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Current Treatment

and Management of

Dry Eye

David I. Geffen, OD, FAAO

David I Geffen, OD, FAAOConsultant/Advisor/Speaker

Accufocus

Alcon

AMO

Annidis

Bausch + Lomb

Bruder Healthcare

EyeBrain

Optovue

Revision Optics

Shire

Tear Lab

Tear Science

TLC Vision

What is Dry Eye Disease (DED)? Multifactorial disease of the tears and ocular surface

Involves: Increased osmolarity of the tear film Inflammation in the ocular surface Dysfunction of one or more tear film components

Results in: Tear film instability Damage to the ocular surface Discomfort (in most) Visual disturbance

International Dry Eye Workshop 2007

Table 4

CORE

mechanisms

High

Evaporation Rate

Refractive Surgery

CL wearTopical anesthesia

Systemic drugs

inhibit flow

Inflammatory

lacrimal damage

SSDE; NSDE; Lacrimal

Obstruction

– –

–

Xerophthalmia

Ocular allergyPreservatives

CL wear?

Lacrimal

Gland

initial lacrimal stimulation

Low

Lacrimal

Flow

neurogenic

inflammation

increased

reflex drive

nerve

stimulation

Activate

Epithelial

MAPK +NFB +

Hyperosmolarity

nerve

injury

Reflex

block

Tear

Film

Instability

Goblet cell,

glycocalyx mucin loss

Epithelial damage- Apoptosis

– –

–

– –

–

++

+

Deficient or

unstable TF

lipid Layer

EnvironmentHigh Air Speed

Low Humidity

MGD

Blepharitis

Lid flora

lipases esterasesdetergents

Tear

Low androgens

Ageing

IL-1+

TNF +

MMPs

neurosecretory

block

International Dry Eye Workshop 2007

Challenges in Dry Eye Disease Patients often present with conflicting signs

Low Schirmers (< 5 mm) with a high TBUT (> 7 seconds)

Evidence of staining, but normal Schirmers & TBUT

Symptoms alone are not diagnostic and insufficient to determine severity Questionnaires are nonspecific

Patients are unsatisfied with current standard of care; they move from practice to practice seeking better options

Existing signs and tests correlate poorly with disease severity Schirmer test, TBUT, staining may not correlate with each other or

symptoms1

1 . Nichols KK. The Lack of Association Between Signs and Symptoms in Patients with Dry Eye Disease. Cornea 2004; 23(8) 762-770.

Dry Eye is a Disease of the

Lacrimal Functional Unit

1

2

3

4

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Dry Eye Prevalence NIH: 7-33% of US population has dry eye

Current US Population: 318.9 Million (2014)

63.8 Million Dry Eye Sufferers

At minimum: 4.5 Million in Southern California alone

33,100 Optometrists in the US

1,927 dry eye patients per OD

National Institutes of Health: nih.gov

Population Data: census.gov

Number of ODs.: Bureau of Labor Statistics: bls.gov

Prevalence0 10 20 30 40 50 60 70 80 90

CVD

Obesity

Dry Eye

Arthritis

Diabetes

Cancer

83.6

78.6

63.8

52.5

29.1

13.8

Prevalence (Millions)

Data obtained from the CDC:

cdc.gov

Economic Impact

0

500

1000

1500

2000

2500

3000

Mild Moderate Severe

$452.00

$744.00

$2,698.00

Annual Out of Pocket Cost

Average Annual Indirect Cost per Patient: $11,302.00

Yu J, Asche C, Fairchild C. The Economic Burden of Dry Eye Disease

in the United States: A Decision Tree Analysis. Cornea 2011; 30(4):

379-387

Patient Demographics

New Demographics Data

65.6% had Definite or Probable Dry Eye

Disease

60.2% of Men

76.5% of Women

78.6% had a TBUT of 5 seconds or less

74.3% of Men

87.2% of Women

Uchino, M., N. Yokoi, Y. Uchino, et al. "Prevalence of Dry Eye

Disease and Its Risk Factors in Visual Display Terminal Users."

American Journal of Ophthalmology 154.4 (2013): 759-66. Print.

