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AIM: To detect the expression of interleukin(IL)-36(α, β, γ)in tears of patients undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT), investigate its correlation with ocular surface microenvironment, and further analyze the relationship between its expression and ocular graft-versus-host disease(oGVHD).METHODS: Prospective study. A total of 35 patients(70 eyes)underwent allo-HSCT in the hematology department of our hospital in January 2020 were selected, and 35 healthy volunteers(70 eyes)with appropriate age and gender were selected as normal control group. The patients in the allo-HSCT group were followed up 3 times after operation once every 3mo. The subjects with postoperative ocular symptoms were divided into oGVHD and Non-oGVHD group.Ocular surface disease index(OSDI)questionnaire, Schirmer test, tear break-up time(TBUT), corneal fluorescein staining(FL), and conjunctival impression cytology(CIC)was conducted in three groups. Furthermore, the expression levels of IL-36(α,β,γ)in tears were detected by ELISA.RESULTS: In the normal control group, IL-36(α, β, γ)expression levels were 74.32±5.27, 70.02±8.43, 97.41±8.66 pg/mL, respectively; in the allo-HSCT group, IL-36(α, β, γ)baseline expression levels were 77.27±7.03, 74.53±7.53, 100.77±9.74 pg/mL, with no statistically significant differences between the two groups(t=1.648, 1.954, 1.262, all P>0.05). There were no significant differences in IL-36α, IL-36β and IL-36γ in Non-oGVHD group at different time points(P>0.05), while there were significant differences in IL-36α, IL-36β and IL-36γ in oGVHD group at different time points(P<0.05). Compared with Non-oGVHD group, the levels of IL-36α and IL-36β at different time points were significantly increased in oGVHD group(all P<0.05).IL-36(α, β, γ)of oGVHD group was positively correlated with OSDI score, FL and CIC, while it was negatively correlated with TBUT and Schirmer test(all P<0.05).CONCLUSION: Evaluation of levels of tear IL-36(α, β, γ)can be of significance in diagnosing oGVHD after allo-HSCT. IL-36(α, β, γ)is highly expressed in the tears of oGVHD patients before the onset of ocular symptoms, and it is correlated with the ocular surface parameters.
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AIM: To investigate the safety and efficacy of intense pulsed light in the treatment of severe chronic ocular graft-versus-host disease.METHODS: Prospective randomized controlled study. A total of 35 cases(35 eyes), who had a history of allogenic hematopoietic stem cell transplantation(allo-HSCT), admitted to the Affiliated Hospital of Xuzhou Medical University from January to September 2022 and were diagnosed by our hospital's hematology and ophthalmology departments with severe chronic ocular graft-versus-host disease(coGVHD)were selected. One eye was randomly selected for inclusion in the study if both eyes met the enrollment criteria, and the eye was selected if a single eye met the enrollment criteria. All patients were administrated with Dextran and Hypromellose eye drops 4 times a day and Cyclosporine eye drops twice a day. The experimental group was additionally treated with intense pulsed light, once every two weeks a week, for 4 times in total. The evaluation indicators were evaluated before treatment and 2wk, 1 and 2mo after treatment. The evaluation indicators include ocular surface disease index(OSDI)score, best corrected visual acuity(BCVA), intraocular pressure(IOP), tear meniscus height(TMH), non-invasive break-up time(NIBUT), conjunctival injection score(CIS), meibomian gland area proportion(MGAP), meibomian gland evaluation(MGE), cornea fluorescein staining(CFS), conjunctival lissamine green staining(CLGS), lid margin abnormality score(LMAS), and Schirmer's Ⅰ test(SⅠt).RESULTS: After treatment, OSDI score, TMH, NIBUT, BCVA, CFS, CLGS, and CIS improved in both groups compared with those before treatment(all P<0.05), with NIBUT, CFS and CLGS showing more significant improvements in the test group. In the control group, MGAP, MGE of the upper and lower eyelids and LMAS did not change significantly before and after treatment(P>0.05), while in the experimental group, MGAP of the lower eyelids, MGE of upper and lower eyelids and LMAS improved compared with those before treatment(P<0.05), except for MGAP of the upper eyelids, which did not differ from that before treatment(P>0.05). There was no difference in SⅠt and IOP between the two groups before and after treatment(P>0.05). Patients did not experience adverse reactions such as skin burns, redness and swelling in the treated area and eyelash loss during the follow-up period.CONCLUSION: Intense pulsed light is safe and effective in the treatment of severe coGVHD, which can significantly improve the symptoms and signs of patients and enhance the stability of tear film.
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Ocular graft-versus-host disease is one of the common complications after hematopoietic stem cell transplantation. Dry eye is the main clinical manifestation. Severe complications, such as corneal ulcer perforation and ocular surface failure may occur along with the progression of ocular graft-versus-host disease, which affects the visual acuity and quality of life of the patients. At present, multiple international researches and clinical guidelines for adult ocular graft-versus-host disease have been available. Nevertheless, pediatric ocular graft-versus-host disease has captivated insufficient attention, and relevant basic data and diagnostic criteria are still lacking. Children possess limited capability to express ocular symptoms, and lack of cooperation in clinical examination. In addition, ophthalmologists have insufficient understanding of this disease, which collectively increase the risk of missing diagnosis and misdiagnosis. In this article, the research progress on the pathogenesis, incidence, risk factors, clinical manifestations, diagnosis and treatment of pediatric ocular graft-versus-host disease was reviewed, aiming to provide ideas for strengthening clinical trials and expanding basic research of this disease in children.
