Corneal degeneration

Rats and mice exposed to 31, 63, or 12 5 ppm 6 hours/day for 16 days developed lesions in the nasal respiratory epithelium and/or olfactory epithelium, and the severity of the lesions generally increased with increasing exposure concentrations. Clinical findings included dyspnea, hypoactivity, and nasal and ocular discharge. At 250ppm all animals died within 4 days. In 2-year inhalation studies at doses of 2, 8, or 32 ppm rats and male mice had increased incidences of nonneoplastic lesions of the nose and increased severity of nephropathy female mice had increased incidences of nonneoplastic lesions of the nose and corneal degeneration. In addition, there was some evidence of carcinogenicity in male rats based on increased incidences of combined neoplasms of the nose and equivocal evidence... 

Mann 3 examined the records of 84 men described as suffering from "delayed mustard gas keratitis." This group had been treated at the Contact Lenses Clinic at Moorfields, England. The eye injuries were described as "typical mustard gas scars with corneal degeneration." Mann found a low incidence of onset of trouble in the early postwar years, with a sharp rise in 1931 and peaks in 1934 and 1937 (Figure 4-1). Most, 19-23 yr old when gassed, were about 33-37 when the eye trouble peaked. The onset of symptoms was commonly provoked by minor eye injuries and followed by ulcers that tended to recur spontaneously and cause steady diminution in visual acuity. These men were all fitted with contact lenses. About half were able to wear them with improved vision the others varied from partial success to total failure. Even those helped most, however, suffered slow deterioration of visual acuity. 

EDS-V is an X-linked form of EDS-I in which skin fragility is prominent. EDS VI is a severe form of EDS-I associated with corneal degeneration. The genetic mutations of both are unknown, but EDS-VI has reduced lysine hydroxylase activity despite no detectable mutation of any of its three genes (Sect. 7.3.1) or of the genes involved in ascorbate metabolism (Sect. 7.4.1). 

Corneal ulceration (X3A, X3B), frequently referred to as keratomalacia, is accompanied most frequently by serious protein malnutrition. This may occur even while some body pools of vitamin A remain in the liver because of an ineffective transport system to peripheral tissues. Hence, although corneal involvement is indicative of vitamin A deficiency in ocular cells, it does not invariably reflect markedly inadequate hepatic vitamin A reserves (McLaren et al., 1965a). In these cases, dietary protein more than vitamin A is critical for long-term recovery, but in the short run, vitamin A alone will usually at least arrest further corneal degeneration (Reddy et al., 1979). Because there is no practical way of differentiating those children with adequate from those with exhausted vitamin A stores, when corneal involvement is assessed, treatment... 

Preferred Practice Patterns from the American Academy of Ophthalmology. Online at http //www.aao.org/aao/education/ library/ppp/index.cfm. Available for keratitis, blepharitis, conjunctivitis, dry eye, and age-related macular degeneration. Wilson SA, Last A. Management of corneal abrasions. Am Fam Physician 2004 70 123-128. 

Percutaneous absorption has been documented in rabbits. The liquid dropped into the eye of a rabbit caused severe but reversible conjunctivitis, iritis, and corneal opacity. Cytotoxic effects on rat bone marrow cells, with reduction in leukocyte counts, and testicular degeneration were observed after intramuscular injections at 400mg/kg/day. 

Rabbits repeatedly exposed to 50 ppm for 7 hours/day, 5 days/week for 6 weeks showed corneal damage, pulmonary irritation, moderate peribronchitis, and slight thickening of the vascular walls at 100 ppm, for the same exposure period, there was striking parenchymatous degeneration of the heart muscle in all exposed animals/... 

Exposure of rats to 8000 ppm for 4 hours was fatal to two of six animals within 14 days. Rabbits survived exposures to 50 ppm daily for 6 weeks but showed pulmonary irritation and some myocardial degeneration corneal damage was observed 2 weeks after exposure. In the rabbit eye, one drop of a 70% solution of ethylamine caused immediate, severe irritation. A 70% solution dropped on the skin of guinea pigs caused prompt skin burns leading to necrosis when held in contact with guinea pig skin for 24 hours, there was severe skin irritation with extensive necrosis and deep scarring. ... 

Ophthalmic Dose-related retinal degeneration and corneal opacities have been found in animal studies at doses equivalent to approximately the maximum recommended dose on a mg/m basis. 

Hughes reviewed mainly British and European reports and cited official British data estimating that 75-90% of mustard gas casualties had some degree of ocular Injury. A rough estimate, based on information reported by Case and Lea,13 indicates a little over 100,000 cases of eye Injury. Hughes stated that about 10% of these injuries resulted In corneal erosion, which he considered predictive of visual degeneration. Corneal transplants or contact lenses could be expected to help many patients. 

The following discussion focuses on the specific corneal dystrophies and degenerations that are most commonly encountered clinically. 

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