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DNB QUESTIONS
Category Question for patients
Ocular symptoms What are your symptoms? How severe are they?
Are your eyes itchy? Do they burn? sting? Are they painful?
Is there discharge from your eyes? If so, is it watery or mucoid?
Does it feel like there is a foreign body in your eyes?
Do you rub your eyes?
Are your eyes dry?
When did your symptoms start?
What is your worst season, if any?
Have you had any previous episodes?
Are your symptoms in one eye or both?
Are there any exacerbating or relieving factors?
Is your vision affected?
Are you sensitive to lights?
Do you wear contact lenses? Are they comfortable?
Is there any history of trauma to your eyes?
Health history Is there associated atopy? Or a family history of atopy?
Is there a diagnosis of ADHD?
Are you on any medications?
Are there any other past medical and surgical concerns (tonsillectomy, sinus surgery)?
Exposures/Environment Do you live with pets?
Is the home carpeted? Forced-air heating? Air conditioning? Humidity level?
Is there exposure to smoke (first- or second-hand)?
Have there been any new exposures (e.g., new pet, renovations, new personal or home hygiene products)?
Are there any potential occupational exposures?
Infectious contacts (possibility of infectious cause of red eye)?
Treatment HaveOTC topical products been used? If so, which product(s)?
HaveOTC oral agents been used? If so, which product(s)?
Have prescription medications, including immunotherapy, been tried?
How often were the therapies used and for how long?
Has there been any relief of symptoms?
Quality of Life Are the symptoms interfering with school/work, activities of daily living or sleep?
Has school/work been missed due to symptoms?
OCULAR ALLERGY
THERAPEUTIC
PERSPECTIVES
DR PRIYA BASAIAWMOIT
INTRODUCTION
■ Ocular allergy – an inflammatory response of the
conjunctival mucosa, that also affects cornea & eye lids
■ In recent years advancement in the understanding &
pathophysiology of ocular allergies has paved way for
the development of newer drug candidates
EPIDEMIOLOGY
The diagnosis of allergic conjunctivitis is on the
increase
SAC (Seasonal AC) & PAC (Perennial AC) –15-20 % of
cases of allergic conjunctivitis
VKC – reported from many Asian countries e.g. Nepal,
Pakistan & India
VKC & AKC may cause corneal & ocular surface
involvement leading to severe visual loss
04
03
02
01
CLASSIFICATION
SEASONAL & PERENNIAL
ALLERGIC
CONJUNCTIVITIS
GIANT PAPILLARY
CONJUNCTIVITIS
VERNAL
KERATOCONJUNCTIVITIS
ATOPIC
KERATOCONJUNCTIVITIS
CAUSATIVE AGENTS &
RISK FACTORS
Changing
climates
Pollution
Genetics
Occurrence of
allergy in
childhood
Mixed Pollen
Thresher dust
Raw Cotton
Allergic
Conjunctivitis &
Rhinitis
VKC patients –
seasonal peak –
April to August
PATHOPHYSIOLOGY
OCULAR SURFACE
IMMUNOLOGICALLY
ACTIVE
INTERNAL OCULAR
STRUCTURES
IMMUNOPRIVILEDGED
CONTACT WITH
ENVIRONMENT
PATHOPHYSIOLOGY
Conjunctiva – vascularized
tissue consisting of
dendritic cells &
macrophages
Most common
site of allergic
reactions
TYPE I HYPERSENSITIVITY REACTION
TYPE IV HYPERSENSITIVITY
REACTION
SAC &
PAC
VKC
+ AKC
PATHOPHYSIOLOGY
TH2 CELLS
PRO INFLAMMATORY
CYTOKINES, IL3,4,5,13
Ig E
B cells
Stimulate
Ig E binding to Mast cells & causing degranulation
PATHOPHYSIOLOGY
EARLY PHASE LATE PHASE
Released mediators cause
1. Pruritis
2. Tearing
3. Redness
4. Conjunctival injection
5. Chemosis
6. Papillary reaction
1. Epithelial infiltration of
inflammatory mediators
2. Continued inflammation
3. Tissue damage
4. Tear hypersecretion carries
inflammatory mediators via
lacrimal passage
SYMPTOMS & SIGNS
Itching
Tearing Edema
Redness
T I R Ed
Photophobia Chemosis Papillary Reaction
OVERLAP WITH DRY EYES
SAC
01
Common among all ages accounting for more than
half the cases of AC
02
Occurs seasonally when pollen is released in
May & June
03 Itching followed by watering is seen
04
Sometimes associated with allergic rhinitis
or rhino conjunctivitis
PAC
Corneal
involvement in
SAC and PAC is rare
Itching, redness &
conjunctival swelling
Similar signs
& symptoms to SAC
Allergy to
animal dander,
feathers, mites
Frequency
of occurrence
increases as the age
increases
As the name
suggests it occurs
throughout the
year
01 Skin Prick test 04 Nonspecific provocation test
02 Patch test 05 Tear film evaluations
03 Conjunctival provocation test 06
Ocular surface staining
procedures
EVALUATION & DIAGNOSTIC
TESTS
Allergic Rhinitis –95%
NasalPolyps–29% Dryeye –50% Contactdermatitis &
Blepharitis seen inchronic forms
Secretory
Otitis media– 23%
Asthma–28-80%
1 2 3
6
5
4
COMORBID CONDITIONS
01 Vernalkeratoconjuntivitis (VKC)
02 Giant papillary conjunctivitis (GPC)
03 Atopic keratoconjunctivitis (AKC)
CHRONIC ALLERGIC CONDITIONS
VKC
Warm tropical
climates
Limbal form in Africans
Boys affected
3.2:1
50% patients
have other
atopic
manifestations
50% family h/o
Atopy
<10 years,
outgrow the disease
after puberty
CLINICAL MANIFESTATIONS
Itching/Pruritis
(Most common)
Photophobia
Thick mucus discharge
Tearing
Burning
Foreign body sensation
Pain
Blurred Vision
PTOSIS
VKC –TYPES
PALPEBRAL BULBAR
MIXED
• Upper tarsal papillae –
discrete, enlarged >1mm
(Cobblestone appearance)
• Ropy discharge
• Subepithelial fibrosis – lid
thickening
• More in dark skinned
• Horner-Trantas dots -
Gelatinous, confluent, yellow-
gray infiltrates are
pathognomonic
• Punctate collections of
epithelial cells, eosinophils &
calcified corneal concretions
SIGHT THREATENING
CORNEAL SIGNS IN VKC
• Superficial peripheral
neovascularization
• Punctate corneal epitheliopathy
• Shield ulcers –upper half – scarring
• Sub-epithelial scarring
• Plaque formation secondary to
accumulation of inflammatory
debris
SHIELD ULCER
01
02
03
Grade I ulcer having a transparent base
Grade II – with a translucent base or with white /yellowish
deposits
Grade III – elevated plaque which is above the level of the adjacent
normal epithelium
Chronic VKC – limbal stem cell deficiency leading to corneal vascularization, pannus
formation, poor ocular surface & persistent epithelial defects
AKC
Occurring
throughout life
Cataract
formation
can occur
B/L disease of
ocular surface &
lids
Bluish
discoloration
below eyes
Eczematous
skin lesions
Papillae or
Trantas dots
Right and left eyes with
periocular eczema and corneal
haze. C and D: Right and left
eyes with progression of the
disease; dense pannus
entering visual axis. E:
symblepharon. F: posterior
subcapsular cataract, which
can be associated with atopic
keratoconjunctivitis.
