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1.
Dry eye disease and risk factors for corneal complications in chronic ocular graft-versus-host disease
Kate, A., Singh, S., Das, A. V., Basu, S.
Indian journal of ophthalmology. 2023;71(4):1538-1544
Abstract
PURPOSE The current study was carried out to evaluate the clinical features and management outcomes of dry eye disease (DED) in chronic ocular GvHD following allogenic hematopoietic stem cell transplantation (HSCT). METHODS A retrospective review of consecutive patients diagnosed with chronic ocular GvHD between 2011 and 2020 was performed at a tertiary eye care network. Multi-variate regression analysis was carried out for identifying risk factors associated with progressive disease. RESULTS A total of 34 patients (68 eyes) with a median age of 33 years [inter-quartile range (IQR) 23-40.5] were studied. The most common indication for HSCT was acute lymphocytic leukemia (26%). Ocular GvHD developed at a median of 2 years (IQR 1-5.5 years) after HSCT. Aqueous tear deficiency was present in 71% of the eyes, of which 84% had a Schirmer value of <5 mm. The median visual acuity at presentation and that after a median follow-up of 6.9 months were comparable at 0.1 log minimum angle of resolution (logMAR) (P = 0.97). Topical immunosuppression was required in 88% of cases, and with this, improvement in corneal (53%, P = 0.003) and conjunctival staining scores (45%, P = 0.43) was noted. A progressive disease was present in 32% with persistent epithelial defects being the most common complication. Grade 2 conjunctival hyperemia [odds ratio (OR): 2.6; P = 0.01] and Schirmer's value <5 mm (OR: 2.7; P = 0.03) were found to be associated with progressive disease. CONCLUSION Aqueous deficient DED is the most common ocular manifestation of chronic ocular GvHD, and the risk of the disease progression is greater in eyes with conjunctival hyperemia and severe aqueous deficiency. Awareness among ophthalmologists of this entity is essential for its timely detection and optimal management.
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2.
Assessment of Corneal Epithelial Changes and Related Factors in Ocular Chronic Graft-Versus-Host Disease (GVHD) by in Vivo Confocal Microscopy
Liu, S., Peng, R., Ma, J., Shen, Z., Hu, B., Zhao, Y., Hong, J.
Ocular immunology and inflammation. 2023;:1-9
Abstract
PURPOSE To evaluate corneal epithelial changes and related factors in chronic ocular graft-versus-host disease (oGVHD) patients. METHODS 21 patients (35 eyes) with chronic oGVHD and 8 patients (12 eyes) without oGVHD after bone marrow transplantation were recruited for assessment involving in vivo confocal microscopy (IVCM) analysis, ocular surface parameter determination and tear cytokine level analysis. The IVCM corneal epithelial scoring system was used to evaluate corneal epithelial changes. RESULTS There was a significant difference in the corneal epithelial score (p = .001) between the two groups. The corneal epithelial scores were significantly correlated with the corneal fluorescein staining scores (CFS, r = 0.463, p < .001), Schirmer's test (r = -0.389, p = .009) and tear cytokine levels of EGF (r = -0.491, p < .001) and APRIL (r = -0.318, p = .030). CONCLUSIONS The depth of corneal epithelial defects can be estimated by the CFS. Corneal epithelial changes of chronic oGVHD are considered to be associated with lacrimal deficiency and a lack of EGF.
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3.
Posterior segment complications and the risk factors after allogeneic hematopoietic stem cell transplantation
Yang, B., Wu, S., Yu, S., Liang, X., Liu, Q., Huang, F., Liang, L.
