Controlled Adverse Environment Chambers Advance the Study of New DED Treatments
By Marguerite McDonald, MD, FACS
Evaluating potential new treatments, and even the effectiveness of existing therapies for dry eye disease (DED), has long been an extraordinary challenge.
Age, neuroendocrine function, meibomian and lacrimal gland status and concomitant chronic disease, particularly type 2 diabetes, all can impact how a patient’s eyes respond to environmental stress, and to treatment. When you add to that variables like temperature, wind, humidity, contact lenses, pollutants and long hours in front of electronic screens, evaluating symptoms and treatment responses across a patient population in a clinical trial becomes extremely difficult.
At the same time, these variables make it necessary to recruit a very large patient population in order to get meaningful results. Yet, these studies of dry eye disease treatments traditionally have had strict inclusion and exclusion criteria, which has produced a very low patient enrollment rate.
Fortunately for physicians and researchers hoping to effectively treat DED, a solution has become available: the controlled adverse environment (CAE).
As its name implies, the CAE is a closed chamber, in which environmental factors are controlled. During a trial using a CAE, study subjects who have been pre-screened for signs and symptoms are seated in the chamber. There they experience a "perfect storm" of highly standardized conditions designed to overwhelm a dry eye patient’s ability to maintain stable tear film: low humidity, increased air flow, and constant visual tasking.
One caveat: reflex tearing can confound results of a CAE exposure, because tearing may produce temporary relief from DED discomfort in some patients. Therefore, clinical trials often exclude patients with reflex tearing.
But when study subjects consistently respond to CAE exposure with worsened symptoms, this produces a consistent baseline. Consequently, the first and most important function of a CAE is to provide a cohort of study subjects with known and reproducible DED.
The second, critical benefit of the CAE is the opportunity it provides to obtain validated and reproduceable data regarding subjects’ response to exposure to the adverse conditions within the chamber, and to the efficacy of a therapy. What’s more, a controlled CAE environment provides an opportunity to immediately measure and evaluate both the disease baseline and the response to therapy. No longer do researchers have to rely on subjects to accurately remember and rate their symptoms and the relief they experienced.
Since its introduction, the CAE has been used to evaluate a number of drugs and devices whose creators were seeking approval from the U.S. Food and Drug Administration. These include an antihistamine, an anti-inflammatory/corticosteroid, a mitochondrial-targeted antioxidant, and contact lenses, among many others.
The CAE chamber is a model that has been widely accepted by both the research and regulatory communities as an effective means to gain reliable data when evaluating the efficacy of potential new dry eye treatments.
Marguerite McDonald, MD, FACS, with OCLI on Long Island, NY, is clinical professor of Ophthalmology at NYU Langone Medical Center, NY, and clinical professor of Ophthalmology at Tulane University Health Sciences Center, New Orleans, Louisiana.