Perspective
Advances in Understanding and Managing Dry Eye Disease

https://doi.org/10.1016/j.ajo.2008.05.016Get rights and content

Purpose

To present evidence from the literature and scientific meetings to support fundamental changes in concepts regarding the prevalence, pathogenesis, definition, diagnosis, management of dry eye disease (DED) and the prospects for the development of new therapies.

Design

Analysis and clinical perspective of the literature and recent presentations.

Methods

Review and interpretation of literature.

Results

The tear film and ocular surface form an integrated physiologic unit linking the surface epithelia and secretory glands via a neural network. This sensory-driven network regulates secretory activity in quantity and composition, supporting the homeostasis of the system. The tear film forms a metastable covering between blinks, subserving clear vision, and maintains the health and turnover of the ocular surface cells. Disturbance of intrinsic factors such as increasing age; hormonal balance; systemic or local autoimmune disease, or both; systemic drugs or extrinsic factors including topical medications; environmental stress; contact lens wear; or refractive surgery result in a final common pathway of events at the tear film and ocular surface, resulting in DED. Diagnosis of DED and the design of clinical trials for new drugs have been hampered by a lack of correlation between signs and symptoms and flawed endpoints; successful new drug applications likely will require new approaches, such as the use of objective biomarkers for disease severity.

Conclusions

Recent advances in our knowledge of the causation of DED open opportunities for improving diagnosis and disease management and for developing new, more effective therapies to manage this widely prevalent and debilitating disease state.

Section snippets

Structure and Function of the Tear Film and the Ocular Surface

Over the last two decades, substantial progress has been made in understanding the structural elements of the tear film, ocular surface, and the associated tissues that form a single integrated unit termed the lacrimal functional unit.1 This information has led to revised concepts about the way in which the tear film is formed and maintained and the pathophysiologic events operative in the development of dry eye. In addition, it has opened paths for new therapeutic interventions.

Traditionally,

Characteristics of Dry Eye Disease

There are a number of recognized risk factors for the development of dry eye. These include: aging; female gender; hormonal changes; systemic autoimmune disease (most prominently Sjögren syndrome); decreased corneal sensation; refractive surgery in which the corneal nerves are either severed or ablated; blinking abnormalities; drug effects; viral infections such as human immunodeficiency virus, cytomegalovirus, and hepatitis C; diabetes mellitus; vitamin A deficiency; and graft-versus-host

Dry Eye as a Disease

Dry eye has a number of names associated with it. These include: keratoconjunctivitis sicca, dry eye syndrome, and the more recently suggested dysfunctional tear syndrome. Dry eye develops in response to the presence of one or more risk factors listed above; in addition, environmental, workplace, or recreational stress—for example, arid atmosphere, constant wind currents, the presence of a contact lens, and prolonged use of video display screens—are factors that can initiate and exacerbate the

Prevalence of Dry Eye Disease

It has been known for many years that DED is a common clinical problem. Only recently, however, have valid quantitative data appeared that document the extent of DED. Surveys over the last 20 years have estimated the prevalence of DED to be between 5% to more than 30% at various ages.5 Different definitions of the disease at use in various studies make comparison difficult. In a survey by the American Academy of Ophthalmology, respondents reported that approximately 30% of patients seeking

Dry Eye Disease and Microbial Infection

The external eye has a number of defense mechanisms that protect the ocular surface against microbial infection.18 These include mechanical factors such as tearing and blinking, which remove noxious agents from contact with the ocular surface. In addition, immunity plays an important role. The immune system operating at the ocular surface is complex, involving both an immediate local innate system comprising cells and mechanisms that defend the host from infection by other organisms. Protective

Dry Eye Disease and its Effect on Vision

Patients with symptoms of ocular irritation suggestive of DED often also report more vague problems such as sensitivity to light, a decrease in reading, night driving difficulties, or ocular fatigue. Only in the past several years has it been recognized that these symptoms can be attributed to the effects of DED on vision. It is a common clinical experience that standard visual acuity (VA) testing with Snellen or Early Treatment Diabetic Retinopathy Study (ETDRS) charts seldom reveals a

Current Challenges in the Diagnosis and Management of Dry Eye Disease

It is a commonly held opinion that DED can be diagnosed largely on the basis of patient symptoms. Recently, a number of studies have called this impression into question. Only a small percent of patients with DED have been diagnosed.25 It has been documented that symptoms of DED do not necessarily reflect the severity of the disease.26 Clinicians have long know that many patients without clinical evidence of DED, such as staining of the ocular surface and decreased Schirmer test scores, are

Current Problems and Future Prospects in the Development of New Therapies

Advances in understanding the mechanisms operative in forming and maintaining a normal tear film and the pathologic breakdowns that occur in DED have led to a variety of novel interventional strategies. These include: secretogogues of aqueous tears, mucins and lipids, antievaporative compounds, immunomodulating agents that have anti-inflammatory effects, corticosteroids, cellular protective formulations, and tear film stabilizers. Although most of the results of clinical trials are proprietary,

Conclusions

What is not known is how effective the new agents are that have undergone clinical trials; what is known is that the methodology used to evaluate them is flawed. As new information becomes available, designs for clinical trials undoubtedly will undergo further evolution. This is critical to surmount the regulatory barriers to successful development of new, more efficacious treatment options for patients with DED. As new products become available, there will be a greater challenge to the

Dr Michael A. Lemp is a corneal specialist and the author of over 200 peer-reviewed scientific papers and editor of five books. He received his undergraduate, medical and residency training at Georgetown University and fellowship at the Massachusetts Eye & Ear Infirmary. Formerly a chair of ophthalmology at Georgetown, Dr Lemp current interests are in tear/ocular surface disease, drug development, and clinical trial design. He is a Clinical Professor at Georgetown and George Washington

References (33)

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Dr Michael A. Lemp is a corneal specialist and the author of over 200 peer-reviewed scientific papers and editor of five books. He received his undergraduate, medical and residency training at Georgetown University and fellowship at the Massachusetts Eye & Ear Infirmary. Formerly a chair of ophthalmology at Georgetown, Dr Lemp current interests are in tear/ocular surface disease, drug development, and clinical trial design. He is a Clinical Professor at Georgetown and George Washington Universities.

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