Guide to Ocular Allergy Causes, Symptoms and Treatment

Ocular Allergy
Onnicha Chaisetsumpan, MD
Division of Allergy, Immunology and Rheumatology Unit,
Department of Pediatrics
King Chulalongkorn Memorial Hospital

Outline
•Anatomy and immunology of the eye
•Allergic diseases of the eye
• Allergic conjunctivitis
• Atopic keratoconjunctivitis
• Vernal keratoconjunctivitis
• Giant papillary conjunctivitis
•Management
•Conjunctival provocation test

Anatomy and physiology of the eye
Topographic anatomy
• Eye and its adnexa lie within the bony orbit
• The thinnest portion of the bony orbit is
found medially
• Critical: spreading of infections, inflammatory
diseases and neoplasms starting in the sinuses
through the bone into the orbit
Neil P. Barney, et al. Middleton’s Allergy. 9th Ed.;2020
Main lacrimal glands

• Lacrimal system
• Eyelids
• Conjunctiva
• Cornea
• Sclera
• Uvea
• Retina and optic nerve
Anatomy and physiology
of the eye

Immunology of the eye
• Eye is a common target of inflammatory response induced by
local and systemic immunologic hypersensitivity reactions
• Highly vascularization and sensitivity of the vessels in the conjunctiva
which are embedded in a transparent medium
• 4 layers commonly involved in immunologic reactions
• Anterior portion (tear fluid layer and conjunctiva): primary barrier
against environmental allergens, chemicals and infectious agents
• Collagenous sclera: primarily involved in connective tissue disorders
• Uvea: involved in inflammatory reactions associated with circulating
immune complexes and cell-mediated hypersensitivity reactions
• Retina: functionally an extension of the CNS
Bielory L. J Allergy Clin Immunol. 2000;106:805-16

Tear film (also called tear fluid)
• Aqueous portion produced by main and accessory lacrimal
glands
• Electrolyte, carbohydrate, urea, amino acids, lipids, enzymes,
tear-specific prealbumin, IgA, IgG, IgM, IgE, tryptase, histamine,
lysozyme, lactoferrim, plasmin, ceruloplasmin
• Mucin components is derived from goblet cells
• Lipid components from meibomian glands
• Inflammatory conditions may alter the volume or composition
• Surface of the eye has tear volume ranging from 2.6-7.4
microliters with normal turnover rate 12-16% per minute

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 of the normal eye
• Conjunctival epithelial cells and mast cells are source of chemokines involved in allergic
inflammation: macrophage inflammatory protein 1, RANTES, eotaxin, IL-8
Connective tissue type, MCT (tryptase) and
mucosal-type, MCTC (tryptase/chymase) phenotype
• Conjunctival epithelium: rarely present, limited to
MCT phenotype
• Substantia propria: 95% MCTC phenotype

Mast cells
Chronic forms of ocular allergy: AKC, VKC
• Change in mast cell types and location
• Migration of mast cells from substantia propria
to epithelial layers
Mast cell mediators
• Histamine
• Vascular permeability, smooth muscle
contraction, mucus secretion, inflammatory cell
migration, cellular activation and modulation of
T cell function
• Arachidonic acid metabolites and tryptase
• Specifically involved in regulation many same
processes

Classification of ocular hypersensitivity disorders
Fauquert JL. Pediatric Allergy and Immunology. 2019 Jun;30(4):405-14.

• Allergic conjunctivitis
• Seasonal AC (SAC)
• Perennial AC (PAC)
• Atopic keratoconjunctivitis
• Vernal keratoconjunctivitis
• Giant papillary conjunctivitis
Classification of ocular hypersensitivity disorders

Allergic conjunctivitis
• Allergic conjunctivitis (AC) is a bilateral, self-limiting conjunctival inflammatory process
• Occur in sensitized individuals, no gender difference
• Initiated by allergen binding to IgE antibody on resident mast cells
• Two forms of AC defined by whether the inflammation and symptoms occur seasonally (spring,
fall) or perennially (year-round)
• Seasonal allergic conjunctivitis (SAC): related to pollens during specific seasons
• Perennial allergic conjunctivitis (PAC): related to animal dander, dust mites or other
allergens that are present in the environment year-round
Neil P. Barney, et al. Middleton’s Allergy. 9th edition
Neal P. Barney, et al. Cornea 4th edition.

Epidemiology
• Prevalence estimates for allergic conjunctivitis are difficult
• Allergy tend to be considerably underreported
• Most reports agree that allergic conjunctivitis affects up to 20% of populations
• In a survey conducted by the American College of Allergy, Asthma and Immunology
(ACAAI): 35% of people responding in family interviews reported having allergies
• At least 50% report associated eye symptoms
• 55% of allergic eye disease in Italy is SAC
• Associated with other allergic diseases: allergic rhinitis, asthma, AD

Pathogenesis
• IgE-mediated hypersensitivity reactions
• Antigen cross-linking of IgE antibody bound to high-
affinity IgE receptor (FcεRI) on mast cells
• Release of both preformed and newly synthesized
mediators
• SAC and PAC: increased mast cells (MCT
phenotype) and eosinophils in the conjunctival
epithelium
• Tear film analysis in AC: IgE antibody, histamine,
tryptase, eotaxin, eosinophil cationic protein
Charles Q, et al. Cornea 4th edition.

