The Phoenician Connection: Translating the Emerging Diagnostics for OSD

Understanding how to bridge the gap with technology.

By Michael S. Cooper, OD

Is it the chicken, the turkey, or the turducken? This portmanteau is quite apropos considering many optometrists and ophthalmologists have been debating for decades on whether to choose history, signs, test results, or a composite as their methodology for diagnosising ocular surface disease. Although leading experts in our profession such as Drs. Christopher Rapuano and Terrence O’Brien acknowledge there is still no gold standard, the tide is beginning to shift in a more focused technological direction.1 Furthermore, the advent of research and of device manufacturers’ interest in the field have spurred an explosion of new diagnostic tools for the eye care community.

The conundrum becomes how to use these sophisticated devices in our everyday practice to ensure both diagnostic efficiency and specificity. With the baby boom generation continuing to mature and dry eye disease’s (DED) prevalence likely to increase 10.2% during the next 10 years in the United States alone, the challenge is to adroitly embrace these technologies.2,3 Subsequently, the purpose of this article is to introduce eye care specialists to these current and future instruments.

THOSE UNABLE TO CATALOG THE PAST ARE BOUND TO REPEAT IT

As a child, my father repeatedly used this expression to remind me never to forget the past. The sentiment left an indelible mark on me, and as I progressed through my training, I linked this life lesson to the pillar that there is absolutely nothing that can substitute a good case history. The “story” has to have a beginning that allows the eye care provider to connect the facts to the data, thereby allowing for the proper diagnosis. Luckily, there have been some excellent tools developed during the past 20 years such as the Ocular Surface Disease Index (OSDI) and Standard Patient Evaluation of Eye Dryness (SPEED) to assist eye care practitoners in obtaining symptom- and sign-based information.4-7

The OSDI was developed by the Outcomes Research Group (Allergan) as a 12-item questionnaire designed to provide a snapshot of the symptoms of ocular surface irritation and discomfort consistent with DED and their visionrelated functional impact. The initial OSDI items were formulated by using patient comments from several years of clinical studies conducted by Allergan, several quality-of-life instruments, and suggestions from clinical investigators. The original questionnaire included 40 items of which were later reduced to the final 12 questions on the basis of validity and reliability data from three groups consisting of DED patients and phase 2 clinical trial data.8

Clinically, the OSDI opens up what I refer to as the “eye surface optimization” conversation between the patient and doctor. An excellent strategy to employ the questionnaire is to fold it into a technician’s workup for an initial DEDfocused visit to educate patients regarding the true nature of their symptoms. Subsequently, the data empower the doctor to treat the pateint medically with myriad products such as Restasis (cyclosporine ophthalmic emulsion 0.05%; Allergan), Lotemax Gel (loteprednol etabonate ophthalmic gel 0.5%; Bausch + Lomb), Cliradex (tea tree oil derivative; Bio-Tissue), azithromycin (AzaSite; Akorn and Zithromax; Pfizer), and Prokera and AmbioDisk (Bio-Tissue and IOP Ophthalmics) amniotic membranes to achieve a rapid result. In addition, by staying proactive, the disease state can be both stabilized and properly managed with far more confidence in patient success when compared to solely using multiple artificial tear agents.9

The caveat to the feedback obtained within this analysis is the discordance between the signs and symptoms of DED. The OSDI was shown to have excellent specificity in determining normal versus DED individuals with more preferential alignment clinically to symptoms rather than signs.4 This limitation impedes the test’s functionality because patients tend to blend their subjective experience of disease severity. Consequently, the ability to capture the sensitivity of ocular surface and tear abnormalities can be potentially muddled depending on the clinical situation.4,10

Enter the relatively new SPEED questionnaire developed at TearScience by Caroline Blackie, PhD, Donald Korb, OD, and their research team. It is a substantial improvement because it is more direct in procuring the information as a chief screening tool. The assessment measures the frequency and severity of patients’ DED symptoms by examining the occurrence of symptoms on the current day, past 72 hours, and past 3 months. Ngo et al illustrated that SPEED score also correlated significantly with ocular surface staining and clinical measures of meibomian gland function.6

By compressing the time taken to obtain the test results with four simple questions, patients’ confusion is significantly reduced, which in turn improves SPEED’s utility for diagnosing OSD. Similar to the OSDI, SPEED can be easily administered while the patient is in the waiting room or it can be merged into the technician’s workup in approximately 2 minutes.5-7 The final take-away message from this survey is simply to enhance the patient’s experience by allowing him or her to connect with the doctor in an efficient and less stressful manner.

THERE IS NOTHING MORE TRANSPARENT THAN AN OBVIOUS FACT

The ancient Phoenicians spread the alphabet throughout the Mediterranean via their maritime trade to improve their ability to communicate with other cultures. The eye care community is seeing a similar situation unfold in terms of new diagnostic equipment.11 With a vast array of test information to drive treatment, here I consider several instruments that show tremendous promise in developing an ongoing ocular surface language. The journey will begin with chemistry, traverse through the grounds of objective digital analysis, and conclude with a novel in-office conjunctival harvesting method.

