Predictive value of fundus autofluorescence for development of geographic atrophy in age-related macular degeneration

It has been suggested that lipofuscin accumulation, as measured by increased fundus autofluorescence (FAF), precedes progression or development of junctional zone geographic atrophy (GA) in age-related macular degeneration (AMD). The tools of biomedical image analysis were used to measure the probabilistic relationship of GA progression to increased FAF.

Serial AF images of eight eyes of six patients with AMD with GA were registered on computer. The images were leveled with a 12-zone quadratic polynomial mathematical model to minimize background variability. Semiautomated segmentation of GA was performed on the leveled images. Increased FAF was defined as a gray level greater than 2 standard deviations above the leveled image mean, identified on the initial image with automated segmentation, and measured as a fraction of the 250-microm border zone surrounding the initial GA lesion. Areas of GA lesions were identified on the final image. The positive predictive value (PPV) of increased FAF was determined as the probability that any pixel with increased FAF in the initial image would become part of new GA in the final image. Relative PPV was determined relative to the total quantity of new GA. The NPV (NPV) of increased FAF was calculated as the probability that any pixels without increased FAF would not become atrophic. The relative NPV was determined similarly. A similar analysis was also conducted with a 500-microm border zone to determine the predictive value of proximity to the original GA lesion ("proximity") for GA progression.

As a fraction of the geographic atrophy border zone, the mean new GA was 0.44+/-0.20, and the mean increased FAF was 0.06+/-0.06. The mean PPV of increased FAF for new GA formation was 0.50+/-0.26. Compared with the relative PPV of chance of 1.0, the mean relative PPV of increased FAF was 1.15+/-0.28. The mean NPV of increased FAF was 0.57+/-0.20. The mean relative NPV of increased FAF was 1.00+/-0.02. In the 500-microm border zone, the mean relative PPV of FAF and of proximity were essentially equal (1.56+/-.70 and 1.52+/-0.26, respectively), whereas the mean relative NPV of proximity was significantly greater than that of FAF (1.26+/-0.19 and 1.01+/-0.01, respectively, P=0.02)

The results of digital image analysis suggest that although increased FAF may have a modest PPV for new GA development, the relative PPV is generally no greater than chance. Similarly, the relative NPV demonstrates negligible difference from chance and is also lower than the relative NPV of proximity. This suggests that increased FAF, though a disease manifestation, is not a strong risk factor for development or extension of GA.