TY - JOUR

T1 - Development of a Novel Valve-Controlled Drug-Elutable Microstent for Microinvasive Glaucoma Surgery

T2 - In Vitro and Preclinical In Vivo Studies

AU - Siewert, Stefan

AU - Kischkel, Sabine

AU - Brietzke, Andreas

AU - Kinzel, Ludmila

AU - Lindner, Tobias

AU - Hinze, Ulf

AU - Chichkov, Boris

AU - Schmidt, Wolfram

AU - Stiehm, Michael

AU - Grabow, Niels

AU - Guthoff, Rudolf F.

AU - Schmitz, Klaus Peter

AU - Stahnke, Thomas

N1 - Funding Information: The authors thank S. Grossmann and F. Kamke (Institute for ImplantTechnology and Biomaterials e.V., Rostock-Warnemünde, Germany) for the scanning electron microscopic examination and for support of pressure–flow characterization of microstents, respectively. The graphic support of A. Dierke (Institute for ImplantTechnology and Biomaterials e.V., Rostock-Warnemünde, Germany) in creating anatomic and technical illustrations (Figs. 1 and 2) is gratefully appreciated. Spray coating of microstents by D. Bajer is gratefully appreciated. The authors also thank the students J. Dostal, E. Fuhrmann, and J. Allahham for mechanical testing of the microstent material as well as the material modeling for the finite element analysis. The authors appreciate the excellent laboratory work as well as animal care of M. Nerger and G. Karsten (Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany), C. Leyh (Department of Ophthalmology, Rostock University Medical Center, Rostock, Germany), and P. Wolff (Institute for Experimental Surgery, Rostock University Medical Center, Rostock, Germany). Financial support by the Federal Ministry of Education and Research within RESPONSE “Partnership for Innovation in Implant Technology” is gratefully acknowledged. The preclinical MRI system in the Core Facility Multimodal Small Animal Imaging was supported by European Regional Development Fund (EFRE funding: UHROM 16). Funding Information: Financial support by the Federal Ministry of Education and Research within RESPONSE “Partnership for Innovation in Implant Technology” is gratefully acknowledged. The preclinical MRI system in the Core Facility Multimodal Small Animal Imaging was supported by European Regional Development Fund (EFRE funding: UHROM 16).

PY - 2023/3

Y1 - 2023/3

N2 - Purpose: Microinvasive glaucoma surgery (MIGS) has become an important treatment approach for primary open-angle glaucoma, although the safe and long-term effective lowering of intraocular pressure with currently available implants for MIGS is not yet achieved to a satisfactory extent. The study focusses on the development and in vitro and in vivo testing of a novel microstent for MIGS. Methods: A silicone elastomer-based microstent was developed. Implants were manufactured using dip coating, fs-laser cutting, and spray coating. Within the current study no antifibrotic drug was loaded into the device. Sterilized microstents were analyzed in vitro regarding pressure–flow characteristics and biocompatibility. Six New Zealand white rabbits were implanted with a microstent draining the aqueous humor from the anterior chamber into the subconjunctival space. Drainage efficacy was evaluated using oculopressure tonometry as a transient glaucoma model. Noninvasive imaging was performed. Results: Microstents were manufactured successfully and characterized in vitro. Implantation in vivo was successful for four animals with additional device fixation. Without additional fixation, dislocation of microstents was found in two animals. Safe and effective intraocular pressure reduction was observed for the four eyes with correctly implanted microstent during the 6-month trial period. Conclusions: The described microstent represents an innovative treatment approach for MIGS. The incorporation of a selectively antifibrotic drug into the microstent drugelutable coating will be addressed in future investigations. Translational Relevance: The current preclinical study successfully provided proof of concept for our microstent for MIGS which is suitable for safe and effective intraocular pressure reduction and offers promising perspectives for the clinical management of glaucoma.

AB - Purpose: Microinvasive glaucoma surgery (MIGS) has become an important treatment approach for primary open-angle glaucoma, although the safe and long-term effective lowering of intraocular pressure with currently available implants for MIGS is not yet achieved to a satisfactory extent. The study focusses on the development and in vitro and in vivo testing of a novel microstent for MIGS. Methods: A silicone elastomer-based microstent was developed. Implants were manufactured using dip coating, fs-laser cutting, and spray coating. Within the current study no antifibrotic drug was loaded into the device. Sterilized microstents were analyzed in vitro regarding pressure–flow characteristics and biocompatibility. Six New Zealand white rabbits were implanted with a microstent draining the aqueous humor from the anterior chamber into the subconjunctival space. Drainage efficacy was evaluated using oculopressure tonometry as a transient glaucoma model. Noninvasive imaging was performed. Results: Microstents were manufactured successfully and characterized in vitro. Implantation in vivo was successful for four animals with additional device fixation. Without additional fixation, dislocation of microstents was found in two animals. Safe and effective intraocular pressure reduction was observed for the four eyes with correctly implanted microstent during the 6-month trial period. Conclusions: The described microstent represents an innovative treatment approach for MIGS. The incorporation of a selectively antifibrotic drug into the microstent drugelutable coating will be addressed in future investigations. Translational Relevance: The current preclinical study successfully provided proof of concept for our microstent for MIGS which is suitable for safe and effective intraocular pressure reduction and offers promising perspectives for the clinical management of glaucoma.

KW - drug-elutable

KW - GDD

KW - glaucoma drainage device

KW - microinvasive glaucoma surgery

KW - microstent

KW - MIGS

KW - valve-controlled

UR - http://www.scopus.com/inward/record.url?scp=85149427307&partnerID=8YFLogxK

U2 - 10.1167/tvst.12.3.4

DO - 10.1167/tvst.12.3.4

M3 - Article

C2 - 36857065

AN - SCOPUS:85149427307

VL - 12

JO - Translational Vision Science and Technology

JF - Translational Vision Science and Technology

SN - 2164-2591

IS - 3

M1 - 4

ER -