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Evidence for Technology

in the Treatment of Dry EyeCOPE: 44090-AS

Chris Lievens, OD MS FAAO

Professor

Chief of staff

Southern college of optometry

Dry eye

Chronic

Multifactorial

Characterized by disturbances in tear film &ocular surface

Females > male

Dry eye

Environmental conditions

Arid

Computer-use

Contact lens wear

Systemic disease

Sjogren’s syndrome

Lupus

Stevens-Johnson syndrome

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Doctors and Patients See Dry Eye Differently

Patients often perceive their dry eye symptoms to be more severe than their ECP suspects based on clinical signs

ECPs lack a gold standard clinical test for dry eye, limiting their ability to objectively assess symptoms in many patients

1. Eisenberg JS. Rev Optom. 2003;140(01). Issue: 1/15/03.

Severity of Dry Eye

Symptoms

Doctor

Assessment

Patient

Assessment

Severe 9% 19%

Moderate 20% 36%

Mild 47% 23%

Dry Eye Demographics

Estimate of dry eye disease in Americans over 50

3.23 million women

1.68 million men

Tens of millions more have less severe dry eye

The prevalence of severe symptoms and/or clinical diagnosis may be greater in Asian and Hispanic women

Public health significance of dry eye is likely to increase: US population aged 65-84 years will grow by 100% between 2000 and 2050

1. The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye

WorkShop (2007). Ocul Surf. 2007 Apr;5(2):93-107.

Dry Eye Can Have a Marked Impact on Quality of Life

Dry eye can have a marked impact on patients’ quality of life (QoL), particularly affecting their daily roles and vitality1

QoL in patients with severe dry eye is comparable to that in patients with severe angina or disabling hip fracture2

Respondents in this study stated that they would be willing to give up 1.6 years of their lives to be free of severe dry eye

In patient with mild dry eye, the QoL value is roughly equivalent to that of psoriasis2

1. Mertzanis P, et al. Invest Ophthalmol Vis Sci. 2005;46:46-50. 2. Schiffman RM, et al. Ophthalmology.

2003;110:1412-19.

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Dry Eye Disease

inflammation of the ocular surface and increased osmolarity of the tear film

common and is often under diagnosed

Signs don’t always correlate with symptoms

negatively impact vision quality, fluctuating vision, reduced contrast sensitivity, and increased glare

Significant psychological impact

Patients have reported a willingness to trade years at the end

of life to be free of dry eye disease

Crucial Factors in Dry Eye Disease

Dry eye is a multifactorial disease of the tears and ocular surface that results in symptomsof discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface.

1. The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye

WorkShop (2007). Ocul Surf. 2007 Apr;5(2):93-107.

Why Is the Eye Dry?DRY EYE

Aqueous-deficient

Sjogren

Syndrome

Dry Eye

Non-Sjogren Dry Eye

Meibomian OilDeficiency

Vitamin A-Deficiency

Disordersof Lid

Aperture

Topical DrugsPreservatives

Low BlinkRate

Contact LensWear

Drug ActionAccutane

Ocular SurfaceDisease

eg, Allergy

Lacrimal Deficiency

LacrimalGland Duct

Obstruction

Reflex Block

Systemic Drugs

Intrinsic Extrinsic

Primary

Secondary

1. Figure adapted from: The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry

Eye WorkShop (2007). Ocul Surf. 2007 Apr;5(2):93-107.

Evaporative (~80%)

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Lid aperture issues

Lid laxity

Lagophthalmous

Floppy eye lid syndrome

Other CAUSES OF DRY EYE symptoms

Medications (BAK)

Ophthalmic

Glaucoma medications

Allergy medications

Other Causes of dry eye symptoms

Demodex

Demodex folliculorum

Demodex brevis

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Causes of dry eye symptoms

blepharitis affects

millions

upwards of 80% of

those patients could have Demodex mites

Causes of dry eye symptoms

Demodex

Men > Women

The incidence of Demodex infestation increases age

84% of the population at age 60

~100% of the population older than 70 years of age

Other Causes of dry eye symptoms

Diabetes

Thyroid disease

Autoimmune disease

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Psychology of dry eye

89 dry eye subjects (13 sjogren’s patients & 73

control subjects

Zung self rating anxiety scales (SAS)

zung self rating depression scales (SDS)

ocular surface disease index (OSDI)

Psychology of dry eye

Anxiety and depression scores of the DES group were significantly higher than the control group

SAS and SDS scores were found to be correlated with OSDI

What are the dry eye

‘personalities’ that we are dealing with?

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Psychology of the examination

Change the single visit mentality

Treatment is a process

Individualized care

Patient’s thoughts?

72% of patients Artificial tears only

82% of patients Demand “something

better”

97% of patients Report condition as

“frustrating”

The Gallup Organization Inc. The 2008 Gallup Study of Dry Eye Sufferers. Princeton, NJ: Multi-

Sponsor Surveys Inc; 2008.

Lid Wiper Epitheliopathy (LWE)

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LWE

New diagnosis?

