Ophthalmic Implants: Current and Future Technologies in Long-Acting Drug Delivery

Introduction

Sustained-release intraocular implants represent a rapidly advancing class of ophthalmic drug-delivery platforms engineered to maintain therapeutic intraocular concentrations over months to years. By providing controlled, localized exposure directly within ocular compartments, these systems reduce dependence on frequent topical administration, systemic immunosuppression or high-frequency intravitreal injections. Clinical utility is established in chronic posterior-segment inflammation (e.g., non-infectious uveitis), macular edema secondary to vascular disease and IOP reduction in glaucoma.

Despite these advantages, long-acting implants introduce risks including corticosteroid-associated cataractogenesis, steroid-responsive IOP elevation, endothelial cell loss (with anterior chamber devices) and mechanical or procedure-related complications. Constraints include implant dimensions, total drug payload, achievable release kinetics and the feasibility of redosing—particularly with non-biodegradable platforms. This review surveys the technical characteristics, clinical performance and translational considerations of currently marketed and emerging implant systems.

Commercially Available Implants

Retisert (fluocinolone acetonide intravitreal implant)

Retisert is a surgically implanted, non-biodegradable device incorporating 0.59 mg fluocinolone acetonide (FAc) within a polyvinyl alcohol/silicone laminate reservoir. It exhibits an initial release of ~0.6 µg/day, tapering to 0.3–0.4 µg/day with near zero-order kinetics for approximately 30 months.

Indicated for chronic non-infectious posterior uveitis, Retisert significantly reduces recurrence rates and the need for systemic therapy. However, its risk profile includes high rates of cataract formation and secondary glaucoma requiring surgical management. The need for pars plana surgical implantation and explantation has restricted its adoption. Production discontinuation anticipated in 2026 may shift demand toward less invasive, office-based long-acting steroid therapies.

Iluvien (fluocinolone acetonide intravitreal implant)

Iluvien is a non-biodegradable cylindrical implant (0.19 mg FAc) delivered via 25-gauge office-based injection. It releases ~0.2–0.25 µg/day for up to 36 months, enabled by its polyimide tube and permeable membrane system.

Initially approved for chronic DME in steroid-tolerant patients, Iluvien received a US label expansion in 2025 for chronic non-infectious posterior uveitis. Pharmacokinetically, it offers sustained nanomolar-level FAc concentrations in the vitreous without the surgical burden of Retisert. Its IOP elevation rates are lower than Retisert but remain a major determinant of patient selection.

Ozurdex (dexamethasone intravitreal implant)

Ozurdex utilizes a PLGA-based biodegradable matrix containing 0.7 mg dexamethasone, engineered for biphasic release over ~3–6 months. Indications include RVO-related macular edema, DME (region-specific approvals) and non-infectious posterior uveitis.

Degradation generates lactic and glycolic acids metabolized via the Krebs cycle, eliminating the need for removal. Clinical management may involve transient visualization of the implant in the vitreous cavity and monitoring for well-characterized steroid-associated IOP excursions.

Durysta (bimatoprost intracameral implant)

Durysta is a biodegradable intracameral implant consisting of a bimatoprost-containing PLGA matrix designed for anterior-chamber placement. It provides sustained prostaglandin analog exposure to the trabecular meshwork and uveoscleral pathway, reducing IOP in open-angle glaucoma and ocular hypertension.

While it demonstrates measurable IOP reduction, its duration of effect is shorter and more variable than posterior-segment implants. Long-term safety requires careful evaluation of endothelial cell density, as PLGA degradation products and implant positioning may impose additional stress on the corneal endothelium. Redosing remains limited due to current labeling and safety considerations.

Pipeline & Emerging Technologies

Ripple Therapeutics — RTC-620 (intracameral)

RTC-620 employs a polymer-free prodrug architecture wherein therapeutic agents are covalently linked within a small-molecule solid monolith that undergoes predictable surface erosion. This allows true zero-order release without residual polymers or excipients.

The system is being investigated for open-angle glaucoma/ocular hypertension, potentially enabling safe, repeatable intracameral dosing—an unmet need with current biodegradable implants. Clinical validation is required to clarify endothelial safety margins, duration of IOP reduction and comparative efficacy versus topical prostaglandin analogs and SLT.

Perfuse Therapeutics — PER-001 (intravitreal)

PER-001 is a biodegradable intravitreal implant releasing an endothelin-receptor antagonist intended to modify vascular dysregulation and neurodegenerative processes in glaucoma and ischemic retinal diseases.

