discovering dry eye
Evaluating Dry Eye Disease and Treatments
BY BARBARA CAFFERY, OD, MS, FAAO
Recently an anti-inflammatory agent, Restasis (topical cyclosporine, Allergan) received FDA approval as an agent to treat dry eye. As usual, clinical trials helped evaluate the product prior to approval. The difficulty of evaluating the efficacy of dry eye treatments is clear when you consider the process and the outcomes. Dry eye is a chronic disease that waxes and wanes with the seasons, visual tasks and fatigue. These variable factors can greatly influence the results of any treatment plan.
Our tools for evaluating the degree of the disease and the outcomes of treatment are fraught with problems. How the patient feels and what the ocular surface looks like are often two entirely different things. Patients with low Schirmer scores and a good deal of staining can feel mildly irritated, while others with severe symptoms appear quite clear under the biomicroscope. How do we then classify the disease: mild, moderate or severe?
The tests themselves have standardization problems. You can perform Schirmer tests with or without anesthetic. Tear film break-up time varies and can be greatly influenced by non-uniform dosages of fluorescein.
The area of the cornea that stains may be diagnostic. You should grade staining of the cornea in several quadrants, the inferior being more diagnostic for lid disease. Conjunctival staining can differ depending on which stain you use and whether you use liquid or strip dye. The wait time between dye instillation and observation can influence the results. Researchers must be very careful when administering tests and grading and comparing treatment results.
There is also so much that we cannot measure. Normal clinical procedure does not allow for measuring osmolarity, tear inflammatory products or protein levels, all of which would help us understand the condition of the ocular surface.
Test repeatability is not reliable. We really have no idea whether the diagnosis day findings would match findings later that week or that month. What if the diagnostic day is a good day, and the day you evaluate the treatment is a bad day?
How should we grade the symptoms? How long does it take to change the symptoms even after the surface appears better? How much of a change is enough?
Variability in Clinical Trials
Consider the subject in the clinical trial. What sorts of complications can he bring to the table? First of all, he may decide to make a "lifestyle change" during the trial. If someone stops smoking, starts exercising or changes his diet to one of low fat, fruits and vegetables, it may affect his tear secretions and/or ocular symptoms. In this age of information, patients consult web sites for the "best" new treatment. From vitamins to minerals to linseed oil, patients may change their intake and possibly affect their tears, or the placebo effect may change the way they feel.
All of these questions demonstrate the challenge of evaluating dry eye treatments. As researchers we can be rigorous about our observations and the exactness of our work. We can also educate our subjects and patients about their need to report all changes in their lifestyles to us. Finally, we must determine new and better ways to evaluate and monitor this chronic condition.
Dr. Caffery has practiced optometry in Toronto, Canada, in a group setting dedicated to contact lens and tear film research since 1977.