2020 Symposia Series 1

New Options for a Common Condition: Management of

Dry Eye Disease

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• Evaluate patients for risk factors, symptoms, and signs of dry eye disease

• Identify pharmacologic and nonpharmacologic approaches to the treatment

of dry eye disease

• Apply strategies to educate patients on management of dry eye disease

Learning Objectives

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Dry Eye Disease: Definition

• From the Tear Film and Ocular Surface Society Dry Eye Workshop II:

“Dry eye is 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.”

Craig JP, et al. Ocular Surf. 2017;15:276-283.

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• Conservatively affects between

5.3% and 6.8% of adults in the

US

‒ As many as 16.4 million people

• Women 2 to 3 times more likely to

be affected than men

• Prevalence increases linearly with

age

Dry Eye Disease is Common

Dana R, et al. Am J Ophthalmol. 2019;202:47-54; Farrand KF, et al. Am J Ophthalmol. 2017;182:90-98; Stapleton F, et al. Ocular Surf. 2017;15:334-365.

0

5

10

15

20

25

18-24 25-34 35-44 45-49 50-54 55-59 60-64 65-69 70-74 75+P

revale

nce (

%)

Age (years)

Diagnosed Dry Eye Disease in the US

Male

Female

18-49 years: 3.4%

50+ years: 11.3%

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Normal Eye Physiology

Clayton JA, et al. N Engl J Med. 2018;378:2212-222.

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Aqueous Deficient

• Lacrimal gland

deficiency/obstruction

• Systemic drugs

• Autoimmune disorders

Pathophysiology and Classification of Dry Eye Disease

Craig J, et al. Ocular Surf. 2017;15:276-283; Rabensteiner DF, et al. Acta Ophthalmol. 2018;96:e707-e711; Wolffsohn J, et al. Pharmaceutical J.

2017;299:7905.

• Patients may have both

aqueous-deficient and

evaporative types

• Evaporative is the most

common

⎻ Meibomian gland

dysfunction (MGD) is

leading cause of dry

eye disease

• ~2/3 of all cases

Deficient tear production

and increased tear

evaporation lead to

hyperosmolarity and

inflammation

Evaporative

• MGD

• Allergic

conjunctivitis

• Contact lens

wear

• Low blink rate

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Case Study: Kate

• 49-year-old white female

• Accountant

• Married with 1 child

• Avid runner

• Ocular history:

⎻ Daily contact lens wearer

for 20 years

• Medical history:

⎻ Nonsmoker, nondrinker

⎻ Migraines, managed with

sumatriptan nasal spray

⎻ Elevated LDL-C, managed

with rosuvastatin

• She is at your office today for her annual wellness exam

LDL-C = low-density lipoprotein cholesterol.

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Case Study (cont’d): Kate’s Chief Complaints and Exam

• Feeling well overall, but her eyes have

been bothering her lately

‒ When she runs outside, especially

on a cold windy day, she starts

tearing profusely

‒ Sometimes she wakes up in the

middle of the night with eyes

“burning and stinging,” like sand was

thrown in them

• It’s hard even to open them just to

add tetrahydrozoline drops

Physical Exam

Vital signs normal

Ocular Exam

Slight redness

No mucus

Cornea clear, no opacities

No sign of crusting on the eyelids

Visual acuity 20/20 with contacts

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Symptoms of Dry Eye Disease Are Nonspecific and May Be

Inconsistent With Clinical Signs in Mild Disease

• Symptoms usually:

⎻ Worsen over the

course of the day

⎻ Have been

occurring

chronically

⎻ Affect both eyes

American Academy of Ophthalmology. www.aao.org/preferred-practice-pattern/dry-eye-syndrome-ppp-2018. Accessed April 25, 2020;

Cronau H, et al. Am Fam Phys. 2010;81:137-144; Shih KC, et al. HK Pract. 2016;38:113-119. Wolffsohn JS, et al. Ocular Surf. 2017;15:539-574.

Common Symptoms of

Dry Eye Disease

Irritation or grittiness

Itching

Redness

Soreness

Fatigue or heaviness

Burning sensation, stinging

Photophobia

Intermittent blurred vision

Ocular discomfort

Excessive tearing

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The First Step in Achieving a Diagnosis of Dry Eye Disease

Is a Detailed Patient History

Milner MS, et al. Curr Opin Ophthalmol. 2017;28(Suppl1):3-47.

