Recent Advances in Age-Related Macular Degeneration (AMD) Management: Essential Updates for MRCP

Age-Related Macular Degeneration (AMD) remains a high-yield topic for the MRCP (Part 1 and Part 2) and Specialist Certificate Examination (SCE) due to its high prevalence and significant impact on public health. While established guidelines on wet (neovascular) AMD treatment (Anti-VEGF) and dry AMD management (lifestyle/supplements) are critical, the field is rapidly evolving. As an expert examiner, I emphasize that success in advanced medical exams requires knowledge of these key therapeutic breakthroughs.

Here, we break down the most pertinent recent research updates in AMD management that every MRCP candidate must know.

1. Advancements in Wet AMD (Neovascular AMD) Treatment

Wet AMD is characterized by the growth of abnormal blood vessels beneath the macula, leading to rapid, severe vision loss. Anti-Vascular Endothelial Growth Factor (Anti-VEGF) agents (Ranibizumab, Aflibercept, Bevacizumab) revolutionized care, but the high injection frequency (often monthly) presents a significant treatment burden.

A. Extended-Duration Anti-VEGF Agents (Dual Inhibition)

Recent research has focused on maximizing duration and efficacy through novel mechanisms:

• Faricimab (Vabysmo): This is a critical development. Faricimab is a bispecific antibody that targets not only VEGF-A but also Angiopoietin-2 (Ang-2). Ang-2 destabilizes blood vessels and sensitizes them to VEGF activity. By targeting both pathways, Faricimab offers potential superior anatomical outcomes and, crucially, allows for extended dosing intervals (up to four months) in suitable patients, significantly reducing the treatment burden. MRCP Tip: Know the dual mechanism of action and the potential for extended dosing.

B. Drug Delivery Systems

To overcome the need for frequent injections, sustained-release systems have been developed:

• Port Delivery System (PDS) with Ranibizumab (Susvimo): This system involves surgically implanting a small, refillable reservoir into the vitreous cavity. It slowly releases Ranibizumab over months, requiring refilling every 6 months. While its use requires surgical expertise, it represents a major step towards long-term, low-frequency treatment. The concept of sustained intraocular delivery is important for understanding future ophthalmology therapeutics.

2. The Breakthrough in Dry AMD (Geographic Atrophy) Management

Dry AMD accounts for 80-90% of cases and progresses slowly. Until recently, the only recommendation was lifestyle modification and antioxidant vitamins (AREDS formulation). The progression to Geographic Atrophy (GA)—an advanced, irreversible stage of dry AMD—causes severe central vision loss.

A. Complement Pathway Inhibitors

GA pathogenesis is strongly linked to chronic inflammation and uncontrolled activation of the complement cascade (specifically C3 and C5).

• Pegcetacoplan (Syfovre): This is a first-in-class treatment for GA. It is a targeted C3 complement inhibitor. Clinical trials demonstrated that monthly or bi-monthly intravitreal injections can slow the rate of GA lesion growth by approximately 20-30%. While it does not reverse existing damage, slowing progression is a major clinical breakthrough.

• Avacincaptad Pegol (Zimura): This agent targets the C5 component of the complement cascade. Similar to Pegcetacoplan, it has been shown to slow GA progression.

• MRCP Significance: The introduction of these complement inhibitors marks the first pharmacological treatment for GA. Expect questions relating to the underlying pathophysiology (complement activation) and the goal of treatment (slowing progression, not restoring vision).

3. Emerging Therapies: Gene Therapy and Neuroprotection

Research is also focusing on future preventative and long-term treatments:

• Gene Therapy: Trials are exploring viral vectors (AAV) delivered subretinally to make the retinal cells produce their own therapeutic proteins (e.g., Anti-VEGF agents or neurotrophic factors). This holds the promise of a single, curative treatment.

• Neuroprotection: Agents aiming to protect the remaining photoreceptors and retinal pigment epithelial (RPE) cells from oxidative stress and inflammation are under investigation, particularly for early to intermediate dry AMD.

Summary Table: Key AMD Research Updates for MRCP

Mastering these recent advances demonstrates not just rote memorization but a comprehensive understanding of evolving clinical ophthalmology, which is essential for success in specialist exams like the MRCP.