One-Year Feasibility Study of Replenish MicroPump for Intravitreal Drug Delivery: A Pilot Study

Abstract

Purpose: To determine the feasibility of the surgical procedure and to collect some safety data regarding the bioelectronics of a novel micro drug pump for intravitreal drug delivery in a Beagle dog model for up to 1 year.

Methods: Thirteen Beagle dogs were assigned to two groups. The experimental group (n = 11) underwent pars plana implantation of MicroPump; the body of which was sutured episclerally, while its catheter was secured at a pars plana sclerotomy. The control group (n = 2) underwent sham surgeries in the form of a temporary suturing of the MicroPump, including placement of the pars plana tube. Baseline and follow-up exams included ophthalmic examination and imaging. The experimental animals were euthanized and explanted at predetermined time points after surgery (1, 3, and 12 months), while the control animals were euthanized at 3 months. All operated eyes were submitted for histopathology.

Results: Eyes were scored according to a modified McDonald-Shadduck system and ophthalmic imaging. Neither the implanted eyes nor the control eyes showed clinically significant pathological changes beyond the expected surgical changes. The operated eyes showed neither significant inflammatory reaction nor tissue ingrowth through the sclerotomy site compared with the fellow eyes.

Conclusion: This study shows that the Replenish Posterior MicroPump could be successfully implanted with good safety profile in this animal model.

Translational relevance: The results of this study in a Beagle dog model are supportive of the biocompatibility of Replenish MicroPump and pave the way to the use of these devices for ocular automated drug delivery after further testing in larger animal models.

Keywords: biocompatibility; intravitreal drug delivery; micropump.

Figure 1.

Schematic representation of the MicroPump implanted at the pars plana position. The green arrow points to the refill port, the red arrow points to a suture tab, while the blue arrow points to the pars plana cannula.

Figure 2.

Color photos of the right eyes of one dog from the experimental group and one from the control group 3 months after surgery, showing comparable conjunctival injection in both dogs.

Figure 3.

OCT scan taken for the right eye from of a dog from the experimental group and the control group after 3 months after surgery showing normal retinal thickness and optic nerve structure.

Figure 4.

H&E-stained slide from the right eye of a dog in the experimental group 12 months after surgery, showing the posterior 2/3 of the globe (magnification is ×10). The inset (magnification is ×40) refers to the sclerotomy site, confirming the absence of any fibrous or epithelial ingrowth.

Figure 5.

Photomicrographs of vertical retinal sections from the midperipheral retina (taken from the right eye of a dog from the experimental group, the right eye of a dog from the control group, and the left eye of a dog from the control group 3 months after surgery) processed for anti-acrolein immunofluorescence (A, D, G) with DAPI nuclear counterstaining shown in images (B, E, H), and merged images (C, F, I). The secondary antibody was Texas red-conjugated anti-mouse IgG. Images show comparable expression of acrolein in the three eyes. Scale bar, 50 μm. GCL, ganglion cell layer; IPL, inner plexiform layer; OPL, outer plexiform layer; IS, inner segments of the photoreceptor layer.

Figure 6.

Photomicrographs of vertical retinal sections from midperipheral retina (taken from the right eye of a dog from the experimental group, the right eye of a dog from the control group, and the left eye of a dog from the control group 3 months after surgery) processed for anticaspase immunofluorescence (A, D, G) with DAPI nuclear counterstaining shown in images (B, E, H) and merged images (C, F, I). The secondary antibody was FITC-conjugated anti-rabbit IgG. Images show comparable expression of caspase-9 in the three eyes. Scale bar, 50 μm.