• Chief complaints and current symptoms

• Medical history

• Ocular history, including surgical history and contact lens use

• Systemic medications

• Allergies

• Prior and current therapy for dry eye disease

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The Next Step in Achieving a Diagnosis Is a Physical Exam

Appropriate to Primary Care

• Inspect eyelid and sclera for inflammation, abrasions, hemorrhage, erythema or lesions

• Evert the upper eyelid if corneal abrasion or foreign body is suspected

• Inspect the eyelid and periorbital region for rashes or vesicles

• Examine the cornea for opacities

• Examine conjunctiva for injection, erythema

• Note evidence of discharge; assess eyelids for crusting

• Assess visual acuity

Kaur S, et al. www.acofp.org/ACOFPIMIS/Acofporg/PDFs/OFP/Articles/2019_MarApr/2019_MarApr_PrimaryApptoEyeCond.pdf. Accessed April 25,

2020; Pflipsen M, et al. Am Fam Phys. 2016;93:991-998.

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Dry Eye Disease vs Other Common Ocular Disorders

That Cause Red Eye

Bilateral presentation with:

• Diffuse hyperemia

• Mild or no pain

• Mild blurring or normal vision

Discharge is…

Continuous

Intermittent

Dry eye

Watery

or

serous

Mucopurulent

to purulent

Viral

conjunctivitis

Allergic

conjunctivitis

Acute

bacterial

conjunctivitis

Chlamydial

conjunctivitis

Itching

Mild to

none

Moderate

to severe

Cronau H, et al. Am Fam Phys. 2010;81:137-144.

Bacterial conjunctivitis image attributed to Tanalai at English Wikipedia. No alterations were made to the image by PCE. Image license:

creativecommons.org/licenses/by/3.0/legalcode; Chlamydial conjunctivitis image attributed to Jonathan Trobe, MD, University of Michigan

Kellogg Eye Center. No alterations were made to the image by PCE. Image license: creativecommons.org/licenses/by/3.0/legalcode.

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Class Individual Factors

Environmental

Conditions

Dry climate ▪ long-term contact lens use ▪ prolonged periods of not blinking

(as when staring at a computer screen) ▪ smoke ▪ wind

Ocular Conditions Contact lens use ▪ ocular disease ▪ ocular surgery (especially LASIK) ▪

eyelid abnormalities

Medications Antidepressants ▪ anticholinergics ▪ antihistamines ▪ antihypertensives ▪

decongestants ▪ eye drops with preservatives ▪ hormone replacement

therapy

Systemic Conditions Androgen deficiency ▪ connective tissue disorders ▪ diabetes ▪ menopause

▪ rheumatoid arthritis ▪ Sjögren’s syndrome ▪ systemic lupus erythematosus

▪ thyroid conditions

Other Botulinum toxin application ▪ cosmetics ▪ eyelash growth enhancements ▪

LASIK ▪ use of a continuous positive airway pressure (CPAP) mask

Conditions/Factors That May Cause or Contribute to Dry Eye Disease

American Optometric Association. www.aoa.org/patients-and-public/eye-and-vision-problems/glossary-of-eye-and-vision-conditions/dry-eye.

Accessed April 25, 2020; Lee BS, et al. Clin Ophthalmol. 2020;14:119-126; Shih KC, et al. HK Pract. 2016;38:113-119; Zhang R, et al. Ocular Surf.

2020;18:158-169.

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• Hormonal influences of menopause can affect the tear film and cause

dry eye

• Women over 50 years of age have twice the risk of dry eye disease as

men of the same age

Menopause

Peck T, et al. J Midlife Health. 2017;8:51-54; Schaumberg DA, et al. Am J Ophthalmol. 2003;136:318-326.

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• Clues: unilateral presentation, sudden onset

Red Flags in a Patient Presenting With Red Eye

That Should Prompt Referral to an Ophthalmologist

Cronau H, et al. Am Fam Phys. 2010;81:137-144; Wolffsohn JS, et al. Ocular Surf. 2017;15:539-574.

