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NEW CONCEPTS IN OCULAR SURFACE INFECTION AND INFLAMMATION

SRC 2013Melbourne, Australia

Blair  B Lonsberry, MS, OD, MEd., FAAODiplomate, American Board of OptometryClinic Director and Professor of OptometryPacific University College of Optometry

blonsberry@pacificu.edu

Disclosures and Special Request

Paid consultant for:Alcon Pharmaceuticals, Bausch and Lomb, Carl Zeiss Meditec, Merck Pharmaceuticals, NiCox, SARcode

Commitment to change:g• write down three “clinical pearls” that you “learned” 

from this presentation that you can incorporate into your practice to improve patient care

• revisit these points a month from now, in 3 months and again in 6 months and see if you have adopted them

• make a commitment to change how you care for patients

Agenda

• What is ocular surface infection and inflammation:

– OSD or Ocular Surface Disease

• What does OSD include?

– Viral Conjunctivitis

– Allergic Conjunctivitis

– Herpes Simplex Keratitis (HSV)

– Dry Eye Disease (DES)

– Bacterial Conjunctivitis

– Blepharitis and MGD

What’s Up with OSD?

• OSD presents a significant  challenge to physiciansphysicians

–Differentiation

–Diagnosis

–Treatment

OSDs are Difficult to Tell Apart: Overlapping Signs/Symptoms

SignsHyperemiaChemosis

Symptoms

Foreign Body SensationChemosisLid Swelling

Burning

Dry, Gritty Ocular Surface

Itchy Eyes

Photophobia 

Tearing

Case

• 27 year old pharmacy student presents to the clinic on emergent basis– complains about red/painful eyes for the past 2 days – started OD then transferred to OS– reports a watery discharge no itching and is not areports a watery discharge, no itching, and is not a contact lens wearer

– reports that others in his class have had a similar red eye

– no seasonal, food or drug allergies– has taken Visine 4‐5 times/day since eyes became red but hasn’t helped much

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ConjunctivitisConjunctivitis

Bacterial Conjunctivitis Allergic Conjunctivitis

Viral Conjunctivitis Blepharo-conjunctivitis

Bacterial Conjunctivitis

Signs and Symptoms of Bacterial Conjunctivitis

Clinical presentation – uni‐ / bi‐lateral

Signs:– Bulbar conjunctival injection

– Purulent discharge

Symptoms:

– Photophobia

– Blurred vision– Morning matting of eyelashes

– Chemosis– Tearing

HyperemiaHyperemia ChemosisChemosis Purulent dischargePurulent discharge

Treatment/Management• Topical antibiotic therapy

– Ciprofloxacin/Ofloxacin QID for 5‐7 days– Azithromycin BID for 2 days then qd for next 5days

– Tobramycin/Gentamicin QID for 5‐7 daysl i i d f d– Polymyxin 4‐6 times per day for 5‐7 days

– Framycetin/Neomycin every 2 hours for first couple of days then QID for next 5 days

– Chioramphenicol 4‐6 x/day for 5‐7 days

Allergic Conjunctivitis Prevalence of Allergic Conjunctivitis

• Allergies affect as many as 40 to 50 million Americans

• Incidence and• Incidence and prevalence of allergic conjunctivitis has been rising over the last 40 years

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Signs and Symptoms of Allergic ConjunctivitisClinical presentation – bilateral

Signs:– Conjunctival edema– Conjunctival hyperemia– Chemosis

Symptoms:– Itching– Burning– Photophobia

– Lid edema– Watery discharge

p– Foreign body sensation– Blurred vision

HyperemiaHyperemiaLid edema and bilateral hyperemiaLid edema and bilateral hyperemia ChemosisChemosis

Mast Cell Cascade

Early PhaseEarly PhaseTreatment

• Ocular allergy sufferers need;

– fast relief of signs and symptoms,

– long-lasting therapeutic effects,

– comfortable and safe topical drugs– comfortable and safe topical drugs,

– convenient treatment regimen

• Therapeutic focus is mostly confined to the suppression of mast cells, their degranulation and the effects of histamine and other mast-cell derived mediators.

Treatment of Ocular Allergy 

Medications:•Topical OTC drops •Oral antihistamines (prescription and OTC) •Topical NSAID drops p p•Topical antihistamines•Topical mast cell stabilizers•Topical steroid drops•Topical dual‐action drugs (antihistamine/mast cell stabilizers)

Viral Conjunctivitis

•Most common infectious keratitis presenting on emergent basis  

• 62% caused by adenovirus

• Two major types:

–Pharyngoconjunctival fever

–Epidemic keratoconjunctivitis

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Viral Conjunctivitis

• PCF:  history of recent/current upper respiratory infection

• EKC:  highly contagious with a history of coming in contact with someone having a red eye.

