Doctors of Optometry | Course Notes · Doctors of Optometry | Course Notes OD21 – 1 CE Modern...

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Doctors of Optometry | Course Notes

OD21 – 1 CE Modern Management of Dry Eye Disease Supported with an unrestricted education grant by Shire Pharma Canada

Monday, February 19, 2018 9:05 am – 10:00 am Georgia A/B – 2nd Fl

Presenter: Dr. Gregory Caldwell Greg Caldwell, O.D., is a 1995 graduate of the Pennsylvania College of Optometry. He completed a one-year residency in primary care and ocular disease at The Eye Institute in Philadelphia Pennsylvania. He is a fellow of the American Academy of Optometry (AAO) and a Diplomate of the American Board of Optometry (ABO). He currently works in Duncansville, Pennsylvania as an ocular disease consultant. Dr. Caldwell’s primary focus is the diagnosis and management of anterior and posterior segment ocular disease and he has been a participant in multiple FDA investigations. Dr. Caldwell has lectured extensively throughout the county and over twelve countries internationally. In 2010 he served as President of the Pennsylvania Optometric Association (POA) and served on the AOA Board of Trustees 2013-2016. He is President of the Blair/Clearfield Association for the Blind.

Course Description

Dry eye is a common yet under diagnosed cause of ocular morbidity such as decreased vision and ocular discomfort. This course will view the modern management of dry eye disease including pharmaceuticals, nutraceuticals, and devices. This case based presentation will aid in the diagnosis, treatment, and guidance around pitfalls.

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Doctors of Optometry | Course Notes

NOTES:

Modern Management of Dry Eye February 19, 2018

Greg A. Caldwell, OD, FAAO [email protected] 814-931-2030 cell 1

Modern Management of Dry Eye Disease

Greg Caldwell OD, FAAOFebruary 19, 2018

Disclosure Statement(next slide)

Disclosures- Greg Caldwell, OD, FAAO

$ Will mention many products, instruments and companies during our discussion

¬ I don�t have any financial interest in any of these products, instruments or companies

$ Pennsylvania Optometric Association –President 2010

2 POA Board of Directors 2006-2011 $ American Optometric Association, Trustee 2013-2016

¬ Thank you to the members and those who join $ I never used or will use my volunteer positions to further my lecturing

career$ Lectured for: Shire, BioTissue, Optovue

$ Advisory Board: Allergan

$ Envolve: PA Medical Director, Credential Committee $ Optometric Education Consultants- Scottsdale and Quebec City, Owner

Course Description and Learning Objectives

Dry eye is a common yet under diagnosed cause of ocular morbidity such as decreased vision and ocular discomfort. This course will view the modern management of dry eye disease including pharmaceuticals, nutraceuticals, and devices. This case based presentation will aid in the diagnosis, treatment, and guidance around pitfalls.

$Review aqueous deficient and evaporative dry eye

$Review the diagnostic techniques to help diagnose aqueous deficient versus evaporative dry eye

$Discuss current and modern treatment of dry eye disease$Discuss current pharmaceutical and nutraceutical therapies

$Review the current devices available for the treatment of dry eye disease

How Many People With

$Diabetes$Thyroid

$Glaucoma$Dry Eye

Vital Dyes $ Fluorescein

¬ Detects disruption of intercellular junctions¬ Positive (stain)-pooling¬ Negative (stain)-high or elevated areas

$ Rose bengal and Lissamine green ¬ Stains devitalized cells and cells that have

lost normal mucin surface¬ Detects abnormal epithelial cells

Why is Conjunctival Staining and SPK Often Missed or Under Scored ?

Wratten Filter



Aqueous Deficient vs Evaporative

$What’s the common denominator?

$What’s the next question?

48 year old manOU red, gritty, sandy and dry feeling

Va 20 20 20cc 20

Current CorrectionR -2.00 sphereL -3.00 sphere

EOMS: full, unrestricted PERRL (-)APDCT: ortho D/N CF: full by FC OU

$Diagnosis¬ Rosacea

$What findings support your diagnosis?¬ Telangiectasias

¬ Erythema of the cheeks, forehead and nose

¬ Rhinophyma2 Indicates chronic

$Let us get a closer look

A Closer LookMeibomian Gland Dysfunction

Exacerbated by Rosacea Evaporative

$Treatment?¬ In my opinion, most under treated condition¬ Warm compresses¬ Lid hygiene

¬ Artificial tears¬ Omega 3 fatty acid

2 EPA and DHA total 1500 mg (1000 mg minimum) ¬ Dermatological consult (Acne Rosacea)¬ Oral antibiotics…???

2 Which one and why??



Minocycline

Leukotrienes

Arachidonic Acid

Staph AureusStaph Epidermidis Lipase

Meibomian Gland Secretions(Lipid)

ProstaglandinsThromboxines

Marginal Foam(Soap)

TurbidInspissated MG

How About Steroids?

