Methodologies for the Study of Ocular Surface Disease

Abstract

The ability to obtain reliable results from clinical trials of therapies for ocular allergic disease and dry eye disease is often limited because of inadequate control of variables, such as environment, patient life style, compliance, and individual fluctuations that occur from one assessment visit to another. The controlled allergen challenge (CAC) model of allergic conjunctivitis allows signs and symptoms of the disease to be elicited in a physiologically accurate and reproducible manner. The rigid criteria for subject selection, the controlled allergic reaction, and the standardized and quantified grading systems allow for a reproducible baseline from which statistically and clinically significant differences between formulations can be assessed. Similarly, the controlled adverse environment (CAE) model for dry eye mimics the environmental stimuli that lead to ocular surface drying. Preselected subjects have a reproducible, homogeneous baseline reaction from which the effects of various treatments can be significantly evaluated and compared.

Introduction

Allergic conjunctivitides and dry eye diseases and conditions are prominent examples of highly variable ocular surface disorders. The unpredictability of each disorder lies in its pathogenesis, as the clinical manifestations can be dramatically modified by external stimuli. Allergic conjunctivitis (AC) is brought on by ocular exposure to airborne allergens in IgE sensitized individuals. The specific type of allergen sensitivity, the exposure level, and the degree of sensitivity to that allergen are the most important variables; yet other factors can further influence these parameters, creating an uncontrollable setting for precise scientific study of a highly heterogeneous population. Dry eye disease and conditions can arise from multiple etiologies that result in decreased tear production. Both the external environment (humidity, wind, sun exposure) and certain visual tasks can facilitate ocular drying and exacerbate signs and symptoms when an underlying pathology is present.

The concept of disease models has a long history, and such models have been used to study diseases in vitro, in animals, and in humans. The relatively benign and selflimiting nature of allergic conjunctivitis and mild dry eye in particular has made them ideal for human clinical study. This review will discuss the use of human models of these diseases, appropriately described as "challenge" models, and how they have increased our knowledge of the pathogenesis and treatment of both seasonal allergic conjunctivitis and dry eye disease.