Low Rates of Fibrosis in Eyes Treated with the Port Delivery Platform with Ranibizumab or with Monthly Ranibizumab in the Archway Trial.

PURPOSE: To evaluate the proportion of eyes with fibrosis in the Archway neovascular age-related macular degeneration trial, which compared efficacy and safety between monthly injections of ranibizumab with treatment via the Port Delivery Platform with ranibizumab (PDS), an intraocular implant providing continuous release of ranibizumab into the vitreous, in eyes that had previously demonstrated a response to anti-VEGF treatment. DESIGN: Archway (NCT03677934) post hoc analysis. PARTICIPANTS: Patients received PDS 100 mg/mL with fixed 24-week refill-exchanges (Q24W; n = 248) or monthly intravitreal ranibizumab 0.5 mg injections (n = 167). Patients with subfoveal fibrosis/atrophy on color fundus photography (CFP) were excluded from the trial. METHODS: Masked graders initially assessed CFP images at baseline, week 48, and week 96 for subretinal fibrosis. If grading was uncertain on CFP, spectral-domain OCT (SD-OCT) scans were used to confirm/rule out fibrosis. Two graders assessed images; a senior grader confirmed all cases and arbitrated disagreement. Subretinal hyperreflective material volumes were quantified using deep learning SD-OCT image segmentation. MAIN OUTCOME MEASURES: Proportion of study eyes with fibrosis at baseline, week 48, and week 96. Mean (95% confidence interval) change from baseline in best-corrected visual acuity up to week 96 by presence/absence of fibrosis. RESULTS: The proportion of eyes with fibrosis was low in both arms (PDS Q24W, monthly ranibizumab) throughout the trial (baseline: 5.4%, 4.7%; week 48: 7.2%, 4.7%; week 96: 7.7%, 5.4%). In eyes without baseline fibrosis on CFP, 2.4% (5/210) in the PDS Q24W arm and 0.7% (1/141) in the monthly ranibizumab arm developed fibrosis by week 96. Subretinal hyperreflective material volumes were low throughout the trial in both arms. At week 96, eyes with fibrosis gained 3.2 (-2.0, 8.4; n = 17) ETDRS letters in the PDS Q24W arm and lost -9.9 (-30.3, 10.6; n = 8) letters in the monthly ranibizumab arm. CONCLUSIONS: Rates of fibrosis were low with both continuous delivery (PDS) and monthly ranibizumab in VEGF-experienced patients with no fibrosis at baseline based on CFP. The PDS, which removes the need for monthly injections, represents a useful strategy to reduce treatment burden while preventing development of fibrosis and maintaining visual acuity. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.