Ординатура / Офтальмология / Английские материалы / Dry Eye and Ocular Surface Disorders_Pflugfelder, Beuerman, Elliot Stern_2004

Austin Mircheff University of Southern California Keck School of Medicine, Los Angeles, California, U.S.A.

Stephen C. Pflugfelder Baylor College of Medicine, Houston,

Texas, U.S.A.

Michael E. Stern Allergan, Inc., Irvine, California, U.S.A.

David A. Sullivan Harvard Medical School, Boston, Massachusetts,

U.S.A.

Donald T. H. Tan Singapore Eye Research Institute, and National University of Singapore, Singapore

Mei-Chuan Yang University of Minnesota, Minneapolis, Minnesota,

U.S.A.

Steven Yeh Baylor College of Medicine, Houston, Texas, U.S.A.

Michael T. Yen Baylor College of Medicine, Houston, Texas, U.S.A.

Figure 1 Pathogenesis of lacrimal keratoconjunctivitis (LKC). Dysfunction of the lacrimal functional unit manifests as altered tear-composition, ocular surface inflammation, and dysfunction of the tear secreting glands. Primary dysfunction of one component can lead to secondary dysfunction in others. All forms of lacrimal functional unit dysfunction can be recognized by the resulting tear film instability. Ocular discomfort and ocular surface disease, including apoptosis of glandular and epithelial cells, are important consequences of tear film instability. The overall disorder, previously called dry eye syndrome, is referred to in this book as lacrimal keratoconjunctivitis (LKC).

dysfunction), causes epithelial disease, and stimulates discomfort (Fig. 1). Primary dysfunction of any component of the lacrimal functional unit may be secondarily transferred across the entire system through its extensive neural connections (2). This concept accounts for the overlap in clinical features observed among the various subgroups of dry eye in the NEI scheme (1). We propose a more comprehensive definition of dry eye: a disorder whereby dysfunction of the lacrimal functional unit causes an unstable tear film which in turn promotes ocular surface inflammation, epithelial disease, and symptoms of discomfort (Table 1).

II.DRY EYE: AN OCULAR SURFACE INFLAMMATORY SYNDROME

Ocular surface inflammation is foremost among the consequences of the unstable and exhausted tear film that results from dysfunction of the integrated lacrimal functional unit. Failure of the tear film incites a constellation of inflammatory events on the ocular surface that involves both cellular and soluble mediators (3,4). This immune-based inflammatory response, which will be elaborated upon in Chapter 4, plays a major role in the corneal epithelial disease of dry eye, and because of the impact of inflammation on corneal sensory nerves, contributes substantially to ocular discomfort. Recognition of the key role of inflammation in the pathogenesis of dry eye underscores the need to consider dry eye as more than just a simple deficiency of one or more tear film components, as proposed in the NEI classification scheme. Continuing to view dry eye solely as a tear deficiency trivializes the complexity of this condition and its impact on ocular surface health.

Based on our current knowledge of dry eye, it is more appropriate to consider it as an ocular surface inflammatory syndrome rather than simply a tear film insufficiency. Indeed, the term keratoconjunctivitis sicca (KCS), used for decades to describe the ocular surface disease that develops in dry eye (5), by definition acknowledges an inflammatory etiology. In keeping with our broader definition of dry eye, the term lacrimal keratoconjunctivitis (LKC) seems more appropriate to describe the ocular surface inflammation that develops from tear film failure (Table 1). We will use this term and unified concept throughout this book.

III.THE CLINICAL IMPACT OF LACRIMAL KERATOCONJUNCTIVITIS

Patients with LKC typically experience ocular discomfort. The most common irritation symptoms include scratchiness, grittiness, foreign body sensation, burning, and itching; these symptoms are exacerbated by prolonged visual activity (e.g., viewing a video display terminal) and environmental stresses, such as low humidity and air drafts (6). LKC patients often complain of blurred and fluctuating vision that stimulates them to blink more frequently to clear their vision. Together, these symptoms are a considerable source of ocular fatigue; many patients report that they are unable to read or concentrate for more than a few minutes at a time.

LKC symptoms significantly impact quality of life as documented by utility scores. Utility scores quantitate how many years a subject would give up from the end of his or her life in exchange for avoiding a particular malady. Utility scores for dry eye (7) (Table 2) were similar to those of angina (8). The chronic and unremitting nature of dry eye syndrome can lead to despair, depression,

Table 2 Utility of Dry Eye in Comparison to Other Health States

a Co-morbidity explicitly incorporated in utility.

TTO = time trade-off method of utility determination: quantitates how many years a subject would give up from the end of his or her life to be free of a particular malady (on a relative scale of 0–1). Source: Data from Ref. 7.

decreased productivity, and, in some cases, permanent job disability (9). The physical and psychological impact of LKC symptoms is similar to that experienced by patients with other chronic regional pain syndromes such as lower back pain (9).

LKC can also cause considerable ocular morbidity. The thinned and unstable precorneal tear layer and the altered corneal epithelial barrier function that accompany LKC are major risk factors for sterile keratolysis (10,11) and microbial keratitis (12). Severe and recurrent corneal ulceration resulting from LKC can lead to reduced vision, blindness, or, in the worst cases, loss of the eye (13,14).

