Ocular allergy

Abdulrahman Al Muammar

Ocular allergy
Allergic eye diseases accounts for up to 3% of all the medical consultations seen in general practice. The milder forms of allergic eye diseases have fluctuating symptoms of itch, tearing, and swelling. Chronic form of the disease give rise, in addition, to more severe symptoms including pain, visual loss from corneal scarring, cataract or glaucoma, and disfiguring skin and lid changes.

Ocular allergy
Clinical classifications:

1) Allergic conjunctivitis (AC):

Acute allergic conjunctivitis:

Seasonal or hay fever. Toxic- induced (induced by acute contact with irritant, drugs, preservatives, etc). Perennial. Toxic-induced (long standing).

Chronic allergic conjunctivitis:

Ocular allergy
2) Contact dermatoblepharitis. 3) Vernal keratoconjunctivitis (VKC 4) Giant papillary conjunctivitis (GPC 5) Atopic keratoconjunctivitis (AKC 6) Atopic blepharoconjunctivitis (ABC).

Sensitization
Acute and chronic diseases have in common:
1) sensitization to environmental allergens. 2)Ig E mast cells activation with subsequent mediator cascade. 3) conjunctival inflammation with prevalence of eosinphils. 4) the presence of lymphocytes with a Th2 profile of cytokines production .

Sensitization
The conjunctiva is normally exposed to pictogram quantities of environmental allergens such as pollens, dust mite fecal particles, animal dander and other proteins . When deposited on the mucosa, these antigens are thought to be processed by lagerhans cells and other antigen presenting cells (APC) in the mucosal epithelium .

Sensitization

antigen is presented to native Th0 cells expressing antigen specific T cell receptors recognize the antigenic peptide. Multiple simultaneous contacts and cytokine exchange between APC and T cells are necessary to trigger antigen specific Th0 cells to differentiate into Th2 lymphocyte .

Sensitization
. The cytokines released by Th2 cells ( IL3,IL4,IL5,IL6,IL13,GM-CSF) stimulate B cell IgE production and inhibit development of Th1 mediated delayed type hypersensitivity reactions . B cells which recognize the same allergen that induce Th2 differentiation, in present of appropriate signals such as IL4,IL6 and IL13 undergo heavy chain switching to produce IgE.

Mast cells

Mast cells particularly abundant in the conjunctival stroma especially at the limbus. The number of the mast cells in the conjunctiva has been calculated to be 5000/mm3 . conjunctival biopsies from symptomatic allergic patients have shown an increase in subepithelial mast cells with evidence of mast cells degranulation Two different types of mast cells have sown in conjunctiva, differentiated by their content of tryptase alone ( mucosal mast cell or MCT) or both tryptase and chymase ( connective tissue type mast cell or MCTC)

Mast cells
Proliferation of these cells in allergic disorders is probably under influence of Th2 cytokins. Mast cells and basophils, bearing high affinity surface receptors for Ig E are the most important cells in IgE mediated reactions.

Mast cells
Mast cells mediators:

Histamine.

Vasodilatation.smooth muscle constriction.

Itching..redness.

Heparin.

Prevent blood coagulation.

Anti-inflammatory.

Tryptase.

Potentiates histamine..activates eosinophils and mast cells

Mast cells

Prostaglandins and leukotrienes

Capillary leakage..smooth muscle contraction..increase granulocyte action..platelet aggregation. Airway hyperresponsivenessasthma.

Mast cells

Eosinophil chemotactic factor-alpha (ECFalpha).

Attract eosinophils. Platelet aggregation.neutrophil chemotaxis.

Bronchoconstrictionhypotensionhyperemia.. Chemosis.

Platelet activating factor (PAF).

Eosinphils

Influx of eosinphils is essential in allergic inflammation and profound changes in conjuncatival mucosa. Eosinophils are activated by interaction with other inflammatory cells such as platelet activating factors. Activated eosinophils release very basic highly charged polypeptide including:

Major basic protein (MBP). Eosinophil cationic protein (ECP). Eosinophil derived neurotoxin (EPX). eosinophil peroxidase (EPO).

Eosinphils

These proteins may bind to basement membrane protoglycans and hyaluran to cause cellular disaggregation and epithelial desquamation. ECP and MBP are epithelial toxic and are involved in corneal damage that may occur in sever chronic allergy. Eosinphils are also important source of leukotriens, prostaglandins and cytokines such as IL3, IL5, and GM CSF, eotaxin and RANTES. ECP and EPX tear level are correlated with clinical signs and symptoms of allergic disease and maybe considered local markers of eosinphil activation.

Neutrophils
Following allergen challenge, neutrophils are the first cells to appear in tear fluid and the predominant infiltrating cells in the conjunctive during late phase. Although the role of neutrophils in allergic disorders is not clear, they can release inflammatory mediators including leukotriens ,PAF and cytokines. Tear level of myeloperoxidase (MPO). a neautrophil activating marker are increased in allergic conjunctivitis.

Lymphocytes

One of the most important process responsible for orchestrating and regulating allergic inflammation is the production of cytokines by T cells lymphocytes. CD4-T cells are the predominant population in conjunctival inflamed tissues. T cells have been subdivided into two functionally distinct subset on the basis of their cytokine profile:

Th1 and Th2 .

Th1 is known to produce IL2 and interferon gamma(INFg). Th2 is known to produce IL3,IL4,IL5.