2002 coined by Korb et al.

lid wiper is the portion of the eye lids that is in apposition to the ocular

surface during a blink

LWE has been reported to occur both with and without contact lens wear

Correlates with symptoms for both dry eye and contact lens discomfort

LWE

LWE is increased friction between the lid wiper and the ocular surface due to inadequate lubrication

The lid wiper comes into contact with the anterior ocular surface over 3,000 to 15,000 times a day

The lid wiper is in apposition to the globe at all times and would be constantly susceptible to mechanical trauma with poor lubrication.

The ocular surface, in contrast, comes in contact with the lid wiper for only a fraction of second (albeit, frequently). \

It would be expected that in any state of dry eye disease, the lid wiper would suffer greater trauma and epithelial compromise than would be ocular surface

LWE

Have we been looking?

Is this diagnosis the ‘missing link’?

How should it be detected?

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Method

Lissamine Green (or NaFl)

Though the lid wiper can be viewed in bright white light, disturbances in the

tissue and LWE can only be observed with the aid of vital dyes

Upper conjunctiva

Wait ~1 minute

Evaluate conjunctiva and lid margin (gently)

The term epitheliopathy is used in LWE to note the uptake of vital dye(s)

thereby implying that the tissue is found to have devitalized cells and/or is in the presence of neighboring cellular apoptosis

1) Grading of Horizontal Length of Fluorescein and/or Lissamine Green Staining of the Epithelium

of the Lid Wiper(Korb et al., 2010)

Horizontal Length of Staining Grade

<2 mm 0

2-4 mm 1

5-9 mm 2

>10 mm 3

2) Grading of Sagittal Height (Width) of Fluorescein and/or Lissamine Green Staining of the

Epithelium of the Lid Wiper(Korb et al., 2010)

Sagittal Height (Width) of Staining Grade

<25% 0

25% - 50% 1

50% - 75% 2

>75% 3

Tear osmolarity

Tear lab osmolarity system (tear lab)

single-use microchip embedded with gold electrodes

50 nl collected

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Tear osmolarity

Osmolarity increases with advancing dry eye disease

Asymmetry of findings also indicative of problems

Inflammadry

Rapid pathogen screening

Detects elevated MMP-9 in tears

Studies indicate MMP-9 as a useful biomarker for diagnosing, classifying and monitoring DED

InflammaDry

Identifies elevated levels of MMP-9 in tear fluid

Rapid: 10 minute results

In-office: point-of-care immunoassay test aids in diagnosis at the time of office visit

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Dry Eye Disease and MMP-9

Matrix metalloproteinases (MMP) are proteolyticenzymes that are produced by stressed epithelial cells on the ocular surface1

MMP-9 in Tears

Normal range between 3-41 ng/ml

Correlates with clinical exam findings1

[1] Chotiakavanich S, de Paiva CS, Li de Quan, et al. Invest Ophthalmol Vis Sci 2009; 50(7): 3203-

3209.

MMP-9

Group MMP-9 Activity (ng/mL)

Normal (n = 18) 8.39 ± 4.70

DTS1 (n = 15) 35.57 ± 17.04*

DTS2 (n = 11) 66.17 ± 57.02*

DTS3 (n = 9) 101.42 ± 70.58*†

DTS4 (n = 11) 381.24 ± 42.83*‡

Tear MMP-9 Activity in Normal Control and DTS Groups.

Data shown are the mean ± SD.*P < 0.008 Compared with normal.†P < 0.003 Compared with normal and DTS1.‡P < 0.001 Compared with normal and the other DTS severity groups

Invest Ophthalmol Vis Sci. Jul 2009; 50(7): 3203–3209.

inflammadry

a small applicator touched to the conjunctiva

snaps into a test cassette

Cassette tip is submerged In solution

results are obtained in 10 minutes

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Inflammadry

Pro’s

Inexpensive

Fast

Identifies presence of inflammation

Con’s

Does not quantify inflammation (per se)

Does not identify cause

Oculus Keratograph 5M

Tear film analysis by non-invasive (non-contact) scanning

NIKBUT

Tear meniscus height

Non-contact meibography (meiboscan)

Tear dynamics

Bulbar redness

topography

Meibomian Gland Dysfunction (MGD) Is the Most Common Cause of Evaporative Dry Eye Disease1-3

“Meibomian gland dysfunction (MGD) may well be the

leading cause of dry eye disease throughout the world.”4

—The International Workshop on Meibomian Gland Dysfunction:

Executive Summary

1. Lemp MA, Nichols KK. Blepharitis in the United States 2009: a survey-based perspective on prevalence and treatment. Ocul Surf. 2009;7(2 Suppl):S1-S14.

2. Lemp MA, Crews LA, Bron AJ, et al. Distribution of aqueous-deficient and evaporative dry eye in a clinic-based patient cohort: a retrospective study. Cornea. 2012;31(5):472-8.

3. Shimazaki J, Sakata M, Tsubota K. Ocular surface changes and discomfort in patients with meibomian gland dysfunction. Arch Ophthalmol. 1995;113(10):1266-1270.

