FLORetina: Inadvertent anti-VEGF interval increases during the COVID-19 pandemic

Pandemic-related disruptions led to widespread delays in anti-VEGF treatment for neovascular age-related macular degeneration (nAMD), raising concerns about vision loss, according to Loredana Smarandache, MD, Medical Retina Fellow, Ophthalmology Department, Royal Victoria Infirmary, Newcastle upon Tyne NHS Foundation Trust.

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 4-7 December in Florence, Italy.

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

What patterns did you observe in treatment intervals during the pandemic? How did the changes affect patient outcomes?

Loredana Smarandache, MD: As we know, neovascular (exudative) age-related macular degeneration (nAMD) is a macular pathology characterised by the growth of abnormal choroidal blood vessels that leak fluid.

Anti-VEGF therapy has transformed nAMD management. Trials such as ANCHOR, MARINA, CATT, and VIEW showed that regular intravitreal injections can prevent, and often improve, vision loss. Fixed dosing schedules proved hard to sustain in real-world practice, leading to more flexible strategies. Treat-and-extend regimens, supported by studies like TREX-AMD, ARIES, and LUCAS, are now widely used to match treatment to disease activity while reducing patient and service burden.

The COVID-19 pandemic significantly disrupted these treatment schedules. Despite guidance from the Royal College of Ophthalmologists, many patients experienced delays, often at critical time points. Interestingly, 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-naïve eyes with neovascular AMD 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 persistent subretinal fluid on OCT in some cases, visual acuity at 12 months was not significantly different.

When eyes were not loaded as planned, visual acuity gain or loss was not statistically significant either.

Although our study did not directly assess a reduced number of loading injections, it suggests that strict adherence to the traditional 3-dose loading phase may not be essential for maintaining visual outcomes. Together with evidence from the FLUID study, our findings challenge rigid treatment schedules and instead support a more clinically guided, flexible approach, particularly in situations of service disruption. These hypothesis-generating results provide a strong rationale for future non-inferiority trials exploring more individualised early treatment strategies, including adjusted timing of the fourth injection and potentially fewer loading doses.

Were certain retinal conditions and/or comorbidities more vulnerable to extended intervals than others?

Smarandache: Published data on the impact of the COVID-19 pandemic on anti-VEGF services consistently show that treatment delays were largely driven by clinic capacity constraints and patient concerns about exposure to infection. In many countries, particularly those with stricter lockdown measures, attendance rates dropped significantly, with priority given to more immediately life-threatening conditions, especially among older and more vulnerable populations who form the majority of the nAMD cohort.

Our observational study specifically focused on treatment-naïve neovascular AMD, so we do not have comparative data on other retinal conditions within our dataset. However, within our cohort, 2 eyes developed retinal pigmented epithelium tears (1 delayed, 1 non-delayed), and 2 eyes in the delayed group developed new macular haemorrhages. However, 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. This highlights the need for further, larger studies that include a broader range of retinal diseases to better define risk profiles in the context of flexible treatment schedules.

How did telemedicine or remote monitoring mitigate these challenges? Did any patient group excel with adherence and preservation of visual acuity?

Smarandache: The Virtual Clinics at the Royal Victoria Infirmary first began during the COVID-19 pandemic in 2020. Back then, the service was run by our photography team on Saturdays, with patients booked every 20 minutes. This gave enough time to check vision, take the necessary images, and clean all equipment before the next patient arrived. We couldn’t see large numbers of patients, but the system allowed us to keep essential care going during an uncertain time.

Once restrictions eased, we were able to fully set up the Imaging Hub, which transformed what we could offer. Today, we’re fortunate to have a hardworking and committed team that runs virtual imaging clinics not only for medical retina but also for several other subspecialties across our ophthalmology department.

In September 2024, we also launched a Fast-Track nAMD Virtual Clinic designed to speed up assessments for suspected nAMD. Our early data are very reassuring: 86% of these patients are reviewed within 20 days, helping us ensure that anyone who needs anti-VEGF treatment can start within the 14-day window recommended by NICE. 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 suggest that the 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 everyone: patients with macular haemorrhages or polypoidal disease clearly need more frequent injections and tight follow-up.

Overall, our experience at the Royal Victoria Infirmary shows how virtual clinics, rapid-access imaging hubs, and new home-monitoring technologies can work together to reduce delays, ease clinic pressure, and give patients a more flexible and personalised experience.

What lessons can we apply from this period to future disruptions in care delivery?

Smarandache: Although major crises throughout history have sometimes pushed us to reflect and improve, we genuinely hope we never face anything as disruptive and 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 may serve as a useful blueprint should services ever face a similar level of disruption in the future.

With the rising number of patients needing anti-VEGF treatment, combined with limits in clinic capacity and the known risks and side effects of intravitreal injections, it is increasingly important to reconsider whether our current rigid treatment intervals are always necessary. Our findings suggest that, in many cases, we may be over-injecting.

Alongside our work, 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 nAMD, and possibly other conditions such as diabetic macular oedema (DMO) or retinal vein occlusions (RVO), can still maintain good outcomes. This is an area that clearly deserves further research and investment.

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. The widely accepted practice of using 4-weekly injections is still largely based on older landmark trials such as ANCHOR, MARINA, CATT, and VIEW.

Laboratory studies on drug longevity are limited, but some published evidence offers useful insight. For example, Fauser et al. (2014) demonstrated that VEGF suppression in the aqueous humour after intravitreal aflibercept remained for up to 71 days. Their study suggested that patients on an 8-week regimen may not necessarily require an aflibercept injection at that exact interval, as pharmacologic activity can persist even toward a 10-week interval. More research into pharmacokinetics and pharmacodynamics would be extremely valuable in helping us understand the true duration of effect of these medications.

At the Royal Victoria Infirmary, we are fortunate to work alongside a strong research team led by our Clinical Director, Mr James Talks, a well-recognised figure in the field of medical retina research. Our vitreoretinal consultants, Miss 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 new studies that reassess the assumptions of older trials and evaluate how these evolving drugs perform in real-world practice and future treatment models.

At this year's FLORetina, which presentations or discussions do you anticipate will be the most valuable for your work?

Smarandache: This is my first time attending the FLORetina Conference, and after looking through the preliminary programme, I’m genuinely overwhelmed, in a good way, by the number of important papers and exciting topics on offer. Both Mr Young-Zvandasara and I have a strong interest in technology and its role in ophthalmology, so I’m particularly drawn to Prof Anat Loewenstein’s lectures. Her session on “AI for home monitoring in retinal diseases: What’s new in 2025?” is especially relevant to our own work.

I’m also very much looking forward to the IVEG Course on 6 December, moderated by Prof Loewenstein with Dr Baruch Kyppermann. It promises to offer valuable, practical insights into current trends and evolving approaches in anti-VEGF treatment.

As a young ophthalmologist, I’m grateful and excited to have been able to book a free 30-minute session with the Haag-Streit Simulator Lab for ROP screening and laser training. Simulation-based training is extremely valuable for junior doctors, as it not only improves knowledge but also builds confidence before transitioning to hands-on procedures in real clinical settings with real patients.

I’m equally excited to attend the sessions of my colleagues at FLORetina. Miss Chin Pey Yap will be presenting her work on ERG findings in multiple evanescent white dot syndrome, and Mr Sandro Di Simplicio will be participating in a live surgery session.

I’m extremely proud to be part of the Royal Victoria Infirmary team in Newcastle upon Tyne and to work alongside such talented and respected professionals.