Ocular allergy

OCULAR ALLERGY
Kullapornpas Benyajirapach, MD

Case: An 8-year-old Thai Boy
CC: คันตา 2 ขาง ตาแดง กระจกตาเปนแผล 3 ปกอนมาโรงพยาบาล
PI: มีอาการจามและนํ้ามูกเรื้อรังรวมดวย
Previous Treatment: Xyzal, Pataday, Zylet ED, Visidic gel, Vislube
PE: Markedly injected conjunctivae Lt > Rt
Giant Papillary Conjunctivitis Lt > Rt (upper tarsal)
Shield ulcer on Left cornea

PE: Markedly injected conjunctivae Lt > Rt
Giant Papillary Conjunctivitis Lt > Rt (upper tarsal)
Shield ulcer on Left cornea

Diagnosis: VKC left eye with shield ulcer left eye
Management: - Remove plaque and pseudogerontoxon
- Levofloxacin 0.5% eye drop
- Fluorometolone 0.1% eye drop
- Ciclosporin eye drop
- Pataday 0.2% eye drop
- Treatment of allergic rhinitis
Further Evaluation and Management?

Investigate: SPT Mite 4+, Dog 2+, Specific IgE DP, DF > 100
Start Subcutaneous Immunotherapy HDM
05/08/18

Investigate: SPT Mite 4+, Dog 2+, Specific IgE DP, DF > 100
Start Subcutaneous Immunotherapy HDM
August 2018
Latest follow-up October 2019:
- Clinical allergic conjunctivitis improved and stable
- Current Medication = Ciclosporin eye drop (wean), Pataday, artificial tear

Outline
● Anatomy and Immunology of the Eye
● Allergic Diseases of the Eye
• Allergic Conjunctivitis (Seasonal/ Perennial)
• Atopic Keratoconjunctivitis
• Vernal Keratoconjunctivitis
• Giant Papillary Conjunctivitis
• Contact Dermatitis
● Management
● Conjunctival Provocation Test

Neil P. Barney, et al. Middleton’s Allergy. 8th Ed.;2013:618-637.
Anatomy

Bielory L. J Allergy Clin Immunol. 2000;106:805-16.
Tear Film
● Eye surface has tear volume 2.6 - 7.4 mcL
● Normal turnover rate for tears = 12 - 16% per minute
● Therapeutic eye drop has volume ~30 μL -> displace tear volume -> then
cleared by tear film turnover in 5 - 10 minutes
● Aqueous portion: electrolytes, carbohydrates, urea, amino acids, lipids,
enzymes, tear-specific prealbumin, IgA, IgG, IgM, IgE, tryptase, histamine,
lysozyme, lactoferrin, plasmin, and ceruloplasmin

Immunology of the Eye
Lymphocytes
● Intraepithelial lymphocytes - predominantly CD8+
● Substantia propria - equally distributed CD4+ and CD8+ populations
Cellular Adhesion Molecules
● Ocular epithelium - expression of intercellular adhesion molecule-1
(ICAM1,CD54)

Mast Cells
● Normally, mast cells found in choroid, ciliary body, iris, and optic nerve,
rarely present in conjunctiva, and NOT found in cornea and retina
● Conjunctival epithelial cells and mast cells - source of chemokines
(macrophage inflammatory protein 1, RANTES, eotaxin, IL-8) involved in
allergic inflammation
● MCT (tryptase) and MCTC (tryptase/chymase) phenotypes
● Conjunctival epithelium: MCT phenotype
● Substantia propria: 95% MCTC

● Histamine - Vascular permeability, smooth muscle contraction, mucus
secretion, inflammatory cell migration, cellular activation, and modulation of
T cell function
● Arachidonic acid metabolites and tryptase originating from mast cells -
specifically involved in regulation many same processes

Allergic Conjunctivitis
● Bilateral, self-limiting conjunctival inflammatory
process in sensitized individuals, no gender
difference
● Initiated by allergen binding to IgE on resident
mast cells
● Seasonal “hay fever conjunctivitis” (spring,
fall) - related to pollens (e.g., grass, trees,
ragweed)
● Perennial - related to animal dander, dust
mites, etc.
● Not sight-threatening

