Route-specific immune risk can obscure durability

A 2025 ocular AAV meta-analysis connects delivery route with immune safety: intravitreal administration was associated with more uveitis than subretinal delivery, while prophylactic immunosuppression affected systemic responses differently by route. This matters for durability because inflammation can damage transduced tissue or shorten functional benefit. FDA materials likewise frame immune monitoring around both vector and transgene responses, with delivery procedure and immunosuppression treated as safety variables. The unresolved decision is whether route-specific inflammation, uncertain persistence of expression, or the burden of immune control most limits the next study design.