Since the introduction of guarded filtration surgery, the leading cause of failed glaucoma drainage surgery is fibrosis and scarring in the sub-Tenon and subconjunctival space. Although they are considered the gold standards of surgical intervention, these procedures require diligent follow-up in the early postoperative period to minimize failure and optimize efficacy.
Glaucoma surgeons have addressed this need in many ways, including with the intraoperative and postoperative use of antimetabolites such as 5-fluorouracil and mitomycin C. These agents enhance bleb management by suppressing fibroblast growth factor 2 (FGF-2) and other growth factors responsible for postoperative pathogenesis. By suppressing FGF-2 and inducing apoptosis, the likelihood of a patent fistula and diffuse, unscarred bleb is increased.
Although it is the preference of many glaucoma surgeons, use of mitomycin C may be associated with risks of cataract formation, hypotony, hypotony maculopathy, and other complications. Thus, my colleagues and I at the University of Dayton Research Institute (UDRI) Materials Research Center considered the following question: As these complications are rooted in the cytotoxic effect of the antimetabolite, is suppression of FGF-2 possible without inducing a cytotoxic effect?
A CLOSER LOOK AT CARBON
It is known that carbon has antiembolitic properties. For this and its demonstrated biocompatibility, carbon is the predominant material used in the construction of mechanical heart valves. However, such antiembolitic properties are a nonsequitur to this investigation because failure of glaucoma drainage devices (GDDs) is commonly related to fibrotic encapsulation and not a loss of tube patency.
As carbon inhibits FGF-2 and VEGF pathogenesis, we wondered whether the biocompatibility properties of carbon could be paired with its FGF-2 and VEGF suppression qualities in an application that improves the efficacy of GDDs and glaucoma surgery. Because silicone stimulates the production of FGF-2, we pursued experiments to determine whether a carbon material might sufficiently suppress fibroblast growth and find utility in GDD implantation and glaucoma surgery. In its preferred embodiment, this concept would apply a secure coating of a carbon-based material to current and future devices, regardless of substrate material and/or geometric configuration.
Experiments were designed to evaluate fibroblast growth on eight varied samples differing in substrate material and material constitution. Results of these experiments suggested that, irrespective of substrate material (eg, carbon fiber, PMMA, silicone, etc.), samples with less exposed surface area were subject to greater encapsulation (data on file with UDRI and Mobius Therapeutics). It was hypothesized that a sufficient relationship exists between exposed surface area and the ability to suppress FGF-2 to inhibit fibroblast encapsulation.
The challenge of increasing exposed surface area in a microscopic device is found in its material construction and material configuration. A pure carbon veil deposited upon a substrate would have little effect on suppression of fibroblast growth. A veil of carbon nanotubes deposited upon a substrate increases the exposed surface area by thousands of times and inhibits fibroblast formation without increasing the overall dimensions of the device. Inspired by this discovery, UDRI researchers grew carbon hairs from the nanotubes, creating what we call fuzzy fiber. As this increases the surface area by a multiple of millions compared with a single carbon veil, fibroblast suppression was complete over the entire period while maintaining consistent dimensions.
Because this material is vapor deposited, its geometry is infinitely variable. We have demonstrated its compatibility with coating devices made from PMMA, silicone, polypropylene, polyvinyl, and polyamide. Due to this broad range of material compatibility, we are led to believe that it might be applied universally to any and all existing GDDs in commercial use.
Although the above capabilities are impressive, we cannot assume that existing GDDs hold optimal basic design features. Therefore, in cooperation with Mobius Therapeutics, UDRI invented and patented a new design for a drainage device (US patents 8,764,696 and 10,137,226). Fibroblast encapsulation of an in situ tube inhibits patency due to constriction of its single fluid path or by obstructing its single terminal orifice. The UDRI/Mobius design defies this convention by replacing a single closed fluid path with multiple independent fluid paths that rely on the capillary action inherent when fluid from a high-pressure environment (the anterior chamber) exits to a lower-pressure environment (the subconjunctival space). Even if a channel is wholly obstructed, other patent channels will continue to function. If a single channel is obstructed at a single point, fluid distal to this point will resume migration as the channel distal to the obstruction remains patent.
This project was not engaged with the hope of reconfiguring existing means of drainage. Rather, it focused on resolving unmet medical needs by following a defined method to resolution. How do we inhibit fibroblast growth while addressing issues of cytotoxicity? How can we improve the success rate of these procedures? When we began, the final design was neither anticipated nor defined. Rather, a dialectic of hypothesis, experience, and resolution produced a new solution with the potential to increase the effectiveness of surgery, minimize interventions, and improve outcomes for both patients and providers.
1. Cairns JE. Trabeculectomy. Preliminary report of a new method. Am J Ophthalmol. 1968;66(4):673-679.
2. Bar-David L, Blumenthal EZ. Evolution of glaucoma surgery in the last 25 years. Rambam Maimonides Med J. 2018;9(3):1-9.
3. Desai MA, Gedde SJ, Feuer WJ, Shi W, Chen PP, Parrish RK 2nd. Practice preferences for glaucoma surgery: a survey of the American Glaucoma Society in 2008. Ophthalmic Surg Lasers Imaging. 2011;42(3):202-208.
4. Bokros JC. Carbon in prosthetic heart valves. Ann Thorac Surg. 1989;48(3 Suppl):S49-50.
5. Murugesan S, Mousa SA, O’connor LJ, Lincoln DW 2nd, Linhardt RJ. Carbon inhibits vascular endothelial growth factor- and fibroblast growth factor-promoted angiogenesis. FEBS Lett. 2007;581(6):1157-1160.
6. Crews RM, Jennings JA, McCanless J, Cole JA, Bumgardner JD, Haggard WO. The characterization and optimization of injectable silicone resin particles in conjunction with dermal fibroblasts and growth factors: an in vitro study. J Biomed Mater Res B Appl Biomater. 2010;93(1):227-235.