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Fig 1.

Diagram showing the study population.

The safety population included all subjects who have received the study treatment. Full analysis set (FAS) included all subjects in the safety set who have had at least 1 post-baseline evaluation regarding occurrence of choroidal neovascularization. Per protocol (PP) population included all FAS subjects without major protocol deviation. Among those withdrawn there were 3 deaths in the docosahexaenoic acid (DHA) group and 6 deaths in the placebo group.

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Fig 2.

Illustration of drusen segmentation methods.

A) Red-free fundus photo. Areas with drusen are circled in black (human supervision) to initialize the segmentation program. This allows the program to exclude from consideration peripapillary changes and other hypo-pigmented or hyper-reflective non-drusen features, resulting in a more rapid and accurate drusen identification. B) original color fundus photograph, cropped to 6 mm field C) contrast-enhanced color photograph D) contrast-enhanced color photograph with superimposed Wisconsin grading template (6 mm diameter circle with central, middle and outer subfields of diameters of 1, 3 and 6 mm). Drusen have been automatically segmented in detail (green) by the custom software within the areas containing drusen identified in A.

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Fig 3.

Segmentation of reticular pseudodrusen.

A) original fundus photograph with large area containing both reticular macular disease (reticular pseudodrusen) and ordinary soft drusen outlined in black. The soft drusen are confined to the central macula. The reticular pseudodrusen extend to the arcades. B) original color fundus photo C) both reticular pseudodrusen and soft drusen are segmented (green) on the color photo within the area identified in A and within the superimposed Wisconsin grading template. D) The area of reticular macular disease is separately enclosed in red, and was excluded from drusen measurements.

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Fig 4.

Segmentation of drusen and geographic atrophy (GA).

A) Original red-free fundus photograph B) Original color fundus photograph with areas of drusen and GA outlined (black) C) Color fundus photograph cropped to 6 mm field. D) contrast enhanced color photo. E) segmentation of drusen (green) within the 6 mm field F) areas of GA masked (black).

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Fig 5.

Drusen regression and its correlation with new geographic atrophy (GA).

A: Color photo, right eye, Visit 1 (V1). B: V1 photo with soft drusen segmented in green, total pixel area 2,452. GA is not present. C: Color photo, right eye, Visit 5 (V5), showing new GA, D: V5 photo with GAs segmented in blue, total pixel area 4,161. Drusen from V1 that were absorbed in the GA are overlaid and segmented in red, total pixel area 381, or 9% of geographic atrophy total area. Compared to the original drusen area present in V1 of 2,452 pixels, the 381 drusen pixels converting to GA in V5 represent 16% of the original drusen area.

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Table 1.

Socio-demographic, genetics and drusen characteristics at baseline.

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Table 2.

Comparison of drusen characteristics between baseline and 3 years according to treatment group.

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Table 3.

Associations of DHA supplementation with drusen remodeling.

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Table 4.

Associations of 3-year drusen number, diameter and area remodeling with socio-demographic and genetics characteristics at baseline.

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