Expert pearls in personalised treatment strategies for neovascular AMD

As next-generation anti-VEGF agents redefine what is possible in terms of disease control and durability in neovascular AMD, the focus is shifting toward truly personalised care, that prioritises retinal stability, interprets advanced imaging biomarkers with clinical nuance, and balances long-term outcomes against treatment burden.

In this expert pearl, Dr Alessandro Arrigo draws on personal experience to share practical insights into individualising anti-VEGF treatment in routine clinical practice.

We are entering a new era of anti-VEGF therapy, in which next-generation molecules offer superior disease control and improved long-term outcomes. The real challenge is no longer drug efficacy per se, but how to fully exploit the therapeutic potential of these molecules through truly personalized treatment strategies.

Conventional disease classifications, such as type 1, type 2, and type 3 macular neovascularization, are increasingly insufficient. Within the same nominal subgroup, we often encounter markedly different disease behaviors, ranging from indolent to highly aggressive phenotypes. Similar limitations apply to other retinal diseases, including diabetic retinopathy and retinal vein occlusion, where conventional staging fails to capture the full spectrum of disease activity and progression.

To overcome these limitations, we must move beyond categorical labels and adopt next-generation quantitative imaging biomarkers capable of more precisely characterizing disease severity, activity, and treatment responsiveness. These metrics allow clinicians to tailor treatment intensity and durability more appropriately to the individual patient. Crucially, this process still requires expert human interpretation. A skilled grader is needed to critically evaluate imaging features, integrate multimodal data, and draw knowledge-based conclusions grounded in clinical experience and pathophysiology. Artificial intelligence can play an important supportive role by increasing efficiency and consistency, but it should remain an adjunct, not a replacement, for expert clinical judgment.

Every eye behaves differently, and a treat-and-extend regimen must be individualized accordingly. However, T&E should no longer be viewed solely as a strategy to keep the retina dry. The more clinically meaningful question is: how can we prevent disease reactivation over time?

Retinal stability, and the minimization of structural and functional fluctuations, is critical to reducing chronic photoreceptor stress. For this reason, achieving a dry retina is no longer a sufficient therapeutic endpoint. Instead, we should shift toward a new clinical target: a stable retina.

Disease activity may persist even in the absence of clinically evident exudation, driven by ongoing inflammatory and degenerative processes that are not fully captured by conventional criteria. In these cases, a standard treat-and-extend approach may underestimate residual disease activity and fail to provide optimal long-term control.

Therefore, treatment strategies must be adapted using next-generation quantitative imaging metrics that better reflect subclinical activity and tissue instability. The focus should move beyond short-term anatomical drying toward long-term disease stabilization, with a treatment horizon aimed at preserving retinal integrity and visual function over time.

A critical first step is to clearly define what we mean by a suboptimal responder, as this term may encompass different clinical scenarios with distinct implications.

A first scenario involves the inability to safely extend treatment intervals. These eyes often exhibit increased retinal fluctuations, which are associated with poorer long-term visual outcomes. In addition, the need for frequent injections may negatively impact patient motivation, adherence, and overall treatment sustainability.

A second scenario is characterized by the persistence of retinal fluid despite regular treatment, again with potential consequences for visual function and structural integrity.

In both situations, it is essential to comprehensively characterize the individual patient using imaging-based biomarkers and to ensure optimal control of concomitant systemic conditions, particularly in diseases such as diabetic retinopathy and retinal vein occlusion, where systemic factors play a major role.

Interval extension within a treat-and-extend regimen should therefore be approached cautiously, with both the decision to extend and the magnitude of extension tailored to the specific characteristics of each retina rather than applied in a standardized manner.

Treatment switching represents another powerful strategy. Transitioning from earlier-generation anti-VEGF agents to newer molecules often provides a clinically meaningful benefit and should be considered early rather than as a last resort. Even in patients already receiving next-generation therapies, switching may remain a valuable option, provided that all other modifiable factors have been carefully evaluated.

OCT offers a wide range of quantitative metrics that allow us to construct a detailed profile of disease characteristics. Many biomarkers and classification systems have been proposed, and in reality, most of them are clinically meaningful.

However, if we are forced to prioritize, one key concept stands out: a dry retina alone is no longer an adequate therapeutic endpoint. Clinical reasoning should not stop at “the retina is dry, therefore the job is done.” Rather, dryness should be considered only the first step. The subsequent and more complex task is to evaluate residual disease activity, tissue instability, and the risk of reactivation.

A major challenge lies in the gap between imaging metrics reported in scientific studies and what is realistically applicable in routine clinical practice. In research settings, a single OCT scan can be analyzed in great detail, whereas in daily practice clinicians often have only a few seconds to interpret images.

For this reason, the most effective strategy is to extract the core take-home messages from the literature and translate them into feasible clinical surrogates. For example, advanced artificial intelligence–based studies have demonstrated the relevance of hyperreflective foci as markers of disease activity. While precise quantification may be impractical in routine care, simply assessing their presence and visually monitoring their evolution over time can provide valuable insight into subclinical activity and treatment response.

This qualitative approach will never match the precision of research-grade analysis, but it meaningfully enhances personalized clinical decision-making.

In this context, AI tools may become increasingly valuable in the near future, provided they are used to support, and not replace, the critical interpretation of the human expert.

Next-generation anti-VEGF agents represent a major step forward in achieving this balance. Across clinical trials and real-world data, these molecules consistently demonstrate superior disease control while significantly reducing the number of required injections. This not only lowers the treatment burden for patients but also improves the overall sustainability of care delivery.

From a healthcare system perspective, fewer injections per patient translate into reduced direct costs, better allocation of human and technical resources, and the capacity to treat a growing number of patients within the same infrastructure. Improved durability also helps address real-life challenges such as treatment delays due to patient-related factors, long waiting lists, and limited injection slots, issues that are increasingly relevant in public health systems. Longer-lasting therapies enable more efficient injection planning at the hospital level, improving workflow organization, and reducing congestion in high-volume retina clinics.

This organizational benefit is crucial for maintaining quality of care in the context of an aging population and the rising prevalence of chronic retinal diseases. When considering the balance between durability and anatomical control, my personal target is to reach a 16-week dosing interval (12-week in more aggressive disease phenotypes).

In my view, this degree of durability is more than sufficient and usually corresponds to approximately three injections per year, which I consider a reasonable and acceptable burden for a chronic disease with a significant risk of legal blindness. I am more cautious about extending treatment intervals beyond this point.

Excessive extension may compromise disease control not only in the treated eye, but also in the fellow eye. Moreover, longer intervals often require more frequent monitoring visits, paradoxically shifting the focus from active treatment to surveillance. My clinical philosophy is to prioritize treatment over visits. In the long term, proactive and durable therapy is not only clinically sound but also the most sustainable strategy for preserving vision, optimizing healthcare resources, and ensuring equitable access to care.

Disclosures: Dr Alessandro Arrigo has nothing to disclose in relation to this article. No fees or funding were associated with this article.

Citation: Alessandro Arrigo. Expert pearls in personalised treatment strategies for neovascular AMD. touchOPHTHALMOLOGY.com. January 28 2026.

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