The antigen(s) responsible for GPC have yet to be identified. From circumstantial evidence, the initiating event is believed to be mechanical irritation and/or antigenic stimulus of the tarsal conjunctiva of the upper lids by a contact lens surface or edge (rigid or flexible) or deposit. Histologic changes in the tissue occur with mast cell degranulation and a secondary inflammatory cascade. This leads to conjunctivitis and further tissue changes with increasing inflammatory markers in the tears.

GPC can be caused by all forms of ocular prostheses, including rigid and hydrogel (soft) contact lenses, prosthetic eyes, extruding scleral buckles, exposed portions of sutures, filters, knots, and even corneal scars. [8] Heat sterilization, poor cleaning, thick or rough contact lens edges, and extended wearing times also predispose to the development of GPC.

Lipid and protein deposits from the tears, as well as debris coating the surface of contact lenses, may also lead to a spiral of inflammation. This, in turn, causes even more lens deposits to form, leading to additional inflammation. [1, 2, 3] The level of coating on the lenses varies among individuals and the polymer of the contact lenses.

High-water hydrogel (HEMA) contact lenses tend to coat more than lower-water HEMA contact lenses. Silicone contact lenses tend to accumulate more lipid deposits than HEMA lenses. First-generation silicone hydrogel contact lenses may be more prone to GPC development, perhaps because of their mechanical stiffness or their higher propensity for lipid deposition. Silicone hydrogel lenses tend to induce more local GPC (similar to the changes seen with rigid lenses), whereas hydrogel lenses tend to induce more generalized GPC reactions in the palpebral conjunctiva. [9]