Corneal neurotization for neurotrophic keratitis

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Introduction

Neurotization or nerve transfer is the technique of relocating a healthy nerve or its proximal stump to reestablish an irreversibly impaired sensory or motor pathway. The restoration of neural pathways may be directly with a local nerve transfer or indirectly with an interpositional nerve graft.

Disease Entity

Neurotrophic keratitis refers to the loss of corneal nerve function and sensation from a degenerative disease. Causes include but are not limited to herpes keratitis, topical anesthetic overuse, contact lens overuse. Pathology arises from the sequelae of corneal anesthesia with resultant loss of blink reflex, reflexive tearing, and poor epithelial wound healing. This leads to gradual thinning of the cornea with subsequent ulceration and perforation. Corneal sensation may be assessed with Cochet-Bonnet esthesiometer, which has a maximum length of 60 mm (most sensitive). Normal corneal sensation is expected to be around 62 mm[1].

Neurotrophic keratitis can be classified in 3 Mackie stages, from mildest (stage 1) to most severe (stage 3). Treatment is aimed at treating symptoms and preventing further progression and is stage dependent. Due to the progressive nature of this condition, addressing the underlying corneal denervation may be required.

Surgical Background

Neurotization has been described since the early 1900’s[2] and has been an established treatment modality for brachial plexus injuries[3] and peripheral nerve injuries with sensory or motor loss[4]. Neurotization as a treatment modality for other conditions are recently described as well, such as facial nerve paralysis[5] and sensation loss post breast reconstruction[6].

The notion of corneal neurotization was possibly first drafted by Samii in 1972 where he described connecting the major occipital nerve to the proximal ophthalmic nerve with a sural nerve graft, albeit with limited success[7] [8] In 2009, Dr. Terzis first presented direct corneal neurotization in cases of facial nerve palsy with ipsilateral trigeminal nerve involvement and corneal anesthesia. The approach consisted of transfer of the contralateral supratrochlear and supraorbital nerves directly to the neurotrophic cornea, yielding substantial recovery of corneal sensation as assessed by the Cochet-Bonnet esthesiometer[1]. Since then, others have achieved similar results using variations of direct neurotization (contralateral supraorbital/supratrochlear[1][9], ipsilateral supraorbital/supratrochlear[10], endoscopic[11]) and indirect neurotization[12], which usually involves coapting a sural nerve graft to the contralateral supraorbital or supratrochlear nerves. Newer grafts with the greater auricular nerve are being explored as well[13].

Indications

Neurotrophic Keratitis without anticipated long-term improvement

Relevant anatomy

Direct neurotization most frequently utilizes the supraorbital and supratrochlear branches of the frontal nerve. The two nerves exit the orbit above the level of the superior orbital rim. The supraorbital nerve exits specifically at the supraorbital notch while the supratrochlear nerve exits 21 mm from the midline between the supraorbital notch and the pulley of the superior oblique[14][15]. These nerves may be difficult to mobilize as they generally exit through the orbital rim foramina[14]. The function of the two nerves overlap over the medial forehead, so harvesting one would leave adequate residual sensation[15]. Generally, thicker and denser nerve fibers are thought to have greater potential for neurotization, so the supraorbital nerve is preferably harvested over the supratrochlear[13][14][15].

Indirect neurotization most frequently utilizes the sural nerve due to its accessibility and is a historically low risk donor graft site in other neurotization procedures[4][13][15]. The sural nerve provides sensation to the calf region of the leg and consists of branches from the tibial and common fibular nerve. The great auricular nerve, sensory function over the parotid, have also recently become another graft of interest[13].

Surgical Technique

There are various surgical approaches and, to date, none have been demonstrated to be superior over others. Direct neurotization offers less chance of scarring but limited in nerve length and need for extensive dissection. Indirect neurotization offers a less extensive procedure but may theoretically have decreased nerve fibers due to perineural scarring[13]. Selection of the proper approach relies on patient anatomy, site of damage, patient preference, surgeon expertise and comfort. Surgeons connect the nerves end-to-end, or end-to-side, although studies have not definitely demonstrated superiority of one technique over the other. Attaching the graft end to the donor nerve side may be technically easier.

Direct Neurotization

While ipsilateral grafts may shorten the operative time and extent of dissection compared to contralateral grafts, this option is only open if solely the ipsilateral long ciliary nerves are damaged. Otherwise, the chance of trigeminal nerve compromise will preclude the usefulness of its distal branches.

