The current evidence-based standard of care for local treatment of neovascular age-related macular degeneration (nAMD) and center-involving diabetic macular edema (CI-DME) are intravitreal anti-VEGF agents. Not only does anti-VEGF treatment reduce vision loss, but also it results in improvement in visual acuity,^1,2 contrast sensitivity,³ reading speed,⁴ and quality of life.⁵ However, the need for frequent injections to maintain therapeutic dosage levels can be fatiguing, and gains have been shown to attenuate over time; diminished gains have been demonstrated in both scientific⁶ and “real-world”⁷ studies.

The Port Delivery System (PDS) with ranibizumab 100 mg/mL supplied in a surgically placed intravitreal reservoir (Susvimo; Genentech/Roche) provides continuous drug delivery to the vitreous, with refills scheduled every 24 to 36 weeks. Therefore, PDS maintains long-term, constant vitreous levels of anti-VEGF ranibizumab.

PDS was first approved by the FDA for the treatment of nAMD in 2021, indicated in adults who have previously responded to at least 2 anti-VEGF injections. In nAMD, PDS refilled every 6 months (24 weeks) showed noninferior efficacy to monthly intravitreal ranibizumab injections through approximately 2 years in the phase 3 Archway trial.⁸ In that trial, approximately 95% of PDS patients did not require supplemental ranibizumab treatment per study protocol. Adverse events were manageable and are expected to decrease because associated issues have been addressed over time. Associated vitreous hemorrhage is distinctly uncommon following direct laser cauterization of the choroidal bed prior to choroidal incision. Endophthalmitis (1.6% of patients in the 2-year Archway results) was mostly associated with conjunctival erosion or retraction. Increased attention to careful conjunctival wound construction and Tenon’s capsule integrity is expected to attenuate endophthalmitis occurrence. Implant dislocation rates are expected to decrease due to strict adherence of a 3.5-mm incision length, with nonabsorbable suture adjustment if necessary. Episodes of septum dislodgement necessitated a period of voluntary recall of the device. Implantations have resumed following a pause of several months, when the reservoir’s septum structure was addressed to the FDA’s satisfaction.

The FDA approved PDS for CI-DME in February 2025, based on positive 1-year results from the phase 3 Pagoda study.⁹ In that study, patients implanted with the PDS refilled every 6 months achieved noninferior improvements in vision compared to those receiving monthly 0.5 mg intravitreal ranibizumab injections (each group gained approximately 2 lines on a Snellen chart). Two-year Pagoda data showed sustained gains in vision and retinal drying, with 95% of PDS patients not needing supplemental ranibizumab injections. The phase 3 Pavilion study assessed the efficacy of ranibizumab PDS for diabetic retinopathy (DR) without CI-DME, recognizing that a 2-step or greater score improvement on the Diabetic Retinopathy Severity Scale (DRSS) is a clinically relevant measure of the decrease in risk for developing vision-threatening complications from DR.¹⁰ In Pavilion, with refills occurring every 9 months (36 weeks), 80% of ranibizumab PDS patients (vs 9% of the control arm) achieved a 2-step or greater improvement in DRSS score at 100 weeks compared to pre-implant baseline. Ninety-eight percent of PDS patients in Pavilion did not need supplemental ranibizumab injections. There were no new safety signals in the diabetic studies.

Having another proven therapy available to treat retinal disease is valuable for individualized patient care. The PDS has demonstrated impressive results in clinical studies. However, the effort required to organize, perform, and follow up on the placement of a surgically implanted PDS device is greater than that for standard in-office intravitreal injections, raising questions about how PDS will integrate into current treatment paradigms.

Future considerations include whether the PDS reservoir could be filled with agents other than ranibizumab and how emerging therapies might influence adoption. For example, the potential availability of long-acting tyrosine kinase inhibitor (TKI) injections or gene therapies could affect both the current use of the PDS and the willingness of retina specialists to undergo the necessary training provided by Genentech. Below, we are fortunate to have insightful comments from Dante Pieramici, MD, FASRS, of California Retina Consultants, and Carl Awh, MD, FASRS, of Tennessee Retina.

Present and Future Prospects for the PDS

Dante J. Pieramici, MD, FASRS

The PDS with ranibizumab, commercially known as Susvimo, represents a groundbreaking advancement in intraocular drug delivery and exemplifies a platform therapy (the port delivery platform, or PD-P). This surgically implanted device, refillable in-office for decades, administers a customized formulation of ranibizumab with predictable first-order kinetic drug release.¹¹ Susvimo is currently FDA approved for the treatment of nAMD, CI-DME, and DR.

