What are the next steps in managing a patient with severe dry eye disease and recurrent PUK despite immunosuppression and topical treatment?

Management of Severe Dry Eye Disease with Recurrent PUK in a Patient with Autoimmune Disease

For a patient with severe dry eye disease and recurrent PUK despite current immunosuppression, the next step should be escalation to biologic therapy, specifically rituximab, while optimizing topical management with autologous serum eye drops and scleral contact lenses.

Current Status Assessment

The patient presents with:

• Severe ocular surface dryness (15-year history)
• Recurrent Peripheral Ulcerative Keratitis (PUK)
• Positive autoimmune markers (Anti-CCP and Rheumatoid factor)
• Current treatment regimen:
  • Systemic: Methotrexate 10mg weekly
  • Topical: Cyclosporine, Lifitegrast, antivirals, lubricants, and intermittent Loteprednol
• Ongoing issues: Unstable tear film, recurrent inflammation, epithelial filament formation

Management Algorithm

Step 1: Optimize Current Topical Therapy

1. Switch to preservative-free formulations of all topical medications 1
2. Add autologous serum eye drops for severe dry eye refractory to conventional therapy 2
   • These contain factors present in tears that promote ocular surface renewal and restore tear film homeostasis 1
3. Consider scleral contact lenses to protect the ocular surface and maintain constant hydration 2

Step 2: Enhance Anti-inflammatory Control

1. Initiate short-term topical corticosteroid therapy during acute flares 1, 2
   • Use preservative-free dexamethasone 0.1% for up to 8 weeks 1
   • Begin corticosteroid-sparing agents early to facilitate tapering 1
2. Increase topical cyclosporine frequency if not at maximum dosage 2
3. Consider combination of tacrolimus ointment and cyclosporine drops for treatment-resistant disease 1

Step 3: Escalate Systemic Therapy

1. Initiate biologic therapy - specifically rituximab 3
   • Rituximab has shown efficacy in severe and refractory PUK cases 3
   • Non-TNFα biologics appear to require less switching than TNFα inhibitors in PUK management 3
2. Consider increasing methotrexate dose if no contraindications exist
3. Monitor closely for adverse effects of combined immunosuppression

Rationale for Recommendations

Why Biologics?

Conventional immunosuppression with methotrexate has proven inadequate in this case. A multicenter study of 34 patients with severe and refractory PUK showed that biologic therapy is effective, with rituximab being one of the most commonly used agents 3. Importantly, patients treated with non-TNFα agents like rituximab required no switching to other biologics, suggesting better sustained efficacy 3.

Why Autologous Serum?

For treatment-resistant severe dry eye disease, autologous serum eye drops provide nutritional factors that promote ocular surface renewal and restore tear film homeostasis 1, 2. These are specifically recommended for cases refractory to licensed topical therapy 1.

Why Scleral Lenses?

Rigid gas-permeable scleral lenses can be considered for severe cases as they provide constant hydration to the ocular surface and protect it from environmental factors and lid friction 2.

Monitoring and Follow-up

1. Regular ophthalmological assessment to monitor:

   • Corneal inflammation and thinning
   • Intraocular pressure (especially during corticosteroid use)
   • Visual acuity
   • Tear film stability

2. Rheumatological monitoring for:

   • Disease activity
   • Response to systemic therapy
   • Medication side effects

3. Long-term management considerations:

   • Ongoing supervision by an ophthalmologist for patients on longer-term corticosteroid therapy 1
   • Baseline retinal nerve fiber layer optical coherence tomography for patients on prolonged corticosteroid therapy 1
   • Regular assessment of systemic immunosuppression efficacy and safety

Cautions and Pitfalls

• Avoid prolonged use of topical corticosteroids without ophthalmological supervision due to risks of increased intraocular pressure, cataract formation, and infection 2
• Avoid overuse of preserved artificial tears (>4 times/day) as they can cause toxicity and worsen symptoms 2
• Be cautious with topical NSAIDs as prolonged use can lead to corneal-scleral melts, perforation, and ulceration 2
• Monitor closely for infections due to combined immunosuppression therapy

By implementing this comprehensive approach, the goal is to control inflammation, improve ocular surface integrity, and prevent further episodes of PUK, ultimately improving the patient's quality of life and preserving vision.