Hypocellular scar formation or aberrant fibrosis induced by an intrastromal corneal ring: a case report
© Cao et al; licensee BioMed Central Ltd. 2011
Received: 4 January 2011
Accepted: 19 August 2011
Published: 19 August 2011
Intrastromal corneal rings or segments are approved for the treatment of myopia and astigmatism associated with keratoconus. We describe a clinicopathological case of intrastromal corneal rings. For the first time, the molecular pathological findings of intrastromal corneal rings in the cornea are illustrated.
A 47-year-old African-American man with a history of keratoconus and failure in using a Rigid Gas Permeable contact lens received an intrastromal corneal ring implant in his left eye. Due to complications, penetrating keratoplasty was performed. The intrastromal corneal ring channels were surrounded by a dense acellular (channel haze) and/or hypocellular (acidophilic densification) collagen scar and slightly edematous keratocytes. Mild macrophage infiltration was found near the inner aspect of the intrastromal corneal rings. Molecular analyses of the microdissected cells surrounding the intrastromal corneal ring channels and central corneal stroma revealed 10 times lower relative expression of IP-10/CXCL10 mRNA and two times higher CCL5 mRNA in the cells surrounding the intrastromal corneal ring, as compared to the central corneal stroma. IP-10/CXCL10 is a fibrotic and angiostatic chemokine produced by macrophages, endothelial cells and fibroblasts.
An intrastromal corneal ring implant can induce hypocellular scar formation and mild inflammation, which may result from aberrant release of fibrosis-related chemokines.
Intrastromal corneal ring segments (Intacs, KeraVision, Inc., Fremont, CA, USA), which have been approved for the treatment of myopia and astigmatism associated with keratoconus, are two tiny half rings made of polymethyl methacrylate . Compared with penetrating keratoplasty or laser surgery, Intacs has the advantage of reshaping the abnormal cornea without removing tissue or injuring the central cornea, which is most critical for clear vision. Studies have shown that Intacs could be easily removed, with reversal of visual, refractive, and topographic changes.
After implantation of Intacs, an extracellular intrastromal material may be found in the lamellar channel surrounding the segments . This material might spontaneously dissolve after removal of the Intacs segments. Histopathology of corneas implanted with Intacs has been reported, and this material has been referred to as acidophilic densification and/or channel haze [3, 4]. We describe, for the first time, the molecular histopathological findings of a corneal button with Intacs rings. The study was approved by the US National Eye Institute Institutional Review Board for human subjects, and the patient signed an informed consent.
Intacs have been used for several years and studied with focuses on clinical and refractive outcomes. Only a few histopathological reports are published [1, 3], in which a dense acellular (channel haze) and hypocellular (acidophilic densification) collagen scar, and slightly edematous keratocytes are described. Our case also presents these findings, which indicate aberrant fibrosis [1, 3].
IP-10/CXCL10, a CXC chemokine, which promotes chemoattraction but inhibits angiogenesis, is secreted by monocytes, endothelial cells, fibroblasts and keratinocytes. IP-10/CXCL10 regulates wound healing and inhibits fibrosis in the lung . IP-10/CXCL10 also induces apoptosis in several cell types. Therefore, it is not surprising that only occasional apoptotic cells are detected in the collagen scar tissue.
In our patient, the whitish deposits and macrophages were mainly located at the inner edge of the Intacs. Thus, the Intacs can induce tissue damage and secondary inflammation, which likely represent the clinical crystalline deposits. CCL5, a CC chemokine, is also called regulated upon activation, normal T-cell expressed and secreted chemokine (RANTES). Secreted by monocytes, neutrophils, T-lymphocytes, dentritic cells and fibroblasts, CCL5 plays an active role in recruiting leukocytes and is a powerful leukocyte activator . The mildly increased CCL5/RANTES mRNA in the tissue surrounding the Intacs, as compared to the central corneal stroma, suggests active inflammation around the Intacs, especially near the inner edge.
An Intacs implant induces hypocellular scar formation or aberrant fibrosis, and mild focal inflammation, possibly through its strong suppression of IP-10/CXCL10 production and mild enhancement of CCL5 secretion.
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Intrastromal corneal ring segments.
The US National Institutes of Health/National Eye Institute Intramural Research program supported the study.
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