Eye (London, England). 2023;37(9):1816-1821
Abstract
PURPOSE To study the posterior segment complications (PSC) and the risk factors in patients after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS This cross-sectional, case-control study enroled 143 patients who received allogeneic HSCT. Comprehensive ocular examinations were performed to evaluate PSC and ocular Graft-versus-Host Disease (oGVHD). PSC was diagnosed based on the characteristic fundus findings and auxiliary examinations. Visual-evoked potential was examined in patients with unexplained visual loss and suspected visual pathway pathology (VPP). Ocular surface disease index, corneal fluorescein staining, conjunctival injection and Schirmer's test were scored to diagnose oGVHD. RESULTS PSC was detected in 36 (25.2%) patients, while 107 (74.8%) patients were not. Among them, 102 (71.3%) patients were diagnosed with oGVHD. The most common PSC included cytomegalovirus retinitis (13/143, 9.1%) and VPP (7/143, 4.9%). Central nervous system relapse of leukaemia was detected in four out of seven cases of VPP. Patients with PSC had worse visual acuity, lower prevalence and milder severity of oGVHD, and more donors from unrelated and human leucocyte antigen (HLA)-mismatch (all P < 0.05). PSC was associated with transplant from unrelated (OR = 6.494, 95% CI: 1.635-25.794, P = 0.008) and HLA-mismatched (OR = 7.193, 95% CI: 2.829-18.291, P < 0.001) donor but not with the occurrence of systemic GVHD or oGVHD. CONCLUSIONS PSC in post-HSCT patients was more common than previously noted, deserving the concern of ophthalmologists, especially in patients with unrelated or HLA-mismatched donors.
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4.
A nomogram model for predicting ocular GVHD following allo-HSCT based on risk factors
Wang, W. H., You, L. L., Huang, K. Z., Li, Z. J., Hu, Y. X., Gu, S. M., Li, Y. Q., Xiao, J. H.
BMC ophthalmology. 2023;23(1):28
Abstract
OBJECTIVE To develop and validate a nomogram model for predicting chronic ocular graft-versus-host disease (coGVHD) in patients after allogenic haematopoietic stem cell transplantation (allo-HSCT). METHODS This study included 61 patients who survived at least 100 days after allo-HSCT. Risk factors for coGVHD were screened using LASSO regression, then the variables selected were subjected to logistic regression. Nomogram was established to further confirm the risk factors for coGVHD. Receiver operating characteristic (ROC) curves were constructed to assess the performance of the predictive model with the training and test sets. Odds ratios and 95% confidence intervals (95% CIs) were calculated by using logistic regression analysis. RESULTS Among the 61 patients, 38 were diagnosed with coGVHD. We selected five texture features: lymphocytes (LYM) (OR = 2.26), plasma thromboplastin antecedent (PTA) (OR = 1.19), CD3 + CD25 + cells (OR = 1.38), CD3 + HLA-DR + cells (OR = 0.95), and the ocular surface disease index (OSDI) (OR = 1.44). The areas under the ROC curve (AUCs) of the nomogram with the training and test sets were 0.979 (95% CI, 0.895-1.000) and 0.969 (95% CI, 0.846-1.000), respectively.And the Hosmer-Lemeshow test was nonsignificant with the training (p = 0.9949) and test sets (p = 0.9691). CONCLUSION We constructed a nomogram that can assess the risk of coGVHD in patients after allo-HSCT and help minimize the irreversible loss of vision caused by the disease in high-risk populations.
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5.
Tear Cytokines Associated With Therapeutic Effects in Chronic Ocular Graft-Versus-Host Disease
Ma, J., Shen, Z., Peng, R., Li, C., Zhao, Y., Hu, B., Hong, J.
Cornea. 2023;42(2):211-216
Abstract
PURPOSE The local application of antiinflammatory and immunosuppressive agents is an effective method for the treatment of ocular graft-versus-host disease (oGVHD); however, we noticed that some patients with oGVHD did not respond to topical therapy as well as many others. This study aimed to determine whether tear cytokines were associated with therapeutic effects in oGVHD. METHODS Forty patients with chronic oGVHD were enrolled and grouped as responders (n = 24) and nonresponders (n = 16) based on the clinical response to 1 month of topical treatment. Tear samples were collected from each participant before and after treatment, and the tear concentrations of 7 cytokines (IL-2, IL-6, IL-8, IL-10, IL-17A, TNF-α, and ICAM-1) were measured using microsphere-based immunoassay analysis. Differences between pretreatment and posttreatment tear samples were analyzed using the Wilcoxon test. RESULTS No significant differences in ophthalmic symptoms or cytokine levels were observed between responders and nonresponders at baseline. After 1 month of topical treatment, ocular surface parameters (including Ocular Surface Disease Index, National Institutes of Health eye score, best-corrected visual acuity, corneal fluorescein staining score, and fluorescein tear film break-up time) were significantly ameliorated in responders, but not in nonresponders. Moreover, none of the cytokines exhibited significant alteration in nonresponders, whereas the tear levels of IL-6 (P = 0.031) and IL-8 (P = 0.037) exhibited significant decreases in responding patients. CONCLUSIONS Our results revealed that tear IL-6 and IL-8 levels were significantly altered in response to topical oGVHD treatment.
