Understanding the course and risk factors of age-related macular degeneration (AMD), as well as evaluating new imaging techniques and clinical endpoints, were hot topics. Drusen deposits and pigmentary changes in the macula—including drusen size—are risk factors for the progression of more advanced forms of AMD. However, the exact role of drusen in the pathogenesis of AMD is not fully understood.
One report (Baratsits et al. ARVO E-Abstract 1579) demonstrated that eyes from early AMD subjects showed a dynamic progression as well as regression of drusen volume, which, surprisingly, occurred simultaneously at different locations within the same retina.
Another group looked for molecular changes in drusen using fluorescence lifetime imaging ophthalmoscopy (FLIO) (Sauer et al. ARVO E-Abstract 3399). This technique distinguishes soft and hard drusen based upon autofluorescence. Using this method, it was possible to differentiate drusen types, distinguishing those in patients with AMD from those of a healthy retina—thus, giving FLIO the potential to provide information on individual risks for the progression to later stages of dry AMD.
In patients with intermediate AMD, the risk and speed of progression to choroidal neovascularization (CNV) or geographic atrophy (GA) is highly variable. A study (Erfurth et al. ARVO E-Abstract 3398) showcased a fully automated machine learning method that was developed to predict individual progression to AMD based on retinal imaging and genetics. Fellow eyes with intermediate AMD from subjects enrolled in the HARBOR trial were used to demonstrate that an automated analysis of OCT biomarkers allowed for a personalized prediction of AMD progression.
A major limitation in the development of novel therapeutic options for AMD has been a lack of sensitive endpoints to evaluate their therapeutic efficacy.
Bagheri et al. (ARVO E-Abstract 3400) carried out a retrospective review of blue auto-fluorescence fundus images, OCT, and Snellen visual acuity in patients with GA due to AMD (18 subjects) in order to understand the relationship between total GA, foveal GA, and visual acuity in AMD. Results suggest the percentage of GA within the fovea may be more sensitive in predicting the degree of visual acuity impairment than the total GA area or foveal involvement. However, further validation is needed in larger cohorts.
The theme of developing sensitive endpoints for the clinical study of retinal degeneration was demonstrated in a number of presentations.
Cocce et al. (ARVO E-Abstract 3765) examined the lack of reliable functional endpoints for proof-of-concept clinical trials in AMD through the evaluation of visual function metrics. This study demonstrated that low luminance visual acuity, mesopic microperimetry with eye tracking, cone contrast test, or dark adaptation may be used as potential functional measures in clinical trials involving patients with early and intermediate AMD.
Other studies explored the use of other visual tests, including critical flicker fusion (Slocum et al. ARVO E-Abstract 2347; Lane et al. ARVO E-Abstract 4714), photostress and photobleach (Rodriguez et al. ARVO E-Abstract 4715), or critical flicker fusion combined with photobleach (Sundstrom et al. ARVO E-Abstract 4713). Each of these methods has the potential to serve as sensitive endpoints for therapies directed at retinal degeneration.