Introduction
Neurotrophic keratopathy is a degenerative corneal disease induced by damage to the trigeminal nerve. Reduced corneal sensitivity (also called corneal anesthesia) leads to poor epithelial healing, generating epithelial keratopathy, ulceration, and corneal perforation1, 2. In addition, there is an alteration in the production of tears, which leads to greater corneal damage3. The most common etiology associated with neurotrophic keratopathy is herpes simplex and zoster ocular infection affecting the trigeminal nerve. Other causes include direct injuries to the trigeminal nerve: tumor resection surgeries, trauma, ablative procedures for trigeminal neuralgia, and repair of maxillary fractures, among others2,4,5.
Corneal anesthesia can lead to permanent vision loss if not treated in time. Due to the high morbidity associated with corneal anesthesia, it is extremely important to offer a safe and effective treatment. Corneal neurotization is an innovative surgical procedure in which a nerve transfer is performed using a healthy sensory donor nerve by “seeding” it on the periphery of the cornea; this allows the regeneration of the damaged plexus and therefore the reversal of neurotrophic keratopathy6,7.
This paper presents the case of a patient with neurotrophic keratopathy who was treated by corneal neurotization with favorable results.
Clinical case
A 39-year-old female, with a surgical history of resection of the right vestibular schwannoma in 2017, who after surgery developed ipsilateral facial paralysis as a complication as well as sensory deficit in V1, V2, and V3 of the trigeminal nerve and motor deficit of 40% in the masseter muscle right. Two years after the resection of the schwannoma, the patient developed corneal neuropathy. The latter was suspected due to the symptoms of foreign body sensation in the right eye, increased sensitivity to light, and corneal opacity. The patient did not present any other chronic degenerative disease.
During the period between resection and neurotization, the patient was maintained with conservative treatment with the use of lubricating drops and ointments. The patient was diagnosed with severe right corneal neuropathy in 2019 and referred for treatment by our service. On physical examination, the patient presented facial asymmetry due to right facial palsy, with involvement of the temporal, zygomatic, and buccal branches, as well as right lagophthalmos, conjunctival erythema, irregular ocular surface, and corneal sensitivity of 0 mm measured with the Cochet-Bonnet esthesiometer, corneal opacity over the entire surface of the cornea. The electromyographic study reported neurotmesis of the right facial nerve and motor trigeminal nerve with 40% activity. With these clinical data, in 2019, a right corneal neurotization and crossed nerve grafts were performed as surgical treatment for neurotrophic keratopathy as the first phase of facial reanimation.
Therapeutic intervention
Right corneal neurotization was performed in 2019 with the following surgical technique: under the effects of general anesthesia, the incision was made in the left upper palpebral sulcus, and it was gently dissected cephalad and deep to the orbicularis oculi muscle to find the left supratrochlear nerve at its emergence through the supratrochlear notch. To take the sural nerve graft, three longitudinal incisions were made in the left leg, starting from the malleolus, thus obtaining 10-15 cm of nerve graft. The sural nerve is kept in gauze moistened with physiological solution until it is time to use it in surgery. A tunnel was then created in the nasal bridge to pass the nerve graft connected to the supratrochlear nerve to the affected eyeball. The corneal surgeon performed a subconjunctival approach to the perilimbic areas of the cornea. For the placement of the sural nerve graft, dissection of the epineurium was performed in the distal portion; likewise, the fascicles were identified and separated, all under magnification with a surgical microscope. The surgical technique performed was described by Elbaz et al. (2014)8 (Figs. 1 and 2). Subsequently, the identification of the zygomatic and buccal nerves was performed on the healthy side with a rhytidectomy approach, isolating the branches that showed adequate palpebral closure and buccal excursion, neurorrhaphy was performed with two sural grafts, and seeding was left. That of the zygomatic toward the affected palpebral region and the preauricular buccal of the contralateral side, both distal ends were left identified with a simple 5-0 Prolene suture (Fig. 3).
Figure 1. Neurorrhaphy of the sural nerve to the cornea, microsurgery.
Figure 2. Identification of the supratrochlear nerve.
Figure 3. The two crossed nerve grafts are observed, one at the palpebral level and the second at the infranasal level.
Follow-up and results
At 6 months, the patient showed improvement in the regularity of the corneal surface, visual acuity by improving corneal opacity, as shown in Fig. 4, improvement in tear breakup time. Baseline corneal sensitivity went from 0 mm to a sensitivity of 25 mm evaluated with the Cochet-Bonnet esthesiometer. Likewise, the patient reported an improvement in the sensation of a foreign body and in the sensitivity to light. As expected, complications of the surgical procedure, the patient reported paresthesia in the left leg at the sural nerve innervation site, without presenting any functional difficulties.
