Causes of Dry Eye Disease: Local and Systemic Factors
Dry eye disease results from two major mechanisms that can occur independently or together: deficient aqueous tear production and tear film instability, with both local and systemic factors contributing to its development. 1
Systemic Causes of Dry Eye
Autoimmune and Inflammatory Conditions
- Sjögren's syndrome - primary autoimmune disorder affecting approximately 10% of patients with clinically significant aqueous deficient dry eye 2
- Rheumatoid arthritis and other connective tissue disorders 1
- Autoimmune thyroid disease 1
- Sarcoidosis, causing lacrimal gland infiltration 3
- Lymphoma - can infiltrate lacrimal glands 3
- Hemochromatosis and amyloidosis - result in infiltration of lacrimal gland and replacement of secretory acini 3
Viral and Infectious Diseases
- HIV/AIDS - dry eye diagnosed in 21% of AIDS patients 3
- Epstein-Barr virus - associated with lacrimal gland swelling and dry eye 3
- Human T-cell lymphotropic virus type 1 3
- Hepatitis C - associated with decreased tear secretion and reduced tear lactoferrin 3
Endocrine and Metabolic Disorders
- Diabetes mellitus - prevalence of 17.5% among diabetic patients, especially with poor metabolic control 1
- Androgen deficiency - contributes to dry eye development 1, 4
- Postmenopausal status - prevalence increases from 5.7% in women under 50 to 9.8% in women over 75 1
Neurological Disorders
- Parkinson's disease - affects blinking mechanics 3
- Bell's palsy - impairs eyelid function and blinking 3
- Migraines - associated with increased dry eye risk 4
Other Systemic Conditions
- Graft-versus-host disease - severe dry eye in hematopoietic stem cell transplant recipients 3
- Mental health disorders - associated with increased dry eye risk 4
- Sleep disorders - contribute to dry eye symptoms 1
- Rosacea - associated with increased dry eye risk 1
Medication-Related Causes
- Antidepressants and antianxiety medications 1, 4
- Antihistamines - reduce tear production 1, 4
- Systemic retinoids (e.g., isotretinoin) 1
- Diuretics 1
- Oral corticosteroids 1
- Hormone replacement therapy (particularly estrogen-only) 1, 4
- Antihypertensive medications - can exacerbate dry eye symptoms 5
Local Causes of Dry Eye
Eyelid Abnormalities
- Meibomian gland dysfunction - leading cause of evaporative dry eye 1
- Blepharitis - inflammation of eyelid margins 4
- Eyelid malposition (entropion, ectropion) 3
- Lagophthalmos - incomplete eyelid closure 3
- Incomplete blinking - associated with two-fold increase in evaporative dry eye 3
- Demodex infestation - contributes to eyelid inflammation 4
Ocular Surface Disorders
- Mucous membrane pemphigoid - causes inflammation, scarring, and destruction of conjunctival goblet cells 3
- Stevens-Johnson syndrome - leads to tear deficiency through inflammation and scarring 3
- Herpes simplex virus keratitis - damages corneal surface 1
- Atopy - can produce dry eye through blepharitis and conjunctival scarring 3
Anatomical/Structural Issues
- Exophthalmos - as seen in thyroid-associated ocular disease 3
- Orbital/eyelid surgery - can disrupt normal tear dynamics 3
- Radiation to ocular/periocular tissues 3
- Ocular injury 3
Iatrogenic Factors
- Refractive surgery (LASIK, SMILE) - disrupts corneal nerves 1
- Topical medications with preservatives - especially benzalkonium chloride in glaucoma medications 1
- Contact lens wear - alters tear film dynamics 4
Environmental/Lifestyle Factors
- Increased screen time - reduces blink rate in both adults and children 3, 1
- Low humidity environments 1
- Air conditioning and heating - decrease ambient humidity 1
- Increased wind and drafts - accelerate tear evaporation 1
- Poor sleep quality 4
- Eye cosmetic use - can destabilize tear film 4
- Smoking - associated with increased dry eye risk 1
Clinical Implications
Dry eye disease can range from mild irritation to severe vision-threatening complications. In severe cases, especially with underlying inflammatory systemic conditions, complications may include:
- Ocular surface keratinization
- Conjunctival fibrosis/cicatricial changes
- Limbal stem cell deficiency
- Corneal scarring, thinning, and neovascularization
- Microbial or sterile corneal ulceration with possible perforation
- Severe visual loss 3
When dry eye occurs in younger patients and males, clinicians should maintain a high index of suspicion for underlying systemic or local conditions, as dry eye is most commonly seen in postmenopausal women 3.