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Clinicopathologic Reports, Case Reports, and Small Case Series
October 01, 2005

Treatment of Recurrent Corneal Erosion With Substance P–Derived Peptide and Insulin-like Growth Factor I

Arch Ophthalmol. 2005;123(10):1445-1447. doi:10.1001/archopht.123.10.1445

A 32-year-old woman was referred to us in September 2002. In February 1999, she experienced a traumatic corneal erosion in her right eye. After initial corneal healing, she developed several episodes of ocular pain, photophobia, and profuse tearing upon awakening. She visited an ophthalmologist and the diagnosis of recurrent corneal erosion (RCE) was made. She was treated with eye drops and ointments containing 5% sodium chloride for several months, but the epithelial erosion did not heal. She visited another ophthalmologist who added a therapeutic contact lens to her treatment, but there was no improvement.

On her initial visit to us, her visual acuity was 20/30 and she had experienced 26 RCE episodes. An epithelial defect with loosely adherent and elevated epithelium was evident in her right eye. Epithelial basement membrane dystrophy, ocular rosacea, and diabetes mellitus were excluded. Confocal microscopy showed islets of highly reflective cells with presumed intracellular deposits surrounded by normal cells in the basal epithelial cell layer. The basal epithelial cell area also showed drop-shaped configurations and ridges. Folding of the Bowman layer was also observed. Anterior keratocytes showed signs of activation (highly reflective nuclei with visible processes). An increased deposition of abnormal extracellular matrix in the anterior stroma was also observed. Posterior corneal keratocytes and endothelium appeared normal. The subbasal nerve plexus showed pathologic changes, such as strangely shaped nerve fiber bundles, faintly visible, long nerve fiber bundles (instead of the normally observed long, parallel-running, interconnected bundles), and increased amounts of Langerhans cells (Figure 1).

Figure 1.
A, Slitlamp image of corneal erosion. B-D, Confocal microscopic findings. B, Round brightly reflecting cells (suspected to be inflammatory cells) or debris in the superficial corneal epithelial layer. C, Abnormal structures (islets), interspersed among normal basal epithelial cells (arrow). D, Hook-shaped nervelike structures and irregular anterior keratocytes (representing activated forms) in the stromal region.

A, Slitlamp image of corneal erosion. B-D, Confocal microscopic findings. B, Round brightly reflecting cells (suspected to be inflammatory cells) or debris in the superficial corneal epithelial layer. C, Abnormal structures (islets), interspersed among normal basal epithelial cells (arrow). D, Hook-shaped nervelike structures and irregular anterior keratocytes (representing activated forms) in the stromal region.

The corneal sensation was normal (6 mm by Cochet-Bonnet esthesiometer). We started treatment with 20% autologous serum, 4 times a day, but there was no improvement.

Another treatment was started using eye drops combining 250 μg/mL of substance P–derived peptide (Sigma-Aldrich Laboratories, St Louis, Mo) with 1 μg/mL of insulin-like growth factor I (Sigma-Aldrich Laboratories) 4 times a day. Treatment was approved by the hospital ethics committee.

Eleven days after the start of treatment, complete epithelial resurfacing was achieved. Treatment was dis continued after 2 months when confocal microscopy findings returned to normal on the area of the recurrent corneal erosion (Figure 2). After the 11-month follow-up, no recurrences were observed.

Figure 2.
A, Normal slitlamp corneal image. B-D, Confocal microscopic findings. B and C, Healthy superficial and basal epithelial cells. D, Subbasal normal nerve plexus with long parallel nerve fiber bundles.

A, Normal slitlamp corneal image. B-D, Confocal microscopic findings. B and C, Healthy superficial and basal epithelial cells. D, Subbasal normal nerve plexus with long parallel nerve fiber bundles.

Recurrent corneal erosion is a common clinical disorder characterised by repeated spontaneous breakdown of the corneal epithelium. The pathophysiology is due to abnormalities of the adhesion complexes between the corneal epithelium and stroma. In vivo confocal microscopy of corneas with RCE and epithelial basement membrane dystrophy have shown altered subbasal nerves in some cases.1 Corneal innervation is important for the maintenance of corneal structure and function. Several case reports have been published regarding the effectiveness of substance P–derived peptide and insulin-like growth factor I in neurotrophic keratitis.2,3 This is the first report regarding the usefulness of this therapy in RCE. This case raises a question about the role of the sensory nervous system in the maintenance of a healthy epithelium. Even in the absence of a neurotrophic cornea, insulin-like growth factor I and substance P–derived peptide may synergistically promote corneal epithelium migration and healing.4 The demonstration of such alterations in corneal innervation in patients with these frequent corneal diseases introduces new ways of treating them. This case report suggests the need for controlled studies for the treatment of RCE with substance P–derived peptide and insulin-like growth factor I.

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Article Information

Correspondence: Dr Benitez-del-Castillo, Unidad de Superficie e Inflamacion Ocular, Hospital Clinico San Carlos, Martin Lagos s/n, 28040 Madrid, Spain (jbs00004@teleline.es).

Financial Disclosure: None.

References
1.
Rosenberg  METervo  TMPetroll  WMVesaluoma  MH In vivo confocal microscopy of patients with corneal recurrent erosion syndrome or epithelial basement membrane dystrophy. Ophthalmology 2000;107565- 573
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2.
Brown  SMLamberts  DWReid  TWNishida  TMurphy  CJ Neurotrophic and anhidrotic keratopathy treated with substance P and insulinlike growth factor 1. Arch Ophthalmol 1997;115926- 927
PubMedArticle
3.
Nakamura  MKawahara  MNakata  KNishida  T Restoration of corneal epithelial barrier function and wound healing by substance P and IGF-1 in rats with capsaicininduce neurotrophic keratopathy. Invest Ophthalmol Vis Sci 2003;442937- 2940
PubMedArticle
4.
Yamada  NYanai  RNakamura  MInnui  MNishida  T Role of the C domain of IGFs in synergistic promotionm with a substance P-derived peptide of rabbit corneal ephithelial migration wound healing. Invest Ophthalmol Vis Sci 2004;451125- 1131
PubMedArticle
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