What is the best treatment approach for dry eyes (keratoconjunctivitis sicca)?

Treatment of Dry Eye Disease

Start with preservative-free artificial tears containing methylcellulose or hyaluronate at least twice daily, escalating to hourly use based on symptom severity, and advance to topical cyclosporine 0.05% twice daily if symptoms persist beyond 2-4 weeks of optimized artificial tear therapy. 1, 2

Step 1: Environmental Modifications and First-Line Therapy

Artificial Tears:

• Preservative-free formulations containing methylcellulose or hyaluronate are the cornerstone of initial treatment, used at minimum twice daily and increased up to hourly based on response 1, 3
• Preservative-free products are mandatory when applying more than four times daily to prevent preservative-induced ocular surface toxicity 4, 1
• Polyethylene glycol-based tears demonstrate superior efficacy compared to carboxymethylcellulose or hydroxypropyl methylcellulose formulations 5
• Lipid-containing artificial tears specifically benefit patients with meibomian gland dysfunction by supplementing the deficient lipid layer 4, 1
• Use liquid drops during daytime, gels for longer-lasting effect, and ointments overnight for nocturnal symptoms 1

Lid Hygiene (Essential for All Patients):

• Warm compresses for 5-10 minutes twice daily with gentle lid massage to express meibomian gland secretions 4, 3
• This addresses the evaporative component present in the majority of dry eye patients 4

Environmental Control:

• Eliminate cigarette smoke exposure, which damages the tear film lipid layer 1, 3
• Humidify ambient air and use side shields on spectacles to reduce evaporation 1, 3
• Lower computer screens below eye level and increase conscious blinking to >10 times per minute during screen use 1, 3

Step 2: Anti-Inflammatory Therapy for Moderate Disease

If artificial tears fail after 2-4 weeks, advance to prescription anti-inflammatory agents:

Cyclosporine 0.05% (Restasis):

• FDA-approved to increase tear production in patients whose tear production is suppressed due to ocular inflammation 2
• Apply twice daily; demonstrated success rates of 74% in mild, 72% in moderate, and 67% in severe dry eye 1, 3
• Increases Schirmer wetting ≥10mm in approximately 15% of treated patients versus 5% with vehicle at 6 months 2
• Critical caveat: Ineffective in patients currently using topical anti-inflammatory drugs or punctal plugs 2
• When used with artificial tears, polyethylene glycol-based formulations (Systane) produce superior outcomes compared to carboxymethylcellulose-based products (Refresh Tears), with significantly less burning, stinging, grittiness, and dryness 6

Lifitegrast 5% (Xiidra):

• Blocks LFA-1/ICAM-1 interaction, preventing T-cell activation 1
• Improves both signs and symptoms of dry eye disease 1

Short-term Topical Corticosteroids:

• Limit to 2-4 weeks maximum (e.g., loteprednol) for acute exacerbations 4, 1, 3
• Never exceed this duration due to risks of increased intraocular pressure, cataracts, and infections 3

Step 3: Advanced Treatments for Severe Disease

Punctal Occlusion:

• Trial with temporary silicone plugs first to screen for epiphora before considering permanent occlusion 4
• Thermal cautery is more effective than laser cautery for permanent occlusion 4
• Use stepwise approach: occlude no more than one punctum per eye per treatment session 4

Autologous Serum Drops:

• Improve ocular irritation symptoms and corneal/conjunctival staining, particularly in Sjögren syndrome and graft-versus-host disease 4, 1
• Allogeneic serum drops are effective alternatives when repeated blood sampling is not feasible 4

Oral Secretagogues (for Sjögren Syndrome):

• Pilocarpine 5mg orally four times daily improves ability to focus during reading and reduces blurred vision 4, 1
• Cevimeline has fewer systemic side effects than pilocarpine 4, 1
• Common pitfall: Over 40% experience excessive sweating; many discontinue due to side effects 4

Specialized Contact Lenses:

• Rigid gas-permeable scleral lenses successfully treat severe dry eye but require careful fitting 4, 1
• Soft contact lenses provide relief in filamentary keratitis but increase infection risk 4
• Use with extreme caution in neurotrophic keratopathy due to infection risk 4

Newer Options:

• Varenicline nasal spray (Tyrvaya) activates trigeminal nerve nicotinic receptors to stimulate natural tear production for moderate-to-severe disease unresponsive to traditional therapy 1
• Perfluorohexyloctane (Miebo) for evaporative dry eye shows improvements as early as 2 weeks with sustained efficacy over 12 months 1

Step 4: Surgical Interventions for Refractory Cases

When all medical therapies fail:

• Permanent punctal cautery (after successful trial with plugs) 4
• Limited tarsorrhaphy to decrease tear film instability 4
• Amniotic membrane grafts for severe surface disease 4
• Self-retaining amniotic membrane for refractory filamentary keratitis (short-term effect) 4

Red Flags Requiring Immediate Ophthalmology Referral

• Moderate or severe eye pain 3
• Lack of response to initial therapy after 2-4 weeks 3
• Corneal infiltration or ulceration 3
• Vision loss, blurred vision, or visual disturbances 3
• Filamentary keratitis (requires debridement or acetylcysteine 10% four times daily) 4

Critical Pitfalls to Avoid

• Failing to recognize when to advance from artificial tears to anti-inflammatory agents leads to inadequate treatment 1
• Overuse of preserved artificial tears causes ocular surface toxicity 1
• Extended corticosteroid use beyond 2-4 weeks risks serious complications 1, 3
• Neglecting concurrent blepharitis or meibomian gland dysfunction exacerbates dry eye 1, 3
• Not correcting eyelid abnormalities (trichiasis, lagophthalmos, entropion, ectropion) perpetuates symptoms 1, 3