AKC
AKC
VS
VKC
GPC
Preservatives
in medicine
Drug induced
Trauma to upper tarsal
conjunctiva by CL,
ocular prosthesis
or sutures
Toxic allergic
reactions
Giant Papillae
formation
Removal of
external agents
reduce papillae
ALLERGIC CONJUNCTIVITIS
CONTACT
HYPERSENSITIVITY
01
02
03
The pattern of involvement depends upon severity of the reaction &
the site of contacts
Patients may have lid swelling, redness, chemosis, follicular reaction
& later sometimes cicatrization
corneal involvement – superficial punctate keratitis, pseudodendrites
or grayish stromal infiltrates
COMPLICATIONS
Poortreatment compliance Dry eye Infection
Corneal scar Chronicity–LSCD Secondary Keratoconus
01. 02. 03.
06.
05.
04.
Steroid response
07.
Complications lead to irreversible visual loss
LSCD & Keratoconus – surgical intervention
DIAGNOSIS
Presence of itching is the
hallmark of allergy
AC is not a single disease &
is not exclusive of
conditions such as tear film
dysfunction
1. SAC & PAC are the
most common allergic
disorders
2. Accurate clinical
history & evaluation of
signs and symptoms
3.
IgE-mediated hypersensitivity &
mast cell degranulation are the
initial pathophysiological
mechanisms
4.
Identification of
specific sensitizing
allergens is useful for
avoidance
5. Prick test is the
primary recommended
allergy test
6.
The cornea may be involved
in VKC, AKC, or contact
blepharo-conjunctivitis but
not in SAC or PAC
7.
AC can occur even if skin
prick test is negative or
IgE is negative 8. Conjunctival allergen
provocation can prove
local hypersensitivity
9.
DIAGNOSIS – SUMMARY
MANAGEMENT
Allergen Avoidance
Non pharmacologic
management
Pharmacologic
treatment
Topical
vasoconstrictors/Decongestants
Antihistamines
Mast cell stabilizers
Dual action agents
NSAIDS
Biologicals
Immunomodulators
Immunotherapy
Immunotherapy
Steroids
Cold compress
Cold artificial tears
THERAPEUTIC PRINCIPLES –
STEPLADDER APPROACH
Topical antihistamines, Mast cell
stabilizers, NSAIDS or multiple
agents
Avoidance, cold compress &
artificial tears
Liposomal drug delivery
systems, Anti-IgE therapy..etc
Topical steroids or
immunotherapy
Cyclosporine & tacrolimus
ALLERGEN AVOIDANCE
1ST LINE
APPROACH –
ACCOMPANY MEDICAL MANAGEMENT
Complete allergen
avoidance
CL associated, CL solution,
switch to disposalble
Punctal occlusion
mechanical barrier gels
In all types of conjunctivitis
In GPC
Allergic rhino conjunctivitis.
NON PHARMACOLOGIC
TREATMENTS
NON PHARMACOLOGIC
TREATMENTS
Cold compress, Saline
Cold artificial tears &
ointments
Probiotics
Prostaglandin D2
receptor anrtagonist
Useful, as they help allevate the symptoms
– acute AC
Dilution of allergens
Clinical trails – Rhino conjunctivitis
Clinical trials – Rhino conjunctivitis
Drug MOA Effects Approved for Side effects Contraindications
Vasoconstrictors &
Decongestants
Alpha
adrenergic
(alpha 1)
Immediate
vasoconstriction
Conjunctival
hyperemia
Rebound
hyperemia,
follicular
reaction,
mydriasis,
blepharitis,
conjunctivitis
Narrow angle
glaucoma, MAO
inhibitors, Children
under 14
1
Naphazoline/Oxymetazoline/Xylometazoline
1. Over the counter medications
2. Inappropriate use by patients
3. Used in cases of episodic itching
4. Short duration with many side
effects
1. Seldom indicated
in our practice
2. Sparingly used
for short term
solution
Drug MOA Effects Approved for Side effects Contraindications
Antihistamine
s
H1
antagonist
Antagonize
venular
permeability &
chemotaxis of
lymphocytes &
eosinophils
Early phase
symptomatology
First generation
crosses BBB,
sedation,
possible
stinging,
keratitis
Nil
2
Emedastine/Levocabastine/Epinastine
1. Most preferred option for treatment
2. Relief of itching & redness
3. Most effective in acute phase
4. Rarely sufficient as monotherapy
1. Antazoline &
Pheneramine –
1st generation
2. Available in
combination with
Naphazoline
Drug MOA Effects Approved for Side effects Contraindications
Mast cell
stabilizers
Inhibit mast
cell
degranulation
5-14 days
onset of
action
Prevents release of
histamine & other
preformed
mediators
Prophylaxis Headaches,
Burning,
Irritation
Nil
3
Cromolyn Sodium/Permirolast Pottasium/Lodoxamide/Nedocromil Sodium
1. Takes several weeks to attain max
efficacy
2. Do not relieve existing symptoms
3. Not effective on mediators once its
released
1. Not useful for acute symptoms
2. Dosing 3-4 times a day may limit
patient compliance
3. Combination with steroid/oral
antihistamine – more potent
Drug MOA Effects Approved for Side effects Contraindications
Dual activity
agents
H1
antagonist +
Inhibit mast
cell
degranulation
Histamine
inhibition and
prevention of
release
Itch
Olapatadine
approved for all
signs & symptoms
Nil Children under 3
years of age
4
Ketotifen/Olapatadine/Bepostatine/Alcaftidine/Azelastine
1. 1st line agents & most commonly
prescribed
2. Provide rapid symptom relief as well
as tolerability
3. Act in early & late phase reaction
1. Once daily administration for
Olapatadine & Alcaftadine
2. Improving patient compliance
3. Combination with steroid can
be done if severe symptoms
Drug MOA Effects Approved for Side effects Contraindications
Topical
NSAIDs
Cyclooxygenase
inhibition
interrupting
prostaglandin
formation
Pain
Short term use
only
Stinging,
Keratitis,
Ocular
hypertension
Asthma, Nasal
polyps
5
Ketorolac/Flurbiprofen/Nepafenac
1. Temporary reduction of severe