Preexisting LKC is an important cause of complications following corneal surgery, including penetrating keratoplasty and LASIK (15), leading to decreased vision, pain, epithelial and stromal wound healing problems, haze, ulceration and predisposition to microbial infections (6). Surgical amputation of the corneal sensory nerves that drive glandular secretion, a direct consequence of LASIK and other refractive procedures (16,17), negatively impacts the integrated ocular surface secretory gland functional unit (18). This exacerbates preexisting LKC (19), and likely results in new cases of dry eye as well.

Treatments for dry eye mostly attempt to increase the volume of the patient’s tear film. They range from over-the-counter artificial or lubricating tears to punctal plugs or surgery to occlude lacrimal drains. Symptoms may be treated with analgesics or anti-inflammatory therapeutics. Despite treatment, most dry eye patients report no improvement in their symptoms (20).

IV. THE SCOPE OF THE PROBLEM

The prevalence of dry eye in the general population is still not precisely known. In epidemiological studies of dry eye performed in a variety of patient populations (Table 3), the prevalence of symptoms has ranged from 6% of an Australian population 40 years and older (23) to 15% of a population over the age of 65 in Maryland, U.S.A. (21). The prevalence was lower when a combination of signs and symptoms were used as diagnostic criteria (i.e., 0.7% of patients with irritation symptoms and a Schirmer score ≤ 5 mm and rose bengal staining) in the Salisbury Eye Study (21). Using an estimated prevalence of 6% and the 2000 U.S. Census data, there are 7.1 million people in the United States over the age of 40 who experience dry eye symptoms. Most studies found increasing prevalence with age. Some studies indicated that the prevalence of dry eye is greater in women (Table 3), an association that has long been suspected by dry eye specialists. The variation in prevalence of dry eye in these studies is likely due to the different subjective and objective criteria used to define dry eye, although the different age ranges and ethnicities of the populations surveyed may have contributed.

constantly or often

NS = non significant association; S = significant association (p 0.05).

Dry eye is also prevalent in patients who have undergone LASIK, because this procedure interrupts corneal sensory nerves important for driving glandular secretion and, ultimately, for maintaining tear film stability. From 32 to 60% of patients experience ocular irritation and LKC in the first 6 months after LASIK (27–29). The high frequency of these symptoms may be due partly to the difficulty in clinically detecting preexisting mild LKC preoperatively. Although many patients may have had preexisting mild LKC that was exacerbated by LASIK, many others may be new cases of dry eye. Given the large numbers of LASIK procedures performed each year, 800,000 to 900,000 per year in the United States alone (30), surgical causes of dry eye are likely to increase its prevalence significantly.

Costs of LKC to society are substantial. Dry eye is one of the most common complaints that patients bring to visit eye care practitioners (6). In one study (20), more than 60% of dry eye patients surveyed (N = 74) had visited a physician for their dry eye symptoms in the year preceding the study; 64% reported using artificial tears regularly, more than 40% had punctal occlusions, and 30% reported the use of medications such as analgesics, antibiotics, and anti-inflam- matory agents to alleviate their symptoms. Despite treatment, over 76% of dry eye patients reported their symptoms as “the same” or “worse” than in the previous year; among the working patients, symptoms interfered with work for an average of 186 days per year, and the estimated cost of lost productivity was over $5000 per year. In another study (21) of an elderly population 65 years and older (N = 2520), 14.6% experienced one or more dry eye symptoms often or all the time; of these subjects, 25% used artificial tears or lubricants and 73% visited an eye care professional during the previous year. These reported figures are substantiated by estimates that global sales of artificial tears exceeded $540 million annually in 2002 (31). The market potential for efficacious therapeutic agents for dry eye is enormous, especially considering the inadequacy of existing therapies.

V.CONCLUSIONS

Dry eye, previously defined only as a tear film insufficiency, is now known to involve disruption of a complex functional unit: the ocular surface, the tearsecreting glands, and the neural network connecting them. Malfunction of any one of these components causes tear film instability and may also alter its composition, which in turn leads to ocular surface inflammation—a key player in the pathogenesis of dry eye. The outcome at best includes ocular fatigue; at worst, ocular surface damage and even morbidity.

Costs of dry eye include decreased productivity at work as well as increased spending for doctor visits and (often ineffective) remedies. The key to solving these problems is a better understanding of dry eye, an important prerequisite for developing more effective therapies.

VI. SUMMARY

1.Disease or degeneration of the lacrimal functional unit results in an unstable and unrefreshed tear film, frequently of altered composition, that can no longer support the normal functioning of the ocular surface.

2.Dysfunction of the lacrimal functional unit is accompanied by ocular surface inflammation that destabilizes the tear film, causes epithelial disease, and stimulates discomfort. We propose the term lacrimal keratoconjunctivitis (LKC) to describe more appropriately the constellation of pathologic events on the ocular surface that occurs in response to tear film failure.

3.LKC is a common condition. It becomes more prevalent with age and is more common in women.

4.LKC decreases quality of life and has a substantial cost to society.

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