Cornea opacity

Several in vitro methods, including the hen s egg chorioallantoic membrane test (HET-CAM) the bovine cornea opacity and permeability assay (BCOP) and the isolated rabbit eye (IRE) test, have gained regulatory acceptance in Europe for the classification of severe eye irritants. Many companies are using such techniques successfully to reduce in vivo testing during development. ... 

None of the in vitro alternative eye tests has proven applicable as a valid replacement for the Draize eye irritation test or has been acceptable for regulatory purposes (Table 5), though some are considered either reliable or reproducible. The most frequently used test has been the ex vivo bovine cornea opacity and permeability assay. The newer human corneal equivalents system, an in vitro culture of immortalized human corneal cells that develops into... 

The conventional test for the irritant and corrosive potential of chemicals is the rabbit eye test, which was developed by Draize et al. (1944), and has become the international standard assay for acute eye irritation and corrosion (EC B.5, Directive 2004/73/EC OECD TG 405, 2002). The test material is applied to the conjunctival sac of the animal s eye and subsequent grading of ocular lesion is established cornea opacity, iris lesion, redness of conjunctivae, and oedema of conjunctivae (chemosis). 

In humans, cases of dermatitis have been described after contact with DHBs. Combined exposure to hydroquinone and quinone airborne concentrations causes eye irritation, sensitivity to light, injury of the corneal epithelium, and visual disturbances (126). Cases with an appreciable loss of vision have occurred (127). Long-term exposure causes staining due to irritation or allergy of the conjunctiva and cornea and also opacities. Resorcinol and catechol are also irritants for eyes. 

Another widespread application of cold storage of tissue for transplantation is that of preservation of the cornea. Inj uries leading to corneal scarring, various kinds of diseases, and the production of comeal opacity are leading causes of blindness. Cornea transplantation is a commonly used and highly successful procedure. It... 

Cornea Replacement for corneal opacity due to congenital diseases, injury, etc. 

TABLE 17.5. Comparison between In Vivo Ocular Irritancy and Opacity Induced in Bovine Cornea... 

Igarashi, H., Katsuta, Y., Matsumo, H., Nakazoto, Y. and Kawasaki, T. (1989). Opacification test by using the pig isolated cornea and its application to a test of corneal opacity induced by befimolol hydrochloride. J. Toxicol. Sci. Japan) 14 91-103. 

Muir, C.K. (1985). Opacity of bovine cornea in vitro induced by surfactants and industrial chemicals compared with ocular irritancy in vivo. Toxicol. Lett. 24 157-162. 

Opaque cornea, iris not discernible through the opacity... 

No neoplastic effect was observed in rats exposed to 0, 15, 45, or 135ppm for 6 hours/ day, 5 days/week for 2 years. Dose-related changes, which include atrophy of the neurogenic epithelial cells and hyperplasia of the reserve cells, mainly affected the anterior part of the olfactory epithelium. In the high-dose group there was opacity of the cornea. After a 6-month postexposure period reconstructive effects were observed in both tissues. 

No exposure-related clinical signs or lesions of systemic toxicity and no oncogenic responses were observed in rats exposed by inhalation at concentrations of 0, 15, 45, or 135ppm 6 hours/day, 5 days/week, for 24 consecutive months." Dose-related changes occurred in the anterior portion of the olfactory epithelium and consisted of atrophy of the neurogenic epithelial cells followed by progressive hyperplasia of the reserve cells and ultimately loss of the upper epithelial cell layer. Opacity and neovascularization of the cornea were also observed in methyl acrylate-exposed animals. 

A solution of rhodium trichloride in the eye of a rabbit gave a delayed injurious reaction 0.1 mg of solution adjusted to pH 7.2 with ammonium hydroxide was placed for 10 minutes in a rabbit eye after the corneal epithelium had been removed an orange coloration of the cornea occurred that faded to faint yellow within 8 weeks. During the first 2-3 weeks, the cornea was slightly hazy in the third week, white opacities gradually developed and, finally, there was extensive opacification and vascularization. 

Administered to mice, 49,000 ppm for 51 minutes resulted in narcosis, muscular hypotonia, disappearance of corneal reflexes, then coma followed by death. The LC50 was estimated to be 21,000 ppm in rats exposed for 3 hours. Repeated exposure of rats to concentrations ranging from 100 to 5000 ppm for 12 weeks caused a dose-related increase in irritation of the mucous membranes. At the 5000 ppm level there was marked edema or opacity of the cornea, salivation, and discharge or bleeding in the nasal mucosa. 

Cornea - Decreased corneal sensitivity punctate to lineal opacities transient edema. 

Opacities of the cornea and lens due to deposition of fine particulate matter are a common complication of chlorpromazine therapy but regress after drug withdrawal. The most serious ocular complication is pigmentary retinopathy associated with high-dose thioridazine administration it is an irreversible condition leading to decreased visual acuity and possibly blindness. 

Studies in rabbits and mice showed that oral and intravenous doses of 100 mg/kg/ day and 2 mg/kg/day of sumatriptan, respectively, to be lethal to embryos, whereas dosages as low as 2 mg sumatriptan/kg/day over a 1-month period led to comeal opacities and defects in the cornea epithelium in dogs (GSK, 2006). No controlled studies have been conducted to investigate this aspect in humans. 

In other acute-duration studies, groups of 4 male albino ChR-CD rats were exposed to 30 ppm HDI for 4 hours daily for 10 days over a 2-week period. A slit-shaped opacity of the cornea (clinically interpreted to be a corneal ulcer) of one eye was reported in one rat that died after exposure had ended (Haskell Laboratory 1961). In another study, male rats (strain not specified) were exposed for 6 hours to an unknown air concentration of HDI. The investigators estimated that 0.4% of the HDI in a bubbler was potentially evaporated, but total air flow through the chamber was not measured, so that it is not possible to precisely calculate the air concentration of HDI inhaled by the test animals. Animals were observed for behavioral changes for 10 days after exposure. All animals survived exposure and the 10-day observation period. The authors concluded that HDI was mildly toxic. The fumes were moderately irritating to the conjunctiva of the eye soon after the start of exposure (Mobay Corporation 1966). 

Toxicity Quinone vapor is highly irritating to the eyes and may be followed by corneal opacities, structural changes in the cornea, and loss of visual acuity. Solid quinone may produce discoloration, severe irritation, swelling, and formation of papules and vesicles.114... 

Dermal/Ocular Effects. Corneal opacity was described in 4 of 6 rats exposed to a concentration of 4,033 mg 4-nitrophenol/m as 4-nitrophenol dust (sodium salt) for 4 hours (Smith et al. 1988) (see Table 2-1 and Figure 2-1). The effect persisted through a 14-day observation period in one rat. This effect may be due to direct contact of 4-nitrophenol with the cornea and, as such, could also be classified under effects caused by dermal exposure. Exposure to a concentration of 2,119 mg 4-nitrophenol/m 6 hours/day for 2 weeks was without effect. Unilateral and bilateral diffuse anterior capsular cataracts were observed in male and female rats exposed to 30 mg 4-nitrophenol dust/m... 

CORNEA A. Opacity Scattered or diffuse area, details of the retina still clearly visible 1... 

---