Dry eyes

Dry eye disease is a multifactorial disorder of the ocular surface with loss of tear film stability, causing discomfort, visual disturbance, inflammation and potential damage. It is common, especially with age, screen use and medication use.

Mechanisms. Hyperosmolarity of the tear film activates inflammation and damages the surface. Aqueous deficiency reflects lacrimal gland failure; evaporative disease reflects meibomian gland dysfunction and incomplete blinking.

Classification. Aqueous deficient (Sjogren and non-Sjogren), evaporative (meibomian gland dysfunction, reduced blink rate, lid disease, contact lens, vitamin A deficiency), and mixed, which is common. Severity grades: mild (occasional symptoms, mild staining), moderate (frequent symptoms, punctate corneal staining), severe (constant symptoms, filaments, erosions or ulceration).

Key distinctions. Dry eye with dry mouth and arthralgia suggests Sjogren syndrome. Symptoms out of proportion to signs suggest neuropathic ocular pain. Unilateral disease suggests lid, corneal or neurological causes.

History. Grittiness, burning, foreign body sensation, redness, fluctuating blur, photophobia, watering, symptoms worse late in the day, with screens, wind or air conditioning, and in the morning (lagophthalmos). Contact lens use, previous eye surgery (laser refractive surgery, cataract), eyelid disease, facial palsy, dry mouth, dry skin, joint pain, rash, thyroid disease, diabetes, rheumatoid arthritis, lupus, sarcoidosis, HIV, hepatitis C, graft versus host disease, radiotherapy, menopause, and diet (vitamin A).

Drug history. Antihistamines, anticholinergics, tricyclic antidepressants, selective serotonin reuptake inhibitors, antipsychotics, diuretics, beta blockers, isotretinoin, hormone replacement and oral contraceptives, antiarrhythmics (amiodarone), preservatives in topical drops (benzalkonium chloride), and drugs for glaucoma.

Examination. Blink rate and completeness, lids (meibomian gland expression, telangiectasia, plugging, anterior blepharitis, lagophthalmos), tear meniscus, tear break up time (under 10 seconds is abnormal), fluorescein staining (cornea), lissamine green staining (conjunctiva), Schirmer test (under 5 mm in 5 minutes without anaesthetic is severe aqueous deficiency; 5 to 10 mm borderline), corneal sensation, conjunctival folds, filaments, and signs of Sjogren syndrome (parotid enlargement, dry mouth, dental caries, purpura).

Red flags

• Corneal ulcer, thinning, perforation or infiltrate
• Vision loss, severe pain or photophobia
• Unilateral disease with lid or corneal anomaly
• Parotid enlargement, lymphadenopathy or purpura (lymphoma risk in Sjogren syndrome)
• Facial palsy or trigeminal anaesthesia (neurotrophic keratopathy)
• Stevens Johnson syndrome, ocular cicatricial pemphigoid, graft versus host disease
• Severe vitamin A deficiency with night blindness and Bitot spots

Special groups. Children: atopic disease, Sjogren, vitamin A deficiency. Pregnancy: hormonal changes; avoid doxycycline. Older adults: very common, with drug contribution. Region specific: vitamin A deficiency, trachoma, onchocerciasis and HIV related disease.

Primary ocular surface

• Evaporative dry eye (meibomian gland dysfunction), anterior blepharitis, Demodex blepharitis
• Aqueous deficient dry eye (age related, lacrimal gland disease, reflex hyposecretion)
• Reduced blinking (screen use, Parkinson disease), lagophthalmos (facial palsy, thyroid eye disease, floppy eyelid, surgery)
• Contact lens related dryness, post-refractive surgery
• Allergic conjunctivitis, vernal and atopic keratoconjunctivitis

Systemic

• Sjogren syndrome (primary and secondary), rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis
• Sarcoidosis, graft versus host disease, HIV, hepatitis C, amyloidosis, IgG4 related disease, lymphoma
• Vitamin A deficiency, thyroid disease, diabetes, rosacea, atopic and seborrhoeic dermatitis
• Stevens Johnson syndrome and toxic epidermal necrolysis, ocular cicatricial pemphigoid, chemical burns, trachoma

Neuropathic and other

• Neurotrophic keratopathy (trigeminal injury, herpes), neuropathic ocular pain, trigeminal neuralgia
• Medication induced dryness, preservative toxicity, menopausal and androgen deficiency

Reasoning. Dry eye is a clinical diagnosis. Assess the severity and the type, look for systemic disease, and exclude infection and other surface disease when signs or symptoms are atypical.

First line. Symptom questionnaire (Ocular Surface Disease Index or Standardised Patient Evaluation of Eye Dryness), tear break up time, fluorescein and lissamine green staining, Schirmer test, and lid and meibomian gland assessment.

Targeted tests.

• Tear osmolarity (over 308 mOsm/L, or an inter-eye difference over 8 mOsm/L, supports the diagnosis), meibography, interferometry, and tear meniscus height by optical coherence tomography.
• Sjogren syndrome screen in aqueous deficient or unexplained dry eye: antinuclear antibody, anti-Ro (SSA) and anti-La (SSB), rheumatoid factor, immunoglobulins, complement, unstimulated salivary flow (under 0.1 mL/min), parotid ultrasound, and labial gland biopsy when needed.
• HIV, hepatitis C, thyroid function, angiotensin converting enzyme, serum protein electrophoresis, vitamin A (retinol), and lipid profile by suspicion.
• Corneal sensation testing (neurotrophic keratopathy), corneal scraping or culture for suspected infection, and biopsy of the conjunctiva for suspected pemphigoid or tumour.
• Allergy testing for atopic disease.

