Deformable image registration across heterogeneous domains remains challenging because coupled appearance variation and geometric misalignment violate the brightness constancy assumption underlying conventional methods. We propose PCReg-Net, a progressive contrast-guided registration framework that performs coarse-to-fine alignment through four lightweight modules: (1)~a registration U-Net for initial coarse alignment, (2)~a reference feature extractor capturing multi-scale structural cues from the fixed image, (3)~a multi-scale contrast module that identifies residual misalignment by comparing coarse-registered and reference features, and (4)~a refinement U-Net with feature injection that produces the final high-fidelity output. We evaluate on the FIRE-Reg-256 retinal fundus benchmark, demonstrating improvements over both traditional and deep learning baselines. Additional experiments on two microscopy benchmarks further confirm cross-domain applicability. With only 2.56M parameters, PCReg-Net achieves real-time inference at 141 FPS. Code is available at https://github.com/JiahaoQin/PCReg-Net.