– Adenovirus 8 common variant leading to “rule of 8’s”

• First 8 days red eye with fine SPKFirst 8 days red eye with fine SPK

• Next 8 days deeper focal epithelial lesions

• Following 8 potential development of infiltrates

• Resolution

• RPS AdenoPlus available in the US to use for adenoviral confirmation.

– Marketed by NiCox (United States)

AdenoPlus

• Have you heard about this?

www.nicox.com

Interpreting the Results

NEGATIVE RESULT• Only a BLUE line appears in the

control zone. – A negative result is indicative of an

absence of Adenovirus Antigens.

POSITIVE RESULTPOSITIVE RESULT• The presence of both a BLUE line

in the control zone and a RED line in the result zone indicates a positive result.

• Even if the RED line is faint in color, incomplete over the width of the test strip, or uneven in color, it must be interpreted as positive.

• A positive result indicates the presence of Adenovirus antigens.www.nicox.com

Patient has “Red Eye”

“Red Eye”Protocol

JOURNEY OF THE JOURNEY OF THE ““RED EYERED EYE””

Patient is taken to “Red Eye Room”

Front Office IDs & Isolate the “Red Eye”

Eye Room

Dr. proceeds with evidence based treatment

“Red Eye” Patient history & work up

Dr. starts clinical evaluation with Adenoviral conjunctivitis

confirmed, or rule out

Tech performs AdenoPlus™ test to rule

out Adenovirus

History  Signs  Symptoms 

Pink eye exposure, spread from one eye to the other, recent upper respiratory symptomsItching, burning, foreign body sensation, tearing, discharge, eyelash mattingPre‐auricular adenopathy, chemosisNosignificantpain,lightsensitivity,orvisualloss

AdenoPlus

POSITIVE

Education: hygiene and hand washingSupportive care: artificial tears, cool compresses and antihistaminesAntiviral medicationNo antibiotics

NEGATIVE

Consider topical antibiotics or antihistamines

Viral Conjunctivitis: Signs and Symptoms

• Gritty sensation• Watery discharge• Sticky in mornings• Follicular response

PseudomembranesPseudomembranes in in severe casessevere cases

SubconjunctivalSubconjunctival hemeshemesp• Chemosis• Injection• SPK• Infiltrates possible• Positive lymph nodes

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Management

• Consider the use of anti-inflammatory treatment to relieve patient symptoms and improve comfort

– E.g. FML TID-QID OU

• EKC patients are typically very uncomfortable and would benefit from anti-inflammatory treatment

– especially if infiltrates or pseudomembranepresent

Management

• Betadine (Melton‐Thomas Protocol):– Proparacaine– 1 or 2 drops of NSAID– 4‐5 drops of Betadine 5%

• Get patient to close eye and gently roll themGet patient to close eye and gently roll them around

– After one minute, lavage the eye– Instill another drop of NSAID– Lotemax 4 times a day for 4 days

• Alternative:  Betadine swabsticks.  

Management

• Antivirals used in HSV keratitis are ineffective in treatment of viral conjunctivitis

• Important to stress limited contact with others, frequent hand washing, not sharing of towels, etc.

Dry Eye

Prevalence of Dry Eye Disease (DED)

• Prevalence estimated from 7.4% to 33.7% depending on study quoted, how DED is defined and patient population studied

• Affects women more than men

• Increases as patient population ages

14 4% f i lf hi f d• 14.4% of patients self‐report history of dry eye

• 7.8% of women aged 45 to 84 were clinically diagnosed with DED (Beaver Dam Study)

• Affect on quality of life (QOL):• Mild DED = psoriasis

• Moderate DED = moderate angina

• Severe DED = class III/IV angina or diabling hip fracture

Case

• 55 yr white female complains of fluctuating vision– Worse at near– Spends 8-10 hours/day on the computer

• Medical Hx:– Hypertension for 10 years – Joint pain

• Medications:– HCTZ for HTN– Celebrex for her joint pain

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Exam Data

• VA (corrected): OD: 6/7.5 (20/25), OS: 6/7.5 (20/25)

• PERRL• EOM’s: FROM• CVF: FTFC• SLE:

