Predictive models for ocular chronic graft-versus-host disease diagnosis and disease activity in transplant clinical practice

Abstract

© F e r r a t a S t o r t i F o u n d a t i o nOcular cGvHD predictive models haematologica | 2015; 100(9) 1229 cGvHD manifestations, a diagnosis of ocular cGvHD can be made. This diagnostic scoring system has not yet been prospectively validated, and exact ophthalmology criteria for cGvHD diagnosis remain to be defined. The National Institutes of Health (NIH) cGvHD Consensus Project in 2005 proposed guidelines for transplant clinicians to assess ocular cGvHD severity; specified measures were the NIH eye score, Schirmer's tear test, Lee cGvHD symptom scoring and chief eye symptom score. 2,13 Apart from removing the Schirmer's tear test from the severity scoring scale, these recommendations did not change in 2014. 14 The ability of these criteria to predict ocular cGvHD diagnosis based on expert ophthalmologic examination is not known. In addition, there are no evidence-based recommendations regarding when transplant clinicians should suspect ocular cGvHD diagnosis and refer patients to an ophthalmologist for evaluation.Accepted therapeutic response measures in ocular cGvHD are also lacking. The NIH cGvHD Consensus conference in 2005 proposed the Schirmer's tear test as a measure of response, but a large prospective longitudinal study by Inamoto et al. demonstrated that the Schirmer's tear test did not correlate well with either provider-or patient-reported perceptions of change in ocular cGvHD severity. 16 Additional investigations are needed to identify which specific measures are most strongly associated with ocular cGvHD activity, and thus might have been expected to have the best performance characteristics in measuring ocular cGvHD response in a clinical trial or in clinical practice.Despite the high frequency of ocular cGvHD post HSCT, risk factors and clinical characteristics of ocular cGvHD are not completely understood. Matched related donor HSCT, male gender, prior acute skin GvHD, and oral and skin cGvHD involvement have been found to be associated with ocular cGvHD. 1,17 Reliable identification of risk factors for ocular cGvHD could select patients that might benefit from early intervention and provide insight into the pathophysiology of this condition.The objective of this study is to determine which aspects of the NIH cGvHD severity scoring criteria are most predictive of ocular cGvHD diagnosis in a large, well-characterized cohort with moderate to severe cGvHD enrolled on a cross-sectional natural history study. Patients underwent a standardized ophthalmology specialist examination and each patient was determined as having ocular cGvHD diagnosis or not. Since there are no standard definitions for ocular cGvHD activity, a second objective of this study was to use ophthalmology expert decision as the gold standard (active vs. inactive ocular cGvHD) and determine which factors of the ophthalmology examination and transplant clinician examination correlate most closely with the presence of active ocular cGvHD. MethodsThe National Cancer Institute (NCI) cGvHD natural history protocol is a cros...

Ocular surface indicators and biomarkers in chronic ocular graft-versus-host disease: a prospective cohort study

“…Sixty two percent of HSCT patients developed oGVHD, consistent with a previous NIH-based study [26]. The incidence of oGVHD in the literature ranges from 12-55% [8,10,25,27].…”

Biomarkers in Ocular Chronic Graft Versus Host Disease: Tear Cytokine- and Chemokine-Based Predictive Model

“…the National Institutes of Health Eye Score and Schirmer's test, 19 and a multiple conjunctival gene-based predictive model. 12 Multiple biomarker-based models, built upon the simultaneous use of a group of biomarkers, may improve performance compared to the use of a single-molecule analysis for diagnosis issues.…”

“…Predictive models have also focused on clinical parameters in an effort to determine which aspects are most predictive of ocular cGVHD diagnosis. 19 Additionally, model validation is necessary as it gives important information about the reliability of the process. Thus, the purpose of this study was to develop and validate a prediction model for the diagnosis of ocular cGVHD based on the levels of a panel of inflammatory mediators in tears and the correlation of those mediators with the clinical ophthalmic phenotype.…”

Ocular Graft-versus-Host Disease after Hematopoietic Cell Transplantation: Expert Review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation

“…These scales are based on findings for the lid margin or meibomian glands, although their utility for ocular GVHD has not been well validated. One study showed the utility of the meibomian gland plugging score (0 = none; 1 = 1 to 2 glands; 2 = 2 to 3 glands; 3 = all 5 glands, lid margin swelling) for diagnosing ocular GVHD [37].…”

“…All other moderately symptomatic situations are assigned a score of 2. The NIH eye score combined with the Schirmer test has shown >90% sensitivity and specificity for the diagnosis of ocular GVHD [37]. In the context of response assessment in clinical trials, the NIH eye score is recommended as a simple and reliable measure [48], whereas the Schirmer test is no longer recommended because of its poor correlation with changes in ocular GVHD symptoms [39].…”