Optimising the Structure-Function Relationship at the Locus of Deficit in Retinal Disease

Technologies such as optical coherence tomography have facilitated the visualization of anatomical tissues such as that of the retina. The availability of in vivo retinal anatomical data has led to the hypothesis that it may be able to accurately predict visual function from anatomical information. However, accurate determination of the structure-function relationship has remained elusive in part due to contributions of non-retinal sources of variability, thus imposing potential limitations in the fidelity of the relationship. Furthermore, differences in manifestation of functional loss due to different retinal loci of change (inner retina or outer retinal elements) have also been the subject of debate. Here, we assessed the application of a novel, more objective psychophysical paradigm to better characterize the relationship between functional and structural characteristics in the eye. Using ocular diseases with known loci of anatomical change (glaucoma, inner retinal loss; and retinitis pigmentosa, outer retinal loss), we compared conventional more subjective psychophysical techniques that may be contaminated by the presence of non-retinal sources of variability with our more objective approach. We show that stronger correlations between underlying retinal structure and visual function can be achieved across a breadth of anatomical change by using a more objective psychophysical paradigm. This was independent of the locus of structural loss (at the ganglion cells for glaucoma or photoreceptors for retinitis pigmentosa), highlighting the role of downstream retinal elements to serve as anatomical limiting factors for studying the structure-function relationship. By reducing the contribution of non-retinal sources of variability in psychophysical measurements, we herein provide a structure-function model with higher fidelity. This reinforces the need to carefully consider the psychophysical protocol when examining the structure-function relationship in sensory systems.