Mild or no pain, with

mild blurring or

normal vision

Moderate to

severe pain

Vision loss,

distorted pupil,

corneal

involvement

Vesicular rash (herpetic keratitis),

severe mucopurulent discharge

(hyperacute bacterial

conjunctivitis), keratitis, corneal

ulcer, acute angle glaucoma, iritis,

traumatic eye injury,

chemical burn, scleritis

Emergency

ophthalmology

referral

Hyperemia

Diffuse

Focal Episcleritis

No discharge Subconjunctival

hemorrhage

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The Workup Is Informed by Classification of Dry Eye Disease Types

Craig JP, et al. Ocular Surf. 2017;15:276-283.

Dry Eye

Aqueous-deficient

Sjögren’s

syndrome dry eye

Evaporative

Extrinsic IntrinsicNon-Sjögren’s

dry eye

Secondary

Primary

Lacrimal gland

duct obstruction

Lacrimal

deficiency

Systemic drugs

Reflex block

Disorders of lid

aperture

MGD

Drug action (eg,

from isotretinoin)

Low blink rate

Topical drugs/

preservatives

Vitamin A

deficiency

Ocular surface disease

(eg, allergy)

Contact lens

wear

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Classification Criteria for Sjögren’s Syndrome

1. Have you had daily, persistent, troublesome dry eyes for more than 3 months?

2. Do you have a recurrent sensation of sand or gravel in the eyes?

3. Do you use tear substitutes more than 3 times a day?

4. Have you had a daily feeling of dry mouth for more than 3 months?

5. Do you frequently drink liquids to aid in swallowing dry food?

Must answer

yes to ≥1 of

these

questions:

Must

score ≥4

Shiboski CH, et al. Arthritis Rheumatol. 2017;69:35-45.

Item Weight/Score

Labial salivary gland with focal lymphocytic sialadenitis and focus score ≥1 3

Anti-SSA (Ro) + 3

Ocular staining score ≥5 (or van Bijsterfeld score ≥4 on ≥1 eye) 1

Schirmer score ≤5 mm/5 min on ≥1 eye 1

Unstimulated whole saliva flow rate ≤0.1 mL/min 1

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Case Study (cont’d):

You Probe Further Into Kate’s Symptomatology

Wolffsohn JS, et al. Ocular Surf. 2017;15:539-574.

Kate’s responses

Mildly irritating How severe is the eye discomfort

No Do you have any mouth dryness or enlarged glands?

A couple months/gets

worse at night

How long have you had symptoms?

Were there any triggering events?

Yes Is your vision affected? Does it clear on blinking?

No Are the symptoms/redness much worse in one eye?

NoDo your eyes itch, are they swollen, crusty, or give off

discharge?

Yes Do you wear contact lenses?

Medications, yesAny diagnosed conditions?

Are you taking any medications?

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Further Clues From Kate’s Symptomatology

Wolffsohn JS, et al. Ocular Surf. 2017;15:539-574.

Kate’s responses

Mildly irritating How severe is the eye discomfort • If severe, could be trauma, infection, ulceration

No Do you have any mouth dryness or enlarged glands? • Trigger for Sjögren’s syndrome workup

A couple months/gets

worse at night

How long have you had symptoms?

Were there any triggering events?

• Dry eye is chronic, typically worsening at the end of

the day

Yes Is your vision affected? Does it clear on blinking? • Should clear on blinking

No Are the symptoms/redness much worse in one eye? • Dry eye is generally bilateral

NoDo your eyes itch, are they swollen, crusty, or give off

discharge?

• Itching associated with allergies

• Mucopurulent discharge associated with infection

Yes Do you wear contact lenses? Contacts can cause dry eye

Medications, yesAny diagnosed conditions?

Are you taking any medications?

• Certain systemic conditions and medications may

cause dry eye

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• Treatment goals

‒ Restore homeostasis of the ocular surface

‒ Provide long-term options to prevent a resurgence of disease and

symptoms

• Management may require treatment individualized to the specific cause(s)

of dry eye disease

• Ongoing management is often required rather than short-term treatments

Management of Dry Eye Disease

Jones L, et al. Ocular Surf. 2017;15:575-628.

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OTC Ophthalmic Products: A Quick Overview

May Contain Pros Cons Comment

Artificial Tears

(drops) Viscous agent,

anti-evaporative,

preservative

Usually effective,

inexpensive

Difficulty with drops?

Tolerance of

preservative?