Phospholipids

Tetracycline Analog Clinical PearlTreatment Failure

$If you continue to think of doxycycline and minocycline as antibiotics, treatment failure will be the result

$From this point on consider them a steroid

Minocycline / Doxycycline$Drug of choice for marginal inflammatory

blepharitis (posterior blepharitis)$AB, anti-inflammatory and anti-collagenase$Inhibits lipase enzyme

$No renal adjustment$50-100 mg qd-bid 2-12 weeks (pulse)

¬Lower maintenance dose

$20 mg Periostat (Doxycycline)¬Helpful in those with stomach or GI sensitivity¬Excellent for those requiring long maintenance dose

My Paradigm for Minocycline / Doxycycline

$Status of MG

¬Inspissated

¬Turbid

¬Clear

$Minocycline / Doxycycline Paradigm

¬Maximum dosage for 2-12 weeks (pulse)2 100 mg BID, QD

¬50-100mg qd while turbid¬20 mg longer treatments

2 Periostat (Doxycycline)

¬20 mg if maintenance dose needed

Precautions With Oral Tetracycline Analogs

$ Enhanced photosensitivity$ Avoid in children and pregnancy

(Category D)$ Can enhance Coumadin$ Can enhance the action of digoxin$ ?Long term use with increase risk

of breast cancer?¬ 1 paper/study, not regarded as

highly reliable study¬ Further investigation discredited

the association$ Benign intracranial hypertension,

reported cases¬ 17 cases from 1978-2002

Benign intracranial hypertension�It�s not rare if it�s in your chair�

8-19-2010

8-31-2010



9-13-2010

10-6-2010

8-19-2010

Successfully Treated

$ Warm Compresses

$ Lid Scrubs$ Artificial Tears, Systane Balance

$ Omega 3 (1500 EPA and DHA)

$ Mino 100 mg PO 6 weeks, 50 mg 3 months, 20 mg maintenance (Doxy)

$ Steroids, Tobradex qid (5 weeks with taper)¬ Moderately red and thickened lid margins¬ Marginal infiltrates

What is an Inspissated MG? I Can�t Believe It�s Not Butter!® Squeeze



6 Month Later 1 Year Later

What Has Changed?

Bruder Moist Heat Eye Compress

Bruder Moist Heat Eye Compress

$ Moist heat treatment ¬ Stabilize the tear film, improve oil gland function, slow tear evaporation

$ Ready in seconds, easy to use¬ Patient compliance increases

$ Patented MediBeads¬ Self-hydrating (no need to add water)¬ Anti-bacterial and non-allergenic¬ Washable and reusable

$ Safe for frequent use ¬ Microwave for 20-25 seconds ¬ Apply for 10 minutes

$ Unique pod design provides improved fit and performance

Dry Eye Relief and Daily Eyelid Hygiene

Micro-fine sheets are designed to cleanse the eyelids

Bruder Cold Therapy Eye Compress



XiidraWhat Have I Learned?

$How many did you write before you called failure?$Only pharmaceutical indicated for the signs and

symptoms of dry eye¬ Prior authorizations

2 CoverMyMeds

2 ParRx

$BID means 11-12 hours apart

$It’s safe, safe, safe… 5-25% report site irritation, blurred vision, or dysgeusia¬ Tell the patients they may taste it

$Use it as a diagnostic


$Restasis when prescribed- how long until you see improvement?

$Xiidra¬ 2 weeks- symptom relief in moderate patient¬ 6 weeks- symptom relief in mild patient

¬ 12 weeks/3months- cornea improvement

$Restasis or Xiidra?

$Use on GPC patient with steroid (Lotemax gel)¬ Then as maintenance

$Seasonal allergic conjunctivitis patient¬ ”need something for 2-3 weeks in spring and fall”

$Superior Limbic Keratoconjunctivitis (SLK)$Rheumatology patients (RA, SLE, Mixed Connective…)

$After cataract surgery patients usually will complain of what at that 2-3 month post-op?