A. Leonardi, et al. Allergy. 2017;72:1485-1498.

Prevalence
● In a survey conducted by the American College of Allergy, Asthma, and
Immunology (ACAAI) - 35% of people responding in family interviews
reported having allergies
● Of affected individuals, at least half described eye symptoms
● Most reports agree that allergic conjunctivitis affects up to 20% of
population
● 60% of all allergic rhinitis sufferers have associated allergic conjunctivitis
AC - Epidemiology

● Antigen cross-linking of IgE antibody bound to the high-affinity IgE receptor
(FcεRI) on mast cells -> release of both preformed (granule-associated -
histamine and tryptase) and newly synthesized mediators (e.g., arachidonic
acid metabolites)
AC - Pathogenesis

• Increased mast cells (MCT phenotype) and eosinophils in the
conjunctival epithelium of individuals with SAC and PAC
• 95% of mast cells in substantia propria are MCTC; total number of mast
cells increased in allergic conjunctivitis
• Cytokines released by mast cells contribute signals initiating infiltration of
inflammatory white blood cells, such as eosinophils
AC - Histopathology and Lab

Tear film analysis:
● Presence of IgE antibody, histamine, tryptase, eotaxin, eosinophil
cationic protein, and TNF-α
● TNF-α shown to upregulate intercellular adhesion molecule 1 (ICAM-1)
expression on conjunctival epithelial cells
● Less of anti-inflammatory cytokine IL-10 and decreased levels of the
Th1 cytokine interferon-γ (IFN-γ)
AC - Histopathology and Lab

● Dominant symptom = Ocular itching (mild to severe)
● Tearing (watery discharge), redness, swelling, burning, a sensation of
fullness in the eyes or eyelids, an urge to rub the eyes, sensitivity to light,
and occasionally blurred vision
● Conjunctival hyperemia and chemosis with palpebral edema
● “Allergic shiners” - periorbital darkening resulting from decreased venous
return
AC - Clinical Features

• History of significant ocular itching and a personal or family history of “hay
fever,” allergic rhinitis, asthma, or atopic dermatitis
• Bilateral VS transmissible infections caused by viruses and bacteria -
unilateral at first
• Itching uncommon during infectious conjunctivitis
• Viral conjunctivitis may cause subepithelial corneal infiltrates not seen in
allergic conjunctivitis
• Palpable preauricular nodes signify infection
AC - Evaluation and DDx

• Type of ocular discharge: watery, mucoid, or grossly purulent can be helpful
in DDx
• A mucoid or purulent discharge, with morning crusting and difficulty opening
the eyelids, strongly suggests a bacterial infection
• Dry eye (secondary to a decrease of the aqueous portion of the tear film)
gives symptoms suggestive of a foreign body in the eye and may result in
conjunctival redness
• Similar symptoms are possible from anticholinergic side effects of systemic
medications. Typically, itching is not reported with dry eye
AC - Differential Diagnosis

● Best treatment = Avoidance of specific allergen
● Avoidance of scratching or rubbing
● Application of cool compresses
● Use of artificial tears
● Refrigeration of topical ocular medications are practical measures to
alleviate discomfort
● Oral antihistamines may help to relieve eye itch, first-generation drugs also
may decrease tear production
AC - Treatment

● Treatment of choice for mild to moderate allergic conjunctivitis -
Dual-acting topical ocular medication
● Benefits most if started before height of symptom severity
● Rapid onset of relief because high histamine H1 receptor affinity
● In severe disease - combination therapy; topical medications
(antihistamines, mast cell stabilizers, nonsteroidal antiinflammatory drugs
[NSAIDs], or combinations), AND oral antihistamines
● Nonsteroidal drugs inhibit cyclooxygenase -> decreased formation of
prostaglandins and thromboxanes, but not leukotrienes
AC - Treatment

● In extreme cases - topical steroid four times a day
● Topical steroids: intraocular pressure measured every 3 months and
evaluated for cataract annually
● Immunotherapy - may be beneficial in decreasing the severity of future
ocular allergy symptoms
● Sublingual immunotherapy specifically for PAC has been demonstrated to
be effective in relieving symptoms
AC - Treatment

Atopic Keratoconjunctivitis
● Chronic, bilateral inflammation of the conjunctiva, cornea and lids
associated with atopic dermatitis
● Onset of disease: 2nd - 5th decades of life (reported ages of 7 and 76)
● Male-to-female ratio 2.4:1.28
● AKC is associated with a family history of atopy, along with a personal
history of atopic dermatitis and asthma

