Drug delivery to the posterior segment from drops

Abstract

The published evidence that instilled drugs can affect the blood supply to the retina and optic nerve head in humans is examined. As a background, seven techniques that have been used to measure flow are briefly described and criticized. For timolol, the corresponding measurements, obtained by a number of investigators are evaluated. The outcome is very erratic and does not allow any conclusion as to the effect of this drug on flow. Consideration is then given to the possible mechanism whereby a drug could affect blood flow; directly, by diffusion to receptors on the vessels, or indirectly, through more anterior receptors. The question is raised whether the small changes in circulation induced by drugs would not be swamped by those resulting from natural alterations in the ambient light level. The literature was analyzed in the hope of identifying discrete entry pathways, for example, through the lens or the suprachoroidal space, that are sufficiently permeable to allow a significant quantity of drug to pass. There was an indication that a drug might diffuse through the lens cortex in sufficient quantity to cause a measurable rise in its concentration in the vitreous. In general, however, there was insufficient quantitative data to allow any meaningful predictions to be made. Stimulated by recent evidence, it is suggested that drug penetration from the tear fluid takes place by direct diffusion across the conjunctiva into the sclera and orbit when the head is supine.