Glaucoma is a leading cause of blindness worldwide, and physicians may need to consider multiple treatment modalities throughout a patient’s lifetime to stabilize the disease. Subconjunctival filtration procedures can be highly effective at controlling intraocular pressure (IOP), and glaucoma drainage devices (GDD) have been a mainstay of surgical glaucoma management for many years. These surgeries are often quite effective, but also carry a certain amount of risk that can hinder long-term success.
Although much attention has been focused on minimally invasive glaucoma surgeries (MIGS) over the past decade, ongoing innovation has advanced traditional surgical techniques as well. Three shunting devices currently in development will be discussed here.
Calibreye
Although GDDs can be highly successful, IOP fluctuations in the postoperative period still pose a significant risk for vision-threatening complications. The Calibreye Titratable Glaucoma Therapy surgical system for IOP control (Myra Vision, Inc) is a novel drainage device that offers the surgeon the option to titrate aqueous flow based on the patient’s IOP and postoperative clinical course.
The Calibreye device is made of silicone and contains 3 flow channels that connect the anterior chamber and subconjunctival space. One microfluidic channel is always open, while the other 2 are controlled by nitinol valves in the anterior chamber that are directly visible through the peripheral cornea (Figure 1). One valve controls a medium-sized microchannel, while the other controls a large microchannel. These valves can be opened or closed using a 532-nm argon laser at the slit lamp after implantation, providing 4 different adjustable settings to modulate aqueous flow resistance and therefore IOP. The entire device is 10 mm long, 1.6 mm wide, and 0.3 mm thick, with a wider segment containing 2 eyelets for suture fixation to the sclera.
A preclinical feasibility study involving 20 rabbit eyes was conducted for a follow-up period of 32 days, with laser valve adjustments performed at 7, 14, and 30 days. The ability of the laser to open and close the valves was assessed both visually and by inspecting the egress of fluorescein through the previously closed channels. The laser was able to successfully open and close the valves at each time point and the rabbit eyes tolerated the procedures well without any serious complications.1
Figure 1. The Calibreye Titratable Glaucoma Therapy surgical system has a silicone body with nitinol valves.
A human feasibility clinical trial is currently under way internationally, evaluating procedural success, efficacy, and feasibility in patients with open-angle glaucoma. In this study, physicians are titrating the device from baseline, or both valves closed, to moderate flow settings, where the “medium” valve has been opened. All adjustments were performed within the first 12 postoperative days, and the IOP was measured prior to and 30 to 60 minutes after adjustment. Twelve adjustments were made in 12 eyes, without any significant adverse effects related to the procedure.2
Further clinical trials are needed to fully assess the safety and practical applications of this device; however, the Calibreye system shows promise to modulate IOP as clinically indicated. Calibreye has the potential to revolutionize the management of GDDs in the postoperative period when adverse events can be unpredictable, and therefore may increase the success rate of this surgery.
VisiPlate
Another shunting device in the pipeline is VisiPlate (Avisi Technologies Inc), an ultrathin, nonfibrotic subconjunctival aqueous shunt that lowers IOP through its unique redundant microchannel design. Through these numerous microchannels, aqueous humor is drained from the anterior chamber to the subconjunctival space in a slow and controlled fashion. This can allow for a more favorable, lower profile bleb that can be more comfortable for the patient as well as longer lasting.3
Figure 2. The VisiPlate device in an open product tray.
VisiPlate is made from an alumina plate that is coated with Parylene-C, a polymer that has been used previously in other medical implants. It is 5 mm wide and 9 mm long, with 1 mm of the device in the anterior chamber and the rest residing in the subconjunctival space (Figure 2). The device thickness is less than 30 µm, making it very low profile (Figure 3). This low profile creates a bleb that is more aesthetically pleasing and potentially reduces biomechanical stress and risk of conjunctival erosion. The corrugated material contains networked microchannels in a hexagonal honeycomb configuration. Its nonfibrotic properties also make it potentially effective without the use of an antifibrotic agent, a helpful feature given the additional complications that can be associated with such medications.3
Figure 3. This optical coherence tomography scan shows the VisiPlate device at a patient’s 3-month follow-up.
Early feasibility trials in rabbits showed a 20% to 40% decrease in IOP compared to baseline over the course of 3 months in 9 implanted eyes. No significant adverse events were noted.4 Since then, Avisi has conducted 2 human clinical trials on VisiPlate. The most recent study, known as the VITA trial, initially enrolled 15 patients and currently has 9-month data on 6 of those patients. On average, those with VisiPlate experienced a 46% drop in IOP (from 24 mmHg at baseline to 12.3 mmHg), and a reduction in average medication use from 2.1 medications at baseline to 0.7 medications. Patients were not required to undergo a medication washout. There were no significant postoperative adverse events or interventions, and no patients required subsequent needling. Further trials are needed to fully evaluate the safety and efficacy of this device; these trials are expected to begin in the United States in late 2024 or early 2025.