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6.
Desiccating-stress significantly increases the risk for chronic ocular Graft-versus-Host-Disease Short Titel: Desiccating-stress increases risk of ocular GVHD
Gehlsen, U., Stern, M. E., Franklin, J., Tahmaz, V., Hallek, M., Holtick, U., Scheid, C., Steven, P.
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Desiccating-stress (DS) is known to induce dry-eye disease but has not been studied in the context of ocular graft-versus-host disease (oGVHD). Patients undergoing allogeneic hematopoietic stem cell transplantation (aHSCT) are exposed to DS on transplantation wards, which are highly climate regulated for hygienic purposes. OBJECTIVE As oGVHD demonstrates features of dry-eye disease this retrospective study aimed to analyze DS as a risk factor for chronic oGVHD. STUDY DESIGN 444 patients undergoing aHSCT were investigated with a maximum follow-up of 5.8 years after aHSCT. Relative humidity (%rH) on the transplantation ward was monitored and data were correlated with the occurrence, severity, and onset of chronic oGVHD, as well as the occurrence of acute skin GVHD. A logistic regression model was used to predict the development of oGVHD. RESULTS 103 of 213 surviving patients developed oGVHD. oGVHD was significantly correlated with a lower %rH (r=0.2, p=0.03), and more patients (73%) developed oGVHD after transplantation under DS compared to patients transplanted under high humidity conditions (30%, p=0.02). Reduced humidity increased the relative risk for oGVHD by 4% with every %rH, but did not affect severity or time of first diagnosis of oGVHD. CONCLUSIONS In this study we demonstrate, that DS is an independent risk factor for oGVHD. Adjusting air humidity during aHSCT has the potential to serve as a preventive measure with clinical relevance.
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7.
Ocular graft-versus-host disease and dry eye disease after paediatric haematopoietic stem cell transplantation - incidence and risk factors
Jeppesen, H., Kielsen, K., Siersma, V., Lindegaard, J., Julian, H. O., Heegaard, S., Sengeløv, H., Müller, K.
Bone marrow transplantation. 2022
Abstract
Ocular graft-versus-host disease (oGVHD) contributes substantially to morbidity after allogeneic haematopoietic stem cell transplantation (HSCT) but is sparsely investigated in children. We assessed incidence and risk factors for oGVHD and dry eye disease (DED) in a nationwide, single-centre study of 484 consecutive children receiving HSCT during the period 1980-2016. Ophthalmological examinations were performed before and annually at least until five years after HSCT. Twenty-five patients had DED before transplantation (5.6%). The cumulative incidence was 1.9% for acute oGVHD, 6.0% for chronic oGVHD, 8.7% for new onset DED, and 12.7% for new onset Corneal Fluorescein Staining (CFS). In adjusted Fine-Gray regression models, the use of Busulfan was a risk factor for developing acute oGVHD (HR 5.01, p = 0.03), and malignant disease was a risk factor for developing CFS (HR 2.00, p = 0.047). Younger recipient age was associated with reduced risk of DED when comparing children aged 0-4 years with 10-16 years (HR 0.33, p = 0.03). These data underscore the need of attention to DED and oGVHD in relation to HSCT leading to our recommendation of performing ophthalmic examinations in all children before HSCT, and after HSCT when needed, in order to secure diagnosis and treatment of these complications.
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8.
Correlative factors of ocular surface lesions after allogeneic hematopoietic stem cell transplantation: A retrospective study
Zhuang, X. Y., Sun, Z. T., Xu, Y., Ren, Y. R., Chen, Y. J., Chen, F., Ma, X., Tang, X. W., Zhang, X. F.
