Aqueous Humor Biomarkers, Efficacy and Safety in Patients with Naïve Diabetic Macular Edema Treated with Faricimab: The ALTIMETER Study
Ophthalmology Science, 2026
Schlottmann P., Fawzi A., Amador M., Dieckmann A., Gibson K., Glittenberg C., Jhaveri C., Kotak A., Mar F., Neubert A., Sheth V., Souverain A., Titz B., Vazquez-Lombardi C., Wykoff C., Ziemssen F., Vujosevic S.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Ophthalmology | Pathophysiology | Aqueous Humor |  Olink Target 96 |
Abstract
Objective
To explore associations between clinical endpoints, multimodal imaging, and aqueous humor (AH) biomarker patterns in patients with diabetic macular edema (DME) treated with faricimab.
Design
Phase 2b, multicenter, open-label, single-arm, 24-week exploratory study.
Participants
Adults with treatment-naïve DME, best-corrected visual acuity (BCVA) of 20–75 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, and central subfield thickness (CST) ≥ 325 μm were eligible to participate.
Methods
Patients received six 4-weekly intravitreal doses of faricimab 6.0 mg. Functional and multimodal imaging assessments were conducted through Week 24. AH samples were collected at baseline and Week 16 for targeted proteomic analysis. Patients were monitored for safety.
Main Outcome Measures
Prespecified exploratory endpoints included changes from baseline over time in BCVA, CST, the proportion of patients with ≥ 2-step ETDRS Diabetic Retinopathy Severity Scale (DRSS) improvement, intraretinal/subretinal fluid and macular leakage on multimodal imaging, and AH biomarker patterns.
Results
Ninety-nine patients were enrolled. At Week 24, treatment with faricimab resulted in clinical and anatomical improvements consistent with phase 3 trials in DME (YOSEMITE/RHINE); the adjusted mean (95% CI) change from baseline was +9.2 (7.5–10.9) letters for BCVA and –200.2 μm (–214.1 to –186.2) for CST, and 50.0% (37.2–62.8) of patients achieved ≥ 2-step DRSS improvement. Macular leakage area reduced from a median (interquartile range) of 28.6 mm2 (16.9–36.5) at baseline to 2.8 mm2 (0.9–15.3) at Week 20. Total AH protein concentration decreased significantly from baseline to Week 16 (P < 0.0001), with reductions across plasma-derived, inflammatory, and hypoxia response proteins. Notably, faricimab treatment significantly reduced the levels of key proteins associated with worse baseline DRSS scores (including angiopoietin-2, placental growth factor, and erythropoietin) and high baseline macular leakage, suggesting normalization of the AH proteomic profile. Safety was consistent with the known safety profile of faricimab.ConclusionsIn patients with treatment-naïve DME, faricimab treatment resulted in meaningful improvements in functional and anatomical outcomes. These clinical gains were accompanied by a significant reduction in the levels of key AH proteins associated with disease severity, which underscores their potential as biomarkers for assessing disease activity and therapeutic response.