In my years of practice, I have seen a fair share of severe corneal injuries caused by blunt trauma, missile damage and chemical burns.
I have a few choice examples to share with you: Several years ago, my office was abuzz when a young man, who was clearly in pain, walked in with a thorn impaling his left cornea and iris. Last year, a young woman presented with corneal decompensation and ulceration caused by head trauma and facial paralysis. Recently, another young girl came in, complaining of a curling iron burn across her cornea.
Chemical burns and/or missile damage can result in severe inflammation, leading to a relentless, chronic scarring response. Often, scarring is the final result when corneal trauma progresses into granulation, and subsequently, necrosis.
If scarring develops in the cornea, commensurate vision loss follows. Should scarring occur in the conjunctiva, motility restrictions and surface breakdown will frequently result in dryness, exposure, inflammation and mechanical trauma.1
The good news is that new treatment options are available for severe corneal trauma. Many topical medications, such as epinastine, bacitracin, cyclosporine A and sodium sulfacetamide, have been adapted for ophthalmic utilization.
This article discusses three treatment options: ProKera (amniotic membrane, BioTissue, Inc.), FKBP and FK-506 protein derivatives, and Thymosin Beta 4 (T4).
ProKera
Scheffer C. G. Tseng, M.D., Ph.D., developed ProKera for corneal wound repair and ocular reconstructive surgery. ProKera combines amniotic membrane with a collagen band. This band handles like a large-diameter contact lens to effectively position the substrate directly over the cornea.
Studies have shown amniotic membrane to be effective in corneal wound repair.2 The amniotic membranes basement membrane contains type IV collagen, laminin 1, laminin 5, fibronectin and collagen VII.3 The collagen IV subchain is identical to that of the conjunctiva, and laminins are particularly effective in facilitating corneal epithelial cell adhesion. The amniotic membranes stroma contains growth factors, anti-angiogenic and anti- inflammatory proteins, and natural inhibitors to several proteases.4
ProKera can be used in cases of ulceration, persistent band keratopathy and stromal scarring. ProKera can reduce cicatricial complications, the frequency of limbal stem cell deficiency (except in severe grade 4 burns) and scarring and inflammation, and it aids in pterygium removal.5 For long-term storage, amniotic membrane must be kept frozen (-50C to -80C). Within one week of use, standard refrigeration is adequate. The ProKera can be left on the eye for up to 30 days.
FKBP and FK-506 (Tacrolimus) Derivatives
FKBP, an FK-506-binding protein, along with FK-506 and its derivatives, are showing promise in the field of wound healing. FKBP represents a family of proteins that have prolyl isomerase activity and are functionally similar to cyclophilins.6
FK-506, also known as tacrolimus, is an immunosuppressant molecule used to treat both patients after organ transplant and individuals who have autoimmune disorders.7
Ophthalmically, we have already been using a form of tacrolimus: cyclosporine A, which binds with cyclophilin. The FKBP-tacrolimus complex and the cyclosporin-cyclophilin complex inhibit calcineurin, a phosphatase that blocks signal transduction in the T-lymphocyte transduction pathway.8
FK-506-related compounds, particularly nonimmunosuppressive derivatives of FK-506, stimulate growth of keratinocytes independently and facilitate the regeneration of nerve fibers into previously damaged skin.
New research indicates that FK506 derivatives can be used as an immunophilin ligand to promote wound healing through re-epithelialization and rapid reinnervation.9
Thymosin Beta 4
Thymosin Beta 4 (RegeneRx) is an actin-regulating molecule that is
synthetically generated from the thymus gland.
It consists of 43 amino acid residues and is found in high concentrations of blood platelets, wound healing agents, immune-mediated responses and white blood cells.
The wound-healing cascade begins with an inflammatory phase, followed by a proliferative phase of cellular, immunomodulator and vascular migration. If successful, this acute wound process moves into a remodeling phase, in which tissue with minimum scar formation is healed. Should the proliferative phase be unsuccessful, the wound moves from an acute state into prolonged inflammation and chronic designation.
Studies have shown that T4 is involved in myriad biological activities, including regulation of actin, epithelialization, angiogenesis, apoptosis and anti-inflammation.5
T4 is currently in clinical trials to determine its efficacy in corneal wound repair.
Substantial research in these three areas holds promise for improved ocular healingfrom dry eye to LASIK (or surface ablation), from post-surgical management to blunt trauma, to ulcerative treatment and modulation of autoimmune response. Ophthalmic applications are just now beginning to garner a lot of research and exploration. With an aging population, the potential of these treatment modalities could be immense. Look for exciting new treatments in as little as five years from now.
Dr. Fuerst is a special guest columnist filling in for Paul Karpecki. He practices in
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10. Sosne G,