Estimates of DED Prevalence Vary Based on How the Disease is Defined

Study Prevalence

Salisbury Eye Study1 14.6%

Beaver Dam2 14.4%

Women’s Health Study3 7.8%

Blue Mountains4 16.6%

Shihpai (Asian)5 33.7%

Sumatra (Asian)6 27.5%

Allergan phone survey7 48.0%

1. Schein OD, Munoz B, Tielsch JM, et al. Am J Ophthalmol 1997;124:723-8. 2. Moss SE, Klein R, Klein BE. Arch Ophthalmol 2000;118:1264-8. 3.Schaumberg DA, Sullivan DA, Buring JE, Dana MR. Am J Ophthalmol 2003:136;318-26. 4. Chia EM, Mitchell P, Rochtchina E, et al. ClinExperiment Ophthalmol 2003;31:229-32. 5. Lin PY, Tsai SY, Cheng CY, et al. Ophthalmology 2003;110:1096-101. 6. Lee AJ, Lee J, Saw SM, et al.Br J Ophthalmol 2002;86:1347-51. 7. http://newsfromaoa.org/2011/11/06/new-allergan-survey-shows-48-have-dry-eye-symptoms/

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Dry Eye Is Prevalent

2.5 million people in the United States1

A top reason for visits to EyeMDs and Ods

Patients often dissatisfied with treatments

Frequent drops inconvenient

Limited symptomatic relief

Frustrated

Want new options

1 Multi-Sponsor Surveys, Inc. The 2005 Gallup Study of Dry Eye Sufferers. 2005.

Dry Eye Patient Factors Older age

Female gender

Post-menopausal

Tobacco smoking

Contact lens wear

Prolonged staring (e.g. computer work)

Environmental Factors Air Pollution

Artificial, forced air

Allergens

Low humidity

Medications Antihistamines

Antidepressants

Antispasmodics

Diruetics

Oral contraceptives

Hormonal therapy

Disease Related Factors Systemic:

Autoimmune disease (TED) Neurologic disease that reduces blink Vitamin A deficiency

Local:

Lacrimal gland infiltration Eyelid malposition, laxity,

lagophthalmos Ocular surface disease

Lacrimal Glands:• Chronic irritation

• T-cell activation

• Cytokine secretion into tears

Interrupted Secretomotor Nerve Impulses

Tears Damage Ocular Surface

Cytokines Disrupt Neural Arc

Disruption of normal neuronal control of tearing

Pathophysiology of

Chronic Dry Eye Disease

Lacrimal Damage

Stern et al. Cornea. 1998.Nelson et al. Adv Ther. 2000.

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Healthy Tears

Complex Mixture Antimicrobial proteins

Growth factors

Cytokines

suppress inflammation

Mucin secreted by goblet cells

Viscosity

Electrolytes

Osmolarity

Image adapted from: Dry Eye and Ocular Surface Disorders. 2004.

Stern et al. In: Dry Eye and Ocular Surface Disorders. 2004.

Functions of a

Healthy Tear Film

Optical clarity, refractive power

Ocular surface comfort, lubrication

Protection from environmental and infectious insults

Antibacterial proteins, antibodies, complement

Reflex tears flush away particles

Trophic environment for corneal epithelium

Necessary electrolytes maintain pH

Protein factors for growth and wound healing

Antioxidants Rolando et al. Dry Eye and Ocular Surface Disorders. 2004.Stern et al. In: Dry Eye and Ocular Surface Disorders. 2004.

Tears in Chronic Dry Eye

Decreased proteins

and growth factors

Altered cytokine

balance promotes

inflammation

Proteases activated

Increased electrolytes

Altered viscosity Solomon et al. Invest Ophthalmol Vis Sci. 2001.Zhao et al. Cornea. 2001.

Ogasawara et al. Graefes Arch Clin Exp Ophthalmol. 1996.Image adapted from: Dry Eye and Ocular Surface Disorders. 2004.

Effects of Altered Tear

Composition in Chronic Dry Eye

Ocular surface tissue environment altered

Lubrication compromised due to poor viscosity

Increased osmolarity

Imbalanced growth factors and cytokines fail to promote

normal epithelial growth

Ocular surface damage

Loss of corneal epithelial integrity

Squamous metaplasia of conjunctival epithelium

Pflugfelder. Am J Ophthalmol. 2004.

Most DED Is Not A Result Of Aqueous Deficiency

Two Main Subtypes of DED asDefined by DEWS

International Dry Eye Workshop 2007

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Majority of DED Patients Have Evaporative Dry Eye (EDE)

Lemp MA, et al. Cornea. 2012;31:472-478.