• TBUT 5 sec OD, OS• Positive NaFl staining and

Lissamine green staining of conjand cornea

• Decreased tear prism

Additional Testing/Questions

• Schirmer: < 5 mm of wetting in 5 minutes OD, OS

• RF and ANA: normal for patients age

• SS-A: 2.0 (normal < 1.0), SS-B: 1.9 (normal <1.0)

• Additional symptoms reported:• Additional symptoms reported:

– Patient experiences dry mouth and taking Salagen

• Diagnosis: Sjogren’s Syndrome

Differential Diagnosis of Dry Eye Signs and Symptoms of Dry EyeSigns:   

– Ocular Surface Damage

• Corneal Staining (Fluorescein and/or Rose Bengal)

• Conjunctival Staining (Lissamine Green )

D d T Q i

Symptoms:

– Grittiness

– Burning

– Irritation

– Stringy discharge

– Blurring of vision– Decreased Tear Quantity

• Schirmer Score• Phenol Red Thread Test• Tear Meniscus Height

– Decreased Tear Quality

• Tear Break Up Time (TBUT)

• Tear Osmolarity

Blurring of vision

– Ocular Surface Disease Index (OSDI) 

Treatment

• We initiated:– Omega-3 supplements (3-4 grams per day)– Recommended warm compresses and lid washes qhs– Testosterone cream 3% applied to upper lid bid

• Patient had significant improvement in symptoms with the use of the topical testosterone cream.– However, she was still symptomatic at the end of the day and she

still had significant staining on her cornea and conjunctiva– Initiated FML tid for 1 month, restasis bid after 2 weeks

• 2 months later patient reported further improvement in her symptoms

• No conjunctival staining was noted and only slight SPK• Schirmer values improved to OD: 9 mm, OS: 10 mm

Transdermal Testosterone Cream

• Recent studies have suggested that androgen deficiency may be the main cause of the meibomian gland dysfunction, tear-film instability and evaporative dry eye seen in Sjogren’s patients

• Transdermal testosterone promotes increased tear production and meibomian gland secretion, thereby reducing dry eye symptoms (Dr. Charles Connor).

• arGentis and Allergan have conducted trials to see if topical androgens are effective in treating dry eye

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SJOGREN’S SYNDROME:  OLD/NEW CLASSIFICATION

• Old:– 1o Sjogrens: occurs when sicca complex manifests by itself

• no systemic disease present– 2o Sjogrens: occurs in association with collagen vascular

disease such as disease such as • RA and SLE • significant ocular/systemic manifestations

• New:– The diagnosis of SS should be given to all who fulfill the

new criteria while also diagnosing any concurrent organ-specific or multiorgan autoimmune diseases, without distinguishing as primary or secondary.

Diagnosis: New Criteria

• Sjogren’s International Collaborative Clinical Alliance (SICCA) was funded by the National Institutes of Health to develop new classification criteria for SS

• New diagnostic criteria requires at least 2 of the following 3:

– 1) positive serum anti-SSA and/or anti-SSB or (positive rheumatoid factor and antinuclear antibody titer >1:320),

– 2) ocular staining score >3, or

– 3) presence of focal lymphocytic sialadenitis with a focus score >1 focus/4 mm2 in labial salivary gland biopsy samples

Ocular Surface Score (OSS)

• The ocular surface score (OSS) is the sum of:

– 0-6 score for fluorescein staining of the cornea and

– 0-3 score for lissamine green staining of both 0 3 score for lissamine green staining of both the nasal and temporal bulbar conjunctiva,

– yielding a total score ranging from 0-12.

Dry Eye and Lid Disease?

• It is estimated that 67-75% of patients who have dry eye have some form of lid disease

– it is often the most overlooked cause for dry eye symptoms

• Important to address the lids in any treatment plans for patients with dry eye

Treatment/Management Blepharitis

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Current Prevalence of Blepharitis• Although blepharitis may be a frequently overlooked 

condition in the United States, ophthalmologists and optometrists report that blepharitis is commonly seen in 37% and 47% of their patients, respectively1,2

Blepharitis PatientsBlepharitis Patients’’ Initial MotivationInitial Motivationfor Seeking Treatmentfor Seeking Treatment

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1. Lemp MA, Nichols KK. 1. Lemp MA, Nichols KK. Ocul SurfOcul Surf. 2009;7(suppl 2):S1. 2009;7(suppl 2):S1--S14; 2. Campbell Alliance Group. Patterns of Practice and Prevalence S14; 2. Campbell Alliance Group. Patterns of Practice and Prevalence Rates for Lid Margin Disease. JulyRates for Lid Margin Disease. July––August 2008.August 2008.

