1. Luu CD, Dimitrov PN, Robman L, et al. Role of flicker perimetry in predicting onset of late-stage age-related macular degeneration. Arch Ophthalmol. 2012;130(6):690-699. Role of Flicker Perimetry in Predicting Onset of Late-Stage Age-Related Macular Degeneration Copyright restrictions may apply

2. Introduction A sensitive functional biomarker is currently needed to determine the rate of disease progression in early age-related macular degeneration (AMD). Such a functional marker should also allow the efficacy of any intervention aimed at slowing disease progression to be determined. Objective: To determine whether flicker perimetry is capable of detecting functional changes over time and of predicting eyes that would develop late AMD. Copyright restrictions may apply

3. Methods Study Design: Prospective longitudinal clinical study. Participants: 151 subjects (127 with early AMD and 24 controls). Measurements: Four consecutive 6- monthly tests of flicker sensitivity within the central 6°. Copyright restrictions may apply Flicker test grid superimposed on the retina of a participant with AMD.

4. Data Analysis: Mean flicker sensitivity and its rate of change over time for normal and AMD groups were compared. Limitations: There was no fundus tracking function on the perimeter, and fundus autofluorescent images were not available for confirmation of geographic atrophy (GA) development. Copyright restrictions may apply Flicker sensitivity and the rate of change in flicker sensitivity (red line) in areas that were nonprogressed and that progressed to GA, which was detected 18 months after the initial visit. Months Flicker Sensitivity, dB Slope = -1.2 GA detected Slope = -0.2 Nonprogressed Progressed to GA Methods

5. Results Best-corrected visual acuity of the study eyes at the initial visit was 20/40 or better. Mean (SD) duration of follow-up: 4.0 (1.1) years. Of the 127 patients (127 eyes) with early AMD at the baseline visit, 21 developed late AMD (16 with GA and 5 with choroidal neovascularization [CNV]); 18 had high-risk characteristics but did not progress either to late AMD or within early AMD during the study period; and 88 eyes progressed within early AMD and were excluded from the analysis. Copyright restrictions may apply

6. Eyes that went on to develop GA or CNV had a significantly reduced mean flicker sensitivity in the months prior to GA or CNV being clinically detected compared with control eyes and nonprogressed eyes. The rate of change in flicker sensitivity was significantly increased in eyes with GA but not in eyes with CNV compared with the control eyes. Copyright restrictions may apply Results

7. Copyright restrictions may apply Flicker Visual Field Parameters of Control Eyes, High-Risk Early-AMD Eyes That Did Not Progress, and Eyes That Developed Clinically Detectable GA or CNV Results

8. Comment Macular flicker sensitivity testing could be used to monitor early AMD and predict which eyes, and which areas of the macula within these eyes, will develop GA. A sudden decrease in sensitivity could also portend imminent CNV. As such, flicker sensitivity measurements may well prove to be a useful tool in monitoring progression of early AMD and in evaluating the efficacy of new treatments aimed at stopping progression. Copyright restrictions may apply

9. If you have questions, please contact the corresponding author: –Robyn H. Guymer, PhD, FRANZCO, Macular Research Unit, Centre for Eye Research Australia, Level 1, 32 Gisborne St, East Melbourne, VIC 3002, Australia (rhg@unimelb.edu.au). Funding/Support This research was supported by grant 350224 RHG/AJV from the National Health and Medical Research Council, grant ARC-LP0211474 from the Australian Research Council Linkage Project, practitioner fellowship 529905 from the National Health and Medical Research Council (Dr Guymer), a Royal Victorian Eye and Ear Hospital Wagstaff Fellowship (Dr Robman), the Royal Victorian Eye and Ear Hospital Research Committee, and the Macular Vision Loss Support Society of Australia. The Centre for Eye Research Australia receives operational infrastructure support from the Victorian government and is supported by Excellence Award 529923 from the National Health and Medical Research Council Centre for Clinical Research. Copyright restrictions may apply Contact Information