Assessing Structure - Function Relationships in Non-Neovascular Age-related Macular Degeneration.

Age-related macular degeneration (AMD), a neurodegenerative disease, is the leading cause of visual impairment in industrialized countries. Challenges in defining structural/functional relationships at various stages of disease especially with non-neovascular AMD, have slowed therapeutic development. Development of such sensitive and specific markers associated with AMD progression could provide the basis necessary for future regulatory outcome variables that will be useful in assessing new, innovative AMD therapies. Advanced imaging technologies such as high-resolution optical coherence tomography, fundus autofluorescence and near infrared imaging; and functional tests including rod-mediated dark adaptation, microperimetry, fluorescence lifetime imaging ophthalmoscopy and others will be important in the evaluation of these structure/function correlations. Development of more advanced methods to study structure such as high-resolution OCT and en face OCT offer further opportunities to better correlate structure and function in clinical trials, and to better define useful biomarkers of visual outcome endpoints. Dark adaptation, although correlated with AMD stage, is difficult to incorporate as endpoint in clinical trials because dark adaptation changes slowly and the technique is time consuming. Microperimetry has become a useful outcome variable in many clinical trials and new methodology may improve its utility in structure-function correlation. These and other newer techniques will require further prospective studies to determine their clinical utility in early AMD detection, prediction of disease progression from intermediate to late stages, and the ability to monitor the advancement of non-neovascular AMD.