Refractive index modification by laser micro-structuration of diffractive optical devices in ophthalmic polymers has recently been applied for refractive correction in the fields of optics and ophthalmology. In this work, Safrofilcon-A hydrogel, used as soft contact lenses, was processed by direct laser interference patterning (DLIP) to fabricate linear periodic patterns on the surface of the samples. Periodic modulation of the surface was attained under two-beam interference by using a Q-switched laser source with emission at 263 nm and 4 ns pulse duration. Features of processed areas were studied as a function of both the interference spatial period and the laser fluence. Optical confocal microscopy used to evaluate the topography of the processed samples showed that both structured height and surface roughness increased with laser fluence. Static water contact angle (WCA) measurements were carried out with deionized water droplets on the structured areas to evaluate the hydration properties of DLIP structures. It was observed that the laser structured areas induced a delay in the hydration process. Finally, microstructural changes induced in the structured areas were assessed by confocal micro-Raman spectroscopy showing that at low laser fluences the polymer structure remained almost unaltered. In addition, Raman spectra of hydrated samples recovered the original shape of areas structured at low laser fluence.