Clinical trials validating the efficacy and safety of the PDS demonstrated outcomes comparable to monthly intravitreal ranibizumab injections. Importantly, patient preference significantly favored the PDS due to reduced treatment frequency and sustained therapeutic effect.¹² Long-term data spanning more than 3 years in phase 3 trials for nAMD (2 years for DME and DR) and more than 5 years in phase 2 trials indicated stable vision and retinal anatomy outcomes.¹³ This may lead to better real-world outcomes, where we often see the initial visual benefits wane over time. In addition, the consistent anti-VEGF suppression provided by the PDS may offer disease-modifying benefits superior to intermittent intravitreal injections. Preliminary evidence from the Archway trial suggests reduced progression of geographic atrophy in patients receiving treatment via the PDS.¹⁴

Despite its clinical promise, widespread adoption of the PDS has encountered challenges. Initially, a higher incidence of endophthalmitis in the Archway trial—threefold compared to intravitreal injections—prompted an FDA-mandated black box warning. A comprehensive root-cause analysis identified conjunctival retraction and erosions as primary contributors. Subsequently, enhanced surgical techniques, including meticulous conjunctival and Tenon’s management, were implemented, significantly reducing complications.¹⁵ These improvements were formally integrated into the 2020 instructions for use and subsequently rates of endophthalmitis have been reduced.¹⁶ In addition, an analysis of fellow eyes being treated with intravitreal injections for DME in the Pagoda trial (Study Eye with PDS for same indication) had similar rates of complications, including endophthalmitis, comparing the PDS eye to the intravitreal eye.¹⁷

A second major setback occurred in 2022, when septum dislodgements prompted a voluntary recall by Genentech. Analysis identified insufficient septum-overmold bond strength and excessive refill needle insertion force as the primary causes. To address these issues, the septum-overmold bond strength was doubled, and silicone lubrication of the refill needle reduced insertion forces by half, effectively minimizing the risk of future dislodgements.¹⁸

Currently, the PD-P continues its global expansion, with ongoing phase 3 trials in Europe and Asia. Additionally, the platform is being adapted to deliver novel therapeutics, such as zifibancimig, a bispecific DutaFab with enhanced affinity for VEGF and Ang-2, currently under evaluation in the Burgundy phase 1/2 trial across multiple US sites. Ongoing efforts are directed toward further refining surgical techniques to minimize procedural complications and optimize clinical outcomes.

A Reliable Long-Term Option 

Carl C. Awh, MD, FASRS

Drs. Colucciello and Pieramici have  nicely summarized much of what we know about the Port Delivery System with ranibizumab 100 mg/mL (Susvimo). This technology provides reliable extended duration anti-VEGF therapy for patients with nAMD, DME, and even select cases of NPDR; accomplished via an initial surgical implantation of the device and subsequent in-office refill-exchange of the drug solution every 6 months.

I am delighted to have this treatment option for my patients. Real-world analyses, and my own experience, have taught me that the greatest risk to the vision of patients treated with anti-VEGF agents is the risk of undertreatment. A case of the flu, a severe winter storm, or any unanticipated event can lead to a delay in treatment, a loss of vision, and a new baseline for the patient. The 6-month refill-exchange schedule for Susvimo is of obvious advantage, but it is even more reassuring for patients to understand that a delayed refill-exchange is unlikely to lead to significant vision loss. In the phase 2 LADDER trial of PDS, the median time to the first required refill was 15 months.¹¹ I explain to patients that using 6 months as the interval for refill-exchanges is akin to filling an automobile gas tank when it is only half empty. There is a tremendous safety margin should a refill-exchange have to be delayed or rescheduled.

There is an obvious barrier to adoption of the PDS—the need to take a patient to the operating room, with the associated inconvenience, stress, and risk, compared to the relative ease of an intravitreal injection. The risk of surgery should never be trivialized. However, in my opinion, the risk associated with the PDS is minimal compared to the risk of undertreatment for patients who need injections at a relatively frequent interval (which I consider to be up to 8 weeks). Far more vision has been lost to delayed injections than to endophthalmitis.

Longer-durability injectable agents are available. Faricimab (Vabysmo; Genentech/Roche) and aflibercept 8 mg (Eylea HD; Regeneron) allow some patients to extend treatment intervals to 3 or 4 months. However, the ability to extend is unpredictable and, in my experience, only a minority of eyes can reliably extend to 4 months.

There are treatments in clinical trials that promise longer duration. Tyrosine kinase inhibitors and gene therapy may allow treatment intervals of 6 months or even many years. However, these treatments are currently unavailable, and we have yet to see what the pivotal clinical trials and longer-term experience will show.

