Meibum Structure in Pediatric Graft Versus Host Disease
Aparna Ramasubramanian; Ryan Blackburn; Samiyyah Sledge; Douglas Borchman
University of Louisville
Introduction: Annually 4500 allogenic hematopeoetic stem cell transplantation are done in US in children less than 20 years of age.(1) Graft versus host disease is the most significant cause of long term morbidity and mortality and ocular manifestations occur in 40-60% of these patients. Meibomian gland disease is common in GVHD and it may be that damage to the gland results in a modification of the composition of meibum from donors with graft verse host disease (GHm) which then contributes to dry eye.
Methods: The structure of meibum from five GVHD patients (GHm) were compared to meibum from 28 donors without signs and symptoms of dry eye (Cm). Infrared spectroscopy was used to measure seven meibum lipid phase transition parameters.
Results: The age range of the donors of GHm and Cm was 13 to 18 and 1 to 20 years, respectively. Age differences in the phase transition parameters for Cm were not significant. The lipid phase transition temperature (Tp) is the temperature at which half the lipids undergo a phase transition. The Tp for GHm was 37.7° C significantly higher (P < 0.001) than that for Cm, 30.6° C. This small change in Tp resulted in a large significant difference (P < 0.001) in the lipid order (fluidity) at 33.4°C, 60% trans and 40% trans for GHm and Cm, respectively. The cooperativity of the phase transition is the measure of how the melting of a lipid affects adjacent lipids. The cooperativity for GHm was 6, significantly lower (P = 0.02) than that for Cm, 9, which indicates that GHm contains a greater variety of lipids, perhaps degradation products. The minimum and maximum frequency, rentropy and renthalpy of the phase transitions were not significantly different (P > 0.05) between GHm and Cm.
Discussion: GHm structure and thus composition was significantly different compared with Cm. These changes could block the meibomian gland orifice and perhaps lead to tear film instability when on the surface of tears. Dry eye is a chronic problem in kids with graft versus host disease and it can cause significant scarring of the ocular surface in addition to causing eye discomfort.
Conclusion: Infrared spectroscopy may be useful to diagnose and to determine the efficacy of dry eye treatment in patients with GH. Future studies designed to measure meibum compositional, structural and functional relationships could aid in developing therapies to ameliorate dry eye symptoms.
References: Baird K1, Cooke K, Schultz KR. Chronic graft-versus-host disease (GVHD) in children. Pediatr Clin North Am. 2010;57(1):297-322.