Self-Adjustable Valve for Glaucoma Treatment: From Concept to First-in-Human Validation

Glaucoma drainage devices (GDDs) are implantable shunts designed to lower intraocular pressure (IOP) by diverting aqueous humor to a subconjunctival reservoir. However, current GDDs often struggle to (i) provide intrinsic protection against early postoperative hypotony, (ii) passively adapt to time-varying distal outflow resistance during bleb maturation and wound healing, (iii) remain sufficiently compact to enable graft-free implantation, and (iv) maintain MRI compatibility without introducing additional design constraints. This thesis addresses these limitations through the development and validation of a passive, self-adjustable glaucoma valve designed to maintain IOP within the physiological range without external control or manual adjustment. The device is based on a pressure-responsive fluid-structure interaction mechanism in which a pre-stressed flexible membrane dynamically modulates the flow cross-section and, consequently, the hydraulic resistance in response to evolving postoperative pressure conditions. The concept is first demonstrated through proof-of-concept prototypes and subsequently refined into a fully implantable, clinically relevant full-scale design. Performance is investigated using fully coupled numerical simulations, parametric analyses, and in vitro experiments under physiologically relevant flow and pressure conditions. Biocompatibility, mechanical integrity, and patency under fibrotic encapsulation are assessed in vivo in a subcutaneous model, while implantation feasibility and anatomical compatibility are further evaluated using ex vivo ocular models. Finally, clinical feasibility is assessed in a first-in-human pilot study of six patients with advanced glaucoma and uncontrolled IOP, followed for up to 9 months. Across these studies, the valve demonstrates sustained pressure reduction while mitigating hypotony and overdrainage risk and enabling graft-free scleral implantation, supporting passive, self-adjustable flow regulation as a promising strategy for glaucoma treatment. In addition, the underlying pressure-regulation principle is extended to hydrocephalus shunting through the design of a compact fixed-pressure valve with integrated anti-siphon functionality, illustrating broader applicability beyond ophthalmology.