Management of Dry Eye Disease (DED) - Recent Diagnostic Modalities

1. OCULAR SURFACE
ANALYSERS
Dr. Mithun Thulasidas
Fellow
Centre for Sight

2. HOW ARE DRY EYES DIAGNOSED ?
 Dry eyes can be diagnosed through a comprehensive eye
examination.
 Testing, with emphasis on the evaluation of the quantity and
quality of tears produced by the eyes, may include:
• Patient history, medications or environmental factors
• External examination of the eye, including lid structure and
blink dynamics.

3. • Measurement of the quantity and quality of tears for any
abnormalities.
• Special dyes may be put in the eyes to better observe tear
flow and to highlight any changes to the outer surface of the
eye caused by insufficient tears.

5. Dry eye disease was recently redefined as a
“multifactorial disease of the ocular surface characterized by a
loss of homeostasis of the tear film, and
accompanied by ocular symptoms, in which tear film instability
and hyperosmolarity, ocular surface inflammation and damage,
and neurosensory abnormalities play etiological roles.” (DEWS
II)

6. Meibomian gland dysfunction (MGD) represents the leading
cause of evaporative dry eye, the most common subtype of
eye.
MGD is characterized by hyperkeratinization of the meibomian
gland ductal epithelium, leading to obstruction and plugging of
the gland orifice.

8. Stasis of meibum inside the gland
promotes proliferation of bacteria
producing lipases and esterases
increase the viscosity and
melting temperature of the meibum

9. The accurate diagnosis and classification of dry eye are
complicated by the heterogeneous nature of the disease and the
variability of signs and symptoms.
Various diagnostic assessments have been proposed to
qualitatively and quantitatively characterize the entire ocular
surface system.
However, to date, no universally accepted diagnostic workup for
the diagnosis of MGD has been established.

10. Several tests used routinely in daily practice require direct
contact with the eye and/or the use of eye drops.
The resulting alteration of the tear film volume and composition
may not only influence the measured variable itself but also have
disruptive effects on the results of subsequent tests.

11. Measurements obtained using traditional tests are often affected
by low values of repeatability and reproducibility.
Recently, new automated noninvasive quantitative tests have
been developed to overcome these drawbacks

12. Interferometry is a technique that studies the surface reflection
pattern and dynamics of the lipid layer of the tear film, thus
allowing the measurement of the tear film stability and the
thickness of the lipid layer.
Meibography allows in vivo observation of the Meibomian
gland morphology; the gland structural changes may be
with different scoring systems.

13. In addition, new digital software allows automated calculation of
the total meibomian gland area in the lower and upper eyelids.
Tear film osmolarity has been reported as the single best
metric to diagnose and grade severity of dry eye.

14. RECENT DIAGNOSTIC DEVICES
 LipiView and LipiScan
• Lipiview II Ocular Surface Inteferometer with Dynamic
Meibomian Imaging (DMI)
- Measures the lipid layer thickness (LLT) with
nanometer accuracy,
- Captures blink dynamics, and
- Images Meibomian gland structure

16. • LipiScan
- High definition meibography
- Small footprint and lightweight (25 lbs) for optimal
versatility
- Gland images available for export as PDF
- Both lower eyelids can be managed in about a minute

18. - Dynamic illumination

19. - Adaptive illumination

20. - Dual-Mode DMI

22. - Efficacy supported by 30 peer-reviewed reports
- Costly ($40,000)

23.  Meibox (Box medical solutions)
- captures high resolution images of the meibomian glands
- The first HD slit lamp mounted meibographer

24. - can also measure tear meniscus and perform pupil
size comparisons to detect neurological abnormalities In
light and dark settings
- Low cost compared to other devices ($8,950)
- Patient data is stored securely on cloud based servers and
can be accessed anywhere in the world
- the design eliminates licensing costs associated with
multiple viewing stations and has the ability to pull up
images in multiple clinic locations
https://www.youtube.com/watch?v=8sQfaHuQVf4

25.  InflammaDry (Quidel)
- First and only, in-office immunoassay test that detects
elevated levels of MMP-9
- Accurate results: 85% sensitivity and 94% specificity
- Samples taken the inside lining of the lower eyelid, the
palpebral conjunctiva
- Results in 10 minutes

26. - Low cost ($13)
- No additional equipment
- Disposable

27. - Direct Sampling Micro-Filtration technology, based on
the principle of lateral flow immunoassay.
MMP-9, if present in the tear sample, is captured between
MMP-9 specific mouse monoclonal and goat polyclonal
antibodies at concentrations ≥ 40 ng/ml. This antigen-
antibody complex is captured by NeutrAvidin immobilized as
the test line.

