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

Department of Ophthalmology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas

AL Molai

Department of Ophthalmology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas

W. Matthew Petroll

Department of Ophthalmology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas

Ron D. Parker

The Procter & Gamble Co, Cincinnati, Ohio

Gregory J. Carr

The Procter & Gamble Co, Cincinnati, Ohio

H. Dwight Cavanagh

Department of Ophthalmology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas

James K. Maurer

The Procter & Gamble Co, Cincinnati, Ohio

Defining the extent of initial injury has proven to be a useful basis for differentiating the ocular irritation potential of surfactants; however, the applicability of this method to other types of irritants has not been demonstrated. In the following studies we characterized the extent of corneal injury following exposure to different concentrations of acetic acid and sodium hydroxide (NaOH) in the rabbit low-volume eye test. Groups of rabbits received 3% acetic acid, 10% acetic acid, 2% NaOH, or 8% NaOH and were evaluated in vivo by macroscopic and in vivo confocal microscopic examination and postmortem using a live/dead staining kit and scanning laser confocal microscopic examination. Quantitative assessment of macroscopic scores, corneal surface epithelial cell size, corneal epithelial thickness, corneal thickness, depth of stromal injury, corneal light scattering (confocal microscopy through focusing, CMTF), and number of dead cells was conducted at various times, including the following: at 3 hours and at 1, 3, 7, 14, and 35 days. Based on macroscopic scores, the order of ocular irritancy potential was 3% acetic acid < 2% NaOH < 10% acetic acid < 8% NaOH. Evaluation of the quantitative in vivo and postmortem microscopic live/dead data revealed a slight decrease in epithelial thickness and an increase in dead epithelial cell numbers with 3% acetic acid. With 2% NaOH, significant focal changes in epithelial cell size, epithelial thickness, corneal thickness, and number of dead surface epithelial cells occurred at 3 hours and at 1 day, with injury to only a very small number of corneal stromal keratocytes, despite the presence of epithelial denudation. Changes with 10% acetic acid were similar to those noted with 2% NaOH at 3 hours and 1 day, but these changes were more diffuse and included stromal injury to a depth of 7.2 ± 9.3% of the corneal thickness, with significant numbers of dead keratocytes. Eight percent NaOH, on the other hand, caused focally extensive injury that averaged 26.3 ± 18.4% of the corneal thickness at 1 day, with significant light scattering from the cornea, which did not return to normal by 35 days postinjury. Overall, these data indicate that ocular irritation as a result of acetic acid and NaOH was associated with changes similar to those observed with surfactants (ie, slight irritants damage the corneal epithelium, mild and moderate irritants damage the corneal epithelium and anterior stromal cells, and severe irritants damage the corneal epithelium and deep stroma). To our knowledge, this is the first time that the ocular irritation potential for different types of materials (acid/alkali, surfactants) has been shown to be primarily dependent on the initial area and depth of injury.

Key Words: Ocular irritation • Draize rabbit eye test • animal alternatives • confocal microscopy • cornea

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Toxicologic Pathology, Vol. 28, No. 5, 668-678 (2000)
DOI: 10.1177/019262330002800506


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Jester, J. V. Articles by Maurer, J. K. Search for Related Content PubMed PubMed Citation Articles by Jester, J. V. Articles by Maurer, J. K. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ACETIC ACID SODIUM HYDROXIDE Social Bookmarking                         What's this?