Review Emphasizes Role of Sustained Anti-VEGF Therapies for nAMD

Christina Y. Weng, MD, MBA

Credit: American Society of Retina Specialists

Intravitreal anti-vascular endothelial growth factor (VEGF) therapy approximately halved the rate of blindness due to neovascular age-related macular degeneration (nAMD), but the heavy therapeutic burden is a limitation leading to undertreatment in real-world practice.¹

A new review reported modern treatment paradigms reduce this burden and lead to acceptable vision outcomes, but often fail to sustain initial vision gains. Novel therapies, including longer-acting anti-VEGF agents and investigational gene therapies, could potentially decrease treatment requirements and improve long-term outcomes.

“In light of the increasing incidence of nAMD among an aging population, there remains an important unmet need for therapies that offer sustained visual outcomes with an acceptable treatment burden,” wrote the investigative team, led by Christina Y. Weng, MD, MBA, Baylor College of Medicine.

Although accounting for only 10% of total AMD cases, nAMD is linked to ≥80% of severe vision loss among AMD patients. Those who are untreated remain at risk of legal blindness within 2 years. Clinical trials have led to monthly or bimonthly injections of anti-VEGF therapy becoming the standard of care, but the need for long-term treatment and monitoring could diminish the observed benefits.

In their review of available literature, Weng and colleagues evaluated current treatment paradigms and their shortcomings in nAMD care. The team assessed Medline and Disqover for studies reporting real-world evidence, patient and caregiver preferences, and the epidemiology of nAMD. In addition, the team reviewed systematic literature reviews and meta-analyses, clinical guidelines, anti-VEGF product labels, and expert surveys from relevant medical societies.

Upon analysis, population-based studies showed that anti-VEGF therapy reduced blindness and vision impairment due to nAMD by 50%.² However, despite randomized controlled trials (RCTs) showing visual acuity improvements over a 2 to 3-year period, there is limited evidence showing improvement with anti-VEGF therapy beyond that treatment interval.

An analysis of nearly 110,000 eyes reported greater visual acuity improvements for RCTs compared with real-world studies and higher functional benefits with more frequent injections (P <.0001).³ Considering the burden of frequent injections, treatment regimens, including treat-and-extend, are used to balance vision outcomes with that burden. Treat-and-extend is used in approximately 87% of United States practices, but real-world regimens often differ from those in trials, with observed declines in injection frequency and vision.¹

Real-world data has shown the overall burden of treatment and monitoring has led to a cycle of undertreatment, treatment discontinuation, and irreversible vision loss. Real-world studies in the US and the United Kingdom have reported decreases in anti-VEGF injections with subsequent declines in vision after 2 to 5 years of treatment. Other data showed annual discontinuation rates ranging from 20-40% compared with an average of 10% in randomized controlled trials (RCTs).⁴

The current treatment model for nAMD also has a substantial impact on patients and caregivers – patients tend to be older and have common comorbidities and poor mobility, while the burden of frequent visits can impact caregivers. Patients in the US have reported an average of nearly 12 hours per visit, including travel, treatment time, and post-appointment recovery, showing a significant time-related burden.

Both ophthalmologists and clinical practices also deal with logistical challenges related to patient treatment and monitoring. A time-and-motion survey of retina specialists in the US reported the average time spent per nAMD visit was 90 minutes, while other research estimated the median time to complete an intravitreal injection of 33 minutes.

Strategies are being developed to reduce the burden associated with anti-VEGF treatment, including personalized OCT-guided dosing regimens and novel delivery methods, but it is not clear if improvement of long-term vision outcomes is possible in real-world practice. Newer anti-VEGF approvals, including faricimab-svoa (Vabysmo) and aflibercept 8 mg (Eylea HD), can be dosed in intervals up to 12 or 16 weeks, but many patients may require ≥4 yearly injections with limited changes to monitoring.

Investigational gene therapies are being studied in clinical trials to elaborate the potential of continuous control of disease activity, prevent progression, and preserve long-term vision. Weng and colleagues noted these gene therapies may improve quality of life and reduce the burden on patients and the health system, but more research is needed to elucidate their potential in the treatment of retinal diseases.

“Further research is needed to demonstrate the safety and durability of gene therapy as well as its various routes of administration under investigation,” investigators wrote.

References

1. _{Weng CY, Singh RP, Gillies MC, Regillo CD. Optimizing Visual Outcomes in Patients With Neovascular Age-Related Macular Degeneration: the Potential Value of Sustained Anti-VEGF Therapy. Ophthalmic Surg Lasers Imaging Retina. 2023;54(11):654-659. doi:10.3928/23258160-20231016-01}
2. _{Finger RP, Daien V, Eldem BMet al.. Anti-vascular endothelial growth factor in neovascular age-related macular degeneration - a systematic review of the impact of anti-VEGF on patient outcomes and healthcare systems. BMC Ophthalmol. 2020; 20(1):294. 10.1186/s12886-020-01554-2 PMID:32680477}
3. _{Veritti D, Sarao V, Soppelsa V, Danese C, Chhablani J, Lanzetta P. Managing neovascular age-related macular degeneration in clinical practice: systematic review, meta-analysis, and meta-regression. J Clin Med. 2022; 11(2):325. 10.3390/jcm11020325 PMID:35054021}
4. _{Khanani AM, Skelly A, Bezlyak V, Griner R, Torres LR, Sagkriotis A. SIERRA-AMD: a retrospective, real-world evidence study of patients with neovascular age-related macular degeneration in the United States. Ophthalmol Retina. 2020; 4(2):122–133. 10.1016/j.oret.2019.09.009 PMID:31812631}