Consider

preservative free

(but expense)

Artificial Tears

(gels, ointments)

Blurred vision Use overnight

Antihistamines Pheniramine For allergy Can increase

dryness

Only if allergy

Vasoconstrictors Naphazoline,

tetrahydrozoline

“Get the red out” Rebound effect Avoid

Cleveland Clinic. health.clevelandclinic.org/choosing-right-eye-drops-itchy-dry-watery-eyes/. Accessed May 11, 2020; Cronau H, et al. Am Fam

Phys. 2010;81:137-144; Horton M, et al. www.reviewofoptometry.com/article/master-the-maze-of-artificial-tears. Accessed April 28, 2020.

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Case Study (cont’d): Management Plan

• You recommend that Kate try OTC artificial tears 4 times daily, with caveats

‒ Look for preservative-free products

‒ Avoid topical antihistamines, vasoconstrictors, or anything marketed to

“get the red out”

• You advise her to

‒ Use warm compresses on her eyes in the morning and at bedtime

‒ Apply an OTC artificial tear ointment at bedtime

• You ask her to take more frequent breaks from her computer and phone screen,

to wear her glasses instead of her contacts more regularly, and to blink more

• You ask her to try this regimen for 4 weeks

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Case Study (cont’d): Kate Comes Back After 4 Weeks

• After 4 weeks, Kate reports that her symptoms are a little better but she’s still

tearing profusely when she runs

• When you ask if she is adhering to her treatment she says she is:

‒ Using her artificial tears 4 times a day

‒ Applying the ointment at night

‒ Using warm compresses in the morning and night

‒ Wearing glasses more regularly

‒ Not taking breaks from her computer screen—she is “working on this”

‒ Blinking more

• You decide to refer her to an ophthalmologist for a full workup

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• Chronic, untreated dry eyes may result in ocular surface damage such as

abrasions and corneal ulcers, leading to vision impairment

• Without adequate tears, there is an increased risk of infection

Chronic Dry Eye Can Become Serious if Not Treated

Mayo Clinic. www.mayoclinic.org/diseases-conditions/dry-eyes/symptoms-causes/syc-20371863. Accessed April 25, 2020.

Corneal ulcer

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The Ophthalmologist’s Basic Diagnostic Algorithm for Dry Eye Disease

Jones L, et al. Ocular Surf. 2017;15:575-628.

Symptoms

+ ≥1 of:

Homeostasis Markers

• Tear breakup time <10

seconds

• Osmolarity

• Ocular surface

staining

• Diagnosis of dry eye disease confirmed if patient has dry eye symptoms

and ≥1 positive homeostasis test result

• Subtype then determined

Triaging

Questions

Risk

Factor

Analysis

Evaporation

Aqueous

deficiency

Subtype

Classification

Tests

Ste

p 1

Ste

p 2

Ste

p 3

Ste

p 4

Aque

ous/E

vapora

tive S

pectr

um

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Classification of Dry Eye Disease Types

Craig JP, et al. Ocular Surf. 2017;15:276-283.

Dry Eye

Aqueous-deficient

Sjögren’s

syndrome dry eyeIntrinsic

Non-Sjögren’s

dry eye

Secondary

Primary

Lacrimal gland duct

obstruction

Lacrimal deficiency

Systemic drugs

Reflex block

Disorders of lid

aperture

MGD

Drug action (eg,

from isotretinoin)

Low blink rate

Topical drugs,

preservatives

Vitamin A deficiency

Ocular surface disease eg,

allergy

Contact lens wear

Evaporative

Extrinsic

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Case Study (cont’d): Examination by the Ophthalmologist

Examination:

• Visual acuity: 20/20 with glasses

• Tear breakup time: 10 seconds (cutoff is 10 seconds)

• Tear osmolarity: 330 mOsm/L (cutoff is 308 mOsm/L)

• Ocular surface staining:

‒ Punctate epithelial staining with fluorescein indicating mild keratopathy

• No evidence of meibomian gland involvement

Diagnosis:

• Aqueous-deficient dry eye disease

Wolffsohn JS, et al. Ocular Surf. 2017;15:539-574.

