Author: Claude, from an owner-approved source list · Reviewed by: Dr Mina Abdelmseih · Reviewed: 2026-11-15 · Review due: 2027-11-15

Educational content only. Not personalised medical advice. Clinical decisions remain the responsibility of the treating clinician.

Next-Generation Anti-VEGF and Long-Acting Retinal Drugs

Newer agents and delivery systems aim to keep the vision gains of standard anti-VEGF injections while reducing how often patients must be injected [S1] [S4] [S6]. The main options are faricimab, high-dose aflibercept 8 mg, the ranibizumab Port Delivery System, biosimilars and, still experimental, gene therapy [S1] [S4] [S6] [S8] [S10].

Resource tiers: this is a specialist research topic outside the Tier A / Tier B / Tier C low-resource focus of this library, so no resource tiers are defined here. Biosimilars and cost are the parts most relevant to low-resource settings [S8] [S11].

Red flags

• Durability is the main gain, not better vision. In the pivotal trials, faricimab and aflibercept 8 mg were non-inferior to aflibercept 2 mg in visual acuity, not superior [S1] [S2] [S4] [S5].
• The Port Delivery System has device-specific complications. In Archway, 4 patients (1.6%) had endophthalmitis and 4 (1.6%) had implant dislocation [S6].
• Vision dips after Port Delivery System insertion. In Pagoda, vision fell by a mean of 6.7 letters 4 weeks after insertion and recovered by about week 16 [S7].
• Gene therapy does not yet improve vision. A 2026 meta-analysis found no significant pooled visual acuity gain, and about 44% of treated eyes needed rescue injections [S10].
• Cost decides access. Bevacizumab showed the greatest economic value for diabetic macular oedema (DMO) across 12 economic studies [S11].

Recognise it

Conditions studied in the trials:

Faricimab is a bispecific antibody against angiopoietin-2 and VEGF-A [S1].

Confirm it

• In the trials, interval extension was guided by protocol-defined disease activity criteria [S1] [S4].

Manage it

Before acting on this section, check the national and local guidelines, product information and regulatory approvals that apply where you practise. See the medical disclaimer.

Specialist management (retina services with intravitreal injection)

1. Faricimab, nAMD. TENAYA and LUCERNE (2022) randomised 1329 patients; faricimab up to every 16 weeks was non-inferior to aflibercept every 8 weeks, with mean gains of 5.8 vs 5.1 letters (TENAYA) and 6.6 vs 6.6 letters (LUCERNE) [S1].
2. Faricimab, DMO. YOSEMITE and RHINE (2022) randomised 1891 patients; faricimab with personalised intervals up to every 16 weeks was non-inferior to aflibercept every 8 weeks [S2].
3. Faricimab, RVO. BALATON and COMINO (2024): with dosing every 4 weeks, faricimab was non-inferior to aflibercept at 24 weeks (about 17 letters gained in both arms) [S3].
4. Aflibercept 8 mg, nAMD. PULSAR (2024): dosing every 12 or 16 weeks was non-inferior to aflibercept 2 mg every 8 weeks at 48 weeks (+6.7 and +6.2 vs +7.6 letters) [S4].
5. Aflibercept 8 mg, DMO. PHOTON (2024): dosing every 12 or 16 weeks was non-inferior to 2 mg every 8 weeks (+8.8 and +7.9 vs +9.2 letters) [S5].
6. Port Delivery System, nAMD. Archway (2023): refills every 24 weeks were non-inferior to monthly ranibizumab through about 2 years, and about 95% of patients needed no supplemental injection in each interval [S6]. Adverse events of special interest occurred in 23.8% vs 10.2% [S6].
7. Port Delivery System, DMO. Pagoda (2025): refills every 24 weeks gave +9.6 vs +9.4 letters with monthly ranibizumab; adverse events of special interest occurred in 27.5% vs 8.9% [S7].
8. Biosimilars. A Cochrane review (2024) of 9 trials with 3814 participants compared anti-VEGF biosimilars with their reference products in nAMD; all trials were industry-funded [S8]. A 2026 meta-analysis of 11 trials found no significant difference between aflibercept biosimilars and reference aflibercept in visual acuity or safety [S9].
9. Gene therapy for nAMD. Experimental: 8 early-phase studies with 203 treated participants showed anatomical improvement without consistent visual gain [S10].
10. Dosing schedules, local approval status and prices are not covered here: check the national formulary and regulator.

Refer when

Pitfalls

• Reading non-inferiority as superiority [S1] [S4].
• Comparing trial intervals with real-world intervals: trial extension followed protocol criteria [S1] [S4].
• Overlooking device complications of the Port Delivery System [S6] [S7].
• Ignoring cost-effectiveness, which varies with setting, pricing and time horizon [S11].

Evidence notes

• All pivotal trials of the new agents were industry-funded [S1] [S2] [S4] [S5].
• 96-week PULSAR and PHOTON results are in the triage sheet (PMIDs 40876598 and 41223900) but not in this shortlist; the EIC may add them.
• Not covered by these sources: brolucizumab, tyrosine kinase inhibitor implants and real-world data.

Related articles

• Anti-VEGF biosimilars and off-label bevacizumab
• Safety of intravitreal drugs: inflammation, vasculitis and endophthalmitis
• Diabetic Macular Oedema

References

See the numbered source list below. Each marker [S#] links to its PubMed and DOI record.