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1.
Ocular manifestations and quality of life in patients after hematopoietic stem cell transplantation
Fan, S. X., Wang, W. H., Zeng, P., Huang, K. Z., Hu, Y. X., Wang, J., Li, Y. Q., Xiao, J. H.
International journal of ophthalmology. 2023;16(7):1138-1144
Abstract
AIM: To explore the relationship between ocular and systemic conditions and the impact of ocular complications on the quality of life (QOL) in patients after allogeneic hematopoietic stem cell transplantation (ALLO-HSCT). METHODS Forty-four patients with severe hematopoietic disease were enrolled after ALLO-HSCT at our center from July 2018 to October 2020. They completed two questionnaires: the Ocular Surface Disease Index (OSDI) and the quality-of-life scale for Chinese patients with visual impairment (SQOL-DV1). Ocular conditions and systemic conditions were also assessed. RESULTS Eye damage was correlated with total bilirubin (P=0.005), and gamma-glutamyl transferase (GGT) (P=0.021). There was no significant correlation between the overall QOL score and OSDI (P=0.8226) or SQOL-DV1 (P=0.9526) scores. The OSDI and the overall QOL score were not correlated with ocular conditions, including best-corrected visual acuity (BCVA), intraocular pressure, Schirmer tear test II, sodium fluorescein staining, tear film breakup time, and tear meniscus height. SQOL-DV1 was correlated with BCVA (P=0.0007), sodium fluorescein staining (P=0.007), and tear film breakup time (P=0.0146). CONCLUSION In some patients, early ocular symptoms are not evident after ALLO-HSCT, while ocular surface complications can be observed after a comprehensive ophthalmological examination. Especially for those with elevated total bilirubin or GGT, regular ophthalmic follow-up visits are essential to diagnose and treat ocular graft versus host disease (oGVHD), especially for patients with elevated total bilirubin or GGT.
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2.
[Clinical characteristics and correlative factors of dry eye disease associated with graft-versus-host disease]
Zhuang, X. Y., Sun, Z. T., Wang, Y. M., Que, L. J., Zhang, X. F.
[Zhonghua yan ke za zhi] Chinese journal of ophthalmology. 2023;59(4):295-301
Abstract
Objective: To investigate the clinical features of dry eye disease in patients with graft-versus-host disease (GVHD) and to identify the correlative factors that contribute to its severity. Methods: It was a retrospective case series study. A total of 62 patients with dry eye disease caused by GVHD after allogeneic hematopoietic stem cell transplantation (HSCT) were recruited from the First Affiliated Hospital of Soochow University between 2012 and 2020. The study population comprised 38 males (61%) and 24 females (39%), with an average age of (35.29±11.75) years. Only the right eye of each patient was evaluated. The patients were divided into two groups based on the severity of corneal epitheliopathy: a mild group (15 eyes) and a severe group (47 eyes). Demographic information, including gender, age, primary disease, type of allogeneic HSCT, donor-to-recipient information, source of hematopoietic stem cells, systemic GVHD, and the time from HSCT to the first visit, was collected. Ophthalmologic assessments, including the Schirmer Ⅰ test, tear breakup time, corneal epithelial staining, and eye margin assessment, were performed during the first visit to the ophthalmology department and compared between the two groups. Results: The average time from HSCT to the first visit to the ophthalmology department among the 62 patients was (20.26±13.09) months. The median corneal fluorescein staining score was 4.5 points. In the mild group, the main characteristic of corneal staining was scattered punctate staining in the peripheral region in 80% of cases, while in the severe group, corneal staining fused into clumps in both the peripheral region (64%) and the pupillary zone (28%). Results of the Schirmer Ⅰ test were significantly lower in the severe group compared to the mild group (P<0.05). The median total eyelid margin score in the severe group was higher than that in the mild group [9 (7, 12) points vs. 6 (5, 8) points] (P<0.05). The median eyelid congestion score in the severe group was, also higher than that in the mild group [2 (1, 3) points vs. 1 (0, 2) points] (P<0.05). The compatibility between the blood types of the donor and recipient was found to be statistically significant (P<0.05). There was no significant difference in gender, age, family relationship, human leukocyte antigen matching, gender consistency, source of hematopoietic stem cells, or the occurrence of systemic GVHD between the two groups (P>0.05). Conclusions: Patients in the mild group had scattered punctate corneal staining in the peripheral region, while those in the severe group showed fusion of corneal staining into clumps in both the peripheral and pupillary zones. The severity of dry eye disease caused by GVHD was strongly correlated with eyelid margin lesions. A higher degree of eyelid margin lesions indicated more severe dry eye disease caused by GVHD. Additionally, compatibility between the blood types of the donor and recipient may play a role in the development of GVHD-associated dry eye.
