What is the management and diagnosis for a condition associated with dry eyes?

Management and Diagnosis of Dry Eye Disease

For patients presenting with dry eyes, establish the diagnosis through a combination of symptom assessment and objective testing including tear osmolarity, tear break-up time, ocular surface staining, and Schirmer testing, while actively screening for underlying Sjögren syndrome in patients with significant aqueous tear deficiency, particularly when accompanied by dry mouth symptoms. 1

Diagnostic Approach

Clinical Evaluation

Comprehensive slit-lamp examination should assess:

• Tear film characteristics: meniscus height, debris, viscosity, mucous strands, foamy discharge, and tear break-up time and pattern 1
• Eyelid margins: meibomian gland abnormalities (orifice metaplasia, reduced expressible meibum, atrophy), character of secretions (turbid, thickened, foamy), vascularization, keratinization, scarring 1
• Conjunctiva: punctate staining with fluorescein, lissamine green, or rose bengal dyes; hyperemia; scarring; follicles; symblepharon 1
• Cornea: interpalpebral drying, punctate epithelial erosions, filaments, epithelial defects, mucous plaques, ulceration 1

Objective Diagnostic Testing

The workup should include one or more of the following tests: 1

• Tear osmolarity: Elevated levels and/or significant inter-eye differences indicate dry eye; correlation with clinical findings over time is more informative than single measurements 1
• Matrix metalloproteinase-9 (MMP-9) point-of-care test: Indicates presence of inflammation and aids in diagnosis, though it does not differentiate dry eye from other inflammatory ocular surface diseases 1
• Schirmer test without anesthesia (Schirmer I): Less than 5.5 mm of wetting after 5 minutes is diagnostic of aqueous tear deficiency 1
• Fluorescein tear break-up time: Rapid break-up indicates unstable tear film 1
• Ocular surface dye staining: Using fluorescein, lissamine green, and/or rose bengal to assess epithelial damage 1

A critical pitfall: Normal subjects have exceptionally stable tear film osmolarity, whereas dry eye patients show unstable values that lose homeostasis quickly with environmental changes, reinforcing that tear film instability due to increased evaporation resulting in hyperosmolarity is a core mechanism 1

Screening for Underlying Systemic Conditions

Approximately 10% of patients with clinically significant aqueous tear deficiency have underlying Sjögren syndrome, making timely diagnosis crucial as primary Sjögren syndrome carries an 18.9% incidence rate of malignancy. 1

For patients with significant dry eye accompanied by dry mouth symptoms or family history of autoimmune disorders, order the following serological tests: 1

• Anti-Sjögren syndrome A antibody (SSA or anti-Ro)
• Anti-Sjögren syndrome B antibody (SSB or anti-La)
• Rheumatoid factor (RF)
• Antinuclear antibody (ANA)
• Consider point-of-care testing that includes additional biomarkers: salivary protein 1 (SP1), carbonic anhydrase 6 (CA6), and parotid secretory protein (PSP) 1

Sjögren syndrome diagnostic criteria require a weighted score ≥4 based on: 1

• Anti-SSA/Ro antibody positivity (3 points)
• Focal lymphocytic sialadenitis with focus score ≥1 foci/4 mm² (3 points)
• Abnormal ocular staining score ≥5 (1 point)
• Schirmer test ≤5 mm/5 minutes without anesthesia (1 point)
• Unstimulated salivary flow rate ≤0.1 ml/minute (1 point)

For other suspected conditions: 1

• Thyroid eye disease: Antithyroid peroxidase antibody, antithyroglobulin antibody, orbital imaging (CT or MRI)
• Sarcoidosis: Serum lysozyme, ACE, chest CT (consult pulmonology), conjunctival biopsy
• Ocular mucous membrane pemphigoid: Conjunctival biopsy with immunofluorescent or immunohistochemical studies

Management Strategy

Classification-Based Treatment

Dry eye is classified as mild, moderate, or severe based on both symptoms and signs, with emphasis on symptoms over signs. 1

• Mild: Intermittent symptoms of irritation, itching, soreness, burning, or intermittent blurred vision 1
• Moderate: Increased discomfort frequency with more consistent negative effects on visual function 1
• Severe: Constant visual symptoms that may become disabling 1

Therapeutic Options

Tear supplementation and stabilization: 2

• Topical artificial tears remain the most widely used therapy 3
• Punctal occlusion to prevent drainage of natural or artificial tears is the most common non-pharmacological treatment 3

Anti-inflammatory therapy for moderate to severe disease: 1

• Topical cyclosporine: Long-term use has shown clinical benefits and can lead to treatment-free remission of symptoms and signs in some instances 1
• Topical lifitegrast 5%: FDA-approved lymphocyte function-associated antigen-1 antagonist showing benefit in both signs (corneal and conjunctival staining) and symptoms (eye dryness score and ocular discomfort) over 3 months, though long-term efficacy beyond 12 months is unknown 1

Oral secretagogues for severe dry eye with Sjögren syndrome: 1

• Cevimeline: FDA-approved for dry mouth in Sjögren syndrome; improves ocular irritation symptoms and aqueous tear production with potentially fewer adverse systemic side effects than pilocarpine 1, 4
• Pilocarpine 5 mg orally four times daily: Demonstrated greater improvement in ability to focus during reading and blurred vision symptoms, though disappointingly showed no improvement in light sensitivity or ocular discomfort; most common side effect is excessive sweating (>40% of patients) 1, 5

Important caveat: Most clinical studies demonstrate greater improvement in dry mouth than dry eye with oral secretagogues 1

Omega-3 fatty acids: A large-scale prospective, multicenter, masked trial of 3000 mg omega-3 fatty acids for 12 months showed no benefit in patient symptoms or signs over placebo 1

Surgical Considerations

All patients undergoing cataract or keratorefractive surgery (particularly LASIK) should be evaluated and managed for dry eye preoperatively, as dry eye is a main reason for patient dissatisfaction following these procedures. 1

• Dry eye symptoms are common in the first few months after surgery and tend to subside with time 1
• Patients can safely undergo LASIK if pre-existing dry eye is improved preoperatively 1
• Dry eye symptoms continuing beyond 3 months postoperatively occur in approximately one-third of individuals 1

Follow-up and Referral

Referral to an ophthalmologist is indicated for: 1

• Moderate or severe pain
• Lack of response to therapy
• Corneal infiltration or ulceration
• Progressive conjunctival scarring
• Vision loss

Patients with systemic disease such as primary Sjögren syndrome or connective tissue disease should be co-managed with an appropriate medical specialist (internist or rheumatologist). 1

Patient education is critical: Inform patients about the chronic nature of the disease process, provide specific instructions for therapeutic regimens, and establish realistic expectations for effective management 1