THE CHEMISTS: Tearlab AND Inflammadry

Dating back to the 2007 Dry Eye Workshop, it has been well established that osmolarity plays a role in ocular surface inflammation.12 The TearLab Osmolarity System (TearLab) fills this space with an easy-to-perform test without the need for topical anesthesia. In addition, the objective results are concrete and available within 10 seconds, allowing the clinician to share the findings with the patient. A recognized diagnostic normal cutoff for DED is 308 mOsm/L in the mild state, to 316 mOsm/L in the moderate state, and up to 400 mOsm/L in the severe state.13

A clinical pearl that I have found helpful in calibrating my TearLab data from visit to visit is to remind the patient to not instill any drops prior to performing the test in the office within 2 hours. Osmolarity is in essence a salinity test, and most topical medications and lubricants contain buffers/prepreservatives that interfere with the quality of the information.

Another important point is that test accuracy can be variable due to the inflammatory state of the ocular surface from intrinsic (ie, systemic autoimmune disease) or extrinsic (environmental/lifestyle) etiology.12,13 In my perspective, TearLab fits into a treatment protocol analogous to intraocular pressure measurements for glaucoma management by providing longitudinal records. Although the assessment might not lead one necessarily to diagnose the disease state, it can guide the clinician in counseling and promoting adherence to the treatment plan.

An additional indication of ocular surface inflammation can be found with the detection of matrix metalloproteinase 9 in the tear film, a known biomarker associated with DED.14 In March 2014, InflammaDry (Rapid Pathogen Screening or RPS) received a US Food and Drug Administration Clinical Laboratory Improvement Amendments or CLIA waiver.15 Similar to TearLab, the test can be administered with ease by the technical staff. A significant difference is in the data collection, as the results are produced after a minimum of 10 minutes. Subsequently, if the doctor or technical staff suspects DED, it would be reasonable to perform the test in the initial workup to ensure the interpretation is shared with the patient by the conclusion of the examination.

The test has a sensitivity and specificity of 85% and 94%, respectively.16 When interpreting the sample, the eye care specialist should look for a pink line; the intensity of the color indicates the severity of the condition. From my clinical experience with the instrument, it is important to realize that if the patient is already on antiinflammatory therapy, the result has a good chance of not “lighting” up the pink segment due to a lack of matrix metalloproteinase 9 in the tear gel. Although this might seem discouraging at first blush, it is actually an indication that the treatment is likely mediating the patient’s condition. Consequently, the InflammaDry can be used for both the early detection and ongoing measurement of therapeutic efficacy.

OBJECTIVITY IS THE NAME OF the TEAR GAME: TEAR STABILITY ANALYSIS SYSTEM

One key stumbling block in diagnosing DED has always been the instability of the tear film. Instability is found in all DED-related problems including meibomian gland dysfunction, conjunctival chalasis, and Sjögren syndrome— whether there is a low tear volume or not.17,18 The RT-7000 Autorefractor-Keratometer (Tomey) instrument helps to measure tear quality and quantity with the noninvasive Tear Stability Analysis System or TSAS. The test runs for a total of 6 seconds by utilizing a digital objective analysis with Placido disk-like rings to gauge bright points and spots to detect corneal surface irregularity.19

Additionally, the literature illustrates TSAS to be reliable for identifying mild to severe levels of DED. The more clinically severe the DED, the more rapidly the irregularity score increased for which can be transformative and useful in exposing early-onset disease.19 Moreover, the test could potentially be performed on every patient and hypothetically eliminate the need for fluorescein staining. There is an overarching financial issue for many practices. How will doctors be able to substantiate a piece of equipment where there is no known reimbursed or billing code even though it is FDA approved? At this time, the instrument appears destined to be employed primarily in the research setting; however, it would not be surprising to find the system permeating into larger DED and refractive surgery practices in the near future to improve the overall efficiency of patient flow.

THE NEXT GENERATION: EYEPRIM

An exciting new avenue that is chiefly being used in clinical trials at the moment is a novel in-office cytology method called EYEPRIM (Opia Technologies). Currently, the device simply harvests cells from the superficial bulbar conjunctival surface in a quick and painless manner to assess a considerable assortment of inflammatory biomarkers. The sterile, single-use pack can procure a sample within a few seconds and yield two to five times more cells than the old impression cytology procedure.1,20

There is tremendous potential for advancement in DED diagnosis with this system because it can also retrieve goblet cells. The implication of obtaining this particular cell type is powerful considering it has a significant correlation with DED severity. Furthermore, clinical success with topical medications could be measured with improved goblet cell density beyond current slitlamp techniques with EYEPRIM.

BEING PROACTIVE: A SHARP KNIFE IS NOTHING WITHOUT A SHARP EYE

Diagnostic testing began to revolutionize glaucoma care during the past 2 decades, which sharpened eye care specialists’ ability to diagnose and manage these patients. The next phase of OSD diagnostic equipment is in at an early, but truly electrifying evolutionary stage. These devices will continue to be honed to help doctors share with patients more concrete and rapid information about their condition rather than abstract detail. Subsequently, the tangible information generated from new instrumentation will allow eye care providers to diagnose patients sooner, prevent ocular damage, and enhance patients’ experiences.

Michael S. Cooper, OD, is in private practice at Windham Eye Group in Willimantic, Connecticut. He is a consultant to Allergan, BioTissue, Epocrates, TearLab, and Vistakon, and has received past honoraria from Alcon and inVentiv Health. Dr. Cooper may be reached at coopadre@gmail.com.

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