Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Jun;26(8):939-952.
doi: 10.1080/14656566.2025.2496424. Epub 2025 May 11.

Beyond the injection: delivery systems reshaping retinal disease management

Lucas W Rowe  1 , Christian Akotoye  1 , Alon Harris  2 , Thomas A Ciulla  1   3
Affiliations
Review

Beyond the injection: delivery systems reshaping retinal disease management

Lucas W Rowe et al. Expert Opin Pharmacother. 2025 Jun.

Abstract

Introduction: Intravitreal injections remain the standard for treating common retinal diseases including age-related macular degeneration (AMD), diabetic macular edema (DME) and diabetic retinopathy. However, frequent administration creates significant treatment burden due to limited drug half-life and the chronic nature of these conditions.

Areas covered: This review summarizes emerging drug delivery techniques and therapies for retinal disease that have achieved FDA approval within the past five years or have advanced to Phase 3 development, including intravitreal sustained-release platforms and alternative delivery routes (suprachoroidal, subretinal, topical, and subcutaneous). Specific innovations discussed include the ranibizumab port delivery system, EYP-1901 (Duravyu, vorolanib implant), KSI-301 (tarcocimab tedromer), KSI-501, OTX-TKI (Axpaxli, axitinib implant), 4D-150, revakinagene taroretcel-lwey (Encelto, NT-501, encapsulated cell therapy), Xipere (triamcinolone acetonide injectable suspension), AU-011 (belzupacap sarotalocan targeted delivery), ABBV-RGX-314, elamipretide, and OCS-01 (high concentration dexamethasone).

Expert opinion: Promising innovations include sustained-release intravitreal implants, topical and subcutaneous delivery systems, and targeted methods like suprachoroidal and subretinal injections, each with unique advantages and limitations. Challenges include overcoming the blood-retinal barrier, surgical complications with implantable devices, and ensuring patient adherence. Advances in smart delivery systems, drug formulations, and predictive models, alongside interdisciplinary collaboration, will be crucial in achieving personalized, effective, and sustainable retinal therapies.

Keywords: Drug delivery; gene therapy; intravitreal injection; port delivery system; retina; subretinal delivery; suprachoroidal delivery; vascular endothelial growth factor.

PubMed Disclaimer

Conflict of interest statement

Declarations of interest

T Ciulla declares consultancy and stock options for Clearside Bio, consultancy and stock options for Nanoscope, consultancy for Ocuphire/Opus and consultancy, stock options, and employment through to Feb 2025 for Viridian Therapeutics.

Figures

Figure 1.
Figure 1.
Illustration of novel, investigative, sustained-release drug delivery technologies with hydrogel and micro/nanoparticles, and FDA-approved sustained-release therapies with Ozurdex® (dexamethasone implant, FDA approved in 2009), Retisert® (fluocinolone acetonide implant, FDA approved in 2005) Iluvien® (fluocinolone acetonide implant, FDA approved in 2014) and SUSVIMO® (ranibizumab port delivery system, FDA approved in 2021). The graph on the right exemplifies the preserved drug concentration within the vitreous compared to the relative rapid clearance of medication with standard intravitreal injection. From Alshaikh RA, Waeber C, Ryan KB. Adv Drug Deliv Rev. 2022;187:114342 [6]. Licensed for reuse under the creative commons CC-BY license.
Figure 2.
Figure 2.
Overview of adenovirus-mediated delivery of recombinant genetic material to host cells for endogenous expression of a desired protein. From: https://commons.wikimedia.org/wiki/File:Viral_mediated_delivery_of_genes_to_neurons_1.jpg [80]. Licensed for reuse under the creative commons attribution-share alike 4.0 international license.
Figure 3.
Figure 3.
Schematic illustrating encapsulated cell therapy. From: https://commons.wikimedia.org/wiki/File:Cell_capsule_schematic.png [88]. Licensed for reuse under the creative commons attribution-share alike 4.0 international license.
Figure 4.
Figure 4.
Illustration comparing (A) intravitreal injection, (B) subretinal injection, and (C) suprachoroidal injection through a microneedle. From Ladha R, Caspers LE, willermain F, de smet MD. Front med [internet]. 2022 Mar 23 [cited 2024 Nov 30];9 [91]. Licensed for reuse under the creative commons CC-BY license.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Peden MC, Suñer IJ, Hammer ME, et al. Long-Term outcomes in eyes receiving fixed-interval dosing of Anti–vascular endothelial growth factor agents for wet age-related macular degeneration. Ophthalmology. 2015;122(4):803–808. doi: 10.1016/j.ophtha.2014.11.018 - DOI - PubMed
    1. Ciulla TA, Huang F, Westby K, et al. Real-world outcomes of anti–vascular endothelial growth factor therapy in neovascular age-related macular degeneration in the United States. Ophthalmol Retina. 2018;2(7):645–653. doi: 10.1016/j.oret.2018.01.006 - DOI - PubMed
    1. Ciulla TA, Hussain RM, Pollack JS, et al. Visual acuity outcomes and anti–vascular endothelial growth factor therapy intensity in neovascular age-related macular degeneration patients. Ophthalmol Retina. 2020;4(1):19–30. doi: 10.1016/j.oret.2019.05.017 - DOI - PubMed

    1. Ciulla TA, Hussain RM, Taraborelli D, et al. Longer-term anti-VEGF therapy outcomes in neovascular age-related macular degeneration, diabetic macular edema, and vein occlusion-related macular edema: clinical outcomes in 130 247 eyes. Ophthalmol Retina. 2022;6(9):796–806. doi: 10.1016/j.oret.2022.03.021

      •Large retrospective study demonstrating that longer-term real-world anti-VEGF outcomes are inferior to those in randomized clinical trials.

    1. Moshfeghi AA, Pitcher JD, Lucas G, et al. Visual acuity outcomes in patients receiving frequent treatment of neovascular age-related macular degeneration in clinical practice. J Vitreoretin Dis. 2021;5(3):221–226. doi: 10.1177/2474126420960896 - DOI - PMC - PubMed