$Use if thinking a specialty IOL, discussing IOL and refractive outcome, monovision

$Take advantage of the free 30 day trial and $10 refill


Nutraceutical Therapies in Dry Eye

$Looking for anti-inflammatory fatty acids¬ Dry eye efficacy

$”Fish oil” will provide nice hair, nails, and skin$Gamma-Linolenic Acid GLA

¬ Specific action that ”fish oil” omegas lack

¬ 7 randomized controlled trials for dry eye2 Aqueous-deficient (Barabino S et al. Cornea 22: 97–101, 2003.)2 PRK (Macri A et al. Graefes Arch Clin Exp Ophthalmol 241:561-6, 2003.)2 Sjögren's (Aragona P, et al. Ophthalmol Vis Sci 46:4474-9, 2005.)

2 Contact lens (Kokke KH et al. Contact Lens Ant. Eye 31:141-6, 2008.) 2 MGD (Pinna et al. Cornea 26:260-264, 2007.)2 Mild-moderate DE (Brignole-Baudouin et al. Acta Ophthalmologica 89:e591-7, 2007.)2 Post-menopausal women (HydroEye) (Sheppard JD, Pflugfelder SC, et al. Cornea 32

:1297-1304, 2013.)

$Prostaglandins¬ Myth buster- they are not all bad

$Prostaglandin E1 (PGE 1) -good¬ Shown to stimulate lacrimal production (Phalpramool, 1980, 1983)

¬ Supports mucin production 2 Conjunctiva, other membranes (Viau, 2009, Willemsen, 2003, Nygren, 1984)

¬ Experimental deprivation of vitamin C a required cofactor for PGE 1 2 Stops lacrimal production, produces Sjögren's-like signs & symptoms Wood,

1970

¬ Precursor GLA

$Prostaglandin E2 (PGE 2) – bad¬ Precursor AA

$Prostaglandin E3 (PGE 3)- good¬ Precursor Omega-3 “fish oil”

Nutraceutical TherapiesAnti-inflammatory Fatty Acids

EssentialFatty Acids

Delta-6desaturase

Elongase Delta-5Desaturase

COX

18:2w3Alpha linolenic

(ALA)

18:4w3SDA

20:4w3ETA

20:5w3

EPA

20:6w3DHA

Omega-618:2w6

Linoleic Acid (LA)

20:3w6DGLA

20:4w6Arachidonic

Acid

Series 2 (“bad”)Prostaglandins

Series 1 (“good”)Prostaglandins

Omega-3

(Parent)

(Parent)

Rate-Limiting

Delta

-4 D

esat

uras

e

18:3w6

GLA

Series 3 (“good”)Prostaglandins, LTB5, Resolvin E1


EPA & GLAare powerhouses of omegas – they are

effective precursors of anti-inflammatory

compounds(DHA is also precursor to a protectin, NPD1 – though no dry

eye role for NPD1 is established)

20:5w3

EPASeries 3 (“good”)Prostaglandins, LTB5, Resolvin E1

20:3w6DGLA

Series 1 (“good”)Prostaglandins15-HETE-rE

18:3w6

GLA

©2016, Zac Denning, ScienceBased Health, [email protected]

Omegas that are common in our diet (ALA from O-3

family, LA from O-6 family) are inefficiently

used, don’t directly affect inflammation




Delta-6desaturase


COX


(ALA)

18:4w3SDA

20:4w3ETA

20:5w3

EPA

20:6w3DHA

Omega-618:2w6

Linoleic Acid (LA)

20:3w6DGLA

20:4w6Arachidonic

Acid



Omega-3

(Parent)

(Parent)

Rate-Limiting

Delta

-4 D

esat

uras

e

18:3w6

GLA



Anti-inflammatory Fatty Acids

But GLA is an omega-6 …What about the pro-inflammatory aspects

of the omega-6s?

20:4w6Arachidonic

Acid



American diet offers gross excess of arachidonic acid (e.g. from meat / dairy). Very little via conversion from other omega-6s.