Lymphocytes

T cells in allergic inflamed tissues are mostly CD4 with cytokine production profile of the Th2 type. An increase in expression of Th2 type cytokine (IL4, IL5, IL3) have been demonstrated in SAC, VKC and AKC. Compared to SAC, VKC maybe considered a disease with an over expression of these cytokines in addition to other mechanism involved. Conversely in AKC and GPC in addition to typical Th2 derived cytokines, increases of IL2 and INF-g has been shown suggesting that in the most severe atopic conditions a cell medicated hypersensitivity may also occur.

Seasonal allergic conjunctivitis

Is the commonest and one of the mildest forms of allergic conjunctivitis. It accounts for 25%50% of all cases of ocular allergy. SAC is often associated by rhinitis and even sinusitis. 70% of patients provide either a personal of familial allergic history. SAC can develop suddenly when patient comes in contact with an appropriate antigen, such as pollens, grasses, or trees.

SAC
Symptoms:
Itching. Watery discharge. Rhinitis. Sinusitis.

SAC
Signs:
Not always present. Lid swelling. Ptosis. Conj hyperemia. Chemosis (=/- dellen). Papillary reaction. Follicular reaction.

SAC
Diagnosis:

Clinically. Family history. Conj scrapings for eosinophils. Tear level of IgE, serum tear. Radioallergosorbent test measures specific IgE levels for a specific antigens. Mast cells activity by measuring tryptase and histamine levels in tear film.

SAC
Pathophysiology:
Type I hypersenstivity. Late phase reaction (LPR):

Clinical, histological, or chemical response to an antigen that occurs 3 to 12 hours after the initial acute (early phase) mast cell-mediated allergic reaction.

SAC
Treatment:

Avoidance of allergen:

Limit outdoor activities. Use air conditioning or air filter system. Drive car with windows closed. Use protective eyegear when outdoor.

Washing allergen. Antihistamines. Mast cell stabilizers. NSAIDs. Steroids. Immunotherapy.

Acute allergic toxic induced conjunctivitis

Usually triggered by external non- airborne antigens such as drugs, contact lens solution, irritants, and preservatives. Type I medicated. Symptoms are similar to SAC but no seasonal component.

Itching, tearing, eyelid erythema and swelling, and conjunctival redness and chemosis. Typically occur within minutes after application of an allergen.

Bactriacin..cephalosporins..sulfacetamide..tetracycline Atropinehomatropine. Epinephrine..pilocarpine..apraclonidine. Antiviral agents. Thimerosal..chlorhexidinebezalkonium chloride.

Acute allergic toxic induced conjunctivitis

Diagnosis:

Clinical presentation. Offending agents. Conj scrapings. Discontinue the offending agents. Tears.. Cold compresses. Antihistamines.. NSAIDs.. Steroid

Treatment:

Symptoms persist throughout the year, with seasonal variation in up to 87% of patients. The clinical signs and symptoms are similar to SAC, but more persistent. Allergens could be house dust mites, animals, etc.. Type I mediated.

Perennial allergic conjunctivitis PAC

PAC
Treatment:

Avoidance of allergen:

Cover for mattress and pillows. Washing bedding regularly. Reduce humidity. Vaccum and damp dust. Eliminate animals from house.

Washing allergen. Antihistamines. Mast cell stabilizers. NSAIDs. Steroids. Immunotherapy

Contact dermatoblepharitis
Reaction that may begin 24-72 hours following instillation of topical medication. Patients are often sensitized by previous exposure to the offending drugs or preservatives. Acute eczema with erythema, leatherlike thickening, and scaling of the eyelid. Lower eyelid ectropion, and hyperpigmentation. Papillary conjunctivitis and mucoid discharge may develop.

Contact dermatoblepharitis
Medications commonly associated with these symptoms:
Atropine..homatropine. Neomycine..gentamycine..tobramycine. Idoxuridine..trifluridine. Thimerosal.

Type IV reaction.

Contact dermatoblepharitis
Treatment:
Allergen withdrawal. In severe casesbrief course of topical steroids applied to the eyelids and periocular skin may speed resolution.

VKC
Epidemiology:

Rarely appear in patients younger than 3 or older than 25 years of age. M:F is 2:1. The disease usually lasts 4 to 10 years and resolved after puberty, but also can still be present and even worsened in some adult patients. Occurs more frequently in the Mediterranean area, central Africa, India, and South America. It also occur in cooler climates, such as Great Britain and other northern European countries, which is possibly as a consequences of migratory movements of the susceptible population. Association with atopy is 15 to 60%.

VKC
VKC is usually bilateral, although monocular forms and asymmetric symptoms do occur. Three clinical forms can be observed : tarsal, limbal (more common in African and Asian patients), and mixed tarsal/limbal. In majority of the cases, the disease is seasonal, lasting from the beginning of spring until fall. Nevertheless, perennial cases have been observed,
especially in warm subtropical or desert climates.

VKC
Symptoms:
Itching. Tearing. Mucus secretion. Photophobia. Pain. Blepharospasm. Decreased visual acuity.

VKC
Signs:

Papillary reaction. Conjunctival redness and edema GPC. Limbal gelatinous infiltrate. Trantas dots. Mucus discharge. Pseudoptosis. Tarsal conjunctival fibrosis.

VKC
Corneal involvement:

SPK (Togby Dusting of flouruppper 1/3) PEE. