Corneal Biomechanical Alterations in Patients with Chronic Ocular Graft Versus-host Disease

Giannaccare, Giuseppe; Pellegrini, Marco; Taroni, Leonardo; Bernabei, Federico; Senni, Carlotta; Grendele, Arianna; Scorcia, Vincenzo; Campos, Emilio C.

doi:10.1101/553867

Cited by 6 publications

(6 citation statements)

References 26 publications

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“…If InflammaDry can reflect tear concentrations of MMP-9 quantitatively, this may play a crucial role in determining the severity of inflammation and improve the outcomes for dry eye patients beyond a simple diagnosis. Furthermore, clinical interpretation of the faint test (red) line during examination can be ambiguous, particularly because conditions involving deficiency of aqueous tears (such as Sjögren syndrome 19 or ocular graft-versus-host disease 20 ) yield negative results despite severe signs and symptoms of dry eye. Therefore, we need to know exactly how the results of the kit change as tear volume changes.…”

Section: Introductionmentioning

confidence: 99%

In vitro validation of the tear matrix metalloproteinase 9 in-situ immunoassay

Bang

Son

Kim

et al. 2020

Sci Rep

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We aimed to validate a tear MMP-9 in-situ immunoassay (InflammaDry) and to identify factors that could affect results or interpretation. Three factors were examined: sample concentration, volume, and time. Recombinant human (rh) MMP-9 (10 or 20 μl; 0, 12.5, 25, 50, 100, 200, 500, and 1,000 ng/ml) was applied to the kit and the detection limit and assay reproducibility were examined. At a rhMMP-9 volume of 10 μl (≥ 50 ng/ml), all positive results were identified by densitometry at 10 and 20 min; however, after 20 min, more than half of the nine ophthalmologists interpreted a positive result. At a rhMMP-9 volume of 20 μl (≥ 25 ng/ml), ophthalmologists and densitometry identified almost all test lines at 10 and 20 min. At 10 μl, densitometry showed a linear dose–response pattern. At 20 μl, densitometry showed a linear dose–response pattern at concentrations up to 500 ng/ml; however, full saturation was achieved at concentrations ≥ 500 ng/ml. When the same amount of rhMMP-9 was applied, the density result increased significantly upon doubling of the solvent volume (i.e., by adding the same volume of PBS to a sample). InflammaDry showed a high inter- and intra-assay coefficient of variation at 10 min (28.4% and 24.7%, respectively). The results of the MMP-9 in-situ immunoassay varied significantly depending on sample volume. Therefore, when interpreting the results, careful attention must be paid to tear volume.

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Section: Introductionmentioning

confidence: 99%

In vitro validation of the tear matrix metalloproteinase 9 in-situ immunoassay

Bang

Son

Kim

et al. 2020

Sci Rep

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“…Measuring corneal hysteresis may improve the severity grading accuracy of oGVHD, as corneal biomechanical changes are closely associated with ocular surface inflammation. 81 Arafat, et al found elevated levels of neutrophil elastase, MMP-8 (matrix metalloproteinase) and MMP-9 and myeloperoxidase in tears of patients with oGVHD. 82 Also, certain proteins neutrophil extracellular traps (NET) and NET associated proteins are seen with the ocular surface desiccation, fibrotic eyelid changes and persistent inflammation in oGVHD.…”

Section: Overview Of Chronic Ogvhdmentioning

confidence: 99%

“…Also, a recent prospective study by Giannaccare et al showed measurably different corneal biomechanical changes in corneal hysteresis and resistance factor as compared to controls. 81 They proposed that corneal stromal collagen fibril architecture changes due to oGVHD may lead to these biomechanical changes. Corneal hysteresis and resistance factor may be used as a possible indicator of disease severity and progression in the future.…”

