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Patient‐Reported Symptoms Associated with Graft Reactions in High‐Risk Patients in the Collaborative Corneal Transplantation Studies

The Collaborative Corneal Transplantation Studies (CCTS) were designed to evaluate the effect of donor-recipient histocompatibility matching and cross-matching on the survival of corneal transplants in high-risk patients. We now report on the role of symptoms in the detection of corneal allograft reactions in the CCTS and on the relationship between symptom reporting and graft survival. The 456 patients transplanted in the CCTS were followed for a minimum of 2 years or until graft failure. The follow-up protocol included 11 scheduled examinations in the first year, four examinations during the second year, and examinations every 6 months thereafter. Interim examinations were performed in response to patient-reported symptoms. At every examination, patients were asked specifically if they had redness, sensitivity to light, loss of vision, or pain (RSVP). Of the 456 patients transplanted, 62% had at least one graft reaction. Patients diagnosed with reactions at scheduled visits in the first postoperative year were 2.5 times more likely to report symptoms than those without reactions. Reports of red eye and vision loss were strongly associated with allograft reaction. However, these symptoms were neither highly sensitive nor specific for reaction (sensitivity = 46%, specificity = 70% at 6 months). The severity of reaction influenced the reporting of symptoms: 69% of patients with severe reactions reported symptoms versus 48% of patients with mild reactions (p < 0.001). The only patient characteristic associated with reliable symptom reporting was age, with younger patients with reactions being more likely to report symptoms. Patients who reported symptoms at the first reaction were more likely to experience graft failure from rejection than patients not reporting symptoms.