For now, Susvimo is the only available treatment that can allow patients to be treated at 6 month or greater intervals, with 95% confidence. In my experience, those few eyes that need a supplemental injection between refill-exchanges of the implant are those that previously needed monthly injections, so even 4 treatments a year offers a huge improvement.

At the recent annual meeting of the American Society of Retina Specialists (ASRS), John Kitchens, MD, presented 5-year outcomes for nAMD patients enrolled in the pivotal Archway trial and treated with the PDS. He reviewed historical long-term vision outcomes with intravitreal anti-VEGF injections, in which patients who participated in CATT, HORIZON, and SEVEN-UP lost from 12 to 17 EDTRS letters over 5 years after exiting the clinical trials. Conversely, patients followed in the Archway to Portal long-term extension trial lost an average of 7 letters over 5 years, with half of patients maintaining at least 20/40 vision. In addition, 95% of PDS patients did not require supplemental injections prior to each 6-month interval refill-exchange.¹⁹

Experience in PDS clinical trials and with the commercial launch of Susvimo has resulted in modifications to the surgical technique that mitigate the risks associated with this treatment. Vitreous hemorrhage has been virtually eliminated as a serious adverse event. The risk of conjunctival retraction and erosion has declined since we learned that retina surgeons must handle conjunctiva and Tenon’s capsule more like our glaucoma colleagues, with meticulous care to close both layers of tissue without tension or buttonholes. This has reduced the risk of endophthalmitis, which has been clearly associated with prior conjunctival retraction and erosion.

The rate of endophthalmitis in the pivotal Archway trial for nAMD was 2.6% (10/380).⁶ Although this may seem high compared to the generally accepted post-injection rate of 0.05% (1/2000), we must remember that the risk of endophthalmitis in a patient receiving intravitreal injections is an aggregate risk. If the 380 PDS-treated eyes in Archway had instead received 10 injections per year, or 19,000 injections over 5 years, a 0.05% incidence of endophthalmitis would have resulted in 10.4 cases—virtually identical to what was seen in the PDS arm. Considered this way, the long-term risk of endophthalmitis with Susvimo is not substantially greater than that seen with intravitreal injections. Also, the visual outcome of patients with PDS who developed endophthalmitis was generally good, with most returning to at least their pre-endophthalmitis visual acuity.

The technical skills required to successfully perform PDS initial implantation surgery and the subsequent in-office refill-exchange procedures are well within the skill set of a capable retina surgeon. Genentech has created a comprehensive suite of training materials, ranging from didactic teaching, simulator surgery, and in-person coaching by company-provided surgical device specialists.

Will Susvimo one day be supplanted by superior treatments? I’m confident that our therapeutic arsenal will look quite different in a decade. Our practice participates in many clinical trials, including some mentioned in this article. In fact, patients are now enrolling in the Burgundy trial, which is investigating the safety, tolerability, and efficacy of zifibancimig, , a therapy that targets both VEGF and Ang-2, in the PDS. This agent may allow refills at 1 year or longer intervals. More durable treatment is a goal of every company and laboratory with a focus on retinal diseases. In Susvimo, we have a durable treatment that offers excellent long-term average outcomes, with a favorable risk-benefit profile. It is available now. RP

Michael Colucciello, MD, is a clinical associate at the University of Pennsylvania School of Medicine in Philadelphia, and a retina specialist with the South Jersey Eye Physicians Division of PRISM Vision Group in Moorestown, New Jersey. He reports no disclosures. He can be reached at maculamd@gmail.com.

Dante J. Pieramici, MD, FASRS, is managing partner of California Retina Consultants in Santa Barbara, California, where he serves as medical director of clinical research. He is on the medical leadership board of Retina Consultants of America, and director of the California Retina Research Foundation. He reports consulting fees from Genentech/Roche, Regeneron, 4DMT, Unity Biotechnology, Adverum Biotechnologies, Perceive, EyePoint Pharmaceutical, RetinaAI, Samsung Bioepis, Neurotech, Opthea, Ocular Therapeutix, and Arrowhead;  and research funding from Genentech/Roche, Regeneron, RegexBio, 4DMT, Unity, Adverum, Novartis, EyePoint, Ocular, Opthea, Janssen, Kodiac, Boehringer, Alimera, Apellis, Outlook, EyeBio, Oculis, ANnexon, and J Cyte.

Carl C. Awh, MD, is a retina specialist and president of Tennessee Retina in Nashville. He is a past president of the American Society of Retina Specialists. He is an investigator, consultant, and speaker for Genentech; an investigator and consultant for Ocular Therapeutix; and an investigator for Adverum, EyePoint, Regenxbio, and 4DMT.

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