Search

Graft versus host disease (GVHD) remains a major and serious complication of allogeneic hematopoietic stem cell transplantation. Based on the time of onset, clinical phenotypes, progression kinetics, and pathophysiology, GVHD is stratified into acute, chronic, and overlapping types. The eyes are among the most commonly affected organs in GVHD. Mouse models have played an important role in understanding the several key elements of GVHD pathobiology. The current review discusses the immunology, pathology, and key phenotypic features of mouse models of systemic GVHD. Furthermore, a critical appraisal of mouse models of ocular GVHD (oGVHD) is provided. The disease mechanisms underlying the ocular surface, meibomian gland, and lacrimal gland injury in these models are reviewed, and the relevance of oGVHD murine models to clinical oGVHD is also included., Competing Interests: Declaration of competing interest Authors do not have any financial conflict of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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 (allo-HSCT) are exposed to DS on transplantation wards, which are highly climate-regulated for hygienic purposes. Because oGVHD demonstrates features of dry eye disease, this retrospective study aimed to analyze DS as a risk factor for chronic oGVHD. A total of 444 patients undergoing allo-HSCT were investigated with a maximum follow-up of 5.8 years post-transplantation. 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. One hundred three of 213 surviving patients developed oGVHD. oGVHD was significantly correlated with a lower %rH (r = .2; P = .03), and more patients (73%) developed oGVHD after transplantation under DS compared with patients after transplantation under high-humidity conditions (30%; P = .02). Reduced humidity increased the relative risk for oGVHD by 4% for each %rH, but it did not affect the severity or time of first diagnosis of oGVHD. In this study, we demonstrate that DS is an independent risk factor for oGVHD. Adjusting air humidity during allo-HSCT has the potential to serve as a preventive measure with clinical relevance., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Ocular graft-versus-host disease (oGVHD) is a fast progressing, autoimmunological disease following hematopoietic stem cell transplantation, leading to severe inflammation of the eye and destruction of the lacrimal functional unit with consecutive sight-threatening consequences. The therapeutic "window of opportunity" is narrow, and current treatment options are limited and often insufficient. To achieve new insights into the pathogenesis and to develop new therapeutic approaches, clinically relevant models of oGVHD are desirable. In this study, the ocular phenotype was described in a murine, chemotherapy-based, minor-mismatch GVHD model mimicking early-onset chronic oGVHD, with corneal epitheliopathy, inflammation of the lacrimal glands, and blepharitis. Additionally, corneal lymphangiogenesis was observed as part of oGVHD pathogenesis for the first time, thus opening up the investigation of lymphangiogenesis as a potential therapeutic and diagnostic tool.

Background: graft-versus-host disease (GvHD) is a common complication after allogeneic haematopoietic stem cell transplantation (allo-SCT) and causes immunological rejection of host tissues, which can occur both acute or chronically. Approximately 40 - 80% of patients with the diagnosis of chronic GvHD (cGvHD) also develop ocular GvHD. For these patients, immediate and uncomplicated access to interdisciplinary patient-centred care is important. We performed this survey to improve understanding of the structure of patient-centred care in Germany., Methods: The GvHD working party of the Cornea Section of the German Society of Ophthalmology sent the "Survey of ocular GvHD 2016" to all university and specialised hospitals in Germany. We evaluated the data and compared the information with survey results from 2014, in order to draw conclusions about the structure and process of patient-centred care in ocular GvHD. Besides the questions from 2014 on the numbers of allo-SCT, frequency of examinations, etc. there were additional questions on the prescription of ciclosporin and autologous serum eye drops. The question on frequency examination was further expanded to include examinations of paediatric patients., Results: Of 30 participating hospitals, 22 had already taken part in the first survey. According to the information they provided, approx. 1860 allo-SCTs were performed in the transplantation units of the participating eye hospitals in 2016. This was more than half of the transplantations performed in Germany. Ophthalmologists examined between 2 and 250 Patients per year per centre. Eight clinics provide a specialised outpatient clinic for ocular GvHD. Nearly all the participating clinics prescribe ciclosporin eye drops. About ⅔ provide autologous serum eye drops, seven obtain them from external sources. Overall approx. 125 - 140 children were examined in 2016., Conclusions: Due to the potential severity of ocular GvHD with immobilisation of the patients and the imminent loss of sight, further improvements in eye care are required. For example, offers such as special consultations, with expertise located close to any transplantation unit are recommended. This requires in particular ophthalmologists to participate in the patient care to enhance quality of life after allo-SCT. In summary, we conclude that the present structures are not sufficient to treat all patients suffering from ocular GvHD in Germany, but the situation has evidently improved., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Autologous submandibular gland transfer for treatment of progressive dry eye symptoms requires a functionally intact submandibular gland. In cases of total function loss of both lacrimal and submandibular glands this procedure has to be modified. Here we report on the first two cases of the allogenic transplantation of a submandibular gland to treat patients suffering from complete functional loss of both glands due to graft-versus-host disease (GvHD) following stem cell transplantation., Methods: We carried out allogenic transplantation of the submandibular gland of the matched former stem cell donor to the temporal fossa of the stem cell recipient suffering from GvHD-induced dry eye. The treatment was carried out in two male patients who showed complete donor chimerism to the stem cell donors, so that no immunosuppressive therapy was applied., Results: Postoperative clinical assessment of the patients revealed primary success of the procedure. The ocular surface showed improvement of lubrication and reduction of inflammatory signs. In the long-term follow-up sialoscintigraphy revealed lower tracer activity than expected and secretion of saliva-tears decreased., Conclusion: Even though the so-called total donor chimerism was assessed allogenic transplantation of the submandibular gland following GvHD-induced dry eye showed signs of organ rejection and therefore initial immunosuppressive therapy after allogenic transplantation has to be considered., (Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

