Vision at the limits: Absolute threshold, visual function, and outcomes in clinical trials

The study of individual differences in perception at absolute threshold has a rich history, with much of the seminal work being driven by the need to identify those with superior abilities in times of war. Although the popularity of such testing waned in the latter half of the 20th century, interest in measures of visual function at the absolute limit of vision is increasing, partly in response to emerging treatments for retinal diseases, such as gene therapy and cellular therapies, that demand "new" functional measures to assess treatment outcomes. Conventional clinical, or clinical research, testing approaches generally assess rod sensitivity at or near absolute threshold; however, cone sensitivity is typically assayed in the presence of adapting backgrounds. This asymmetry may artifactually favor the detection of rod abnormalities in patients with outer retinal disease. The past decade has seen the commercialization of devices capable of assessing absolute threshold and dark adaptation, including specialized perimeters and instruments capable of assessing "full-field sensitivity threshold" that seek to integrate responses over time and space in those with unstable fixation and/or limited visual fields. Finally, there has also been a recent recapitulation of tests that seek to assess the subject's ability to interpret the visual scene at or near absolute threshold. In addition to assessing vision, such tests simultaneously place cognitive and motor demands on patients in line with the activities of daily living they seek to replicate. We describe the physical and physiological basis of absolute threshold and dark adaptation. Furthermore, we discuss experimental psychophysical and electrophysiological approaches to studying vision at absolute threshold and provide a brief overview of clinical tests of vision at absolute threshold.