The Mathematical Institute, University of Oxford, Eprints Archive

Predicted phenotypes of dry eye - proposed consequences of its natural history

Bron, A J and Yokoi, N and Gaffney, E. A. and Tiffany , J M (2009) Predicted phenotypes of dry eye - proposed consequences of its natural history. The Ocular Surface, 7 (2). pp. 78-92.

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This paper reviews current knowledge of the pathophysiology of dry eye and predicts that the clinical picture in late disease differs in both severity and quality from that in early disease. It is hypothesized that hybrid forms evolve, in which aqueous-deficient dry eye (ADDE) takes on features of evaporative dry eye (EDE) and vice versa. As a consequence, early and late forms may require different diagnostic criteria and respond to different therapeutic regimes. Tear hyperosmolarity plays a key role in the damage mechanism of dry eye, and ADDE is recognized to be a low-volume, hyperosmolar state. As ADDE advances, a progressive decrease in lacrimal secretion occurs, exacerbated by loss of the corneal reflex. This causes a decrease in tear volume, thinning of the aqueous tear film, and retarded spreading of the tear film lipid layer. The latter is hypothesized to cause an increase in evaporative water loss and an added evaporative component to the dry eye. Thus, in advanced disease, the hybrid state would be an organic ADDE, accompanied by a functional EDE in the absence of meibomian gland dysfunction. This functional EDE would respond to agents that expand the tear volume, restore corneal sensitivity, or provide an artificial tear film lipid layer. Conversely, we propose that in EDE, a compensatory lacrimal flow is reflexly maintained via the Lacrimal Functional Unit, by sensory drive from the ocular surface, so that EDE is initially a normal-to-high volume hyperosmolar state. It is suggested that this compensation is lost in advanced disease, as hyperosmolar and inflammatory damage reduce sensory drive. Thus, when the primary phenotype is EDE, it is predicted that with disease progression, a hybrid form evolves in which an aqueous-deficient component is added to the dry eye. The unique features of this functional ADDE are a reduced Schirmer test score with normal tear proteins of lacrimal origin. Since the lacrimal gland is envisaged to be normal in structure, it would be anticipated that the aqueous-deficient component would respond to lacrimal secretagogues in addition to agents that would expand tear volume and restore corneal sensitivity.

Item Type:Article
Subjects:A - C > Biology and other natural sciences
Research Groups:Centre for Mathematical Biology
ID Code:887
Deposited By: Eamonn Gaffney
Deposited On:15 Jan 2010 07:45
Last Modified:15 Jan 2010 07:45

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