Matrix Metalloproteinase 9 Point-of-Care Immunoassay Result Predicts Response to Topical Cyclosporine Treatment in Dry Eye Disease

Park, Jae Yong; Kim, Bum Gi; Kim, Jae Suk; Hwang, Je Hyung

doi:10.1167/tvst.7.5.31

Cited by 53 publications

(55 citation statements)

References 31 publications

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“…These results are consistent with the results herein, which show that tear volume plays an important role in positive results generated by the MMP-9 immunoassay. A previous study examined the utility of the MMP-9 in-situ immunoassay for predicting responses to antiinflammatory treatments in dry eye patients with confirmed ocular surface inflammation 44 . The authors used semi-quantitative evaluation of band density to distinguish the severity of inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…MMP-9 participates in remodeling of the extracellular matrix after wounding of the corneal surface and is implicated in the pathogenesis of sterile corneal ulceration, ocular allergy, fungal keratitis, burns, advanced keratoconus with irregular surface, active pterygia, conjunctivochalasis, blepharitis, and dry eye [9][10][11][12][13][14][15][16] . In addition, MMP-9 levels in cases of dry eye or keratoconus are used to guide the decision to use anti-inflammatory treatments such as topical cyclosporine 9,17 . The MMP-9 immunoassay is a type of lateral flow immunoassay (LFIA).…”

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confidence: 99%

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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: Discussionmentioning

confidence: 99%

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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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“…Normal MMP-9 levels (ng/ml) in human tears vary between 3 ng/ml and 40 ng/ml. The InflammaDry test has a sensitivity of 85% and a specificity of 94% in the detection of pathological levels of MMP-9 in tears [11] In previous studies, elevated levels of MMP-9 in patients with moderate to severe dry eye disease has been correlated with the severity and intensity of the symptoms and the corneal alterations of these patients, and the reduction in these with good response to the treatments [5] [6] [7]. MMP-9 plays a role in the regulation of corneal epithelial desquamation.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have shown a correlation between tear MMP-9 levels and the various clinical and anatomical parameters of dry eye, especially the Ocular surface disease index (OSDI), conjunctival staining and corneal staining. Several studies have also demonstrated a significant reduction in tear MMP-9 levels, indicated by a negative InflammaDry test, following different anti-inflammatory treatments such as corticosteroids, tacrolimus and topical cyclosporine [6] [7].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Isotonic Seawater Solution on Inflammation of the Ocular Surface in Matrix Metalloproteinase MMP-9-Positive Dry Eye Disease Patients

Manuel¹,

Dolores²,

Diaz-Guiñon³

et al. 2020

OJOph

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Purpose: Prospective study to evaluate the anti-inflammatory efficacy of isotonic seawater solution on metalloproteinase 9 (MMP-9) levels in the tears of patients with dry eye disease (DED). Methods: A total of 50 patients were included, with the following dry eye criteria in both eyes: InflammaDry ® test initially positive, ocular surface disease index (OSDI) score ≥ 12 and <33, tear film breakup time (TBUT) ≤ 10 seconds, Shirmer I test result ≤ 10 mm/5 minutes, corneal staining ≥ 1. Additionally, all the patients selected corresponded to a dry eye type 2-3 severity degree-mild and moderate-Dry Eye Workshop Study (DEWS) classification. The InflammaDry test is used to measure levels of MMP9 at the beginning and the end of the study. All patients were treated exclusively with isotonic seawater solution 5 times a day for 3 weeks. Results: The InflammaDry test was positive in 100% of the patients (n = 50) and in 100% (n = 100) of the eyes before treatment. In 14 (28%) patients the test became negative in both eyes, and in 15 (30%)

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“…In the pathology of DE, from the initiation of tear hyperosmolarity in the early phase of DE, a vicious cycle of DE likely induces inflammatory processes and triggers the release of MMP-9 in a relatively late phase of DE [12]. As detection of elevated tear MMP-9 could be an ideal tool for diagnosis and management of DE, a tear MMP-9 immunoassay could be valuable to clinicians [13].…”

Section: Introductionmentioning

confidence: 99%

Importance of tear volume for positivity of tear matrix metalloproteinase-9 immunoassay

et al. 2020

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The tear matrix metalloproteinase-9 (MMP-9) immunoassay (Inflammadry) exhibits variable results in dry eye (DE) patients. We investigated if the tear volume in DE patients affects the results of MMP-9 immunoassay in clinical and in vitro settings. This cross-sectional study enrolled 188 eyes of 188 DE patients. The clinical symptoms and signs of DE were assessed using the Ocular Surface Disease Index and visual analog scale, strip meniscometry, tear break-up time, and tear meniscus height (TMH), area (TMA), and depth (TMD) using swept-source optical coherence tomography and corneal and conjunctival staining scores. For quantitative evaluation, the bands produced by the InflammaDry test were analyzed with ImageJ. DE subjects were grouped according to MMP-9 positivity and TMH. The InflammaDry-positive group showed greater TMH, TMA, and TMD than the MMP-9-negative group (p < 0.05). InflammaDry test band density in the high TMH group was significantly greater than that in the low and normal TMH groups (p < 0.05). InflammaDry test band density correlated positively with TMH, TMA, and TMD (all p < 0.05). InflammaDry test results were influenced by tear volume. Low tear volume in aqueous tear-deficient DE may induce false-negative results, and reflex tearing during the test may induce false-positive results.

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Matrix Metalloproteinase 9 Point-of-Care Immunoassay Result Predicts Response to Topical Cyclosporine Treatment in Dry Eye Disease

Cited by 53 publications

References 31 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

Efficacy of Isotonic Seawater Solution on Inflammation of the Ocular Surface in Matrix Metalloproteinase MMP-9-Positive Dry Eye Disease Patients

Importance of tear volume for positivity of tear matrix metalloproteinase-9 immunoassay

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