Differential Diagnosis of Blepharitis

Spectrum of BlepharitisSpectrum of Blepharitis

AnteriorAnteriorPosterior Posterior 

i di dAnterior Anterior BlepharitisBlepharitis

BlepharitisBlepharitis

(MGD*)(MGD*)MixedMixed

Most CommonMost Common

Anterior Anterior BlepharitisBlepharitis

Posterior BlepharitisPosterior Blepharitis

**Meibomian Gland DiseaseMeibomian Gland Disease

Tear Film & Ocular Surface Society(TFOS): Meibomian Gland Workshop 

• The MGD Workshop was conducted to provide an evidence‐based evaluation of meibomian gland structure and function in health and disease. 

• MGD is an extremely important condition, conceivably underestimated, and very likely the most frequent cause of dry eye disease. 

• The Report required over 2 years to complete and involved the efforts of more than 50 leading clinical and basic research experts from around the world. 

• The International Workshop on Meibomian Gland Dysfunction: March 2011; 52 (4) 

Signs and Symptoms of Blepharitis• Symptoms

– Burning

– Irritation

– Foreign body sensation (FBS)

•• SignsSigns

–– Injected lid margin / conjunctivaInjected lid margin / conjunctiva

–– Telangiectasia (dilated blood Telangiectasia (dilated blood vessels)vessels)

–– Swollen lid marginSwollen lid margin

–– Plugged inflamed meibomian glandsPlugged inflamed meibomian glands (FBS)

– Itching

– Tired eyes

– Photophobia

– Contact lens intolerance

Plugged, inflamed meibomian glandsPlugged, inflamed meibomian glands

–– Thickened meibomian gland Thickened meibomian gland secretionsecretion

–– SaponificationSaponification

–– Lid debrisLid debris

Physicochemical Differences in Normal vs MGD Patients

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FoulksFoulks GN, GN, BronBron AJ. AJ. OculOcul SurfSurf. 2003;1:107. 2003;1:107--126; 126; FoulksFoulks GN et al. Modification of GN et al. Modification of meibomianmeibomian gland lipids by topical azithromycin. gland lipids by topical azithromycin. Poster presented at: ARVO 2009 Annual Meeting; May 3Poster presented at: ARVO 2009 Annual Meeting; May 3--7, 2009; Fort Lauderdale, FL.7, 2009; Fort Lauderdale, FL.

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The thickened and turbid MG secretions in The thickened and turbid MG secretions in patients with MGD can be attributed to a more patients with MGD can be attributed to a more

ordered lipid structure. ordered lipid structure.

Increased phase transition temperature noted Increased phase transition temperature noted with MGD correlates with the more ordered lipid with MGD correlates with the more ordered lipid

structure seen in the graph on the left.structure seen in the graph on the left.

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Contact Lens Basics

• Between 3‐5 million people in Canada wear contact lenses (CL)

– 30‐35 million US wearers

– and approximately. 135 million world wide.and approximately. 135 million world wide.

• Estimated that 10% of CL wearers will drop out every year

Value of CL Patient to a Practice

• CL wearers produce more revenue than spectacle wearers

– CL wearers seen more often generating more professional fees 

CL i ll l hil l• CL patient generally seen yearly while spectacle wearers seen on average 2‐3 years

– Professional fees higher for CL exams than spectacle exams

– CL wearers still require glasses and sunglasses in addition to purchasing CL’s and supplies

Contact Lens Dropout

• 50% of patients report dryness/discomfort as reason they discontinued CL wear

– remaining reasons include:

• CostCost

• Considering/getting LASIK

• Belief that CL wont/don’t meet their visual needs

• 50% of current CL wearers report comfort issues with their lenses 

Total SCLTotal SCLDropoutsDropouts

Went to EyeWent to EyeDoctor to SolveDoctor to SolveProblem BeforeProblem BeforeDropping out?Dropping out?

YesYes46%46%

Tried any differentTried any differentbrands/types priorbrands/types priorto dropping out?to dropping out?

YesYes9%9%

NoNo

““My patients will tell me if they are not My patients will tell me if they are not happyhappy””

WRONG!WRONG!

