Anti-VEGF injections: the IOI protocol
In wet AMD, anti-VEGF injections are the reference treatment — but the number of injections needed varies enormously from one patient to another. The IOI protocol of the Fédération France Macula proposes observing each patient's recurrence pattern in order to give exactly the injections that are necessary and sufficient, no more and no less. Page written by Dr Mayer Srour, co-author of these recommendations.
Injections in wet AMD: the essentials in 30 seconds
- How many injections? It depends on each patient: 13 to 20% have no recurrence after the first 3 injections, while others need regular treatment for years. No fixed protocol suits everyone.
- The IOI protocol in 3 phases: Injection — 3 initial monthly injections; Observation — monthly follow-up for 6 to 9 months, with an injection as soon as a sign of activity reappears on OCT; Individualisation — the rhythm is then set according to the patient's own recurrence interval.
- Why individualise? Systematic injections carry a risk of over-treatment (risk of infection, cost, possible atrophy); poorly monitored “as-needed” injections carry a risk of under-treatment and loss of vision. Observation makes it possible to avoid both.
- Do not wait: treatment should start no later than 7 days after the diagnosis of wet AMD with exudative signs (HAS and FFM recommendation).
Why does the number of injections vary so much?
Anti-VEGF drugs (ranibizumab, aflibercept, and more recently faricimab and brolucizumab) have transformed the outlook for wet AMD. But studies have shown a wide variability in response: in a series followed for 4 years, there are good responders (about 21%), poor responders (15%) and a majority of regular responders (64%) who need maintenance treatment. Up to 40% of patients have a remission of more than 6 months, and in a French series, 63% had at least one year without injections over 5 years of follow-up.
The factors involved: age, type of neovessel, its size and duration, the presence of fibrosis or atrophy, initial visual acuity and genetic background. It is impossible to predict in advance which category a patient falls into: you have to observe them.
Existing protocols and their limits
No single protocol suits everyone. The FFM recommendations are a compromise aiming for the “necessary and sufficient” injections for the best possible vision.
Phase 1 — Injection: induction
Treatment starts no later than 7 days after the diagnosis of wet AMD with intraretinal or subretinal fluid, whatever the clinical form (except in the particular case of so-called quiescent neovessels, which may be monitored). The choice of drug is left to the practitioner.
The induction phase comprises 3 injections 4 weeks apart. Tests (acuity, OCT, fundus examination) are not essential between these three injections, unless the patient reports a drop in vision.
Phase 2 — Observation: 6 to 9 months of monthly follow-up
This is the heart of the protocol. For 6 to 9 months, the patient is seen every month: visual acuity, OCT, fundus examination or retinal photography. An injection is given promptly (within 7 days) as soon as a sign of activity reappears:
If in doubt, an angiography with fluorescein or indocyanine green (to look for polypoidal vasculopathy or type 3 neovessels) is performed. Both eyes are examined at every visit: detecting involvement of the second eye early improves its outlook.
Phase 3 — Individualisation
At the end of the observation period, a retrospective analysis of the recurrence dates determines the patient's own recurrence interval and checks that it is reproducible. Follow-up and injections are then set to this interval: for example, a patient who relapses 4 to 8 weeks after each injection will be retreated and seen again at 6 weeks.
Patients are then classed as without recurrence (spaced-out monitoring), those with regular recurrences (injections scheduled at their interval) and those with an unfavourable profile (fibrosis, atrophy), for whom the benefit/risk balance of each injection is reconsidered. The protocol thus adapts to the natural history of each person's disease.
What this means for you
In practical terms, at the practice: a rapid start, three initial injections, then rigorous monthly follow-up for several months with OCT at every visit, and an injection given on site within the week if needed. Then a personalised schedule, explained and reassessed. The aim is twofold: to protect your vision and to avoid injecting you unnecessarily.
Care in Noisy-le-Grand
Dr Mayer Srour, a retina and macula specialist trained at the Centre Hospitalier Intercommunal de Créteil and author of this publication, sees patients from eastern Paris (93, 94, 77) at the Grand Paris Ophtalmologie practice (67 rue de Malnoue, Noisy-le-Grand, 93). The practice’s equipment allows a complete assessment on site: OCT Spectralis, OCT angiography, angiography, retinal photography, and intravitreal injections are performed at the practice.
Anti-VEGF injections: the IOI protocol, your questions
Answers from Dr Mayer Srour, ophthalmologist specialising in the retina in Noisy-le-Grand.
How many injections will I receive in the first year?
On average 5 to 8, but with large differences: some patients stop after the 3 induction injections, others need an injection every 4 to 8 weeks. The observation phase is precisely what determines this for you.
Are the injections for life?
Not necessarily. Some patients enter lasting remission; others keep active disease for years and benefit from maintenance treatment. In every case, monitoring continues for life, because a late recurrence remains possible.
What happens if I miss a check-up?
The risk is under-treatment: a recurrence left untreated for several weeks can cause permanent loss of vision. If you cannot attend, tell the practice so that it can be rescheduled quickly; if you notice a drop in vision or new distortion, be seen without delay.
Why not inject every month, to be sure?
Because an unnecessary injection is not trivial: each injection carries a small risk of infection (endophthalmitis), and studies suggest that prolonged monthly treatment may promote atrophy. The IOI protocol seeks the right number.
Which drug is used?
Ranibizumab or aflibercept in the 2017 recommendations; since then, faricimab and brolucizumab have widened the options, with sometimes longer intervals. The choice is made with you according to your lesion and your response.
Can another treatment be combined?
In polypoidal vasculopathy, photodynamic therapy may be combined with anti-VEGF drugs. For classic wet AMD, anti-VEGF drugs remain the reference treatment; vitamin supplements (AREDS formula) have a role in dry forms and in protecting the second eye.
Related reading
Wet AMD diagnosed or under treatment?
Management within the week, injections performed at the practice and personalised OCT follow-up with Dr Srour, in Noisy-le-Grand.
The Grand Paris Ophtalmologie practice in Noisy-le-Grand provides consultations, screening and surgery for patients from neighbouring towns: