FLORetina 2025: Real-world aflibercept data supports clinically guided, flexible nAMD dosing

Editor's Note: This content was generated with the assistance of AI.

Loredana Smarandache, MD, medical retina fellow at the Royal Victoria Infirmary, discusses a retrospective study of 135 treatment-naive neovascular AMD (nAMD) eyes treated with aflibercept 2 mg during the Covid-19 pandemic.

The conversation highlights that current rigid 4‑weekly regimens may lead to over‑injection, and that newer, longer-acting anti‑VEGF agents warrant reassessment of legacy trial assumptions, with further research into pharmacokinetics, sustained‑release delivery, and broader retinal disease cohorts.

Dr Smarandache presented "Inadvertent Anti-VEGF interval increases during the covid-19 pandemic" at the FLORetina 2025 Congress, the 13th International Congress on OCT and OCT Angiography (ICOOR), held from December 4-7, in Florence, Italy.

Key clinical takeaways:

Moderate delays may be safe for many patients

• In this cohort of 135 treatment‑naive nAMD eyes on aflibercept 2 mg, delays of ~4–5 weeks to the first post‑loading injection did not significantly worsen 12‑month visual acuity, even with some residual fluid.

Rigid loading and fixed intervals may not be essential

• Outcomes were similar even when loading wasn’t perfectly completed, supporting clinically guided flexibility rather than strict adherence to traditional loading schedules and fixed 4‑weekly intervals.

No clearly “high‑risk” comorbidity subgroup identified here

• A few RPE tears and macular haemorrhages occurred, but were not statistically tied to delay length in this dataset.

Service redesign can protect vision during disruption

• Virtual clinics, fast‑track imaging hubs, and emerging home OCT can reduce delays and enable more personalized treat‑and‑extend strategies.

Newer, durable agents need updated evidence

• Real‑world data and pharmacokinetic evidence suggest longer effective duration of aflibercept, supporting trials of longer intervals and sustained‑release systems.

The Eye Care Network caught up with Dr Smarandache ahead of the conference.

Editor's note: Transcript lightly edited for length and clarity.

Loredana Smarandache, MD: Hello. My name is Dr Loredana Smarandache, and I'm a medical retina fellow working at the Royal Victoria Infirmary, hospital for the Newcastle Upon Tyne NHS Foundation Trust. And I want to thank you for allowing us to talk about our paper that assesses inadvertent anti-VEGF interval increases during the Covid-19 pandemic.

Kassi Filkins, editor: Could you tell us about what patterns you observed in treatment intervals during the pandemic, and how did the changes affect patient outcomes?

Smarandache: As we know neovascular, or exudative, age-related macular degeneration is a macular pathology characterized by the growth of abnormal choroidal blood vessels that leak fluid. Anti-VEGF therapy has transformed neovascular AMD management. Trials such as ANCHOR, MARINA, CATT, and VIEW show that regular intravitreal injections can prevent and often improve vision. Fixed loading schedules proved hard to sustain in real world practices, though, leading to more flexible strategies. Treat and extend regimens supported by studies such as TREX-AMD, ARIES and LUCAS are now widely used to match treatment to disease activity while reducing patient burden in services. The Covid-19 pandemic significantly disrupted these treatment schedules. Despite guidance from the Royal College of Ophthalmologists, many patients experience delayed [treatment], often at critical time points. Interesting, though, some returned with stable or even dry OCT findings—raising important questions about how much flexibility these regimens can safely tolerate. In our retrospective observational study of 135 treatment naive eyes with neovascular age-related macular degeneration treated with aflibercept 2 mg; nearly half experienced a delay of at least 2 weeks to the first post loading injection, with an average delay of 4.5 weeks. Despite this and despite persisted sub retinal fluid on the OCT in some cases, visual acquity at 12 months was not significantly different. When eyes were not loaded as planned, visual acquity gain or loss was not statistically significant either. Although our study did not directly assess a reduced number of loading injections, it suggested that strict adherence to the traditional pre loading dose phase may not be essential for maintaining visual outcomes. Together with the evidence from FLUID study, our findings challenge rigid treatment schedules and instead support a more clinically guided, flexible approach—particularly in situations like service disruption. These results can work as strong rational for future trials exploring more individualized treatment strategies, including adjusting timing of the fourth injection and potentially fewer loading doses.

Filkins: Were certain retinal conditions and/or comorbidities more vulnerable to extended intervals compared to others?