NoNo54%54%

37%37%

•• Less than 50% even saw an ECP Less than 50% even saw an ECP

•• Only 9% tried a different brand before dropping outOnly 9% tried a different brand before dropping out

CIBA Vision data on file, 2006CIBA Vision data on file, 200620072007‐‐0505‐‐05350535

““My patients will tell me if they are not My patients will tell me if they are not happyhappy””

Eyes dried out when wearing CLEyes dried out when wearing CL’’ss 81%81% 44%44%Contact lenses felt uncomfortable at EOD 73%Contact lenses felt uncomfortable at EOD 73% 34%34%

WRONG!WRONG!% experiencing % experiencing at at

appointmentappointment% telling % telling

the doctorthe doctor

Eyes felt irritated when wearing CLEyes felt irritated when wearing CL’’ss 60%60% 26%26%Ability to see changed throughout the dayAbility to see changed throughout the day 52%52% 18%18%Eyes got redEyes got red 48%48% 16%16%Vision was blurry or hazy when waking up Vision was blurry or hazy when waking up

after sleeping in lensesafter sleeping in lenses 39%39% 7%7%Cleaning and disinfecting too much of a hassle Cleaning and disinfecting too much of a hassle 36% 3%36% 3%Contact lenses required too much effortContact lenses required too much effort 35%35% 4%4%

*Among patients switching to another brand of lens at last appointment*Among patients switching to another brand of lens at last appointment

CIBA Vision data on file, 2007.CIBA Vision data on file, 2007. 20072007--0505--05350535

CL’s and Dry Eye

• A CL on the eye splits the tear film into pre‐lens and pre‐corneal layers– Been demonstrated that the pre‐lens tear film evaporates 25% faster in CL patients

– Reduced tear volumes results in increased tear osmolarity which is noted in dry eye patients, and increases risk of infection

• CL wearers may also be increased risk of dry secondary to age, sex, occupation, medications, allergies, etc.

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CL and the Lids

• Lid disease has a reported association in 67‐75% of dry eye patients

– Lack of adequate lipids in the tear film can result in evaporative dry eye even if aqueous production is normal

• As CL increase evaporation of tear film, even mild cases of lid disease can result in CL related dryness; decreasing wear time, comfort and visual performance.

CL and the Lids

• Recent studies have shown that CL wear is associated with a decrease in the number of functional meibomian glands

– this decrease is proportional to the duration of CL d t ib t t d i CLwear and may contribute to dry eye in CL wearers

– Two hypotheses:

• Aggregation of desquamated epi cells at the orifices of the glands resulting in chronic irritation

• Mechanical trauma from the CL’s causes duct blockage

DOES THE ANTERIOR SEGMENT AFFECT THE POSTERIOR SEGMENT?AFFECT THE POSTERIOR SEGMENT?

Surgical Outcomes

• For ocular surgery patients with blepharitis, proper preoperative management is essential

• Patients’ external tissues are an important source of organisms that  adversely affect surgical outcomes

5858

– Endophthalmitis results from patients’ own lid and surface flora

– Surgical outcomes may be adversely affected by inflammation and dysfunctional tears 

Surgical Outcomes

• Treatment potentially enhances ocular surgery outcomes

– Improving meibomian gland secretions improves the tear film, which improves quality of vision

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• particularly important in refractive and multifocal intraocular lens implantation where achieving optimal vision requires a stable tear film

Corneal Topographies

Topographies compliments of Tracy Swartz, OD Topographies compliments of Tracy Swartz, OD

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LASIK and Dry Eye

• LASIK may increase pro‐inflammatory cytokines

– Cytokines could stimulate further release of inflammatory mediators

– Exacerbate LASIK‐induced nerve damageExacerbate LASIK induced nerve damage

• Healthy ocular surface and normal tear function require for clear vision and stable refraction

• Potential for increased regression towards pre‐LASIK refractive state correlated with dry eye

Treatment Goals for Blepharitis

• Long‐term control of underlying pathophysiology: 

– bacteria, inflammation and meibomian gland secretions

• Improvement of signs and symptomsp g y p

• Improve health of tear film lipid layer 

– Reduce risk of fluctuating visual acuity 

• Reduce possible risk of progression to other conditions such as dry eye disease or chalazion

• Improve outcomes in surgical procedures and comfortable contact lens wear time

Treatment/Management

• Warm compresses and lid washes

• Oral doxycycline 

– 50 mg bid for 7‐14 days then qd for next 6‐8 weeksweeks

• Topical azithromycin (off label use)

– 1 gtt qd for 30 days 

• Omega 3 supplements