Clinical manifestations
• Dominant symptoms reported in allergic conjunctivitis is ocular itching
• Itching can range from mild to severe
• Other symptoms: tearing-watery discharge, redness, swelling, burning, a sensation of fullness in
the eyes or eyelids, urge to rub the eyes, sensitivity to light and occasionally blurred vision
• SAC: recurrent conjunctivitis only during pollen season; timing dependent on which particular
pollen or mold
• PAC: similar to SAC, but the time course of disease is not seasonal
• House dust mite is the most common sensitizing allergens
• May be able to correlate symptomatology with exposure or particular location

• Often associated with symptoms of allergic rhinitis
• Conjunctival hyperemia and chemosis with
palpabral edema are typical
• Hyperemia = result of vascular dilatation
• Edema (chemosis) occurs due to altered permeability of
postcapillary venules
• Allergic shiners (periorbital darkening)
• Caused by an increase of periorbital pigmentation resulting
from the decreased venous return in the skin and
subcutaneous tissue
chemosis

Diagnosis
History: ocular, medical and medication history
• Acute, subacute, chronic or recurrent
• Unilateral or bilateral
• AC is secondary to environmental allergens ≠
transmissible infections by eye-hand contact (infectious
etiology: virus, bacteria)
• Unless in the context of petting an animal then rubbing
one’s eye
• Associated with any specific environmental or work-
related exposure

Diagnosis
Ocular and medical symptoms
• Non-specific: tearing, irritation, stinging and burning
• Significant ocular itching and a personal or family
history of hay fever, allergic rhinitis, asthma or
atopic dermatitis are suggestive of ocular allergy
• Type of ocular discharge: watery, mucoid, grossly
purulent
• Water discharge: most associated with viral or allergic
ocular conditions
• Mucoid or purulent discharge, with morning crusting
and difficulty opening the eyelids: strongly suggest
bacterial infection
• In allergic inflammation: red eye with
normal vision, pupil shape, ocular
movement, light reactivity and red
retinal reflex
• Dry eye (secondary to a decrease of
the aqueous portion of the tear film)
gives symptoms suggestive of foreign
body and may result in conjunctival
redness
• Typically, itch is not reported with dry eye
• Possible from anticholinergic side effects

Diagnosis
Medication history
• Patient’s use of over-the-counter topical ocular medication, cosmetics, contact lenses and
systemic medications
• Include direct questions and should not rely on the patient to volunteer information
• Many individuals do not appreciate the potential for nonprescription topical ocular medication to cause eye
symptom or partially treat AC

• Allergic conjunctivitis symptoms may be worse than the nasal symptoms in those suffering from
rhinoconjunctivitis
• Treatment of the nasal symptoms may help the rhinitis but not be as effective for relieving ocular
symptoms
• Management of allergic conjunctivitis is aimed at preventing and alleviating symptoms
• Best treatment = avoidance of specific allergens
• Seasonal allergens: staying indoor, keep home and windows closed, use air conditioning systems to
reduce the influx from outdoors
• Perennial allergens: HDM, mold or fungus sources, pet removal
Treatment

Local treatment
• Avoidance of scratching or rubbing
• Artificial tears
• Wash out and reduce the allergen concentration on
ocular surface
• This can be adequate for mild cases
• Cold artificial tears and cool compresses can be helpful in
reducing inflammatory symptoms
• Topical medications: antihistamine and mast cell
stabilizers, alpha-agonists, NSAIDs, steroids,
cyclosporine
Treatment

Topical antihistamine
• Competitively block histamine receptors => reduce
ability of histamine to activate the inflammation cycle
of itching and vasodilation
• High H1 receptor affinity: rapid onset of relief of itch
upon drop instillation
• May take 1-2 weeks to reach full effect but start to
have efficacy within minutes of use
• 1-2 times per day dosing
Treatment
Mast cell stabilizers
• Often used in conjunction with antihistamine therapy
• Reduce ability of mast cells to degranulate and release
inflammatory mediators
• Take 1-2 weeks to have any effect and require dosing
frequency of 4 times a day due to shorter half life
• Benefits most if started before the height of symptom
onset
• Mostly used by patients who can predict the onset of
symptoms or can be used as second line to supplement
the dual acting antihistamine

