Introduction: The aim of this study was to evaluate radiologically the effects of long-term luteinizing hormone-releasing hormone (LHRH) agonist therapy on extraocular muscle thickness, retrobulbar orbital fat (ROF), and the optic nerve (ON) in prostate cancer (PCa) patients. Methods: The retrospective study included patients with primary or recurrent PCa who received androgen deprivation therapy (ADT) for at least 12 months. Each patient underwent gallium-68 prostate-specific membrane antigen positron emission tomography-computed tomography both before and at the end of the 12-month treatment. Thickness of the ON, lateral rectus muscle, medial rectus muscle, superior rectus muscle, and inferior rectus muscle were measured by using the coronal CT sections in soft tissue window. ROF, ocular protrusion, and ON length were measured in sagittal and coronal planes. Changes in these anatomical structures induced by LHRH analogs were investigated by comparing pre- and post-treatment measurements. Results: A total of 57 patients were included in the study. Median PSA and TT values of the patients before treatment were 36.5 (range, 19.6–51.2) ng/mL and 614.0 (range, 472.0–743.0) ng/dL, respectively, and these values decreased significantly after the treatment (10.6 [range, 5.2–14.2] ng/mL and 36.5 [range, 19.6–51.2] ng/dL, respectively, p < 0.001 for both). After the treatment, there was a statistically significant decrease in the areas of inferior rectus muscle, superior rectus muscle, lateral rectus muscle, and medial rectus muscle (p < 0.001 for all), while significant increases were observed in ROF (11.9%, p < 0.001) and ON thickness (14.3%, p = 0.004). The amount of ocular protrusion also showed a significant increase of approximately 14% after the treatment (14.0 [range, 12.0–16.0] mm vs. 16.0 [range, 14.0–17.2] mm, p < 0.001). Discussion/Conclusion: Our findings, for the first time in the literature, indicated that ADT causes a decrease in extraocular muscle mass and an increase in ROF with ocular protrusion. It can be asserted that these changes are similar to the changes in skeletal muscle and fat mass in other body parts. Further studies with a higher level of evidence are needed to clinically evaluate the increase in ocular protrusion and ON enlargement, which are likely to be caused by the increase in ROF.
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