Dry eye disease


Dry eye disease (DED) is one of the most common causes of visits to eye care professionals, with one in five eye care patients presenting with DED. Worldwide, the prevalence of DED is as high as 50%, with both signs and symptoms of DED increasing with age and occurring more frequently in women than in men. Furthermore, DED prevalence based on signs alone is as high as 75% in some populations. This makes DED a major global health concern with significant economic consequences for individuals and society through its detrimental effect on work productivity, quality of life, and vision, as well as the psychosocial impact of pain. In the United States alone, the average cost of DED management is over $10,000 per patient and $55 billion overall. The Tear Film & Ocular Surface Society Dry Eye Workshop II (TFOS DEWS II) was formed in March 2015 to achieve a global consensus concerning multiple aspects of DED from 150 clinical and basic science research experts around the world. Using the TFOS DEWS II report, published in July 2017, along with current DED knowledge, this chapter provides a comprehensive approach to the DED patient.


The definition of DED, as defined by TFOS DEWS II, is:

Dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles .

Classification of DED can be split into two large pathophysiologic categories: aqueous deficient and evaporative ( Fig. 27.1 ). Aqueous deficient DED describes conditions affecting lacrimal gland function, whereas evaporative DED describes conditions affecting the eyelid and/or ocular surface. These two categories exist as a continuum, and thus must both be evaluated and managed for every DED patient.

Fig. 27.1

Tear Film and Ocular Surface Society ( TFOS ) classification for dry eye. Schematic of a clinical decision algorithm to approach a patient with dry eye syndrome.

(From Craig JP, Nelson JD, Azar DT, et al. TFOS DEWS II Report Executive Summary. Ocul Surf . 2017;15(4):802–812.)

Subjective evaluation

The first step in evaluating a DED patient involves careful and thorough collecting of subjective information, which can be separated into nonocular and ocular risk factors and stratified by consistent, probable, or inconclusive risk factors for DED. Basic demographic information of age, sex, and race is important, as DED risk increases with increasing age, female sex, and Asian race. Systemic conditions such as connective tissue disease, Sjögren syndrome, androgen deficiency, and history of hematopoietic stem cell transplantation have all been identified as consistent risk factors for DED, whereas diabetes, rosacea, viral infection, thyroid disease, and psychiatric conditions are probable risk factors for DED. Reviewing the medication list is important because antihistamines, antidepressants, anxiolytics, isotretinoin, and estrogen replacement therapy are all consistent risk factors for DED. Anticholinergics, diuretics, and beta-blockers are probable risk factors for DED. Social history is crucial in the evaluation of DED, with environment factors, such as pollution, low humidity, and sick building syndrome, as well as computer use, all as consistent risk factors for DED and low fatty acid intake a probable risk factor for DED. Last but not least, a careful ocular history is necessary as contact lens wear is a consistent risk factor for DED, whereas pterygium and history of refractive surgery are probable risk factors for DED. Inconclusive risk factors for DED include Hispanic ethnicity, sarcoidosis, menopause, pregnancy, acne, history of botulinum toxin injection, multivitamins, oral contraceptives, smoking, and alcohol use ( Fig. 27.2 ).

Fig. 27.2

Risk factors for dry eye disease based on demographics, past medical history, medications, and social history. These factors should be asked when eliciting a history from the patient.

DED symptoms broadly include, but are not limited to, eye discomfort and visual disturbance. To help quantify DED symptoms, there are several validated questionnaires commonly used in clinical practice. One of the most comprehensive DED questionnaires is the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25), which consists of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question that takes approximately 10 minutes on average to administer in the interviewer format. Several shorter DED questionnaires exist, such as the Ocular Surface Disease Index (OSDI), which is a 12-item questionnaire designed to provide a rapid assessment of the symptoms of ocular irritation consistent with DED and their impact on vision-related functioning that provides a final score ranging from 0 to 100, which can stratify patients into normal (i.e., no DED), mild, moderate, or severe DED ( Fig. 27.3 ). Another quick option is the Dry Eye Questionnaire 5 (DEQ-5), which queries eye discomfort, eye dryness, and watery eyes, with scores over 6 suggesting DED and scores over 12 warranting testing to rule out Sjögren syndrome. The Standard Patient Evaluation of Eye Dryness (SPEED), like its name suggests, is fast and evaluates both the frequency and severity of DED symptoms in eight questions, each scored zero (no symptoms) to four (intolerable symptoms) for a final score out of 28. For preoperative refractive surgery patients, the American Society of Cataract and Refractive Surgery (ASCRS) modified the SPEED questionnaire (SPEED II) to include extra questions relevant to identifying DED in preoperative patients. The importance of neuropathic-like ocular pain in DED has garnered more attention recently and can be quantified using the Neuropathic Pain Symptom Inventory (NPSI) modified for eye pain (NPSI-Eye) that is composed of 12 questions, with 10 of the questions scored, giving a total score range of 0 to 100.

Fig. 27.3

Ocular Surface Disease Index ( OSDI ). A 12-item questionnaire for rapid assessment of a patient’s symptoms and functioning to stratify patients into normal, mild, moderate, or severe dry eye disease.

