Abstract

PurposeTo compare corneal biomechanics between patients with ocular graft versus-host disease (oGVHD) and healthy subjects (controls), and to further correlate these values with ocular and hematological characteristics.Materials and methodsThe following procedures were performed in oGVHD patients and controls: Schirmer test (ST), break-up time (BUT), corneal and conjunctival staining, tear matrix metalloproteinase-9 (MMP-9) assay (InflammaDry test, Rapid Pathogen Screening, Inc, Sarasota, FL). Corneal biomechanics were calculated by using ocular response analyzer (ORA, Reichert Instruments, Depew, New York, USA). The Mann-Whitney U test was used to compare continuous variables between oGVHD patients and controls. Correlations of corneal biomechanics with ocular and hematological parameters were examined using Spearman's correlation.ResultsA total of 45 oGVHD patients (mean age ± SD, 51.5 ± 7.1 years) and 34 controls (47.8 ± 6.1 years) were included. Patients with oGVHD showed significantly lower values of corneal hysteresis (CH) and corneal resistance factor (CRF) compared to controls (respectively, 9.4 ± 1.8 mmHg vs 11.6 ± 1.6 and 9.7 ± 1.4 mmHg vs 12.3 ± 1.3; always p<0.001). Twenty-nine of the oGVHD eyes (64.4%) were strong-positive for MMP-9, while 16 (35.6%) were weak-positive. Conversely, only 4 of the control eyes (11.8%) were weak-positive for MMP-9. In patients with oGVHD, CH was significantly correlated with corneal staining (Rs = -0.316, p = 0.035), conjunctival staining (Rs = -0.437, p = 0.003), ST (Rs = 0.390, p = 0.008), BUT (Rs = 0.423, p = 0.004), oGVHD severity grade (Rs = -0.383, p = 0.009), and MMP-9 positivity grade (Rs = -0.429, p = 0.003), while CRF was correlated only with corneal staining (Rs = -0.317, p = 0.034).ConclusionsCorneal biomechanics are reduced in patients with oGVHD, and CH is negatively correlated with disease severity grade and MMP-9 tear levels.

Highlights

  • Allogeneic hematopoietic stem cell transplantation (HSCT) is an established and potentially curative treatment for a variety of malignant and non-malignant hematological disorders

  • Corneal biomechanics are reduced in patients with ocular Graft versus-host disease (GVHD) (oGVHD), and corneal hysteresis (CH) is negatively correlated with disease severity grade and matrix metalloproteinase9 (MMP-9) tear levels

  • We hypothesized that higher tears levels of matrix metalloproteinases (MMPs)-9 might affect the ultrastructure of the corneal stroma, producing changes in corneal biomechanics

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Summary

Introduction

Allogeneic hematopoietic stem cell transplantation (HSCT) is an established and potentially curative treatment for a variety of malignant and non-malignant hematological disorders. Recent proteomic studies evaluated the various constituent compositions of tears inflammatory mediators in eyes with oGVHD and detected increased levels of cytokines and matrix metalloproteinases (MMPs).[8,9] Among these, MMP-9 is a proteolytic enzyme involved in the degradation of corneal extracellular matrix components, whose dysregulation is implicated in impaired wound healing and stromal keratolysis.[10,11,12] The excessive proteolytic activity in the cornea determines the degradation of stromal components, that are known to be the main determinants of biomechanical corneal behavior. We hypothesized that higher tears levels of MMP-9 might affect the ultrastructure of the corneal stroma, producing changes in corneal biomechanics

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