symptoms of discomfort
2. Not often used in AC
3. Useful when symptoms continue to
be inadequately controlled
1. Can also be used if
prescription of steroid not
optimal for a patient
Drug MOA Effects Approved for Side effects Contraindications
Topical
Corticosteroids
Block
phospholipase
A2, inhibits
proliferation of
mast cells,
reduces
histamine,
inhibits T-cell
activation
Prevention of
prostaglandin
and leukotriene
synthesis,
reduced
permeability of
vascular walls
All signs and
symptoms
Short term use only
Cataracts, ocular
hypertension,
delayed healing,
infection,
immunosuppressi
on
General
contraindications for
corticosteroids
6
Prednisolone/Dexamethasone/Fluromethalone/Loteprednol
1. Preferable to use low strength steroids
2. 2 treatment types – Pulsed or Prolonged
3. Pulse – 3-4 drops/day for 3-5 days - AKC &
VKC
4. Prolonged – 3-4 drops per day for 1-3 weeks
then taper – chronic disease
1. PAC & SAC rarely require
steroids
2. Loteprednol – metabolized
efficiently – ocular surface
inflammation
3. Used in seasonal AC
STEROID FORMULATIONS
Intranasal
steroids
Local
application
Supratarsal/
Periocular
Oral
Steroids
Glucocorticoid
Receptor
antagonists
Effective in
reducing nasal &
ocular symptoms
of SAC & PAC as
ocular symptoms
can be due to
naso-ocular
reflex
Eg: Fluticasone
Local application
over skin in AKC
& PAC
steroids in
regular or depot
formulations are
effective in very
recalcitrant
cases of AKC &
VKC
Eg:
Triamcinalone
acetonide
Short courses
effective in AKC
& VKC
Experimental
drugs
Clinical trials
IMMUNOMODULATORS
CYCLOSPORINE
• T cell & mast cell inhibitor effective
in controlling ocular inflammation
by blocking Th2 lymphocyte
proliferation & IL2 production
• Also inhibits histamine release
from mast cell & basophils & by
reducing IL5 production
• Concentration: 0.05-2%
• GPC, VKC, AKC
TACROLIMUS
• Similar/Superior effectivity as
compared to cyclosporine
• Ointment preparation
• Concentration: 0.03-0.1%
• Used when unresponsive to
cyclosporine
• Lid Eczema in AKC
• Severe AKC & VKC
Calcineurin inhibitors
Side effects – stinging/burning sensation & the possibility of molluscum contagiosum virus, papillomavirus, or
herpesvirus infection
ORAL ANTIHISTAMINES
2nd generation considered
2nd generation does not cross
BBB
Slower onset of action, not
much effective in VKC
Associated with drying of
mucosal membranes &
reduced tear production
LEUKOTRINE ANTAGONISTS
Decreases symptoms of PAC
& SAC
Not as effective as oral
antihistamines
Combination therapy can be
used
Cetrizine,
Fexofenadine,Azelastine
01.
03.
04.
01.
02.
03.
05.
ORAL MEDICATIONS
02.
IMMUNOTHERAPY
01 Goal – to diminish symptoms of rhinitis & conjunctivitis
triggered by known allergens & to prevent recurrence
02
03
04
Administering gradually increasing amounts of the allergen to induce
an immunological tolerance
Allergen administered subcutaneously (SCIT) – Induction phase &
maintenance phase
Considered in Allergic conjunctivitis IgE & non IgE mediated
BIOLOGICALS
01 Goal – Binding to specific biological molecules thereby
blocking inflammatory pathway
02
03
04
Clinical trials on Omalizumab for asthma & Dupilumab
for dermatitis inVKC
Not yet approved for allergic conjunctivitis
Insunakinra – IL1 receptor antagonist, documented to diminish
ocular surface symptoms
TREATMENT
SURGERY
Conjunctival resection
with bulbar conjunctival
autograft or amniotic
membrane graft inVKC
Superficial keratectomy
for shield ulcer inVKC
Complex surgery in AKC,
of lids, ocular surface and
Boston K-PRO
SPECIAL CONSIDERATIONS
ELDERLY ATHLETES PREGNANCY
• Similar causes as in other age
groups
• Age related changes
• Oral antihistamines closely
monitored
• Tear film dysfunction to be
considered
• Athletic performance can be
affected
• Appropriate management of
symptoms with safe, effective
medications is needed
• Ability to compete should not
be affected
• Limited data that ocular
medications are found in
breast milk
• Oral decongestants are
avoided
• Cromolyn Na is safe
• Intranasal steroids safe &
effective
OTHER CONSIDERATIONS
CONTACT LENSES OCULAR SURFACE
• Avoided in patients with
seasonal allergy
• Bandage contact lenses can be
used
• Daily disposable lenses better
than Extended wear in AC
• Soft silicone with
increased gas permeability
contact lenses have a higher
satisfaction of comfort (56%) than
RGP lenses (14%), with 63% of
Non atopic & 47% of atopic
subjects describing their lenses as
very comfortable to wear
• Recommendation is for 1 drop at a time,
with closure of the eyelids for a few
seconds after drug instillation
• When multiple eye drops are to be used,
allow time between individual
medications (3-5 minutes) to permit
proper absorption of the medication into
the ocular tissue and to prevent washout
TREATMENT SUMMARY
Identification & avoidance of
irritants and sensitizing agents
is the most effective way to
prevent ocular allergy
Cold compresses & refrigerated
topical medications
Lubricants help to remove &
dilute allergens that come in
contact with the ocular surface
Oral 2nd gen antihistamines
preferred over 1st gen
In cases of dry eye oral
antihistamines are to be
discontinued
Topical antihistamines are
effective in the treatment of
AC
Topical decongestants should
not be used long term because
of a potential “paradoxical
effect.”