• Alpha-agonists
• Vasoconstriction: provide immediate redness
reduction
• Not recommended to use for extended periods
due to concern for systemic side effects and
rebound redness
• Nonsteroidal anti-inflammatory agents
• Inhibit cyclooxygenase pathway of prostaglandin
production
• Less favorable side-effect profile; reports of
keratolysis with corneal melt
Treatment
• Steroids
• Bind glucocorticoid receptors to reduce
transcription of inflammatory genes
• Mild potency can be used in short courses
• Higher potency is very rarely needed for AC
• Limit to several weeks due to potential long-
term side effects: ocular hypertension,
cataract formation
• Cyclosporine
• Low-dose anti-metabolite, generally used for
treatment of dry eye
• Off label used to treat allergic conjunctivitis

Systemic treatments
• Oral antihistamine
• May help to relieve eye itch
• First-generation drugs also may decrease tear production => cause more ocular symptoms
• Not as effective in treating local eye symptoms as topical ocular medications
• Allergen desensitization immunotherapy
• May be beneficial in decreasing the severity of future ocular allergy symptoms in patients with a known
allergen or allergens that typically involve more than eye
• Sublingual immunotherapy specifically for PAC has been demonstrated to be effective in relieving
symptoms
Treatment

Norris MR, et al. Current Opinion in Allergy and Clinical Immunology. 2020 Dec 1;20(6):609-15.

• 42 RCT trials (3958 participants) in patients with symptoms of ARC or AC
• 35 (88%) of studies evaluated seasonal allergens, 7 (12%) trials focussed on perennial
diseases
• 19 (45%) used grass pollen extracts, 10 (24%) tree pollen extracts, 6 (14.5%) mites, 6
(14.5%) weeds and 1 (2%) standardized cat extract
• Objective: to evaluate the effectiveness of SLIT in reducing ocular symptoms, the need for ocular
treatments and the threshold exposure for conjunctival immediate allergen sensitivity (CIAS)
• Primary outcome: total ocular symptoms scores, individual ocular symptoms scores, eye drop
use and CIAS
Calderon MA, et al. Clinical & Experimental Allergy. 2011 Sep;41(9):1263-72.

• SLIT induced a significant reduction on both
total ocular symptom scores (-0.41, 95%CI
-0.53 to -0.28: I2 59%) and individual ocular
symptoms scores (red eye, itchy and watery
eyes) compared to placebo
• SLIT showed increase in the theshold dose
for the CIAS
• No significant reduction on eye drops use
(-0.1, 95%CI -0.22 to 0.33)
Conclusion: SLIT is effective in reducing
total and individual ocular symptom
scores in subjects with ARC or AC
Calderon MA, et al. Clinical & Experimental Allergy. 2011 Sep;41(9):1263-72.

Vernal keratoconjunctivitis (VKC)
• Chronic, bilateral conjunctival inflammatory condition
• Found in individuals predisposed by their atopic background

• Onset of disease: before age of 10 years and last 2-10 years with resolution usually occur
during late puberty
• Male predominant in younger ages, male-to-female ratio nearly equal in older patients
• Atopic history such as eczema or asthma present in 40-75% of patients
• Family history of atopy found in 40-60% of patients
• Incidence of VKC varies depending on geographical region
• Limbal VKC: central and southern African countries
• Palpabral VKC: Europe and US
• Seasonal exacerbation, but patients may have symptoms year-round
Epidemiology

• Exact pathogenesis of VKC are not
fully known
• IgE-mediated (type I hypersensitivity)
and type IV hypersensitivity
• Activate innate and adaptive immune
cells during VKC
• T lymphocytes and eosinophils
predominate, with mast cells,
neutrophils and other cell types
infiltraing the conjunctival epithelium
and stroma
Pathogenesis
Clinical Immunology

• T lymphocyte: TH2 CD4+ cells à hypersensitivity to
substances commonly contact conjunctiva; allergens,
nonspecific stimuli
• Mast cells: key role in development of IgE-mediated reaction
• Predominantly MCTC
• Release inflammatory mediators à stimulate fibroblast activity and
production of collagen I and III à formation of giant papillae
• Increase expression of histamine receptors
• Eosinophil major basic protein deposited diffusely
throughout the conjunctiva
• Substantia propria: increased mast cells (predominantly
MCTC) with fibroblast growth factor (β-FGF)
Pathogenesis
Clinical Immunology

• VKC is named because severe symptoms most commonly occur in the spring (‘vernal’)
• Severe itching and photophobia are the main symptoms
• Bilateral > unilateral
• Foreign body sensation
• Ptosis
• Thick mucous discharge
• Blepharospasm

• Signs are confined mostly to the conjunctiva and cornea
• The skin of lids and lid margin are relatively uninvolved
compared with AKC
Palpebral form Limbal form
Diffuse papillary hypertrophy
predominantly on upper tarsus
Gelatinous and confluent, occur more
commonly in African and West Indian
patients
Giant papillae with cobblestones
appearance (>1 mm)
Hornea-Trantas dots: collections of
epithelial cells and eosinophils, found at
any meridian around limbus
Usually, no forniceal shortening
or symblepharon
Neil P. Barney, et al. Middleton’s Allergy. 9th
edition

Eversion of the upper eyelid by clinician is mandatory to rule out severe forms

Cornea
• Sight threatening
• Punctate epithelial keratitis: mediators from the inflamed tarsal conjunctiva
• Coalescence of lesions => frank epithelial erosion, leaving Bowman’s
membrane intact
• Cornea plaque: contain fibrin and mucus deposit over the epithelial defect
• Shield ulcer: usually at lower border in the upper half of visual axis
• Subepithelial ring-like scar
• Peripheral cornea may show waxing and waning, superficial stromal, grey-
white deposition termed pseudogerontoxon

Bonini S, et al. Current opinion in allergy and clinical immunology. 2007 Oct 1;7(5):436-41.

