Dry%20eye%20syndrome Diagnosis

Etiopathogenic Classifications

• Aqueous tear-deficient dry eye
  • Also known as tear-deficient dry eye or lacrimal tear deficiency
  • Secondary to failure of lacrimal tear secretion
  • Subdivided into Sjögren syndrome, which is an autoimmune disorder, or non-Sjögren syndrome, which may be secondary to lacrimal gland insufficiency, lacrimal duct obstruction, or reflex hyposecretion
• Evaporative dry eye
  • Has normal lacrimal secretory function but causes excessive loss of water from the exposed ocular surface
  • May be secondary to intrinsic factors (eg meibomian gland dysfunction, eyelid aperture disorder or lid/globe incongruity, blink disorders) or extrinsic factors (eg ocular surface disease, contact lens wear, vitamin A deficiency, topical drug preservatives)
• Mixed dry eye is a combination of aqueous tear-deficient and evaporative dry eye, which is more pronounced in DES patients as the disease progresses

• Important to inquire about the following which may predispose or contribute to DES:
  
  • Duration of symptoms
  • Use of medications (eg artificial tears, eyewash, ophthalmic or oral antihistamines, glaucoma medications, ophthalmic vasoconstrictors, diuretics, hormones, antidepressants, cardiac antiarrhythmic drugs, Isotretinoin, beta-adrenergic antagonists, chemotherapeutic drugs, or any drug with anticholinergic effects)
    
    • >4-6x/day use of preserved eye drops may contribute to DES
    • A study found that angiotensin-converting enzyme (ACE) inhibitors are associated with lower risk for DES
  • Ocular history including contact lens wear and care, allergic conjunctivitis, ocular surface disease (eg herpes simplex or varicella-zoster virus infection, Stevens-Johnson syndrome, aniridia, ocular mucous membrane pemphigoid)
  • Systemic history such as smoking or exposure to 2nd-hand smoke, dermatological diseases, frequency of facial washing, atopy, menopause, systemic inflammatory diseases (eg Sjögren syndrome, graft vs host disease, rheumatoid arthritis, systemic lupus erythematosus, scleroderma), trauma, chronic viral infections (eg hepatitis C, HIV), radiation of the orbit, or neurological disorders (eg Parkinson’s disease, Bell’s palsy, trigeminal neuralgia)
  • Ocular surgical history (eg keratoplasty, cataract surgery, keratorefractive surgery) or nonocular surgery (eg bone marrow transplant, head and neck surgery, trigeminal neuralgia surgery)
    • Refractive surgery disrupts corneal innervation and may contribute to aqueous deficiency
  • Occupations like those that require sustained visual attention (eg working at a microscope or computer) or those performed with upward or horizontal gaze (eg computer use)
    
    • May result in decreased blink rate and increased evaporation
    • Upgaze widens the palpebral aperture that exposes the ocular surface more to evaporation
  • Nutritional factors such as low intake of vitamin A or omega-3 fatty acid, or diet with high ratio of omega-6 to omega-3 fatty acids which may predispose to DES

• Includes measurement of visual acuity, external examination, and slit-lamp biomicroscopy to record the signs of dry eye, to evaluate the severity of decreased aqueous tear production and/or increased evaporative loss, and to identify possible causes of eye irritation
  
  • Inspect the skin for possible signs of scleroderma or rosacea; eyelids for abnormal secretions, entropion or ectropion, incomplete closure, infrequent blink, eye lid lag or retraction, proptosis, adnexa for enlargement of lacrimal glands; or hands for possible signs of rheumatoid arthritis, Raynaud phenomenon and splinter hemorrhages underneath the nails
  • Assess function of cranial nerves V (trigeminal) and VII (facial)
  • Slit-lamp biomicroscopy should examine the tear film, eyelashes, anterior and posterior eyelid margins, puncta, conjunctiva, and cornea

• Useful in confirming the diagnosis but often poorly correlate with symptoms
• Evaluate the tear film instability, ocular surface damage, and aqueous tear flow

Fluorescein Dye Disappearance Test or Tear Function Index

• Used to assess clearance or turnover of tears on the ocular surface
• Evaluates aqueous tear production, tear volume, and tear drainage
• More correlated with the severity of ocular irritation symptoms and corneal fluorescein staining than the Schirmer test
• Delayed clearance is associated with high tear cytokine concentration which may contribute to chronic inflammation

Lacrimal Gland Function Test

• Measures lactoferrin, the most abundant tear protein being secreted by the lacrimal gland
  • Low lactoferrin concentration is noted in patients with Sjögren syndrome and other causes of lacrimal gland dysfunction

Matrix Metalloproteinase-9 (MMP-9) Test

• May be used to assess presence of inflammation and changes in disease states which may aid in the management

Ocular Surface Dye Staining

• Evaluates the ocular surface 
• Uses fluorescein, rose bengal, or lissamine green dyes
  • Fluorescein dye stains area of the corneal and conjunctival epithelia with disruption of intercellular junctions that are adequate to allow the dye to penetrate into the tissue
    
