our hypothesis that ocular irritation is principally de ned by the extent of initial injury despite clear differences in the means by which irritants cause tissue damage. Importantly, we have identi ed unique differences in the ocular injury and responses occurring with bleaching agents that are important to consider in the development and validation of alternative ocular irritation tests to characterize a broad range of materials differing in type and irritancy.

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Extent of Initial Corneal Injury as the Mechanistic Basis for Ocular Irritation: Key Findings and Recommendations for the Development of Alternative Assays

Maurer

Parker

Jester

2002

Regulatory Toxicology and Pharmacology

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Quantitative Characterization of Acid- and Alkali-Induced Corneal Injury in the Low-Volume Eye Test

Cited by 17 publications

References 22 publications

Pathology of Ocular Irritation with Acetone, Cyclohexanol, Parafl uoroaniline, and Formaldehyde in the Rabbit Low-Volume Eye Test

Pathology of Ocular Irritation with Acetone, Cyclohexanol, Parafl uoroaniline, and Formaldehyde in the Rabbit Low-Volume Eye Test

Pathology of Ocular Irritation with Bleaching Agents in the Rabbit Low-Volume Eye Test

Extent of Initial Corneal Injury as the Mechanistic Basis for Ocular Irritation: Key Findings and Recommendations for the Development of Alternative Assays

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