Diagnosis
• No established diagnostic criteria for VKC
• Diagnosis is based on the history, physical findings and typical epidemiology
• History: intense photophobia, ocular pruritus, ptosis
• Physical finding: characteristic finding of giant papillae
• VKC occur predominantly in young boys living in warm climates
• Tear fluid analysis and cytology, conjunctival scraping for cytology and biopsy are rarely needed
to assist in establishing the diagnosis

Treatment
• Allergen avoidance
• Patients with positive skin test to multiple allergens will find avoidance difficult but many affected are skin
test negative
• Seasonal removal of affected children from their home to a reduced allergen climate is usually not practical
for most families
• Alternate occlusive therapy
• As allergen avoidance strategy
• Practical and should not be overlooked
• Avoid touching or rubbing eyes, wash hand frequently
• Supportive treatment: climatotherapy
• Cool compress, maintenance of air-conditioned environment or relocation to cool, dry climate
• Patient education Neil P. Barney, et al. Middleton’s Allergy. 9th edition

Treatment
• Topical medication
• Topical antihistamine
• Topical mast cell stabilizers
• Topical corticosteroids
• Topical steroid sparing agents: cyclosporin,
tacrolimus
• Systemic treatment
• Corticosteroid, antihistamine and NSAIDs
• Allergen-specific immunotherapy
• Supratarsal injection of corticosteroid
• Corneal shield ulcer

Treatment
• Allergen immunotherapy in VKC has limitations
• Not feasible to desensitize to all allergens
• Some suggest that whole skin and lung symptoms are responsive to immunotherapy, the
conjunctiva is not
• SCIT did result in significant reduction in symptoms and serum IgE compared with topically
treated patients

Group 1 (32 patients)
Topical medications
Group 2 (32 patients)
Immunotherapy
• Topical fluoromethonolone 5 times/day for 10 days
during exacerbation with gradual tapering for 10 days
• Topical antihistamine, mast cell stabilizer 3 times/day
for the warm season
• Ophthalmological examination weekly for 2 months and monthly
• Total serum IgE before and 24 months after treatment
• Study design: prospective
randomized study 2007-2009
• Objective: to evaluate the treatment
of cases with VKC by SCIT vs topical
treatment according to clinical
improvement and total IgE
Patients with bilateral VKC (excluded negative intradermal test)
Mahdy RA, et al. Cornea. 2012 May 1;31(5):525-8.

• Greater reduction in symptoms in
group 2 of immunotherapy (72%) >
group 1 of medical treatment (59%),
p<0.05
• Significant reduction in total IgE in
group 2 > group 1, p<0.05
• Conclusion: treatment of vernal
keratoconjunctivitis by SCIT was more
effective than topical treatment in
improving the clinical symptoms and
reducing the total IgE
Mahdy RA, et al. Cornea. 2012 May 1;31(5):525-8.

• Prospective randomized study
• Objective: to compare between SLIT and SCIT
in treatment of pollen-induced VKC in children
• 46 patients with grass pollen-induced VKC
were enrolled and divided into
• Group A: SLIT
• Group B: SCIT
• Assessed for sIgE and clinical scoring
system (Total subjective symptom score-
TSSS, Total ocular sign score-TOSS)
Ibrahim BM, et al. Delta Journal of Ophthalmology. 2018 Jan 1;19(1):1.

• SLIT and SCIT led to significant effect in the
improvement of pollen-induced VKC
• No significant different between two routes of
administration of immunotherapy in specific
IgE test, TSSS and TOSS at all follow-up visit
• 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 more convenient schedule
compared with SCIT
Ibrahim BM, et al. Delta Journal of Ophthalmology. 2018 Jan 1;19(1):1.