(1) Neil P. Barney, et al. Middleton’s Allergy. 8th Ed.;2013:618-637.
(2) Tuft SJ, et al. Clinical features of atopic keratoconjunctivitis. Ophthalmology 1991; 98:150–158.
(3) Nimesh Patel, et al. Ocular involvement in atopic disease: a review. Curr Opin Ophthamol 2018; 29:576-81.
● Reported prevalence of atopic dermatitis in the general population ranges
from 3 - 17% and from 15 - 76% of the affected patients exhibit ocular
involvement, usually AKC (1)
● Over 95% of AKC patients have eczema and 87% have asthma (2)
● Frequency of ocular involvement in patients with atopic dermatitis ranges
from 25 - 42% (2)
● Presentation of AKC may be influenced by Staphylococcal aureus via the
toll like receptor (3)
AKC - Epidemiology

● Consist of both type I and type IV hypersensitivity mechanisms
● Mast cells in epithelium of these patients contain predominantly tryptase
● High CD4/CD8 ratio in conjunctival epithelium and substantia propria
● Increased mucin proteins and messenger RNA (mRNA) in epithelium
● Substantia propria - increased mast cells, eosinophils, mononuclear
cells
● Increased fibroblasts and collagen
AKC - Pathogenesis

Nimesh Patel, et al. Ocular involvement in atopic disease: a review. Curr Opin Ophthamol 2018; 29:576-81.
● Th1 cells produce IFNg, IL2 and IL-12 -> further induce Th1 production
● Cytokines and adhesion molecules implicated: IL-8, RANTES, IL-33,
basophils and thymic stromal lymphopoetin
● AKC also exacerbated by dryness leading to an itch-scratch cycle
● Tears and serum: increased levels of IgE, eosinophil cationic protein,
activated B cells, eotaxin, eosinophil-derived neurotoxin, soluble IL-2
receptor, IL-4, IL-5, IL-6, house dust mite- specific secretory IgA, and
osteopontin
AKC - Pathogenesis

● Major symptom = itching
● Watering, mucous discharge, redness, blurring of vision, photophobia, and
pain
Skin and lids:
● Periocular skin scaling, flaking dermatitis with red base or
hyperpigmentation
AKC - Clinical Features

Nimesh Patel, et al. Ocular involvemeview. Curr Opin Ophthamol 2018; 29:576-81.
● Lids may become leatherlike, with consequent development of cicatricial
ectropion, entropion and lagophthalmos
● Lid thickening and edema -> linear lid creases “Dennie–Morgan lines”
● Reactive ptosis
● Lateral canthal ulceration and cracking
● Lash loss (madarosis)
● Absence of lateral eyebrows “Hertoghe sign”

Conjunctiva:
● In contrast with VKC, AKC papillary hypertrophy prominent in inferior
conjunctival fornix
● Subepithelial fibrosis
● Symblepharon
● Perilimbal, gelatinous hyperplasia

● Horner-Trantas dots (whitish aggregates of degenerated epithelial and
eosinophils that accumulate at the surface of the hyperplastic, gelatinous
limbus)

Cornea:
● Significant vision loss
● Punctate epithelial keratopathy -
most common corneal finding
● Persistent epithelial defects, scarring,
microbial ulceration, and
neovascularization - main causes
for decreased vision
● Herpetic keratitis 14 - 17.8%

● Keratoconus - noninflammatory progressive corneal thinning 6.7 - 16.2%
● Increased prevalence of cataract -> lens opacity associated with AKC is
anterior or subcapsular cataract VS steroid -> posterior subcapsular
cataract

● Family history of atopic disease
● Other atopic manifestations
● Lack of contact lens wear aids in differentiating AKC from GPC
● Patients with AKC usually are older and exhibit major lid skin involvement
compared with patients with VKC
AKC - Evaluation and DDx

● Environmental controls as well as topical and systemic medications
● Artificial tears help prevent the development of corneal epithelial defects
● Topical vasoconstrictor-antihistamine combination may transient relief
symptoms
● Topical steroids such as prednisolone acetate 4 times per day for 7 - 10
days - beneficial in controlling symptoms and signs
● Non-steroid medications - effective reducing itching, tearing, and
photophobia
AKC - Treatment

