Keratoconus and related noninflammatory corneal thinning disorders

Biomechanical properties of keratoconus and normal corneas

Chemical injuries of the eye: current concepts in pathophysiology and therapy.

Deep anterior lamellar keratoplasty as an alternative to penetrating keratoplasty a report by the american academy of ophthalmology

Summary
This review of connective tissue repair has attempted to place into historical perspective information obtained by newer approaches. The literature review is incomplete, as it was unfortunately necessary to leave many interesting studies out of the discussion. Emphasis has been placed upon what is known of the inflammatory response, the fine structure of the connective tissue cells in healing wounds and with correlated chemical findings in these tissues.

An optimal inflammatory response appears to be an important, rapid, non-specific stimulus for fibroplasia. It is not clear how inflammation exerts this effect. The inflammatory cells and their enzymes markedly alter the extracellular matrix of injured tissue. The matrix of connective tissue may itself participate in the control of its own synthesis and degradation. It is possible that modification of this environment by injury and/or inflammation with ensuing matrix alteration may provide a stimulus for cell migration and protein synthesis. The converse may also be true, that is, a given level of matrix concentration may have an inhibitory effect upon the connective tissue cells. The inter-relationships between the connective tissue matrix and the cells, and the possibilities of feedback mechanisms playing a role in maintaining a balance between these two are important areas for future investigation. In this regard, additional questions may be asked concerning the role of the fibroblast in remodelling and degradation of connective tissue. It is not yet clear how important a balance between collagenolytic enzymes and the solubility states, or stability, of collagen are in each connective tissue. It will be interesting to determine which cells make collagenolytic and/or proteolytic enzymes upon appropriate stimulus.

It is possible to distinguish between the fibroblast and the monocyte, or potential macrophage with the electron microscope. The rough endoplasmic reticulum with its large numbers of attached ribosomes is extensively developed in the fibroblast in contrast to the monocyte. The endoplasmic reticulum sequesters collagen precursors and other secretory proteins for transport either directly to the extracellular space, as appears to be the case for collagen, or to the Golgi complex as is the case for other exportable proteins. Collagen precursors are secreted into the environment and are not shed from within the cell surface.

A number of cytoplasmic alterations have been described for fibroblasts and other cells during various pathological states. The significance of these alterations is not clear. It will be important to distinguish between specific and non-specific responses to injury, if these alterations are to aid us in understanding the various cellular responses.

The source of the fibroblasts in granulation tissue appears to be mesenchymal cells from adjacent tissues rather than blood-borne precursors. Although contact inhibition can be demonstrated in vitro, it is not clear how important this phenomenon is in vivo, nor are the reasons for the ability of some tissues to heal by regeneration rather than by scar tissue formation understood.

These and many other questions remain to be answered. The healing wound is multifaceted and presents the opportunity for systematic investigation into the problems of cell proliferation, cell and matrix interactions, and protein synthesis in vivo and it also can help to further our understanding of the ubiquitous fibroblast and its complex extracellular matrix.

The fibroblast and wound repair

The tensile strength of central and peripheral penetrating corneal wounds was measured. The gain of strength of central wounds at different time intervals was recorded up to 100 days. Peripheral corneal wounds healed faster than central wounds. Permanent closure of eye lids had no effect on the gain of tensile strength, nor did the presence of a fornix-based conjunctival flap affect the healing of limbal wounds. Absence of corneal epithelium markedly decreased the gain of tensile strength of central wounds. During the first 12 postoperative days, no tensile strength could be measured; after that time a slow healing began. A conjunctival flap restored normal healing of the denuded wounds; however, a silicone membrane between the flap and the cornea again drastically reduced wound healing.

The tensile strength of corneal wounds.

A comparison of penetrating keratoplasty and lamellar keratoplasty in the surgical management of keratoconus.

hitact calf corneas and calf corneas with epithelium and endothelium removed were incubated in vitro with inorganic sulfate-S for 6 hours at 38° C. The incorporation of S into the nondialyzable substances (essentially mucopolysaccharides) was measured. No significant difference was found between the S incorporation of the denuded stroma and that of the intact cornea. Calf corneal stromas, swollen and normally hydrated, were similarly incubated in vitro. The siuelling per se had no effect on the S incorporation. The corneal epithelium was removed from one eye of rabbits in vivo, and inorganic sulfate-S was immediately injected intravenously. The absence of epithelium caused a more rapid diffusion of the sulfateS ion into the stroma than occurred in the control eye. Isotope incorporation, in the absence of epithelium, ivas lower near the anterior surface and slightly higher in the posterior stroma within the first 24 hours as compared with the normal cornea. When the endothelium toas removed from the rabbit cornea in vivo and sulfate-S was administered intravenously, the results showed only a slight decrease in the rate of mucopolysaccharide synthesis in the stroma. Histologic studies were carried out on rabbit corneas from which the epithelium had been removed and kept away for up to 10 days. The stroma cells survived throughout the stroma unless undue trauma had occurred. Near the anterior surface, however, some of the keratocytes transformed into fibroblasts. Following removal of the endothelium, the corneas could be folloived histologically for up to 6 weeks. Here also, the keratocytes survived and the picture was similar when both epithelium and endothelium had been removed. Following removal of the endothelium, eosinophilic and metachromatic material accumulated in the anterior stroma and, eventually, in the basal cells of the epithelium, seemingly washed through the stroma to the corneal surface by a flow of fluid from the anterior chamber. It icas concluded that—at least for a limited time—the stromal cells can function independently of the epithelium and the endothelium.

Antonio R. Gasset

Papers

The tensile strength of corneal wounds.

A comparison of penetrating keratoplasty and lamellar keratoplasty in the surgical management of keratoconus.

The effect of the absence of corneal epithelium or endothelium on the stromal keratocytes.

Corticosteroids in corneal wound healing.

Tear glucose detection of hyperglycemia.