Intravitreal Implants – The Port Delivery System and its Contemporaries

Ocular disease treatments have long made use of the vitreous to deliver medication, but the relatively recent advent of intravitreal implants has revolutionized the entire treatment landscape. Even the earliest implant offered long-term, targeted delivery of high-concentration drugs directly into the posterior segment: the years since have seen this technology grow by leaps and bounds, providing a variety of medications for a slew of conditions.

With the US Food and Drug Administration (FDA)’s approval of the Port Delivery System on October 22, 2021, intravitreal implants have opened a variety of new treatment pathways for several ocular diseases. Based on the variety of devices currently making their way through the pipeline, the growth of the intravitreal landscape will not slow down any time soon. From less invasive devices such as contact lenses to biodegradable implants, the horizon for these therapies seems just as promising as it did almost 30 years ago.

The Early Days

Intravitreal implants have existed in a clinical setting since 1996, with the FDA’s approval of vitrasert, manufactured by Bausch and Lomb, for the treatment of cytomegalovirus retinitis. It contained 4.5mg ganciclovir and dispensed roughly 1 mcg/hour for anywhere from 5-8 months. It was constructed from a discontinuous hydrophobic ethylene vinyl acetate (EVA) film, which was surrounded by inner and outer permeable PVA layers.1

Vitrasert acted by diffusing fluid within itself, which in turn led to the dissolution of the drug pellet. This then released the drug into the vitreous cavity at a constant rate, which would control inflammation, reduce recurrences, and improve visual acuity. Vitrasert was initially indicated for acquired immune deficiency virus-associated cytomegalovirus (CMV) retinitis.1

Still in use today, vitrasert has since proven its safety despite the residual inactive shell it leaves behind. However, data from a 2024 trial have indicated the necessity of intraocular therapy in addition to vitrasert when treating CMV retinitis. Of the 16 eyes included in this study, 10 required intraocular surgery for the removal of cataracts and the implant itself, as well as pars plana vitrectomy.2

The next intravitreal implant would not be approved until almost a decade later, with the advent of retisert for the treatment of chronic non-infectious posterior uveitis in 2005. This implant, created by pSivida and marketed via a partnership with Bausch & Lomb, awas a nonbiodegradable (NBI) of the corticosteroid fluocinolone acetonide. It consists of a small 5x2 mm reservoir with roughly 0.59 mg of fluocinolone acetonide coated with PVA and silicone laminates.1

Retisert was designed to administer roughly 0.6 µg into the vitreous cavity per day. The implant was designed to last up to 3 years. During its clinical use, retisert was also found effective in treating diabetic macular edema (DME) and macular edema secondary to central retinal vein occlusion (RVO).1

Although retisert has long been included in the ophthalmic treatment cascade, specifically for patients with uveitis, primary parent company Bausch & Lomb announced earlier this year that the implant will be discontinued in April of 2026. The company cited difficulties in obtaining manufacturing components and advised patients to consider alternative treatments. However, no currently approved implants match retisert’s 0.59 mg dose and effect duration.3

The next critical advancement in intravitreal implants, approved by the FDA in 2009 for treating vein occlusion-associated macular edema and in 2010 for non-infectious posterior uveitis, was DEX. DEX is the first biodegradable implant to receive approval, appearing as a rod-shaped pellet roughly 6.5x0.45 mm in size. In addition to dexamethasone, DEX contains a biodegradable PLGA polymer matrix which degrades into lactic and glycolic acid over 6 months.1

A 2024 systematic review comparing DEX with standard anti-VEGF therapy found that the implant achieved distinctly superior outcomes in both best-corrected visual acuity (BCVA) and central macular thickness (CMT). DEX did, however, demonstrate a higher risk of elevated intraocular pressure (IOP), suggesting a potential limitation to its applicability. Investigators also noted the relatively small number of studies included in this review, noting that results should be interpreted with caution.4