● Topical mast cell stabilizers 1 - 4 times daily: recommended year-round in
perennial symptoms
● Exacerbation -> initiated mast cell stabilizers 1 - 4 times daily concurrent
with a short burst of topical steroids 7 - 10 days
● Cyclosporine and tacrolimus, both oral and topical - effective for treating
AKC, reducing topical steroid use
● Systemic antihistamines
● Uncontrolled dermatitis with vision-threatening complications - oral steroids
indicated
● Plasmapheresis
AKC - Treatment

● Staphylococcal blepharitis - antibiotic treatment
● Re-epithilialization -> surgery
● Lid or ocular herpes simplex virus (HSV) infection - topical antiviral agents
● Recurrent episodes of epithelial HSV keratitis - oral acyclovir (400 mg orally
twice daily) prophylaxis
AKC - Treatment

AKC - Immunotherapy
Jongkhajornpong P., et al. Case Rep Ophthalmol. 2017;8:562-567.

A 22-year-old woman refractory AKC presented with severe allergic
conjunctivitis and failed to respond to topical anti-allergic medications, topical
corticosteroid, as well as topical cyclosporine A and oral corticosteroids.
Positive skin prick test to Der f and Der p, cat hair, and cockroach
Total IgE 1,636 kUA/L of total IgE
Specific IgE for Der p 58.2 kUA/L (class 5), specific IgE for Der f 45.2 kUA/L
of(class 4), specific IgE for GCR 0.51 kUA/L (class 1), and specific IgE for cat
<0.35 kUA/L (negative)
She received a conventional protocol of SCIT using Der f and Der p allergen
extracts
AKC - Immunotherapy

Results:
The patient’s ocular signs and symptoms were dramatically improved 2
months after the initiation of SCIT, and oral corticosteroids could be discontinued
within 3 months of the treatment.
She was maintained with mast cell stabilizers and preservative-free tears
without any episodes of exacerbation
Conclusions:
SCIT may contribute to successful outcomes in controlling symptoms and
preventing exacerbation in AKC patient.
AKC - Immunotherapy

● Chronic, bilateral conjunctival inflammation predisposed by atopic
background
● Seasonal exacerbation, but patients may have symptoms year-round
Vernal Keratoconjunctivitis

● Onset before age of 10 years with resolution usually occur during late
puberty
● Males predominate in younger ages
● Male-to-female ratio nearly equal in older patients
● Young males in dry, hot climates
● Atopic history such as eczema or asthma present in 40 - 75% of patients
● Family history of atopy found 40 - 60%
VKC - Epidemiology

1. Bonini S., et al. Ophthalmology. 2000;107(6):1157-63.
2. Kosrirukvongs et al. APJAI 2003;21:25-30.
● SPT positive 57.8%, RAST positive 52.2%
● Rye grass allergen, Parietaria officinalis, and Dermatophagoides
pteronissinus - most common sensitizing allergens (1)
● In Thailand, study showed SPT positive 67% (2)
● Study conducted at Siriraj hospital, 48 patients
● SPT positive 67% - most common: HDM 56%,
House dust 31%, Johnson grass 26%, cockroach 26%, food 26% (mainly
shrimp), cat 19%, fungus 16%, careless weed 14%, and dog 8%
VKC - Epidemiology

● Epithelium contains large numbers of mast cells (predominantly
MCTC) and eosinophils
● Basophils, neutrophils, and mononuclear cells in hyperplastic epithelium
● Some neurotransmitters and receptors: integrins, growth factors, Toll-like
receptor 2 (TLR2), and the inflammation-modulating peptide thymosin-β4
are found greater amounts in VKC epithelium
● Eosinophil major basic protein deposited diffusely throughout the
conjunctiva
VKC - Pathogenesis

● Substantia propria - increased mast cells (predominant again MCTC)
with fibroblast growth factor (b-FGF) -> fibroblast growth and production of
collagens, increased eosinophils and basophils
● CD4+ T cells
● Substantia propria stains positive for metalloprotease 9 (MM9), epidermal
growth factor receptor (EGFR), vascular endothelial growth factor receptor
(VEGR), transforming growth factor-β (TGF-β), b-FGF, platelet-derived
growth factor (PDGF), and thymosin-β4 associated with inflammatory cells
● Increased collagen and fibroblasts
VKC - Pathogenesis

● Corneal epithelium express ICAM-1
● Tear analysis: allergen-specific IgE and IgG, elevated histamine,
tryptase, and soluble IL-6 receptor (sIL-6R)
● VKC reported occur in patients with hyper-IgE syndrome
VKC - Pathogenesis

