MSCohi-O lenses for long-term retention of mesenchymal stem cells on ocular surface as a therapeutic approach for chronic ocular graft-versus-host disease
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ABSTRACT:
SUBMITTER: Liu Y
PROVIDER: S-EPMC10724054 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
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Project description:To examine safety and efficacy of bandage soft contact lenses (BSCLs) for ocular chronic graft-versus host disease (GVHD), we conducted a phase II clinical trial. Extended-wear BSCLs were applied under daily topical antibiotic prophylaxis. Patients completed standardized symptom questionnaires at enrollment and at 2 weeks, 4 weeks, and 3 months afterward. Ophthalmologic assessment was performed at enrollment, at 2 weeks, and afterward as medically needed. Assessments at follow-up were compared with baseline by paired t-test. Nineteen patients with ocular GVHD who remained symptomatic despite conventional treatments were studied. The mean Lee eye subscale score was 75.4 at enrollment and improved significantly to 63.2 at 2 weeks (P = .01), to 61.8 at 4 weeks (P = .005), and to 56.3 at 3 months (P = .02). The ocular surface disease index score and 11-point eye symptom ratings also improved significantly. According to the Lee eye subscale, clinically meaningful improvement was observed in 9 patients (47%) at 2 weeks, in 11 patients (58%) at 4 weeks, and in 9 patients (47%) at 3 months. Visual acuity improved significantly at 2 weeks compared with enrollment values. Based on slit lamp exam at 2 weeks, punctate epithelial erosions improved in 58% of the patients, showed stability in 16%, and worsened in 5%. No corneal ulceration or ocular infection occurred. BSCLs are a widely available, safe, and effective treatment option that improves manifestations of ocular GVHD in approximately 50% of patients. This study was registered at www.clinicaltrials.gov as NCT01616056.
| S-EPMC4604037 | biostudies-literature
Project description:Ocular GVHD (oGVHD), manifested by severe injury of corneal epithelial cells, meibomian and lacrimal glands' dysfunction, is a serious complication of systemic GVHD which develops as a consequence of donor T and natural killer cell-driven inflammation in the eyes of patients who received allogeneic hematopoietic stem cell transplantation. Mesenchymal stem cells (MSC) are, due to their enormous differentiation potential and immunosuppressive characteristics, considered as a potentially new remedy in ophthalmology. MSC differentiate in corneal epithelial cells, suppress eye inflammation, and restore meibomian and lacrimal glands' function in oGVHD patients. MSC-sourced exosomes (MSC-Exos) are extracellular vesicles that contain MSC-derived growth factors and immunoregulatory proteins. Due to the lipid membrane and nano-sized dimension, MSC-Exos easily by-pass all biological barriers in the eyes and deliver their cargo directly in injured corneal epithelial cells and eye-infiltrated leukocytes, modulating their viability and function. As cell-free agents, MSC-Exos address all safety issues related to the transplantation of their parental cells, including the risk of unwanted differentiation and aggravation of intraocular inflammation. In this review article, we summarized current knowledge about molecular mechanisms which are responsible for beneficial effects of MSC and MSC-Exos in the therapy of inflammatory eye diseases, emphasizing their therapeutic potential in the treatment of oGVHD.
| S-EPMC9656879 | biostudies-literature
Project description:Chronic graft-versus-host disease (cGVHD) of the ocular surface and lacrimal gland is a vision-threatening condition that occurs after allogeneic bone marrow transplantation. In this study, we used immunohistochemistry and electron microscopy to investigate whether epithelial mesenchymal transition (EMT) contributed to the pathogenesis of ocular cGVHD. We detected down-regulation of E-cadherin and translocation of beta-catenin from the intercellular junction to the cytoplasm and nucleus of cGVHD conjunctival basal epithelia and lacrimal gland myoepithelia. Notable findings included expression of Snail, an inducer of EMT, in the nucleus of ocular cGVHD epithelia. The fibrosis markers heat shock protein 47, alpha-smooth muscle actin, and fibroblast specific protein-1 were overexpressed in ocular cGVHD epithelia. In addition, p63, a marker of conjunctival basal epithelia, was observed in the nuclei of subconjunctival cells beneath disrupted basal lamina. Disrupted basal lamina and the presence of altered collagen bundles were observed in the cytoplasm and beneath cGVHD epithelia. In contrast, these observations were rarely observed in the normal conjunctiva and in Sjögren's syndrome lacrimal gland epithelia. These findings together indicate that ocular cGVHD epithelia gain the mesenchymal phenotype and the capacity to migrate into the subepithelial stroma. Our findings suggest that EMT may be partially responsible for the conjunctival and lacrimal gland fibrosis found in patients with cGVHD.