28. - The InflammaDry test includes two foil pouches, containing
the following materials, and one buffer vial.

29. The sample collector (A) is a separately packaged sterile
component that can easily be assembled onto the test cassette
(B). Additionally, the test cassette (B) guarantees correct sample
transfer onto the lateral flow assay strip.
Do not touch the sterile sampling fleece (C) prior to
collecting the patient sample.
https://www.youtube.com/watch?v=3geY7V8JDzc

30. - The buffer vial contains a buffered salt solution
containing:
200 mM Tris
10% Fish 81 (sea block)
0.8% Tergitol
100 mM NaCl
0.1% Sodium Azide
0.0126% Gentamycin
pH 9.5 ± 0.05

32. • Limitations
- MMP-9 is a nonspecific indicator for the presence of
inflammation.
- Patients with severe aqueous deficient dry eye, who
produce a sample volume of less than 6 μl, may yield a
false negative result.
- InflammaDry should not be used within 20 minutes of
performing a Schirmer tear test, as this may stimulate
degranulation of MMP-9 and cause a false positive result.

33. - A recent history of ocular surgery or infection, allergic
conjunctivitis, or other ocular surface diseases
- Patients with a history of contact lens use or recent ocular
surgery were not studied; no data supports any claims for
safety and efficacy in these populations.
- Certain medications such as systemic
immunomodulators, topical or oral steroids, cyclosporine,
tetracycline, and topical azithromycin, are known to inhibit
metalloproteinase activity.

34. - Running the test in an environment with a temperature of
45˚C or above, and humidity of 60% or above, may increase
sensitivity and cause a false positive result.
- InflammaDry should not be performed in conditions such
as Stevens Johnson Syndrome or other cicatricial conditions.

35.  TearLab osmolarity system (TearLab)
- Quick and simple method for determining tear film
osmolarity using nanolitre (nL) volumes of tear fluid
collected directly from the eyelid margin
- fast, repeatable, actionable results
- utilizes a temperature-corrected impedance
- Positive predictive value of 89%
- Comparatively low cost ($9500)

36. - Consists of 3 components: a pen, a test card and system
reader.
The pen holds the test card which collects and analyses the
tear fluid.
The system reader displays the osmolarity measurement
Proper calibration of the pen before testing

37. - The single-use polycarbonate microchip in the test card
has a micro-fluid channel that collects the tear fluid by passive
capillary action
- Gold electrodes, embedded in the microchip within the
pen, allow measurement of tear osmolarity by electrical
impedence
- The composition and concentration of ions in tear fluid
affects its electrical conductivity, which gives a measurement
of tear film osmolarity
- Test takes 1-2 minutes
https://www.youtube.com/watch?v=g0uSw4F4OMI

38. - Caffery et al (2014) - No significant correlation between
tear osmolarity and self-reported ocular symptoms
- Jacobi et al (2011) – TearLab can be an effective
objective diagnostic tool in the diagnosis of DED
- Messmer et al (2010) - TearLab test not sensitive enough to
discriminate between people with DED and healthy people
- Lemp et al (2011) – Tear osmolarity is the best single
metric for diagnosing and classifying DED

39.  I-Pen osmolarity system (I-Med Pharma)
- hand held device that measures the tear osmolarity
- uses single-use sensors to measure the electrical
impedance in the tear soaked tissues 192 times in <5
seconds and calculates tear film osmolarity
- Cost ($1500)
https://www.youtube.com/watch?v=uZs_UjeYsds

40.  Ocular Surface analyser (Grafton Optical SBM Sistemi)
- The instrument is mounted in the slit lamp tonometer
It is designed to do all tearfilm tests, from the quality of tears
to analysis of the meibomian glands using international grading
scales.

