How often does an 80-year-old woman with diabetic macular edema need anti-vascular endothelial growth factor (anti-VEGF) injections, such as ranibizumab (Lucentis) or aflibercept (Eylea)?

Anti-VEGF Injection Frequency for Diabetic Macular Edema

This 80-year-old woman with diabetic macular edema should receive monthly (every 4 weeks) anti-VEGF injections initially for 4-6 months, then transition to an individualized schedule based on treatment response, with injections continuing as long as vision or edema improves, and follow-up intervals extending to 8-16 weeks only after 3 consecutive visits show no need for treatment. 1

Initial Treatment Phase (First 4-6 Months)

The standard approach requires monthly injections during the loading phase:

• Start with 4-6 consecutive monthly injections of ranibizumab 0.3 mg, bevacizumab 1.25 mg, or aflibercept 2 mg 1
• All patients should receive at least 4 injections at 4-week intervals before considering any treatment modifications 1
• Monthly visits are mandatory during this initial period regardless of response 1

Continuation Phase Criteria

After the initial loading phase, injection frequency depends on treatment response:

• Continue monthly injections as long as vision OR central macular thickness continues to improve compared to the previous visit 1
• Treatment should continue until vision reaches 20/20 or better, OR edema completely resolves 1
• If improvement plateaus (no change in vision or OCT thickness for 2 consecutive visits after week 24), injections may be held at investigator discretion 1

When to Hold Treatment

Injections can be withheld only under specific circumstances:

• "Success" criteria met: Visual acuity ≥20/20 OR OCT central subfield thickness <250 μm 1
• No improvement: OCT central subfield thickness decreased by <10% AND visual acuity improved by <5 letters compared to prior injection 1
• Treatment may be held if additional injection seems unlikely to provide further benefit 1

Resuming Treatment After Holding

If injections are withheld, close monitoring is essential:

• Resume monthly injections immediately if edema recurs or worsens at any follow-up visit 1
• Return to 4-week visit intervals once injections resume 1
• Continue monthly treatment until edema stabilizes again for 3 consecutive visits 1

Extended Follow-Up Intervals

Follow-up can be extended only after prolonged stability:

• After year 1 (52 weeks), if treatment withheld for 3 consecutive monthly visits: extend follow-up to 8 weeks 1
• If still no treatment needed at 8-week visit: extend to 16 weeks 1
• Maximum extension is 4 months between visits 1
• If edema recurs at extended intervals, immediately return to monthly visits and injections 1

Expected Treatment Burden

Real-world injection frequency based on clinical trial data:

• Year 1: Median of 9-10 injections (range: 6 initial injections plus 3-4 additional) 1, 2
• Year 2: Median of 5-6 injections (approximately half of year 1) 1, 2
• Over 2 years: Median total of 15-16 injections 2
• Most patients require near-monthly administration during the first 12 months, with fewer injections in subsequent years 1

Drug Selection Considerations

For this 80-year-old patient, drug choice matters based on baseline vision:

• If vision is 20/50 or worse: Aflibercept provides superior outcomes at 1 year (18.3 letter gain vs 13.3 for bevacizumab, 16.1 for ranibizumab) 1, 2
• If vision is 20/40 or better: All three drugs (aflibercept, ranibizumab, bevacizumab) provide similar visual outcomes 1, 2
• By 2 years, aflibercept and ranibizumab achieve similar results, both superior to bevacizumab 1, 2

Critical Follow-Up Schedule

For center-involving DME with vision loss (20/30 or worse):

• Monthly visits (every 4 weeks) are required during active treatment 1
• Every 1-3 months for stable DME after achieving treatment goals 1
• Every 2-4 months only for good visual acuity (better than 20/30) with center-involving DME where treatment may be deferred 1

Common Pitfalls to Avoid

Critical errors that compromise outcomes:

• Never extend follow-up intervals before 52 weeks of treatment, even if edema appears stable 1
• Do not stop treatment simply because vision is stable—continue if anatomic improvement (OCT thickness reduction) is ongoing 1
• Avoid under-treatment: Real-world outcomes are often worse than clinical trials due to insufficient injection frequency 3
• Do not wait for vision loss to resume treatment—restart injections as soon as edema recurs on OCT 1

Alternative Approach: Treat-and-Extend

An alternative protocol with comparable outcomes:

• Treat-and-extend regimens adjust visit intervals based on treatment response 1
• This approach provides comparable visual and anatomic results to monthly dosing with fewer injections at 2 years 1
• However, the protocol-driven approach described above (DRCR.net protocol) has the strongest evidence base 1