Ocular Manifestation and Treatment of
Allergic Disorders
April 18, 2015
Disclosures
Ocular Manifestation and
Treatment of Allergic Disorders
Greg Caldwell OD, FAAO
Nebraska Optometric Association
2015 Spring Conference
Lincoln, NE
April 18, 2015
$ Greg A. 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.
$ In the past 12 months I have lectured or
participated in a focus group which I received a
honorarium for:
¬ Allergan, Alcon, and Optovue
$ All of these cases have entered/referred to my
practice
Disclosure Statement
(next slide)
Learning Objectives
$ Develop a better understanding about ocular allergic
diseases and their treatments
$ Identify new therapeutic options and discuss their benefits
$ Review immune reaction and hypersensitivity reaction
$ Prepare you to educate peers and patients about allergic
conjunctivitis and its treatment
Ocular Allergy Statistics
$ Ocular allergies affect 20% of the population
¬ 90% of all allergy patients have ocular symptoms
¬ 50 million people suffer from ocular allergies
It’s not just an opportunity
it is an
Optom-portunity
What is an Allergy?
$ Allergy-is a result of a beneficial immune
Normal Immune Response
Antigen is eliminated
response that has gone awry
B lymphocyte
$ Hypersensitivity-is a result of a beneficial
immune response that has gone awry
Antibodies
IL-4
Major
Histocompatibility
Complex
Allergy = Hypersensitivity
T lymphocyte
Plasma cell
IgG, IgA, IgM, IgE
Antigen-presenting cell
Greg Caldwell, OD, FAAO
[email protected] 814-931-2030 cell
1
Ocular Manifestation and Treatment of
Allergic Disorders
April 18, 2015
Coombs and Gell Classification
Hypersensitivity
When a specific immune response is not
appropriately controlled,
a phenomenon termed
hypersensitivity ensues.
$ Type I
$ Type II
$ Type III
$ Type IV
Allergy
Cytotoxic, antibody-dependent
Immune Complex disease
Delay Type Hypersensitivity
$ Type 5- often used in Britain used to help differentiate
Type II
Allergy = Hypersensitivity
Why This Language Gets So Confusing?
$ The same language is used to describe
¬ Hypersensitivity-Type I, II, III and IV
¬ Autoimmune disease-Type I, II, III and IV
$ Immune disorders=Hypersensitivity + Autoimmune diseases
¬ Instead of binding to cell surface, the AB binds to the cell surface
receptor
¬ Graves and Myasthenia Gravis
¬ Rare to use
Why This Language Gets So Confusing?
$ Type I-allergy, atopy, IgE
¬ Only hypersensitivity-atopic dermatitis, allergic conjunctivitis
¬ There are no autoimmune disease
$ Type II-antibody dependent cell mediated cytotoxicity IgM, IgG
¬ Hypersensitivity-Pernicious anemia
¬ Autoimmune-Rheumatic fever, Graves, Myasthenia gravis
$ Type III-Immune Complex
¬ Hypersensitivity-Reactive arthritis
¬ Autoimmune-Systemic lupus erythematosus, rheumatoid arthritis
$ Type IV-cell mediated, T-cells
¬ Hypersensitivity-contact dermatitis
¬ Autoimmune-DM type 1, Hashimoto’s and GCA
Conclusion
$ True ocular allergy
¬ Hypersensitivity Type I and IV
$ We may see ocular side effects from Type
I thru IV hypersensitive and autoimmune
diseases but they are secondary and not
true ocular allergy
Greg Caldwell, OD, FAAO
[email protected] 814-931-2030 cell
Hypersensitivity
$ Type I
¬ Allergy (immediate)
¬ Atopy syndrome, anaphylaxis, asthma
2 Atopy-affecting parts of the body not in direct
contact with the allergen. Elevated levels of IgE in
the blood…result positive skin prick test to
common allergens.
¬ IgE
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Ocular Manifestation and Treatment of
Allergic Disorders
April 18, 2015
Hypersensitivity
Hypersensitivity
$ Type I- IgE response to a particular antigen termed
an allergen
¬ Typically mediated by mast cells and
particularly histamine
¬ Ex. Allergic conjunctivitis
$ Type II- IgM or IgG response. Antibody
binds to cell surface antigens on cells or
tissues
¬ IE. Autoimmune hemolytic anemia,
thrombocytopenia, pemphigus
IgE
antibodies
IgM or IgG
antibodies
One’s own cells
Sensitized
mast cell
Hypersensitivity
Hypersensitivity
$ Type III- Immune complex disease. Normally antibody antigen
combine, an immune complex is formed. These complexes usually
are cleared from systemic circulation by phagocytes. Poorly cleared
immune complexes that persist in circulation can lead to systemic
disease.
