Intravitreal therapy—success stories and challenges

main topic Wien Med Wochenschr (2025) 175:162–174 https://doi.org/10.1007/s10354-024-01070-8 Intravitreal therapy—success stories and challenges Daniel Egger · Katharina A. Heger · Matthias Bolz · Max P. Brinkmann · Katharina Krepler · Pia Veronika Vecsei-Marlovits · Andreas Wedrich · Sebastian M. Waldstein Received: 5 September 2024 / Accepted: 20 December 2024 / Published online: 3 March 2025 © The Author(s) 2025 Summary Intravitreal injections have revolutionized the treatment of various sight-threatening diseases of the posterior segment of the eye. Initially explored for treatment of bacterial endophthalmitis, intravitreal injections rapidly expanded to combat retinal vascular disease in particular. Especially anti-vascular endothelial growth factor agents have emerged as a cornerstone of intravitreal therapy, targeting neovascular age-related macular degeneration and diabetic macular edema as important examples. Advances continue, with novel therapies such as complement inhibitors now available as treatment for geographic atrophy secondary to non-neovascular age-related macular degeneration, offering hope for a previously untreatable condition. Pioneering approaches such as the port delivery system and intravitreal gene therapy aim to improve treatment efficacy while minimiz- ing patient burden. Despite notable successes, challenges for intravitreal therapies persist, including ocular and systemic complications and high treatment burden. Future research endeavors aim to address these challenges and enhance treatment outcomes. This comprehensive review critically evaluates the efficacy, safety, and cost-effectiveness of intravitreal injections, delving into emerging trends and future directions. D. Egger, MD () · K. A. Heger · S. M. Waldstein Department of Ophthalmology, Landesklinikum Mistelbach-Gänserndorf, Mistelbach, Austria K. Krepler Karl Landsteiner Institute for Retinal Research and Imaging, Vienna, Austria D. Egger, MD · K. A. Heger · S. M. Waldstein Karl Landsteiner University of Health Sciences, Krems, Austria D. Egger, MD Paracelsus Medical University Salzburg, Salzburg, Austria M. Bolz Department of Ophthalmology, Kepler University Clinic, Linz, Austria Department of Ophthalmology, Johannes Kepler University, Linz, Austria Keywords Anti-vascular endothelial growth factor therapy · Diabetic retinopathy · Intravitreal gene therapy · Intravitreal injections · Neovascular agerelated macular degeneration Department of Ophthalmology, Klinik Landstraße, Vienna, Austria P. V. Vecsei-Marlovits Department of Ophthalmology, Klinik Hietzing, Vienna, Austria Karl Landsteiner Institute for Processoptimization and Quality Management in Cataract Surgery, Vienna, Austria A. Wedrich Department of Ophthalmology, Medical University of Graz, Graz, Austria M. P. Brinkmann Department of Ophthalmology, Klinikum Klagenfurt, Klagenfurt, Austria Department of Ophthalmology, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany 162 Intravitreal therapy—success stories and challenges K main topic Intravitreale Therapie – Erfolge und Herausforderungen Zusammenfassung Intravitreale Injektionen haben die Behandlung verschiedener Augenerkrankungen revolutioniert, indem sie einen wirksamen Therapieansatz für Krankheiten des posterioren Augenabschnitts bieten. Anfangs für die Behandlung der bakteriellen Endophthalmitis erforscht, haben sich intravitreale Injektionen rasch in anderen Bereichen etabliert. Insbesondere haben sich Injektionen mit „anti-vascular endothelial growth factor“ als Eckpfeiler für die Therapie von Gefäßerkrankungen der Netzhaut behauptet. Diese Fortschritte setzen sich mit neuartigen Therapien wie Komplementinhibitoren fort, die nun für die geografische Atrophie bei nicht-neovaskulärer altersbedingter Makuladegeneration zur Verfügung stehen. Neue Therapieoptionen wie das Port-Delivery-System und intravitreale Gentherapien zielen darauf ab, die Wirksamkeit der Behandlungen zu verbessern und gleichzeitig die Belastung für die Patienten zu minimieren. Trotz bemerkenswerter Erfolge gibt es gleichermaßen wichtige Herausforderungen, wie beispielsweise okuläre und systemische Komplikationen sowie den hohen Behandlungsaufwand. Künftige Forschungsbestrebungen zielen darauf ab, diese Probleme zu bewältigen und die Behandlungsergebnisse zu verbessern. Im vorliegenden Übersichtsartikel werden die Wirksamkeit, Sicherheit und Kosteneffektivität intravitrealer Injektionen kritisch bewertet, und es wird auf neue Trends und zukünftige Entwicklungen eingegangen. Schlüsselwörter Anti-VEGF-Therapie · Diabetische Retinopathie · Intravitreale Gentherapie · Intravitreale Injektionen · Neovaskuläre altersbedingte Makuladegeneration Introduction Intravitreal injections (IVI) are nowadays the most commonly performed ophthalmic procedure worldwide, with steadily rising numbers [1]. Few interventions in ophthalmology can claim to have had such a transformative impact on the landscape of ocular therapeutics as IVI, which provide a reliable and effective tool against various sight-threatening conditions. Before the era of IVI, most diseases of the posterior segment of the eye were largely inaccessible to drug therapy. Intraocular infections, for example, were mostly treated by systemic antibiotics. Although there is evidence that parenteral or oral administration of antibiotics provides measurable intraocular drug levels, those levels were often found to be below the minimum concentration needed to effectively inhibit the pathogen [2]. This can be explained by the avascularity of the vitreous body and the highly effective blood–ocular barrier, which together consid- K erably limit penetration of systemically administered drugs [3]. Only in the early 1980s did ophthalmologists start to explore the possibility of administering drugs directly into the vitreous cavity. At first, this approach was primarily used to treat bacterial endophthalmitis with injections of intravitreal antibiotics [4], which was at that time established as the standard of care by a landmark clinical trial, the Endophthalmitis Vitrectomy Study [5]. With the advent of the acquired immunodeficiency syndrome (AIDS) epidemic in the 1980s/90s, ophthalmologists were facing another challenge. The spread of the cytomegalovirus (CMV), the most frequent opportunistic infection in AIDS patients, frequently resulted in CMV retinitis, with devastating effects on the retina and vision if left untreated [6]. Systemic administration of ganciclovir had limited success, and both ganciclovir and the only available drug to treat human immunodeficiency virus (HIV) infection at that time, zidovudine, were myelosuppressive [3]. Facing this conundrum, ophthalmologists began to inject ganciclovir intravitreally, which led to superior clinical outcomes but carried the disadvantage of requiring weekly injections due to ganciclovir’s short half-life [7, 8]. To target this issue, a sustained-release implant for ganciclovir wa (...truncated)