Evaluation of Corneal Epithelial Thickness and Dry Eye Disease Tests in Thalassemic Adolescents.

PURPOSE: To assess dry eye disease (DED) in thalassemic adolescents by evaluating corneal epithelial thickness (CET) and various dry eye clinical tests and correlate them to tissue iron overload. METHODS: The study included 120 Beta-thalassemia patients (11 to 18 years) and 120 matched controls. CET maps were captured using anterior segment optical coherence tomography. OSDI questionnaire was completed. Dry eye tests included Schirmer test, tear film breakup time (TBUT), and ocular surface staining (OSS) with fluorescein and lissamine green. We recorded serum ferritin level, and liver iron concentration (LIC) measured by magnetic resonance imaging. RESULTS: Superior and inferior CET was thinner, while map standard deviation (MSD) was higher in thalassemics compared to controls (all P <0.001 ). Thalassemic group also showed higher OSDI scores (P <0.001), shorter TBUT (P <0.001 ), and higher OSS grades (P <0.001 ). Both superior and inferior CET was correlated positively with TBUT, and negatively with OSS (all P < 0.001). Serum ferritin and LIC showed negative correlations with CET (superior and inferior, both P< 0.001), positive correlations with MSD, P< 0.001, as well as with TBUT (P< 0.001), OSS (P< 0.001), and OSDI scores (P< 0.001). CONCLUSION: Thalassemic adolescents had thinner CET with higher thickness' variability, shorter TBUT and more marked OSS than controls. Correlation of higher serum ferritin and hepatic iron overload with irregular epithelial thinning and more affected dry eye tests results supports our hypothesis that high tissue iron levels could play a pivotal role in DED pathogenesis in thalassemic patients.

Polymorphisms of the receptor for advanced glycation end products as vasculopathy predictor in sickle cell disease.

BACKGROUND: The genetic variants of the receptor for advanced glycation end products (RAGE) gene have been associated with vascular disease risk. The objective of this work was to explore the association of three single-nucleotide polymorphisms (SNPs) of RAGE gene (374T/A, 429T/C, and G82S) with vascular complications in SCD. METHODS: The study was conducted on 40 children with SCD and 40 healthy children served as controls. All participants were genotyped for the three studied RAGE polymorphisms by polymerase chain reaction (PCR). RESULTS: Regarding 374T/A polymorphism, the frequency of TA, TT genotypes and T allele were higher in patients (p < 0.001). T allele was associated with higher incidence of sickling crisis and stroke (p < 0.05). In the subgroup analyses of 429T/C polymorphism, an association between C allele and SCD vascular complications was observed (p < 0.05). Concerning the frequency of G82S genotypes of RAGE, GG variant was detected in 39 (97.5%) of the patients, as compared with 40 (100%) of controls (p = 0.3). A regression analysis proved that HbS%, serum ferritin, and the -374T and 429C alleles were significant independent predictors of frequent sickling episodes (p < 0.05). CONCLUSIONS: The C allele of -429T/C and T allele of 374T/A RAGE polymorphisms may be considered as predictors for vascular dysfunction in SCD. IMPACT: The C allele of -429T/C and T allele of 374T/A RAGE polymorphisms may be considered as predictors for vascular dysfunction in SCD patients. To our knowledge, our study is the first exploring the association of three single-nucleotide polymorphisms of RAGE gene (374T/A, 429T/C, and G82S) with vascular complications in SCD. Early identification of patients carrying these genetic variants might be of great importance not only to identify subjects at risk of vasculopathy but also to direct them to RAGE-targeted treatments.

Soluble receptor for advanced glycation end products as a vasculopathy biomarker in sickle cell disease.

BACKGROUND: Soluble forms of RAGE (sRAGE) have been found circulating in plasma and tissues. Evidence is accruing in human subjects linking levels of sRAGE to oxidative stress in many disorders. Because sickle cell disease (SCD) is a state of oxidative stress, we tested the hypothesis that circulating sRAGE levels may be involved in the vascular pathology of SCD. OBJECTIVES: To determine the sRAGE levels in children and adolescents with SCD and investigate their association with markers of hemolysis, iron overload, and SCD-related organ complications. SUBJECTS AND METHODS: The level of sRAGE was measured in 40 children and adolescent with SCD compared with 40 healthy controls using enzyme-linked immunosorbent assay (ELISA). RESULTS: sRAGE was significantly higher in patients compared with controls (p < 0.001) and was elevated in patients with history of stroke, acute lung syndrome, and frequency of sickling crisis or serum ferritin > 2500 (p < 0.05). Patients with high sRAGE levels are candidates for chelation. sRAGE was positively correlated with HbS% (r = 0.422, p = 0.007), LDH (r = 0.329, p = 0.038), and serum ferritin levels (r = 0.516, p = 0.001). Multivariable regression analysis proved that both HbS% and serum ferritin were significant independent factors affecting sRAGE level (p < 0.05). CONCLUSION: Our findings suggest that sRAGE may be considered as a marker for vascular dysfunction in SCD patients.