Due to the trend towards minimization of optical space instruments, in combination with ever increasing performance requirements, their optical and mechanical design are becoming more and more intertwined. As a result, it is invaluable to have insights into how mechanical and thermomechanical disturbances influence the system’s optical performance already in early stages of the design process. In this work, a differential ray tracer is implemented into a topology optimization framework, allowing for direct optical performance analysis of optical instruments under disturbance loads. The gradient information of the optical performance is provided by semi-automatic differentiation. A wide range of optics can be used including freeform optics, that have become frequently used in state-of-the-art instruments. The method has been verified and shows a strong agreement with ZEMAX. To demonstrate the advantages of the STOP-based computational design workflow, a fully coupled opto-thermo-mechanical topology optimization is performed on a case inspired by CHAPS-D, a hyperspectral air pollution sensor. The results show the potential of direct optical performance analysis in topology optimization, creating a structure that maintains optical performance at or above nominal performance, while highlighting challenges posed by the optimization process.