A Review of Ocular Graft-versus-Host Disease: Pathophysiology, Clinical Presentation and Management

Carreno-Galeano, Jimena Tatiana; Dohlman, Thomas H.; Kim, Stella; Yin, Jia; Dana, Reza

doi:10.1080/09273948.2021.1939390

Cited by 30 publications

(28 citation statements)

References 108 publications

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“…Dry eye is also the most common clinical manifestation of coGVHD. Symptom assessment is essential for the diagnosis of coGVHD (15,23). Recently, a set of ICCGVHD diagnostic criteria for coGVHD was proposed as a more detailed disease assessment.…”

Section: Discussionmentioning

confidence: 99%

Ocular surface disease index questionnaire as a sensitive test for primary screening of chronic ocular graft-versus-host disease

Yang¹,

Zhao²,

Liao³

et al. 2022

Ann Transl Med

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Background: After 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.Methods: This 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.Results: There 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. Conclusions:The 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.

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Section: Discussionmentioning

confidence: 99%

Ocular surface disease index questionnaire as a sensitive test for primary screening of chronic ocular graft-versus-host disease

Yang¹,

Zhao²,

Liao³

et al. 2022

Ann Transl Med

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“…Pre-clinical animal models have been critical not only in understanding the immune mechanisms of systemic but also oGHVD ( 35–37 ). Acute and chronic GVHD are immune-mediated diseases involving a variety of immune cells such as macrophages, T cells and B cells ( 11 , 19 , 38 , 39 ). Figure 1 depicts the immunological activation leading to ocular surface inflammation and lacrimal gland fibrosis.…”

Section: Pathophysiology Of Gvhd and Ocular Gvhdmentioning

confidence: 99%

“…After the first HCT in 1968 survival rates have increased in the last decades, due to human leukocyte antigen (HLA) matching, continuously improved preconditioning protocols and immunosuppressive regimen ( 7 , 9 , 10 ). Both, acute and chronic GVHD occur in about 30%–70% of patients after HCT depending on transplant regimens and GVHD prophylaxis strategies ( 7 , 11 ). A variety of risk factors for GVHD related to donor as well as to recipients’ characteristics have been identified.…”

Section: Introductionmentioning

confidence: 99%

Challenges and concepts in the diagnosis and management of ocular graft-versus-host disease

Tappeiner

Heiligenhaus²,

Halter³

et al. 2023

Front. Med.

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Graft-versus-host disease (GVHD) is characterized by tissue inflammation in the host following an allogeneic hematopoietic cell transplantation (HCT). The pathophysiology is complex and only incompletely understood yet. Donor lymphocyte interaction with the histocompatibility antigens of the host plays a crucial role in the pathogenesis of the disease. Inflammation may affect multiple organs and tissues, e.g., the gastrointestinal tract, liver, lung, fasciae, vaginal mucosa, and the eye. Subsequently, alloreactive donor-derived T and B lymphocytes may lead to severe inflammation of the ocular surface (i.e., cornea and conjunctiva) and the eyelids. Furthermore, fibrosis of the lacrimal gland may lead to severe dry eye. This review focuses on ocular GVHD (oGVHD) and provides an overview of current challenges and concepts in the diagnosis and management of oGVHD. Ophthalmic manifestations, diagnostic procedures, grading of severity and recommendations for ophthalmic examination intervals are provided. Management of ocular surface disease with lubricants, autologous serum eye drops, topical anti-inflammatory agents and systemic treatment options are described based on the current evidence. Ocular surface scarring and corneal perforation are severe complications of oGVHD. Therefore, ophthalmic screening and interdisciplinary treatment approaches are highly relevant to improve the quality of life of patients and to prevent potentially irreversible visual loss.

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“…T-cell infiltration of these tissues initiates an immunoinflammatory cascade. Reportedly, the cascade response primarily consists of apoptosis induction, immune cell recruitment, and the production of inflammatory cytokines and chemokines ( 12 ). Thus, summarizing the underlying pathogenic mechanism in different parts of the ocular surface helps to understand the onset and development of ocular GVHD and facilitates the search for new therapeutic targets and treatment pathways.…”

Section: Pathogenic Mechanism and Novel Therapeutic Targetsmentioning

confidence: 99%

Recent advances in ocular graft-versus-host disease

Cheng

Huang

et al. 2023

Front. Immunol.

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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.

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A Review of Ocular Graft-versus-Host Disease: Pathophysiology, Clinical Presentation and Management

Cited by 30 publications

References 108 publications

Ocular surface disease index questionnaire as a sensitive test for primary screening of chronic ocular graft-versus-host disease

Ocular surface disease index questionnaire as a sensitive test for primary screening of chronic ocular graft-versus-host disease

Challenges and concepts in the diagnosis and management of ocular graft-versus-host disease

Recent advances in ocular graft-versus-host disease

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