Date Published: April 11, 2019
Publisher: Public Library of Science
Author(s): Birthe Schwerk, Lisa Harder, Claudia Windhövel, Marion Hewicker-Trautwein, Anna Wagner, Jan-Peter Bach, Lena Carolin Voigt, Ulf Hinze, Boris Chichkov, Heinz Haferkamp, Holger Lubatschowski, Stephan Nikolic, Ingo Nolte, Demetrios G. Vavvas.
Glaucoma drainage devices are used in surgical glaucoma therapy. Success of controlling the intraocular pressure is limited due to fibrous implant encapsulation and fibrin coating on the implant which lead to drainage obstructions. An innovative implant with a magnetically adjustable valve was developed. The valve opening of the implant should eliminate inflammatory products from the outflow area and affect fibrous tissue formation to achieve a sufficient long-term aqueous humour outflow. Lifting of this valve should disturb cell adhesion by exerting mechanical forces. Before testing this hypothesis, the flow characteristics of glaucoma drainage devices, especially the outflow resistance by regular IOP, should be considered in a pilot study, as they are important in preventing too low postoperative intraocular pressure known as ocular hypotony. Therefore, two prototypes of the innovative implant differing in their valve area design were examined regarding their flow characteristics in a limited animal experiment lasting two weeks. Ten healthy New Zealand White rabbits were divided into two groups (A & B) with different implanted prototypes. Daily, tonometry and direct ophthalmoscopy were performed to assess the intraocular pressure and the inflammatory reaction of the eye. After two weeks, the rabbits were euthanised to evaluate the initially histological inflammatory reaction to the implant. In group A, one case of hypotony emerged. When considering the entire observation period, a highly statistically significant difference between the intraocular pressure in the operated eye and that in the control eye was detected in group A (p < 0.0001) in contrast to group B (p = 0.0063). The postoperative inflammatory signs decreased within two weeks. Histologically, a typical but low level foreign body reaction with macrophages and lymphocytes as well as mild to moderate fibrosis was seen after the short experimental period. Based on our tonometric results, prototype B seems to be the system of choice for further research assessing its long-term function and biocompatibility.
Glaucoma affects 64.3 million people worldwide . An imbalance between aqueous humour production and outflow leads to high individual intraocular pressure (IOP), which is supposed to be a main risk factor in pathogenesis. Due to ischemia and nutritional deficits, retinal ganglion cells are destroyed [2, 3], which in turn leads to irreversible blindness .
In the present study, New Zealand White rabbits, considered as an established animal model for ophthalmic studies [23, 28–30], were chosen. Since the anatomy of rabbit eyes [31, 32] and conjunctiva  are similar to those in humans, the practicable and rapid positioning of the present implant, enabling the opening of the anterior eye chamber, are probably feasible in humans. The general functionality of the implant, undisturbed basic health and the rapid decline in clinical irritation in the present study might be expected in humans. However, it is important to note that the rabbits presented an animal model and were not suffering from glaucoma. Aqueous humour of glaucomatous eyes has a different composition of cytokines and growth factors [34, 35], certainly affecting the inflammatory reaction to the implant. Therefore, it is essential to further investigate the present GDD in a glaucoma model which could reveal the potential of the used GDD to decrease pathologically high IOP and the extent to which the postoperative IOP decreases in glaucoma patients as well as the inflammatory reaction to the present implant in glaucoma-affected eyes.
The novel glaucoma implant examined in the present study showed its efficacy as a drainage device by allowing aqueous humour outflow from the anterior eye chamber to the subconjunctival space. The prototype B with its specially designed valve proved itself as a better flow restrictor and control element of regular IOP in comparison to prototype A with open laser kerf by minimising the postoperative IOP decrease. Its long-term effectiveness in controlling pathologically high IOP remains to be seen in future experiments with an appropriate control GDD. Regarding the inflammatory reaction, the chosen silicone material and design of the new GDD led to satisfactory results in healthy rabbits after two weeks. A longer experimental period with a higher number of glaucoma-affected animals is recommended to verify the sustained functionality of the special valve mechanism, its effect on the encapsulation process and the biocompatibility of the implant in long-term.