Figure 3-8 Corneal pannus. (Courtesy of Kirk R. Wilhelmus, MD.)
Clinical Approach to Dry Eye
The term dry eye has been defined as “a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear-film instability with potential damage to the ocular surface” (Dry Eye Workshop, 2007).
Dry eye represents a disturbance of the lacrimal functional unit (LFU), an integrated system comprising the lacrimal glands, ocular surface (cornea, conjunctiva, and meibomian glands), and eyelids, as well as the sensory and motor nerves that connect them (see Chapter 1, Fig 1-2). The LFU regulates the major components of the tear film and responds to environmental, endocrinologic, and cortical influences. Its overall functions are to preserve
tear-film integrity (by carrying out lubricating, antimicrobial, and nutritional roles)
ocular surface health (by maintaining corneal transparency and surface stem cell population) the quality of the image projected onto the retina
Dry eye is one of the most common reasons for ophthalmic consultation. It becomes increasingly prevalent with age, affecting approximately 10% of those age 30–60 and 15% of adults over age 65. Most epidemiologic studies have demonstrated a higher prevalence among women; it seems to occur
with equal prevalence in all racial and ethnic groups.
The psychological problems associated with a highly symptomatic, incurable, chronic disease can require considerable support. Quality-of-life studies have shown that the impact of moderate to severe dry eye is similar to that of having moderate to severe angina. Organizations such as the Sjögren’s Syndrome Foundation (www.sjogrens.org) can provide valuable resources to these patients. In certain settings, consultation with physicians who specialize in pain management can be very useful.
Mechanisms of Dry Eye
The core mechanisms of dry eye are believed to be driven by tear hyperosmolarity, tear-film instability, and inflammation. The cycle of events is shown in Figure 3-9. Tear hyperosmolarity stresses the surface epithelium and leads to the release of inflammatory mediators, which disrupt the junctions between the superficial epithelial cells. T cells can then infiltrate the epithelium and in turn produce cytokines such as tumor necrosis factor-positive and interleukin-1-positive. These cytokines promote accelerated detachment of the epithelial cells and apoptosis (programmed cell death). This results in further barrier disruption and influx of inflammatory cells, creating a vicious circle.
Figure 3-9 The mechanisms of dry eye. (Modified with permission from The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007;5(2):75–92.)
A diagnostic classification scheme has been established; it separates dry eye patients into those
with aqueous tear deficiency (ATD) and those with evaporative dry eye (Fig 3-10). In ATD, T-cell– mediated inflammation of the lacrimal gland occurs, leading to diminished tear production and the propagation of inflammatory mediators on the ocular surface. By contrast, the primary abnormality in evaporative dry eye is meibomian gland dysfunction (MGD), in which altered lipid metabolism causes the transition from unsaturated to saturated fats, altering the meibum and obstructing the glands. This leads to tear-film instability, tear evaporation, and tear hyperosmolarity, initiating the inflammatory cycle.
Figure 3-10 Diagnostic classification scheme for dry eye disorders. (Courtesy of Minas T. Coroneo, MD.)
Tear-film instability can also be initiated by other conditions, including xerophthalmia, ocular allergy, contact lens wear, dietary consumption of a high ratio n-6 to n-3 essential fatty acids, diabetes
mellitus, cigarette smoking, prolonged usage of video displays, and long-term use of medications with topical preservatives such as benzalkonium chloride.
Epithelial injury stimulates corneal nerve endings, leading to symptoms such as ocular discomfort, increased blinking, and, potentially, compensatory reflex lacrimal tear secretion. Loss of normal mucins at the ocular surface contributes to symptoms by increasing frictional resistance between the eyelids and globe. During this period, the high reflex input may cause neurogenic inflammation within the lacrimal gland.
Tear delivery may be obstructed by cicatricial conjunctival scarring or reduced by a loss of sensory reflex drive to the lacrimal gland from the ocular surface; etiologies may include refractive surgery (eg, LASIK dry eye), contact lens wear, and chronic abuse of topical anesthetics. Individual etiologies often cause dry eye via several interacting mechanisms.
American Academy of Ophthalmology Cornea/External Disease Panel. Preferred Practice Pattern Guidelines. Dry Eye Syndrome. San Francisco: American Academy of Ophthalmology; 2011. Available at: www.aao.org/ppp.
The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007;5(2):75–92.
Nichols KK, Foulks GN, Bron AJ, et al. The international workshop on meibomian gland dysfunction: executive summary. Invest Ophthalmol Vis Sci. 2011;52(4):1922–1929.
Pflugfelder SC. Tear dysfunction and the cornea: LXVIII Edward Jackson Memorial Lecture. Am J Ophthalmol. 2011;152(6):900–909. Epub 2011 Oct 22.
Stevenson W, Chauhan SK, Dana R. Dry eye disease: an immune-mediated ocular surface disorder. Arch Ophthalmol. 2012;130(1):90–100.
Aqueous Tear Deficiency
The clinical presentation of ATD ranges from mild ocular irritation with minimal ocular surface disease to severe and disabling disease. Symptoms tend to be worse toward the end of the day, with prolonged use of the eyes (exacerbated by the reduced blink rate associated with computer usage), or with exposure to environmental extremes (eg, lower levels of humidity associated with indoor heating). Patients commonly report burning, a dry sensation, photophobia, and blurred vision. Rapid assessment of dry eye can be achieved by the “stare test”: after a few blinks, a patient is asked to look at a visual acuity chart; the time until the image blurs should be more than 8 seconds.
Signs of ATD include bulbar conjunctival hyperemia, a decreased tear meniscus, an irregular corneal surface, and debris in the tear film. Slit-lamp examination of the inferior tear meniscus (which is normally 1.0 mm in height and convex) is essential. A tear meniscus that is 0.3 mm or less is considered abnormal. Epithelial keratopathy, which can be fine and granular, coarse, or confluent, is best demonstrated following the instillation of lissamine green, rose bengal, or fluorescein. Rose bengal and lissamine green staining can be more sensitive than fluorescein staining in revealing early or mild cases of keratoconjunctivitis sicca (KCS); the staining may be seen at the nasal and temporal limbus and/or inferior paracentral cornea (exposure staining).
In severe ATD, filaments and mucous plaques may be seen. Filaments are strands of epithelial cells attached to the surface of the cornea over a core of mucus. Filamentary keratopathy can be quite painful, as these strands are firmly attached to the richly innervated surface epithelium (Fig 3-11). Marginal or paracentral thinning and even perforation can occur in severe dry eye. Incomplete blinking is frequently noted. Advanced disease may also involve corneal calcification (band keratopathy), particularly in association with certain topical medications (especially glaucoma medications), and keratinization of the cornea and conjunctiva. Clinicians may find useful a classification based on disease severity (Table 3-4).
See Chapter 2 for further discussion of tests for tear production.