| S-EPMC2789626 | biostudies-literature
Project description:This longitudinal cohort study compared ocular surface indicators in forty allogeneic hematopoietic stem cell transplant (HSCT) subjects with twenty healthy controls at baseline and identified changes in ocular graft-versus-host disease (oGVHD). Outcome measures included: Ocular Surface Disease Index (OSDI), tear osmolarity, Schirmer's test, Oxford corneal staining score, tear break-up time (TBUT), and tear and serum biomarkers (IFN-γ, IL-10, MMP-9, IL-12, IL-13, IL-17α, IL-1β, IL-2, IL-4, IL-6, IL-8, CXCL10, MCP-1, MIP-1α, RANTES, TNF-α). At baseline the HSCT group had higher median Oxford corneal staining score (1.7 vs. 0.0; P < 0.0001), higher tear TNF-α (20.0 vs. 11.2 pg/mL; P < 0.0001), lower tear RANTES (70.4 vs. 190.2 pg/mL; P < 0.0001), higher serum IL-8 (10.2 vs. 4.5 pg/mL; P = 0.0008), and higher serum TNF-α (8.7 vs. 4.2 pg/mL; P < 0.0001). The incidence of oGVHD was 62% and associated changes included increased Oxford corneal staining score (4.6 vs. 1.8, P = 0.0001), decreased Schirmer's test (3.0 vs. 10.0; P < 0.0001), and decreased TBUT (4.7 vs. 9.0 s; P = 0.0004). Baseline differences in ocular surface indicators suggest a tendency toward ocular dryness in individuals with hematologic disorders preparing for HSCT. Individuals who developed oGVHD showed changes in corneal staining score, Schirmer's test, and TBUT.
| S-EPMC8338548 | biostudies-literature
Project description:Ocular graft-versus-host-disease (GVHD) remains a significant clinical complication after allogeneic hematopoietic stem cell transplantation. Impaired visual function, pain, and other symptoms severely affect affected individuals' quality of life. However, the diagnosis of and therapy for ocular GVHD involve a multidisciplinary approach and remain challenging for both hematologists and ophthalmologists, as there are no unified international criteria. Through an exploration of the complex pathogenesis of ocular GVHD, this review comprehensively summarizes the pathogenic mechanism, related tear biomarkers, and clinical characteristics of this disease. Novel therapies based on the mechanisms are also discussed to provide insights into the ocular GVHD treatment.
| S-EPMC9905686 | biostudies-literature
Project description:BackgroundAfter allogeneic hematopoietic stem cell transplantation (allo-HSCT), patients are followed up by transplant clinicians. Finding an effective primary screening method that transplant clinicians or patients can master is essential in the early referral of suspected chronic ocular graft-versus-host disease (coGVHD) to an ophthalmologist. This study investigated if the ocular surface disease index (OSDI) questionnaire could be used for coGVHD primary screening.MethodsThis case-controlled, cross-sectional study enrolled 161 allo-HSCT patients. All participants completed an OSDI questionnaire and underwent a silt-lamp examination. Bulbar conjunctival injection (BCI) was assessed using torchlight, while tear volume was measured via the Schirmer test (ST). The receiver operating characteristic curve was used to evaluate the sensitivity, specificity, and cutoff values of OSDI, ST, and BCI grading. Performance comparisons of the 3 tests applied in isolation, parallel, and series were made.ResultsThere were 84 patients with and 77 patients without coGVHD. Compared to those without coGVHD, patients with coGVHD had significantly higher median values of OSDI, corneal fluorescein staining, conjunctival injection, conjunctival fibrosis, and meibum quality, but lower ST scores (All P values <0.001). The cutoff values for OSDI, ST, and BCI grade in the diagnosis of coGVHD were 19.4 points, 7 mm, and grade 0, respectively. The sensitivity and specificity of the tests based on the cutoff values were, respectively, 89.3% and 89.6% for OSDI, 91.7% and 59.7% for ST, and 78.6% and 70.1% for BCI. The area under the curve (AUC) value of OSDI was significantly higher than that of ST (0.931 vs. 0.826; P=0.010) and BCI grade (0.931 vs. 0.781; P<0.001). The AUC values of the combinations were lower than that of OSDI alone.ConclusionsThe OSDI questionnaire can be used as a simple screening test for coGVHD as demonstrated by its high sensitivity and specificity in the transplant clinic and patients' self-monitoring. An OSDI greater than 19.4 could be considered an ophthalmology referral criterion.