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. [ABSTRACT FROM AUTHOR]

Purpose: Ocular graft-versus-host disease (oGvHD) following allogeneic hematopoietic stem cell transplantation develops as severe dry eye disease (DED) and is initially treated with lubricants, although no clinical trials are available using artificial tears in oGvHD. This trial was set up to test perfluorohexyloctane (NovaTears®) as nonpreserved layer-forming agent for the treatment of DED in oGvHD. Methods: 25 patients with severe DED due to oGvHD received 1 drop perfluorohexyloctane 4 times daily during a prospective, multicenter, observational 12-week study on top of established topical therapy. Clinical parameters included Schirmer test, tear film breakup time, corneal staining, meibum secretion and ocular surface disease index. Adverse events, visual acuity and intraocular pressure were key safety parameters. Results: From 25 patients recruited, 23 presented for the second visit. Perfluorohexyloctane treatment did not lead to any changes in clinical or safety parameters but led to fast relief in symptoms in 57% of the patients. One adverse reaction occurred. Conclusions: This study showed no change in clinical signs in severe DED due to oGvHD, which was not unexpected due to the underlying pathomechanisms. However, the study showed improvement of symptoms in individual patients allowing application of perfluorohexyloctane as an additional symptomatic therapy in oGvHD. [ABSTRACT FROM AUTHOR]

Despite decades of experience with hematopoietic stem cell transplantation, we are still faced with the delicate equipoise of achieving stable ocular health post-transplantation. This is because ocular graft-versus-host disease (oGvHD) following hematopoietic stem cell transplantation frequently occurs (≥50%) among transplant patients. To date, our understanding of the pathophysiology of oGvHD especially the involvement of the meibomian gland is still limited as a result of a lack of suitable preclinical models among other. Herein, the current state of the etiology and, pathophysiology of oGvHD based on existing pre-clinical models are reviewed. The need for additional pre-clinical models and knowledge about the involvement of the meibomian glands in oGvHD are emphasized. [ABSTRACT FROM AUTHOR]

Chronic graft-versus-host disease (cGVHD) is one of the most frequent complications experienced after allogeneic hematopoietic stem cell transplantation. Reportedly, dysbiosis and severe damage to the microbiome are also closely associated with GVHD. Herein, we aimed to elucidate the positive and negative effects of the administration of various antibiotics in a murine model of cGVHD. For allogeneic bone marrow transplantation (allo-BMT), bone marrow from B10.D2 mice were transplanted in BALB/c mice to induce cGVHD. The cGVHD mice were orally administered ampicillin, gentamicin (GM), fradiomycin, vancomycin, or the solvent vehicle (control group). Among the antibiotic-treated mice, the systemic cGVHD phenotypes and ocular cGVHD manifestations were suppressed significantly in GM-treated mice compared to that in control mice. Inflammatory cell infiltration and fibrosis in cGVHD-targeted organs were significantly attenuated in GM-treated mice. Although regulatory T cells were retained at greater levels in GM-treated mice, there were significantly fewer Th17 cells and interleukin (IL)-6-producing macrophages in cGVHD-targeted organs in these mice. Collectively, our results revealed that orally administered GM may exert positive effects in a cGVHD mouse model. [ABSTRACT FROM AUTHOR]