What is the protocol for treat and extend (treat and extend protocol) using aflibercept (aflibercept) for diabetic macular edema (DME)?

Treat and Extend Protocol for Diabetic Macular Edema (DME)

Standard Aflibercept Treat and Extend Protocol for DME

The treat and extend protocol for DME using aflibercept begins with a loading phase of three monthly injections of 2 mg, followed by a maintenance phase where treatment intervals are gradually extended based on clinical response, with potential extension up to 16 weeks between injections if stability is maintained. 1

Initial Loading Phase

• Start with 3 monthly injections of aflibercept 2 mg
• Assess response after the loading phase using:
  • Best-corrected visual acuity (BCVA)
  • Central subfield macular thickness (CST) on optical coherence tomography (OCT)

Extension Phase

1. After the loading phase, if improvement is observed (stable or improved vision and reduced macular edema):

   • Extend treatment interval by 2 weeks (to 6 weeks)
   • Continue extending by 2-week increments at each visit if stability is maintained
   • Maximum extension typically reaches 12-16 weeks 2, 3

2. If worsening is observed at any visit (increased fluid or decreased vision):

   • Reduce interval by 2 weeks
   • Resume treatment at this shorter interval until stability is regained

Criteria for Stability

• No new or worsening retinal hemorrhages
• Stable or improved visual acuity
• No increase in retinal thickness on OCT
• Absence of new intraretinal or subretinal fluid

Adjunctive Therapy

• Consider focal/grid laser as adjunctive therapy for persistent edema despite anti-VEGF therapy 1
• Focal/grid laser may be added when edema persists but is no longer improving with anti-VEGF injections 4

Monitoring and Follow-up

Follow-up Schedule

• During loading phase: Every 4 weeks
• During extension phase: According to the current treatment interval
• For center-involving DME: Follow-up every 1-3 months 4, 1

Assessment at Each Visit

• Best-corrected visual acuity
• OCT imaging to assess central subfield thickness and presence of fluid
• Dilated fundus examination to assess diabetic retinopathy status

Clinical Outcomes and Expectations

Research shows that treat and extend regimens with aflibercept can achieve:

• Significant reduction in central subfield thickness (approximately 187 μm reduction over 1 year) 3
• Visual acuity gains of approximately 4-6 letters over 1 year 3
• Successful extension to 12-16 week intervals in 61.3% of patients after 1 year 3

Important Considerations and Pitfalls

Common Pitfalls

• Extending intervals too rapidly before stability is confirmed
• Failing to reduce intervals promptly when recurrence is detected
• Overlooking systemic factors like uncontrolled diabetes that may limit treatment response

Special Considerations

• Early response to aflibercept (≥4 letter gain after induction phase) predicts better final visual outcomes 3
• Patients with baseline visual acuity of 20/50 or worse may require more intensive treatment 5
• Improved blood sugar control is essential for optimal outcomes 1

Treatment Resistance

• For patients with incomplete response to other anti-VEGF agents (ranibizumab/bevacizumab), switching to aflibercept may provide anatomic improvement in approximately 79% of cases 6

The treat and extend protocol offers the advantage of individualizing treatment frequency while minimizing the number of injections and clinic visits, making it a practical approach for long-term management of DME while maintaining visual and anatomic improvements.