Intravitreal Anti-VEGF Injections
Intravitreal injections are the cornerstone of wet age-related macular degeneration (AMD) management. These agents work by inhibiting vascular endothelial growth factor (VEGF), thereby reducing the abnormal blood vessel growth and leakage that rapidly impair vision.
Avastin (bevacizumab), though originally developed for cancer therapy, is extensively used off-label due to its cost-effectiveness and comparable efficacy.
Lucentis (ranibizumab) was purpose-designed for ocular conditions and holds licencing approval specifically for wet AMD.
Eylea (aflibercept) not only binds VEGF but also placental growth factor, offering prolonged durability and a potentially extended dosing interval, while a higher-dose variant,
Eylea HD ( aflibercept 8mg) further advances treatment longevity.
Vabysmo (faricimab) has emerged as a dual-action agent targeting both VEGF and angiopoietin-2, which may reduce treatment burdens even further.
Beovu and Macugen are no longer in common use in the UK
Ongoing studies seek to optimize dosing intervals and tailor therapy according to individual patient responses, refining these paradigms further.
Choice of Agent
Choosing among Avastin, Lucentis, Eylea (including Eylea HD), and Vabysmo largely depends on a balance of efficacy, durability, cost, and patient-specific factors.
Ultimately, the treatment choice will hinge on individual patient characteristics, response patterns, treatment adherence potential, and financial considerations, alongside local clinical experience.
Treatment Protocols
Treatment protocols for wet AMD aim to effectively suppress VEGF while balancing treatment burden.
The fixed monthly regimen delivers injections every four weeks, providing continuous disease control at the expense of frequent clinic visits.
The treat-and-extend approach begins with monthly injections until the eye stabilises; treatment intervals are then progressively lengthened (typically by 2–4 weeks) as long as imaging shows no recurrence or fluid buildup. This method seeks to reduce the number of injections and visits while maintaining adequate disease suppression.
In contrast, the Pro Re Nata (PRN, or “as needed”) dosing protocol involves regular monitoring—often monthly—with injections administered only upon evidence of disease reactivation on clinical examination or OCT imaging. Although PRN can minimise overtreatment, it requires rigorous follow-up to prevent delays in addressing exacerbations.
In addition, patient-specific factors and physician judgment guide therapy decisions.
Photodynamic Therapy
Photodynamic therapy (PDT) emerged as a landmark treatment for wet (neovascular) age-related macular degeneration (AMD) around the turn of the millennium. Before its introduction, treatments like thermal laser photocoagulation and surgical removal of neovascular tissue were tried , though these methods often came with significant collateral damage to surrounding healthy retinal tissue. PDT provided a crucial alternative because it allowed for a more targeted approach, aiming to occlude abnormal blood vessels while sparing the normal retinal structures. This historical shift marked an important evolution in managing a disease that was a leading cause of vision loss among older adults.
The methodology behind PDT is elegantly strategic. First, a photosensitising drug—most commonly verteporfin—is administered intravenously. This agent selectively accumulates in the abnormal blood vessels that proliferate beneath the retina in wet AMD. After a prescribed period that allows for adequate uptake, a laser emitting a specific wavelength is directed at the affected area of the eye. When activated by the light, verteporfin produces reactive oxygen species that induce localized damage, effectively sealing off or eliminating the problematic neovascular tissue. This dual-stage process minimises damage to adjacent healthy tissues, offering a precise and controlled treatment modality that contrasts sharply with earlier, less discriminating techniques
Today, while anti-vascular endothelial growth factor (anti-VEGF) therapies have largely become the frontline treatment for neovascular AMD due to their superior visual outcomes, PDT still holds a valuable niche in clinical practice. It is particularly beneficial for certain specific subtypes of neovascular AMD—such as polypoidal choroidal vasculopathy and pachychoroid neovasculopathy—where PDT can be used either alone or in combination with anti-VEGF treatments. This combination strategy can enhance treatment efficacy by addressing aspects of the disease that may not fully respond to anti-VEGF monotherapy. Thus, even in an era dominated by molecular therapies, PDT continues to be an important tool, offering a minimally invasive option to manage lesion size and preserve visual acuity in carefully selected patient populations .
Beyond these core aspects, ongoing research into PDT aims to refine its use and potentially expand its indications. Questions remain about optimising treatment protocols, exploring synergistic effects with emerging therapies, and identifying biomarkers that can help select the patients most likely to benefit from PDT. The story of PDT remains a compelling example of how targeted, technology-driven interventions can transform the treatment landscape for chronic, vision-threatening diseases.
Corticosteroid Injections
Corticosteroid intravitreal injections, such as triamcinolone acetonide, have been investigated for wet AMD largely due to their potent anti-inflammatory properties. Unlike the primary anti‑VEGF agents—which directly target the neovascular process—corticosteroids can help reduce associated inflammation and vascular permeability, potentially mitigating macular oedema.
Injections of corticosteroid were sometime used before anti- VEGF agents but nowadays their use is generally considered as an adjunct or in cases where patients exhibit a suboptimal response to anti‑VEGF monotherapy, rather than as first‑line treatment.
The clinical evidence supporting corticosteroid use in wet AMD is limited and inconsistent. Side effects include cataract formation and increased intraocular pressure, which can complicate long‑term management. Consequently, corticosteroids are rarely employed as a stand‑alone therapy for wet AMD
Radiotherapy
Radiotherapy for wet age‐related macular degeneration (AMD) has been explored as an adjunct or alternative treatment to anti‑VEGF therapy by targeting abnormal neovascular tissue with localised radiation—most notably through epiretinal plaque brachytherapy applied to the surface of the eye. Several randomised controlled trials have examined its efficacy, with mixed results. Some studies reported modest reductions in the rate of vision loss compared to control groups, while others found no significant benefit regarding visual acuity improvements when compared to sham treatments or observation. Concerns over safety remain significant, particularly the potential for radiation-induced damage to healthy retinal tissue and other ocular structures.
IRay radiotherapy was developed as an innovative, noninvasive approach to treating wet age-related macular degeneration (AMD). Its history traces back to early studies that explored using focused radiation to impede the aberrant growth of fragile blood vessels beneath the macula. The IRay system was specifically engineered to deliver a narrow, low-energy X‑ray beam precisely to the diseased retinal area. The procedure aimed to target abnormal neovascular tissue while sparing the surrounding healthy retina, potentially reducing the need for frequent intravitreal injections.
The rationale behind this method was twofold. First, by inflicting localised DNA damage in the pathological vasculature, IRay sought to cause regression of neovascularisation, thereby stabilising or improving vision. Second, the one-off or limited-treatment nature of radiotherapy offered the promise of lowering the overall treatment burden—a critical consideration given the often chronic, intensive anti‑VEGF injection schedules. However, clinical experience revealed several limitations. Although initial studies showed some potential to reduce injection frequency, the precision required for effective radiation delivery proved challenging. Concerns also emerged regarding the long-term safety of radiation exposure to delicate ocular tissues.
As anti‑VEGF therapies—such as ranibizumab, aflibercept, and, more recently, faricimab—demonstrated superior efficacy and predictable safety profiles in large, randomised controlled trials, the enthusiasm for IRay diminished. In the UK, where robust evidence and cost‐effectiveness are paramount, these newer agents quickly became the standard of care, relegating radiotherapy approaches like IRay to a historical footnote in wet AMD management.