Topical cromolyn Na has
been the prototypic
compound among mast cell
stabilizer
TREATMENT SUMMARY
Topical dual or multiple actions
newer drugs are widely &
effectively used
Topical NSAIDs, although
effective in treating ocular
allergy, may cause ocular &
systemic side effects
Topical steroids should be
restricted to brief courses for
the most severe forms of ocular
allergies
Topical cyclosporin A & other
immunomodulators used in
severe chronic disease
Allergen immunotherapy
should be considered for
patients with AC & AR
Safety profile of drugs
considered during
pregnancy
Evidence accumulated that
intranasal corticosteroids
reduce ocular symptoms
associated with allergic rhinitis
Stepwise approach utilized
for treatment of AC
THANK YOU

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OCULAR ALLERGY THERAPEUTIC PERSPECTIVES

  • 2. Category Question for patients Ocular symptoms What are your symptoms? How severe are they? Are your eyes itchy? Do they burn? sting? Are they painful? Is there discharge from your eyes? If so, is it watery or mucoid? Does it feel like there is a foreign body in your eyes? Do you rub your eyes? Are your eyes dry? When did your symptoms start? What is your worst season, if any? Have you had any previous episodes? Are your symptoms in one eye or both? Are there any exacerbating or relieving factors? Is your vision affected? Are you sensitive to lights? Do you wear contact lenses? Are they comfortable? Is there any history of trauma to your eyes? Health history Is there associated atopy? Or a family history of atopy? Is there a diagnosis of ADHD? Are you on any medications? Are there any other past medical and surgical concerns (tonsillectomy, sinus surgery)? Exposures/Environment Do you live with pets? Is the home carpeted? Forced-air heating? Air conditioning? Humidity level? Is there exposure to smoke (first- or second-hand)? Have there been any new exposures (e.g., new pet, renovations, new personal or home hygiene products)? Are there any potential occupational exposures? Infectious contacts (possibility of infectious cause of red eye)? Treatment HaveOTC topical products been used? If so, which product(s)? HaveOTC oral agents been used? If so, which product(s)? Have prescription medications, including immunotherapy, been tried? How often were the therapies used and for how long? Has there been any relief of symptoms? Quality of Life Are the symptoms interfering with school/work, activities of daily living or sleep? Has school/work been missed due to symptoms?
  • 4. INTRODUCTION ■ Ocular allergy – an inflammatory response of the conjunctival mucosa, that also affects cornea & eye lids ■ In recent years advancement in the understanding & pathophysiology of ocular allergies has paved way for the development of newer drug candidates
  • 5. EPIDEMIOLOGY The diagnosis of allergic conjunctivitis is on the increase SAC (Seasonal AC) & PAC (Perennial AC) –15-20 % of cases of allergic conjunctivitis VKC – reported from many Asian countries e.g. Nepal, Pakistan & India VKC & AKC may cause corneal & ocular surface involvement leading to severe visual loss 04 03 02 01
  • 6. CLASSIFICATION SEASONAL & PERENNIAL ALLERGIC CONJUNCTIVITIS GIANT PAPILLARY CONJUNCTIVITIS VERNAL KERATOCONJUNCTIVITIS ATOPIC KERATOCONJUNCTIVITIS
  • 7. CAUSATIVE AGENTS & RISK FACTORS Changing climates Pollution Genetics Occurrence of allergy in childhood Mixed Pollen Thresher dust Raw Cotton Allergic Conjunctivitis & Rhinitis VKC patients – seasonal peak – April to August
  • 9. PATHOPHYSIOLOGY Conjunctiva – vascularized tissue consisting of dendritic cells & macrophages Most common site of allergic reactions TYPE I HYPERSENSITIVITY REACTION TYPE IV HYPERSENSITIVITY REACTION SAC & PAC VKC + AKC
  • 10. PATHOPHYSIOLOGY TH2 CELLS PRO INFLAMMATORY CYTOKINES, IL3,4,5,13 Ig E B cells Stimulate Ig E binding to Mast cells & causing degranulation
  • 11. PATHOPHYSIOLOGY EARLY PHASE LATE PHASE Released mediators cause 1. Pruritis 2. Tearing 3. Redness 4. Conjunctival injection 5. Chemosis 6. Papillary reaction 1. Epithelial infiltration of inflammatory mediators 2. Continued inflammation 3. Tissue damage 4. Tear hypersecretion carries inflammatory mediators via lacrimal passage
  • 12. SYMPTOMS & SIGNS Itching Tearing Edema Redness T I R Ed Photophobia Chemosis Papillary Reaction
  • 13.
  • 14.
