Alterations of Extracellular Matrix Components and Proteinases in Human Corneal Buttons With INTACS for Post-Laser In Situ Keratomileusis Keratectasia and Keratoconus

Abstract

Purpose-To perform an immunohistochemical evaluation of corneas with INTACS for post-laser in situ keratomileusis (LASIK) keratectasia and keratoconus, obtained after corneal transplantation.Methods-Corneas from 1 patient with INTACS for post-LASIK keratectasia and 2 patients with INTACS for keratoconus were obtained within 3 hours after penetrating keratoplasty, and cryostat sections were analyzed by immunostaining for 35 extracellular matrix (ECM) components and proteinases.Results-In the stroma of all corneas next to an INTACS implant, ECM components typically associated with fibrosis were observed. These included tenascin-C, fibrillin-1, and types III, IV (α1/ α2 chains), and XIV collagen. Also, significant deposition of perlecan, nidogen-2, and cellular fibronectin was revealed in the same locations. The keratoconus cases displayed typical Bowman layer breaks and subepithelial fibrosis with deposition of various ECM components. In all cases, some keratocytes around INTACS were positive for specific proteinases associated with stromal remodeling, including cathepsins F and H, matrix metalloproteinase (MMP)-1, MMP-3, and MMP-10. Staining for MMP-7 was variable; MMP-2 and MMP-9 were mostly negative. Patterns of type IV collagen α3, α4, and α6 chains; types VI and VIII collagen;α4, α5,β1, β2, and γ1 laminin chains; vitronectin; thrombospondin-1; urokinase; EMMPRIN; and cathepsins B and L were unchanged around INTACS in all 3 cases compared with normal. Recently, INTACS has acquired new interest as an alternative treatment of keratoconus. [5][6][7][8][9][10] The rationale is that INTACS not only flattens the central cornea but also corrects some of the astigmatic component. The corneal profile becomes more symmetrical, usually allowing better correction with glasses and contact lenses. Given that, for these patients, the alternative would be penetrating keratoplasty, INTACS may delay the need for this option. 10,11 Midstromal semicircular channels for INTACS ring insertion are created by a mechanical system with a blunt spiral device. 1,12,13 Despite the streamlined mechanistic procedure, attempts were made to improve control over the depth and shape of the channels. A femtosecond laser mounted on a delivery system capable of creating an intrastromal pattern of virtually any shape was recently used to create channels for INTACS insertion. 10 This method may be technically easier and more precise, reflecting better final outcomes. Conclusions-AbnormalKeratectasia is a rare but serious complication of laser vision correction of any refractive errors. It occurs mostly after LASIK but was also described after surface excimer laser ablation (photorefractive keratectomy). 14-16 It involves severe refractive changes mostly occurring several years after the surgery, which are caused by thinning and sagging of the corneal profile, similar to keratoconus.The etiology of this complication remains uncertain. In some cases, preexisting forme fruste keratoconus was documented. 17,18 Other cases could be caused by a me...

Intrastromal Corneal Ring Segments Implantation in Patients with Mild Keratoconus

“…That suggests that the ICRS promote indirectly a kind of reorganization by collagen lamellas of corneal stroma contributing for better values of keratometry, asphericity and visual acuity, which raises the possibility of corneal shrinkage after the procedure. Such a presumption is corroborated based on other studies that demonstrated the formation of collagen and other extracellular matrix components 21 after ICRS implantation.…”

Validation of an Experimental Animal Model for Corneal Additive Surgery

“…Some histological studies of human corneas that were removed for keratoplasty due to ICRS complications or refractive failure have been reported. However, these studies do not established a temporal sequence of events, and the number of eyes analyzed was small [27,28]. For these reasons we thought it was necessary to develop an experimental animal model to study clinical, optical, and histological events together throughout the wound healing process after Ferrara ICRS implantation in good and complicated eyes.…”

Tissue reaction after intrastromal corneal ring implantation in an experimental animal model

“…However, these techniques are not able to describe the cellular events of corneal wound healing around the implanted segments. The histological studies in human corneas were performed on corneas explanted for keratoplasty at different time points, but no temporal sequence of events was established, and the number of eyes analyzed was generally very small [19][20][21].…”

“…Histopathological studies in animals have been performed in rabbits [17] and hens [22]. However, there are relatively few studies that have reported the complete histological changes that occur during the wound healing process of both human and animal corneas [17,18,20,21]. These studies included only a small number of eyes and did not show the evolution of the process over a sufficient amount of time, especially soon after surgery, to document all of the changes that take place.…”

“…Understanding this process could contribute to the safety and efficacy of refractive surgical procedures, and it may also permit the development of methods for avoiding complications that can arise. Most of the histological studies after ICRS implantation have been carried out in human corneal tissue after complications or when the cornea was removed for keratoplasty [18][19][20][21]. Histopathological studies in animals have been performed in rabbits [17] and hens [22].…”