Ophthal. Physiol. Opt. Vol. 17, Suppl. 1, pp. S17-S22, 1997 Q 1997 The College of Optometrists. Published by Elsevier Science Ltd Printed in Great Britain 027%5408/97 $17.00 + 0.00 PII: SO275-5408(96)00078-6 Cornea1 sensitivity in health and disease J. G. Lawrensont Department of Optometry and Visual Science, City University, London EC 1 V 7DD, UK Introduction The cornea is the most richly innervated surface tissue of the body. It receives its predominantly sensory nerves from ciliary branches of the ophthalmic division of the trigeminal nerve, which enter the cornea radially’at mid stromal level and divide repeatedly as they pass superficially to contribute to a dense plexus of nerves immediately under Bowman’s membrane. The epithelium receives its rich supply of terminal axons from this plexus via branches which penetrate Bowman’s membrane (Figure I). The existence of a modest sympathetic nerve supply has recently been demonstrated (Marfurt and Ellis, 1993), and may play a role in the modulation of epithelial ion transport mechanisms and possibly the regula- tion of cell proliferation. Interest in the sensitivity of the cornea dates back to the last century. The German physiologist von Frey con- cluded that pain was the only sensation perceived by the cornea (von Frey, 1894). This was consistent with his theory of specificity of sensory recep- tors which maintained that each sensory modality was subserved by a separate anatomically distinct nerve terminal. Since the cornea contained only free (unspecialised) nerve endings and in his experiments he and his colleagues could only illicit a sensation of pain from the cornea, von Frey concluded that free nerve endings were the exclusive receptors for pain. Although this specificity theory has been sub- tMCOptom sequently challenged in terms of this exclusivity, the question as to whether pain is the only modality mediated by cornea1 receptors remains. Several studies have shown that corneal stimu- lation with a variety of mechanical and thermal stimuli evoke a sensation of irritation or pain. In contrast, equiva- lent stimulation of the conjunctiva and facial skin are sensed as touch, warm or cold. Although electrophysiological re- cordings from cornea1 afferent neurones have identified sub-populations of re- ceptors which respond to mechanical, thermal or chemical stimulation, there is no unequivocal evidence for the conscious differentiation of these stimuli (Belmonte and Gallar, 1996). Interest- ingly, this electrophysiological data provides an explanation for the inability of the cornea to accurately localise a stimulus since the receptive fields of afferent neurones are often large and overlapping. Notwithstanding the debate as to whether painful and non-painful stimu- lation of the cornea can be differen- tiated, the assessment of cornea1 sensi- tivity remains a valuable clinical meas- urement and provides a useful indicator of cornea1 health. The object of this review is to summarise the factors which influence the sensitivity of the cornea: including normal physiological variation as well as the effects of ocular surgery, contact lenses, drugs and disease. Aesthesiometry: development of instrumentation Von Frey is usually credited with being the first to develop an exact s17 method for measuring cornea1 sensi- tivity (von Frey, 1894). The first aesthesiometer consisted of hairs of different lengths and caliber which were attached to the end of light wooden rods. When these were applied to the cornea they exerted a pressure which was dependent on the length and dia- meter of the hair. This principle has been utilised in the Cachet-Bonnet aesthesiometer which remains the clinical standard. Its development owes much to an earlier design by Boberg- Ans (Boberg-Ans, 1955). The aes- thesiometer essentially consists of a nylon filament (0.12 mm or 0.08 mm in diameter) which can be varied in length from O-6 cm. When the filament is applied to the cornea the pressure exerted at its tip is inversely propor- tional to its length (Figure 2). Although the Cachet-Bonnet aesthesiometer was originally designed as a hand-held in- strument, various attempts have been made to mount the aesthesiometer onto a slit-lamp, which allows fine control over the placement of the stimulus and ensures a smooth perpendicular ap- proach (Figure 3). Despite its wide- spread use the Cachet-Bonnet aesthesiometer suffers from several drawbacks: in particular the minimum stimulus exerted by the aesthesiometer is often supra-threshold even when using the smaller diameter filament. Various attempts have been made to develop a less invasive instrument which is able to present a range of liminal and sub-liminal stimuli, e.g. the CO, laser aesthesiometer dev- eloped by Brennan and Maurice which produces a range of thermal stimuli