  • 16. SAC 01 Common among all ages accounting for more than half the cases of AC 02 Occurs seasonally when pollen is released in May & June 03 Itching followed by watering is seen 04 Sometimes associated with allergic rhinitis or rhino conjunctivitis
  • 17. PAC Corneal involvement in SAC and PAC is rare Itching, redness & conjunctival swelling Similar signs & symptoms to SAC Allergy to animal dander, feathers, mites Frequency of occurrence increases as the age increases As the name suggests it occurs throughout the year
  • 18. 01 Skin Prick test 04 Nonspecific provocation test 02 Patch test 05 Tear film evaluations 03 Conjunctival provocation test 06 Ocular surface staining procedures EVALUATION & DIAGNOSTIC TESTS
  • 19. Allergic Rhinitis –95% NasalPolyps–29% Dryeye –50% Contactdermatitis & Blepharitis seen inchronic forms Secretory Otitis media– 23% Asthma–28-80% 1 2 3 6 5 4 COMORBID CONDITIONS
  • 20. 01 Vernalkeratoconjuntivitis (VKC) 02 Giant papillary conjunctivitis (GPC) 03 Atopic keratoconjunctivitis (AKC) CHRONIC ALLERGIC CONDITIONS
  • 21. VKC Warm tropical climates Limbal form in Africans Boys affected 3.2:1 50% patients have other atopic manifestations 50% family h/o Atopy <10 years, outgrow the disease after puberty
  • 22. CLINICAL MANIFESTATIONS Itching/Pruritis (Most common) Photophobia Thick mucus discharge Tearing Burning Foreign body sensation Pain Blurred Vision PTOSIS
  • 23. VKC –TYPES PALPEBRAL BULBAR MIXED • Upper tarsal papillae – discrete, enlarged >1mm (Cobblestone appearance) • Ropy discharge • Subepithelial fibrosis – lid thickening • More in dark skinned • Horner-Trantas dots - Gelatinous, confluent, yellow- gray infiltrates are pathognomonic • Punctate collections of epithelial cells, eosinophils & calcified corneal concretions
  • 24. SIGHT THREATENING CORNEAL SIGNS IN VKC • Superficial peripheral neovascularization • Punctate corneal epitheliopathy • Shield ulcers –upper half – scarring • Sub-epithelial scarring • Plaque formation secondary to accumulation of inflammatory debris
  • 25. SHIELD ULCER 01 02 03 Grade I ulcer having a transparent base Grade II – with a translucent base or with white /yellowish deposits Grade III – elevated plaque which is above the level of the adjacent normal epithelium Chronic VKC – limbal stem cell deficiency leading to corneal vascularization, pannus formation, poor ocular surface & persistent epithelial defects
  • 26.
  • 27. AKC Occurring throughout life Cataract formation can occur B/L disease of ocular surface & lids Bluish discoloration below eyes Eczematous skin lesions Papillae or Trantas dots
  • 28.
  • 29. Right and left eyes with periocular eczema and corneal haze. C and D: Right and left eyes with progression of the disease; dense pannus entering visual axis. E: symblepharon. F: posterior subcapsular cataract, which can be associated with atopic keratoconjunctivitis. AKC
  • 31. GPC Preservatives in medicine Drug induced Trauma to upper tarsal conjunctiva by CL, ocular prosthesis or sutures Toxic allergic reactions Giant Papillae formation Removal of external agents reduce papillae
  • 32.
  • 34. CONTACT HYPERSENSITIVITY 01 02 03 The pattern of involvement depends upon severity of the reaction & the site of contacts Patients may have lid swelling, redness, chemosis, follicular reaction & later sometimes cicatrization corneal involvement – superficial punctate keratitis, pseudodendrites or grayish stromal infiltrates
  • 35. COMPLICATIONS Poortreatment compliance Dry eye Infection Corneal scar Chronicity–LSCD Secondary Keratoconus 01. 02. 03. 06. 05. 04. Steroid response 07. Complications lead to irreversible visual loss LSCD & Keratoconus – surgical intervention
  • 36. DIAGNOSIS Presence of itching is the hallmark of allergy
  • 37. AC is not a single disease & is not exclusive of conditions such as tear film dysfunction 1. SAC & PAC are the most common allergic disorders 2. Accurate clinical history & evaluation of signs and symptoms 3. IgE-mediated hypersensitivity & mast cell degranulation are the initial pathophysiological mechanisms 4. Identification of specific sensitizing allergens is useful for avoidance 5. Prick test is the primary recommended allergy test 6. The cornea may be involved in VKC, AKC, or contact blepharo-conjunctivitis but not in SAC or PAC 7. AC can occur even if skin prick test is negative or IgE is negative 8. Conjunctival allergen provocation can prove local hypersensitivity 9. DIAGNOSIS – SUMMARY
  • 38. MANAGEMENT Allergen Avoidance Non pharmacologic management Pharmacologic treatment Topical vasoconstrictors/Decongestants Antihistamines Mast cell stabilizers Dual action agents NSAIDS Biologicals Immunomodulators Immunotherapy Immunotherapy Steroids Cold compress Cold artificial tears
  • 39. THERAPEUTIC PRINCIPLES – STEPLADDER APPROACH Topical antihistamines, Mast cell stabilizers, NSAIDS or multiple agents Avoidance, cold compress & artificial tears Liposomal drug delivery systems, Anti-IgE therapy..etc Topical steroids or immunotherapy Cyclosporine & tacrolimus
  • 40. ALLERGEN AVOIDANCE 1ST LINE APPROACH – ACCOMPANY MEDICAL MANAGEMENT Complete allergen avoidance CL associated, CL solution, switch to disposalble Punctal occlusion mechanical barrier gels In all types of conjunctivitis In GPC Allergic rhino conjunctivitis.
  • 41. NON PHARMACOLOGIC TREATMENTS NON PHARMACOLOGIC TREATMENTS Cold compress, Saline Cold artificial tears & ointments Probiotics Prostaglandin D2 receptor anrtagonist Useful, as they help allevate the symptoms – acute AC Dilution of allergens Clinical trails – Rhino conjunctivitis Clinical trials – Rhino conjunctivitis
  • 42. Drug MOA Effects Approved for Side effects Contraindications Vasoconstrictors & Decongestants Alpha adrenergic (alpha 1) Immediate vasoconstriction Conjunctival hyperemia Rebound hyperemia, follicular reaction, mydriasis, blepharitis, conjunctivitis Narrow angle glaucoma, MAO inhibitors, Children under 14 1 Naphazoline/Oxymetazoline/Xylometazoline 1. Over the counter medications 2. Inappropriate use by patients 3. Used in cases of episodic itching 4. Short duration with many side effects 1. Seldom indicated in our practice 2. Sparingly used for short term solution
  • 43. Drug MOA Effects Approved for Side effects Contraindications Antihistamine s H1 antagonist Antagonize venular permeability & chemotaxis of lymphocytes & eosinophils Early phase symptomatology First generation crosses BBB, sedation, possible stinging, keratitis Nil 2 Emedastine/Levocabastine/Epinastine 1. Most preferred option for treatment 2. Relief of itching & redness 3. Most effective in acute phase 4. Rarely sufficient as monotherapy 1. Antazoline & Pheneramine – 1st generation 2. Available in combination with Naphazoline
  • 44. Drug MOA Effects Approved for Side effects Contraindications Mast cell stabilizers Inhibit mast cell degranulation 5-14 days onset of action Prevents release of histamine & other preformed mediators Prophylaxis Headaches, Burning, Irritation Nil 3 Cromolyn Sodium/Permirolast Pottasium/Lodoxamide/Nedocromil Sodium 1. Takes several weeks to attain max efficacy 2. Do not relieve existing symptoms 3. Not effective on mediators once its released 1. Not useful for acute symptoms 2. Dosing 3-4 times a day may limit patient compliance 3. Combination with steroid/oral antihistamine – more potent
  • 45. Drug MOA Effects Approved for Side effects Contraindications Dual activity agents H1 antagonist + Inhibit mast cell degranulation Histamine inhibition and prevention of release Itch Olapatadine approved for all signs & symptoms Nil Children under 3 years of age 4 Ketotifen/Olapatadine/Bepostatine/Alcaftidine/Azelastine 1. 1st line agents & most commonly prescribed 2. Provide rapid symptom relief as well as tolerability 3. Act in early & late phase reaction 1. Once daily administration for Olapatadine & Alcaftadine 2. Improving patient compliance 3. Combination with steroid can be done if severe symptoms
  • 46.