Implant development then fell by the wayside for a few years – the next approved model was ILUVIEN, another fluocinolone acetonide implant for the treatment of diabetic macular edema (DME). ILUVIEN is designed to last 36 months, steadily releasing 0.25 µg/day of fluocinolone acetonide. It was approved by the FDA in 2014, and was followed shortly in 2018 by Yutiq, a similar model also for the treatment of DME. Yutiq is unique in that it contains 0.18 mg of fluocinolone acetonide, and releases roughly 0.25 µg/day for 3 years.1,5

The Port Delivery System

In 2021, the FDA approved Genentech’s port delivery system (PDS), also known as Susvimo, a nonbiodegradable permanent implant for delivering the anti-vascular endothelial growth factor (VEGF) antibody ranibizumab in patients with neovascular age-related macular degeneration (nAMD). In addition to entering an entirely new style of treatment into the implant field, the PDS revolutionized the industry in 1 other key aspect: it was refillable.1

Comprised of a central implant and 4 ancillary devices designed to initially fill ranibizumab, for surgical implantation, for explanation, and for eventual refill exchange. Additionally, an extra-scleral flange allows the device to anchor to the sclera, a silicon self-sealing septum allows it to be refilled, an implant body holds the drug reservoir, and a titanium release control element manages titration of the ranibizumab diffusion into the vitreous. The PDS can hold roughly 20 µl and releases a minimum of 2.3 µg/day for 6 months.1

The PDS allows clinicians to maintain results comparable to monthly ranibizumab injections without the treatment burden of repeated clinic visits. In fact, existing data from the phase II LADDER trial indicate an extended median time to first refill of 15.8 months (with 100 mg/mL PDS). Currently, the FDA has approved treatment interval extension of up to 6 months, making the PDS the longest interval of any currently approved nAMD therapies.6

This significant reduction in total visits per year also helps clinicians circumvent many of the main factors contributing to undertreatment among patients with nAMD. Time constraints, caregiver burdens, and the simple discomfort associated with repeated intravitreal injections are all addressed by the extended treatment interval. Data from the phase III ARCHWAY trial support this, with 218 of 234 patients who received the PDS stating that they preferred the implant over intravitreal injections at the end of the study period. An accompanying questionnaire indicated fewer treatments and less discomfort as the driving forces behind these preferences.6

“At first, some patients are understandably hesitant about the idea of an implant, but once they understand the long-term benefits—especially fewer injections and clinic visits—they’re often very receptive,” Veeral Sheth, MD, told HCPLive in an interview. “Many of my patients have said they wish this had been available sooner. The concept of a ‘set it and forget it’ approach really resonates with them.”

Sheth went on to discuss his patients’ preferences for extended dosing intervals, reinforcing existing literature.

“Patients love [extended dosing]. Longer intervals mean fewer disruptions to their daily lives, and many report feeling less anxious knowing they don’t have to come in so often or, if they are coming in, knowing that they are not likely to get an injection at that time. It also gives them a sense of progress—like they’re ‘graduating’ from more intensive treatment.”

Additionally, Sheth reported the relative ease with which clinicians can adapt to the relatively uncomplicated implant procedure.

“There is a learning curve, no question—but it’s manageable,” Sheth said. “The surgical procedure requires precision and attention to detail, but with proper training and support, most retina specialists can become proficient fairly quickly. Once you’ve done a few, the workflow becomes second nature.”

The Future of Ophthalmic Implants

Even with the groundbreaking improvements in treatment and practice that the PDS has wrought, intravitreal implant technology shows no sign of running out of steam. More devices are rapidly appearing in the ophthalmic pipeline, promising better and faster treatment over longer durations with fewer clinic visits.