Contralateral supraorbital/supratrochlear neurotization[1][13][15]

  1. Dissect the contralateral supraorbital and supratrochlear nerves through bicoronal incision and flap proximal to supraorbital margin
  2. Tunnel nerve branches over the nasal bridge to the ipsilateral/neurotrophic eye
  3. Thread nerve branches through a small supratarsal incision along the upper lid crease
  4. Tunnel nerve branches through blepharotomy into the superior conjunctival fornix
  5. Incision through superior bulbar conjunctiva and create tunnels in the sub-Tenon’s space perilimbally
  6. Dissect nerve endoneurium to expose fascicles
  7. Distribute fascicles to the perilimbal area, suture with 10-0 nylon
  8. Repair conjunctival incisions with buried sutures
  9. Temporal tarsorrhaphy may be considered to facilitate healing

Ipsilateral supraorbital/supratrochlear neurotization[10][13][15]

  1. Dissect the ipsilateral supraorbital and supratrochlear nerves through a hemicoronal incision just behind the hairline
  2. Incise the periosteum 2cm above the superior orbital rim and continue the dissection of the deep branches of the supraorbital nerve
  3. Tunnel nerve branches through supratarsal incision along the upper lid crease
  4. Tunnel nerve branches through blepharotomy into the superior conjunctival fornix
  5. Incision through superior bulbar conjunctiva and create tunnels in the sub-Tenon’s space perilimbally
  6. Dissect nerve endoneurium to expose fascicles
  7. Distribute fascicles to the perilimbal area, suture with 10-0 nylon
  8. Repair conjunctival incisions with buried sutures
  9. Temporal tarsorrhaphy may be considered to facilitate healing

Indirect Neurotization

Indirect sural nerve neurotization[12][13][15][16]

  1. Dissect and mobilize nerve graft (sural, great auricular)
  2. Dissect the contralateral/ipsilateral supratrochlear or supraorbital nerves with sub-brow incisions
  3. End-to-end or end-to-side coaptation of the graft with supraorbital nerves using fibrin glue and 10-0 nylon sutures
  4. **Contralateral cases require subcutaneous tunneling over the nasal bridge to the ipsilateral eye
  5. Tunnel nerve branches through supratarsal incision along the upper lid crease
  6. Tunnel nerve branches through blepharotomy into the superior conjunctival fornix
  7. Incision through superior bulbar conjunctiva and create tunnels in the sub-Tenon’s space perilimbally or through a scleral-corneal tunnel incision
  8. Dissect nerve endoneurium to expose fascicles
  9. Distribute fascicles to the perilimbal area, suture with 10-0 nylon
  10. Repair conjunctival incisions with buried sutures
  11. Temporal tarsorrhaphy may be considered to facilitate healing

Minimally invasive/Endoscopic approach

Recently, Leyngold discussed a novel endoscopic approach mobilize either the contralateral or ipsilateral nerve branches for either direct[11] or indirect neurotization[17]. The authors also explored the use of acellular nerve allografts (Avance Nerve Graft, AxoGen) for indirect neurotization with good results[17]. The endoscopic approach involves the dissection through the subgaleal plane using blunt endoscopic elevator to the superior orbital rim to visualize the supraorbital nerves.

Postoperative management

Patients may be patched for a short time postoperatively and discharged with non-opioid pain medications, prophylactic antibiotic drops, steroid drops, and lubrication drops. Clinic followup is typically at one day, one week, and one month after the procedure. Sutures are removed at the appropriate followup appointments, and corneal sensation is measured with esthesiometry or cotton wisp test.

Complications

  • Hemorrhage: minimize with anesthetic vasoconstriction and cautery
  • Surgical site infection: minimize with prophylactic antibiotics and close follow up
  • Loss of sensation from initial donor location
  • Ineffective neurotization
  • Neuromas from neurrorhaphy (indirect neurotization)

Prognosis

The physiology of reinnervation likely occurs from a combination of direct sprouting from proximal nerve endings (after Wallerian degeneration of the distal)[1] and release of neurotrophic factors[9].

Restoration of corneal sensation may occur as early as one-week postoperatively, which may paradoxically lead to worsening ocular pain and discomfort. Over time, patients usually experience an increase in subjective corneal sensation followed by objective improvement[13][15] and consequent reduction in corneal vascularization. An interesting phenomenon may be observed where the patient can feel the donor nerve concomitant with corneal stimulation, and vice versa[1][13]. Complete neurotization of the basal and central cornea may be seen from 6 months to 2 years post-operatively, affected by patient’s age and comorbidities[13]. Patients usually experience improvements in visual acuity, corneal sensation, and reduction in symptoms in the months after surgery and will maintain these improvements over years[1][9][10][11][12][17][18]. Patients may even expect maintenance of corneal sensation even up to 20 years post-operation[1].

Additional Resources

  • Domeshek LF, Hunter DA, Santosa K, Couch SM, Ali A, Borschel GH, Zuker RM, Snyder-Warwick AK. Anatomic characteristics of supraorbital and supratrochlear nerves relevant to their use in corneal neurotization. Eye (Lond). 2019 Mar;33(3):398-403.
  • Koaik M, Baig K. Corneal neurotization. Curr Opin Ophthalmol. 2019 Jul;30(4):292-298.
  • Malhotra R, Elalfy MS, Kannan R, Nduka C, Hamada S. Update on corneal neurotisation. Br J Ophthalmol. 2019 Jan;103(1):26-35.

