Purpose: To characterize the natural history of drusen using spectral-domain optical coherence tomography (SD-OCT) imaging of eyes from patients with nonexudative age-related macular degeneration (AMD). Design: Prospective, longitudinal, natural history study. Participants: We included 143 eyes of 100 patients with at least 6 months of follow-up. Methods: Patients with drusen secondary to nonexudative AMD were scanned using the Cirrus SD-OCT instrument. Eyes were imaged using the 200×200 A-scan raster pattern contained within a 6×6 mm area. Custom software was used to quantify volumetric changes in drusen over a period of <6 months and for as long as 24 months. Drusen volume and drusen area were measured within circular regions centered at the fovea having diameters of 3 and 5 mm. The measurements were analyzed using a suitable scale transformation. For drusen volume, a cube root transformation strategy was used. Main Outcome Measures: Change in drusen volume and area over time. Results: We analyzed 143 eyes of 100 patients with 69 eyes followed for 6 months, 106 eyes followed for 12 months, 48 eyes followed for 18 months, and 48 eyes followed for 24 months. The 3 mm circle baseline drusen volume ranged from 0.0009 to 0.7479 mm 3 or 0.10 to 0.91 mm using the cube root scale. On average, drusen volume and drusen area increased over time with the magnitude of the increase dependent on the length of follow-up (P = 0.001, 3 mm circle). In the eyes with a decrease in drusen volume, the magnitude of this decrease was dependent on the baseline drusen volume (P = 0.001, 3 mm circle) and independent of the follow-up interval. After 12 months, drusen volume increased in 48% of eyes, remained stable in 40%, and decreased in 12%. Conclusions: Imaging with SD-OCT revealed a dynamic, undulating growth pattern for drusen with a tendency for drusen to increase in volume and area over time. An appreciation of the quantitative changes in drusen volume over time using SD-OCT imaging provides a novel strategy for following normal disease progression and for identifying novel clinical trial end points to be used when investigating therapies for the treatment of nonexudative AMD.
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