Atopic keratoconjunctivitis (AKC)
• Bilateral, chronic inflammation of the conjunctiva and lids associated with
atopic dermatitis
• In 1993, Hogan was the first to describe the finding of chronic conjunctivitis and
keratitis in patients with atopic dermatitis
• Epidemiology
• 15-76% of patients with atopic dermatitis have ocular involvement, usually AKC
• Onset of disease: second to fifth decade, although the majority of patients with atopic
dermatitis are diagnosed by age 5 years
• Highest male to female ratio is reported as 2.4:1
• No racial or geographical predilection is reported

• Type I and type IV hypersensitivity mechanisms
• The skin and conjunctiva are more likely to be colonized with
enterotoxin-producing Staphylococcus aureus bacteria than normal
• Predominant cell types infiltrating the conjunctival tissues: T cells,
eosinophils and neutrophils
• T cells
• Increased number of activated CD4 T cells, HLA-DR expression,
expression of IL-3, IL-4 and IL-5 in the stroma
• Increased expression of IL-2 mRNA and numbers of IFN-𝝲-expressing
T cells: Th1-mediated inflammation
• Eosinophils: present in substantia propria (rarely found in normal
structure) and increased numbers of activation markers on surface
• Mast cells: found in epithelium and increased in substantia propria
Pathogenesis
Neal P. Barney, et al. Cornea 4th
edition.

• Itching is the major symptom of AKC
• May be more pronounced in certain seasons or it may be perennial
• Watering, mucous discharge, redness, blurring of vision, photophobia and pain
• Exacerbation of symptoms most frequently occurs in the presence of fur-bearing
animals and pets

Signs of AKC: skin, lid margin, conjunctival, corneal
and lens changes
• Periocular skin:
• Scaling, flaking dermatitis with reddened base
• Skin of lids may become leather-like, cicatricial ectropion
(turning outward of the lid from skin scarring) and
lagophthalmos (incomplete closure of eyelids)
• Lateral canthal ulceration and cracking, lash loss
(madarosis)
• Lid margins: meibomitis, keratinization and punctal
ectropion

Scaling, flaking dermatitis with reddened base

Conjunctiva
• Conjunctiva of tarsal surfaces
• Papillary reaction, possibly pale white edema
• In contrast to VKC, the papillary hypertrophy of AKC
is more prominent in the inferior conjunctival fornix
• Subepithelial fibrosis, fornix foreshortening and
symblepharon (scar of conjunctival surface of lid to
conjunctiva of the globe)
• Bulbar conjunctiva: few signs
• Erythema, chemosis
• Perilimbal gelatinous hyperplasia may occur
• Horner-Trantas dots: reported to occur in AKC
Neal P. Barney, et al. Cornea 4th
edition.
Neil P. Barney, et al. Middleton’s Allergy. 9th
edition

Cornea
• Punctate epithelial keratopathy: the most
common corneal finding
• Significant vision loss
• Usually results from pathologic conditions of the
cornea
• Persistent epithelial defects, scarring, microbial
ulceration, neovascularization are the main
corneal causes of decreased vision
• Herpes simplex keratitis is reported to occur
in 14-17.8% of patients
• Keratoconus occurs in 6.7-16.2% of patients
Lens
• Anterior uveitis and iris abnormality are not
reported
• Lens opacity, anterior or subcapsular cataract
“milk splash”- multi-lobed opacity configuration
• Retinal detachment with or without previous
cataract surgery is reported

Diagnosis
• Careful history: severe, persistent, periocular itching associated with dermatitis
• History of seasonal or exposure-related exacerbation is usually present
• The significant past history or concurrent presence of eczema cannot be emphasized enough as
a finding in patients with AKC
• Family history of atopic disease and personal history of other atopic manifestations: asthma
(65%), allergic rhinitis (65%)
• Serum level of IgE is often elevated in AKC
• Biomarkers
• Disease activity: transepithelial leakage of fluorescein and extravascular interstitial accumulation of ICG
• Clinical severity: CCL24 (eotaxin-2) mRNA expression levels on the ocular surface

Differential diagnosis
• vs VKC: older, major lid skin involvement
compared to VKC
• vs GPC: lack of contact lens wear
• vs SAC: SAC patients have no or markedly
diminished symptoms out of their season
and show no evidence of chronic
inflammation in conjunctiva
Diagnosis

Treatment
Approach to treatment is multifaceted and
includes environmental controls, topical and
systemic medications
Environmental controls
• Remove environmental irritants in both
home and the employment or school
setting
• Nature of the irritants may be better
defined through allergy testing
Topical medication
• Vasoconstrictor-antihistamine combination:
transient relief of symptoms but unlikely to alter the
immunopathologic process or sequelae
• Topical antihistamine
• Topical steroids: short course for 7-10 days to
control symptoms and signs
• Topical NSAIDs: effective in reducing itching, tearing
and photophobia
• Topical mast cell stabilizers: 1-4 times daily,
recommended year-round in patients with perennial
symptoms
• Cyclosporine-A and tacrolimus: effective at treating
AKC and reducing the amount of topical steroid use

• Systemic medications
• Oral antihistamine: recommended maximizing the use of antihistamine
• Oral corticosteroid: only in rare cases of uncontrolled dermatitis with vision-threatening
complications
• Other managements
• Plasmapheresis: effective treatment in AKC
• Correction of lid and ocular surface abnormalities
• Get rid of infections
• Staphylococcal blepharitis: adequate antibiotic treatment
• Lid or ocular surface HSV infection: oral and topical antiviral agents, if frequent recurrent
episodes of epithelial HSV keratitis occur à consider acyclovir as prophylaxis
Treatment

