Introduction 1 2 ® 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Because of changing trends in adjuvant breast cancer treatment, the present study also assessed the effect of age on optic nerve head (ONH) parameters. The results support the inference that tamoxifen usage can lead to small cups, although apparently mainly for women older than about 50 years. All measurements for this study were obtained using confocal scanning laser ophthalmoscopy with the Heidelberg Retina Tomograph II (HRT). This commercial instrument was introduced in 1999 for routine clinical use, but until now, it has been used mainly to assess glaucoma and related conditions. Methods Subjects 19 20 12 21 22 All tamoxifen and anastrozole users had completed primary treatment for breast cancer, and all were fully active and able to perform their daily pre-cancer activities without restriction. None of the control subjects had positive breast cancer histories or had previously used breast cancer medication for any purpose. Similarly, none of the tamoxifen users had previously used a hormonally acting breast cancer medication other than tamoxifen, and none of the anastrozole users had previously used a hormonally acting breast cancer medication other than anastrozole. In addition, none of the subjects in any group had ever used the SERM raloxifene. With one exception, all analyses for this report are based on data from subjects who had been amenorrheic for at least 6 months at the time of testing. The one exception is an analysis comparing data from control subjects with data from an additional group of women (the fourth subject group overall) who met the same eligibility criteria as the control group, except for the absence of menses. 12 19 23 1 24 25 Table 1 Demographic data for each of the subject groups  Amenorrheic subjects 40–69 years old Amenorrheic subjects 51–69 years old n n n n n n n Age (years) 58.2 (SD = 6.8) 54.5 (SD = 5.2) 57.2 (SD = 6.0) 59.6 (SD = 5.4) 56.5 (SD = 4.7) 58.2 (SD = 5.1) 48.0 (SD = 3.3) IOP (mmHg) 15.7 (SD = 2.9) 15.5 (SD = 2.3) 15.6 (SD = 2.9) 15.7 (SD = 3.0) 15.5 (SD = 2.5) 15.7 (SD = 3.0) 15.5 (SD = 2.3) Duration of medication use (years) 1.07 (SD = 0.45) 1.31 (SD = 0.49) 0 1.09 (SD = 0.47 1.36 (SD = 0.48) 0 0 IOPs are from subjects’ test eyes only 19 Procedures 26 12 12 27 28 12 Data analyses 29 P 30 2 Table 2 ONH indices: between-group comparisons (subjects 40–69 years old)  ANOVA (Kruskal–Wallis) Anastrozole versus tamoxifen  Tamoxifen versus control  Anastrozole versus control  Cup volume P  = 0.021 P  = 0.007 P P Maximum cup depth P  = 0.016  P  = 0.008 P P Mean cup depth P  = 0.028 P  = 0.011 P P Cup area P P P P Cup/disk area ratio P  = 0.030 P  = 0.013 P P Cup shape P P P P Rim area P P P P Rim volume P P P P Disk area P P P P Mean RNFL thickness P P P P RNFL cross sectional area P P P P Height variation contour P P P P P P U P P P P Results 2 P 1 Fig. 1 Graph of cup volume versus age for all amenorrheic subjects. Filled circles represent tamoxifen users, shaded circles represent anastrozole users, and unfilled circles represent control subjects  1 r P r r r P 3 3 r r P 3 Table 3 ONH indices: between-group comparisons (subjects 51–69 years old)  ANOVA (Kruskal–Wallis) Anastrozole versus tamoxifen  Tamoxifen versus control  Anastrozole versus control  Cup volume P  = 0.006 P  = 0.003 P  = 0.019 P Maximum cup depth P  = 0.007 P  = 0.005 P  = 0.014 P Mean cup depth P  = 0.016 P  = 0.007 P P Cup area P  = 0.025 P  = 0.009 P P Cup/disk area ratio P  = 0.011 P  = 0.005 P  = 0.020 P Cup shape P P P P Rim area P P P P Rim volume P  = 0.030 P P P Disk area P P P P Mean RNFL thickness P P P P RNFL cross sectional area P P P P Height variation contour P P P P 2 4 2 6 2 3 4 5 6 Table 4 ONH indices: means and standard errors of the mean, and medians (subjects 51–69 years old)  n n n 3 0.107 ± 0.017 0.043 ± 0.015 0.090 ± 0.017 0.104 0.012 0.073 Maximum cup depth (mm) 0.611 ± 0.047 0.423 ± 0.040 0.559 ± 0.040 0.591 0.378 0.594 Mean cup depth (mm) 0.207 ± 0.017 0.145 ± 0.014 0.189 ± 0.014 0.206 0.130 0.198 2 0.476 ± 0.059 0.275 ± 0.050 0.423 ± 0.057 0.523 0.139 0.385 Cup/disk area ratio 0.207 ± 0.022 0.123 ± 0.021 0.193 ± 0.022 0.229 0.079 0.192 Cup shape −0.229 ± 0.015 −0.199 ± 0.012 −0.219 ± 0.013 −0.229 −0.205 −0.210 2 1.724 ± 0.066 1.895 ± 0.071 1.697 ± 0.061 1.797 1.867 1.732 3 0.453 ± 0.025 0.593 ± 0.042 0.475 ± 0.028 0.461 0.580 0.506 2 2.200 ± 0.094 2.169 ± 0.074 2.120 ± 0.067 2.316 2.156 2.154 Mean RNFL thickness (mm) 0.245 ± 0.010 0.264 ± 0.014 0.246 ± 0.008 0.246 0.262 0.242 2 1.281 ± 0.059 1.366 ± 0.014 1.266 ± 0.049 1.282 1.335 0.242 Height variation contour (mm) 0.359 ± 0.019 0.401 ± 0.019 0.383 ± 0.015 0.375 0.388 0.391 Fig. 2 D D D D  Fig. 3 2  Fig. 4 2  Fig. 5 2  Fig. 6 2  3 2 4 4 2 3 Discussion 9 10 31 10 19 20 32 32 32 12 33 38 9 10 38 39 39 16 40 18 41 17 41 41 42 10 43 44 45 25 46 47 48 49 49 50 51