Current Concepts in Ocular Surface Reconstruction

Diseases that affect the limbal stem cells are multifactorial and present with different stages of severity. The most important features to be considered in evaluating these patients include the degree of limbal stem cell loss, the extent of conjunctival disease, and the presence and etiology of ocular surface inflammation. Other important factors are tear film and eyelid abnormalities, keratinization of the ocular surface, laterality of the disease process, health and age of the patient. Careful consideration of all of these factors help tremendously in tailoring the most suitable method of treatment for each patient. The management of severe ocular surface disease has benefited from numerous advances in recent years. At one time, available techniques for visual rehabilitation consisted of superficial keratectomy, use of artificial tears, tarsorraphy as well as lamellar and penetrating keratoplasty. A lamellar or penetrating keratoplasty procedure resulted in a stable surface only for as long as the donor epithelium was present and once the epithelium sloughed off, the ocular surface failed due to conjunctivalization. The last few decades enjoyed the development and, especially, progress of new ocular surface reconstruction techniques such as amniotic membrane transplantation, limbal stem cell transplant procedures, transplantation of cultivated oral mucosal or limbal stem cell sheets. This review will briefly focus on the indications and methodology of each procedure and the currently available clinical data on the results of these procedures.     

Immunoregulation on the Ocular Surface: 2nd Cullen Symposium

A one-day symposium with 20 invited participants was held to review current knowledge regarding immunoregulation in the ocular surface and cornea. The program consisted of 11 lectures on various aspects of ocular and systemic immunoregulation, followed by a group discussion to formulate regulatory pathways. The ocular surface and its secondary lymphoid tissues contain numerous components of the innate and adaptive immune systems, which modulate the immune response to suppress or prevent excessive damaging immune reactions. These include factors that regulate induction of the immune response (afferent loop), as well as effector cells and soluble factors (efferent loop). The ocular surface is an immunologically active mucosal site that contains numerous mechanisms to regulate the immune response to prevent tissue destruction and vision loss.     

Wakayama Symposium: New Therapies for Modulation of Epithelialization in Corneal Wound Healing

Many factors are involved in the corneal wound healing mechanism, including adhesion, migration, and proliferation of corneal epithelial cells. Abnormal corneal wound healing leads to corneal edema, neovascularization, scar formation, and poor vision. Three agents, 17β-estradiol, nicergoline, and β-glucan, have demonstrated positive effects on the wound healing response in laboratory experiments and may be of help in controlling wound healing in corneas that have suffered epithelial damage or have undergone refractive surgery.     

Wakayama Symposium: Dependence of Corneal Epithelial Homeostasis on Transient Receptor Potential Function

Transient receptor potential (TRP) protein expression in the corneal epithelial layer contributes to the maintenance of tissue transparency. These proteins are members of a superfamily that form nonselective cation channels. This superfamily is a product of 28 different genes that are subdivided into six different subfamilies according to differences in amino acid sequence homology. The six subfamilies have very diverse functions. They are: 1) canonical (C); 2) vanilloid (V); 3) melastatin (M); 4) ankyrin (A); 5) polycystin (PP); 6) mucolipin (ML). TRP channels are composed of four monomeric subunits that are either members of the same or different subfamilies. In the corneal epithelium, C, V, and A subfamily subtype expression was identified. These include TRPV1-4, TRPC4, and TRPA1, which upon activation by either environmental stresses or selective ligands induce adaptive responses to stresses through transient increases in Ca²⁺ influx. Even though TRPs' Ca²⁺ permeability is variable relative to other cations, TRP activation is sufficient to stimulate mitogen-activated protein kinase cascade signaling through epidermal growth factor receptor transactivation. The host of TRP-mediated responses includes stimulation of cell proliferation, migration, regulatory volume behavior, and the release of a host of proinflammatory cytokines and chemoattractants. This review describes the multiple roles of these different channel subtypes in eliciting responses underlying maintenance of corneal epithelial function in health and disease.     

Current and Upcoming Therapies for Ocular Surface Chemical Injuries

Chemical injuries frequently result in vision loss, disfigurement, and challenging ocular surface complications. Acute interventions are directed at decreasing the extent of the injury, suppressing inflammation, and promoting ocular surface re-epithelialization. Chronically, management involves controlling inflammation along with rehabilitation and reconstruction of the ocular surface. Future therapies aimed at inhibiting neovascularization and promoting ocular surface regeneration should provide more effective treatment options for the management of ocular chemical injuries.     

Wakayama Symposium: Epithelial-Mesenchymal Interaction Regulates Tissue Formation and Characteristics: Insights for Corneal Development

Epithelial-mesenchymal interactions and epithelial-to-mesenchymal transition (EMT) are essential during tissue formation and organ morphogenesis. The roles of Wnt/β-catenin signaling have been studied in many organ systems. In this review, we describe the importance of Wnt/β-catenin signaling by comparing skin and corneal development of Wnt/β-catenin gain of function (GOF) mutant mice. In the skin, Wnt/β-catenin signals have been suggested to play essential roles in regulating cell-cell interaction, cell proliferation and differentiation. Wnt signaling may be associated with basal cell carcinoma (BCC) of the skin. In the case of cornea, β-catenin GOF mutation leads to epithelial hyperplasia. Investigation of the mechanisms of growth factor signaling as a reference to general organogenesis could provide profound insights for understanding corneal development and pathogenesis.     

Wakayama Symposium: Modulation of Wound Healing Response in the Corneal Stroma by Osteopontin and Tenascin-C

The extracellular matrix components osteopontin and tenascin-C are ligands of α9 integrin, and both play roles in corneal wound fibrosis and neovascularization. It has been shown that loss of osteopontin impairs closure of incisional wounds in the mouse cornea. Detailed analyses suggest that the loss of osteopontin reduces macrophage invasion and myofibroblast differentiation in the healing stroma in association with suppression of fibrogenic gene expression in response to injury. Cultured ocular fibroblasts derived from knockout mice showed an impairment of activation of p38 MAPK and Smad3 upon exposure to transforming growth factor β1. The loss of tenascin-C delays stromal healing in association with suppression of fibrogenic gene expression and macrophage invasion. With regard to neovascularization, the loss of either osteopontin or tenascin-C suppressed the growth of new blood vessels from the limbal region toward the central cornea in response to corneal cauterization in mice. Gene expression analysis further showed that lack of osteopontin or tenascin-C resulted in inhibition of angiogenic and proinflammatory gene expression. In conclusion, osteopontin or tenascin-C, α9 integrin ligands, play an important role in stromal healing (or fibrosis) and neovascularization in mouse cornea.     

Eye Cancer Related Glaucoma: Current Concepts

Eye cancer-related glaucomas occur through a variety of mechanisms. They can be challenging to diagnose and are often refractory to treatment. The literature reveals the variety of ways eye cancers cause glaucoma. Mechanisms include direct invasion, infiltration, or seeding of the aqueous outflow structures as well as indirect processes, such as compressive angle closure and anterior segment neovascularization. This review describes established, evolving, and new diagnostic techniques (e.g., high-frequency ultrasound and aspiration biopsy techniques). Treatment options typically depend upon the tumor type (primary or secondary), its location, and mechanism of glaucoma. However, they include standard pharmacologic, laser, incisional, and radiotherapeutic approaches. We hope this review leads to early detection and optimum treatment of eye cancer-related glaucomas. Clearly, prompt diagnosis and management of eye cancer-related glaucoma offers an opportunity to both preserve vision and the patient's life.