Giant papillary conjunctivitis
• Giant papillary conjunctivitis (GPC)
• Chronic inflammatory process leading to the production of giant papillae on the
tarsal conjunctiva lining of the upper eyelids
• Most often associated with soft contact lens wear
• Reported in patients wearing soft, hard gas-permeable contact lenses
• In patients with ocular protheses and exposed suture in contact with the conjunctiva

Classification of contact lens
Nature of lens
• Rigid (hard) contact lens
• Non-gas permeable
• Gas permeable
• Soft contact lens
Wearing schedule
• Daily wear contact lens
(hard contact lens)
• Extended wear contact
lens (soft contact lens)
• Disposable contact lens
Giant papillary conjunctivitis

Epidemiology
• Affect 20% of soft contact lens wearers
Risk factors
• Regular (as opposed to disposable) soft contact lens: 10 times more susceptible to GPC than
rigid (gas-permeable) contact lens wearers
• Daily-wear disposable contact lenses and rigid contact lenses: equally affected
• Wearing disposable contact lenses during sleep
• Patients with asthma, SAR, animal dander allergies: greater risk for GPC
• No gender or race predilection

Pathogenesis
• Pathogenesis of GPC involves both mechanical and immunologic mechanisms
• Mechanical trauma secondary to poor contact lens fit or chronic irritation of the upper eyelid with
each blink => provide port of entry of antigens and induce immune response
• Debris built up on contact lens surface recognized as foreign to mucous membrane of the
conjunctiva => initiate immunologic reaction
Release of inflammatory mediators
Increased lymphocytes, papillary formation,
fibroblast proliferation and collagen production
Lead to giant papillae formation

Pathogenesis
• Decrease tear clearance => protein in tear film longer contact time with contact lens
• Cytologic scrapings from the conjunctiva: lymphocytes, plasma cells, mast cells, eosinophils and
basophils
• Mast cells
• Like VKC, mast cells = MCT type in the conjunctival epithelium
• No significant increase in mast cells in the substantia propria is seen
• No overall increase in number of mast cells in conjunctival tissue
• Histamine: normal tear histamine level in GPC: mast cell degranulation is less (30%) than that observed in
patients with VKC (80%)
• Tryptase also has been found

• Ocular itching after lens removal
• Redness, burning, increased mucous discharge in the
morning, photophobia and decreased contact lens
tolerance
• Blurred vision
• Deposits on the contact lens
• Displacement of the contact lens secondary to the superior
eyelid papillary hypertrophy
• Initial presentation may occur months or even years after
the patient has begun wearing contact lenses

Diagnosis
Mild case
• Small papillae, caused by the contact lens riding high on the surface of the eye with each blink
• Very mild case: tendency of the contact lens to ride up on the eye may contribute to the
diagnosis in the absence of visible papillae
Chronic GPC
• Tear deficiency may be contributing factors

Diagnosis
Physical examination
• Redness of the upper eyelid = the earliest signs of GPC
• Abnormal thickening of the conjunctiva may progress to opacification as inflammatory cells enter
tissue
• Recurrent irritation => enlarged papillae: source of increased mucous and inflammatory
mediators and decrease in wear time
• DDx: VKC in young boys not wearing contact lenses

Treatment
• Primary aim for management is reducing
symptoms of GPC
• Primary treatment is removing of the source
of mechanical irritation
• Improve cleaning and storage of the lens to
prevent protein adherence
• Reduce wear time
• Increase the frequency of lens replacement
• Change the type and design of lens
• Reduction in the wearing time of contacts
from a few hours a day to total abstinence
may be required
• Persistent cases of GPC: once a day use
contact lenses
• Serious cases: more aggressive approach
may be required to prevent ocular tissue
damage => complete holiday from lens wear
im conjunction with topically applied anti-
inflammatory drug

Treatment
• Topical mast cell stabilizers: effective in the treatment of GPC
• Combination drugs with mast cell stabilizing and antihistamine activity: relieve itch and decrease
inflammation
• Topical steroids and tacrolimus
• Return to contact lens wear can usually be accomplished but may require a change in contact
lens style or lens material
• Signs and symptoms usually resolve in <1 week if source of mechanical irritation is removed

Definition
• SAC: acute, bilateral, self-limiting allergic conjunctivitis occur seasonally (spring, fall)
• PAC: chronic, bilateral, self-limiting allergic conjunctivitis occur year-round
• VKC: bilateral chronic allergic conjunctivitis and develop a papillary response, principally
manifesting in limbus or upper tarsus
• AKC: bilateral, chronic allergic conjunctivitis and periocular dermatitis
Retrospective medical records of children
with allergic conjunctivitis aged 4-18 years
Outcome: remission with standard treatment, complete remission and partial remission
Jongvanitpak R, et al. Asian Pacific Journal of Allergy and Immunology. 2020 Feb 16.

