Transcript Measuring Tear Film Osmolarity in Dry

Measuring Tear Film
Osmolarity in Dry Eye
Disease:
A Review of the Literature
Christopher J. Rapuano, MD
Cornea Service, Wills Eye Hospital
Sidney Kimmel Medical College at Thomas Jefferson University
Philadelphia, PA
Richard Potvin, MASc, OD
Science in Vision, Akron, NY
Dr. Rapuano is a consultant for TearLab but received no financial support for this presentation.
Financial support was provided to Science in Vision for conducting this review.
Dr. Potvin has no financial interest in any product mentioned or reviewed.
Purpose
•To evaluate the evidence in the peer-reviewed
literature
– Use of tear osmolarity as a physiological marker to
diagnosis, grade severity, and track therapeutic
response.
– Role of tear osmolarity in the pathophysiology of dry
eye and ocular surface disease.
Methods
•Literature review
– Keyword search: ‘tear osmolarity’
– Abstracts reviewed to ensure
» Relevance to tear osmolarity
» Articles after year 2000 was considered
» Primary focus on tear osmolarity as a diagnostic
tool
Grading the peer-reviewed literature
• GRADE scoring1
GRADE Scoring Criteria
– Sample size
– Financial disclosures
• University of Michigan
guidelines2
– A: Randomized controlled trial
– B. Controlled trials, non randomized
– C. Observational trials
– D. Expert panel opinion
Grading criteria
• Final manuscript grading
– An article was rated in the “High” category if it fulfilled
both the A criteria in the University of Michigan
Practice Guideline and fulfilled the definition in the
“High” requirement under the GRADE system.
– Similarly, B and/or “Moderate”, C and/or “Low”, as
well as D and/or “Very Low” were used from the
University of Michigan Practice Guideline and the
GRADE rating systems respectively to identify the
rating of the relevant articles.
– The final grade was the lower rank based on the 2
grading systems.
• Articles were also reviewed for the conclusion
or impression they left with the reader on use of
tear osmolarity as a diagnostic tool for dry eye
disease: positive / neutral / negative
Results
•164 articles identified as
relevant
•163 available for review
impression
– One foreign language article
excluded
•51/163 articles rated
moderate to high quality
– Randomization, sample size
& control group limited
grading
•3/163 not graded, could
not be obtained for review
– Author reply (1), unknown
source (2)
Topic
# of
articles
Total articles on tear
osmolarity
407
Published in 2000 or
later
271
Osmolarity used as
diagnostic tool
164
Final grading /
impression
163
Results - Osmolarity in dry eye diagnosis
• 51 articles graded high to moderate quality
• 73% (37/51) had a positive impression
• 10% (5/51) had a negative impression
Rated
Not Rated
(3)
Impression/Quality
High
(1)
Moderate
(50)
Total High/Moderate
(51)
Low
(105)
Very Low
(4)
Positive (117/163 or 72%)
1
36
37 (73%)
74
3
3
Neutral (35/163 or 21%)
0
9
9 (18%)
26
0
0
Negative (11/163 or 7%)
0
5
5 (10%)
5
1
0
• Financial support
• 72% (117/163) of all articles had a positive impression
• 72% (75/104) of independent articles had a positive
impression vs 7% (7/104) that were negative
Impression/Funding
Independent (104)
TearLab (12)
Other (19)
Not Disclosed (28)
Positive (117/163 or 72%)
75 (72%)
12
12
18
Neutral (35/163 or 21%)
22 (21%)
0
6
7
Negative (11/163 or 7%)
7 (7%)
0
1
3
Results–Osmolarity in DED diagnosis
• Objective single value metric for diagnosis and grading
severity of DED3-6
– Core mechanism in dry eye regardless of the disease
process7
» Normal subjects have low and stable osmolarity
» DED subjects have elevated and unstable readings, which increases with
disease severity8,10,11
» Does not distinguish aqueous deficient vs evaporative DED3,8,9
– Variability in measurement between eyes is an indicator of
DED severity8
• Good accuracy and repeatability
– Variance ranging from 0.8%12 - 2.9%13
– No significant inter-observer or inter-instrument variability14
• Threshold values
– Specificity and sensitivity of test dependent on cutoff value
used6,15-18
– 308 mOsm/L is reported to have most sensitive value3,5,8,16
– 315 mOsm/L is reported to have more specificity5
Tear osmolarity – Ocular/systemic conditions19-38
Condition
Increased No increased
osmolarity
osmolarity
(# of
(# of
articles)
articles)
Ocular mucous
membrane
pemphigoid
1
Medicated & posttrabeculectomy
1
Unilateral HSV
1
Pterygium (& reoccurrence)
Condition
Increased
osmolarity
(# of
articles)
No increased
osmolarity
(# of
articles)
Sjogren’s
syndrome
2
Graft vs host
disease
1
Diabetes
3
1
2
Early
rheumatoid
arthritis (nontreated)
Pseudoexfoliation
1
Fibromyalgia
1
Conjuctivochalasis
1
Post-menopause
1
Thyroid
ophthalmopathy
2
Oestradiol,
oesterone, total
testosterone
1
Nasolacrimal
obstruction
1
Keratoconus
1
Epiphora
1
Results–Osmolarity in DED therapy
• DED treatment tracker
– Signs and symptoms of DED are often uncorrelated29,39-44
– Effective treatment is evidenced by low and stable
osmolarity11
– Osmolarity offers lower variability vs. other DED tests
over a 3 month period11
» Staining and MGD grade
– Different effects on osmolarity measured and reported
with regard to application of different eye drops45-64
– “Change in osmolarity” is a leading indicator of
therapeutic efficacy8,11,40,53
» Precedes change in subject symptoms
» May precede changes in ocular surface staining
Effect of tx on osmolarity8,11,21,45-51,54-64
Treatment
Reduction in
osmolarity
(# of articles)
No reduction in
osmolarity
(# of articles)
Anti-inflammatory (cyclosporine/Restasis)
2
2
Lubricating eye drops (artelac, AT)
4
3
Topical 1% methylprednisolone &
preservative-free 0.1% sodium hyaluronate
1
LipiFlow
1
Switching to preservative free glaucoma
drop
2
Cord blood serum
1
Allogenic serum
1
Punctal occlusion
1
Phytoestrogen (steroid hormone)
1
Oral contraceptives
1
Azithromycin
1
Conclusion
• Systematic review of peer-reviewed literature
– 72% (117/163) of all articles communicated a positive
impression of tear osmolarity in DED diagnosis
» 7% (11/163) reported negative of role for osmolarity in DED
– 73% (37/51) of articles graded high/moderate quality
supported osmolarity in DED diagnosis
» 10% (5/51) had a negative impression
– 72% (75/104) of all independent articles (no corporate
funding) had a positive impression
» 7% (7/104) had a negative impression
– Of the 32 independent articles graded high/moderate
quality
» 72% (23/32) had a positive impression
» 9% (3/32) had a negative impression
• Tear osmolarity is an objective numerical
measure for diagnosis, grading severity, and
treatment monitoring of dry eye disease
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