New Approaches to Neurotrophic Keratitis

Amnion membrane and extract promote epithelial healing and enhance visual outcomes.

BY KENNETH R. KENYON, MD

NEUROTROPHIC KERATOPATHY is a major clinical challenge. Reduced corneal sensation is a sequela of many corneal conditions, most notably herpes zoster and simplex as well as trigeminal nerve lesions, but also may result from such common conditions as diabetes. The progression of neurotrophic keratopathy can be rather innocuous in the early stages, perhaps appearing as only superficial fluorescein staining. Of far greater concern is the development of persistent epithelial defects (PEDs), which can precipitate noninfectious stromal ulceration (keratolylsis) that resists conventional treatments. Such patients are at high risk for ulceration or even perforation that may require therapeutic keratoplasty, which is also at enhanced post-operative risk for surface and wound-healing complications.

There are many traditional management strategies for PEDs, including lubrication and soft lenses, autologous serum tears, punctum occlusion, tarsorrhaphy and tissue adhesives.

Here we emphasize the newer developments of amnion membrane extract (AMX; KEERA, srl) and lamellar keratoplasty with amnion membrane (AM) transplantation.

Amnion membrane extract (AMX): Amnion membrane has ocular surface protective capabilities due to various neurotrophins and epidermal growth factors as well as inhibitors of inflammation and neovascularization. Amnion membrane products include fresh frozen (Bio-Tissue) and dehydrated amnion (IOP Ophthalmics) for inlay or overlay surgical application (secured with suture or fibrin adhesive) plus the self-retaining Prokera ring (Bio-Tissue) and AmbioDisk (IOP Ophthalmics), which simplify their nonsurgical application.

AMX, a lyophilized AM extract, retains the growth factor bioactivity of AM but moreover affords straightforward topical eye drop application that can be continued to prolong and enhance its biotrophic effects. In a prospective multicenter European study of sterile PEDs that were resistant to conventional therapies, topical AMX therapy demonstrated convincing efficacy of healing (96% of cases) with excellent safety.¹ Consequently, AMX was approved for use in Europe. Hopefully it may ultimately become available in the United States. Currently, Dr. Ghinelli’s group in Italy are also developing the use of freeze-dried, non-lyophylized amnion refined into very small particles called Human Amniotic Membrane Elemental Units. Retaining the micro-structure ad bioactivity of AM, these units also can be used as a topical suspension, thereby simplifying and sustaining their delivery.

Lamellar Keratoplasty with Amniotic Membrane Transplantation: Deep anterior lamellar keratoplasty (DALK) in combination with adjunctive AM overlay grafting and mini-lateral tarsorrhaphy supports the ocular surface recovery of corneas requiring keratoplasty for tectonic and/or visual indications while reducing the risks of post-op PED and of stromal structure or clarity loss. In performing this procedure, I usually create a 7.5 mm diameter non-perforating trephination to 100% of the thinnest intraoperative peripheral pachymetry. A crescent blade dissection of one or more layers, with or without intrastromal air, facilitates the approach to Descemet’s membrane. The donor graft is oversized by 0.25 mm, strip off Descemet’s membrane, thinned peripherally and sutured with interrupted and/or running 10-0 nylon. A large (approximately 12 mm) overlay graft, preferably of frozen AM, is secured with 9-0 Vicryl (Ethicon) sutures and/or Tisseel fibrin sealant (Baxter). A 3 mm marginal lateral tarsorrhaphy and a Kontur soft contact lens afford optimal ocular surface protection.

Postoperatively, these eyes quiet quickly with minimal need for antibiotics and steroids. The bandage soft contact lens is retained for a few weeks until reepithelialization is complete. The amnion either dissolves within 2 months or is easily stripped at the slit lamp. Suture removal and/or adjustment is performed at 2 months to reduce astigmatism. The mini-tarsorraphy is retained for at least 3 months, and undergoes staged release at the slit lamp. In my current series of 30 such patients, the mean acuity at 2 years was 20/80 (improved from CF) with a stable corneal surface in 27 cases, clear grafts in 28, and recurrent epithelial defects in only two, hence an overall 93% success rate.

Summary: Amnion membrane extracts are of great potential utility as a topical strategy. They help patients avoid surgery, may enhance the effect of amnion and prolong its capability of application. The European clinical trial demonstrating 96% successful healing of recalcitrant epithelial defects suggests potential additional applications, such as keratoplasty, refractive surgery and other surface diseases.¹

Surgically, the simple combination of lamellar keratoplasty with amnion overlay and lateral mini-tarsorrhaphy substantially improves epithelial healing and surface stability (Figure 1). DALK also enhances safety by reducing wound-healing problems and obviating the rejection risks of penetrating keratoplasty. My own 93% success rate with respect to increased visual acuity, surface stability plus tectonically intact and clear stroma suggests substantial potential for visual as well as tectonic rehabilitation in this intrinsically high-risk keratoplasty setting.

FIGURE 1. Lamellar keratoplasty and amnion membrane transplantation: 36-year-old male with herpes zoster ophthalmicus.
Pre-operative: dense stromal neovascularization scarring and lipid/cholesterol deposition have reduced vision to 20/400.
Pre-operative: at 6 months, vision is improved to 20/70 with no recurrence of neovascularization. This eye has remained visually and anatomically stable for more than 8 years.

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