FLORetina 2025: Long-term follow-up in paediatric gene therapy

Prof Siegfried G. Priglinger, MD, FEBO, talked with the Eye Care Network about the unique challenges and evolving insights in long-term follow-up of paediatric patients receiving gene therapy.

At the FLORetina 2025 Congress, the 13th International Congress on OCT and OCT Angiography (ICOOR), held from 4-7 December in Florence, Italy, Prof Priglinger presented "From Hope to Evidence: Long-Term Follow-Up in Paediatric Gene Therapy."

Maintaining continuity over many years is inherently difficult, as children move through developmental stages that disrupt care; additionally, long-term follow-up also demands repeated imaging and functional testing, creating practical and emotional burdens for families.

Ensuring data integrity and retention requires both technical consistency and family-centered communication, Prof Priglinger said. Standardised imaging parameters, harmonised functional assessments, and central reading centres help minimise variability over time. Retention, however, depends on early and ongoing engagement: families must understand that long-term monitoring is integral to treatment safety. Flexible scheduling, travel support, a dedicated point of contact, and a structured transition into adult care substantially reduce drop-out.

Ethical considerations are central in paediatrics, including evolving assent, minimising testing burden, safeguarding long-term data, and ensuring equitable access to follow-up. Registries and real-world evidence complement trial data by capturing broader populations, rare late events, centre-level variability, and patient-reported outcomes.

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

What are the key challenges in maintaining long-term follow-up in paediatric populations

One of the main challenges is that children move through several developmental stages, and each transition increases the risk of losing them from follow-up. School changes, adolescence, and later the transfer to adult clinics often disrupt continuity. In addition, long-term gene therapy follow-up requires repeated imaging and functional testing, which can be burdensome for families in terms of time, travel, and cost.

Motivation may also decline over time if families perceive their child as “stable,” and psychological factors—such as anxiety about disease progression—can influence attendance. Finally, long-term monitoring often extends far beyond the duration of a formal clinical trial, which makes sustaining structured follow-up in routine care more difficult.

How do you ensure data integrity and patient retention over extended periods?

Ensuring data integrity starts with standardised protocols: identical imaging settings, harmonised functional assessments, and use of central reading centres to reduce variability. Strong electronic data capture systems with automated quality checks help maintain long-term consistency.

Retention relies heavily on communication and support. Families must understand from day one that long-term monitoring is part of the therapy and essential for safety. Flexible scheduling, travel support where possible, and a dedicated long-term contact person significantly improve adherence. A structured transition plan into adult care is also essential to prevent drop-out during adolescence.

What trends have emerged regarding the durability and safety of gene therapy in children?

We see rapid early improvements in light sensitivity and functional vision after RPE65 gene therapy, and many of these gains appear to be durable for several years. However, structural degeneration of the retina might continue in these treated children, however definitively at a slower rate. Today we still cannot tell whether gene therapy modifies the disease course or, in selected cases, does completely halt it.

The safety profile remains favourable overall. Most adverse events are related to the surgical procedure or short-term inflammation, which is usually manageable. Long-term concerns include the progression of retinal atrophy despite treatment and questions around immune responses decades after AAV exposure, especially in children treated at a very young age.

Are there ethical considerations unique to paediatric follow-up?

Yes, several. Children cannot give informed consent themselves, so consent by parents must be supplemented with age-appropriate assent as children mature. Because follow-up can last 10–20 years, information must be revisited and autonomy respected as the child grows.

The burden of testing must also be ethically justified; repeated, time-consuming assessments should be required only when they provide clear clinical or scientific value. Data privacy is another area of concern, as gene therapy generates long-term genetic, imaging, and functional datasets. Finally, equitable access is essential; long-term follow-up should not exclude families who live far from treatment centres or face socioeconomic challenges.

How might registries or real-world evidence complement clinical trial data?

Registries extend observation far beyond the timelines of clinical trials and capture a broader, more representative patient population, including children who are younger, older, or in more advanced stages of disease than typical trial participants. They are invaluable for identifying rare late adverse events, comparing outcomes across centres, and understanding real-world variability in surgical techniques or follow-up routines.

Importantly, registries also allow integration of patient-reported outcomes and quality-of-life measures, which help us evaluate the real-life impact of gene therapy on independence, education, and long-term development.

What is the most important trend or emerging area you hope to understand better after FLORetina?

I am particularly interested in the long-term structural-functional relationship: how retinal imaging markers over 5–10 years correlate with the functional improvements we see early after therapy. We need clearer biomarkers to predict which children will maintain benefits longest.

Equally important are questions around optimal timing of treatment and how early intervention influences lifelong visual and developmental trajectories. Finally, a better understanding of long-term immunological responses and the feasibility of future retreatment will be crucial as our paediatric patients age.