  • 47. Drug MOA Effects Approved for Side effects Contraindications Topical NSAIDs Cyclooxygenase inhibition interrupting prostaglandin formation Pain Short term use only Stinging, Keratitis, Ocular hypertension Asthma, Nasal polyps 5 Ketorolac/Flurbiprofen/Nepafenac 1. Temporary reduction of severe symptoms of discomfort 2. Not often used in AC 3. Useful when symptoms continue to be inadequately controlled 1. Can also be used if prescription of steroid not optimal for a patient
  • 48. Drug MOA Effects Approved for Side effects Contraindications Topical Corticosteroids Block phospholipase A2, inhibits proliferation of mast cells, reduces histamine, inhibits T-cell activation Prevention of prostaglandin and leukotriene synthesis, reduced permeability of vascular walls All signs and symptoms Short term use only Cataracts, ocular hypertension, delayed healing, infection, immunosuppressi on General contraindications for corticosteroids 6 Prednisolone/Dexamethasone/Fluromethalone/Loteprednol 1. Preferable to use low strength steroids 2. 2 treatment types – Pulsed or Prolonged 3. Pulse – 3-4 drops/day for 3-5 days - AKC & VKC 4. Prolonged – 3-4 drops per day for 1-3 weeks then taper – chronic disease 1. PAC & SAC rarely require steroids 2. Loteprednol – metabolized efficiently – ocular surface inflammation 3. Used in seasonal AC
  • 49. STEROID FORMULATIONS Intranasal steroids Local application Supratarsal/ Periocular Oral Steroids Glucocorticoid Receptor antagonists Effective in reducing nasal & ocular symptoms of SAC & PAC as ocular symptoms can be due to naso-ocular reflex Eg: Fluticasone Local application over skin in AKC & PAC steroids in regular or depot formulations are effective in very recalcitrant cases of AKC & VKC Eg: Triamcinalone acetonide Short courses effective in AKC & VKC Experimental drugs Clinical trials
  • 50. IMMUNOMODULATORS CYCLOSPORINE • T cell & mast cell inhibitor effective in controlling ocular inflammation by blocking Th2 lymphocyte proliferation & IL2 production • Also inhibits histamine release from mast cell & basophils & by reducing IL5 production • Concentration: 0.05-2% • GPC, VKC, AKC TACROLIMUS • Similar/Superior effectivity as compared to cyclosporine • Ointment preparation • Concentration: 0.03-0.1% • Used when unresponsive to cyclosporine • Lid Eczema in AKC • Severe AKC & VKC Calcineurin inhibitors Side effects – stinging/burning sensation & the possibility of molluscum contagiosum virus, papillomavirus, or herpesvirus infection
  • 51.
  • 52. ORAL ANTIHISTAMINES 2nd generation considered 2nd generation does not cross BBB Slower onset of action, not much effective in VKC Associated with drying of mucosal membranes & reduced tear production LEUKOTRINE ANTAGONISTS Decreases symptoms of PAC & SAC Not as effective as oral antihistamines Combination therapy can be used Cetrizine, Fexofenadine,Azelastine 01. 03. 04. 01. 02. 03. 05. ORAL MEDICATIONS 02.