● Severe itching and photophobia - main
symptoms
● Foreign body sensation, ptosis, thick mucous
discharge, and blepharospasm
● Uninvolved skin and lid margin compared with
AKC
● Conjunctiva - papillary response, principally in
limbus or upper tarsus, greater than 1 mm in
diameter and flattened tops
● “Cobblestone” papillae
● Thick, ropy mucus
VKC - Clinical Features

● Horner-Trantas dots
● Superficial corneal neovascularization
● Symblepharon formation
● Corneal findings may be sight-threatening
● Mediators from inflamed tarsal conjunctiva -> punctate epithelial keratitis
● Shield ulcer
● Peripheral cornea may show waxing and waning superficial stromal,
gray-white deposition termed pseudogerontoxon
VKC - Clinical Features

● Predominantly in young boys living in warm climates
● Characteristic finding of giant papillae
VKC - Evaluation and DDx

● Allergen avoidance
● Cold Compress
● Allergen immunotherapy in VKC has limitations - not feasible to desensitize
these polysensitization children and skin and lung symptoms are
responsive to immunotherapy, but not the conjunctiva
● Significant seasonal exacerbation: short-term, high-dose pulse regimen of
topical steroids - Dexamethasone 0.1% or Prednisolone phosphate 1% 8
times daily for 1 week and tapered rapidly
● Cromolyn sodium, mast cell stabilizer - effective
● Exacerbation: steroid pulse dose and begin using a mast cell–stabilizing
drug topically or dual-acting drug
VKC - Treatment

● Oral medications: steroids, antihistamines, and nonsteroidal
antiinflammatory agents
● Severe bilateral vision-threatening disease - oral steroids
● Topical calcineurin inhibitors of cyclosporine and tacrolimus - effective
● Corneal shield ulcer - antibiotic-steroid ointment and occlusive therapy ->
superficial keratectomy promote epithelial healing
VKC - Treatment

● Phototherapeutic keratectomy and keratectomy with amniotic membrane
graft placement
● Surgical removal of the upper tarsal papilla in combination with forniceal
conjunctival advancement or buccal mucosal grafting
● Injection of short- or long-acting steroids into the tarsal papilla
● Excision of upper tarsal papillae with or without adjunctive mitomycin C
VKC - Treatment

Basem M. Ibrahim, et al. Delta Journal of Ophthalmology.;2018:19:1-8.
VKC - Immunotherapy

VKC - Immunotherapy
Prospective randomized case series
46 patients with grass pollen-induced VKC were enrolled and divided
randomly into group A included 23 children treated by SLIT and group B
included 23 children treated by SCIT
Assessed for specific IgE/ 6 months and by clinical scoring system/3
months - total subjective symptom scores (TSSS) and the total ocular sign
score (TOSS)

Protocol
SCIT build-up - 2 injections/week
(1/1000, 1/100, 1/10), volume injected
(0.2, 0.4, 0.6, 0.8 and 1 ml of each vial)
for 3 months
SCIT maintenance - 1 ml of
concentration #3 weekly
SLIT (drop) build-up 2 months
During both build-up and the
maintenance stage, the dose of SLIT
was once a day

VKC - Immunotherapy
Results:
Both routes, SLIT and SCIT, led to a statistically significant effect (P< 0.001)
in the improvement of these cases of pollen-induced VKC, and this was evident
from all of the follow-up variables including specific IgE test, TSSS, and TOSS.
No statistically significant difference between two routes of administration of
immunotherapy in the specific IgE test, TSSS, and TOSS at all the follow-up visits
(P<0.05)
Conclusion: SLIT had the same efficacy as SCIT in the treatment of children with
grass pollen-induced VKC, but with less pain and a shorter and a more
convenient schedule compared with that of SCIT -> ???

VKC - Immunotherapy
Tolga K, et al. Delta Turk J Med Sci. 2012;42(3):485-490.

VKC - Immunotherapy
Tolga K, et al. Delta Turk J Med Sci. 2012;42(3):485-490.
Subcutaneous immunotherapy was applied to 8 (42%) PAC patients and 4
(17%) VKC patients. After a decrease in symptoms and signs, the
immunotherapy applied group did not need further medical treatment.
All of the patients who underwent immunotherapy were treated. After 8
months of therapy, itching, photophobia, burning, symptoms of epiphora and
conjunctival hyperemia, chemosis, and signs of mucous discharge
decreased in all of the patients who had immunotherapy.
Moreover, after 1 year of immunotherapy, patients did not need any further
antiallergic medications.