• PAC= most common type
(61.6%) > SAC (21.3%), VKC
(12.2%), AKC (4.9%)
• Mean age of onset 6.8 years
• Male predominant
• Allergic rhinitis is the most
common comorbidity (97.6%)

• The most common presentation: eye itching,
followed by allergic shinner and hyperemia
• Photophobia is found only in severe form
(VKC, AKC)
Among 20 patients with VKC
• 90% palpebral type, 10% limbal type
• Most common signs: giant papillary and
Trantas dot
• Corneal ulcers were found only in VKC
• 1 patient had unilateral ptosis, reversible during 1
year of treatment
Blepharitis was found only in AKC

• Common sensitized allergen is house
dust mite (86.1%)
• Distribution types of aeroallergen
sensitization were not different
between each type of ocular allergy
• No correlation between number of
allergen sensitizations and mean
wheal diameters of specific allergen
with the severity of disease

• Overall remission was found in 35% VKC group and 63% in AKC group
• Median duration of treatment was 20.5 months in VKC and 11 months in AKC
• History of topical corticosteroid use was 68.8% in VKC and 12.5% in AKC
Conclusion: In severe forms of AC, most patients needed add-on medication. The use of topical
calcineurin inhibitors as an add-on therapy can decrease the use of topical corticosteroid

• Topical medication
• Antihistamine
• Mast cell stabilizers
• Dual-acting agents
• Vasoconstrictor
• Corticosteroids
• Calcineurin inhibitors
• Systemic medications
• Allergen-specific immunotherapy
• Biologicals
Leonardi A, et al. Allergy. 2019 Sep;74(9):1611-30.

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 led to a quicker onset symptom relief,
compared to mast cell stabilizers
• Dual-acting agents with combined mast cell stabilizers and antihistaminic function provide better
symptom control
• Mast cell stabilizers require multiple daily doses and have delayed onset of action, less
preferable

Topical alpha-adrenergic agonists (vasoconstrictors)
• Frequently used as first-line treatment due to availability over the counter
• Vasoconstrictors alleviate only hyperemia with little to no relief from itch
• Should be used with caution and for a short period of 5-7 days because of side effects and
tachyphylaxis
• Tetrahydrozoline
• Naphazoline
• Usually pair with topical first-generation antihistamine, to relieve both itching and redness

Topical antihistamines
• Pheniramine maleate (Naphcon-A)
• 0.05% Antazoline HCl (Hista-oph, Opsil)
• 0.5% Levocabastine hydrochloride (Livostin)
• 0.05% Emedastine difumarate (Emadine)
Pheniramine maleate and Naphazoline
Antazoline and Tetrahydrozoline

Topical mast cell stabilizers
• 0.1% Lodoxamide (Alomide)
• 2% Nedocromil sodium (Alocril)
• 2%, 4% Sodium cromoglicate (Vividrin, Opticrom)
• 0.1% Pemirolast (Alamast, Permirox)

Topical dual-acting agents
• 0.025% Ketotifen fumarate (Zaditen)
• 0.2% Olopatadine HCl (Pataday, Olopamac)
• 0.05% Epinastine HCl (Relestat)
• 0.05% Azelastine HCl (Optivar)

Nonsteroid anti-inflammatory drugs (NSAIDs)
• Effective for short-term use but do not target specific
inflammatory mechanisms
• Local side effects: burning, stinging after application
• In adult SAC patients, leukotriene inhibitors are less effective
than oral antihistamines
• 0.1% Nepafenac (Nevanac)
• 0.5% Ketorolac
• 0.1% Diclofenac
• 1% Indomethacin

Topical corticosteroids
• Should be used with caution under ophthalmologist’s monitoring and preferably for shorter
duration due to high risk of local and potential blinding side effects
• SAC and PAC: topical corticosteroids are rarely needed
• VKC and AKC: used as short, pulsed therapy in acute exacerbations of ocular allergy or
when the cornea is involved, under ophthalmologist supervision
• Inhaled corticosteroids are effective and well-tolerated in the treatment of ocular symptoms
associated with ARC
• Should not be used if only ocular signs and symptoms are present
• Topical skin corticosteroid applications should be used in severe acute phase of eyelid
eczema (AKC, contact blepharoconjunctivitis), with a preference for low potency corticosteroids

• 0.5% loteprednol etabonate (Lotemax, Alrex)
• 0.1% fluorometholone (FML)
• 1% prednisolone phosphate
(Methylprednisolone)
• 1% prednisolone acetate (Pred Forte)
Anti-infective with corticosteroids
• Dexamethasone and neomycin (Dexoph)
• Dexamethasone, neomycin and polymyxin B (Maxitrol)
• Dexamethasone and gramicidin and framycetin
(Sofradex)
• Dexamethasone phosphate and moxifloxacin HCl
(Vigadexa)
• Dexamethasone and tobramycin (Tobradex)
• Prednisolone acetate and ofloxacin (Exopred)
• Loteprednol etobanate and tobramycin (Zylet)

