In a patient receiving Brikinsa (zanubrutinib) who develops new or worsening eye redness, what is the appropriate management?

Management of Eye Redness in Patients on Brikinsa (Zanubrutinib)

Immediately refer the patient to ophthalmology for urgent evaluation within 24-48 hours while initiating preservative-free artificial tears, as eye redness in a patient on zanubrutinib may represent serious ocular complications including cystoid macular edema or uveitis that require prompt specialist assessment and potential drug modification.

Initial Assessment and Immediate Actions

When a patient on Brikinsa develops new or worsening eye redness, you must act quickly to rule out vision-threatening complications:

Key Clinical Features to Assess

• Visual acuity changes - Any decrease in vision is a red flag requiring same-day ophthalmology referral
• Associated symptoms - Ask specifically about:
  • Blurry vision (suggests macular edema)
  • Eye pain or photophobia (suggests uveitis or keratitis)
  • Foreign body sensation or dry eye symptoms
  • Duration and progression of redness

Immediate Management Steps

1. Start preservative-free artificial tears immediately (4-6 times daily) while awaiting ophthalmology evaluation 1

2. Refer to ophthalmology urgently:

   • Within 24 hours if patient has visual impairment, significant pain, or severe redness 2, 1
   • Within 2-7 days if mild-to-moderate redness without vision changes 2, 1

3. Do NOT hold zanubrutinib until ophthalmology has evaluated the patient and determined the cause

Understanding Zanubrutinib-Associated Ocular Complications

The most concerning ocular complication reported with zanubrutinib is bilateral cystoid macular edema (CME), which presents with decreased vision and may show macular edema on OCT 3. This case report from 2023 represents the first documented CME with zanubrutinib therapy in a mantle cell lymphoma patient.

Critical Distinction from Other Drug-Related Eye Issues

The evidence provided focuses heavily on other medications (belantamab mafodotin, dupilumab, immune checkpoint inhibitors), but these management algorithms don't directly apply to zanubrutinib. The key difference: zanubrutinib-associated CME was refractory to topical corticosteroids alone and required sub-Tenon's steroid injections plus drug hold 3.

Ophthalmology Evaluation Requirements

The ophthalmologist should perform:

• Visual acuity testing (both eyes)
• Slit-lamp biomicroscopy to assess for:
  • Anterior uveitis (cells/flare in anterior chamber)
  • Conjunctival injection pattern
  • Corneal involvement
• Dilated fundus examination
• Optical coherence tomography (OCT) if any vision changes present to evaluate for macular edema 3

Treatment Algorithm Based on Ophthalmology Findings

If Simple Conjunctival Hyperemia (No Uveitis/CME)

• Continue zanubrutinib
• Preservative-free lubricants 4-6 times daily 4
• Consider topical antihistamine (olopatadine twice daily) if allergic component 1
• Follow-up in 1-2 weeks

If Anterior Uveitis Confirmed

Based on immune checkpoint inhibitor guidelines (closest available framework) 2:

• Grade 1-2 (mild-moderate): Hold zanubrutinib, coordinate with ophthalmology for topical corticosteroids + cycloplegic agents
• Grade 3-4 (severe/vision-threatening): Permanently discontinue zanubrutinib, urgent ophthalmology management with systemic corticosteroids

If Cystoid Macular Edema Confirmed

Based on the single case report 3:

• Hold zanubrutinib immediately
• Sub-Tenon's corticosteroid injections (topical steroids alone were ineffective)
• Monitor closely - vision loss may not be fully reversible even with treatment
• Discuss with hematology/oncology regarding alternative BTK inhibitor or treatment strategy

Common Pitfalls to Avoid

1. Don't assume it's "just dry eye" - Zanubrutinib patients with eye redness need formal ophthalmology evaluation to rule out CME or uveitis

2. Don't start topical corticosteroids empirically - This can worsen infectious causes and delay proper diagnosis. Let ophthalmology make this decision after slit-lamp examination

3. Don't use preserved artificial tears if frequent dosing needed (>4 times daily) - preservative toxicity can worsen conjunctival hyperemia 5

4. Don't delay ophthalmology referral waiting for symptoms to improve - CME requires prompt intervention to prevent permanent vision loss 3

Coordination with Hematology/Oncology

After ophthalmology evaluation, coordinate closely with the prescribing oncologist:

• If drug hold required, discuss alternative BTK inhibitors (acalabrutinib, ibrutinib) or venetoclax-based regimens 6
• Document that zanubrutinib modification was for ocular toxicity, not disease progression
• Consider that other BTK inhibitors may have different ocular side effect profiles

Follow-Up Monitoring

If zanubrutinib is continued after ophthalmology clearance:

• Baseline and periodic ophthalmology monitoring is prudent, though no formal guidelines exist for zanubrutinib specifically
• Instruct patient to report immediately: vision changes, increased redness, pain, or photophobia
• Consider ophthalmology re-evaluation every 3-6 months while on therapy

The key message: eye redness on zanubrutinib is not benign until proven otherwise by ophthalmology - the documented case of bilateral CME demonstrates this can be a serious, vision-threatening complication requiring aggressive intervention 3.