Giant Papillary Conjunctivitis

● Chronic inflammatory process -> production of giant papillae on tarsal
conjunctiva lining upper eyelids
● Most often associated with soft contact lens wear, ocular prostheses
and exposed sutures
Giant Papillary Conjunctivitis

● Affect 20% of soft contact lens wearers
● Regular (as opposed to disposable) soft contact lenses - at least 10 times
more susceptible than rigid (gas-permeable) contact lens
● Daily-wear disposable contact lenses and rigid contact lenses - equally
affected
● Wear disposable contact lenses during sleep
● Patients with asthma, SAR, or animal dander allergies may be at greater
risk for GPC, but sensitization not necessary
● No gender or race predilection
GPC - Epidemiology

● Mechanical trauma secondary to poor contact lens fit or chronic irritation
of the upper eyelid with each blink
● Decreased tear clearance -> protein in the tear film longer contact time with
contact lens
● Epithelial layer in GPC contain mast cells MCT type
● No significant increase in mast cells in substantia propria is seen
● Tear analysis: Normal tear histamine levels, tryptase found (rubbing
alone can result in significant increases of tryptase in tears)
● Cytologic scrapings from conjunctiva: lymphocytes, plasma cells, mast
cells, eosinophils, and basophils -> formation of papillae
GPC - Pathogenesis

• Ocular itching after lens removal, redness,
burning, increased mucus discharge in
the morning, photophobia, and decreased
contact lens tolerance
• Blurred vision can result from deposits on
contact lens, or from displacement of the
contact lens secondary to the superior
eyelid papillary hypertrophy
• Initial clinical presentation months - years
after wearing contact lenses
GPC - Clinical Features

● Mild cases - small papillae, absence of visible papillae
● Chronic GPC - tear deficiency may be contributing factor
● Redness of the upper eyelid - earliest signs of GPC
● Abnormal thickening of conjunctiva may progress to opacification as
inflammatory cells enter the tissue
● Recurrent irritation -> formation of enlarged papillae, increased mucus,
inflammatory mediators, and decrease in wear time
● DDx - VKC
GPC - Evaluation and DDx

● Reducing symptoms
● Reduction to abstinence in wearing contact lens
● Once-a-day use contact lenses may be a consideration for persistent
cases of GPC
● Topical mast cell stabilizers
● Dual-action drugs - relieve the itch and decrease the inflammation
● Topical steroid Loteprednol etabonate, 0.5% used 4 times daily for 4 weeks,
reduced signs of GPC
GPC - Treatment

• Delayed inflammatory hypersensitivity from contact with specific antigen or
irritant
• Often ophthalmic agents and also through eye rubbing after manual contact
Contact Dermatoconjunctivitis

● Rash over eyelids, tearing, redness, itching, stinging and burning
sensations, and sensation of fullness in the eye or eyelid when swelling is
involved
● Eyelid may thickened, red, and ulcerated
● Conjunctiva - vasodilation, chemosis, watery discharge, reactive papillae
● Chronic inflammation - occlusion of lacrimal ducts, conjunctival scarring,
and corneal neovascularization and keratinization
● But sight loss is uncommon

Common substances:
● Topical drugs and antibiotics
(anesthetics, neomycin, antivirals,
pilocarpine, timolol)
● Preservatives in ophthalmic solutions
(thimersol, benzalkonium chloride,
chlorobutanol, chlorhexidine, EDTA)
● Cosmetics (eye and lip glosses containing
waxes, fats, and dyes)
● Perfumes
● Sunscreens containing paraamino benzoic
acid (PABA)
● Fingernail products (containing
formaldehyde resins and sulfonamide
derivatives)
● Hair products (dyes, permanent solutions),
adhesives (false eyelashes)
● Nickel (eyelash curlers and eyeglass
frames)
● Irritant plants (poison ivy, sumac, oak)
● Latex (gloves)
● Soaps, detergents, bleach, and solvents

● DDx - ulcerative blepharoconjunctivitis from staphylococcal infection or
AKC
● Patch testing - useful diagnostic tool
Treatment
● Avoidance offending agent
● Non-irritating medications (e.g., contact lens solutions, cosmetics)
● Cool compresses
● Avoidance of hot water and soaps
● Low-potency steroid cream (rather than ointment, which can be irritating)