86% of patients with a classified DED subtype demonstrated signs of Meibomian Gland Dysfunction

Pure Aqueous Deficient Dry Eye (ADDE) subtype represented the smallest percentage of patients (~10%) DED Is Not Defined By Symptoms

Signs and Symptoms of DED are Poorly Correlated

Sullivan BD, et al. Acta Ophthalmologica. 2012; doi: 10.1111/aos.12012.

Many Asymptomatic Patients Are Hyperosmolar

Normal Subjects1

Hyperosmolar Subjects2

Overall population, % 52 48

Patients reporting at least one symptom of DED, %

51 49

Asymptomatic patients, % 56 44

1 ≤ 308 mOsm/L2 > 308 mOsm/L

Sullivan BD, et al. Acta Ophthalmologica. 2012; doi: 10.1111/aos.12012.

Symptoms: Normal vs Elevated Osmolarity

Normal osmo but Ocular Surface Irritation/complaints

• Adequately treated DED• C.L. &/or solution irritation• Mild allergic conjunctivitis

• Epithelial Basement Membrane Dystrophy

• Pinguecula/early pterygia• Infection

• Anterior blepharitis• Demodex

Elevated >308 or inter-eye difference of >8 mOsml/L

•Meibomian Gland Dysfunction•Lacrimal Gland Insufficiency

•Contact Lens Induced DE (CLIDE)•Androgen deficiency

•Post Refractive/Cataract surgery•SjÖgren’s Syndrome

DED Can Decrease Visual Acuity

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Optics Of The Tear Film

Tear film stability is critical for the maintenance of visual quality Uniform reductions of tear film thickness have little effect

Irregular thickness degrades image quality

Patients with DED have larger optical aberrations compared with normal eyes (by a factor of ~2.5)

Artificial tears reduce these abnormalities and improve image quality in patients with DED

Montes-Mico R. J Cataract Refract Surg. 2007.

Osmolarity is Very Well Correlated

With Visual Function

Data Courtesy of Pisella PJ, Habay T, Nochez YDepartment of Ophthalmology University Francois Rabelais Tours, France

The Look of Dry

Normal Abnormal

Tear Breakup Time

(TBUT)

Tear film instability is a hallmark of dry eye

Correlates with aqueous and evaporative tear deficiency (Pflugfelder et al,

1998)

TBUT measures tear film quality

Fluorescein introduced from strip, yellow filter increases sensitivity

TBUT = time from completed blink to 1st dry spot (3 repetitions)

TBUT < 10 seconds abnormal (Lemp, 1995)

Anesthesia decreases TBUT (de Paiva et al, 2004)

Abnormal corneal surface - > break-up spots

Lissamine Green Staining

in Dry Eye

Lissamine green detects dead or degenerated conjunctival cells

Exposure zone staining with limbal sparing

Exposure zone staining with limbal staining

Intense diffuse staining of exposure zone, limbal staining

Images from Dry Eye and Ocular Surface Disorders. 2004.

Vital Stains

Fluorescein Rose Bengal Lissamine Green

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Schirmer’s Strips

38

Behrens et al. Cornea. 2006.

Consensus Treatment Algorithm Guidelines

Dry Eye Management

Mild to Moderate Symptoms

Minimal or no signs

Add Essential fatty acids (EFA) Flaxseed oil, Hydroeye®

Add tear replacement Osmolarity

Viscosity

Combination

Restasis

Xiidra

Dry Eye Management

Moderate to Severe Symptoms Signs present: Abnormal tear film, corneal and

conjunctival staining

Essential fatty acids (EFA) Flaxseed oil, Hydroeye®

Topical anti-inflammatory agents Cyclosporine

Lifitegrast

If dry mouth also present: consider oral cholinergics Pilocarpine (Salagen®)

Cevimeline

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Cyclosporin and / or LifitegrastDosing and Administration

Not “as needed” like traditional eye drops

One drop-each eye in morning & evening

Vials should be discarded after each use

Two vials per day are required, and that’s why it’s

important for patients to receive 2 trays for 30 days

Artificial tears may be used for concomitant relief (no

preservatives much better !)

