14 Aug, 2025
Over the past two decades, the treatment landscape for wet age-related macular degeneration (nAMD) has been transformed by the advent of anti-vascular endothelial growth factor (anti-VEGF) injections. Before the introduction of these agents, nAMD often led to irreversible vision loss and blindness. The development of anti-VEGF therapies has significantly improved the prognosis for patients with nAMD, making the condition more manageable and preventing vision loss in many cases.[1][2]
The first anti-VEGF agent, pegaptanib, was approved in the early 2000s, followed by more effective agents such as ranibizumab, bevacizumab (off-label), aflibercept, brolucizumab, faricimab, and, most recently, high-dose aflibercept 8mg. These agents work by inhibiting VEGF, a key molecule in forming abnormal retinal blood vessels, thereby reducing fluid leakage and neovascularisation. Clinical trials have demonstrated that these treatments can maintain or improve visual acuity in a significant proportion of patients, with over 90% of patients maintaining vision and up to one-third experiencing significant visual improvement.[2][3][4][5]
In Australia, the introduction of anti-VEGF therapies has had a profound impact on the management of nAMD. The availability of these treatments has reduced the incidence of severe vision loss and blindness due to nAMD, improving the quality of life for many elderly Australians. The treatment regimen typically involves monthly or bimonthly intravitreal injections initially, which, while effective, pose a significant burden on patients and the healthcare system due to the need for frequent visits and injections.[2][6][7]
The significant reduction in blind registration among people receiving anti-VEGF injections for wet macular degeneration has been well-documented. A study using patient-level simulation modelling estimated that intravitreal ranibizumab injections could reduce incident blindness by 72% with monthly treatment and by 68% with as-needed treatment over two years in Australia. Similarly, data from the UK and Sweden have shown substantial reductions in the incidence of severe visual impairment and blindness following the introduction of anti-VEGF therapies. These findings underscore the transformative impact of anti-VEGF treatments on reducing blindness and improving visual outcomes in patients with nAMD.[10][11][12]
Data from the Fight Retinal Blindness (FRB) registry, a prospective observational database, has provided valuable insights into the long-term outcomes of anti-VEGF treatment in Australia. A study analysing 10-year treatment outcomes from the FRB registry reported that the mean visual acuity (VA) in Australian patients who completed 10 years of treatment dropped by only 0.9 letters from baseline, with 42% achieving a VA of ≥20/40. This contrasts with Swiss patients, who experienced a mean loss of 14.9 letters, highlighting the effectiveness of the treat-and-extend regimen commonly used in Australia.[1]
Research has focused on developing longer-acting anti-VEGF agents and sustained-release delivery systems to address the burden of frequent injections. Newer agents such as faricimab and aflibercept 8mg have shown promise in extending the interval between injections to 12 or even 16 weeks for some patients. Additionally, the ranibizumab port delivery system (PDS) is a novel sustained-release device that can be refilled periodically, potentially reducing the frequency of intravitreal injections. This device has shown efficacy in maintaining visual acuity with fewer treatments, thus alleviating the treatment burden.[2][7][8][9] Retinal specialists at QEI, A/Prof Anthony Kwan and A/Prof Abhishek Sharma, have been involved in an international clinical trial to implant this new device in selected patients. QEI is the only centre in Queensland that can provide this opportunity, and four patients are part of this ongoing trial. We hope this device will be available in the routine care of nAMD in Australia.
Gene therapy is another emerging approach that aims to provide long-term treatment for nAMD. Gene therapies such as RGX-314 and ADVM-022 involve the introduction of viral vectors that enable retinal cells to produce anti-VEGF proteins, potentially offering a one-time treatment solution. These therapies are currently in early-phase clinical trials and hold promise for the future management of nAMD.[8]
In summary, introducing anti-VEGF therapies has revolutionised the treatment of wet macular degeneration, significantly reducing the incidence of vision loss and blindness worldwide, including in Australia. The development of longer-acting agents and sustained-release delivery systems represents the latest advancements in this field, aiming to reduce the treatment burden and improve patient outcomes. Continued research and innovation are essential to enhance the efficacy and convenience of nAMD treatments.
Author: A/Prof Anthony Kwan
References
1. Ten-Year Treatment Outcomes of Neovascular Age-Related Macular Degeneration From Two Regions. Gillies M, Arnold J, Bhandari S, et al. American Journal of Ophthalmology. 2020;210:116-124. doi:10.1016/j.ajo.2019.10.007.
2. FIVE-YEAR INCIDENCE AND VISUAL ACUITY OUTCOMES FOR INTRAVITREAL THERAPY IN BILATERAL NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: Fight Retinal Blindness! Project. Cornish EE, Teo KY, Nguyen V, et al. Retina (Philadelphia, Pa.). 2021;41(1):118-124. doi:10.1097/IAE.0000000000002798.
3. Changes in 12-Month Outcomes Over Time for Age-Related Macular Degeneration, Diabetic Macular Oedema and Retinal Vein Occlusion. Bhandari S, Nguyen V, Hunt A, et al. Eye (London, England). 2023;37(6):1145-1154. doi:10.1038/s41433-022-02075-6.
4. Neovascular Age-Related Macular Degeneration: A Review of Findings From the Real-World Fight Retinal Blindness! Registry. Nguyen V, Barthelmes D, Gillies MC. Clinical & Experimental Ophthalmology. 2021;49(7):652-663. doi:10.1111/ceo.13949.
5. Lifetime Outcomes of Anti-Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration. Finger RP, Puth MT, Schmid M, et al. JAMA Ophthalmology. 2020;138(12):1234-1240. doi:10.1001/jamaophthalmol.2020.3989.
6. A Pharmacoepidemiologic Study of Ranibizumab and Aflibercept Use 2013-2016. The Fight Retinal Blindness! Project. Barthelmes D, Nguyen V, Walton R, Gillies MC, Daien V. Graefe’s Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2018;256(10):1839-1846. doi:10.1007/s00417-018-4061-2.
7. Treat-and-Extend Versus Fixed Bimonthly Treatment Regimens for Treatment-Naive Neovascular Age-Related Macular Degeneration: Real World Data From the Fight Retinal Blindness Registry. Figueras-Roca M, Parrado-Carrillo A, Nguyen V, et al. Graefe’s Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2021;259(6):1463-1470. doi:10.1007/s00417-020-05016-9.
8. PAVBLU. Food and Drug Administration. Updated date: 2025-03-04.
9. LUCENTIS. Food and Drug Administration. Updated date: 2024-11-18.
10. Estimated Cases of Blindness and Visual Impairment From Neovascular Age-Related Macular Degeneration Avoided in Australia by Ranibizumab Treatment. Mitchell P, Bressler N, Doan QV, et al. PloS One. 2014;9(6):e101072. doi:10.1371/journal.pone.0101072.
11. Incidence and Baseline Clinical Characteristics of Treated Neovascular Age-Related Macular Degeneration in a Well-Defined Region of the UK. Keenan TD, Kelly SP, Sallam A, et al. The British Journal of Ophthalmology. 2013;97(9):1168-72. doi:10.1136/bjophthalmol-2013-303233.
12. Reduced Occurrence of Severe Visual Impairment After Introduction of Anti-Vascular Endothelial Growth Factor in Wet Age-Related Macular Degeneration – A Population- And Register-Based Study From Northern Sweden. Granstam E, Westborg I, Barkander A, et al. Acta Ophthalmologica. 2016;94(7):646-651. doi:10.1111/aos.13187.