Changes in Treatment-Naive Pigment Epithelial Detachments Associated With the Initial Anti-Vascular Endothelial Growth Factor Injection: A Post Hoc Analysis From the HARBOR Trial
Related Experiment Video
Updated: Nov 25, 2025
Author Spotlight: Overcoming Anti-VEGF Resistance Through Advanced Vascular Morphology Assessment in Choroidal Neovascularization
Published on: August 11, 2023
Michael Javaheri1, Lauren Hill2, Avanti Ghanekar2
1Retina Specialists of Beverly Hills, Beverly Hills, California.
Importance:
Pigment epithelial detachment (PED) is a feature commonly associated with neovascular age-related macular degeneration (nAMD) and may be perceived as being difficult to treat. Therefore, this investigation explored changes in PEDs and visual acuity outcomes following an initial anti-vascular endothelial growth factor (VEGF) injection and identified factors associated with positive response.
Objective:
To describe changes in treatment-naive pigment epithelial detachments associated with the initial anti-VEGF injection.
Design, Setting, And Participants:
Post hoc analysis of patients from the Phase III, Double-masked, Multicenter, Randomized, Active Treatment-controlled Study of the Efficacy and Safety of 0.5 mg and 2.0 mg Ranibizumab Administered Monthly or on an As-needed Basis in Patients With Subfoveal Neovascular Age-Related Macular Degeneration (HARBOR) trial (NCT00891735) with PED at baseline. The HARBOR trial was a phase 3, randomized, multicenter, double-masked, active treatment-controlled trial. Participants included treatment-naive patients with subfoveal nAMD and PEDs at baseline; intervention arms were pooled for analysis (n = 586). The HARBOR study began in July 2009 and was completed in August 2012, and the post hoc analyses were conducted between October 2016 and May 2018.
Interventions:
Intravitreal injections of ranibizumab, 0.5 mg and 2.0 mg, administered monthly or on an as-needed basis over 24 months.
Main Outcomes And Measures:
Post hoc analyses of flattened PED frequency at month 1, univariate and multivariable analysis of patient and ocular characteristics at baseline and PED status at month 1, and total number of ranibizumab injections received stratified by PED status at month 1.
Results:
A total of 35.5% of patients (208 of 586) with PED at baseline achieved a flattened PED after a single ranibizumab injection. An additional 17.3% subsequently achieved a flattened PED at month 2. Univariate analysis identified an association between older age, lower PED height, and lower subretinal fluid thickness with PED flattening after a single injection. Multivariable analysis identified PED height as a factor associated with this anatomical outcome. Best-corrected visual acuity scores were not superior based on PED flattening at month 1. On average, patients in the as-needed arm who achieved a flattened PED after a single ranibizumab injection required fewer injections by month 24 vs patients whose PED remained present at month 1 (11.0 vs 14.2; difference, 3.3; 95% CI, 1.9-4.6; P < .001).
Conclusions And Relevance:
In this group of treatment-naive patients with PED from nAMD, after the initial ranibizumab injection approximately one-third and after the second injection approximately one-half had flattened PEDS, although visual outcomes were not superior among those that did vs did not have flattening. The findings suggest flattening may serve as a marker for less intensive as-needed injection frequencies.
Trial Registration:
ClinicalTrials.gov Identifier: NCT00891735.