OSDI was originally developed by the Outcomes Research Group at Allergan Inc. See jamanetwork.com/journals/jamaophthalmology/fullarticle/413145 for more information.

Objective evaluation

Given the multifactorial nature of DED, the objective evaluation likewise must be multifaceted. The TFOS DEWS II diagnostic approach to DED begins with triaging questions and risk factor analysis (see earlier), followed by diagnostic tests and subtype classification tests ( Fig. 27.4 ). ASCRS recommends a focused clinical examination dubbed “Look, Lift, Pull, Push” to confirm the subtype, severity, and visual significance of DED. Asia Dry Eye Society created a tear film-oriented dry eye classification which suggests three types of dry eye: aqueous-deficient, decreased wettability, and increased evaporation, which can be practically diagnosed based solely on the patterns of fluorescein breakup. Regardless of the diagnostic approach used, it is important to understand what to look for on examination and what diagnostic testing is available to assess DED.

Fig. 27.4

Tear Film and Ocular Surface Society diagnostic approach to dry eye disease. The algorithm starts with triaging questions, followed by risk factor analysis. If the patient has dry eye disease based on screening questions, diagnostic testing will be indicated to allow classification into dry eye disease etiology and severity.

(From Craig JP, Nelson JD, Azar DT, et al. TFOS DEWS II report executive summary. Ocul Surf . 2017;15(4):802–812.)


DED can be associated with Sjögren syndrome, which is an autoimmune disease affecting the minor salivary glands and causing the clinical triad of keratoconjunctivitis sicca (dry eye), xerostomia (dry mouth), and inflammatory arthritis. Thus it is important to ask DED patients about mouth dryness or swollen glands. Classic markers of Sjögren syndrome are anti-Ro/SS-A, anti-La/SS-B, antinuclear antibody, and rheumatoid factor. Early makers of Sjögren syndrome include antibodies against salivary protein 1, parotid secretory protein, and carbonic anhydrase 6, and may be more accurate signals of early Sjögren syndrome. A diagnostic test kit is commercially available (Sjö®) that incorporates both the classic and early markers of Sjögren syndrome ( Table 27.1 ).

Table 27.1

Biomarkers for Sjögren syndrome

The Sjo test is a diagnostic test kit that assesses for both traditional and novel biomarkers of Sjögren syndrome. The novel biomarkers may help detect Sjögren syndrome earlier in the disease trajectory.

Biomarkers tested in Sjo® test

  • Salivary gland protein1 (SP-1)

  • Carbonic anhydrase VI (CA-6)

  • Parotid secretory protein (PSP)


  • Antinuclear antibody (ANA)

  • SS-A (Ro) antibody

  • SS-B (La) antibody

  • Rheumatoid factor (RF)


Several external signs exist that can help determine the etiology of DED. Periocular dermatitis, which can be associated with atopic dermatitis, is characterized by small red scaly papules and pustules around the eye. Allergic shiners, which can be associated with allergic conjunctivitis, appear as dark circles under the eyes from periorbital venous congestion because of swelling of tissues in the nasal cavity. Rosacea has a strong association with meibomian gland dysfunction (MGD) and can manifest as small, red, pus-filled bumps on the face or a large, red, bulbous nose (rhinophyma). Autoimmune disorders that may cause DED can manifest as rashes, such as the malar rash in systemic lupus and the heliotrope rash in dermatomyositis. Herpes zoster ophthalmicus (shingles) is caused by reactivation of varicella-zoster virus in the ophthalmic (V1) division of the trigeminal nerve, which can manifest as a dermatomal unilateral painful vesicular rash. Risk of ocular involvement is increased in the presence of Hutchinson’s sign, which is vesicles present on the tip of the nose indicating involvement of the nasociliary nerve. Proptosis, which can be associated with a variety of diseases, such as thyroid eye disease, can cause exposure keratopathy and can be assessed rapidly by having the patient tip his/her chin up and viewing the eye position from a worm’s-eye view, or can be assessed formally using an exophthalmometer.

Lids and lashes

Evaluation of the eyelid starts by examining the patient’s blink for quantity (normal or hypometric) and quality (complete closure or lagophthalmos). Next, the positioning of the eyelid is assessed for lid retraction causing scleral show and presence of entropion (inward turn) or ectropion (outward turn) of either the eyelid or puncta. The puncta should also be assessed for patency or stenosis. Checking the eyelid for masses, for example, benign lesions such as chalazia or hordeola, as well as malignant lesions, such as sebaceous cell carcinoma, is important and should include inspection, palpation, and lid eversion. Pulling on the eyelid can reveal floppy eyelid, which has been associated with obstructive sleep apnea and papillary conjunctivitis. The eyelashes should be assessed for loss of eyelashes (madarosis), inward turning of eyelashes (trichiasis), and various types of debris, including sleeves (Demodex), collarettes (Staphylococcal), and scurf (seborrheic blepharitis) ( Fig. 27.5 ).

Jun 26, 2022 | Posted by in OPHTHALMOLOGY | Comments Off on Dry eye disease
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