Toward successful retinal drug delivery after intravitreal injection: Current strategies to overcome the inner limiting membrane.

The global prevalence of retinal disorders leading to vision impairment and blindness is rising to significant numbers and is estimated to continuously increase in the coming years. Although many groundbreaking therapies are available in the expanding field of retinal gene and cell therapy, troublesome delivery after intravitreal (IVT) injection is currently complicating their clinical translation. In this regard, the inner limiting membrane (ILM), the basement membrane located between the vitreous and the retina, is recognized as the main obstacle hindering retinal entry. Overcoming this barrier might hence advance a plethora of potent therapeutics currently available but failing to enter the retina. Aware of the importance to address this drug delivery issue, this review will discuss the current proposed methods to tackle the ILM barrier. First, we will provide an overview of ILM characteristics in health and disease after which we will reflect on the relevance of the ILM barrier role for emerging advanced therapeutic strategies. Seeing the significance of ILM removal for those therapeutics, the current proposed surgical, pharmacological and physical strategies to bypass the ILM will furthermore be highlighted to encourage the entire field of retinal drug delivery after IVT injection forward.