Smarandache: Published data on the impact of Covid-19 pandemic on anti-VEGF services consistently show that the treatment delays were largely driven by clinic capacity constraint and patient concerns about exposure to infection. In many countries, particularly in those countries with stricter lockdown measurements, attendance rates drop significantly with priority being given to more immediate life threatening conditions—which are more prevalent in elderly and vulnerable patients who form the majority of our neovascular AMD cohort. Our observational studies specifically focused on treatment, naive, neovascular AMD, so we don't have comparative data on other retinal conditions within our data set. However, we had 2 cases that developed a retinal pigment epithelium tear and 2 cases that developed macular hemorrhages. But these events were not statistically linked to the length of treatment delay. Overall, while individual complications did occur, our data did not identify a specific subgroup or comorbidity that appeared to be disproportionately vulnerable to extended treatment intervals. But this highlights the need for further, larger studies that include a broader range of retinal diseases to define risk profiles in the context of flexible treatment schedules.

Filkins: How did telemedicine or remote monitoring mitigate these challenges, and did any patient groups excel with adherence and preservation of visual acuity?

Smarandache: The virtual clinics at the Royal Victorian Infirmary first began during the Covid-19 pandemic in 2020. Back then, the service was run by our photography team on Saturdays, with patients being booked every 20 minutes. This gave them the time needed to check the vision, take the images and clean all the equipment before the next patient arrived. We couldn't use see large number of patients, but the system allowed us to keep essential care going during an uncertain time. Once restrictions aged, we were able to fully set up the imaging hub, which transformed what we could offer. Today, we're fortunate to work alongside a very hard working and dedicated team to run virtual clinics, not only in the medical retina field, but also for several other subspecialties within our ophthalmology department. For example, in September 2024 we launched a fast-track neovascular AMD virtual clinic, designated to speed up assessment for patients suspected of neovascular AMD. Our early data is very assuring, showing that 86% of these patients are being reviewed within 20 days from their referral—helping us to make sure that anyone who needs anti-VEGF treatment can start within the 14 day window recommended by the NICE guidelines. This has made a meaningful difference in getting the right patients treated at the right time. Technology is also creating new opportunities as at home OCT devices become more accessible, they could help us monitor patients more closely and potentially extend treatment intervals with more confidence. For example, if a patient has a completely dry OCT scan at their second injection visit, we may be able to extend sooner than we typically would. Our own data suggests that standard treatment intervals we use may sometimes be stricter than necessary. Some patients who didn't complete an ideal loading phase still kept good vision, and even those who had an 8 week delay often remained stable. Of course, this isn't true for certain conditions such as polypoidal diseases or macular hemorrhages that clearly need more frequent injections and tight follow up. Overall, our experience at the Royal Victorian Infirmary showed us how virtual clinics fast-track imaging hubs and new at home monitoring devices can work together to reduce delays, to ease the clinic pressure, and give patients a more personalized experience.

Filkins: So what lessons can we apply from this period to future disruptions in care delivery?

Smarandache: Unfortunately, although major crisis to our history have sometimes pushed us to reflect and improve, we genuinely hope we never face anything as disrupting and as devastating as the Covid-19 pandemic again. Still, our study shows that even from such a difficult period, there are lessons worth carrying forward. What we present here may serve as a blueprint, should services ever face a similar level of disruption again in the future. With the rising numbers of patients needing anti-VEGF treatment, combined with limited clinic capacity and the known risks and side effects of intravitreal injections, it's very important to reconsider if our current rigid treatment intervals are always necessary. Our findings in our study suggest that in many cases, we may be over injecting. Therefore our work, together with the results from the FLUID study and a growing amount of real world experience provide reassurance that for a large proportion of patients, a less aggressive approach to neurovascular age-related macular degeneration can still maintain good vision. This is an area that clearly deserves more research and investment.

Filkins: What do these results say about the role of sustained release or enhanced durability anti-VEGF formulations?

Smarandache: We reviewed our data on aflibercept 2 mg, and our results highlight how newer agents appear to be more effective and longer acting than earlier options available in the market. The widely accepted practice of using 4 weekly injections is still largely based on old, landmark trials such as ANCHOR, MARINA, CATT, and VIEW. Laboratory studies on drug longevity are limited, but we have some published evidence that offers some useful insight. For example, a publication of Fauser et al from 2014 demonstrated that VEGF suppression in the aqueous humor after intravitreal aflibercept remained for up to 71 days. Therefore their study suggested that patients on an 8 week regimen may not necessarily require an aflibercept injection at the exact interval—as pharmacological activity can persist even towards a 10 week interval. More research into pharmacokinetics and pharmacodynamics would be extremely valuable in helping us understand the true duration of effect of this medication. At the Royal Victorian Infirmary, we are fortunate to work with a strong research team led by our clinical director, Mr James Talks, a well recognized figure in the field of medical retinal research, and our vitreolretinal consultants, Ms Roxane Hillier and Mr Young-Zvandasara are currently conducting a study exploring port delivery systems for anti-VEGF therapy. As anti-VEGF agents continue to advance, there is a clear need for a new study, or new studies, to reassess the assumptions of older trials and evaluate how these drugs perform in real world practice and future treatment models.