<qa>  What is the main cause of periorbital fat loss?Periorbital changes observed with topical prostaglandin analogues are primarily due to effects on aponeurotic and deep orbital adipocytes. Prostaglandins activate the adipocyte mitogen-activated protein kinase MAPK pathway, leading to inactivation of peroxisome proliferator-activated receptor PPAR-gamma, inhibition of adipocyte differentiation, and decreased fat accumulation within adipocytes. Bimatoprost concentration-dependent contractions of ciliary muscles and activation of matrix metalloproteinases may also contribute to periocular changes. Patients using topical ophthalmic prostaglandin analogues commonly develop periorbital fat loss, which has been well characterized in the ophthalmology literature. 