41. - interferometry
- tear meniscus
- NIBUT
- meibography
- blepharitis
- ocular redness classification
- pupillometry
- white to white measurement
https://www.youtube.com/watch?v=STkWNRxyYms

44.  ME-CHECK

45. RECENT THERAPEUTIC DEVICES FOR DRY
EYE TREATMENT
 LipiFlow thermal pulsation system (Johnson & Johnson
Vision)
- uses vectored thermal pulse technology to deliver heat
and peristaltic motion to a patient’s eyelid to help remove
gland obstruction and stagnant gland content

47. - A study by Kerry Hagen and colleagues in ‘Clinical
Ophthalmology’ showed a single 12-minute vectored
thermal pulsation procedure with the LipiFlow system
resulted in a clinically significant improvement in gland
function and reduced dry eye symptoms compared with 3-
month use of oral doxycycline.
- 31 peer reviewed articles – Gland blockages can be
removed and gland function restored with LipiFlow
- More than 10 years of dedicated research and protected
by more than 30 patents

48. - The procedure centers around the breakthrough Vector
Thermal Pulse Technology (VTP)
- After an initial anaesthetic drop, no drugs are required for the
procedure
- Safely delivers therapeutic energies to the Meibomian glands
while protecting the delicate structures of the patients eye
- The obstructed meibum is liquified and pushed up and out of
the gland orifices
https://www.youtube.com/watch?v=HD5rE6igkHk

49. - Contoured design vaults the cornea and protects the eye
- Heat and pressure are regulated with redundant sensors
- Costly ($20000)

50.  TrueTear (Allergan)
- intranasal tear neurostimulation device
- stimulates nerve in the nasal cavity and triggers the
nasolacrimal reflex pathway, which temporarily increases
production

51. - It does not involve the use of any preservatives or
chemicals on the eye
- It increases tear production immediately
- It increases Meibomian gland lipid production
- It can be used as needed by the patient
- It is safe with no long term risks
https://www.youtube.com/watch?v=8b2nP9-2B3s

52. - At the 2017 American Academy of Ophthalmology annual
meeting, Edward J Holland reported the results of a prospective,
single arm, open-label study of 97 subjects who used the
TrueTear device a minimum of twice a day and upto 10 times
per day for upto 180 days. Acute tear production was
significantly greater during intranasal stimulation in the
TrueTear eye compared with an unstimulated fellow eye at
days.

55. - Not approved for
a, patients with implanted neurostimulator devices like
pacemakers or wearable defribillators
b, patients under 22 years of age or pregnant women
c, use in water or around flammable gases or shortwave devices
d, patients with nasal or sinus surgery or untreated nasal
infections
e, patients with chronic or frequent nosebleeds, a bleeding
disorder
f, patients with a known allergy to the hydrogel material the
nasal tip is made from.

56.  Intense Pulse Light (IPL) therapy

57. - Utilizes pulses of light to liquefy and release hardened
oils that have clogged Meibomian glands in the eyelids
- Affects vascularization and inflammation of the eyelids,
reducing eyelid redness and stimulating healthy gland
function
- Usually performed once a month for a course of four
months
https://www.youtube.com/watch?v=8SFaErUrk60

58. - Class II broad-spectrum light device
- Significant improvement in MMP-9 levels and
physiologic osmolarity
- A prospective study published by Steven J. Dell and
colleagues evaluated IPL therapy and Meibomian
expression for the treatment of dry eye disease due to
Meibomian gland dysfunction. In patients with moderate
to severe Meibomian gland dysfunction, IPL combined with
Meibomian gland expression reduced the number and
severity of symptoms of dry eye disease and improvement
TBUT.

59. - Uses a xenon flash lamp to produce light in the 500-
1000nm wavelength range that can be pulsed and filtered to
allow specific wavelengths of energy to be released

60.  Lumenis M22
- Combines Intense Pulsed Light (IPL) with unique
Pulse Technology(OPT).
- IPL is selectively absorbed in the haemoglobin of
abnormal blood vessels and destroys them by thrombosis.
- Thus it removes the inflammatory telangiectasic vessels
MGD.

62. - IPL treatment intensity ranges from a low power of 8 J/cm2
to 20 J/cm2, with higher power levels indicated as age and lid
margin disease severity increase.
- Patented disposable IPL eye pads are placed over closed
eyes to cover the area completely.

63. - Ultrasound gel is placed on the patient's face from tragus
to tragus including the nose. The patient's skin area receives one
full pass with overlapping flashes.
- Following the initial pass, a second pass is performed.
- After completion of the second pass, the patient is
brought to the slit lamp where a drop of 1% proparacaine
is administered and a meibomian gland expression is performed
(using a sterile cotton tip applicator).

