To report on a case of recurrence of paraproteinemic keratopathy (PPK) associated with monoclonal gammopathy after bilateral penetrating keratoplasty.

Penetrating keratoplasty was performed on both eyes of a 45-year-old man due to bilateral progressive corneal stromal clouding. Recurrence of the corneal stromal opacities accompanied by a decrease in visual acuity was observed on slit-lamp examination already two years after penetrating keratoplasty. Confocal laser scanning microscopy (CLSM) of the corneal grafts performed three years after penetrating keratoplasty showed bilateral morphological changes identical to that found in the patient's corneas prior to penetrating keratoplasty. A hematological work-up revealed monoclonal gammopathy of type IgG kappa. The histochemical examination of the explanted corneas confirmed the diagnosis of PPK.

Paraproteinemic keratopathy is an underdiagnosed ophthalmological condition, which may be associated with potentially life-threatening hematologic disorders. A hematological workup should be performed in patients with corneal opacities of uncertain etiology. Penetrating keratoplasty should be performed with caution in patients with monoclonal gammopathy due to the possibility of a very fast recurrence of PPK in the corneal graft. This is the first presentation of the recurrence of flake-like PPK after penetrating keratoplasty assessed with CLSM.

Corneal transplantation is the most common surgical procedure amongst solid organ transplants with a high survival rate of 86% at 1-year post-grafting. This high success rate has been attributed to the immune privilege of the eye. However, mechanisms originally thought to promote immune privilege, such as the lack of antigen presenting cells and vessels in the cornea, are challenged by recent studies. Nevertheless, the immunological and physiological features of the cornea promoting a relatively weak alloimmune response is likely responsible for the high survival rate in “low-risk” settings. Furthermore, although corneal graft survival in “low-risk” recipients is favourable, the prognosis in “high-risk” recipients for corneal graft is poor. In “high-risk” grafts, the process of indirect allorecognition is accelerated by the enhanced innate and adaptive immune responses due to pre-existing inflammation and neovascularization of the host bed. This leads to the irreversible rejection of the allograft and ultimately graft failure. Many therapeutic measures are being tested in pre-clinical and clinical studies to counter the immunological challenge of “high-risk” recipients. Despite the prevailing dogma, recent data suggest that tissue matching together with use of systemic immunosuppression may increase the likelihood of graft acceptance in “high-risk” recipients. However, immunosuppressive drugs are accompanied with intolerance/side effects and toxicity, and therefore, novel cell-based therapies are in development which target host immune cells and restore immune homeostasis without significant side effect of treatment. In addition, developments in regenerative medicine may be able to solve both important short comings of allotransplantation: (1) graft rejection and ultimate graft failure; and (2) the lack of suitable donor corneas. The advances in technology and research indicate that wider therapeutic choices for patients may be available to address the worldwide problem of corneal blindness in both “low-risk” and “high-risk” hosts.

• “High-risk” grafts
• Graft rejection
• Systemic immunosuppression
• Cell-based immunomodulation
• Keratoprosthesis
• Collagen-based hydrogels