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Aflibercept 8 mg extended dosing maintains visual gains with fewer injections versus 2 mg every 8 weeks in DMEAflibercept 8 mg every 16 weeks matches standard dosing for diabetic macular edema

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Key Takeaway
Consider aflibercept 8 mg extended dosing for DME to reduce injections while maintaining visual gains and safety.

A randomized, double-masked, noninferiority phase 2/3 trial enrolled 658 patients aged ≥ 18 years with center-involved diabetic macular edema and best-corrected visual acuity of 78 to 24 letters. Participants received initial monthly dosing followed by intravitreal aflibercept 8 mg every 12 weeks, 8 mg every 16 weeks, or 2 mg every 8 weeks.

At week 96, change from baseline in best-corrected visual acuity was comparable for the 8 mg groups versus the 2 mg group, with values of +8.8 [9.9] and +7.5 [9.9] versus +8.4 [11.1] letters. Central retinal thickness changes were -185.3 (146.5) μm, -155.0 (144.9) μm, and -187.0 (146.3) μm for the 8 mg every 12 weeks, 8 mg every 16 weeks, and 2 mg every 8 weeks groups, respectively.

The mean number of active injections through week 96 was 9.5, 7.8, and 13.8 for the 8 mg every 12 weeks, 8 mg every 16 weeks, and 2 mg every 8 weeks groups, respectively. Maintenance of dosing intervals at week 96 showed that 88% and 83% of patients randomized to 8 mg every 12 weeks and 8 mg every 16 weeks maintained ≥ 12-week or ≥ 16-week dosing intervals.

Incidence of ocular treatment-emergent adverse events in the study eye was similar across groups, ranging from 37.1% to 45.4%. Tolerability was similar to aflibercept 2 mg every 8 weeks. The study setting was not reported, and p-values or confidence intervals were not reported for the primary outcomes.

A randomized trial tested three dosing schedules for aflibercept in patients with diabetic macular edema. The study included 658 adults aged 18 or older who had vision loss ranging from 20/32 to 20/320. Participants received initial monthly injections followed by extended intervals of either 8 mg every 12 weeks, 8 mg every 16 weeks, or the standard 2 mg every 8 weeks. The researchers followed the patients for 96 weeks to compare outcomes.

Results showed that the two higher-dose regimens produced visual and anatomical improvements comparable to the standard lower-dose schedule. Specifically, changes in best-corrected visual acuity and central retinal thickness were similar across all groups. Patients receiving 8 mg every 16 weeks maintained their dosing intervals in 83 percent of cases, while those on the standard schedule maintained theirs in 47 percent of cases.

Safety profiles were similar across all treatment groups. The incidence of ocular adverse events ranged from 37.1 percent to 45.4 percent in the study eye. No discontinuations due to safety issues were reported. This trial suggests that using aflibercept 8 mg at extended intervals can maintain treatment benefits while reducing the number of injections required over time.

What this means for you:
Aflibercept 8 mg every 16 weeks offers similar vision gains to standard dosing with fewer injections for diabetic macular edema.

Study Details

Study typeRct
Sample sizen = 328
EvidenceLevel 2
Follow-up1.8 mo
PublishedMay 2026
View Original Abstract ↓
PURPOSE: To follow up the previously published comparison of aflibercept 8 mg at extended dosing intervals versus aflibercept 2 mg every 8 weeks (2q8) in patients with diabetic macular edema (DME) through 48 weeks, we now report efficacy, durability, and safety analyses through 96 weeks. DESIGN: PHOTON (ClinicalTrials.gov identifier, NCT04429503) was a randomized, double-masked, 96-week, noninferiority phase 2/3 trial. PARTICIPANTS: Patients aged ≥ 18 years with center-involved DME and best-corrected visual acuity (BCVA) of 78 to 24 letters (Snellen equivalent, 20/32-20/320). METHODS: Patients were randomized 1:2:1 to intravitreal aflibercept 2q8, aflibercept 8 mg every 12 weeks (8q12), or aflibercept 8 mg every 16 weeks (8q16) after initial monthly dosing. Dosing intervals for the aflibercept 8-mg groups were modified based on defined criteria. MAIN OUTCOME MEASURES: Key outcome measures included change from baseline in BCVA and central retinal thickness (CRT) at week 96, proportion of aflibercept 8 mg-treated patients whose randomized dosing intervals were maintained or extended, and safety outcomes. RESULTS: Overall, 658 patients (8q12, n = 328; 8q16, n = 163; 2q8, n = 167) received treatment, and 534 completed week 96. Mean (standard deviation [SD]) BCVA change from baseline at week 96 was comparable for 8q12 and 8q16 versus 2q8 at week 96 (+8.8 [9.9] and +7.5 [9.9] vs. +8.4 [11.1] letters). Mean (SD) CRT change from baseline was -185.3 (146.5) μm, -155.0 (144.9) μm, and -187.0 (146.3) μm for 8q12, 8q16, and 2q8, respectively. Mean number of active injections through week 96 in the 8q12, 8q16, and 2q8 groups was 9.5, 7.8, and 13.8, respectively. Of patients completing week 96, 88% and 83% randomized to 8q12 and 8q16, respectively, maintained ≥ 12-week or ≥ 16-week dosing intervals, 43% and 47% qualified for ≥ 20-week dosing intervals, and 24% and 32% qualified for 24-week dosing intervals at week 96. Incidence of ocular treatment-emergent adverse events in the study eye was similar across groups (37.1%-45.4%). CONCLUSIONS: Aflibercept 8 mg at extended dosing intervals maintained visual and anatomic improvements and similar safety to aflibercept 2 mg every 8 weeks with fewer injections over 96 weeks in patients with DME. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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