RESULTS: 144 patients (age 4 -18 years)
● SAC - most common (52.1%), PAC (31.3%), VKC (11.1%), and AKC (5.6%)
● Male preponderance in all groups
● Mean age of onset was 6.9 +/- 2.7 years
● Sensitized to house-dust mites (84.7%), cockroaches (47.9%), pollen (34.7%), and
animal dander (29.9%)
● Severity of AC was not related to number of sensitized allergens
● Standard treatment in all groups was topical olopatadine
● History of topical corticosteroid use was 68.8% and 12.5% in VKC group and AKC
group, respectively
Jongvanitpak et al. JACI 2015.

RESULTS: 144 patients (age 4 -18 years)
● All AKC and VKC patients can discontinue topical corticosteroid when topical
tacrolimus was applied
● Complete remission was found 18.8% in VKC group and 50% in AKC group
● Median duration of treatment was 19 months in VKC group and 11 months in AKC
group
CONCLUSIONS: Most Thai children with AC sensitized to house-dust mites. AKC is not
uncommon in children and had better prognosis than VKC.
Jongvanitpak et al. JACI 2015.

Conclusion
Management in Ocular Allergy
A. Leonardi, et al. Allergy. 2019;1-20.

1. Topical antihistamines, mast cell
stabilizers and dual-acting agents
● All topical drugs are effective in reducing signs and symptoms
● Topical antihistamines and dual‐acting drugs may have lead to a quicker
onset symptom relief when compared to mast cell stabilizers
● Dual‐acting agents with combined mast cell stabilizer and
antihistaminic function provide better symptom control
● Mast cell stabilizers such as chromones require multiple daily doses and
have a delayed onset of action, hence are less preferable
● SAC and PAC can be managed using the same drugs
● The duration of treatment is longer in PAC compared to SAC
● Topical antihistamines and mast cell stabilizers can be used in VKC
and AKC
● All these drugs can be used in combination

2. Topical alpha-adrenergic agonists
(vasoconstrictors)
● Vasoconstrictors alleviate only hyperemia
● They should be used with caution and for a short period of 5‐7 days
because of side effects and tachyphylaxis

3. NSAIDs (topical prostaglandin
and oral leukotriene inhibitors)
● NSAIDs are effective for their short‐term use but do not target specific
inflammatory mechanisms
● In adult SAC patients, leukotriene inhibitors are less efficacious than oral
antihistamines

4. Systemic antihistamines
● Systemic antihistamines should be used in case of comorbidities that
require it use
● Some systemic antihistamines may induce drying effects, particularly
relevant at the ocular surface barrier

5. Corticosteroids
● Topical corticosteroids eye drops should be used with caution under
ophthalmologist's monitoring and preferably for shorter duration due to
the high risk of local and potential blinding side effects
● For the treatment of SAC and PAC, topical corticosteroids are rarely
needed
● Corticosteroid eye drops can be used preferably as short, pulsed
therapy in acute exacerbations of OA, especially in VKC and AKC or
when the cornea is involved under ophthalmologist supervision
● INCs are effective and well tolerated in the treatment of ocular symptoms
associated with ARC
● INCs should not be used if only ocular signs and symptoms are present
● Topical skin corticosteroid applications should be used in the acute
phase of eyelid eczema, with a preference for low potency corticosteroids

6. Calcineurin Inhibitors
● CsA eye drops are not recommended for SAC and PAC
● CsA eye drops may be used as a steroid‐sparing agent in
steroid-dependent cases of VKC or AKC
● Tacrolimus off‐label eye drops/ointment should be reserved for use in
severe VKC and AKC cases refractory to CsA

7. Allergen-specific immunotherapy
● AIT may be considered in cases of failure of first‐line treatments or to
modify the natural course of ocular allergic disease
● AIT can only be considered only when IgE‐mediated hypersensitivity is
evidenced
● Before AIT is recommended, control of symptoms of allergic conjunctivitis
and other systemic symptoms to assess suitability should be taken into
account
● AIT is effective for the treatment of allergic conjunctivitis due to grass
pollen and house dust mite

8. Biologics
Omalizumab
• Used in refractory VKC and AKC and reported in a few case reports/series
• Control of the disease was partial or complete in most patients, but poor
response was noted in some with very severe presentation
Dupilumab
• Dupilumab‐associated ocular inflammation leading to cicatricial ectropion
has been reported suggesting that this drug may not be ideal for the
treatment of AKC with eyelid eczema

