The study of Gliem et al1 in this issue of JAMA Ophthalmology appears to be the first application of the powerful quantitative autofluorescence (qAF) technology to age-related macular degeneration (AMD) and warrants our full attention. To appreciate the significance of this study, recall that the retinal pigment epithelium (RPE) has been clinically imaged for nearly 2 decades by AF scans that record the AF of its lipofuscin granules. The value of clinical AF imaging for phenotype description and as a qualitative disease marker has continued to grow exponentially, not only in retinal degenerations such as AMD, Stargardt disease, and Best disease, but also in the wide spectrum of inflammatory disorders and choroidal tumors. Quantitative AF, introduced in 2011, is performed by calibrating the AF image to an embedded reference of known fluorescence efficiency, making it possible to reproducibly quantify and compare the AF intensity of the RPE, a surrogate for its lipofuscin content, between patients and across time. For example, a broad increase in qAF with age in individuals with healthy eyes was confirmed, documenting how lipofuscin accumulates. Interesting and unexplained sex and ethnic variations in these trends were found. The addition of qAF to the study of genotype/phenotype correlation in Stargardt disease has begun, with milder disease phenotypes generally associated with lower qAF levels. In Best disease, qAF levels are normal outside the Best vitelliform lesion itself, which is an interesting conundrum in a panretinal disease. More applications will follow.