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Impaired adhesion, migration, and/or mitosis can compromise corneal
epithelial healing. Persistent epithelial defects can progress to ulceration,
perforation, or endophthalmitis. Currently, our options are limited to methods
that address the underlying cause of the epithelial defect. In addition to
addressing exposure keratopathy, mechanical irritation to the eye, and systemic
diseases, clinicians supplement the tear film, minimize the mechanical aspects
of delayed wound healing, and use collagenolytic enzyme inhibitors. Specific
therapy includes preservative-free artificial tears, pressure patching, bandage
contact lens, and N-acetylcysteine. The more recent
use of nerve growth factor,1 amniotic membrane
and scleral lens2 has been reported. Nonsurgical
therapeutic options have limited effect, and surgical procedures such as lamellar
or penetrating keratoplasty become necessary to preserve the anatomic integrity
of the globe. Vision-threatening procedures (Gunderson flap, tarsorrhaphy,
evisceration, or enucleation) may also become necessary.
Recently, growth factors,1,5-8
and fibronectin6 have promoted epithelial
wound healing. Topical substance P (SP) and insulinlike growth factor 1 (IGF-1)
circumvented surgical intervention in this case.
Report of a Case
A 79-year-old monocular woman with a persistent epithelial defect following
penetrating keratoplasty in the left eye visited the University of Wisconsin
(Madison) Cornea Service for consultation.
Her medical history was significant for Fuchs endothelial dystrophy,
cataracts, and primary repair of a traumatic ruptured globe with subsequent
evisceration of the right eye. In her pseudophakic left eye, penetrating keratoplasty
was performed. A small suture tract leak and a small epithelial defect associated
with a trace graft override were present on the first day following surgery.
The suture tract leak healed quickly.
The defect persisted despite discontinuing polymyxin B sulfate, adding
erythromycin, and reducing the frequency of 1% prednisolone. Four postoperative
months of artificial tears, pressure patching, bandage contact lens, autologous
serum combined with artificial tears, and anterior stromal micropuncture were
ineffective at healing the defect.
The defect and the threat of complications persisted. At consultation,
her pinhole visual acuity was 20/80 OS; medications included erythromycin
and 0.2% brimonidine tartrate for ocular hypertension. The anesthetic epithelial
defect measured 1.0 × 2.0 mm (Figure
1). The sutures were intact. Graft override still occurred adjacent
to the epithelial defect.
Epithelial defect adjacent to
region of graft override.
This elderly monocular woman was offered an option of vision-threatening
surgical procedures or topical SP with IGF-1. The patient understood the investigational
and compassionate-use nature of SP and IGF-1. Informed consent was obtained.
Sterile SP (250 µg/mL) and IGF-1 (1.0 µg /mL) were prepared,
dispensed, refrigerated, and discarded after 1 week. One drop of each compound
was administered every 15 minutes for 2 hours each morning and night for the
first week. Polymyxin B and brimonidine were continued. This treatment frequency
was chosen on the basis of in vitro data (Christopher J. Murphy, DVM, PhD
oral communication, January 2001), suggesting a persistent trophic effect
after 2 hours of cellular contact with SP.
Complete healing occurred within 1 week (Figure 2). Symptomatic itching was mild and temporary. Her epithelium
remained intact during a 2-week taper of SP and IGF-1 administration. Polymyxin
B and both SP and IGF-1 were discontinued at the end of the second and third
weeks of treatment, respectively. Her epithelium remained intact on follow-up
examination at 3 weeks after discontinuing therapy, and it has remained healed
without epithelial breakdown throughout the ensuing 8 months.
Intact epithelium after treatment
with topical substance P and insulinlike growth factor 1. Fine superficial
punctate staining and a whorl pattern lie in the previously defective area.
Our armamentarium for corneal epithelial wound healing is limited. The
trigeminal nerve and the neuropeptide it releases, SP, contribute to the maintenance
of healthy corneal epithelium. Substance P has been shown to be synergistic
with IGF-1 in the promotion of cellular processes conducive to wound healing.5
Three reported cases describe the complete resurfacing of persistent
epithelial defects in human corneas in response to SP used synergistically
Our patient responded to this therapy and did not require surgical intervention,
suggesting a therapeutic advantage of this combined therapy. Our case, collectively
with those cited, demonstrates the need for prospective clinical trials to
declare the clinical value of this treatment modality in preventing the devastating
consequences of nonhealing epithelial defects.
This study was supported by an unrestricted grant from Research to Prevent
Blindness Inc (New York, NY), and grants EY1252601 and EY10841-04 from the
National Institutes of Health, Bethesda, Md.
Corresponding author and reprints: Neal P. Barney, MD, Department
of Ophthalmology and Visual Sciences, University of Wisconsin, 2870 University
Ave, Suite 206, Madison, WI 53705 (e-mail: firstname.lastname@example.org)
Lee CH, Whiteman AL, Murphy CJ, Barney NP, Taylor PB, Reid TW. Substance P, Insulinlike Growth Factor 1, and Surface Healing. Arch Ophthalmol. 2002;120(2):215–217. doi:
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