CAM 155

InflammaDry Test

Category:Laboratory   Last Reviewed:April 2019
Department(s):Medical Affairs   Next Review:April 2020
Original Date:December 2016    

Description
The Inflammadry test from Rapid Pathogen Screening test the tears for the enzyme known as matrix metalloproteinase-9. The company says MMP-9 on the ocular surface is a sign of Inflammation, and that its presence means that a dry-eye patient may respond to anti-inflammatory therapy.

Background 
Dry eye disease, or dysfunctional tear syndrome, is an extremely common condition that is often underdiagnosed. According to the report of the Epidemiology sub-committee of the International Dry Eye Workshop, 2007, it affects 5-30% of the population ages 50 and over. InflammaDry® is the first and only, rapid, in-office test that detects MMP-9, an inflammatory marker that is consistently elevated in the tears of patients with dry eye disease (Chotikavanich et al., 2009).  

The Test
The Inflammadry test doesn’t provide a quantitative result, just basically a yes or a no. The test uses a sample of tears and takes less than 2 minutes to complete, with results available in 10 minutes. To administer the test, the tech or physician collects a tear sample, then activates it with a buffer solution. In 10 minutes, the test will either show a solitary blue line, indicating a negative result, or a blue line accompanied by a red line, which is positive (figure below). The test uses 40 μg/ml of MMP-9 as a cutoff point; anything above that will yield the red line, anything below will register as negative.

Literature Review
In a study partially sponsored by RPS (published in Review of Ophthalmology, Nov. 2014), researchers analyzed 46 dysfunctional tear syndrome patients and 18 controls. They found significantly higher mean MMP-9 activity in the test groups (as high as 381.24 μg/ml for one group) than in the controls, which registered a mean of 8.39 μg/ml. The researchers say that the MMP-9 levels showed significant correlation with symptom severity scores, decreased low-contrast visual acuity, fluorescein tear breakup time, corneal and conjunctival fluorescein staining, topographic surface regularity and the percentage area of abnormal superficial corneal epithelia.

"InflammaDry will help clinicians confirm the diagnosis of dry eye before the patient leaves their office, resulting in more timely and appropriate management of their disease," Robert Sambursky, M.D., chief executive officer, president and chairman of RPS, said in a news release (Megan Brooks, Dec. 2, 2013).

Reached for outside comment, Glenda Secor, OD, communications chair of the American Academy of Optometry, told Medscape Medical News, "This is a pretty good test. It delineates whether the eye doctor should use an anti-inflammatory drug like a steroid or Restasis [cyclosporine, Allergan] for the patient with dry eye, with pretty good reliability." Dry eye is a "common complaint," she added, "one that increases with age," and "all tools are valuable; professional judgment is still key in differentiating etiology and determining proper treatment plans to maximize outcomes," Dr. Secor said. 

"The big issue," she told Medscape Medical News, "is that it is not reimbursable by insurance and if patients will pay for the additional testing out of pocket is unknown (Megan Brooks, 2013)."

RPS said the 510(k) clearance allows the InflammaDry test to be used in physician offices that are certified to perform moderately complex tests under the Centers for Medicare & Medicaid Services' Clinical Laboratory Improvement Amendments (CLIA).

Dr. Darrell E. White, in his article, ‘Turning results into action: InflammaDry vs. Tear Osmolarity" (Ocular Surgery News, July 24, 2014) observes that, essentially, anyone who would have a Tear Osmolarity (TearLab) test performed is also getting an InflammaDry (Rapid Pathogen Screening) test. "We are trying to determine several very important things — namely, who should be tested and what do the results mean? Here’s what we have come up with so far:

"The InflammaDry gives us complimentary, but not duplicative, information when mated with Tear Osmolarity. We are still parsing the data, but it appears we are receiving enough actionable information from both positive and negative results that we do not feel it is time to start paring down our protocol. For the time being, we will continue to do both tests whenever our protocol calls for Tear Osmolarity."

Dr. White further comments that, "How to turn the results into action is a bit trickier. A positive result for the presence of MMP-9 seems to mean different things in different settings. For example, a patient with dry eye syndrome symptoms, low tear osmolarity, a borderline tear breakup time and a positive InflammaDry test now pushes us to treat meibomian gland dysfunction as the primary culprit, whereas a negative result pushes us more toward an ocular surface source. For example, InflammaDry Rx protocol v1.0 is giving us some better scientific justification for the prescription of Azasite (azithromycin ophthalmic solution 1%, Akorn).

"In all likelihood, the 'how we use the results' part of our evaluation will drive the 'who do we do the test on' part of our protocol."

Sambursky R. et al. (2013) in a study Sensitivity and specificity of a point-of-care matrix metalloproteinase 9 immunoassay for diagnosing inflammation related to dry eye, studied the clinical sensitivity, specificity, negative predictive value and positive predictive value of a rapid point-of-care diagnostic test to detect elevated matrix metalloproteinase 9 levels (InflammaDry). The results showed InflammaDry had sensitivity of 85% (in 121 of 143 patients), specificity of 94% (59 of 63), negative predictive value of 73% (59 of 81) and positive predictive value of 97% (121 of 125).The authors concluded that "compared with clinical assessment, InflammaDry is sensitive and specific in diagnosing dry eye."

