Download A Clinical and Research Perspective of Dry Eye and Contact Lens

1/20/2017
What’s New, What’s Different:
A Clinical and Research
Perspective of Dry Eye and Contact Lens Wear
David Kading, OD, FAAO, FCLSA
Andrew Pucker, OD, PhD, FAAO
Two Primary Forms of Dry Eye
What is Contact Lens Discomfort?
Definition: “Contact lens discomfort is a condition characterized by episodic or persistent adverse ocular sensations related to lens wear, either with or without visual disturbance, resulting from reduced compatibility between the contact lens and the ocular environment, which can lead to decreased wearing time and discontinuation of contact lens wear.” The Tear Film Has Two Layers
• Aqueous deficient dry eye (DEWS, 2007)
Non‐Polar Lipids (Pucker, 2012)
• Prevents evaporation
– Typically lachrymal gland deficiency, which results in decreased tear production
Polar Lipids (Pucker, 2014)
• Creates interphase
Creates interphase
• Evaporative dry eye (DEWS, 2007)
– Typically meibomian gland dysfunction, which results in decreased tear volume from evaporation • Evaporative dry eye is 3‐6x more prevalent than aqueous deficient dry eye (Lemp, 2012)
• Both forms can be simultaneously exist (Lemp, 2012)
Image: http://eyeopia.blogspot.com/2013/01/keratitis‐dry‐eye‐blurry‐vision.html
Meibum Lipids
Table 3. Type and amount of lipids present in the meibum.
Lipid
Free Fatty Acids
Wax Esters
Cholesterol Esters
Diesters
Free sterols
Monoglycerides
Diglycerides
Triglycerides
Hydrocarbons
Phospholipids
Sphingolipids
Hydroxy Fatty Acids
Polarity
Nonpolar
Nonpolar
Nonpolar
Nonpolar
Nonpolar
Nonpolar
Nonpolar
Nonpolar
Nonpolar
Polar
Polar
Polar
log P
0.09-14.55
12.41
12.38
12.40
6.73
4.28
9.37
14.46
9.47
5.29
9.12
4.32
Amount
0.0-10.4% 1,5,9,13-18
25.0-68.0%1,10,12,13,63,77
0.0-65.0% 1,5,14,16,19,20,64,80
2.3-17.6% 1,16,18,80
Trace-30.0%1,13,15,16,18,21,80,81
Trace-2.6% 6 9,13
Trace-3.3% 6,9,13
Trace-9.0% 1,6,9,13-16,18,21,64,80
Trace-7.5% 1,9,13,14,23,75
0.0-14.8% 1,14,24,64
Unknown14,25,26
Trace-3.5% 5,27,28,64,80
Meibomian Gland Dysfunction (MGD)
MGD is “a chronic, diffuse abnormality of the meibomian glands, commonly characterized by terminal duct obstruction and/or qualitative/quantitative changes in glandular secretion. It may result in alteration of the tear film symptoms of eye irritation
result in alteration of the tear film, symptoms of eye irritation, clinically apparent inflammation, and ocular surface disease.” (Nichols, 2011)
Pucker, 2012
Image: http://boomerhealthinstitute.com/can‐you‐self‐heal‐your‐chronic‐pain/
1
1/20/2017
Meibomian Gland Anatomy
Meibomian Gland Anatomy
Location: upper and lower eyelids (Andrews, 1973)
Number: 30‐40 upper, 20‐30 lower (Andrews, 1973)
Structure: simple branched acinar (Jester, 1981)
Expression Type: holocrine (Jester, 1981)
Products: primarily lipids and a few proteins (Pucker, 2012; Pucker, 2014)
Image: http://www.contactlens.org.nz/extra1.aspx
Meibomian Gland Anatomy
Meibomian Glands
• Meibomian glands are simple branched acinar glands
– Each gland has a single duct that empties on to the eyelid margin Normal Meibomian Gland
Image: http://www.mc.vanderbilt.edu/histology/labmanual2002/labsection1/GlandularEpithelium03.htm
The Lipid Layer is Important
•
Meibum produces the external tear film lipid layer (Mackie IA, 1985; Zhao Z, 2010) •
Disruption of the tear lipid layer correlates with increased evaporation and dry eye (Foulks GN, 2007; Craig JP, 1997; Goto E, 2003) •
Evaporation likely leads to an increased tear osmolarity and inflammation •
Ocular symptoms significantly increase with a poor tear lipid layer (Foulks, 2007)
•
NaFl staining is correlated with meibomian gland obstruction and/or atrophy (Shimazaki 1995)
Dysfunctional Meibomian Gland
Image 1: http://www.reviewofophthalmology.com/content/d/therapeutic_topics/i/1302/c/25069/Image 2: http://www.finemd.com/newsletters/newsletter_spring_2013.html
How is MGD Related to CL Wear?
