Validation of measurement scales in ocular graft-versus-host disease

Purpose: To validate measurement scales for rating ocular chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation. Candidate scales were recommended for use in clinical trials by the National Institutes of Health (NIH) Chronic GVHD Consensus Conference or have been previously validated in dry eye syndromes. Design: Prospective follow-up study. Participants: Between August 2007 and June 2010, the study enrolled 387 patients with chronic GVHD in a multicenter, prospective, observational cohort. Methods: Using anchor-based methods, we compared clinician or patient-reported changes in eye symptoms (8-point scale) with calculated changes in 5 candidate scales: The NIH eye score, patient-reported global rating of eye symptoms, Lee eye subscale, Ocular Surface Disease Index, and Schirmer test. Change was examined for 333 follow-up visits where both clinician and patient reported eye involvement at the previous visit. Linear mixed models were used to account for within-patient correlation. Main Outcome Measures: An 8-point scale of clinician or patient-reported symptom change was used as an anchor to measure symptom changes at the follow-up visits. Results: In serial evaluations, agreement regarding improvement, stability, or worsening between the clinician and patient was fair (weighted kappa = 0.34). Despite only fair agreement between evaluators, all scales except the Schirmer test correlated with both clinician-reported and patient-reported changes in ocular GVHD activity. Among all scales, changes in the NIH eye scores showed the greatest sensitivity to symptom change reported by clinicians or patients. Conclusions: Our results support the use of the NIH eye score as a sensitive measure of eye symptom changes in clinical trials assessing treatment of chronic GVHD. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.