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3.
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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4.
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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5.
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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6.
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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7.
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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8.
Outcomes and complications of cataract surgery in patients with chronic ocular graft-versus-host-disease-a multicenter, retrospective analysis
Gehlsen, U., Faust, C., Blecha, C., Dietrich-Ntoukas, T., Eberwein, P., Issleib, S., Meyer-Ter-Vehn, T., Braun, R., Westekemper, H., Steven, P.
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2022
Abstract
PURPOSE To evaluate the outcome of phacoemulsification in patients with chronic ocular Graft-versus-host disease (oGVHD) after allogeneic hematopoietic stem cell transplantation (aHSCT). METHODS Retrospective, observational multicenter study from 1507 oGVHD patients. From the patient files, data were collected including best-corrected visual acuity (BCVA), intraocular pressure (IOP), Schirmer's test I, tear film break-up time (TFBUT), corneal fluorescein staining score, postoperative complications, and pre- and post-operative topical therapy. RESULTS Seventy-three patients underwent cataract surgery in 104 eyes. In n = 84 eyes, the oGVHD NIH grade was documented; 12% (n = 12) of analyzed eyes were staged oGVHD NIH grade 1, 31% (n = 32) NIH 2 and 39% (n = 41) NIH 3. The mean BCVA improved in 82% of the eyes (n = 86 eyes). BCVA significantly increased from 0.7 ± 0.5 to 0.4 ± 0.4 LogMAR after surgery independent from oGVHD severity. The mean IOP decreased from 14 ± 4 to 13 ± 4 mmHg after surgery. Visual acuity was moderately correlated to the pre-operative degree of corneal staining (Pearson p = 0.26, p = 0.002, Cohen's effect size f = 0.29). The visual acuity decreased by 0.078 LogMar units (95% CI = 0.027-0.141) with each increase of corneal staining by one grade (p = 0.05). After surgery, corneal epitheliopathy increased significantly in 42% (n = 44) of the eyes. Postoperative complications included corneal perforation (n = 6, 6%), cystoid macular edema (n = 4, 4%), and endophthalmitis (n = 1, 1%). CONCLUSION Phacoemulsification in patients with chronic oGVHD significantly improves visual acuity, but is associated with an increased risk of complications in particular corneal epitheliopathy and corneal perforations.
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9.
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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10.
Ocular Chronic Graft-Versus-Host Disease and Its Relation to Other Organ Manifestations and Outcomes After Allogeneic Haematopoietic Cell Transplantation
Jeppesen, H., Gjærde, L. K., Lindegaard, J., Julian, H. O., Heegaard, S., Sengeløv, H.
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Ocular chronic graft-versus-host disease (cGVHD) has been shown to significantly reduce quality of life after allogeneic haematopoietic stem cell transplantation (HSCT). OBJECTIVE To learn more about this bothersome complication, we investigated the relation between ocular cGVHD and cGVHD in other organs. Furthermore, we investigated the associations between ocular cGVHD and overall mortality, non-relapse mortality and relapse. STUDY DESIGN In this single center study, we retrospectively included 1221 consecutive adults who received allogeneic HSCT. Patients were examined by an ophthalmologist before HSCT and annually for five years after HSCT, or more frequently if needed. Patients with dry eye disease before HSCT were excluded. The International Chronic Ocular GVHD Consensus Group's criteria were used to diagnose ocular cGVHD. Non-ocular cGVHD was diagnosed using the NIH criteria. RESULTS Out of 601 patients who were diagnosed systemic cGVHD during follow-up, 279 (46%) developed ocular cGVHD. Ocular cGVHD was more frequent in patients with extensive cGVHD compared to limited cGVHD (50% vs. 29%, p<0.0001), and was associated with cGVHD in skin (p<0.0001), oral cavity (p=0.0024), genitals (p=0.0023) and nails (p=0.031). The frequency of ocular cGVHD was higher in patients with skin cGVHD with sclerosis (70%) compared to skin cGVHD without sclerosis (49%) (p=0.0003). In an adjusted time-dependent Cox model, ocular cGVHD was associated with increased non-relapse mortality (adjusted HR 1.61, 95% CI:1.17-2.21, p=0.003), whereas we did not find support for an association with relapse (adjusted HR 0.85, 95% CI:0.53-1.36, p=0.5). CONCLUSIONS Special attention to eye problems after HSCT should be given patients with extensive cGVHD and cGVHD in ectodermal derived organs (skin, mouth, nails, and genitals). Furthermore, ocular cGVHD is a potential risk factor of non-relapse mortality.