Figure 4. Clinical improvement of corneal opacity.
Discussion
Neurotrophic keratopathy is a degenerative disease secondary to damage to the trigeminal nerve that produces corneal anesthesia. When the sensitivity of the cornea is altered, epithelialization and healing are altered, making the cornea more susceptible to continuous trauma, which, in turn, can cause ulcers, perforation, decreased visual acuity, and blindness. A frequent complication of brain tumor resection surgeries is facial paralysis, which increases corneal injury as there is no complete occlusion and the corneal reflex is affected, associated with corneal anesthesia due to damage of the V cranial nerve if there is corneal injury.
Corneal anesthesia can be congenital or acquired. The most common cause of acquired anesthesia is trigeminal neuropathy following herpes virus infection. The second most recognized cause is trigeminal deficit after surgery for resection of posterior fossa tumors. Corneal denervation compromises epithelial healing and leads to chronic ulceration and opacity from scarring7.
With the absence of protective sensitivity, even small repetitive traumas can cause blindness due to the chronic scarring process in the cornea, becoming a serious pathology. It is important to note that the insensitive cornea cannot be successfully treated by corneal transplantation, since the new cornea could be subject to the same underlying pathological process. For this reason, faced with the challenge of treating “neurotrophic corneas,” a novel surgical technique called corneal neurotization has been developed, which requires the intervention of specialists in ophthalmology and plastic and reconstructive surgery.
Corneal neurotization is a novel surgery used for cases of severe corneal anesthesia. This procedure has been associated with several benefits, including improving corneal sensitivity, visual acuity, and avoiding corneal ulceration in the post-operative period. However, as it is a new procedure, the largest series reported is 26 patients by Fogagnolo et al., showing improvement in corneal sensitivity in 100% of patients9.
Treatment of corneal insensitivity depends on the degree of severity. In stage 1, epithelial changes are mild and require treatment with artificial tears and ointments. Stage 2 is characterized by presenting major epithelial defects and inflammation of the anterior chamber; therapeutic options include therapeutic contact lenses, artificial tears, amniotic membrane transplantation, and tarsorrhaphy. In stage 3, treatment is surgical, with corneal neurotization being the most innovative and useful surgical option2–4,10.
In 2009, Terzis et al. performed the first corneal neurotization procedure to treat six patients with unilateral facial nerve palsy. Through a bicoronal dissection, they mobilized the contralateral supratrochlear nerve at its proximal end near the orbital rim, redirected it under the nasal bridge, opened the endoneurium of the nerve, separated the fascicles, and sutured them to the conjunctiva6. The six post-operated eyes with this technique presented improvement in corneal sensitivity in a follow-up of 2.8 ± 2.17 years (p < 0.016). Contralateral nerve transfer has also been performed endoscopically11.
In 2014, Elbaz et al.,8 made a modification to the Terzis technique, where access to the supratrochlear nerve is achieved through a small incision on the upper eyelid, preserving the supraorbital nerve. Once the contralateral supratrochlear nerve to the damaged eye has been located, a tunnel is made at the level of the nasal bridge and with the use of sural nerve grafts, the nerve coaptation of the supratrochlear nerve to the cornea is performed.
Being able to offer patients with corneal keratopathy an option for their treatment increases their chances of recovery and, where appropriate, being candidates for a corneal transplant.
The result with this surgical technique is promising. In our experience, as well as in the few world centers familiar with this surgical technique, the main limitation is the number of patients to treat. Neurotrophic keratopathy is commonly underdiagnosed, since patients who suffer from it are usually treated only with conservative treatment and the laboratory studies necessary to diagnose it, such as esthesiometry or confocal microscopy, are not performed. Another of the limitations is that this surgical technique is only performed in specialized centers where there is a multidisciplinary team made up of ophthalmology, otolaryngology, and plastic surgery.
Conclusion
Corneal neurotization is a technique that offers a short-term resolution of corneal keratopathy, and it can be performed in specialized centers with experience in this technique. Clinical trials and long-term monitoring of patients are needed for its use to become widespread in the adult and pediatric population. The resolution of keratopathy improves people’s quality of life and prevents long-term complications.
This technique can be performed together with other facial resuscitation procedures, to obtain the best result for the patient.
Funding
The authors declare that they have not received funding.
Conflicts of interest
The authors declare no conflicts of interest.
Ethical considerations
Protection of human and animal subjects. The authors declare that no experiments were performed on humans or animals for this study.
Confidentiality, informed consent, and ethical approval. The authors have obtained approval from the Ethics Committee for the analysis of routinely obtained and anonymized clinical data, so informed consent was not necessary. Relevant guidelines were followed.
Declaration on the use of artificial intelligence. The authors declare that they have not used any type of generative artificial intelligence for the writing of this manuscript.
