Some clinical aspects of ocular manifestations of toxicity in laboratory animals.

  • Ralph Heywood

Student thesis: Doctoral ThesisPhD

Abstract

Ocular Toxicity can be caused by the direct application of chemicals to the eye or following systemic administration. The assessment of eye irritation following local application is subjective. The eye test system is subject to such wide variation that it will never be possible to make precise measurement of irritancy. Clinical appraisal, supported by measurement of corneal thickness, is probably the best that can be achieved. The use of local anaesthetics should be considered when carrying out eye irritation tests in the rabbit. The eye and its adnexa are subject to the entire spectrum of toxic reactions, and may appear to be highly sensitive to toxic substances. The eye is derived from ectodermal, mesodermal and endodermal elements. Certain anatomical and physiological features contribute to the high incidence of ocular toxicity. The cornea is clear, permitting observation of pathological processes. It is an avascular structure, bathed externally by the tears and other secretions and internally by the aqueous humour. The lens is avascular and contains specific lens proteins. The nutritional supply to the lens is essentially from the aqueous humour. The anterior chamber of the eye contains the aqueous humour, which is actively secreted by the ciliary body. The aqueous humour is drawn from the eye through the drainage angle. The blood/aqueous barrier can prevent the entry of some chemicals. Toxic levels of a chemical can be reached in the aqueous humour by high daily dosage, by slow excretion, or by prolonged administration. The retina and underlying choroid are very vascular structures. The mechanisms of retinal toxicity are poorly understood, but often involve the vasculature. The low frequency at which ocular toxicity can occur has to be interpreted against the wide range of spontaneous pathology, therefore, emphasis has been placed on describing the normal eye and its variation and then differentiating drug-induced lesions. The ocular toxicity of a compound cannot be anticipated from its chemical structure or its pharmacological activity. It is apparent from the observations presented that there are considerable qualitative differences in ocular toxicity between the species. Caution must be exercised in extrapolating the data across the species. The clinical data allows some speculation as to the mechanisms involved. The development in this field of ocular toxicity is dependent on a better understanding of the metabolism of the tissues of the eye and the mechanisms of toxicity. The impairment or loss of vision by chemical agents is a highly emotive subject. Human clinical experience has shown many unfortunate incidents; dinitrophenol, corticosteroids, triparanol, phenothiazines, clioquinol and practolol have caused major problems. Any compound which has been shown to be ocular toxic in any of the laboratory species should be developed with caution.
Date of Award1977
LanguageEnglish
Awarding Institution
  • University of Bath

Cite this

Some clinical aspects of ocular manifestations of toxicity in laboratory animals.
Heywood, R. (Author). 1977

Student thesis: Doctoral ThesisPhD