How should dry eye (keratoconjunctivitis sicca) be managed?

Management of Dry Eye (Keratoconjunctivitis Sicca)

Start with preservative-free artificial tears containing methylcellulose or hyaluronate at least twice daily, escalating frequency up to hourly based on symptoms, and add topical cyclosporine 0.05% if symptoms persist beyond 4-6 weeks of optimal lubrication. 1

Step 1: Initial Management - Artificial Tears and Environmental Modifications

• Use preservative-free artificial tears when applying more than 4 times daily to avoid preservative-induced ocular surface toxicity 1, 2
• Apply methylcellulose or hyaluronate-based formulations at minimum twice daily, increasing to hourly as needed based on symptom severity and objective signs like corneal staining 1, 2
• Apply ophthalmic ointments at bedtime for overnight symptom control, followed by morning lid hygiene to prevent blepharitis 1, 2
• Address environmental triggers: eliminate cigarette smoke exposure, reduce air drafts from fans or vents, humidify ambient air, and position computer screens below eye level to decrease lid aperture 1
• Review and modify systemic medications that worsen dryness (antihistamines, diuretics) when medically feasible 1

Common pitfall: Using preserved artificial tears more than 4 times daily causes additional ocular surface damage rather than relief. 2

Step 2: Anti-Inflammatory Therapy for Persistent Symptoms

Short-Term Topical Corticosteroids

• Initiate topical corticosteroids for 2-4 weeks maximum to rapidly control inflammation while transitioning to longer-term immunomodulatory therapy 1, 3
• Monitor intraocular pressure at baseline and every 1-2 weeks during corticosteroid use; avoid in patients with glaucoma or ocular hypertension 3
• Never extend corticosteroid use beyond 4 weeks without specialist supervision due to risks of infections, increased intraocular pressure, and cataract formation 1, 2, 3

Topical Cyclosporine 0.05%

• Add topical cyclosporine 0.05% twice daily as first-line immunomodulatory therapy for moderate-to-severe dry eye unresponsive to artificial tears alone 1, 3, 4
• Expect 15% of patients to achieve clinically significant improvement (≥10mm Schirmer wetting) versus 5% with vehicle at 6 months 4
• Warn patients about transient burning sensation, which is more frequent with cyclosporine than other treatments but typically improves with continued use 1
• Do not use cyclosporine in patients currently taking topical anti-inflammatory drugs or using punctal plugs, as increased tear production was not demonstrated in these populations 4

Critical evidence: The FDA label for cyclosporine demonstrates blood concentrations remain below quantitation limits (0.1 ng/mL) after 12 months of topical use, confirming safety of long-term therapy. 4

Step 3: Tear Conservation and Advanced Topical Therapies

Punctal Occlusion

• Consider punctal occlusion (upper and lower puncta) for patients with persistent symptoms despite maximal topical therapy 1, 2
• Research demonstrates significant improvement in rose Bengal scores and subjective discomfort in severe Sjögren syndrome-related dry eye at 6 weeks post-occlusion 5
• Avoid punctal plugs during active inflammation until controlled, as they may worsen inflammatory mediator retention 3

Autologous Serum Tears

• Use autologous serum tears for cases unresponsive to topical cyclosporine, particularly in autoimmune conditions like Sjögren syndrome or graft-versus-host disease 1, 3
• These are especially effective for severe corneal epithelial defects and inflammatory dry eye 1

Alternative Prescription Agents

• Topical lifitegrast (LFA-1 antagonist) can be used as an alternative immunomodulatory agent 1
• Topical varenicline nasal spray provides cholinergic neuroactivation via the trigeminal parasympathetic pathway 1
• Perfluorohexyloctane (water-free lipophilic liquid) addresses evaporative dry eye 1

Step 4: Systemic and Surgical Interventions for Severe/Refractory Disease

Systemic Immunosuppression

• Mycophenolate mofetil, dapsone, azathioprine, or methotrexate for slowly progressive disease in autoimmune conditions like ocular mucous membrane pemphigoid or Sjögren syndrome 1, 3
• Cyclophosphamide for severe inflammation or disease unresponsive to other agents 1
• Oral tetracycline or macrolide antibiotics for meibomian gland dysfunction component 1
• All systemic immunosuppression must be administered by physicians with expertise in these therapies to minimize and manage side effects 1, 3

Critical warning: Check G6PD levels before starting dapsone to avoid hemolytic anemia. 1

Surgical Options

• Surgical punctal cautery for permanent occlusion after successful trial with temporary plugs 1
• Amniotic membrane grafts for severe corneal surface disease 1
• Tarsorrhaphy or moisture chamber devices for exposure-related severe dry eye 1
• Scleral lenses provide both vision correction and symptom relief in severe cases, particularly graft-versus-host disease 1, 2

Disease-Specific Considerations

Sjögren Syndrome

• Follow the stepped algorithm above, with particular emphasis on early topical cyclosporine and consideration of systemic immunosuppression for severe cases 1, 3
• Oral muscarinic agonists may be added for systemic sicca symptoms but avoid during active ocular inflammation 1, 3

Graft-Versus-Host Disease

• Aggressive lubrication is particularly critical in this population 1
• Topical cyclosporine and autologous serum tears are specifically effective for GVHD-associated dry eye 1
• Scleral lenses are especially helpful for both vision correction and symptom relief 1, 2

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

• Early intervention is critical to prevent late ocular complications 1
• Combine topical lubricants, antibiotics, and anti-inflammatories 1
• Perform periodic sweeping of conjunctival fornices to interrupt synechiae formation 1

Monitoring and Follow-Up

• Schedule follow-up visits based on disease severity, including interval history, visual acuity measurement, slit-lamp biomicroscopy, and documentation of corneal/conjunctival changes 1, 2
• If cataract surgery or other ocular procedures are needed, provide perioperative immunosuppression and close postoperative follow-up, as these procedures may worsen underlying dry eye disease 1, 3

Critical pitfall: Failing to treat underlying blepharitis or meibomian gland dysfunction will cause treatment failure regardless of dry eye therapy intensity. Address lid hygiene and warm compresses from the outset. 1