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Nonspecific Management of Dry Eye Disease

• Education

⎻ The condition, its management, treatment, and prognosis

⎻ Potential dietary modifications (including oral essential fatty acid supplementation)

• Modification of local environment and lifestyle

⎻ Humidification, breaks from screen time, avoiding smoke, avoiding direct fan

exposure to eyes in car and at home

• Identification and potential modification/elimination of offending systemic and topical

medications

• Ocular lubricants of various types

⎻ If MGD is present, consider lipid-containing supplements

• Lid hygiene and warm compresses of various types

American Academy of Ophthalmology. www.aao.org/preferred-practice-pattern/dry-eye-syndrome-ppp-2018. Accessed April 25, 2020.

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• Supplementation

‒ Randomized, placebo-controlled DREAM study (N = 535)

• No significant differences between omega-3 and placebo

• Both groups experienced similar, significant improvement in signs/symptoms

‒ In contrast, a meta-analysis of 17 randomized clinical trials (N = 3363)

• Supported efficacy of omega-3 supplementation in improving

signs/symptoms vs placebo

• Diet

‒ A diet high in omega-3 fatty acids may protect against development of dry eye

disease

Essential Fatty Acids in Dry Eye Disease: Evidence Not

Compelling, But Little Harm in Trying

DREAM = Dry Eye Assessment and Management Study.

Asbell PA, et al. N Engl J Med. 2018;378:1681-1690; Giannaccare G, et al. Cornea. 2019;38:565-573; Miljanović B, et al. Am J Clin Nutr.

2005;82:887-893.

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Examples of Specific Therapies for Dry Eye Disease

Conventional Therapy for all

Subtypes:

Artificial tears, artificial tear

ointment, warm compresses/

lid scrubs

Doxycycline/ azithromycin

+/– Topical steroids

+/– Omega-3

BlephEx

or

Maintenance antibiotics

Thermal pulsation

or

IPL with manual expression

or

Probing

Punctal plugs

or

CsA 0.05%

Punctal plugs or

lifitegrast or

Frequency of CsA 0.05%

Autologous serum tears

&

Consider systemic workup

Aqueous-deficient dry eye disease

Evaporative Dry Eye Disease

IPL = intense pulsed light.

American Academy of Ophthalmology. www.aao.org/preferred-practice-pattern/dry-eye-syndrome-ppp-2018. Accessed April 25, 2020;

Milner MS, et al. Curr Opin Ophthalmol. 2017;28(Suppl1):3-47.

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Therapeutic Expression of the Meibomian Glands

Arita R, et al. Clin Exp Optom. 2020. [epub ahead of print].

• Therapeutic expression of

thickened and toothpaste-like

meibum in a patient with MGD

with use of a meibomian gland

compressor

Image courtesy of Arita R, et al.

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IPL

Procedures for Dry Eye Disease

Lee BS, et al. Clin Ophthalmol. 2020;14:119-126; Milner MS, et al. Curr Opin Ophthalmol. 2017;28(Suppl1):3-47.

Beye. www.beye.com/product/eyexpress-eye-hydration-system. Accessed April 25, 2020.

TrueTear

iLux

Aqueous tear deficiency

• Punctal plugs

• Cautery occlusion

• Amniotic membrane

transplantation

• Intranasal tear

stimulation (TrueTear)

Blepharitis/MGD (evaporative or

nonevaporative)

• In-office thermal pulsation and/or

lid massage

• Debridement of the lid margin

• Intense pulsed light (IPL)

• Meibomian gland probing

⎻ Light-based heat and

compression (iLux)

⎻ Open-eye wearable therapy

(TearCare)

⎻ EyeXpress (goggle system)

TearCare

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Case Conclusion

• Ophthalmologist recommends 8-week trial of the following:

‒ Continue warm compresses, morning and night

‒ Prescription CsA, 0.05%, 4 times daily (may take 6-8 weeks to see results)

‒ Prescription tear ointment at night

• After 8 weeks, Kate reports:

‒ Symptoms have subsided dramatically

‒ No longer tearing profusely when running

‒ Has not experienced burning or stinging at night

• She is advised to continue her regimen indefinitely

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PCE Action Plan

✓ Bilateral involvement and gradual onset should prompt suspicion of dry

eye disease

✓ Examine the eyelids, conjunctiva, cornea, sclera, and periorbital region

when assessing for dry eye disease

✓ Advise patients with dry eye disease to avoid topical antihistamines,

vasoconstrictors, or anything promising to “get the red out”

✓ Be sure to educate patients that management of dry eye disease may be a

long-term process

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PCE Promotes Practice Change

2020 Symposia Series 1