(Foulks GN, 2007; King‐Smith PE, 2008; Rashid S, 2008) • Study analyzed ocular surface differences between 71 CL wearers and 71 non‐CL wearers – Subjects were matched on gender and age
– All CL wearers were successful CL wearers 2
1/20/2017
Summary Statistics for Ocular Surface Assessments
Procedure
Contact Lens Wearers (mean ±
SD)
Non‐Contact Lens Wearers (mean ± SD)
Difference (P‐Value)
0.4 ± 0.6
0.5 ± 0.6
0.04
Area of Sodium Fluorescein Corneal Staining (0‐20 scale)
1.2 ± 1.4
0.7 ± 1.1
0.005
Lissamine Green Conjunctival Staining (0‐20 scale)
4.2 ± 3.9
2.6 ± 2.7
0.006
0.6 ± 0.5
0.8 ± 0.7
0.02
Eyelid Margin Erythema (0‐3 scale)
Line of Marx (0‐3 scale)
Note: Only significant tests are listed (worse eye). MG ATROPHY WAS NOT DIFFERENT BETWEEN GROUPS!
External Factors Affecting Contact Lenses
•
Normal blinking is important – Using tablets and computers significantly decreases blinking
– Fewer blinks can result in tear evaporation and contact lens discomfort (Nosch 2015)
(Blehm 2005; Agreement with Past Studies
• Significant signs are inconsistent across studies • Some
Some studies have
studies have found MG atrophy to be found MG atrophy to be
associated with CL use (Arita 2009; Alghamdi 2016)
• Some studies have not found MG atrophy to be associated with CL use (Pucker 2015; Machalinska 2015; Pucker 2017)
We Need to Prevent Ocular Surface Damage
• Contact lens fitting is all about patient motivation and expectations
Martin‐Montanez 2015) •
Environment – Wind, humidity, temperature, and comfort are not related to contact lens dehydration – Outdoor temperature likely has little effect on contact lens diameter and base curve (Young 2011 and 2015)
– Eye temperature, tears, and blinking likely protect against the environment (Morgan 2004; Martín‐Montañez 2014; Dillehay 2007 )
– About half of all contact lens wearers who About half of all contact lens wearers who
discontinue contact lens use due to discomfort (Young 2002)
– Some patients are willing to do anything to continue wearing their contact lenses (Morgan 2004)
Contact Lens Symptoms 84 Eye Care Providers in the United States and Canada
DRY EYE
Riley C, et al. Eye & Contact Lens, 2006.
3
1/20/2017
78%
DRY EYE
Patients
MGD
1.25g/mm2
Non‐Obvious MGD
This is WAY more common
NUMBER OF FUNCTIONAL MGs in the Lower Lid
0-4
5
SYMPTOMATIC FOR DRY EYE1
6
7
8
9
10+
ASYMPTOMATIC2
When the total number of functional glands is 7 or higher, but there is evidence of
compromise to gland function and/or structure, therapy should still be considered.
4
1/20/2017
Interferometry
Prevalence of Ocular Inflammation in the General Population
Charissa Young, OD and David Kading, OD, FAAO
Specialty Dry Eye and Contact Lens Research Center, Seattle, W A
Grade Your Meibomian Meibomian
Glands
Introduction
Methods & Materials
Dry eye is a multifactorial disease. Factors that adversely affect tear film stability and osmolarity can initiate inflammatory mediators that lead to ocular surface damage, including corneal barrier disruption and apoptosis.
One of these mediators is matrix metalloproteinase 9 (MMP‐9). The Dry Eye Workshop (DEWS) Report defined levels of MMP‐9 ≥ 40 ng/mL corresponding to moderate‐to‐
severe dry eye disease (1). RPS’s InflammaDry yields positive results when levels of MMP‐9 of 40 ng/mL or more are detected in a tear fluid sample taken from the palpebral conjunctiva.
Twenty‐seven subjects between the ages of 16 and 68 years old participated in this study. The average age of the participants was 40 years old, with almost equal male and female involvement (14:13). Of the 27 encounters, the majority were annual eye examinations, 16/27 (59.3%); the remaining encounters were medical office visits at 11/27 (40.7%).
The right eye of subjects was tested and all test results were read by the primary investigator to maintain consistency of interpretation. Testing was interpreted on a scale ranging from Strong Positive to Weak Positive to Trace to Negative. Results
63% of subjects in the general patient
population tested positive for MMP-9 ≥ 40 ng/mL
Of the 27 subjects, 63% tested positive and 37% tested negative. Of the positive results, 3/17 (17.6%) were strong positive, 8/17 (47.1%) were weak positive, and 6/17 (35.3%) were trace (see graph below).