| S-EPMC9469159 | biostudies-literature
Project description:PurposeTo identify the ocular surface changes of ocular graft-versus-host disease (GVHD) using anterior segment optical coherence tomography (AS-OCT) and examine the efficacy of disposable bandage soft contact lens (BSCL) treatment in ocular GVHD patients.MethodsThis study is a prospective, Phase II clinical trial. Nineteen patients diagnosed with chronic GVHD based on the NIH criteria and ocular symptoms of NIH eye score 2 or greater were enrolled. Disposable BSCL was applied to the GVHD-affected eyes with topical antibiotic coverage. Ocular exams, eye symptom surveys, and AS-OCT were performed with signed informed consent. Patients were followed for one to three months.ResultsThirty-eight eyes of 19 patients with ocular GVHD underwent BSCL treatment in this study. AS-OCT scans were done in 14 out of 19 patients. The mean best-corrected visual acuity at enrollment, 2-week, and 4-week visits was 0.180, 0.128, and 0.163 logMAR, respectively. Twenty-four out of 25 eyes (96 %) that initially presented with conjunctival inflammation, twenty-three out of 30 eyes (76.7 %) that initially presented with punctate epithelial erosion, and 8 out of 15 (53.3 %) eyes that initially presented with filamentous keratopathy showed improvement after wearing BSCL for 2 to 4 weeks. AS-OCT revealed corneal epithelial irregularity, abnormal meibomian gland orifice, and conjunctival hyperemia, in patients with ocular GVHD.ConclusionsBSCL treatment provided significant subjective and objective improvements in ocular GVHD patients. Meanwhile, we found that AS-OCT can be a promising diagnostic tool to characterize the ocular surface changes associated with ocular GVHD.
| S-EPMC8254955 | biostudies-literature
Project description:We investigate long-term clinical outcomes and predictive factors associated with poor vision outcomes in patients with ocular graft-versus-host disease (oGVHD). This retrospective cohort study involved 94 patients with chronic oGVHD, classified into severe (n = 25) and non-severe (n = 69) groups. Factors associated with oGVHD severity and poor vision outcomes were examined using multivariate logistic regression. In the severe oGVHD group, the disease activity pattern tended to be persistent, whereas flare-up episodes were more frequent and occurred over shorter intervals in this group. Myelodysplastic syndrome (MDS) and lung GVHD were more common and systemic calcineurin inhibitors were used more frequently in the severe group than in the non-severe group. Finally, 5-year survival rates were poorer in the severe group. Multivariate analysis revealed that MDS, lung GVHD involvement, and no history of systemic calcineurin inhibitor use were risk factors for severe oGVHD. Risk factors for poor vision outcomes were conjunctival scarring and persistent epithelial defects. In conclusion, MDS, lung GVHD, and no history of systemic calcineurin inhibitors are associated with severe oGVHD. Conjunctival scarring and persistent epithelial defects are risk factors for poor vision outcomes.
| S-EPMC9338251 | biostudies-literature
Project description:IL-35 is a newly discovered inhibitory cytokine secreted by regulatory T cells (Tregs) and may have therapeutic potential in several inflammatory disorders. Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation and caused by donor T cells and inflammatory cytokines. The role of IL-35 in aGVHD is still unknown. Here we demonstrate that IL-35 overexpression suppresses CD4(+) effector T-cell activation, leading to a reduction in alloreactive T-cell responses and aGVHD severity. It also leads to the expansion of CD4(+)Foxp3(+) Tregs in the aGVHD target organs. Furthermore, IL-35 overexpression results in a selective decrease in the frequency of Th1 cells and an increase of IL-10-producing CD4(+) T cells in aGVHD target tissues. Serum levels of TNF-α, IFN-γ, IL-6, IL-22 and IL-23 decrease and IL-10 increases in response to IL-35. Most importantly, IL-35 preserves graft-versus-leukemia effect. Finally, aGVHD grade 2-4 patients have decreased serum IL-35 levels comparing with time-matched patients with aGVHD grade 0-1. Our findings indicate that IL-35 has an important role in reducing aGVHD through promoting the expansion of Tregs and repressing Th1 responses, and should be investigated as the therapeutic strategy for aGVHD.
| S-EPMC4391991 | biostudies-literature
Project description:PurposeTo validate measurement scales for rating ocular chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation. Candidate scales were recommended for use in clinical trials by the National Institutes of Health (NIH) Chronic GVHD Consensus Conference or have been previously validated in dry eye syndromes.DesignProspective follow-up study.ParticipantsBetween August 2007 and June 2010, the study enrolled 387 patients with chronic GVHD in a multicenter, prospective, observational cohort.MethodsUsing anchor-based methods, we compared clinician or patient-reported changes in eye symptoms (8-point scale) with calculated changes in 5 candidate scales: The NIH eye score, patient-reported global rating of eye symptoms, Lee eye subscale, Ocular Surface Disease Index, and Schirmer test. Change was examined for 333 follow-up visits where both clinician and patient reported eye involvement at the previous visit. Linear mixed models were used to account for within-patient correlation.Main outcome measuresAn 8-point scale of clinician or patient-reported symptom change was used as an anchor to measure symptom changes at the follow-up visits.ResultsIn serial evaluations, agreement regarding improvement, stability, or worsening between the clinician and patient was fair (weighted kappa = 0.34). Despite only fair agreement between evaluators, all scales except the Schirmer test correlated with both clinician-reported and patient-reported changes in ocular GVHD activity. Among all scales, changes in the NIH eye scores showed the greatest sensitivity to symptom change reported by clinicians or patients.ConclusionsOur results support the use of the NIH eye score as a sensitive measure of eye symptom changes in clinical trials assessing treatment of chronic GVHD.
| S-EPMC3294118 | biostudies-literature