In Vivo Comparison of Intracameral and Intravitreal Implantation of a Timolol Maleate Miniaturized Injectable Delivery System Device

Purpose: Miniaturized injectable delivery system (MIDS) devices engineered for zero-order release of timolol maleate are evaluated for intracameral (IC) or intravitreal (IVT) injection for ocular safety, effects on intraocular pressure (IOP) reduction, and target tissue drug concentrations.

Design: Preclinical study with in vitro testing of MIDS drug delivery devices together with intraocular injection of the devices in normotensive rabbit eyes.

Subjects: Twenty-four New Zealand rabbits received intraocular injections of MIDS devices.

Methods: Timolol maleate MIDS devices were injected IC or IVT into normotensive New Zealand rabbit eyes (n = 24), with weekly ophthalmic examinations and IOP measurements for 8 or 16 weeks. Eight weeks post-implantation, eyes were enucleated for quantification of tissue drug concentrations by liquid chromatography with tandem mass spectrometry and histology on whole globes.

Main outcome measures: Drug release pharmacokinetics; ocular safety and biocompatibility; IOP; and blood and target tissue drug concentrations.

Results At 8 weeks, IOP in experimental eyes was lowered by 11.1 ± 2.9% (n = 5, P = 0.019) and 18.1 ± 2.6% (n = 6, P < 0.001), for IC and IVT devices, respectively. In extended studies of IVT devices, IOP was numerically lower at 16 weeks by 8.5 ± 5.1% (n = 3, P = 0.24). Intracameral versus IVT injections achieved different tissue distributions (in ng/g; except for aqueous in ng/mL): aqueous 28.5 ± 2.7 vs. 4.5 ± 1.2 (P < 0.001), vitreous 0.3 ± 0.1 vs. 37.2 ± 11.0 (P = 0.010), and ciliary body 14.4 ± 1.8 vs. 50.9 ± 10.8 (P = 0.011). Intraocular inflammation and drug- or device-related adverse effects were absent on examinations and histopathology. Blood drug concentration was below the quantification limit.

Conclusions: Intravitreal and IC devices showed similar IOP reductions; IVT injection led to a higher drug concentration in the target ciliary body tissue, and in normotensive rabbit eyes showed a general reduction of IOP over 8 weeks, indicating the potential of MIDS technology to address issues of patient adherence with glaucoma eye drops.

Author(s): Chu Jian Ma, Youning Zhang, Daniel A. Bernards, Michele Bloomer, John Dickson, Jayakumar Rajadas, Murty Vyakarnam, Tejal A. Desai, Robert B. Bhisitkul

Journal: Ophthalmology Science

Doi: 10.1016/j.xops.2025.100868

Link: https://www.ophthalmologyscience.org/article/S2666-9145(25)00166-6/fulltext

Experimental Paper of the Month manager: Nestor Ventura-Abreu

Editors in Chief: Francesco Oddone, Manuele Michelessi