Study Reviews Surgical Management of Neurotrophic Keratopathy

Neurotropic keratopathy is an orphan disease that affects only 5 people or fewer per every 10,000 patients. Due to its relative rarity, the condition remains poorly understood, but is associated with numerous complications including persistent epithelial defect, secondary infection, stromal thinning, scarring, vascularization, perforation, and potential eye loss. 

Medical therapies are the first-line treatment, and generally involve removing offending agents and treating both the infection and its concurrent surface problems. However, these  medical therapies are not always successful. When they fail, physicians have a number of surgical options they may turn to,  including tarsorrhaphy, amniotic membrane transplant, corneal neurotization and other techniques. A research team’s literature review published in Eye & Contact Lens provides a detailed oversight of the current options.

Tarsorrhaphy. During tarsorrhaphy, the superior and inferior eyelids are brought together to reduce ocular surface exposure and protect the cornea. These procedures have demonstrated corneal healing across multiple scenarios and are associated with a success rate of up to 90%. Tarsorrhaphies can be central or peripheral and may be either temporary or permanent. 

Temporary tarsorrhaphies are performed under local anesthesia and the most common technique — passing a double-armed nonabsorbable suture through the inferior and superior eyelids — allows for a “large area of temporary apposition. Permanent tarsorrhaphies are utilized when a patient’s neurotrophic condition is more severe, and ocular surface health cannot be maintained. Popular techniques include dekeratization of the eyelid margin to generate permanent scarring. More invasive techniques include internal fixation and performs the closure in 2 different planes. 

Botulinum toxin can be used as an alternative to surgical tarsorrhaphy to induce upper eyelid ptosis. Toxins are injected in the superior eyelid skin, with an effective dose of 5 to 15 IU. Ptosis typically occurs after 2 to 8 days and lasts for a mean of 46 days. 

Amniotic Membrane Transplant. Amniotic membranes have mechanical, biological, and anti-inflammatory properties that make it an integral part of ocular surface reconstruction. Amniotic membrane transplants (AMTs) can be placed either epithelial or stromal side up, after which re-epithelialization by the host epithelium occurs. Multiple layers of amniotic membrane can be placed, resulting in increased corneal thickness at the expense of degradation in tissue transparency. 

In neurotrophic keratopathy with good visual potential, the investigators suggest that when fresh, frozen AMTs are used, epithelial-side down placement is preferred to best preserve vision. 

AMT is suggested as a treatment for moderate or severe neurotrophic keratopathy, but because of low resolution rates, it should be considered only for emergent cases. 

Most eye bank amniotic membranes are cryopreserved, and several commercial products also contain cryopreserved amniotic membrane tissue, including Prokera® (Bio-Tissue). Prokera can be applied during an in-office procedure using topical anesthetic drops and a slit-lamp. 

Commercial products utilizing dehydration preservation methods are also available, including AmbioDisk® (Katena), BioDOptix® (Labtician), and Aril® (Seed Biotech). These are also applied via topical anesthesia. 

Keratoplasty. According to the authors, corneal surgeries performed in eyes with dry ocular surfaces and reduced sensations are at a high risk of failure. For this reason, neurotropic corneas that undergo deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PKP) are usually associated with the development of postoperative epithelial defects. Augmenting DALP or PKP with tarsorrhaphy or tarsorrhaphy plus AMT can promote faster, more complete epithelial healing. 

Drawbacks of this procedure include temporary sight obstruction and cosmetic concerns. Esthetic concerns and ocular surface concerns should be weighed and preoperatively addressed. 

Gunderson and Conjunctival Pedicle Flaps. These flaps were first described in 1958; however, due to retraction and other difficulties, these techniques became uncommon. To utilize Gunderrson flaps, physicians apply local anesthesia and expose the superior conjunctival bed. The patient’s cornea is de-epithelialized and necrotic stromal tissue is debulked. From there, underlying tendons are dissected, and the conjunctiva is horizontally incised to create a bridge, where the flap is placed onto the corneal surface and assessed for traction. 

Conjunctival flaps promote epithelialization, stop inflammation, reduce or eliminate the need for frequent medication use, and prevent progression to perforation. These flaps require a pedicle to ensure continuous blood supply. Disadvantages include iatrogenic limbal stem cell deficiency, limitation of corneal and anterior chamber visualization, inaccurate intraocular pressure measurements, and potential for perforation among the flap, among others. 

Buccal Graft Transplantation Technique. Autologous oral mucosa is an alternative to AMT for periorbital reconstruction due to the biological properties of the conjunctiva. Secretions are primarily mucous or seromucinous and have a similar composition to natural tears, which creates increased mucin production to coat the corneal surface and stabilize tear film. Benefits of this technique include the cost, accessibility to oral mucosa, technical simplicity, and good oral regeneration. Complications are typically rare and self-limiting, but may include postoperative discomfort, infection, neurosensory deficit, and wound dehiscence, among others. 

Neurotization. Corneal neurotization is a relatively new development for the treatment of neurotrophic cornea, developed in 2009. This technique addresses directly the patient’s underlying problem: deficient corneal innervation. The corneal neurotization technique includes surgical reinnervation of a hyposthetic or anesthetic cornea through a fully functioning sensory nerve. Both direct and ipsilateral supraorbital nerve transfers have been utilized. Preoperative planning must consider conjunctival scarring and glaucoma drainage device placement, which can limit donor nerve selection. 

“The surgical treatment options for managing neurotrophic keratopathy are varied and are aimed at optimizing the ocular surface and promoting epithelial healing,” the study says. “Surgical options should be targeted according to stage of neurotrophic keratopathy.” 

Disclosure: Several study authors declared affiliations with the pharmaceutical, biotech, or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Trinh T, Mimouni M, Santaella G, Cohen E, Chan CC. Surgical management of the ocular surface in neuropathic keratopathy: amniotic membrane, conjunctival grafts, lid surgery, and neurotization. Eye Contact Lens. 2021;47(3):149-153. Doi: 10.1097/ICL.0000000000000753