Delta-6desaturase


COX


(ALA)

18:4w3SDA

20:4w3ETA

20:5w3

EPA

20:6w3DHA

Omega-618:2w6

Linoleic Acid (LA)

20:3w6DGLA

20:4w6Arachidonic

Acid



Omega-3

(Parent)

(Parent)

Rate-Limiting

Delta

-4 D

esat

uras

e

18:3w6

GLA




20:4w6Arachidonic

Acid


20:5w3

EPA

EPA blocks this step

1) GLA heavily favors the anti-inflammatory

pathway

2) As back up1, adding EPA to GLA in proper

balance, blocks production of pro-

inflammatory pathway

20:3w6DGLA

18:3w6

GLA

Reference: 1. Barham et al. 2000.



Delta-6desaturase


COX


(ALA)

18:4w3SDA

20:4w3ETA

20:5w3

EPA

20:6w3DHA

Omega-618:2w6

Linoleic Acid (LA)

20:3w6DGLA

20:4w6Arachidonic

Acid



Omega-3

(Parent)

(Parent)

Rate-Limiting

Delta

-4 D

esat

uras

e

18:3w6

GLA




This combo has added benefit of

delivering a 2 prong attack on

inflammation

20:5w3

EPA

20:3w6DGLA

Series 1 (“good”)Prostaglandins15-HETE-rE

18:3w6

GLA



Gamma-Linolenic Acid GLA$Consistently shown improvement in markers of inflammation /

inflammatory mediators in dry eye$Shown promise in other inflammatory diseases, like

rheumatoid arthritis, IBD, dermatitis, and diabetic retinopathy$In Sjögren's increases tear production, raises PGE1 in tears

(Aragona, 2005)

$Supports meibomian glands ((Pinna, 2007)

¬ Probably through anti-inflammatory action

$2,000-3,000 mg omega-3s usually required to have significant effect¬ In contrast 235 mg of GLA significantly reduced 2 different

inflammatory markers (HLA-DR, CD11c) in the HydroEye trial (Sheppard, Pflugfelder, Whitley et al. Cornea, 2013)

$ Aren’t all Omega-6s Bad?

¬ Most assume omega-6 are bad / pro-inflammatory¬ Most people have also heard that we get too much omega-6 in our

diet and that we need more omega-3 ¬ The aka Omega-6 / omega-3 ratios

¬ This is based on studies that use dietary info – and therefore this info applies only to dietary omegas

$ GLA is not a dietary omega¬ except at trace levels

¬ It’s not valid to apply dietary info to GLA

$ GLA is a potent anti-inflammatory omega¬ Like EPA/DHA in the omega-3 family¬ Backed by a number of dry eye clinical trials

$ GLA has a unique dry eye specific action

Gamma-Linolenic Acid GLA Is GLA offered in the triglyceride (TG) form? aka “re-esterified”

$These forms of omegas triglyceride (TG) vs ethyl ester (EE) mainly apply only to fish oils

$ Fish oil when it’s purified is transformed from the natural TG form in fish to the EE form¬ Which allows the omegas to be concentrated & purified

$ Fish oil companies have heavily marketed re-esterified or TG fish oils as vastly more absorbable and bioavailable

$ GLA only comes as TG form¬ No other form

¬ TG vs EE discussion is purely about different fish oils



$Pick the right nutraceutical not “fish oil” ad get:¬ Improvement in irritation symptoms

¬ Better cornea smoothness¬ Significantly lower levels of inflammatory markers

Nutraceutical Therapies Amniotic Membrane

$To help reset the eye from a stage 3-4 back to something manageable

$Failure on multiple therapies$Sjogren’s and the rheumatological patient

Dry Eye and Amniotic Membrane

In-Office Lab Testing

In-Office Lab Testing

$Helps with:¬ Switching patient to dailies

¬ Starting nutraceuticals¬ Starting pharmaceuticals

¬ Following patients over time

TearLab Osmolarity Test



InflammaDry®InflammaDry®

For inflammatory dry eye detection

Normal levels of MMP-9 in human tears ranges from 3-41 ng/ml

NEGATIVE TEST RESULT

MMP-9 < 40 ng/ml

POSITIVE TEST RESULTMMP-9 ≥ 40 ng/ml

InflammaDry Sjö Diagnostic Test

$Uses proprietary biomarkers to create an advanced diagnostic panel

$ Early detection of Sjögren’s syndrome in your patients

Thank-Youand

Hope You Enjoyed

Greg Caldwell, OD, [email protected]

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