APPLICATION TO CLINICAL PRACTICE
Dry eye is often underdiagnosed, resulting from poor communication between the clinical assessment of dry eye severity between clinicians and patients. This often leads to a lack of effective treatment. Matrix metalloproteinase 9 is an inflammatory biomarker that has been shown to be elevated in the tears of patients with dry eyes. The clinical benefits may be summarized as follows:

  • The ability to accurately detect elevated matrix metalloproteinase 9 levels may lead to earlier diagnosis, more appropriate treatment and better management of ocular surface disease.
  • Preoperative and perioperative management of inflammation related to dry eyes may reduce dry eyes that develop after laser in situ keratomileusis, improve wound healing and reduce flap complications.
  • Recognition of inflammation may allow for targeted perioperative therapeutic management of care for patients who undergo cataract and refractive surgery and improve outcomes.
  • Reduce post-surgical complications, such as corneal wound healing, by identifying dry eye prior to surgery.
  • Therapeutic treatment of dry eye will improve patient quality of life.

The Southern College of Optometry (SCO) states that "InflammaDry is the first and only rapid, in-office test that detects MMP-9, an inflammatory marker that is consistently elevated in the tears of patients with dry eye disease. Using direct sampling microfiltration technology, InflammaDry accurately identifies elevated levels of MMP-9 in tear fluid samples taken from inside of the lower eyelid, the palpebral conjunctiva" (SCO website accessed in August 2016).

c. Applicable Federal Regulations
The US Food and Drug Administration (FDA) has approved a rapid in-office test for diagnosis of dry eye disease called InflammaDry, the developer Rapid Pathogen Screening Inc. (RPS) of Sarasota, FL, has announced (Megan Brooks, Dec. 2, 2013).

Rapid Pathogen Screening, Inc. (RPS) announced that it has received a Clinical Laboratory Improvement Amendments (CLIA) waiver from the FDA for InflammaDry – a rapid, disposable, in-office test to aid in the diagnosis of dry eye disease, according to a company news release (RPS, Feb 27, 2014).

Obtaining the CLIA waiver, in addition to its FDA 510(k) clearance, enables the InflammaDry test to be used throughout the United States, an expansion from its current use internationally. CLIA waived status is granted to tests that are simple to perform and have an insignificant risk of producing an erroneous result. The InflammaDry test can be administered by any medical office personnel in health care facilities with a CLIA Certificate of Waiver.

The InflammaDry test is CE-marked, 510(k) cleared and commercially available in Europe, Canada and many countries throughout the rest of the world. Per RPS, InflammaDry inventory is available for sale in the United States from March 2014

Policy 
Testing for MMP-9 protein in human tears IS NOT MEDICALLY NECESSARY to aid in the diagnosis of patients suspected of having dry eye disease based on comprehensive eye examination.

Testing of tear osmolarity in patients suspected of having dry eye IS NOT MEDICALLY NECESSARY to aid in determining the severity of dry eye disease, as well as to monitor effectiveness of therapy.  

Testing for lactoferrin and/or IgE to aid in the diagnosis of patients suspected of having dry eye disease IS NOT MEDICALLY NECESSARY.

All other testing used in the diagnosis of patients suspected of having dry eye disease IS NOT MEDICALLY NECESSARY.

References 

  1. Chotikavanich S, de Paiva C, Quan Li D et al, production and activitry of matrixmetallo proteinase-9 on the ocular surface increase in dysfunctional tear syndrome; Invest Opthalmol Vis Sci 2009;50:7:3203
  2. Darrell E White, Ocular Surgery News; July 24, 2014; link
  3. Kaufman HE. The practical detection of MMP-9 diagnoses ocular surface disease and may help prevent its complications. Cornea. 2013 Feb;32(2):211-6.
  4. Megan Brooks, FDA Clears Rapid Test for Dry Eye Disease; Medscape Medical News; Dec 02, 2013; link
  5. Review of Ophthalmology, Nov 2014; link
  6. RPS Receives CLIA waiver for InflammaDry test for Dry Eye disease; link
  7. Sambursky R, Davitt WF 3rd, Latkany R, Tauber S, Starr C, Friedberg M, Dirks MS, McDonald M.; Sensitivity and specificity of a point-of-care matrix metalloproteinase 9 immunoassay for diagnosing inflammation related to dry eye; JAMA Ophthalmol. 2013 Jan;131(1):24-8. doi: 10.1001/jamaophthalmol.2013.561. link
  8. Rob Sambursky, MD; Eye World; (2013) link
  9. Southern College of Optometry website, accessed Aug, 2016 link

Coding Section  

Code Number Description
CPT  82785  Gammaglobulin (immunoglobulin); IgE 
  83516 Immunoassay for analyte other than infectious agent antibody or infectious agent antigen; qualitative or semiquantitative, multiple step method
  83520  Immunoassay for analyte other than infectious agent antibody or infectious agent antigen; quantitative, not otherwise specified 
  83861  Microfluidic analysis utilizing an integrated collection and analysis device, tear osmolarity 
ICD-10 Diagnoses Codes All H04.12 Codes Dry eye syndrome
  H53.141-H53.149    Visual discomfort 
  H53.8   Other visual disturbances  
  H57.10- H57.13  Ocular pain 
  H57.89  Other specified disorders of eye and adnexa 

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each Policy. They may not be all-inclusive. 

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross and Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

"Current Procedural Terminology© American Medical Association.  All Rights Reserved" 

History From 2016 Forward     

04/03/2019 

Annual review, no change to policy intent, but, expanding specificity of tests that are not medically necessary. Also updating coding. 

04/17/2018 

Interim review, month of review changed, no other changes. 

12/04/2017 

Interim Review. Updated policy section. No other changes made.

10/19/2017 

Annual review, no change to policy. 

 04/26/2017

Updated category to Laboratory. No other changes.

12/05/2016

New Policy


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