According to an estimate by Crofton and Sheets,¹⁶ almost half of all neurotoxic chemicals affect some aspect of sensory function, the visual system being most frequently affected. Grant and Schuhman,³⁶ in their encyclopedic Toxicology of the Eye, list approximately 3000 substances that produce unwanted side effects in the visual system. Quite often, alterations in visual function are the first symptoms following chemical exposure,²⁶ occurring in absence of any clinical signs of toxicity.⁴ This not only suggests that the sensory systems, in particular the retina and the central visual system, are especially vulnerable to toxic insults, but also requires highly sensitive tests to be applied at a stage at which neither subjective function nor biomicroscopic morphology indicates such side effects. On the other hand, many of these effects are not necessarily toxic but may indicate undesired (though quite physiological) side effects on metabolic processes in one or several of the various stages of transforming the optical image of an object into the perceived neuronal image. Numerous proteins, such as transmitters or enzymes, and their metabolic processes are involved in processing information in photoreceptors and in the many connected neurons transmitting visual information to perceptual centers (table 54.1), whose function can be affected by neurotropic agents, drugs, food, and environmental agents. Additionally, there are numerous non-neuronal cells whose function is important for the integrity of the information processing, such as pigment epithelial cells, glial cells, and vascular structures, that are easily affected by immunological processes, for example. Considering the incredibly large number of substances that potentially affect visual function, this chapter can only discuss principal considerations and procedures recommended in cases of suspected adverse reactions of the more common potentially toxic compounds in the visual system.

Of further general concern are the factors that determine whether a particular chemical can reach a particular ocular site: concentration and duration of exposure, mode of application, and interaction with the various ocular structures as well as integrity of natural barriers. The blood-retinal barrier formed by the continuous type of capillaries is largely impermeable under normal physiological conditions to such chemicals as glucose and amino acids.³ However, in certain areas of the retina, e.g., around the optic disk, the continuous type of capillaries is lacking, and hydrophylic molecules can enter the optic nerve head by diffusion from the extravascular space.

The outer retina is supplied by the choriocapillaris, and these capillaries have loose epithelial junctions and multiple fenestrae and are highly permeable to large proteins. During systemic exposure to chemicals and drugs by inhalation, transdermally, or parenterally, compounds can be distributed to all parts of the eye via the bloodstream.

The chapter aims at mediating a basic understanding of toxic mechanisms by pointing out cell-specific functional changes and typical symptoms in unwanted, toxic side effects. In an individual case, I strongly recommend consulting referenced publications such as Grant and Schuhman³⁶ and Fraunfelder,³² where references on the primary literature on the various substances can be found. Additionally, there are very interesting general chapters and books that concern ocular toxicology that can often be of help.^{5,15,26,47,73}