Roels Dimitri, Delie Anke, Mazure Dominiek, De Grove Katrien, van Gremberghe Ineke, Deprez Joke, Peene Isabelle, Elewaut Dirk, Leroy Bart, Claerhout Ilse, Kerre Tessa
Department of Ophthalmology, Ghent University Hospital, Ghent, Belgium.
Department of Hematology, Ghent University Hospital, Ghent, Belgium.
Cornea. 2025 May 21. doi: 10.1097/ICO.0000000000003897.
The objective of this longitudinal cohort study was to identify predictors of progression to ocular graft-versus-host disease in allogeneic hematopoietic stem cell transplant recipients.
Patients (n = 49) were examined before hematopoietic stem cell transplantation (HSCT) and 3, 6, 12, 24, and 36 months after HSCT. Outcome measures included ocular surface disease index questionnaire, Schirmer I test, corneal fluorescein staining, tear break-up time, and tear cytokine concentration. Diagnosis of ocular GVHD (oGVHD) was made in accordance with the International Consensus Criteria for chronic oGVHD. A group of healthy controls (n = 20) without dry eye disease was recruited for comparison.
At baseline, the intended HSCT group had a lower Schirmer test value, a higher corneal fluorescein staining score, and a lower tear film break-up time compared with the control group. There was no significant difference in ocular surface disease index score. The intended HSCT group had significantly higher tear interleukin (IL)-1, IL-6, IL-8, IL-10, interferon gamma-induced protein (IP)-10, and TNF-α concentrations at baseline. When considering an increase of at least 2 points of the International Consensus Criteria for chronic oGVHD score after HSCT to exclude preexisting dry eye disease, only 19% (n = 7) developed either probable (11%, n = 4) or definite (8%, n = 3) oGVHD. In a longitudinal analysis, a significant association between progression to oGVHD and tear IL-6, IL-8, IL-17A, and IP-10 concentration was detected.
This study highlights the added value of performing a baseline ophthalmological examination in intended HSCT recipients. Posttransplant oGVHD rates may be overestimated if pretransplant ocular surface disease is not considered. Longitudinal tear cytokine analysis in our cohort suggests that IL-6, IL-8, IL-17A, and IP-10 may be useful as biomarkers for oGVHD.
这项纵向队列研究的目的是确定异基因造血干细胞移植受者发生眼部移植物抗宿主病进展的预测因素。
对49例患者在造血干细胞移植（HSCT）前以及HSCT后3个月、6个月、12个月、24个月和36个月进行检查。观察指标包括眼表疾病指数问卷、Schirmer I试验、角膜荧光素染色、泪膜破裂时间和泪液细胞因子浓度。眼部移植物抗宿主病（oGVHD）的诊断依据慢性oGVHD的国际共识标准。招募了一组无干眼疾病的健康对照者（n = 20）进行比较。
在基线时，与对照组相比，预期的HSCT组Schirmer试验值较低，角膜荧光素染色评分较高，泪膜破裂时间较短。眼表疾病指数评分无显著差异。预期的HSCT组在基线时泪液白细胞介素（IL）-1、IL-6、IL-8、IL-10、干扰素γ诱导蛋白（IP）-10和肿瘤坏死因子-α浓度显著更高。当考虑HSCT后慢性oGVHD评分至少增加2分以排除既往存在的干眼疾病时，只有19%（n = 7）发生了可能（11%，n = 4）或确定（8%，n = 3）的oGVHD。在纵向分析中，检测到进展为oGVHD与泪液IL-6、IL-8、IL-17A和IP-10浓度之间存在显著关联。
本研究强调了对预期HSCT受者进行基线眼科检查的附加价值。如果不考虑移植前的眼表疾病，移植后oGVHD的发生率可能会被高估。我们队列中的纵向泪液细胞因子分析表明，IL-6、IL-8、IL-17A和IP-10可能作为oGVHD的生物标志物。