12
Test Results in General Population
10
Top: Positive InflammaDry results
Bottom: Negative InflammaDry results
Developed by Heiko Pult
In comparing the results by age, subjects 40 years and older tested 72.7% positive compared to those under 40 testing 56.3% positive.
Discussion
InflammaDry is a rapid point‐of‐care test commonly incorporated into dry eye clinics due to its strong sensitivity to detect inflammation on the ocular surface. A previous study, 2013 Sambursky et al, concluded that InflammaDry
showed sensitivity of 85% (in 121 of 143 dry eye patients) and specificity of 94% (59 of 63 healthy controls) (2).
This study sought to detect the prevalence of MMP‐9‐
related inflammation in a general patient population to determine the utility of InflammaDry
determine
the utility of InflammaDry as a dry eye screening as a dry eye screening
tool. Sixty‐three percent of subjects tested positive for MMP‐9 levels above 40 ng/mL, much higher than expected in an population without dry eye diagnoses. Prevalence of higher positive results was found in the medical office visit encounters, which ranged from cataract post‐operative appointments to blepharitis follow‐ups. These diagnoses are typically associated with some degree of ocular inflammation, so this result was not surprising. Conclusion
MMP‐9 inflammation ≥ 40 ng/mL in the tears has a prevalence of 63% in a general patient population without prior dry eye diagnosis. Implementing MMP‐9 testing in a primary care setting can be a useful objective tool to educate patients about the implications of inflammation on the ocular surface and provide clinicians with another screening test to capture non‐
obvious dry eye patients. Most importantly, clinical exam alone may not be appropriate to guide therapeutic decision‐making to start an anti‐inflammatory treatment or to monitor the impact of treatment.
Acknowledgements
g
This study was supported by Specialty Dry Eye and Contact Lens Research Center. Special thanks to RPS Diagnostics for supplying InflammaDry tests.
References
1.
2.
8
Males and female tested equally positive for MMP‐9 above 40 ng/mL, unlike most reports exhibiting an increased prevalence of dry eye in females (3). This may be due to the small sample size of the study. 6
While the prevalence of elevated MMP‐9 in inflammatory dry eye has been well established in the literature, this study sought out to discover the prevalence of elevated MMP‐9 in a more general population not undergoing dry eye treatment. The ability to screen for an objective sign of inflammation regardless of symptoms could support earlier diagnosis and improved management of the condition.
In comparing the results by gender, female and male participants tested about equally positive. Females tested 61.5% positive. Males tested 64.3% positive. 4
2
0
Strong Postive
Weak Positive
Trace
Negative
In comparing the results by encounter, there was an increased prevalence of positive MMP‐9 at or above 40 ng/mL results in the medical office visit subset versus annual eye examinations. Of the 11 medical office visit encounters, 8 (72.7%) tested positive. Of the 16 eye examination encounters, 9 (56.3%) were positive. Annual eye examination encounters
yielded 56.3% positive I nflammaD ry
results
3.
2007 Report of the International Dry Eye Workshop (DEWS). The Ocular Surface: April 2007.
Sambursky et al. “Sensitivity and Specificity of a Point‐of‐Care Matrix Metalloproteinase 9 Immunoassay for Diagnosing Inflammation Related to Dry Eye.” JAMA Ophthalmology. 2013; 131(1): 24‐28.
Miljanović, B. “Impact of dry eye syndrome on vision‐related quality of life.” Amer. Journal of Ophthalmology. March 2007.
Contact I nformation
For more information, please contact Dr. Charissa Young at [email protected]. Even more relevant for primary care practitioners, annual eye examination encounters yielded 56.3% positive InflammaDry results, reflecting the often subclinical nature of inflammatory dry eye, as many of these patients were either asymptomatic or without strong signs of inflammation.
Dry Eye Cascade
T‐Cell Activation
Abnormal Tear Film Causes & Contributors
5
1/20/2017
Dry Eye Exams Should be Standardized • Develop an exam protocol with a set battery of tests that is ordered from least to most invasive (Bron 2003)
• Protocol should have – At least one questionnaire about symptoms – A battery of graded tests that covers the primary ocular structures (DEWS 2007) Implementing a Standardized Exam
• Testing protocol should allow for differentiation between evaporative and aqueous deficient dry eye
aqueous deficient dry eye
• A balance must be struck between number of tests and the amount of information needed to make an informed diagnosis 2 Questions?
Tear Dysfunction?
T
D f
ti ?
Gland Flow?
6
1/20/2017
Inflammatory
Mediating
Dry Eye – Contact Lens Wearers
a. Consider least invasive CL options when possible
a.
b.
c.
Part time wear
Single Use Lenses
Solutions Considerations
b. ASSUME DRY EYE ON ALL CL Wearers
c. Treat patients based on their progression rather than their current state
• If a patient is worse than last year, anticipate that they will advance
7