Surgical taming of neurotrophic keratopathy: From amniotic membrane grafting to neurotization

(Image Credit: AdobeStock/Kitreel)

Neurotrophic keratopathy (NK) is best treated early, but when that is not the case there are several surgical approaches that can be used. Clara Chan, MD, from the University of Toronto, Ontario, Canada, noted the importance of early recognition and aggressive medical treatment of NK to avoid the need for surgery, and maintaining the integrity of the corneal epithelial surface following healing.

A surgical overview

Chan and colleagues evaluated a series of patients with NK from a tertiary care clinic to ascertain the contributory factors to the disease. They found that 54% had herpes simplex virus (HSV) or herpes zoster virus, 24% had neurosurgical causes, 21% had retinal surgery, and ocular surface disorders characterized by extreme dry eye disease were a contributing factor among others. Most patients needed a surgical procedure (ie, tarsorrhaphy, amniotic membrane grafts, conjunctival flaps, or tectonic or optical keratoplasty). The visual prognosis was guarded and healing occurred over an extended period (85 days); 20% had a perforation, 2 eyes were eviscerated, and only 60% maintained their best-corrected visual acuity.

When medical treatments failed and stage 2 NK was present, aggressive surgery is needed. In Canada, unlike the United States, cenegermin, a nerve growth factor, is unavailable, and presentation with or progression to stage 2 requires immediate, aggressive attention.

In patients with stage 2 NK, the ocular surface still must be optimized, infection and inflammation controlled, and nutritional support provided. The surface can be optimized with instillation of nonpreserved lubricating drops and discontinuation of toxic agents. Chan reported that 65% of patients achieved healing of the ocular surface without surgery when using cenegermin in the FDA studies. In the presence of stage 3 NK, surgery is critical because of the condition of the cornea where melting may have occurred, and the tissue is thinning and possibly perforated.

Surgical options for NK

The surgical pearls for amniotic membrane grafting include debriding the uneven necrotic edges of the epithelial defect and avoiding the use of toothed forceps when handling the amniotic tissue. When positioning the tissue, the stromal side (ie, the sticky side), if placed down, can facilitate integration of the amnion into the corneal stroma. Chan said she prefers to place the basement membrane side (ie, the nonsticky side) down because it acts as a patch graft, dissolves faster, and the corneal epithelium grows underneath. Amniotic membrane grafting is generally performed before corneal scarring develops to facilitate rapid healing of the defect.

In a retrospective study covering an 8-year period, 335 patients (354 eyes) out of 305,351 had NK; HSV was the most frequent etiology. Amniotic membrane grafting was used in patients with stage 2 disease with a success rate of 57.2% and a mean healing time of 15 days. In stage 3, the success rate was 63.6% with a mean healing time of 16 days. The risk factors for a worse final corrected distance visual acuity were advanced age, advanced NK stage, and decreased corrected distance visual acuity at presentation.

Use of dehydrated amniotic membrane is another option for treating persistent epithelial defects. In a pilot study of this tissue,2 Chan et al found that the amnion was absorbed within 2 weeks in all patients, and the corneal defect resolved in 89%, with a mean time to resolution of 17.8 days. The patient follow-up times ranged from 90 to 265 days and the best-corrected visual acuity improved from 10/174 to 20/47, which reached significance (P = .036), she reported.

Tarsorrhaphyis another possible surgical option, although patients are reluctant to accept it. The procedure offers the best rate of defect resolution.

Chan recounted a study¹ that followed 77 patients for 5 years. Of these, 24 patients had a temporary tarsorrhaphy and the rest a permanent one. The results showed that after tarsorrhaphy, the defect resolved fully in 91% and the time to healing was a mean of 18 days. An alternative to suturing the eyes shut is a tape tarsorrhaphy, which may be more acceptable to patients.

The glue patch technique (tectonic patching) using cyanoacrylate glue is another treatment option for corneal perforations or leaks; it requires a cotton swab, small amount of ointment, Weck-Cel spears, and a bandage contact lens. This procedure requires about 2 to 3 mm of epithelium-free area for the glue to stick to the cornea surface and plug the perforation. The most frequent mistake is the use of excessive glue.

