Purpose: High-resolution spectral domain OCT/SLO (SD-OCT) has become an increasingly useful tool for differentiating drusen morphologic parameters such as shape, internal reflectivity, homogeneity, and presence of overlying hyperreflective foci. Our purpose was to evaluate which types of drusen may respond to Copaxone (glatiramer acetate) treatment of dry age-related macular degeneration (AMD) patients by shrinking or disappearing. Methods: A prospective and interventional clinical trial of patients with dry AMD who received subcutaneous treatment with Copaxone or sham injections was conducted. SD-OCT images were used for analysis of drusen ultrastructure. Morphologic characteristics for specific drusen within the macular region were assessed with serial studies. Pre- and posttreatment statuses of drusen were compared. Main outcome measure was a change of drusen morphologic parameters in Copaxone-treated and sham-treated dry AMD patients between baseline and 12 weeks of treatment. Results: Three hundred eleven drusen from 26 eyes of 14 dry AMD patients were evaluated. One hundred seventy-two drusen from 14 eyes (7 patients) of Copaxone-treated and 139 drusen from 12 eyes sham-treated (7 patients) were included. Overall, between baseline and 12-week visit, the percentage of drusen that disappeared/shrank in the Copaxone-treated group was 19.2% versus 6.5% in the sham-treated group (P = 13). The percentage of convex drusen that shrank or disappeared after 12 weeks of treatment was significantly higher in the Copaxone-treated group (27.8%) in comparison with the sham-treated group (6.8%) (P = 008). The difference between the groups was found to be statistically significant for drusen with low and medium internal reflectivity (P = 019 and P = 036, respectively). Conclusions: Convex shape and low/medium internal reflectivity were found to be favorable parameters in prediction of drusen reduction in the Copaxone-treated patients. This study represents a preliminary attempt to identify SD-OCT features of drusen that may predict susceptibility to Copaxone treatment and therefore help clinicians decide which patients to treat.