A rigorous treatment schedule places a high burden on patients and caregivers,^1–3 and can lead to poor adherence/dropout over time, which further exacerbates the disease, thus compromising outcomes.^1,3 The ranibizumab PDS was designed for long-term, continuous drug delivery into the vitreous to maintain constant ranibizumab levels.³ The ranibizumab PDS with fixed refill-exchanges q24w is FDA approved for the treatment of nAMD in adults who have previously responded to at least two anti-VEGF injections,⁴ and remains investigational in Europe.

Patients may receive ranibizumab 0.5 mg on a q12w schedule via a treat-and-extend regimen; however, treatment intervals should be extended stepwise, by no more than 2 weeks at a time, once maximum visual acuity has been achieved.⁵

Abbreviations

FDA, US Food and Drug Administration; nAMD, neovascular age-related macular degeneration; PDS, port delivery system; q12w, every 12 weeks; q24w, every 24 weeks; VEGF, vascular endothelial growth factor.

References

1. Khachigian LM, et al. J Transl Med. 2023;21:133.
2. Tran E, et al. Eur J Ophthalmol. 2024;34:641–8.
3. Regillo C, et al. Ophthalmology. 2023;130:735–47.
4. FDA. Ranibizumab injection for intravitreal use via ocular implant PI. Available at: https://bit.ly/4kl91RR (accessed 12 March 2025).
5. EMA. Ranibizumab SmPC. Available at: https://bit.ly/410hjqn (accessed 12 March 2025).

The PHOTON trial compared aflibercept 8 mg vs aflibercept 2 mg in patients with treatment-naive or previously treated DMO. After the initial monthly loading doses, patients were randomized 1:2:1 to receive aflibercept 2 mg q8w, aflibercept 8 mg q12w or aflibercept 8 mg q16w, with the potential for patients receiving aflibercept 8 mg to extend the treatment interval in the second year. At week 96, among the patients treated with aflibercept 8 mg (n=395), 27% were receiving q24w dosing; 44% ≥q20w dosing, 72% ≥q16w dosing and 93% ≥q12w dosing.

Abbreviations

DMO, diabetic macular oedema; q8w, every 8 weeks; q12w, every 12 weeks; q16w, every 16 weeks; q20w, every 20 weeks; q24w, every 24 weeks.

Reference

Do DV, et al. Presented at: 41st Annual ASRS Meeting, Seattle, WA, USA. 28 July–1 August 2023.

Brolucizumab 6 mg is approved for patients with nAMD, dosed q8w or q12w after the initial loading doses, with the potential to extend if there are no signs of disease activity.¹ The phase IIIa MERLIN trial assessed brolucizumab 6 mg q4w vs aflibercept 2 mg q4w in patients with recalcitrant nAMD (persistent fluid despite previous frequent anti-VEGF therapy).² Brolucizumab was non-inferior to aflibercept in BCVA change at 1 and 2 years; brolucizumab significantly reduced CST and achieved a significantly greater proportion of fluid-free eyes vs aflibercept (both p<0.001).² However, brolucizumab 6 mg q4w was associated with higher rates of IOI, including retinal vasculitis and retinal vascular occlusion vs aflibercept across the trial period, which led to early termination of the study and the recommendation for ≥q8w dosing.² The brolucizumab SmPC includes a special warning and precaution for IOI, including retinal vasculitis and/or retinal vascular occlusion.¹

Abbreviations

BCVA, best-corrected visual acuity; CST, central subfield thickness; IOI, intraocular inflammation; nAMD, neovascular age-related macular degeneration; q4w, every 4 weeks; q8w, every 8 weeks; q12w, every 12 weeks; SmPC, summary of product characteristics; VEGF, vascular endothelial growth factor.

References

1. EMA. Brolucizumab SmPC. Available at: https://bit.ly/42WS75D (accessed 12 March 2025).
2. Brown DM, et al. Ophthalmology. 2025;132:131–40.

Early treatment of nAMD is key to vision improvement, vision preservation and preventing or delaying total blindness.¹ Patients with persistent or recurrent SRF and/or IRF, or a trend toward decreased vision 3–6 months after starting treatment may benefit from switching treatments.² A real world study evaluating outcomes in patients treated with aflibercept 8 mg included 36 eyes that switched from another anti-VEGF treatment (range 3–98 previous injections).³ Results showed a trend towards improved mean CST and visual acuity in the pretreated group with recalcitrant disease (SRF and/or IRF fluid prior to switch; n=29/40) and the group who switched from aflibercept 2 mg (n=14/40).³ Ophthalmologists should, therefore, retain the option of switching anti-VEGF agents in nonresponders.²

Abbreviations

CST, central subfield thickness; IRF, intraretinal fluid; nAMD, neovascular age-related macular degeneration; SRF, subretinal fluid; VEGF, vascular endothelial growth factor.

References

1. Seluarize G, et al. Cureus. 2023;15:e41169.
2. Gale RP, et al. Eye (Lond). 2019;33:1–21.
3. Sambhara D, et al. BMJ Open Ophthalmol. 2025;10:e002091.