Dr. Harshavardhan Ghorpade, G14398, Dr. Moreker Sunil Ratilal
Introduction:
Corneal anesthesia can be classified according to etiology into acquired or congenital causes. Acquired causes include infectious, inflammatory, traumatic, neoplastic, and iatrogenic. All of these cause impairment of the function of the ophthalmic division of the trigeminal nerve and lead to neurotrophickeratopathyCorneal sensation is a necessary component of corneal maintenance. Corneal anesthesia renders the cornea susceptible to non-healing epithelial ulceration, scarring and perforation. Corneal transplant is usually the last option treatment of perforation to maintain the eye globe. But even corneal transplant is known to fail and perforations occur even in corneal grafts if the corneal nerves are absent.
Corneal anesthesia can be either confined to the ophthalmic nerve or alternatively associated with other ocular conditions, such as strabismus, lagophthalmos, or paralytic ectropion, depending on the etiology and the extent of involvement of other cranial nerves. Herpes simples usually involves only cornea.
Corneal sensory reconstruction has been performed using a segment of the medial cutaneous branch of the sural nerve with direct neurotization of cornea by using the contralateral supraorbital and supratrochlear nerves. (1,2,3) However, this technique requires an extensive dissection and bicoronal incision. Direct nerve transfer has been done successfully in diabetic neuropathy. (4)
Herpes viruses are known to cause loss of corneal sensations. For nonhealing corneal epithelial defect , a tarsorrhaphy may be done but corneal perforation occurs cyanoacrylate gluing or tectonic corneal transplantation is the only option. However, in the absence of corneal nerves there is substantial reduction in corneolimbal stem/progenitor cells (6) and grafted corneas do not heal well and therefore graft too may show central perforation
Cruzat et al (7) showed that new nerves growing from the periphery into the corneal graft in herpes zoster patient who had a graft and so showed that regaining corneal innervation as well as corneal function is possible in patients with herpes zoster as shown by corneal sensation, in vivo confocal microscopy, and ex vivo immunostaining, suggesting that zoster neural damage is not always permanent and it may recover over an extended period of time. But if a patient presents with recurrent perforation in a corneal graft due to neurotrophism , a third graft too will perforate unless the cornea is reinnervated by a nerve graft.
Herpes Simplex usually does not affect the supra orbital and supra trochlear divisions as may be seen with Herpes Zoster Ophthalmicus. Hence the supra trochlear and supraorbital sensations may be normal in patients with herpes simplex keratitis. But in extensive corneal damage and corneal nerve damage direct nerve transfer may not suffice and the length of nerve is not adequate. The sural nerve is preferred because of its growth potential
Case report:
A seventy year old female patient with history of Herpes Simplex Virus (HSV) keratitis and total leucomatous corneal opacity had undergone a penetrating keratoplasty.Six months after her surgery she presented with corneal ulceration and central perforation with no corneal sensations.
The patient was taken for a second corneal graft but this time the corneal transplant was combined with corneal re-innervation surgery for which the sural nerve was harvested from her foot. Corneal anesthesia was evaluated preoperatively and post-surgical intervention centrally and in 4 quadrants using a Cochet-Bonnet esthesiometer. Harvesting of the median cutaneous branch of the sural nerve was done by a plastic surgeon .