Section: Diagnosis Of Chronic Ogvhdmentioning

confidence: 99%

Chronic Ocular Graft Versus Host Disease: An Update and Review

Groth

Conto

Pasquini

2020

JDED

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An updated comprehensive literature review was completed of chronic ocular graft versus host disease (oGVHD) to identify current and future considerations as to the causes, diagnosis, and treatment of this complication after allogenic hematopoietic cell transplantation (HCT). Graft-versus-host disease involves multiple organ systems, including the eye, and is a leading cause of mortality and morbidity in these patients. This review consisted a comprehensive search of the PubMed, ClinicalTrials.gov and NIH.gov databases. oGVHD is a debilitating and potentially sight threatening condition. Commonly involved ocular structures include the cornea, conjunctiva, meibomian glands, eyelids, lacrimal gland and tear film. Identifying and treating the ocular complications at the early stages may improve final outcomes and quality of life in these patients. Aggressive lubrication, preservation of tear film and inflammation control, including minimizing surface scarring, are treatment goals. Co-management with HCT and other pertinent health care providers is critical for early diagnosis and to initiate prompt therapy to minimize the ocular damage. Stepped therapy, including the use of emerging systemic treatments can be useful in the management of oGVHD with stable visual function, quality of life and complication management as goals of treatment.

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“…Previous immunohistochemical analyses of conjunctival samples disclosed the expression of MMP-9 in severely affected ocular GVHD forms [14]. Moreover, MMP-9 was found to be increased in tears and ocular surface tissues of chronic GVHD patients, compared with healthy subjects [15,16].…”

Section: Introductionmentioning

confidence: 99%

Conjunctival Matrix Metalloproteinase-9 Clinical Assessment in Early Ocular Graft versus Host Disease

Berchicci

Aragona

Arrigo

et al. 2021

Journal of Ophthalmology

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Purpose. Graft versus Host Disease (GVHD) typically affects the ocular surface, with a presentation resembling Dry Eye Disease (DED). Although the etiopathology is not completely known, the conjunctiva might be a key site of T-cell activation. The differential diagnosis might be tricky at early stages, because of the lack of dedicated clinical and laboratory tests. To meet these needs, we evaluated the suitability of ocular surface matrix metalloproteinase-9 (MMP-9) clinical test. Methods. Consecutive GVHD patients, referred to IRCCS San Raffaele Scientific Institute, were recruited. DED patients served as controls. MMP-9 was tested through InflammaDry immunoassay kit in both groups; Ocular Surface Disease Index (OSDI) questionnaire, tear osmolarity, fluorescein Tear Break-up Time (TBUT), corneal and conjunctival staining, and Schirmer test I were also collected. Parametric and nonparametric statistical tests were used to analyze the intergroup differences; Receiver Operating Characteristics (ROC) curve analysis was carried out to perform sensitivity and specificity evaluations. Results. Forty-five GVHD and 40 DED patients were included. MMP-9 expression was significantly higher in GVHD group than in DED (84.4% vs 33%, p ≤ 0.001 ). Corneal and conjunctival staining scores resulted worse in GVHD than in DED (0.95 ± 1.16 vs 0.40 ± 0.63, p = 0.02 ; 0.77 ± 0.42 vs 0.40 ± 0.49, p = 0.0005 , respectively). No significant differences regarded the other collected parameters. GVHD group was characterized by positive correlations between MMP-9 and conjunctival staining (rho = 0.55, p = 0.0002 ) and between MMP-9 and OSDI (rho = 0.3, p = 0.01 ); a faint inverse correlation was found between MMP-9 and Schirmer test (rho = −0.25, p = 0.04 ). Conclusion. MMP-9 has a role in physiologic cellular remodeling; when a proinflammatory stimulus occurs, MMP-9 molecules are overreleased in the extracellular matrix. The positive expression of MMP-9 in GVHD may be interpreted as the consequence of a T-cell aggression against self-antigens and may be considered a reliable biomarker to detect ocular surface inflammation in GVHD, even in early stages of the disease.

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Corneal Biomechanical Alterations in Patients with Chronic Ocular Graft Versus-host Disease

Cited by 6 publications

References 26 publications

In vitro validation of the tear matrix metalloproteinase 9 in-situ immunoassay

In vitro validation of the tear matrix metalloproteinase 9 in-situ immunoassay

Chronic Ocular Graft Versus Host Disease: An Update and Review

Conjunctival Matrix Metalloproteinase-9 Clinical Assessment in Early Ocular Graft versus Host Disease

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