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RESTASIS®

increases tear production

in some patients

In pivotal trials, the use of RESTASIS® twice a day for 6 months (2000)

Increased goblet cell density

Increased tear production

Decreased corneal staining

Reduced reliance on artificial tears

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Xiidra Xiidra

By Blocking ICAM-1/LFA-1 Interaction,

Lifitegrast May Inhibit:

T-Cell Activation

T-Cell Migration

Cytokine Release

Dry Eye

Surgical Management

Punctal occlusion

Plugs

Cautery

Distribution of dry eye

subtypes

MGD49.7%

Aq. Deficient14.5%

Mixed35.8%

MGD

Aq. Deficient

Mixed

Lemp, M., Crews, L., Bron, A., et al. “Distribution of Aqueous-Deficient and

Evaporative Dry Eye In…” Cornea: The Journal of Cornea and External Disease 31.5

(2012): 472-78. Print.

DEWS Dry Eye

Categorization:

Adapted from DEWS 2007

report

Most Common Methods of:Diagnosis:

Schirmer’s Testing

NaFl/Rose

Bengal/Lissamine Green

Staining

TBUT

Symptom Surveys:

OSDI/SPEED Testing

Treatment:

Artificial Tears

Restasis

Punctal Plugs

Warm Compresses

Johnson & Johnson’s ™

Baby Shampoo Lid

Cleansing

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Time for a paradigm shift DEWS (2007): Symptoms are an essential component to Dry Eye

Disease

2014 Correlation Study: 43% of patients with Dry Eye are

asymptomatic

Missed Opportunities

Early intervention

Sullivan, B. D., L. A. Crews, and E. M. Messmer. "Correlations between

Commonly Used Objective Signs and Symptoms for the Diagnosis of

Dry Eye Disease: Clinical Implications." Acta Ophthalmologica 92

(2014): 161-66.

The Psychology of dry eye Falls into the psychology of chronic illness

Frustration

Hopelessness

Suffering from symptoms others can’t see

Our most effective tool: objective in-office testing

Patients need proof

SPEED testing, Schirmer’s/Zone Quick, tear break up test

New Methods of Diagnosis: LipiView II Imaging

Interferometry

Blink Analysis

Meibography

Miebomian Gland Evaluator

Systemic Disease Testing

LipiView II & MGE

Interferometry & Blink Analysis

Meibography MGE

Systemic Testing

www.bausch.com

Sjogrens.org

New Methods of Treatment Problem-specific Artificial Tears

Supplements

Advanced Lid Hygiene

LipiFlow

Bio-Tissues

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Problem Specific Artificial Tears Evaporative Dry Eye Multi-factoral Dry Eye Night time Lagohphthalmos

Supplements (And Masks)

Advanced Lid Hygiene Bio-Tissues

Dehydrated amniotic tissues

Aril

Moria

AmbioDisk

Cryo-preserved

BioTissues: Prokera

Prokera Patient OutcomesBefore 2 Days After

LipiFlow FDA Study Results

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Lipiflow 1 Year Study LipiFlow GWSVI Outcomes SPEED Scores Pre- & Post- LipiView (1 month)

0

5

10

15

20

25

Pre-Procedure Post procedure

21

8.5Spee

d S

core

s

How Patients Should Prepare:

No drops, gels, ocular medications 4 hour

prior

No ointments for a minimum of 12 hours

prior

No moisturizers, creams, sun block, or

make-up around the eye the day of

Types of MeibumClear Cloudy Semi-Solid

Insipissated Obstruction w/ Neo Notching

Non-Obvious MGD

NOMGD

MGD

In Office Dry-Eye Testing:

Krob Meibomian Gland Evaluator

Line of Marx Evaluation

Transillumination Estimation of MG

structure

KB Lid-Light Test

LipiFlow Keys to Success

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Korb Meibomian Gland

Evaluator

Standardize clinical findings

Force = deliberate blink

How to: Wipe lid margin clean

Press in along three zones at base of lashes

Temporal Nasal

Angle face of MGE to be tangential to globe

Evaluate secretions (if no secretions, asses for 15 sec)

Line of Marx Evaluation

Mild Moderate Severe

Transillumination Test

Complete Lid Closure Incomplete Lid Closure

Transillumination for MG

Structure

Non-Truncated

Truncated

LipiFlow Keys to Success

Accurate Pre- & Post-procedure

measurements

Managing patient expectations

Improving compliance with home

maintenance

Post-LipiFlow Managing post-procedure expectations

Well lubricated Period of increased dryness

Maximal benefits can be seen at 9 months out

Post-procedure inflammation management

Re-evaluation at regular intervals

Continued home maintenance