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Abstract
Purpose: There is a substantial literature showing that the selective estrogen receptor modulator tamoxifen can block swelling-activated chloride channels, such as those in astrocytes. This study aimed to test the hypothesis that anatomic characteristics consistent with swelling may be measured within the optic nerve head (ONH) of tamoxifen users whose ONH appearance is considered within normal limits. Methods: Indices of ONH topography were measured using the Heidelberg Retina Tomograph II (HRT) for two populations of women ages 40–69 years: (1) subjects using tamoxifen (20 mg/day) as adjuvant therapy after successful primary treatment for breast cancer and (2) control subjects not using any hormonal medication. All subjects had excellent visual acuity (with 20/20 or better in the test eye), and all appeared to be free of eye disease, as based on conventional photographic assessment. The study design was cross-sectional. The various ONH indices were assessed as functions of the duration of tamoxifen use. Results: The optic cups of short-term tamoxifen users (≤2 years) were significantly smaller in both the lateral and axial directions than the optic cups of the control subjects. Of the 27 short-term users, 23 had cup volumes smaller than the median value for the control subjects. The cup sizes of long-term users (> 2 years, ≤5 years) were not distinguishable from those of the control subjects. The presence of small cups among short-term users did not depend on subjects' medical histories prior to tamoxifen use. Disk margin indices were not related significantly to the duration of tamoxifen use. Conclusions: Small cup sizes consistent with localized subclinical swelling are not rare among short-term tamoxifen users. Thus, small cups are not likely to be a manifestation of a cumulative-dose toxicity. Instead, they probably result from other causes, possibly involving the action of tamoxifen on estrogen receptors. Further investigation with longitudinal and interventional methodologies is needed to definitively interpret the results.