The long-term goal is to elucidate the roles that female hormones have on the eye and vision. The information gained is expected to provide quantitative means of assessing duration-dependent effects of medications that affect estrogen receptors or that alter estrogen levels. The clinical emphasis will be on 2 types of medications - selective estrogen receptor modulators (SERMS) and aromatase inhibitors. Both are used as adjuvant therapy for early-stage breast cancer, or are likely to be used for this purpose or for breast cancer prophylaxis. SERMS can act either as estrogen agonists or antagonists depending on the target tissue. Aromatase inhibitors block the production of estrogen. The main objective is to identify the functional and anatomical changes that occur in the eye and visual system as a result of estrogen-receptor action and to elucidate the effects of 2 SERMS, tamoxifen and raloxifene, as functions of their durations of use. Because tamoxifen has long been the medication of choice for adjuvant breast cancer therapy and has been shown to affect the eye and vision, it will serve as the focus. In this way, potential side effects of newer medications can be compared against those of the standard of care. The main use of raloxifene at present is to prevent osteoporosis. The aromatase inhibitor to be evaluated, anastrozole, currently is used for treating advanced breast cancer. There are 4 specific aims: (1) To define the changes of visual function that occur during the 5-year period of tamoxifen use. A longitudinal design will be used to test 2 hypotheses: a) that tamoxifen alters the adaptation properties of SWS-cone pathways in the visual-field periphery, and b) that 2 distinct tamoxifen-user response groups can be defined on the basis of visual changes that occur after several years. Psychophysical measures will be compared with results of automated perimetry. (2) To determine the time course of tamoxifen-induced changes of ocular anatomy. A longitudinal design will be used to test the hypothesis that the retinal nerve fiber layer often thickens during year 1 of tamoxifen use but later thins. Anatomical measures will be made using the Heidelberg Retina Tomograph and the Zeiss Ocular Coherence Tomograher. (3) To distinguish the effects of raloxifene and anastrozole from those of tamoxifen. The same techniques will be used as for Specific Aims 1 and 2. (4) To determine the prevalence of cyclic changes of SWS-cone-mediated sensitivity across the menstrual cycle. Data from healthy women who are identified as having large cyclic sensitivity changes will be obtained from high and low estrogen-response portions of the menstrual cycle, and the visual changes that occur over weeks will be used to help interpret effects of prolonged exposure to SERMS.