    • Mild staining may be seen in normal eyes especially in the morning
    • Blotchy or exposure-zone punctate staining is consistent with DES
  • Rose bengal stains the ocular surface cells that are deficient in mucous coating and debris in the tear film
    • May detect involvement of the conjunctiva by staining cells in the interpalpebral zone
  • Lissamine green stains similar to that of rose bengal dye but is well tolerated as fluorescein dye
    
    • Not to be used in evaluating corneal epithelial disease
• Viral keratoconjunctivitis and medicamentosa show diffuse staining of the cornea and conjunctiva
• Staphylococcal blepharitis, meibomian gland dysfunction, or lagophthalmos shows staining on the inferior cornea and bulbar conjunctiva
• Superior limbic keratoconjunctivitis presents with staining on the superior bulbar conjunctiva
• Aqueous tear deficiency is usually observed to have staining on the interpalpebral cornea and bulbar conjunctiva

Schirmer Test 

• Used to assess aqueous tear production or flow
• Performed by placing a narrow filter paper strip in the inferior cul-de-sac and measures the length the strip wets during the test period (5 minutes)
  
  • May be done with or without anesthesia to measure reflex tearing or with anesthesia to measure basal tearing by minimizing ocular surface reflex activity
  • Schirmer test with anesthesia is considered abnormal if the result is ≤10 mm
    • Isolated abnormal result may be nonspecific but consistent low result highly suggests aqueous tear deficiency
  • Usually has variable results, hence, should not be used as the only criterion to diagnose DES

Tear Film Break-up Time (TFBUT) Test

• Measures time that lapsed between the last blink and the appearance of the 1st break in the fluorescein-stained tear film
• Used to evaluate the tear film stability
• Localized anterior basement membrane abnormality may be considered if tear break-up in the same area is recurrent
• Abnormal result is considered when TFBUT is <10 seconds which may be seen in both aqueous tear deficiency and meibomian gland disease

Tear Osmolarity Test

• Shown to be more sensitive and specific in diagnosing and grading the severity of DES as compared to corneal and conjunctival staining, TFBUT, Schirmer test, and meibomian gland grading

Other Tests

• Videokeratography may be used to objectively diagnose and evaluate the severity of DES, screen patients prior to LASIK and identify their post-LASIK chronic DES risk
• Impression cytology is a less invasive alternative to ocular biopsy that is used to determine abnormalities like goblet cell loss and squamous metaplasia

Specific Tests in Patients with Underlying Conditions

• Anti-Rho (SSA), anti-La (SSB), anti-nuclear antibody (ANA), and rheumatoid factor (RF) for Sjögren syndrome
  • Additional biomarkers such as salivary protein 1 (SP1), carbonic anhydrase 6 (CA6) and parotid secretory protein (PSP) may be used to determine early Sjögren syndrome or other forms of autoimmune DES
• Anti-thyroid peroxidase antibody, antithyroglobulin antibody, and orbital imaging such as computed tomography (CT) and magnetic resonance imaging (MRI) scan (to assess extraocular muscle thickness) for thyroid eye disease
• Serum lysozyme, ACE test, chest CT scan (to determine the extent of disease), and conjunctival biopsy for sarcoidosis
• Conjunctival biopsy with light microscopy, immunofluorescent or immunohistochemical studies for ocular mucous membrane pemphigoid

Questionnaires

• Eg Ocular Surface Disease Index (OSDI), McMonnies Dry Eye Questionnaire, Canadian Dry Eye Epidemiology Study (CANDEES) Questionnaire, Dry Eye Epidemiology Projects (DEEP) Questionnaire, Women’s Health Study Questionnaire, NEI-Visual Function Questionnaire (NEI-VFQ), Dry Eye Questionnaire (DEQ) and Contact Lens Dry Eye Questionnaire (CLDEQ), Dry Eye Disease Impact Questionnaire (DEDIQ), Ocular Comfort Index (OCI)
• Used to evaluate the effects of treatments or to grade the severity of the disease, screen individuals for clinical research, or to study the natural history of disease for epidemiologic research
• Usually contain clinician-based or other diagnosis of dry eye, frequency or intensity of symptoms, effect of symptoms on daily activities, effect of environmental triggers on symptoms, effect of treatment on symptoms, etc

Severity Classification of Dry Eye Syndrome (DES)

• Based on combination of signs and symptoms
• Indefinite classification due to overlapping characteristics at each level

Mild DES

• Has symptoms of irritation, itching, soreness, burning, or intermittent blurring of vision
• Diagnosis is complicated due to inconsistent symptoms and signs and relatively low specificity and/or sensitivity of clinical tests

Moderate DES

• Increased discomfort and frequency of symptoms and more consistent visual dysfunction

Severe DES

• Increasing frequency of symptoms and visual dysfunction that may become constant