Flicker Fusion Thresholds Between Young and Old Subjects at Various Luminance Levels

Age-related macular degeneration (AMD) is a chronic, progressive eye disease. AMD is one of the leading causes of visual impairment and blindness among elderly populations in economically developed countries . Due to the aging of the population, the incidence and prevalence of AMD is likely to increase substantially over the next decade, potentially posing a significant impact on society.

AMD is a complex and progressive degenerative disease, with both genetic and environmental risk factors. AMD affects the outer retina, retinal pigment epithelium (RPE), Bruch's membrane, and choroid. The retina is among the most metabolically active tissues in the body, in part due to rods, which frequently discard their outer segments tips, and the RPE, which phagocytoses the discarded tips . The retina's metabolism causes accumulation of toxic by-product by the following: 1. Energy metabolism (oxidative stress); 2. Visual cycle modulator (lipofuscin); 3. Local inflammation (complement activation). The local inflammation, and the accumulation of lipofuscin material within the RPE, may lead to drusen formation, RPE dysfunction, and degeneration of macular rods and cones, finally leading to the irreversible loss of vision.

AMD occurs in two forms - a non-exudative "dry" form and an exudative "wet" form. Non-exudative AMD accounts for 80-90% of AMD cases and it involves a diverse phenotype that may include drusen and/or RPE pigmentation abnormalities. Advanced non-exudative AMD is characterized by geographic atrophy, which is characterized by the presence of an expanding region of irreversible RPE and photoreceptor loss in the macula.

At the present time, there are no approved treatments for non-exudative AMD. The clinical development of therapeutic agents for the treatment of non-exudative AMD is limited by slow disease progression, unsuitability of commonly used efficacy endpoints such as visual acuity, and difficulty in identifying those subjects with early stages of disease most likely to progress. Visual function testing may prove to be useful tools in detecting the early non-exudative AMD.

In early age-related macular degeneration, outer retinal metabolism is known to be compromised. The detection of a flickering stimulus imposes a higher metabolic requirement than does a static stimulus , . Inability to detect a flickering stimuli may identify earlier stages of disease than the inability to detect static stimuli. Early work by Mayer, et.al. has shown that AMD subjects experience functional deficits in the mid range of visual phenomenon most notably at 10HZ and 14Hz. Phipps, et.al. found early AMD subjects to have larger deficits for flickering than static stimuli . Later work has shown that a flicker test based on mid-range frequencies has been shown to have effective diagnostic and reproducibility characteristics relative to other functional tests . In addition to the diagnostic potential of flicker stimuli, this test has been shown to be predictive of AMD progression and correlated to AMD severity . Therefore, a flicker test may prove useful in identifying early dysfunction in macular performance and for assessment treatment in future interventional clinical trials.

Critical Flicker Fusion (CFF) is a type of flicker test that involves increasing the frequency of a flashing stimulus until that stimulus appears static to an observer. The frequency at which critical flicker fusion occurs is recorded as a patient specific endpoint of visual function. In this study, we will investigate CFF across a wide range of luminance levels, from photopic to scotopic ranges, in young and old subjects with normal ocular health. The impact of age on CFF threshold will be the focus of this study, with the primary objective being to highlight luminance levels where maximum differences between young and old subjects occur.