Calcineurin inhibitors
• Cyclosporine eye drops are not recommended for SAC and PAC
• Cyclosporine eye drops may be used as a steroid-sparing agent in steroid-dependent cases of
VKC and AKC
• Tacrolimus off-label eye drops/ointment should be reserved for use in severe VKC and AKC
cases refractory to cyclosporine
• 0.05% cyclosporine (Restasis)
• 0.1% cyclosporine (Ikervis)
• 1% cyclosporine
• 2% cyclosporine

Systemic antihistamines
• Systemic antihistamine should be used in case of allergic co-morbidities that require it use
• Some systemic antihistamines may induce drying effects, particularly relevant at the ocular
surface barrier
• Mucosal dryness à reduce barrier function at mucosal interface against environmental
allergens and pollutants à lower threshold for allergen response

Allergen-specific immunotherapy
• AIT may be considered in cases of failure of first-line treatments or to modify the natural
courses of ocular allergic disease
• AIT can only be considered only when IgE-mediated hypersensitivity is evidenced, and all
following criteria are met
• Moderate to severe symptoms strongly suggestive ARC
• Interfere with usual daily activities or sleep despite regular and appropriate
pharmacotherapy and/or avoidance strategies
• Evidence of IgE sensitization (positive SPT and/or serum-specific IgE) to one or more
clinically relevant allergens
• Consider in less severe ARC to take advantage of long-term benefit on AR and potential
prevention of asthma

Allergen-specific immunotherapy
• Conjunctival allergen provocation test may be helpful
• Detection of the most relevant allergen before initiating AIT
• Follow-up tool in assessing response of AIT
• Before AIT is recommended, control of symptoms of allergic conjunctivitis and other systemic
symptoms to assess suitability should be considered
• AIT is effective for the treatment of allergic conjunctivitis due to grass pollen and house dust
mite

Conjunctival provocation test (CPT, CAPT)
• Traditionally used as a means for diagnosis ocular allergy
• Currently used routinely as human model system to study allergic conjunctivitis and drug efficacy
• Indications
• Polysensitization
• Relation between sensitization and symptoms is not clear-cut
• History-taking suggests the allergy was triggered in a child with negative systemic tests
• Perform in the hospital in severe cases or outpatient setting for benign cases

Conjunctival provocation test
• Skin testing to determine appropriate allergen
• Conduct out of season for the allergen of interest and observe published local pollen counts to
ensure that no environmental exposure occurs during the course of the study
1st baseline visit
• Increase doses of allergen extract applied bilaterally into the conjunctival sac of the eye at 10-
minute intervals
• Observation for hyperemia, itching, chemosis and lid swelling
• Threshold of reactivity 2+: considered to reflect the severity of allergic conjunctivitis in season
2nd baseline visit (7 days later)
• Establish reproducibility of ocular allergic reaction to threshold dose of allergen extract

CPT protocol
• Double-blind, randomized design
• Application of test drug to one eye and of placebo to the
other
• After 10 minutes: challenge with previously determined
threshold dose of allergen
• Symptom evaluation
• Immediate reactions: approximately 20 minutes
• Late reactions: up to 6 hours

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
• May not be ideal for the treatment of AKC
with eyelid eczema
Barnes AC, et al. American Journal of Ophthalmology Case Reports. 2017 Sep 1;7:120-2.

Non-pharmacological therapy
• Patients and caregivers should receive educative support regarding the anticipated duration and
prognosis of the ocular allergy, and possible complications from suboptimal control
• First line of management is identification of offending allergens and avoidance measures
• During exacerbations in VKC, patients should use measures such as sunglasses, hats with visors, and
swimming goggles: to minimize the exposure to nonspecific triggering factors; sun, wind, salty water
• Frequent hand, face, lid hygiene, and eye washing
• Cold compresses may provide decongestant effect
• Tear substitutes aid in stabilization of the tear film
• Avoid products with herbal extracts: chamomile-containing eye drops
• Psychological support especially in severe cases of VKC and AKC

Management

Management
Pregnancy
• Careful evaluation of allergic status and need of drug administration
• Allergen avoidance and environmental measures
• Topical antihistamines or double-acting drugs can be safely used (C category)
• Short courses of topical corticosteroids if required are cautiously permitted
• Avoid vasoconstrictors and decongestants during pregnancy
• Minimize the use of systemic medications
• Immunotherapy may be continued but not initiated

Management
Children
• Topical eye drops used for adults are also approved for children over
the age of 3 years
• Giving the advice to subjects to close the punctum with a finger to
avoid systemic absorption
Elderly people
• Systemic and local corticosteroids should be limited to short-time
administration
• Side effects: diabetes, hypertension, osteoporosis, cataract and glaucoma
• Avoid topical/systemic decongestant and systemic antihistamine =>
dryness

Guide to Ocular Allergy Causes, Symptoms and Treatment

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