Sliding bolster temporary tarsorrhaphy technique resembles a pulley system to allow the eye to be opened for examination and closed afterward. The procedure uses double-armed 6-0 nylon that is passed through the lower and then the upper lid margins with bolsters made of 25-gauge butterfly tubing cut to size.

Use of a mattress suture facilitates creation of a temporary lateral tarsorrhaphy that can be performed at the bedside. It requires a spatulated double-armed 5-0 Prolene or nylon suture passed through the tarsus at the gray line and will stay tight for about 6 months to 1 year. Chan believes this is the most efficient way to perform a tarsorrhaphy.

Injection of about 15 units of botulinum toxin (Botox) into the superior orbital rim is a simple surgical method of achieving a continuously drooping eyelid that lasts up to 3 months. A downside is that the Bell reflex can be lost if the superior rectus muscle is inadvertently hit.

Conjunctival flaps can be created that are total (Gundersen flaps) or partial. In a study of shingles and HSV that caused NK, the main issue is that the flap can retract; this can be addressed by regluing/resuturing the flap. One eye in the study required a tarsorrhaphy and ultimately needed grafting.

When creating Gundersen flaps, all of the corneal epithelium must be removed. The limbus is cauterized to achieve a smooth surface for the conjunctiva to rest upon. The flap should be a few millimeters larger than needed because of the tendency for the tissue to shrink. The flap is secured with 9-0 Vicryl at the inferior margin and some glue at the base. Chan also advised removing the Tenon capsule, which causes retraction.

Surgical pearls for NK

Chan enumerated the key takeaways:

• Surgical treatments are used to treat stage 2 and stage 3 NK to avoid melting/perforation.
• Almost everything can be glued.
• Tape tarsorrhaphy gives the patient control.
• Amniotic grafts are best when used early before the development of stromal scarring (~60% success).
• If grafting is unsuccessful, tarsorrhaphy works well (~90% success).
• Tarsorrhaphy and tectonic grafting “go together like a horse and carriage.”
• Send the recipient button for HSV testing to rule out subclinical active disease.
• Gundersen flaps are the least intensive option for eyes with poor vision potential.

Neurotization: A new approach to a difficult problem

Neurotization is defined as restoration of corneal sensation with regional nerve transfers and nerve grafts. The beauty of neurotization is that it restores corneal nerve sensation. The sural nerve in the calf can be harvested and connected from the patient’s contralateral eye to the eye with NK. Once embedded into the cornea in a few insertion sites in each corneal quadrant, a corneal transplantation procedure can be performed, Chan explained. The procedure was developed at The Hospital for Sick Children, Toronto.

“This procedure prevents scarring, allows corneal transplant grafting to be performed, and amblyopia is minimized,” she said. In addition to the absence of corneal sensation, patients, such as the one described, cannot blink and this leads to substantial corneal exposure and risk of perforation.

One neurotization option is using the contralateral supratrochlear and supraorbital nerve, which was reported by Elbaz et al.³ Robert Pineda, MD, and Rong Guo, MS, from Massachusetts Eye and Ear and Harvard Medical School, both in Boston, Massachusetts, also developed a neurotization procedure using the great auricular nerve. The advantages of using this nerve are the availability of more axons, ipsilateral sensation with minimal donor site morbidity, and avoidance of facial incisions.

Clara Chan, MD

E: clarachanmd@gmail.com

Chan is with the University of Toronto and has no financial interest in this subject matter.

References:

1. Cosar CB, Cohen EJ, Rapuano CJ, et al.Tarsorrhaphy: clinical experience from a cornea practice. Cornea. 2001;20(8):787-791. doi:10.1097/00003226-200111000-00002

2. Mimouni M, Trinh T, Sorkin N, et al. Sutureless dehydrated amniotic membrane for persistent epithelial defects. Eur J Ophthalmol. Published online April 22, 2021. doi:10.1177/11206721211011354

3. Elbaz U, Bains R, Zuker RM, Borschel GH, Ali A. Restoration of corneal sensation with regional nerve transfers and nerve grafts: a new approach to a difficult problem. JAMA Ophthalmol. 2014;132(11):1289-1295. doi:10.1001/jamaophthalmol.2014.2316