  • 53. IMMUNOTHERAPY 01 Goal – to diminish symptoms of rhinitis & conjunctivitis triggered by known allergens & to prevent recurrence 02 03 04 Administering gradually increasing amounts of the allergen to induce an immunological tolerance Allergen administered subcutaneously (SCIT) – Induction phase & maintenance phase Considered in Allergic conjunctivitis IgE & non IgE mediated
  • 54. BIOLOGICALS 01 Goal – Binding to specific biological molecules thereby blocking inflammatory pathway 02 03 04 Clinical trials on Omalizumab for asthma & Dupilumab for dermatitis inVKC Not yet approved for allergic conjunctivitis Insunakinra – IL1 receptor antagonist, documented to diminish ocular surface symptoms
  • 56. SURGERY Conjunctival resection with bulbar conjunctival autograft or amniotic membrane graft inVKC Superficial keratectomy for shield ulcer inVKC Complex surgery in AKC, of lids, ocular surface and Boston K-PRO
  • 57. SPECIAL CONSIDERATIONS ELDERLY ATHLETES PREGNANCY • Similar causes as in other age groups • Age related changes • Oral antihistamines closely monitored • Tear film dysfunction to be considered • Athletic performance can be affected • Appropriate management of symptoms with safe, effective medications is needed • Ability to compete should not be affected • Limited data that ocular medications are found in breast milk • Oral decongestants are avoided • Cromolyn Na is safe • Intranasal steroids safe & effective
  • 58. OTHER CONSIDERATIONS CONTACT LENSES OCULAR SURFACE • Avoided in patients with seasonal allergy • Bandage contact lenses can be used • Daily disposable lenses better than Extended wear in AC • Soft silicone with increased gas permeability contact lenses have a higher satisfaction of comfort (56%) than RGP lenses (14%), with 63% of Non atopic & 47% of atopic subjects describing their lenses as very comfortable to wear • Recommendation is for 1 drop at a time, with closure of the eyelids for a few seconds after drug instillation • When multiple eye drops are to be used, allow time between individual medications (3-5 minutes) to permit proper absorption of the medication into the ocular tissue and to prevent washout
  • 59. TREATMENT SUMMARY Identification & avoidance of irritants and sensitizing agents is the most effective way to prevent ocular allergy Cold compresses & refrigerated topical medications Lubricants help to remove & dilute allergens that come in contact with the ocular surface Oral 2nd gen antihistamines preferred over 1st gen In cases of dry eye oral antihistamines are to be discontinued Topical antihistamines are effective in the treatment of AC Topical decongestants should not be used long term because of a potential “paradoxical effect.” Topical cromolyn Na has been the prototypic compound among mast cell stabilizer
  • 60. TREATMENT SUMMARY Topical dual or multiple actions newer drugs are widely & effectively used Topical NSAIDs, although effective in treating ocular allergy, may cause ocular & systemic side effects Topical steroids should be restricted to brief courses for the most severe forms of ocular allergies Topical cyclosporin A & other immunomodulators used in severe chronic disease Allergen immunotherapy should be considered for patients with AC & AR Safety profile of drugs considered during pregnancy Evidence accumulated that intranasal corticosteroids reduce ocular symptoms associated with allergic rhinitis Stepwise approach utilized for treatment of AC

Editor's Notes

  1. ADHD-allergic decongestants should NOT be taken alongside prescription medications for ADHD. ANTIHISTAMINES increase ADHD symptoms in children with ATOPIC DERMATITIS Treating allergies can improve their ability to finish their work and concentrate . Attention deficit hyperactivity disorder
  2. Immunopriviledged means ability to tolerate introuduction of antigens without eliciting inflammatory immune response Eg of immunoprivilidged organs eyes,placenta,foetus,CNS,
  3. Role of mast cell and T lymphocyte in allergic conjunctivitis
  4. Pain if corneal involvement,
  5. Mediterranean, the Middle East, Central and West Africa, South America, and Asian countries, such as Japan, Thailand, and India Other atopic manifestations such as allergic rhinitris and asthma
  6. Skin prick test- Epicutaneous tests (“prick,” intradermal) (SPT) remain the most simple, rapid, and inexpensive procedure for the diagnosis of allergen sensitivity in patients with ocular allergy. Skin tests provide evidence of specific sensitivity to external environmental allergens within 20 minutes after placement on the skin. A positive wheal-and-flare reaction reinforces the concept of specific allergen sensitization to the patient. The test is highly sensitive for systemic allergies, such as allergic rhinitis and allergic asthma, but it does not always correlate with allergic sensitization of the ocular surface. PATCH TEST: presence of eczematous blepharitis or blepharo-conjunctivitis may suggest the possibility of a delayed-type reaction, and patch testing may be necessary to delineate the specific antigen. This involves applying a series of potential chemical sensitizers in aluminum or cellulose disks to the skin of the back; these are removed after 48 hours and the patches examined at multiple time points. Benzalkonium chloride and thimerosal, preservatives present in ophthalmic and contact lens solutions, are common culprits. Periorbital skin is quite different from other sites such as that of the back, not only for the depth of epithelial and dermal layers, but also for the limited number of mast cells present and for its limited exposure to the external environment compared with the eyelid. For example, possibly sun exposure exacerbates specific and nonspecific hyperreactivity reactions only on the lid skin. Conjunctival provocation test :can be likened to “skin testing” of the eye, because known quantities of specific allergen are instilled onto the ocular surface, and the resulting allergic response is measured at 15 to 30 minutes, similar to skin testing. Mediator release and cellular infiltration are relatively easily measured in tear samples. This technique is primarily used in the assessment of new drugs for ocular allergies, but it can sometimes be used to define suspected sensitizing allergens that appear to be limited to the ocular surface.26 ,27  The immediate positive response is characterized by the same signs (redness, chemosis, and lid swelling) and symptoms (itching and tearing) as those the patients experience after natural exposure to the antigen. The positive reaction usually subsides gradually, within 20 minutes. A late-phase inflammatory reaction also may occur, depending on allergen dose and patient sensitivity. The CPT is a safe and simple procedure that provides valuable clinical information with limited systemic side effects (generalized itching, bronchospasm, anaphylaxis) that are rarely seen. Nonspecific provocation test: Ocular challenge with histamine or hyperosmolar solutions has been used to verify a nonspecific hyperresponsiveness of the conjunctiva in allergic patients.29  Vernal keratoconjunctivitis patients were shown to respond with lower concentrations of histamine, although this remains experimental at this point Tear film evaluations:Measurement of total IgE in tears Normal values of IgE in tears are normally very low, less than 2.5 kUI/L (3 ng/mL), because of the blood–tear barrier. Detectable tear IgE levels indicate local production of antibodies and suggest a diagnosis of allergic conjunctivitis.  Tear osmolarity Tear osmolarity should be evaluated for supporting the diagnosis of tear film dysfunction (previously known as dry eye syndrome).31 ,32  Hyperosmolarity suggests a form of dry eye.  Schirmer test The Schirmer tear test is the most commonly used and easily performed test for tear production by the lacrimal gland in the evaluation of dry eye. The Schirmer I test (without anesthesia) measures both basal and reflex tearing (abnormal, ≤5 mm of wetting after 5 minutes). The Schirmer II test (with anesthesia) measures only the basal secretion of tearing (abnormal, ≤3 mm of wetting after a 5-minute interval) Ocular surface staining procedures :  Fluorescein Fluorescein is a water-soluble dye used to examine the cornea, conjunctiva, and the precorneal tear film by staining denuded areas of corneal epithelium and pooling into surface irregularities
  7. Mediterranean, the Middle East, Central and West Africa, South America, and Asian countries, such as Japan, Thailand, and India Other atopic manifestations such as allergic rhinitris and asthma
  8. KC is named as such because severe symptoms most commonly occur in the spring (hence "vernal") Bilateral disease ROPY DISCHARGE
  9. Subepithelial fibrosis resulting from papillae hypertrophy can cause increased eyelid thickening and ptosis. Thick, ropy mucus secretions are usually present and associated with tarsal papillae. The skin or lid margins are rarely involved, and the cornea is also typically not involved. These dots are seen when the disease is active and indicate severity of the disease
  10. Corneal involvement in VKC may occur as corneal epithelial punctate keratitis, and where the epithelial erosions may coalesce and form a vernal or Shield ulcer.(TOGBYS ULCER) Presence of shield ulcer will worsen patients symptoms and affect vision . These ulcers are oval and usually present in the upper part of cornea The shield ulcers are classified based on the presence of white material at the base of the ulcer
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  12. to drugs as neomycin,atropine,epinephrine Toxic allergic reactions may also be due or preservatives in medicines such as thiomersol.
