No one relishes the idea of receiving injections into their eyes. The mere thought sends a shiver down the spine. For millions suffering from retinal degenerative diseases, frequent eye injections are a grim reality – an ordeal that patients endure to stave off the creeping darkness of vision loss. By 2040, it is projected that age-related macular degeneration will affect 288 million people worldwide (1). To maintain their vision, these patients would need at least ten injections a year. However, many patients can't keep up with the grueling schedule of injections, particularly those in non-urban areas where access to specialized care is limited.
As an industry, we must explore how we can help patients maintain their vision without subjecting them to the constant stress and inconvenience of frequent injections. One solution lies in the development of new drug-device combination products that can extend the durability of therapies. The field of ophthalmology, particularly in retinal delivery, is already beginning to shift toward treat-and-extend regimens, with emerging biologics offering the potential for treatments that last up to six months after an initial loading dose.
Innovations such as the port delivery system – an FDA-approved implantable drug chamber that can be refilled periodically – can extend the durability of treatments beyond six months. However, the device requires a surgical procedure in an operating room. It’s an expensive process with risks of infection and septum dislodgement, but it is being continually improved. For example, a relaunch updated the ocular implant and refill needle, as well as improved the manufacturing process (2).
Delivery innovation
Since the approval of Lucentis in 2014, intravitreal delivery has become the go-to procedure for retinal drug delivery, with 10 million intravitreal injections performed annually in the US (3). But intravitreal delivery is far from perfect. For emerging treatments like gene therapies, intravitreal injections pose serious risks, including inflammation from systemic leakage. And let’s not forget the challenge of delivering drugs directly to the inner retina, where they need to cross multiple biological barriers to reach their target. Intravitreal is also far less effective for geographic atrophy as drugs delivered by intravitreal injection are less targeted to the site of damage.
Sub-retinal injections offer a more direct route but are highly invasive and require extreme precision. So, what’s the alternative? Suprachoroidal delivery could be the answer as it offers a middle ground that offers targeted delivery without the invasiveness of surgery. This method is still emerging, with only one approved drug on the market, but there’s a real opportunity to improve tissue access, streamline the injection process, and ultimately make these treatments more accessible to the millions who need them.
The leading edge of retinal treatment is gene therapy with a one time solution that could potentially transform the eye into a self-sustaining ocular biofactory. A single injection could prompt the retina to produce its own therapeutic proteins, potentially for a lifetime, but these therapies are still in the trial phase, and long-term durability remains to be seen.
In the near term, the key to making drug delivery technologies truly impactful in ophthalmology lies in integrating containment and delivery solutions that are both effective and easy to implement in clinical settings, while offering a straightforward development path for pharma companies. Sustained-release platforms such as hydrogels, microparticles, or bioconjugated polymers could help slow the release of active components, keeping the therapeutic concentration stable for longer periods, but also have their challenges. Delivering viscous monoclonal antibody formulations through narrow cannulas, for example, poses hurdles because of high injection forces and needle clogging issues. There are also challenges in air-bubble-free filling, understanding the effect of cold storage on viscosity variations, and the need to prepare ahead with an “extendable” delivery metric for the device. Drug delivery or deployment devices for these complex products must be a true platform to enable tailorability of the solid or liquid formulation.
Some of the key considerations in device design are providing usability and ease of use that fits a busy retina clinic. Any innovation in this space must stay as close as possible to the current standard of care intravitreal injections, which can be easily adopted in a retina clinic. The device design must also take into consideration the pain and perception of pain in patients receiving intravitreal or suprachoroidal injections. Some of the considerations around these are higher gauge needles (30 g and above) and lower injection pressure to deliver drugs, especially viscous drug products. The delivery devices acting as primary containers must also meet the requirements of low particulates to reduce the risk of floaters in the eye (4). Precision is another key requirement in intravitreal injections where delivery volume discrepancies can lead to transient or prolonged increases in the intraocular pressure (5). Therefore, devices in this space must have low dead volume and high accuracy in delivering precise volume of drugs into the vitreous compartment.
The future of ophthalmic drug delivery lies in transforming the durability of therapies and developing the right delivery technologies and devices. For medical device manufacturers, this means being a close partner in early-stage platform development. Bespoke presentations will be necessary for cell and gene therapies. Platform approaches that can open the way to more accelerated paths to the market must be adopted whenever possible.
The bottom line is this: better delivery technologies aren't just a nice-to-have; they are a necessity to improve treatment outcomes, patient compliance, and reduce the burden on healthcare systems.
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References
- WL Wong et al., “Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis,” Lancet Glob. Health, 2 (2014). DOI: 10.1016/S2214-109X(13)70145-1.
- Genentech, “Genentech to Reintroduce Susvimo for People With Wet Age-Related Macular Degeneration (AMD),” (2024). Available here.
- R Wang et al., “Quantifying burden of intravitreal injections: questionnaire assessment of life impact of treatment by intravitreal injections (QUALITII),” BMJ Open Ophthalmol., 19 (2022). DOI: 10.1136/bmjophth-2022-001188.
- SM Dounce, O Laskina, RA Goldberg, “Particulate matter from syringes used for intravitreal injections,” Retina (2021). DOI: 10.1097/IAE.0000000000002947.
- LLM Agra et al., “Accuracy, Precision, and Residual Volume of Commonly Used Syringes for Intravitreal Injections and the Impact on Intraocular Pressure,” Ophthalmol Retina, 7, 892-900 (2023). DOI: 10.1016/j.oret.2023.06.003.