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Terzis JK, Dryer MM, Bodner BI. Corneal neurotization: a novel solution to neurotrophic keratopathy. Plast Reconstr Surg. 2009 Jan;123(1):112-20.
  2. Elsberg CA. Experiments on motor nerve regeneration and direct neurotization of paralyzed muscles by their own and by foreign nerves. Science. 1917 Mar 30;45(1161):318-20.
  3. Maldonado AA, Bishop AT, Spinner RJ, Shin AY. Five Operations That Give the Best Results after Brachial Plexus Injury. Plast Reconstr Surg. 2017 Sep;140(3):545-556.
  4. 4.0 4.1 Korus L, Ross DC, Doherty CD, Miller TA. Nerve transfers and neurotization in peripheral nerve injury, from surgery to rehabilitation. J Neurol Neurosurg Psychiatry. 2016 Feb;87(2):188-97.
  5. Garcia RM, Hadlock TA, Klebuc MJ, Simpson RL, Zenn MR, Marcus JR. Contemporary solutions for the treatment of facial nerve paralysis. Plast Reconstr Surg. 2015 Jun;135(6):1025e-1046e.
  6. Weissler JM, Koltz PF, Carney MJ, Serletti JM, Wu LC. Sifting through the Evidence: A Comprehensive Review and Analysis of Neurotization in Breast Reconstruction. Plast Reconstr Surg. 2018 Mar;141(3):550-565.
  7. Samii M. Autologe Nerven-Transplantation im Trigeminusbereich. Med Mitt. 1972;46:189–94.
  8. Samii M. Reconstruction of the trigeminal nerve. In: Samii M, Jannetta PJ, The cranial nerves. Berlin Heidelberg New York: Springer-Verlag, 1981:352–8.
  9. 9.0 9.1 9.2 Ting DSJ, Figueiredo GS, Henein C, et al. Corneal neurotization for neurotrophic keratopathy: clinical outcomes and in vivo confocal microscopic and histopathological findings. Cornea 2018; 37:641–646.
  10. 10.0 10.1 10.2 Jacinto F, Espana E, Padilla M, et al. Ipsilateral supraorbital nerve transfer in a case of recalcitrant neurotrophic keratopathy with an intact ipsilateral frontal nerve: a novel surgical technique. Am J Ophthalmol Case Rep 2016; 4:14–17.
  11. 11.0 11.1 11.2 Leyngold I, Weller C, Leyngold M, Tabor M. Endoscopic corneal neurotization: technique and initial experience. Ophthalmic Plast Reconstr Surg 2018; 34:82–85.
  12. 12.0 12.1 12.2 Elbaz U, Bains R, Zuker RM, et al. Restoration of corneal sensation with regional nerve transfers and nerve grafts. JAMA Ophthalmol 2014; 132:1289.
  13. 13.00 13.01 13.02 13.03 13.04 13.05 13.06 13.07 13.08 13.09 13.10 Malhotra R, Elalfy MS, Kannan R, Nduka C, Hamada S. Update on corneal neurotisation. Br J Ophthalmol. 2019 Jan;103(1):26-35.
  14. 14.0 14.1 14.2 Domeshek LF, Hunter DA, Santosa K, Couch SM, Ali A, Borschel GH, Zuker RM, Snyder-Warwick AK. Anatomic characteristics of supraorbital and supratrochlear nerves relevant to their use in corneal neurotization. Eye (Lond). 2019 Mar;33(3):398-403.
  15. 15.0 15.1 15.2 15.3 15.4 15.5 15.6 15.7 Koaik M, Baig K. Corneal neurotization. Curr Opin Ophthalmol. 2019 Jul;30(4):292-298.
  16. Jowett N, Pineda II R. Corneal neurotisation by great auricular nerve transfer and scleral-corneal tunnel incisions for neurotrophic keratopathy. Br J Ophthalmol. 2019 Sep;103(9):1235-1238. doi: 10.1136/bjophthalmol-2018-312563. Epub 2018 Nov 23.
  17. 17.0 17.1 17.2 Leyngold IM, Yen MT, Tian J, Leyngold MM, Vora GK, Weller C. Minimally Invasive Corneal Neurotization With Acellular Nerve Allograft: Surgical Technique and Clinical Outcomes. Ophthalmic Plast Reconstr Surg. 2019 Mar/Apr;35(2):133-140.
  18. Catapano J#1,2,3, Fung SSM#3,4,5, Halliday W3,6, Jobst C2, Cheyne D2, Ho ES1, Zuker RM1,3, Borschel GH1,2,3, Ali A7,4. Treatment of neurotrophic keratopathy with minimally invasive corneal neurotisation: long-term clinical outcomes and evidence of corneal reinnervation. Br J Ophthalmol. 2019 Dec;103(12):1724-1731. doi: 10.1136/bjophthalmol-2018-313042. Epub 2019 Feb 15.