Dry Eye

The serum is thought to be effective because of the growth factors and cytokines contained in the serum. Many protein factors, such as Keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF), are paracrine factors that maintain the tear film function and a healthy cornea, such as through the regulation of the proliferation, migration and differentiation of the limbal epithelial cells. Recent studies of the tear film using laser interferometry and confocal microscopy indicates that the human tear film is 30 to 40 microns thick, more than four times thicker than earlier estimates (see for example Prydal, et al. 1992 and Prydal, et al. 2005).

Based on tear film physiology and clinical observations, tear film abnormalities are commonly designated by focus on a specific deficiency, such as an aqueous tear deficiency, keratoconjunctivitis sicca (KCS), a mucin deficiency, a lipid abnormality, an impaired lid function, or an epitheliopathy. Although clinically useful, the simplistic concept of a lack of one component of the tear film as the cause of dry eye has given way to a much more sophisticated view of ocular surface disease that involves: (1) the health and regulation of the various glands contributing secretions to the tear film, (2) changes in the tear film itself, such as in osmolality and content of proteins and inflammatory mediators, and (3) what is viewed as a sort of final common pathway, the subsequent changes to the ocular surface (See McKenzie, et al. 2000). In fact, many clinicians and authors prefer the term “ocular surface disease” over “dry eye”, for it is change to the ocular surface, whatever the original cause, that results in the significant signs and symptoms of dry eye. The discomfort of ocular surface disease is expressed in ocular symptoms, such as dryness, grittiness, burning, soreness or scratchiness, with variation among individuals. These symptoms can also be exacerbated by factors such as environmental conditions and contact lens wear. The combination of varying clinical signs and symptoms has also been termed dry eye syndrome. Unique characteristics of normal human secreted ocular mucins are their wide size range and short oligosaccharide side chains.

The secreted ocular mucins are relatively large molecules, and have a significant role in the gel-forming nature of the tear film. The model of the greater part of the tear film being a highly hydrated mucus gel, rather than simply a watery aqueous layer, is becoming increasingly accepted. The viscoelasticity of the tear film derives from the specific structure and gel-forming properties of the ocular mucins, and allows the tear film to absorb the sheer force of the blink, which would otherwise irritate and damage the ocular surface.

The transmembrane mucin, on the other hand, serves more as a protective layer on the actual cellular surface of the ocular epithelium, functioning to directly protect and lubricate the ocular surface, as well as to anchor the highly hydrated gel (mucus) of the tear film gelforming mucins, thereby assisting in the spreading and stability of the tear film over the ocular surface.

The belief that the tear film is aqueous based and the ocular surface changes seen in Sjogren’s syndrome are due to desiccation, cause eye care practitioners to water the dry eye. However, studies show that, as stated above, the tear film is dominated by proteins and mucin and not water. (See Nelson, et al. 1992) The human tear film is not a 7-10 thin film, but a 30-35 p.m thick mucin gel. Bicarbonate may be critical to forming this gel as it is in forming the bicarbonate mucin gel that protects the stomach from autodigestion. (See Ubels, et al. 1995) The hallmark of the aqueous deficient dry eye, rose bengal staining of the conjunctiva, is not produced by desiccated cells, but is due to a deficiency in the protective mucin gel. (See Gilbard, et al. 1992) The ocular surface changes in dry eye include conjunctival squamous metaplasia, loss of integrity of cell membranes and junctional structures (fluorescein staining), and loss of the integrity of the mucin layer (rose bengal staining).

Rose bengal staining and squamous metaplasia are not improved by the frequent application of non-preserved preparations. (See Nelson 1998) Bicarbonate and electrolyte solutions promote recovery of barrier function and ultrastructure in damaged ocular surface cells and increase corneal glycogen and goblet cell density. (See VanSetten 1990 and Kiatazawa, et al. 1990, respectively) These solutions, however, do not totally reverse ocular surface disease seen in Sjogren’s syndrome. Even with the addition of electrolytes and bicarbonate to artificial tears, watering the dry eye is not enough. It has been found that the application of autologous serum improved fluorescein and rose bengal scores and squamous metaplasia. This treatment also resulted in significant upregulation of MUC-1 in conjunctival epithelial cell cultures. The authors believed that the epidermal growth factor (EGF), vitamin A, and transforming growth factor (TGF) found in serum represent critical components missing from the tears of patients with Sjogren’s syndrome.

Others have speculated on the use of serum tears. (See Fox, et al. 1984) Tsubota et al. suggests that serum tears, alone, may not be sufficient to treat dry eye. For example it has been found that the presence of cytokines and retinol are critical for the growth, differentiation, and wound healing of the ocular surface. Artificial tears flush out debris; dilute substances trapped in the tear film, and increase tear clearance. They do not, however, provide all the factors critical for the maintenance and repair of the ocular surface.