¬  IE. Systemic Lupus Erythematosus and Polyarteritis nodosa
Antigen is eliminated
$ Type IV- Delayed type hypersensitivity
¬ Regulated by T-cells
¬ Sub-categories:
2 Contact
Ø  Medicated by Langerhan’s cells and keratinocytes
B lymphocyte
Antibodies
Major
IL-4
Histocompatibility
Complex
T lymphocyte
2 Tuberculin
2 Granulomatous
¬ IE. Contact Dermatitis
Plasma cell
IgG, IgA, IgM, IgE
Antigen-presenting cell
Classification of Ocular Allergy
$ Allergic conjunctivitis
¬ Seasonal
¬ Perennial
$ Atopic keratoconjunctivitis
$ Vernal keratoconjunctivitis
32 year old man
$ My eyes itch so bad I want to claw them out
$ I went golfing today (May)
$ Rubbing them feels good but I think it makes it
worse
$ Vision and externals are normal
$ Giant papillary conjunctivitis
$ Contact dermatitis
Greg Caldwell, OD, FAAO
[email protected] 814-931-2030 cell
3
Ocular Manifestation and Treatment of
Allergic Disorders
Seasonal Allergic Conjunctivitis
$ Happened the last 2
April 18, 2015
Allergic Conjunctivitis
Seasonal
years but not this bad
$ Occurs in spring, fall or both
$ Grass, tree pollen or ragweed
Perennial
$ Year round with periods that are
more pronounced
$ Animal dander, dust mites, mold,
grass
$ History of other atopic diseases
Signs and Symptoms of
Allergic Conjunctivitis
Seasonal
$ Itching
$ Redness
$ Burning
$ Excessive tearing
$ Stringy white mucus
$ Rhinitis
Perennial
$ Similar to seasonal allergic
conjunctivitis
$ Milder than seasonal
allergic conjunctivitis
$ More constant than
seasonal allergic
conjunctivitis
$ Seasonal exacerbations
Non-pharmacologic Interventions
$ Allergen avoidance
¬ Pet control
¬ Use air conditioning, HEPA filters
¬ Avoid outdoor activities during high pollen
periods
$ Cold compresses
$ Lubricating eye drops
$ Wash your hair before going to bed
Pharmacologic Interventions
$ Lastacaft™
$ Pataday™
$ Pazeo™
$ Alrex™
$ Lotemax™
$ Topical eye drops
2  Vasoconstrictors
2  Antihistamines
2  Antihistamine/vasoconstrictor
combination
2  Antihistamine/mast cell
stabilizer combination
2  Mast cell stabilizers
2  Non-steroidal antiinflammatory drugs (NSAIDs)
2  Corticosteroids
What is happening and how do
these pharmaceuticals work?
$ Oral antihistamines
$ Allergen immunotherapy
Greg Caldwell, OD, FAAO
[email protected] 814-931-2030 cell
4
Ocular Manifestation and Treatment of
Allergic Disorders
April 18, 2015
Allergic Sensitization
Ocular Allergy is Mainly
Type I Hypersensitivity
Antigen in tears
$ Consists of three phases
¬ Sensitization phase- patient unaware
¬ Activation phase (early allergic response)
¬ Late allergic response
Conjunctival epithelium
B lymphocyte
IL-4
Major
Histocompatibility
Complex
“Treatment failure may occur if you fall short to
IgE
antibodies
T lymphocyte
identify which phase the hypersensitivity is in”
Plasma cell
Sensitized
mast cell
Antigen-presenting cell
Early Allergic Response
Late Allergic Response
(Second Exposure)
Leukotrienes
Antigen in tears
Conjunctival epithelium
Histamine
m
Im
e
iat
ed
Activated mast cell
ECF-A
$ 
Leukotrienes
Arachidonic
Acid
Newly-Formed
Peroxidase
Eosinophil
Prostaglandins
Leukotrienes
Cationic Proteins
Thromboxines
Lysosomal Enyzmes
Platelet Activating Factor
Cell-Mediated
Cytotoxicity
Tissue damage
Edema
28 year old man
Three subtypes of the histamine receptor have
been pharmacologically defined (H1, H2, H3)
$ Was helping set up tents and tables for a
Selective stimulation of ocular H1 receptors results
in ocular itching and vasodilation
$ Eye became itchy, he rubbed it and within
Selective stimulation of ocular H2 receptors
produces vasodilation and redness without
itching
H2
H1
church event
H1
H1
$ 
Histamine
Prostaglandins
Histamine Receptors
$ 
Tryptase
Chymase
Pre-Formed
Synthesis
Phospholipids
Basophil
Histamine
ECF-A
Heparin
Prostaglandins
H1
one hour it became very swollen
$ The eye is still very itchy and watery
H2
Greg Caldwell, OD, FAAO
[email protected] 814-931-2030 cell
5
Ocular Manifestation and Treatment of
Allergic Disorders
April 18, 2015
Is this a Type 1 or Type 4
Hypersensitivity Reaction?