Paul Implant
The Paul Glaucoma Implant (PGI, Advanced Ophthalmic Innovations) is a valveless tube shunt designed to decrease IOP with a more favorable side effect profile compared to other GDDs available in the United States. The PGI was designed by Dr. Paul Chew. It is not currently available in the United States, but is already in use internationally.
The device has many features that make it a unique option for surgical glaucoma management. It is a valveless GDD made of silicone, making it flexible and easy to implant. The internal and external tube diameters are significantly smaller than those of other GDDs currently used in the United States. For example, the lumen can be easily occluded by a 6-0 or 7-0 polypropylene suture, compared to the 3-0 suture typically used to occlude currently available tube shunts. This smaller diameter can reduce the risk of early hypotony and associated complications and may also reduce the risk of endothelial cell loss. Further, the smaller diameter of the extraocular portion of the tube may also reduce the risk of tube erosion.5
At 21.9 mm width and 16.1 mm depth, the end plate is slightly smaller than a Baerveldt 350 mm2 glaucoma implant (Johnson & Johnson) and larger than an Ahmed FP7 glaucoma valve (New World Medical) with a maximum thickness of 0.95 mm. The larger anteroposterior depth of the plate allows the device to be more posterior on the eye, resulting in a more posterior bleb, while the shorter width allows it to interact less with the rectus muscles, which may reduce the risk of postoperative diplopia.
Many studies have been conducted assessing the PGI’s efficacy and safety. Koh et al were among the first to conduct a prospective, multicenter, single arm study. Eighty-two patients across 6 ophthalmology centers were enrolled and 74 had at least 1 year of follow-up. There was a statistically significant reduction in the mean IOP from 23.1±8.2 mmHg preoperatively to 13.2±3.3 mmHg, and a statistically significant reduction in the mean number of glaucoma medications from 3.3±0.9 preoperatively to 0.3±0.6 at the 12-month follow-up visit. The most common postoperative complications included shallow anterior chamber (11 eyes), hypotony requiring intervention (7 eyes), tube occlusion (5 eyes), and tube exposure (3 eyes). One eye developed postoperative endophthalmitis.5
The PGI has also been studied in childhood glaucoma, although this literature is limited. A recent study by Vallabh et al retrospectively evaluated 25 eyes with pediatric glaucoma that underwent surgery with the PGI. A significant reduction in the mean IOP was observed, from 30.9±5.9 mmHg preoperatively to a mean of 13.2±4.9 mmHg at 12 months and 11.8±4.6 mmHg at 24 months with a significant reduction in the number of glaucoma medications. Eleven eyes were able to achieve medication-free control of IOP.6
The Paul Glaucoma Implant has shown success in other parts of the world at reducing IOP and medication dependence. However, more studies are needed to further evaluate its safety and efficacy compared to currently available GDDs in the United States.
Conclusion
Subconjunctival surgical options continue to evolve, and ongoing innovation in aqueous shunting devices may offer effective ways to lower IOP with potentially improved safety profiles. GP
References
1. Varma R, De Francesco T, Sheybani A, et al. Proof of principle laser titration of glaucoma drainage device. Presented at: American Glaucoma Society annual meeting; February 29-March 3, 2024; Huntington Beach, CA.
2. De Francesco T, Sheybani A, Engelman C, et al. First in human proof of principle laser titration of a glaucoma drainage device. Presented at: American Society of Cataract and Refractive Surgery annual meeting; April 5-8, 2024; Boston, MA.
3. Miller-Ellis E. A multichannel approach to a better bleb. Glaucoma Today. May/June 2023. Accessed July 19, 2024. https://glaucomatoday.com/articles/2023-may-june/a-multichannel-approach-to-a-better-bleb?c4src=home:feed.
4. Kao BW, Meer E, Barbolt TA, et al. Biocompatibility and feasibility of VisiPlate, a novel ultrathin, multichannel glaucoma drainage device. J Mater Sci Mater Med. 2021;32(12):141. doi:10.1007/s10856-021-06613-8
5. Koh V, Chew P, Triolo G, Lim KS, Barton K; PAUL Glaucoma Implant Study Group. Treatment outcomes using the PAUL glaucoma implant to control intraocular pressure in eyes with refractory glaucoma. Ophthalmol Glaucoma. 2020;3(5):350-359. doi:10.1016/j.ogla.2020.05.001
6. Vallabh NA, Mohindra R, Drysdale E, Mason F, Fenerty CH, Yau K. The PAUL glaucoma implant: 1-year results of a novel glaucoma drainage device in a paediatric cohort. Graefes Arch Clin Exp Ophthalmol. 2023;261(8):2351-2358. doi:10.1007/s00417-023-06000-9