9. Nonpharmacological
• First line of management is identification of offending allergens and
avoidance measures
• During exacerbations in VKC, to minimize the exposure to nonspecific
triggering factors, such as sun, wind, and salty water, patients should use
measures such as sunglasses, hats with visors, and swimming
goggles. Frequent hand, face, lid hygiene, and eye washing should
also be suggested
• Cold compresses may provide decongestant effect
• Tear substitutes aid in stabilization of the tear film providing a better
mucosal barrier against allergens, acting as an eyewash and diluting the
concentration of mediators in the tear film
• Psychological support

Anti-inflammatory &
Anti-allergic Eye Preparations
Anti-allergics
● Epinastine (RELESTAT)
● Ketotifen Fumarate (ZADITEN, ZADITEN SDU)
● Loteprednol Etabonate (ALREX)
● Olopatadine HCl (PATADAY)
● Pemirolast Potassium (PEMIROX)
● Sodium Cromoglycate (VIVIDRIN)
Vasoconstrictors
● Antazoline & Tetryzoline (HISTA-OPH)
● Naphazoline (ALBALON)
● Naphazoline & Pheniramine Maleate
(NAPHCON-A)
Anti-infectives with Corticosteroids
● Dexamethasone & Gramicidin & Framycetin
(SOFRADEX)
● Dexamethasone & Neomycin (DEXOPH)
● Dexamethasone & Neomycin & Polymyxin B
(MAXITROL)
● Moxifloxacin HCl & Dexamethasone Phosphate
(VIGADEXA)
● Ofloxacin & Prednisolone Acetate (EXOPRED)
● Tobramycin & Dexamethasone (TOBRADEX)
● Tobramycin & Loteprednol Etobanate (ZYLET)
Corticosteroids
● Fluoromethalone (FML)
● Loteprednol Etobanate (LOTEMAX)
● Methyprednisolone (METHYPREDNISOLONE)
● Prednisolone Acetate (INF-OPH)

Topical Treatments
Topical Corticosteroids
● Betamethasone Dipropionate (DIPROSONE)
● Betamethasone Dipropionate & Salicylic Acid (DIPROSALIC, BEPROLIC)
● Betamethasone Valerate (BETAMEHASONE, BETNOVATE)
● Clobetasol Propionate (CLOBEX, CLOBET (G), DERMAVATE)
● Desoximethasone (ESPERSON, TOPICORTE)
● Flumethasone Pivalate & Salicylic Acid (LOCASALEN)
● Hydrocortisone (CHULACORT)
● Hydrocortisone & Coal Tar (CHULACORT1% + 5%LCD)
● Hydrocortisone & Urea (CHULACORT1% + 10%UREA)
● Momethasone (ELOMET, MOMATE (G))
● Prednicarbate (DERMATOP)
● Triamcinolone Acetonide (T.A., T.A. CLEAR)
● Triamcinolone Acetonide & Liquid Coal Tar (T.A.0.1% + 5%LCD)
● Triamcinolone Acetonide & Urea (T.A.0.1% + 10%UREA)

Topical Treatments
Topical Calcineurin Inhibitors
● Pimecrolimus 1% cream (ELIDEL)
● Tacrolimus 0.1%, 0.03% ointment (PROTOPIC)

● Developed by Abelson and co-workers
● Examine ocular response to allergen in controlled setting
● Before a CPT, skin-testing is required to determine allergen
● 2 baseline visits (7 days apart) are required to establish threshold dose of
allergen
● At 1st baseline visit, increasing doses of allergen extract are applied
bilaterally into the conjunctival sac of the eye at 10-minute intervals,
followed by observation for hyperemia, itching, chemosis, and lid swelling
quantified according to well-established scales
● Threshold of reactivity of 2+ is considered to reflect the severity of allergic
conjunctivitis in season.
Conjunctival Provocation Test

• 2nd baseline (7 days later) visit - establish reproducibility of ocular allergic
reaction to threshold dose
• The CPT protocol: double-blind, randomized design - application of test
drug to one eye and of placebo to the other
• After 10 minutes, challenged with previously determined threshold dose of
allergen.
• Symptom evaluation (approximately 20 minutes for immediate and up to 6
hours for late reactions)

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