Slit Lamp Exam
$ Type 1 hypersensitivity
$ Diagnosis?
(immediate)
$ Treatment?
2 days later
¬  Occur within minutes of
challenge by antigen
¬  Etiology: pollens, insect stings,
insect bites, foods, systemic
drugs
¬  IGE mediated
¬  Lid manifestations
2  Red, swollen, itchy lids
6 year old boy
$ Eyes are red and itchy again since the
beginning of April, now May 10th
$ “He rubs them all the time”
$ He is already using Pataday 1 gtt qd OU,
Rxed by pediatrician, uses it everyday
$ Used to get mucous and discharge from
the eye but has not since on Pataday™
$ Let’s take a look
Vernal Conjunctivitis
$ Ages 3-25, peak incidence 11-13y/o, lasts 4-11 yrs
$ males>females
$ Thick ropy discharge, severe itching and corneal involvement
Worse spring and summer
¬ Important clinical signs:
2  Large papillae, Horner-Trantas dots
2  SPK
2  Well demarcated sterile ulcer (shield ulcer)
$ Type I hypersensitivity
¬ With early and late phases
$ Children generally will outgrow this allergy
¬ Their super-immune system slows down
Greg Caldwell, OD, FAAO
[email protected] 814-931-2030 cell
6 year old boy
$ Take a shower and
wash hair before
going to bed
$ NP AT
$ Cont Pataday™
$ Add Alrex™ qid
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Ocular Manifestation and Treatment of
Allergic Disorders
April 18, 2015
25 year old man
$ My eyes are red and itchy all year round
¬ At times of the year they are worse, like today
$ I do cold compresses, artificial tears and Pataday
¬ This seems to help but my eyes are really never white, clear and
have some itch
¬ “I thought allergies occurred in the spring and summer”
$ I work with the public and my clients always ask about
my eyes
$ Patient has eczema and avoids many detergents and
fragrances/colognes
$ Patient also suffers from asthma and uses inhalers
$ Let’s take a look
Atopic Keratoconjunctivitis
$ Atopic keratoconjunctivitis (AKC) is the result of a
condition called "Atopy"
$ Atopy is a genetic condition whereby the immune system
produces higher than normal antibodies in response to a
given allergen
$ There is usually a family history of multiple allergies
$ Although AKC is a perennial disease, symptoms tend to
worsen in the winter (dryness)
$ Atopic dermatitis which is generally seen early in
childhood
64 year old woman
$ Diagnosed with bacterial conjunctivitis 8
days ago OD
$ Used tobramycin qid OD, appeared to be
worsening, was told to use q2 hours
$ In today for second opinion
¬ Atopic keratoconjunctivitis appears during late adolescence
¬ Men are more commonly affected than women.
Discussion
Diagnosis: contact dermatitis
Type 4 Hypersensitivity
Treatment
$ Delayed/cell mediated
¬ Occur in hours, days to months after antigen challenge
¬ T cell mediated
¬ Etiology: contact dermatitis, topical medications,
jewelry, nail polish
¬ Manifestations:
2 Itching
2 Red lids
2 Superficial skin changes
6 days later
Greg Caldwell, OD, FAAO
[email protected] 814-931-2030 cell
7
Ocular Manifestation and Treatment of
Allergic Disorders
Contact Dermatitis
$ Causes:
¬ Topical Medications
73 year old man
$ In today because his “pink eye” that he
2  Alpha agonists, B-blocker, Pilocarpine, Atropine
¬ Contact lens solutions
¬ Cosmetics
¬ Fingernail polish
¬ Pet dander
¬ Molds
¬ Detergents
¬ Latex
¬ Hair dye
¬ Metals: nickel
Discussion
$ Glaucoma patient using
April 18, 2015
Conjunctivitis?