One such device is in development by Dubai-based tech startup XPANCEO. These prototype smart contact lenses are intended to be used in the same fashion as standard daily or weekly lenses. The main 3 prototypes were presented at MWC 2025 in Barcelona, Spain. Most prominent was the Smart Contact Lens with an IOP Sensor, which utilizes an artificial intelligence-powered smartphone app to collect real-time readings of intraocular pressure (IOP).7

“We currently have several prototypes at different stages. One is a passive lens designed exclusively for intraocular pressure (IOP) monitoring, while another combines IOP monitoring with drug delivery capabilities,” Valentyn Volkov, PhD, founder and scientific partner of XPANCEO, said in an interview with HCPLive. “The former lens, being disposable and not requiring refills, is intended to be worn like standard dailies or weeklies—for the whole day, typically 8 to 12 hours from morning until evening.”

Additionally, the EYP-1901, a bioerodible, sustained-release intravitreal insert dispensing vorolanib, has recently successfully achieved noninferiority in a phase 2 trial versus aflibercept 8 mg. The recent DAVIO 2 trial, presented at the American Society of Retina Specialists, indicated the efficacy of vorolanib in extending the duration of wet age-related macular degeneration treatment. During the study, patients assigned to EYP-1901 received an average of <1 anti-VEGF injection in 6 months, indicating its clear superiority to aflibercept in treatment duration.7

“Our patients with wet macular degeneration are elderly, they have trouble getting to appointments, they oftentimes need somebody to accompany them to appointments, which means someone else has to take a day off work to bring them in,” said Avni Finn, MD, MBA, associate professor of ophthalmology, vitreoretinal diseases, and surgery at Vanderbilt Eye Institute, during an interview with HCPLive. “Putting in something that is sustained release and can really give patients more durability…it’s really going to change the burden of coming in for regular visits, for regular injections.”8

References

1. Mohan S, Ratra D. Intravitreal Implants. [Updated 2023 Jul 3]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK587356/

2. Caranfa JT, Duker JS. Long-Term Follow-up of Patients With Cytomegalovirus Retinitis Treated With a Ganciclovir Implant. J Vitreoretin Dis. 2024;8(4):415-420. Published 2024 Apr 14. doi:10.1177/24741264241247610

3. Arepalli S. An Update on Local Steroids for Uveitis. Retinal Physician. July 11, 2025. Accessed August 26, 2025. https://retinalphysician.com/issues/2025/julyaugust/uveitis-corner/#:~:text=Earlier%20this%20year%2C%20Bausch%20+%20Lomb,dose%20and%20duration%20of%20effect.

4. Tang HX, Li JJ, Yuan Y, Ling Y, Mei Z, Zou H. Comparing the efficacy of dexamethasone implant and anti-VEGF for the treatment of macular edema: A systematic review and meta-analysis. PLoS One. 2024;19(7):e0305573. Published 2024 Jul 10. doi:10.1371/journal.pone.0305573

5. Massa H, Nagar AM, Vergados A, Dadoukis P, Patra S, Panos GD. Intravitreal fluocinolone acetonide implant (ILUVIEN®) for diabetic macular oedema: a literature review. J Int Med Res. 2019;47(1):31-43. doi:10.1177/0300060518816884

6. Eichenbaum DA, Ahmed A, Hiya F. Ranibizumab port delivery system: a clinical perspective. BMJ Open Ophthalmol. 2022;7(1):e001104. doi:10.1136/bmjophth-2022-001104

7. XPANCEO. XPANCEO Unveiled Three New Smart Contact Lens Prototypes at MWC 2025. March 3, 2025. Accessed August 25, 2025. https://www.xpanceo.com/blog/xpanceo-unveiled-three-new-smart-contact-lens-prototypes-at-mwc-2025

8. Finn A. EYP-1901 Implant Extends Duration of Wet AMD Treatment, with Avni Finn, MD, MBA. HCPLive. August 7, 2025. Accessed August 25, 2025. https://www.hcplive.com/view/eyp-1901-implant-extends-duration-of-wet-amd-treatment-with-avni-finn-md-mba