Frontiers in oncology. 2022;12:1040679
Abstract
BACKGROUND Ocular graft-versus-host disease (oGVHD) is one of the complications after allogeneic hematopoietic stem cell transplantation (HSCT), which impairs the quality of life and may indicate poor prognosis. In this retrospective study, the aim was to investigate the characteristics of ocular surface after HSCT, and analyze the risk factors related to the severity of ocular surface lesions. METHODS 248 post-HSCT patients were enrolled in this retrospective study. Subjects were divided into no lesion group, mild lesion group and severe lesion group, according to the severity of ocular surface lesions. The correlations between grades of ocular surface lesions and gender, age, primary disease, donor source, human leukocyte antigen (HLA) type, kinship, donor-recipient relationship, blood type, source of stem cell and systemic GVHD were analyzed. RESULTS The median scores of corneal epitheliopathy, lid margin lesions and meibomian gland loss were 3, 6 and 2 points, respectively. The grade of corneal epitheliopathy was related to donor source (P<0.001), kinship (P=0.033), HLA-matching (P<0.001), and systemic GVHD (P=0.007), especially oral GVHD (P<0.001) and liver GVHD (P=0.002). The grade of lid margin lesions was related to donor source (P=0.019), HLA-matching (P=0.006), and systemic GVHD (P=0.013), especially skin GVHD (P=0.019) and oral GVHD (P=0.019). The grade of meibomian gland loss was related to age (P=0.035) and gastrointestinal GVHD (P=0.007). The grade of corneal epitheliopathy after HSCT was related to the lid margin lesion score (P<0.001). CONCLUSIONS The occurrence and development of ocular GVHD are mostly accompanied by the history of systemic GVHD. While in few cases, ocular surface lesions related to GVHD can be observed prior to the rejection of other tissues and organs. Severe corneal epitheliopathy occurs in patients with severe lid margin lesions in ocular GVHD. The lesions of corneal epithelium and lid margin are milder in HLA partially matching transplantation.
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9.
Seeing the unseen: Use of a modified OSDI questionnaire to accurately detect chronic ocular GVHD in a hematology clinic
Greenan, E., Vandenberghe, E., Conneally, E., Murphy, C. C., Ní Gabhann-Dromgoole J
The ocular surface. 2022
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10.
Ocular Graft-versus-Host Disease Underdiagnosis: A Survey Study
Colarusso, B. A., Bligdon, S. M., Ganjei, A. Y., Kwok, A., Brocks, D., Luo, Z. K.
Clinical ophthalmology (Auckland, N.Z.). 2022;16:1419-1426
Abstract
PURPOSE To understand the degree and explore the possible causes of ocular graft-versus-host disease (oGVHD) underdiagnosis in patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT). PATIENTS AND METHODS A 15-question survey was emailed to 6032 subscribers to the Blood and Marrow Transplant Information Network. A total of 371 respondents confirmed the history of allo-HSCT, of which 335 were symptomatic. Their self-reported symptoms, onset, treatments tried, degree of symptom control and established diagnoses of systemic chronic graft-versus-host disease (cGVHD) and oGVHD were analyzed. RESULTS Among the 335 symptomatic survey respondents, 306 reported their ocular symptom onset was after allo-HSCT, with only 170 [55.6% (170/306)] ever receiving a diagnosis of oGVHD; 23 reported worsening pre-existing ocular symptoms after allo-HSCT, with only 5 [21.7% (5/23)] ever receiving a diagnosis of oGVHD; 6 reported stable symptoms before and after allo-HSCT, with 1 ever receiving a diagnosis of oGVHD. Of the 176 respondents carrying the diagnosis of oGVHD, 167 [94.9% (167/176)] also had the diagnosis of cGVHD. Logistic regression analysis showed that the diagnosis of oGVHD was highly correlated with the number of symptoms and treatments one reported. Furthermore, 35% of the respondents with new onset ocular symptoms reported onset within the first 6 months after allo-HSCT (previously reported), as well as 39% of the respondents with worsened existing symptoms. CONCLUSION oGVHD underdiagnosis is likely associated with the previous diagnostic criteria, in which cGVHD of another organ system was required. The correct notion that oGVHD commonly causes severe dry eye disease has likely led to its underdiagnosis in patients with fewer number of symptoms and/or who tried fewer treatments.