Correlation of Conjunctival and Corneal Staining With Elevated Matrix Metalloproteinase-9 on the

Ocular Surface of Dry-Eye Patients

Authors:Allister Gibbons, MD Felipe Valenzuela, MDDaniel Waren, MSPHVictor L. Perez, MD

The authors have no financial interests to disclose, relevant to the topic of this poster.

Paper #13545

Introduction• Dry eye is a multifactorial disease of the tears and

ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface.1

1The Definition and Classification of Dry Eye Disease: Report of the Definition and Classification Subcommittee of the International Dry Eye Work Shop (2007). Ocul Surf. 2007 Apr;5(2):93-107.

Introduction• Ocular surface inflammation is both a marker

for dry eye and is also involved in its pathophysiology

• Matrix Metalloproteinase-9 (MMP-9) is one of the main mediators identified in the inflammatory cascade associated with dry eye

Pflugfelder SC, et al. Dry eye and delayed tear clearance: "a call to arms". Adv Exp Med Biol. 2002;506(Pt B):739-43.

Purpose

• To evaluate the clinical correlation between a point-of-care MMP-9 immunoassay with ocular surface staining and other objective tear film and subjective ocular surface parameters

Methods

• Retrospective non-comparative case series– Included all patients referred for dry eye.• 82 Eyes of 41 patients (70.7% women)

–All received a full dry eye evaluation– Eye with highest score on dry eye battery

testing was used for analysis

Methods - Staining• Corneal Fluorescein Staining– 10 ul 1 % Fluorescein – Scored from 0-3 (per quad) at 2’

• Conjunctival Staining– 15 ul 1% Lissamine Green– Each sector scored from 0-3 at 2 minutes

Methods – MMP 9• The commercially available MMP-9

kit comes calibrated to indicate a positive response when levels are > 40 ng/ml

• The sampling fleece is saturated in the patient’s tear from the inferior fornix and then left in the test cassette for 10 minutes.

ResultsOcular surface test n (%)

OSDI > 12 36 Patients (87.8%)

TBUT < 10 sec 79 Eyes (96.3%)

Schirmer’s < 10 sec 35 Eyes (42.7%)

Osmolarity > 316 mOsm/L 53 Eyes (64.6%)

MMP 9 (+) 24 Eyes (29.0%)

Unilateral (+) 8 patients (19.5%)

Bilateral (+) 8 patients (19.5%)

OSDI = Ocular Surface Disease Index // TBUT = Tear Break-Up Time

ResultsMMP (-) MMP (+) p value

Fluorescein Stain 3.4 ± 3.4 8.6 ± 4.2 <0.001

Lissamine Green Stain 6.0 ± 4.2 12.0 ± 4.9 <0.001

OSDI 48.0 ± 25.6 50.5 ± 26.2 NSS (0.76)

Osmolarity (osm) 337.5 ± 26.2 336.0 ± 25.0 NSS (0.89)

Schirmer’s test (mm) 11.6 ± 8.3 10.13 ± 7.6 NSS (0.59)

TBUT (sec) 4.2 ± 2.6 3.8 ± 1.1 NSS (0.51)

Age (years) 57.48 ± 13.5 60.38 ± 14.5 NSS (0.52)

OSDI = Ocular Surface Disease IndexTBUT = Tear Break-Up Time

Results

Results• There was a strong correlation with having more

ocular surface staining and a positive MMP 9 test.

• If the test was unilaterally positive for MMP 9– The eye with higher test scores was the one positive

• No adverse effect from testing was observed

Conclusion• Detection of supra-threshold MMP-9 levels

correlates significantly with ocular surface staining• This supports evidence that there is an underlying

inflammatory process ongoing in the ocular surface of these eyes

• Detection of ocular surface inflammation can be used clinically to guide anti-inflammatory therapy in dry eye patients