Abstract
Purpose :
The PDS is an investigational treatment for neovascular age-related macular degeneration (nAMD). It consists of a refillable, indwelling, intraocular implant that provides diffusion-mediated continuous intravitreal delivery of ranibizumab. Key aspects of the PDS implant insertion procedure were optimized to mitigate postsurgical complications.
Methods :
Ladder (NCT02510794) was a randomized phase 2 clinical trial in patients with nAMD comparing the PDS with 3 customized formulations of ranibizumab with monthly intravitreal ranibizumab 0.5 mg injections. At trial initiation, the original PDS implant insertion procedure involved a sclero-pars plana stab incision 4 mm posterior to the limbus in the superotemporal quadrant. The prefilled implant was then inserted in the scleral wound, followed by suturing of the conjunctiva and Tenon’s capsule; no scleral suturing was needed. Because of the high rate of vitreous hemorrhage (VH) using this technique for PDS implant insertion, a preclinical surgical study was performed to evaluate potential mitigation strategies.
Results :
At Ladder study start, postsurgical VH occurred in 11 (50%) of the first 22 patients within 7 days of implantation. The trial was paused and a surgical study in minipigs was conducted to identify the root cause and a mitigation strategy. The pars plana (uvea) at the incision site was identified as the source of postsurgical VH. Among alternative surgical methods tested, careful lamellar scleral dissection and edge-to-edge 532-nm laser ablation of the exposed pars plana (uvea) using overlapping 1000-ms laser spots from a vitrectomy probe were the most effective methods to reduce both the incidence and extent of postsurgical VH in minipigs. Following the implementation of this optimized procedure in Ladder, postsurgical VH incidence was reduced to 4.5% (7/157) of PDS-treated patients. Surgery video review showed that adherence to the specified surgical methodology was key to mitigating VH occurrence and other postsurgical events.
Conclusions :
The optimized PDS implant insertion procedure with prophylactic laser ablation of the exposed pars plana before incision and PDS implant insertion reduced the VH rate in the Ladder trial. A robust training plan has been implemented for the ongoing phase 3 Archway trial (NCT03677934) to ensure procedural consistency and maximize surgical outcomes.
This is a 2020 ARVO Annual Meeting abstract.