Limitations. Signs and symptoms correlate poorly. Tests vary between visits. Tear osmolarity and break up time are affected by instillation of drops.

Education and environment (all patients). Explain the chronic nature, blink fully and often during screen work, take breaks (every 20 minutes look 20 feet or 6 metres away for 20 seconds), lower screens below eye level, humidify rooms, avoid fans and air flow onto the face, stop smoking, wear wraparound glasses outdoors, and optimise hydration. Review drugs causing dryness and substitute where possible.

Step 1: lubricants and lid care.

• Artificial tears: hypromellose 0.3 percent, carbomer 0.2 percent gel, or sodium hyaluronate 0.1 to 0.4 percent, 1 drop 4 to 6 times daily as needed; preservative free single dose units when used over 4 times daily or in severe disease. Ointment (white soft paraffin and liquid paraffin) at night.
• Warm compresses (5 to 10 minutes) and lid massage then lid hygiene twice daily for meibomian gland dysfunction and blepharitis. Tea tree oil or other lid cleaning products for Demodex blepharitis under specialist advice.
• Omega 3 fatty acid supplements and dietary fish intake (evidence is mixed).

Step 2: anti-inflammatory and secretagogue treatment (moderate disease).

• Ciclosporin 0.05 percent eye drops 1 drop twice daily (effect in 1 to 3 months; stinging common) or lifitegrast 5 percent 1 drop twice daily (dysgeusia), by ophthalmology.
• Short course topical corticosteroid (fluorometholone 0.1 percent or loteprednol 0.5 percent 1 drop 2 to 4 times daily for 1 to 2 weeks, with intraocular pressure and cataract monitoring) for flares.
• Doxycycline 100 mg orally daily (or 50 mg twice daily) for 6 to 12 weeks for meibomian gland dysfunction (avoid in pregnancy, breastfeeding and children under 12 years); azithromycin 500 mg orally daily for 3 days in monthly pulses, or azithromycin 1 percent drops, are alternatives.
• Punctal plugs (temporary then permanent) for aqueous deficiency, after inflammation is controlled.
• Intense pulsed light, thermal pulsation and mechanical meibomian gland expression for evaporative disease.
• Pilocarpine 5 mg orally three to four times daily with meals (maximum 30 mg daily; avoid in asthma, uncontrolled chronic obstructive pulmonary disease, angle closure glaucoma, and cardiac conduction disease; reduce in hepatic impairment) or cevimeline 30 mg orally three times daily for Sjogren related dryness.

Step 3: severe disease.

• Autologous serum eye drops 20 to 50 percent, 1 drop 4 to 8 times daily (specialist service), amniotic membrane, and scleral contact lenses for refractory or neurotrophic disease.
• Bandage contact lens for epithelial defects (monitor for infection).
• Oral immunosuppression or hydroxychloroquine 200 to 400 mg daily (maximum 5 mg/kg actual body weight daily) by rheumatology for systemic Sjogren syndrome.
• Tarsorrhaphy or surgery for persistent defects.

Underlying and associated conditions.

• Sjogren syndrome: rheumatology care, dental care with fluoride, saliva substitutes, and annual lymphoma risk review (persistent gland swelling, purpura, low C4, cryoglobulins).
• Vitamin A deficiency: retinol 200,000 units orally on days 1, 2 and 14 for adults and children over 12 months (100,000 units for 6 to 11 months; 50,000 units for under 6 months); avoid in pregnancy except for severe deficiency under specialist direction.
• Lagophthalmos: tape at night, ointment, and surgical correction.
• Allergic disease: olopatadine 0.1 percent drops 1 drop twice daily.
• Stevens Johnson syndrome and pemphigoid: specialist ocular surface care.
• Graft versus host disease: transplant and ophthalmology care.
• Neurotrophic keratopathy: cenegermin 20 micrograms/mL 1 drop 6 times daily for 8 weeks (specialist).
• Rosacea: lid hygiene and doxycycline 100 mg daily.

Infection or ulcer. Same day ophthalmology: corneal scraping and fluoroquinolone drops (ofloxacin 0.3 percent 1 drop every 1 to 2 hours initially).

Monitoring. Review at 4 to 6 weeks for treatment response, and every 6 to 12 months in chronic disease. Corneal staining and intraocular pressure with steroids.

Referral and escalation. Same day for ulcer, infiltrate or reduced vision. Ophthalmology for moderate or severe disease and neurotrophic keratopathy. Rheumatology for suspected systemic autoimmune disease. Dentistry for dental care in Sjogren syndrome.

Admission criteria. Corneal perforation, severe infection, Stevens Johnson syndrome, or severe graft versus host disease.

Discharge and safety netting. Return for severe pain, reduced vision, light sensitivity, redness, discharge, or no improvement within 4 to 6 weeks.