  13. The corneal involvement may be in the form of superficial punctate keratitis, pseudodendrites or grayish stromal infiltrates
  14. Poor compliance to treatment on the part of the patient or inadequate control of disease when it presents in its severe form Common complications - Dry eye, infection and corneal scar Chronicity of untreated disease may lead to vision threatening problems like limbal stem cell deficiency(LSCD) and secondary keratoconus due to rubbing of eyes Steroid induced raised IOP and cataract have been reported in these patients
  15. 3. Accurate clinical history & evaluation of signs and symptoms allow the diagnosis of ocular allergy & the definition of possible sensitizing antigens
  16. Patients often self-medicate with purchased over-the-counter (OTC) medications and fail to seek help even when those therapies are ineffective [22, 23]. In one study, 56% of patients diagnosed with AC started with self-treatment measures as first action. Washing the eyes with water or saline were the most commonly chosen therapies [23]. Many OTC drugs have limited efficacy for AC (e.g., topical vasoconstrictors) and can lead to undesirable side effects (e.g., rebound vasodilation from topical vasoconstrictors; mucosal dryness or drowsiness from oral antihistamines).
  17. Cold compresses, saline, and cold artificial tears or ointments are useful because they alleviate the symptoms and dilute the allergen, especially in acute allergic conjunctivitis.6,7,9 Recent studies demonstrate the additive effect on the pharmacology of topical agents when combined with cold compresses and artificial tears.7 Other treatments such as ingestion of probiotics like mandarin orange yogurt or antagonists of the prostaglandin D2 receptor 2 have shown promising results in clinical trials, decreasing the symptoms of patients with rhino-conjunctivitis.
  18. They have a rapid onset of action and may be used in cases of episodic itching and redness but have a potential for inappropriate use by patients.6 They have a short duration and have many side effects such as tachyphylaxis, ocular irritation, and hypersensitivity.6,7 In our practice they are seldom indicated, should be used sparingly, and only as a short-term solution.  Available either alone or in conjunction with antihistamine Short term relief of vascular injection and redness Problem of REBOUND INJECTION on stoppage Not effective against AKC & VKC
  19. topical antihistamines have no effect on other mediators of the allergic response like leukotrienes and prostaglandins. Therefore, they are best used in the acute phase reaction and are rarely sufficient as monotherapy. Other antihistamines such as cetirizine eye drops are available in the U.S. only. As a rule, topical antihistamines have been usurped by the topical dual-activity agents.
  20. Permirolast Potassium 0.1%(Alamast) Pemirolast potassium is a more potent mast cell stabilizer than cromolyn sodium and tranilast. It acts by inhibiting type-1 immediate hypersensitivity reaction. Pemirolast inhibits eosinophil chemotaxis and blocks the antigen induced release of inflammatory agents such as histamine, leukotrienes C4, D4 and E4.it blocks Ag mediated calcium ion influx into mast cells.
  21. topical dual-activity agents are generally clinically superior due to both symptom/sign relief and tolerability Ketotifen, Olopatidine,Bepotastine and Alcaftidine have a dual action of antihistaminic effect and prevention of mast cell degranulation These dual action topical agents act during both ocular early and late phase reactions providing rapid and sustained relief In addition, alcaftadine and olopatadine eye drops are approved for once daily administration which may improve patients compliance
  22. Anti-inflammatory ophthalmic solutions are not often used in AC, but may be useful when symptoms continue to be inadequately controlled despite the use of dual-activity agents or when the prescription of a steroid is not optimal for a particular patient. By blocking the cyclooxygenase pathway, these agents inhibit production of prostaglandins, one of the newly formed mediators of inflammation in IgE mediated allergic responses
  23. LOTEPREDNOL ETABONATE – ester-based steroid rapidly metabolized on entering AC Extremely useful in treating ocular surface inflammation This steroid is metabolized more efficiently therefore reducing the risk of adverse side effects [63]. The 0.2% concentration of loteprednol etabonate is indicated for the treatment of seasonal AC. Only 1% of patients showed a significant IOP rise of ≥ 10 mmHg with this concentration, and its long-term use did not correlate with cataract development
  24. These agents need to be used under close supervision owing to the chance of secondary glaucoma, cataract and secondary infections Shield ulcers esp those who are opaque base respond well to corticosteroids and mechanical debridement
  25. Side effects usually with tacrolimus
  26. This side effect can usually be countered with the liberal application of artificial tears. Cetirizine causes sedation in a subset of patients, despite its categorization as nonsedating.
  27. Changes involve downregulation of Th2 response and upregulation of regulatory T-cells.5 It is carried out by administering gradually increasing amounts of the allergen to induce an immunological tolerance  it is indicated in patients with a documented IgE-mediated hypersensitivity to airborne agents, with severe forms of rhinoconjunctivitis that affect their quality of life in spite of allergen avoidance and pharmacotherapy
  28. biological treatments could have superior results because they block the underlying inflammation pathways by bonding with specific biological molecules, whereas the above-mentioned treatments use unspecific ways of decreasing conjunctival inflammation Omalizumab shows generally good results, though it has not yet been approved for allergic conjunctivitis, while dupilumab may increase the risk of blepharoconjunctivitis, which is tacrolimus-responsive in patients with severe atopic disease or previous AKC
  29. Oral decongestants should be avoided during the first trimester. Sodium cromolyn is a safe treatment for allergic rhino-conjunctivitis during pregnancy. Intranasal corticosteroids may be used in the treatment of nasal symptoms during pregnancy because of their safety and efficacy profile, and they have a potential positive impact on ocular allergy.
  30. 1-day disposable lenses may be an effective strategy for managing OA in contact lens wearers