¬ ½ Betimol™ qd OU AM
¬ Alphagan-P™ 0.15% bid
OU
¬ Travatan Z™ qd OU PM
contracted from his granddaughter will not
clear up
$ Started 3 weeks ago, worsened for 2
weeks, now stable
Is this a Type 1 or Type 4
Hypersensitivity Reaction?
$ Type 4 hypersensitivity
(delayed/ cell mediated)
¬  Occur in hours, days to
months after antigen challenge
¬  Etiology: contact dermatitis,
topical medications, jewelry,
nail polish
¬  Manifestations:
2  Itching
2  Red lids
2  Superficial skin changes
Which is most likely
the offending agent?
$ Patient has been using
Alphagan-P™ 0.15% for 9
months
$ Contact Dermatitis
Another 0.2% Brimonidine
Hypersensitivity
Type 1 and Type 4
Ocular Allergy
Giant Papillary Conjunctivitis
1 week later
Greg Caldwell, OD, FAAO
[email protected] 814-931-2030 cell
8
Ocular Manifestation and Treatment of
Allergic Disorders
37 year old woman
$ Previously treated for contact lens overwear
with Maxitrol™ (antibiotic and steroid) qid, told
she had sterile ulcers
$ With Maxitrol eyes feel better in 2 days
$ Her eyes are red and irritated, 3rd time this year,
wants 2nd opinion and treatment
$ Wore contact lens for 3 weeks, average wearing
time 8-10 hrs, before this episode started
Giant Papillary Conjunctivitis
$ Condition characterized by formation of large papillae (>0.3mm) on
the superior palpebral conjunctiva
$ No seasonal variation
$ Etiology
¬ Contact lens wear
¬ Exposed sutures (conjunctiva or cornea)
¬ Prosthesis
April 18, 2015
Slit lamp exam
$ Any thoughts?
¬  Why so recurrent?
$ Treatment?
¬  D/C CL wear
2  Until resolved
¬  Pataday™
¬  Tobradex™
2  Until cornea clear
¬  Lotemax™
¬  Artificial tears
$ Once resolved
¬  Maintenance dose of mast cell
stabilizer
¬  SCL - vs – GP – vs - vision
correction
Giant Papillary Conjunctivitis
$ Treatment
¬ Decreased CL wearing time
¬ Change to disposable soft CL’s, Dailies SCL, RGP
¬ Mast cell stabilizers (Pataday™)
¬ Topical steroids (short term)
2  Lotemax™
$ Pathophysiology
¬ Mechanical trauma induces inflammatory cascade and mast cell
degranulation
¬  No increase in histamine levels
¬  Plasma cells, mast cells, eosinophils and basophils are found in cytologic
scrapings. (Type I & IV)
2  Over-reaction of body’s immune system
¬  Arachidonic acid cycle main component
14 year old boy
Diagnosis and Treatment?
$ My eye is red, watery and very painful
$ Started about 10 days ago
$ Tried artificial tears without help
$ Child is healthy
$ Does not wear contact lens
$ Let’s look at the photo
Greg Caldwell, OD, FAAO
[email protected] 814-931-2030 cell
9
Ocular Manifestation and Treatment of
Allergic Disorders
Phlyctenulosis
$  Focal nodule of inflammatory tissue
$  Two forms
¬  Conjunctival
¬  Corneal
$  Focal nodule can migrate from conjunctiva to cornea
$  Etiology
¬  Staphylococcus (most common)
¬  Rosacea
¬  Tuberculosis
$  Treatment
¬  Rule out tuberculosis if suspicious
2  Chest X-ray and PPD
¬  Combination antibiotic/steroid
¬  Treat underlying lid disease
2  Blepharitis
2  Rosacea
Greg Caldwell, OD, FAAO
[email protected] 814-931-2030 cell
April 18, 2015
Thank-You
and
Hope You Enjoyed
Greg Caldwell OD, FAAO
[email protected]
10