4. Nichols KK, et al. The international workshop on meibomian gland dysfunction: executive summary. Invest Ophthalmol Vis Sci. 2011;52(4):1922-1929.

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Classification of Meibomian Gland Dysfunction

Meibomian Gland Disease

Congenital Neoplastic Acute Other

Meibomian Gland Dysfunction (MGD)

Low Delivery High Delivery

Primary Secondary(e.g., medications)

Primary Secondary• Trachoma

• Ocular Pemphigoid

• Erythema

Multiforme

• Atopy

Primary Secondary• Seborrheic

Dermatitis

• Acne Rosacea

• Atopy

• Psoriasis

Primary Secondary• Seborrheic

Dermatitis

• Acne Rosacea

Alteration of Tear Film Eye IrritationClinically Apparent

Inflammation

Ocular Surface Disease

Including Dry Eye

Hyposecretory (Meibomian Sicca)

Hypersecretory (Meibomian Seborrhea)

Obstructive

Cicatricial Non-Cicatricial

1. Nichols KK. Invest Ophthalmol Vis Sci. 2011;52:1922-29.

Challenges of Current MGD Therapies38

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Therapy

• Warm compresses

• Eyelid scrubs

• Manual gland expression

Challenges

• External heat application is

inadequate

• Significant discomfort

• Limited compliance

• Only the upper portion of the

glands are treated or expressed

LipiView

Uses interferometry to measure lipid layer thickness between blinks

Quantitative assessment in interferometric color units (ICU)

Pilot study: 137 consecutive patients completed SPEED test, then measured LLT by Lipiview

SPEED >10, 74% had LLT of 60nm or less

SPEED = 0, had LLT 75nm or greater

As LLT increases, symptom score decreases

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microscopy

Demodex visible at slit lamp

Cylindrical dandruff @ Base of lashes

Most common ecoparasite

Microscopy for patient education

Upper 1/3 has four pairs of legs that

allows it to move from one follicle to

the next

Remaining body is an abdomen-tail

Demodicosis

Demodex folliculorum

Buries within hair follicle (tail protrudes)

Demodex brevis

Favor sebum-rich environments like Meibomian glands

Organisms inhabit hair follicles & glands Feed on sebaceous oils & dead skin cells; carry

pathogenic bacteria

Avoid light: most active at night

Overpopulation causes localized inflammation

Demodicosis

Demographics:

More prevalent in elderly

Male > female

More common in rosacea patients

Symptoms:

Grittiness and/or burning

Itching of eyelids

Crusting of eyelashes

Poor cosmesis (i.e. eye & eyelid redness)

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Demodicosis

Key objective findings:

Cylindrical dandruff (“sleeves”) at lash base (especially lash

line most inward)

Possible to see mite tails with lash manipulation

Demodicosis - Management Options

1. In-office: microblepharoexfoliation

(BlephEx™)

2. In-office: Cliradex Complete

3. Home therapy:

Tea-Tree oil tx

Key Reasons to Control Lid Flora and

Associated Inflammation

Blepharitis

Rosacea / Ocular Rosacea

MGD & secondary staph overpopulation

Pre-op surgical prophylaxis

Refractive

Cataract

Retinal

Contact lens wear

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Dr. O’Brien Recommended Pre-Op Lid

Hygiene Regimen with Avenova

No lid disease

1 week prior to surgery*

Some Blepharitis or MGD Dry Eye

2 weeks prior to surgery*

Moderate Blepharitis or MGD Dry

Eye

3 weeks prior to surgery*

Severe Blepharitis or MGD Dry Eye

4 weeks prior to Surgery*

* Apply to both eyelids and lid margins twice a day

Terrance P. O’Brien, MDBascom Palmer Eye Institute

Contact Lens Infiltrative Events

“The presence of substantial (>100 colony-forming units)

coagulase-negative staphylococci bioburden on lid margins was associated with about a five-fold increased risk for the development of a CIE (p

= 0.04).”Szczotka-Flynn L, Jiang Y, Raghupathy S, Bielefeld RA, et. al. Corneal inflammatory events with daily

silicone hydrogel lens wear. Optom Vis Sci. 2014;91(1):3-12.

“Lid hygiene should be as common

place and accepted as regularly brushing your teeth”

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Future Work:Surface Health and Visual Acuity

Disruptions in tear film can lead to wavefront aberrations and reduction in visual performance1-3

Contact lenses divide the tear film into two layers, increasing tear film breakup and potentially degrading

visual acuity4

Tear film disruption appears to be a common factor in reducing visual acuity in contact lens patients and those with dry eye3

TBU, tear breakup.

1. Koh S, et al. Am J Ophthalmol. 2002;134:115-7. 2. Tutt R, et al. Invest Ophthalmol Vis Sci. 2000;41:4117-23. 3.

Himebaugh NL, et al. Optom Vis Sci. 2012;89:1590-1600. 4. Craig J, et al. Invest Ophthalmol Vis Sci.

2013;54:TFOS123-TFOS156.

Prevent papillae in CL wearers