Abstract
Multiple gene therapy trials are occurring for a variety of ophthalmic diseases around the world. The safety of gene therapy in the eye has been established, and the next step is to reliably assess efficacy. This is primarily done through the use of imaging techniques and visual function measures. Standardized visual function assessments, however, were originally developed for a clinical setting and may not be suitable for detecting and quantifying therapeutic changes. This scoping review takes a comprehensive look at current practice in terms of the outcome measures defined at trial registration. These were compared to the outcome measures reported in the literature. All published trials reported the pre-registered primary outcome measure. A range of additional secondary outcomes were reported that were not originally planned. Gaps in gene therapy assessment exist and further discussion are required to find a way forward, particularly as more conditions progress to phase 2 and 3 trials. Several factors impacting on trial design and outcome measure choice are discussed.
Highlights
The eye presents the perfect organ for gene therapy
We identified 50 unique clinical trials on the registers for 17 ophthalmic indications (Supplementary Figure)
Outcome measures were analyzed according to clinical trial phase and were separated into four categories: safety, validated tests, novel test methods, and non-specific (Supplementary Table)
Summary
The eye presents the perfect organ for gene therapy It is an immune privileged site, which is protected by the blood retinal barrier. The target cells, such as photoreceptors and retinal pigment epithelium are frequently non-dividing, meaning any intervention is likely to last for life. Many disease processes have a degree of symmetry This means that, when treating one eye, the other eye can act as a control for comparison. There are established techniques to measure both structural and functional changes, with work ongoing in this field to evaluate the different diseases being treated. The success of gene therapy can be determined by the pattern of change seen in visual function measurement. Since visual function is the major marker for success of gene therapy, it is critical to establish guidelines for best practice
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