Phase 1/2a data (2025) reported improvement in functional endpoints and a +3 µm increase in RNFL thickness at 24 weeks, suggesting potential neuroprotective activity. The implant uses a 25-gauge insertion system and provides ~6 months of exposure. Long-term safety—particularly in relation to IOP, inflammatory response and durability of neuroprotective effects—remains under investigation. Expansion into diabetic retinopathy targets ischemia-mediated pathology beyond conventional anti-VEGF pathways.

Ocular Therapeutix — OTX-TKI (Axitinib hydrogel implant)

OTX-TKI (Axpaxli) consists of a bioresorbable hydrogel incorporating axitinib, a potent small-molecule VEGFR inhibitor. Its pharmacologic profile supports durable anti-angiogenic activity without reliance on biologics, offering theoretical resistance advantages. Controlled resorption enables prolonged intravitreal exposure for nAMD and NPDR. Ongoing clinical programs aim to determine whether this TKI-based approach can achieve injection intervals >6–9 months with acceptable inflammation risk.

EyePoint Pharmaceuticals — EYP-1901 (vorolanib intravitreal insert)

EYP-1901 (DURAVYU™) combines vorolanib—a selective VEGFR TKI—with EyePoint's bioerodible Durasert E™ platform optimized for zero-order kinetics. Designed for ~9 months of delivery, the insert demonstrated non-inferiority in BCVA compared to aflibercept in the Phase 2 DAVIO 2 trial and achieved an ~80% reduction in supplemental anti-VEGF injections at six months.

Safety findings indicate a favorable local tolerability profile, with a low incidence of intraocular inflammation and no device-related serious adverse events. The agent is positioned as a long-acting maintenance therapy for wet AMD after initial anti-VEGF induction.

PolyActiva — PREZIA™ Polymer-Drug Conjugate Implants

PolyActiva’s PREZIA™ platform uses a covalently bound polymer–drug conjugate, forming implants that release drug through controlled cleavage of linker chemistry rather than diffusion, providing highly linear kinetics and complete biodegradation.

Lead candidate PA5108 delivers a latanoprost prodrug for IOP lowering in POAG and ocular hypertension. Phase 2a data demonstrated consistent 21-week IOP lowering across two implant cycles, supporting predictable pharmacokinetics and mechanical stability. A US Phase 2b trial is assessing repeat-dosing feasibility, dose–response and safety across ~75 patients at 12 clinical sites.

Conclusions

Long-acting intraocular drug-delivery implants continue to expand therapeutic options across retinal disease, uveitis and glaucoma. Current commercial products span biodegradable and non-biodegradable designs, steroidal and non-steroidal mechanisms and anterior versus posterior segment delivery. Each technology exhibits unique pharmacokinetic behaviors, structural considerations and patient-specific risk profiles.

Next-generation implants emphasize:

• polymer-free or polymer–drug conjugate architectures for improved biocompatibility
• true zero-order drug release
• extended duration beyond biologic anti-VEGF agents
• mechanisms targeting vascular, inflammatory and neurodegenerative pathways
• repeat-dosing safety in both the vitreous and anterior chamber

Ultimately, clinical adoption will hinge on demonstrable long-term safety (particularly regarding IOP and endothelial integrity), durability sufficient to meaningfully reduce treatment burden and economic viability.

Nathan Lockwood, PhD

Director of Science and Technology

ProMed Pharma

Nathan Lockwood, PhD

Director of Science and Technology
ProMed Pharma

Nathan Lockwood is Director of R&D at ProMed Pharma, LLC, where teams develop processes to manufacture long-term complex dosage forms for women’s health, ophthalmology, oncology, and other clinical indications. A focus of his team’s work has been the formulation of bioresorbable implants for sustained release applications and scale up for clinical and commercial manufacturing.  Prior to joining ProMed Pharma, he held roles at Boston Scientific and Surmodics leading pharmaceutical aspects of combination medical devices for the treatment of vascular disease and cancer.  He also worked on teams to develop lubricious and drug delivery coatings for medical devices.  Nathan holds Ph.D. and B.S. degrees in Materials Science and Engineering from the University of Minnesota and Northwestern University, respectively.

James Arps, PhD

Director, Pharma Services

ProMed Pharma

James Arps, PhD

Director, Pharma Services
ProMed Pharma

Jim has over 20 years of experience managing product development and commercialization of medical devices, advanced coatings, and drug delivery technologies.  He has worked with both industry and academic partners, guiding products through all stages of development from conceptualization through to customer release.   At ProMed Pharma, he oversees program development activities for polymer-based drug releasing implants and combination device components, working with a team of engineers to develop new drug delivery vehicles as well as robust manufacturing processes and platforms for controlled release of drugs from a variety of materials for applications in cardiovascular, women’s health, and ophthalmology.  He has a Ph.D. in Applied Physics from Vanderbilt University and an M.S. in Management of Technology from the University of Texas-San Antonio.