The dissection of the donor supratrochlear nerve were carried out by the oculoplastic surgeon trained and certified in the process The supratrochlear nerve and supra orbital nerves were accessed through a transverse incision over the medial upper eyelid just inferior to the brow, deep to the origin of the frontalis and supra trochlear nerve found on the surface of the corrugator supercilii muscle as it is seen passing from the supratrochlear notch. An epineural window was fashioned in the side of the nerve for end-to-side coaptation of the sural nerve graft. End-to-side coaptation was done to preserve forehead sensation. The distal nerve graft was reversed and tunneled subconjunctivally to the perilimbal area of the cornea where the epineurium was removed and the individual fascicles were separated. The fascicles were then placed around the entire limbal circumference to reinnervate all 4 quadrants and secured to the sclera with 10-0 nylon sutures
Results:-
The vision improved from perception of light pre-operative to finger counting close to face immediate post operatively to finger counting at 5 meters after one week. However, the epithelial defect persisted for 8 weeks after which it started healing. Anterior segment OCT images showed evidence of nerve infiltrating the cornea. The corneal sensations improved only after 3 months and her vision improved to 6/18. There was no corneal thinning or perforation as had occurred after the first surgery
Discussion:-
Neurotrophic ulcers usually have a bad prognosis . The mainstay of treatment used to be protection of corneal surface by using frequent artificial tears or using punctal pugs and by either doing a tarsoraphy or using gold weight implants to cover the cornea. But the cornea ulcer does not heal as stem cells do not function properly in absence of nerves (6) .Corneal neurotization is a new approach which is viewed as a definitive treatment for the neurotrophic corneal disease since it directly helps nerves grow and so eventually the progenitor stem cells may function properly. The first report of corneal reinnervation in literature was in 2009 by Terzis et al (3). Elbaz et al (1) performed four cases using a segment of the medial cutaneous branch of the sural nerve with end-to-side coaptation of the graft to an isolated contralateral supratrochlear nerve using transverse upper lid incisions and all patients had markedly improved corneal sensation at 6 months with no corneal anesthesia-related complications after the surgery. Moreker et al (4) reported their case of corneal sensations returning after an ipsilateral nerve transfer. Jacinto et al (5) also presented positive results by ipsilateral nerve transfer. Our patient had good supra orbital and supratemporal sensations but the nerve transfer was not possible as a long nerve would be required for reinnervating a whole cornea. So the sural nerve graft was taken to connect the cornea to the supra orbital and supra trochlelar nerves
Namavari et al (8) studied nerve regeneration after transection and found that corneal nerve fibre density recovers to normal levels by 8 weeks after nerve transection. Epithelization depends on corneal nerves. We started seeing graft epithelization after 8 weeks and this could possibly be due to corneal nerves just developing. We were able to identify corneal nerves by imaging at around this time.The corneal sensations were almost normal by three months . Since we did an end to side anastomosis even the forehead sensations were not lost .
Allevi et al (9) published a case with acquired ipsilateral V and VII cranial nerve palsies due to removal of a vestibular schwannoma. Their patient regained corneal sensibility after direct corneal neurotization with the contralateral supraorbital and supratrochlear nerves. The patient regained vision after successful penetrating keratoplasty 6 months later. Our patient had a corneal perforation and needed a tectonic graft. If it failed an optical graft could be done later
References :-
1) Elbaz U, Bains R, Zuker RM, Borschel GH, Ali A. Restoration of Corneal Sensation With Regional Nerve Transfers and Nerve GraftsA New Approach to a Difficult Problem. JAMA Ophthalmol. 2014;132(11):1289–1295. doi:10.1001/jamaophthalmol.2014.2316
2) Bains RD, Elbaz U, Zuker RM, Ali A, Borschel GH. Corneal neurotization from the supratrochlear nerve with sural nerve grafts: a minimally invasive approach. PlastReconstr Surg. 2015 Feb;135(2):397e-400e. doi:10.1097/PRS.0000000000000994
3) Terzis JK, Dryer MM, Bodner BI. Corneal neurotization: a novel solution to neurotrophickeratopathy. PlastReconstr Surg. 2009 Jan;123(1):112-20. doi:10.1097/PRS.0b013e3181904d3a.
4) Moreker SR, Restoration of corneal sensitivity and reduction of opacity in diabetic neurotrophickeratopathy by nerve transfer. Comment to “Elbaz, U., et al.,Restoration of Corneal Sensation with Regional Nerve Transfers and Nerve Grafts: A New Approach to Difficult Problem. JAMA Ophthalmol, 2014.” Dec. 14, 2015
5) Jacinto, Frances et al.Ipsilateral supraorbital nerve transfer in a case of recalcitrant neurotrophickeratopathy with an intact ipsilateral frontal nerve: A novel surgical technique.American Journal of Ophthalmology Case Reports , Volume 4 , 14 – 17
6) Ueno H, Ferrari G, Hattori T, et al. Dependence of corneal stem/progenitor cells on ocular surface innervation. Invest Ophthalmol Vis Sci. 2012;53(2):867-872.
7) Cruzat A, Hamrah P, Cavalcanti BM, Zheng L, Colby K, Pavan-Langston D. Corneal Reinnervation and Sensation Recovery in Patients With Herpes Zoster Ophthalmicus: An In Vivo and Ex Vivo Study of Corneal Nerves. Cornea. 2016 May;35(5):619-25.doi: 10.1097/ICO.0000000000000797.
8) Abed Namavari, Joy Sarkar, Shweta V. Chaudhary, OkanOzturk, LisetteYco, SnehalSonawane, VishakhaKhanolkar, NeelimaKatam, Joelle Hallak, Sandeep Jain; Corneal Reinnervation Following Surgical Transection. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1809.
9) Allevi F, Fogagnolo P, Rossetti L, Biglioli F. Eyelid reanimation, neurotisation, and transplantation of the cornea in a patient with facial palsy. BMJ Case Rep.2014 https://dx.doi.org/10.1136/bcr-2014-205372.
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