Port System Cuts Injection Burden in Diabetic Eye Disease

Continuous administration of ranibizumab with a port delivery system provides an alternative to frequent intravitreal injections for diabetic macular edema and helps delay progression of nonproliferative diabetic retinopathy, researchers have found.

Data from two phase 3 trials — Pagoda and Pavilion — demonstrate how the delivery system, which the US Food and Drug Administration approved for diabetic macular edema in February, can reduce treatment burden for select patients, according to Arshad M. Khanani, MD, MA, director of Clinical Research at Sierra Eye Associates and clinical professor at the University of Nevada, Reno School of Medicine.

The findings, published in JAMA Ophthalmology, show how “continuous delivery of anti-VEGF [vascular endothelial growth factor] can really benefit patients with diabetic eye disease,” Khanani, who led the Pagoda trial, told Medscape Medical News.

The Pagoda trial involved 634 patients with diabetic macular edema who received ranibizumab (100 mg/mL) by port refilled every 24 weeks or monthly intravitreal ranibizumab injections (0.5 mg).

At week 64, mean gains in best corrected visual acuity were 9.6 letters in the port group and 9.4 letters in the injection group, confirming noninferiority, according to the researchers.

Adverse events of special interest, including conjunctival blebs and vitreous hemorrhage, were more common in the port group (27.5% vs 8.9%). Transient vision loss was also observed in the port group, with a mean decrease in best corrected visual acuity of 6.7 letters. Although no cases of endophthalmitis were reported in the first 64 weeks of the Pagoda trial, Khanani said some cases have occurred in the second year, mostly due to contamination during the refill exchange procedure.

The Pavilion trial involved 174 patients with moderately severe to severe nonproliferative diabetic retinopathy without center-involved macular edema. Patients received the port delivery system refilled every 36 weeks or standard-of-care monitoring without anti-VEGF treatment.

By week 52, 80.1% of port patients had at least a two-step improvement on the diabetic retinopathy severity scale compared with 9% of those in the control group. Rates of participants developing center-involved macular edema, progressive diabetic retinopathy, or anterior segment neovascularization were 7.1% in the port group vs 47% among contr ol individuals. Transient vision loss occurred in the port system at 4 weeks after implantation, with a mean loss of visual acuity of 7.4 letters that resolved within 8 weeks.

“Transient vision loss postimplantation is a significant concern, as it may deter both patients and physicians from adopting” the port system as a first-line therapy, Rishi Singh, MD, a professor of ophthalmology at the Cleveland Clinic Lerner College of Medicine, Cleveland, told Medscape Medical News.

Andrew Barkmeier, MD, an ophthalmologist at Mayo Clinic in Rochester, Minnesota, agreed the complication is concerning, but he predicted greater pushback against the port system due to the risk of more serious adverse events.

“I suspect that more attention will be focused on potential long-term risks of port site complications and endophthalmitis, and how those risks are weighed against the potential benefit of a more durable treatment,” Barkmeier said.

Khanani said the port system is best suited for patients struggling with treatment adherence, where the risk-benefit analysis is relatively straightforward.

“Anytime you do surgery, there is risk,” Khanani said. “But there’s also risk associated with patients not getting their injections. We have many patients who come in for injections and then disappear because they can’t take time off work, or they don’t like the injections, and they come 2 years later, completely blind.”

Khanani said the latest data failed to capture the tangible emotional benefits of treatment with the port delivery system.

“My experience is that the patients who receive [the therapy] are very, very happy, and that’s something I don’t see with patients who come back for injections,” Khanani said. “You won’t understand how happy these patients are unless you actually do that procedure yourself and see the outcomes.”

Although the treatment is now approved for diabetic macular edema, both Barkmeier and Singh emphasized the need for more data.

“Long-term data are crucial before widespread adoption, particularly to assess whether the port delivery system maintains its efficacy over extended periods and to determine whether refilling procedures remain effective over years of use,” Singh said. “Further research is also needed to evaluate cost-effectiveness compared to conventional treatments. Until these questions are answered with robust real-world data, the port delivery system may remain a niche option rather than a mainstream therapy.”

This study was funded by F. Hoffmann-La Roche Ltd. The investigators disclosed additional relationships with AbbVie, Novartis, Janssen, and other companies. Singh disclosed relationships with F. Hoffmann-La Roche Ltd., Bausch & Lomb, Genentech, and other companies. Barkmeier reported no relevant financial conflicts.