Risantini Murugan

Introduction

The cornea is a transparent, extremely specialised structure that supplies nearly two-thirds of the eye’s refractive power and is the protection against environmental irritants, pathogens and ultraviolet radiation in the eyes. The cornea is one of the most densely innervated tissues in human anatomy, involving nerves in the cornea to provide ocular surface integrity by reflex tearing and blinking. Neurotrophic keratopathy (NK) is a rare, degenerative condition caused by trigeminal denervation and the corneal epithelium is susceptible to breakdown, ulceration and perforation. Neurotisation is a microsurgical technique that has traditionally been used to restore sensory or motor function following peripheral nerve injury (including brachial plexus repair) but was adapted to ophthalmology in a pioneering manner starting with the corneal neurotisation procedure in 2009 – signalling a move towards complete restoration of corneal innervation rather than symptomatic therapy (1,2).

Technique and rationale

Neurotrophic keratopathy (NK) has been traditionally treated with supportive measures including lubrication, bandage contact lenses, and tarsorrhaphy. Emerging medical therapies including Cenegermin (recombinant human nerve growth factor), Substance P and Thymosin β4 demonstrated potential to foster corneal healing but their expense, scarcity and variable efficacy have limited their application (3). Thus, this article specifically describes the surgical reconstructing of corneal innervation – corneal neurotisation. The methods are classified as direct and indirect methods (4).

Direct neurotisation consists of the direct transfer of a healthy donor nerve into the anaesthetic cornea without an interpositional graft. This strategy yields a strong axonal regrowth process and accelerated reinnervation but can be restricted by the available nerve length and potential for visible scarring. Techniques include:

1. Contralateral or ipsilateral supraorbital/supratrochlear nerve direct neurotisation – useful but can lead to large incisions and risk of alopecia.
2. Minimally invasive transblepharoplasty approach – cosmetically superior and avoids large scars; though nerve length is limited.
3. Ipsilateral infraorbital nerve neurotisation – no grafting is done and numbness in upper lip or cheek can occur.
4. Endoscopic methods – less visible scarring but need specialist equipment and expertise.

Indirect neurotisation involves an interpositional nerve graft (autograft or allograft) between the donor and target nerve and provides more flexibility during surgeries. Although these procedures help to restrict surgical sites along the face, they require longer surgical time, and require axonal regeneration via two coaptation sites, which can prolong reinnervation. Common methods include:

1. Sural or greater auricular nerve interpositional grafts – provide more length but need a second surgical site.
2. Acellular nerve allografts – spare the donor site morbidity and decrease operative time, however, cost and availability remain a prohibitive factor limiting their potential.

An indirect approach using an interpositional graft (such as the sural nerve) is sometimes preferred when the donor nerve cannot be mobilised close enough to the corneal limbus, in cases which involve bilateral or severe neurotrophic keratopathy, or when large facial incisions are undesirable (4).

Clinical Outcomes

Overall, corneal neurotisation can be found to be a novel and progressively more prominent option. Although the early outcome is encouraging, it should be stressed that this procedure is still relatively novel and long-term data regarding functional sensory recovery and visual outcomes are still limited. Additional studies are necessary to standardise surgical methods, evaluate the durability of reinnervation, and assess patient-reported results to establish its functionality within day-to-day clinical practice.

References

1. Terzis JK, Dryer MM, Bodner BI. Corneal neurotization: review of the literature and case report. Plast Reconstr Surg. 2009;123(1):98–107.
2. Fogagnolo P, Sacchetti M, Giannaccare G, et al. Corneal neurotization: current perspectives. Eye (Lond). 2020;34(9):1705–1716.
3. Bonini S, Lambiase A, Rama P. Neurotrophic keratitis: current challenges and future prospects. Eye (Lond). 2022;36(2):227–236.
4. EyeWiki. Corneal Neurotization. American Academy of Ophthalmology. Updated 2024. Available at: https://eyewiki.aao.org/Corneal_Neurotization.