Sustained-Release Drug Delivery for Retinal Disease

Sustained-release drug delivery for retinal disease tries to solve one of the biggest problems in retina care, the burden of repeated injections.

An implant or insert placed once can release a drug for months to years, keeping levels steady and sparing the patient frequent visits.

Regulators have also approved several platforms, and many more are in trials.

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Why Sustained-Release Drug Delivery for Retinal Disease?

The vitreous clears anti-VEGF drugs in weeks, so patients need frequent injections for years (see anti-VEGF therapy).

Also, missed visits lead to loss of vision, and each injection carries a small risk of infection.

A steady supply could also lower the peaks and troughs of drug levels, reduce visits, and improve outcomes.

Sustained-Release Drug Delivery for Retinal Disease: Steroid Implants

These were the first sustained-release devices for the retina.

• A dexamethasone implant lasts about three to six months (see dexamethasone intravitreal implant)
• Fluocinolone implants last up to three years (see fluocinolone acetonide implants)
• Main risks are cataract and raised pressure

Port Delivery System

The refillable ranibizumab port gives continuous delivery, and trials showed vision equal to monthly injections, with refills every six months, but with surgical risks (see port delivery system with ranibizumab).

Sustained-Release Drug Delivery for Retinal Disease: Tyrosine Kinase Inhibitor Inserts

• Drugs such as vorolanib and axitinib block several VEGF receptors and other pathways
• Surgeons place them in the vitreous in a sustained-release insert or hydrogel, with the goal of dosing once every six months
• Phase 3 trials in neovascular AMD are under way, and we await results (see tyrosine kinase inhibitors for wet AMD)

Other Platforms

• Biodegradable implants and microparticles that release drug as they dissolve
• Hydrogels that gel in the vitreous and release drug slowly
• Suprachoroidal depots that place drug between the sclera and choroid
• Gene therapy that makes the eye produce its own anti-VEGF protein
• Encapsulated cell therapy, which secretes a protein continuously (see NT-501 for macular telangiectasia)

Sustained-Release Drug Delivery for Retinal Disease: Challenges

• Placing a device in the eye can cause inflammation, cataract, or pressure rise
• A drug that is sustained cannot be stopped quickly if a problem arises
• Some devices need surgical placement, and removal is not simple
• Cost and reimbursement differ between systems
• Long-term safety data are limited

Who Benefits Most?

• Patients who live far from care, or cannot attend often
• Those with a good response to a drug, who need frequent injections to keep it
• Patients who find injections painful or stressful

Patients who respond poorly to the drug will not gain from a sustained dose of the same drug.

Sustained-Release Drug Delivery for Retinal Disease: Counselling

Explain that these devices are the future of chronic retinal care, but that each has risks, and that regular review is still needed.

Discuss what will happen if the device fails or the disease changes.

Example Case

A 70-year-old man lives in a remote area and travels four hours for each injection, with missed visits causing recurrent fluid.

After discussion, he receives a sustained-release option, with visits every six months, and his retina remains dry with stable vision.

This case shows how a delivery system can solve a problem of access as well as a medical problem.

Monitoring After Placement

• Check the pressure, the lens, and the position of the device at each visit
• Use OCT to confirm that the retina stays dry, and plan rescue injections if fluid returns
• Educate the patient about signs of infection and inflammation

What to Ask Before Choosing a Device

• How long does it last, and what is the refill or replacement plan?
• What are the specific risks of surgery and of the drug?
• Is there a rescue option if the response is poor?
• What are the costs and coverage rules?

Looking Ahead

The next generation of devices may combine several drugs, respond to disease activity, and be removed or refilled simply, and the field is moving from prototypes toward routine use.

Clinicians should follow trial results and updates in guidelines, and discuss options with patients who are strongly affected by the burden of injections.

Questions for the Clinic Team

• Which patients in our clinic would gain most, based on injection history and attendance?
• Who will manage complications, such as raised pressure or inflammation, and how quickly?
• Do we have a protocol for rescue treatment if fluid returns?
• How will we record outcomes, so that we can audit our results?

Having answers before adopting a device protects patients and supports good decisions.

For the latest studies, see the PubMed results for sustained-release drug delivery for retinal disease.

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References

1. Kang-Mieler JJ, Rudeen KM, Liu W, Mieler WF. Advances in ocular drug delivery systems. Eye (Lond). 2020;34:1371-1379.
2. Holekamp NM, Campochiaro PA, Chang MA, et al. Archway randomized phase 3 trial of the port delivery system with ranibizumab for neovascular age-related macular degeneration. Ophthalmology. 2022;129:295-307.
3. Jackson TL, Boyer D, Brown DM, et al. Oral tyrosine kinase inhibitor for neovascular age-related macular degeneration: a phase 1 dose-escalation study. JAMA Ophthalmol. 2017;135:761-767.
4. American Academy of Ophthalmology. Basic and Clinical Science Course, Section 12: Retina and Vitreous. AAO; current edition.