Epiretinal membranes occur in a number of pathogenetically different diseases, such as proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR), macular pucker, and ischemic, inflammatory, and degenerative vitreoretinal disorders. The formation of epiretinal membranes is characterized by the proliferation of histogenetically different cell types. Knowledge of the proliferating potential of surgically excised epiretinal membrane tissue might be clinically relevant to determine which patients face a high risk of recurrences. The monoclonal antibody Ki-67 specifically stains a cell-cycle associated nuclear antigen that is only expressed by cells in the G1, S, and G2/M phases of the cell cycle. With this antibody, the actively proliferating growth fraction can be stained in frozen tissue samples of surgically removed epiretinal membranes by the indirect immunoperoxidase method. In this study, the monoclonal antibody Ki-67 was used to screen 37 epiretinal membranes in PVR, PDR, macular pucker, and in recurrences after intraocular silicone oil tamponade for the presence of actively proliferating cells. Additionally, the number of Ki-67 positive cells in a section of the membrane was quantitatively set in relation to the total cell number of this section. Thus a proliferative index (PI) was ascribed to each membrane as a decimal quotient. The proliferative indices can be graded into four subgroups for missing or very low (PI 0.1), low (PI 0.1-0.3), moderate (PI 0.3-0.6), and high (PI 0.6) proliferative activities. High proliferative activities were found in 4 of 5 PVR membranes, in 9 of 14 PDR membranes, in 6 of 11 recurrent membranes after intraocular silicone oil tamponade, and in 2 of 6 macular pucker membranes. According to the results of this study, the growth fraction within epiretinal membranes seems to be activated to various degrees. This might be due to the presence or lack of mitogenic substances within the intraocular environment. The relative quantitative determination of the proliferating cells by a proliferative index of surgically removed epiretinal membranes might become a useful addition to clinical classifications of proliferative vitreoretinal diseases. The Ki-67 labelling index directly reflects the cellular proliferative activity at the time of surgery and might promote more understanding about the dynamics of proliferative vitreoretinal diseases and add a biologic base for clinical trials. Its clinical value still has to be proven by long-term follow-up studies.
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