Macular Neovascularization Type 3 Associated with Macular Atrophy in nAMD Eyes

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A post-hoc analysis of the HARBOR trial suggests MNV type 3 was a strong risk factor for new macular atrophy development at month 24 in ranibizumab-treated eyes with nAMD.

Results from a recent post-hoc analysis of the phase 3 HARBOR trial revealed macular neovascularization (MNV) type 3 was a strong risk factor for new macular atrophy development at month 24 in eyes with neovascular age-related macular degeneration (nAMD) treated with ranibizumab.1

The analysis, led by Giovanni Staurenghi, MD, Eye Clinic, Luigi Sacco Hospital, Department of Biomedical and Clinical Science, University of Milan, suggests fellow eye macular atrophy was additionally identified as a prediction, but did not identify other variables as risk factors.

“No other variables, including ranibizumab treatment, were identified as risk factors for new macular atrophy development,” investigators wrote.1

THE HARBOR trial was a randomized, multicenter, double-masked, controlled trial investigating the efficacy and safety of intravitreal ranibizumab injection administered to patients with choroidal neovascularization (CNV) secondary to AMD. The primary outcome of the trial included the change from baseline in best-corrected visual acuity (BCVA) at month 12. Upon the primary analysis, the trial reported that ranibizumab 2.0mg monthly did not meet the prespecified superiority comparison compared to ranibizumab 0.5mg monthly and 2.0 mg as needed, but all treatment groups showed clinically meaningful vision improvement and improved anatomic outcomes.2

In the current analysis, the investigative team set out to use multimodal assessment to reevaluate macular atrophy and MNV type in the HARBOR trial, according to nAMD nomenclature criteria. Assessments included fluorescein angiography (FA), color fundus photography (CFP), and spectral-domain optical coherence tomography (SD-OCT). Additionally, the team aimed to determine any associations between baseline demographic factors, ocular characteristics, and treatment for nAMD and the 24-month development of macular atrophy.

In total, 922 study eyes and 919 fellow eyes were included in the analysis from the HARBOR trial. The analysis included patients with multimodal assessments on FA, CFP, and SD-OCT at baseline. The investigative team performed a risk analysis for the development of macular atrophy by multimodal assessment and SD-OCT on study eyes without macular atrophy at baseline that had completed SD-OCT assessments for MA at month 24. The main outcome for the analysis was the development of macular atrophy in study eyes at month 24, as well as a risk analysis for developing macular atrophy at month 24 in study eyes that had no macular atrophy at baseline as determined by multimodal assessment.

Of the 1097 patients in the HARBOR trial with nAMD and active subfoveal MNV, a total of 922 study eyes and 919 fellow eyes were included in the multimodal analysis of MNV. Specifically, macular atrophy assessment was performed on SD-OCT. Of the patient population, 593 had no baseline macular atrophy and were included in the risk analysis for developing macular atrophy.

In eyes without detectable macular atrophy at baseline, the analysis showed a larger proportion of eyes with any MNV type 3 (including mixed type) developed new macular atrophy at month 24 (49.2%) compared to eyes with MNV type 1 (26.5%), type 2 (29.1%), or mixed type 1 and 2 (34.6%). As a result, investigators identified MNV type 3 and fellow eye macular atrophy as risk factors for new macular atrophy development at month 24.


  1. Staurenghi G, Cozzi M, Sadda S, Hill L, Gune S. Characteristics that Correlate with Macular Atrophy in Ranibizumab-Treated Patients with Neovascular Age-Related Macular Degeneration. Ophthalmol Retina. 2023;7(4):300-306. doi:10.1016/j.oret.2022.11.002
  2. Busbee BG, Ho AC, Brown DM, et al. Twelve-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration. Ophthalmology. 2013;120(5):1046-1056. doi:10.1016/j.ophtha.2012.10.014