NEI-Supported Age-Related Macular Degeneration Research: Past, Present, and Future

Abstract

To review past and current National Eye Institute (NEI)-supported age-related macular degeneration (AMD) activities and initiatives and preview upcoming coordinated efforts for studying AMD. Methods: We conducted and summarized a portfolio analysis and literature review of NEI intramural and extramural AMD activities. Results: The NEI supports a broad range of AMD research, both by individual independent investigators as well as through networks and consortia. The International AMD Genomics Consortium, Age-Related Eye Disease Study, Age-Related Eye Disease Study 2 (AREDS2), and Comparison of AMD Treatments Trial legacy work probed the complex genetics, clinical presentation, and standards of patient care, respectively. The NEI AMD Pathobiology Working Group identified gaps and opportunities for future research efforts. The AMD Ryan Initiative Study and clinical trials testing the efficacies of minocycline to modulate retinal microglia activity and induced pluripotent stem cells-derived retinal pigmented epithelium (RPE) patch implants to rescue photoreceptor cell death are among the future directions for NEI-supported AMD research. Finally, NEI commissioned the creation of AREDS2 participant-derived induced pluripotent stem cell (iPSC) lines linked to their associated genomic and phenotypic datasets. These datasets will also be linked to the data obtained using their associated iPSC-derived cells (RPE, retina, choroid) and made publicly available. Conclusions: Investments by NEI for AMD research will continue to provide invaluable resources to investigators committed to addressing this complex blinding disease and other retinal degenerative diseases.

Clinical Perspectives and Trends: Microperimetry as a Trial Endpoint in Retinal Disease

“…So far, it has not been shown whether a large, high-quality MP data set can be acquired under such circumstances. Each with 20 international sites, MACUSTAR [12] and the AMD Ryan Initiative Study (ARIS) [14] will offer further insight into this within the context of AMD. In contrast, gene therapy trials typically recruit at a small number of specialist tertiary centres, potentially making practical considerations somewhat easier to manage.…”

“…Despite there being no examples of scotopic MP being employed as a primary or secondary endpoint in an interventional clinical trial so far, it is very encouraging that the SMART study, which scrutinises the potential role of scotopic MP as an endpoint in Stargardt disease, has recruited 118 participants [57]. Furthermore, scotopic MP has also been included in endpoint development studies in AMD [12-14].…”

“…The need for new, validated endpoints in both acquired and inherited retinal disease (IRD) has been widely discussed [9-11], with endpoint development clinical studies currently underway in early and intermediate age-related macular degeneration (AMD) [12-14], Stargardt disease [8], and retinitis pigmentosa [15]. An ideal endpoint would be capable of being easily and frequently measured; be repeatable with minimal measurement and ascertainment error; be sensitive to change over time and treatment effect; have clinical relevance and be meaningful to patients [6, 16].…”

Use of Composite End Points in Early and Intermediate Age-Related Macular Degeneration Clinical Trials: State-of-the-Art and Future Directions

“…However, continuous composite end points have a high potential because they allow integration of different outcome categories and thus can lead to an increase in statistical power within treatment studies when carefully validated [49]. Sensitivity testing and a validation of different composite end points in AMD research have yet to be performed which is why the MACUSTAR and ALSTAR2 studies as well as the AMD Ryan Initiative Study (ARIS) are currently being conducted [43][44][45]50].…”