64. - Costly ($25000)

65.  E- Eye IPL with E- Swin

68. - Advantages over Lumenis M22
a. Medical certification for treatment of dry eye (MGD)
b. Neurological stimulation
c. Flash delivered is regulated, divided into sub-pulses,
with different durations and light intensities for each sub-
pulse
d. Patented air cooling system without required
maintenance

69. e. New lamp technology
f. Activation card system allowing multi-user management
g. Exclusively to ophthalmologists

70.  BlephEx (BlephEx LLC)
- eliminates bacterial debris from a patient’s eyelids
(blepharitis)
- removes biofilm from the lid margin
- technique dependent
- 6-8minute well tolerated procedure
- Studies demonstrate a 60-66% increase in TBUT
(Rynerson et al)

71. https://www.youtube.com/watch?v=rnVYXqk8D28

72.  iLux device (Tear Film Innovations)
- Hand held device that allows to look at specific sections
of the Meibomian gland with a magnifier and evaluate their
expressibility
- LED light is applied to raise the eyelid temperature and
melt the blockages
- Eyelid is gently compressed to clear the blocked
- Treated in less than 8 minutes

75. - The sterile, single-patient-use, disposable iLux Smart Tip
has an inner pad and an outer pad.
- The inner pad slips behind the eyelid being treated, while
the outer pad is pressed against the outer surface of the eyelid
during heating and compression.
- Both pads are covered with a soft, biocompatible
silicone material

76. - Cost-effective, increasing patient acceptance
- Studies show similar outcomes with LipiFlow and one-
third the cost (David R. Hardten et al)
https://www.youtube.com/watch?v=wo8aaQ2abhk

77.  TearCare system (Sight Sciences)
- delivers a sufficient level of energy to liquefy meibum
coupled with gland expression to improve oil flow from
the glands
- only wearable, open eye and fully customizable eyelid
technology
- 12 minutes of thermal eyelid treatment (41-45degree
Celsius) immediately followed by manual expression of the
Meibomian glands

78. - A pilot study by David Badawi in Clinical Ophthalmology
2018, suggested that the TearCare system is an effective
treatment option for patients with DED, with the effects on
the signs and symptoms persisting for atleast 6 months
- OLYMPIA trial

80.  Neurolens glasses (eyeBrain Medical)
- specialized lenses to correct the overcompensation of
eyes during digital device use
- reduces eye movement misalignments
- first and only prescription lenses that add a contoured
prism to bring the eyes into alignment

81. - Contoured prisms has been shown in studies (Teitelbaum
et al) to relieve the headaches and eyestrain, that many
patients experience when using digital devices, reading or
doing detail work

82.  Bruder
- Moist heat eye compresses

83. - Helps stabilize the tear film, improves oil gland function
found in the lids, and slows tear evaporation.
- The patented Medibeads inside the mask absorb water
from the air and after the mask is heated in the microwave,
the beads release moist heat.

84. - Non allergenic
- Opens oil glands and allows natural oils to flow back
into the eye relieving discomfort
- Self hydrating: no need to add water
- Washable & reusable
- Microwave for 20-25 seconds (1000W) and apply for
10minutes twice a day

85. - A study by Jacqueline Tan et al (2017) compared Bruder to
traditional warm compresses in MGD and found Bruder as a
more convenient treatment due to its once-only heating
advantage with effects on NITBUT, TNH and TFLLT

86.  Evolve Eye Mask
- Designed as per DEWS 2 (1) norms
- Stabilizes tear film by improving gland function, thus
slowing down evaporation
- Unique distribution of heat over application area
- use of natural fabrics and quilting for user comfort
- Washable and reusable outer bag
- Adjustable comfort strap
- Self hydrating beads

88.  My-Mask
- MGD treatment for photobiomodulation
- Easy to use
- Affordable to use
- Very effective

89.  Diagnostic
Lipiview and Lipiscan (Johnson and Johnson TearScience)
OSA (Grafton Optical SBM Sistemi)
TearLab osmolarity System

90.  Treatment
Lipiflow (Johnson and Johnson)
iLux device (Tear Film innovations)

91. THANK YOU 