Corneal nerves in health and disease.

The cornea is the most sensitive structure in the human body. Corneal nerves adapt to maintain transparency and contribute to corneal health by mediating tear secretion and protective reflexes and provide trophic support to epithelial and stromal cells. The nerves destined for the cornea travel from the trigeminal ganglion in a complex and coordinated manner to terminate between and within corneal epithelial cells with which they are intricately integrated in a relationship of mutual support involving neurotrophins and neuromediators. The nerve terminals/receptors carry sensory impulses generated by mechanical, pain, cold and chemical stimuli. Modern imaging modalities have revealed a range of structural abnormalities such as attrition of nerves in neurotrophic keratopathy and post-penetrating keratoplasty; hyper-regeneration in keratoconus; decrease of sub-basal plexus with increased stromal nerves in bullous keratopathy and changes such as thickening, tortuosity, coiling and looping in a host of conditions including post corneal surgery. Functionally, symptoms of hyperaesthesia, pain, hypoaesthesia and anaesthesia dominate. Morphology and function do not always correlate. Symptoms can dominate in the absence of any visible nerve pathology and vice-versa. Sensory and trophic functions too can be dissociated with pre-ganglionic lesions causing sensory loss despite preservation of the sub-basal nerve plexus and minimal neurotrophic keratopathy. Structural and/or functional nerve anomalies can be induced by corneal pathology and conversely, nerve pathology can drive inflammation and corneal pathology. Improvements in accuracy of assessing sensory function and imaging nerves in vivo will reveal more information on the cause and effect relationship between corneal nerves and corneal diseases.

Survival of corneal nerve/sheath structures in organ-cultured donor corneas.

PURPOSE: To study the morphology of human corneal nerves in eye bank organ-cultured corneas and in corneal grafts post-transplantation. METHODS: Thirty-seven organ-cultured corneas were divided into: Group-A, anterior 300-400 µm of 20 corneas used for Descemets stripping endothelial keratoplasty, and Group-B, 17 full-thickness corneas unsuitable for transplantation. Corneas whole mounts were stained for nerves using acetylcholinesterase technique and examined by NanoZoomer digital pathology microscope. Central and sub-Bowman's stromal nerves and the sub-basal nerve plexus including perforation sites and terminal bulbs were studied. Ten eyes were imaged following penetrating keratoplasty using in-vivo confocal microscopy (IVCM) for the presence of sub-basal and stromal nerves at 1, 4-5 and 7-8 weeks postoperatively (five eyes) and in all the other five eyes, the final follow-up was at 12 weeks. RESULTS: Fifteen of twenty (75%) corneas had stromal nerves in Group-A and 15 of 17 (88.2%) in Group-B. Average number of stromal nerves entering peripherally were 9.1 (range: 1-36). 7.5 in Group-A and 10.8 in Group-B. Central stromal nerves were seen in eight samples in Group-A and nine in Group-B. Many stromal nerves terminated abruptly without demonstrable continuity through Bowman's membrane. No terminal bulbs or sub-basal nerves were detected. In-vivo confocal microscopy (IVCM) showed 4 of 5 in 9 of 10 (90%) donor corneas had stromal nerves 1 week postoperatively, which remained present in 8 of 10 (80%) corneas at 4-5 weeks and in 9 of 10 (90%) at 7-8 weeks postoperatively. All 5 corneas analysed at 12 weeks showed the same stromal nerves from 1 to 12 weeks postoperatively. Sub-basal nerves were absent in all corneas over the 12-week study period. CONCLUSION: This study provides further insight into the behaviour of corneal nerves in transplanted corneas. Corneal stromal nerves/nerve-sheaths are preserved in organ-cultured eye bank eyes and persist post-transplantation up to 3 months. These could provide directional guidance to regenerating nerves from host stroma.

Corneal hypoesthesia with normal sub-basal nerve density following surgery for trigeminal neuralgia.

PURPOSE: To evaluate the corneal sub-basal nerve plexus in patients presenting with hypoesthesia following surgery for trigeminal neuralgia. METHODS: Twenty-one patients who had unilateral medically uncontrolled trigeminal neuralgia and underwent ipsilateral surgery from 2006 to 2012 were included. Of these, 10 had microvascular decompression (MVD group) and 11 had balloon compression of the trigeminal ganglion (BC group). Slit lamp examination, Cochet-Bonnet aesthesiometery and in vivo confocal microscopy were carried out on both eyes of each patient. Nerve density data were statistically analysed. RESULTS: Corneal sensations and sub-basal nerve densities in MVD group were normal and equal in both the operated and unoperated sides, indicating that there was no intra-operative damage of the ophthalmic division of the trigeminal nerve (V1). However, those in BC group, despite having significantly reduced corneal sensations on the operated side (p = 0.007), did not demonstrate any significant difference in their sub-basal nerve densities (p = 0.477). No patient had any ocular symptoms. CONCLUSIONS: This study supports the hypothesis that complete ganglionic damage and/or postganglionic damage of V1 results in corneal hypoesthesia and neurotrophic keratitis, but partial ganglionic or preganglionic damage would preserve trophic function despite hypoesthesia and not result in clinically significant symptoms or signs of neurotrophic keratitis. The trophic and sensory functions of V1 are therefore independent and can be dissociated by disease or injury.