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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) could effectively treat multiple hematological diseases. At present, with persistent improvement of transplantation techniques and rapid development of economy, more and more patients with hematological diseases are able to survive for a long time due to allo-HSCT treatment. Chronic ocular graft-versus-host disease (coGVHD) is the most common ocular complication after allo-HSCT, which is primarily manifested with refractory dry eye. In severe cases, it may cause imbalance of ocular surface homeostasis and limbal stem cell insufficiency, further leading to a series of complications that threaten the visual function and eye health, such as corneal perforation and symblepharon, etc. It is highly difficult to cure these symptoms. At present, relevant studies of clinical manifestations, diagnostic criteria, treatment specification and pathogenesis of coGVHD have been gradually deepened within the international community. However, related research and the establishment of clinical specification are still in the primary stage in China. In this article, research progress on clinical characteristics and related mechanisms of coGVHD was reviewed, aiming to deepen the understanding of this disease by ophthalmologists, especially specialists in corneal and ocular surface diseases, and provide novel ideas for subsequent in-depth research.
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Ocular graft-versus-host disease (GVHD) is a major complication of hematopoietic stem cell transplantation (HSCT). However, the diagnostic criteria for ocular GVHD are controversial and mainly based on clinical experience.Objective and reliable diagnostic parameters for this disease are limited.As a result, most patients can not get early diagnosis and effective management.Tear cytokine profile analysis is a safe, convenient and noninvasive examination which reflects immune mechanisms of systemic and ocular diseases.Levels of certain cytokines in tear can serve as specific biomarkers of GVHD and thus have the potential to act as accurate diagnostic and prognostic tools.In this article, the current status of ocular GVHD diagnosis was summarized, the role of cytokines in immune mechanism and diagnosis of ocular GVHD were reviewed.
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PURPOSE: To evaluate the therapeutic effects of 0.03% tacrolimus eye drops on dry eye associated with chronic ocular graft-versus-host disease (GVHD). METHODS: This study included 24 eyes of 12 patients with refractory dry eye associated with chronic ocular GVHD who were unresponsive to topical steroid and 0.05% topical cyclosporine. The topical steroid and cyclosporine were discontinued for 2 weeks before treatment and 0.03% tacrolimus eye drops were applied twice a day for 1 month. Artificial tears, ointment, and lid cleanser were used in the same manner before initiating tacrolimus treatment. Ocular staining score, tear break-up time, ocular surface disease index (OSDI), and Schirmer I test score were evaluated. RESULTS: Ocular staining score, tear break-up time, and OSDI improved with statistical significance (p < 0.05) after 28 days of treatment. Schirmer I test did not show statistical improvement after treatment. CONCLUSIONS: The use of 0.03% tacrolimus eye drops were effective for refractory dry eye associated with chronic ocular GVHD.
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Humanos , Ciclosporina , Enfermedad Injerto contra Huésped , Soluciones Oftálmicas , Tacrolimus , LágrimasRESUMEN
PURPOSE: To investigate the incidence, clinical manifestations, and risk factors of ocular graft-versus-host disease (GVHD) as well as the survival of the patients after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: The medical records of 99 patients who visited our clinic and were screened for ocular GVHD after allogeneic HSCT were reviewed retrospectively. Subjects were divided into 2 groups depending on the occurrence of ocular GVHD on slit-lamp biomicroscopy. We compared clinical manifestations and survival between the 2 groups and analyzed the risk factors associated with the development of ocular GVHD. RESULTS: Ocular GVHD was diagnosed in 38 patients (38.38%) at a mean of 315 days after HSCT. Out of the 38 patients who developed ocular GVHD, 22 patients (57.89%) were diagnosed with dry eye only and 16 patients (42.11%) were diagnosed with conjunctival disease. The presence of extraocular GVHD (hazard ratio (HR) 35.76, p < 0.001), the number of extraocular GVHD (HR 3.07, p < 0.001), skin GVHD (HR 2.31, p = 0.029), oral GVHD (HR 8.16, p < 0.001), and gastrointestinal tract GVHD (HR 5.00, p = 0.002) were independent risk factors of ocular GVHD. Comparisons of the survival demonstrated decreased survival of patients with conjunctival disease compared to patients without ocular GVHD and patients with dry eye only, but there was no statistically significant differences (log rank test, p = 0.208). CONCLUSIONS: Ocular GVHD is common after allogeneic HSCT. The majority of ocular GVHD occurs in the chronic stage and is associated with decreased survival. Therefore, more intensive and long-term follow-up with ophthalmic and systemic monitoring is necessary, especially in patients who have extraocular GVHD, for early recognition and proper treatment of ocular GVHD.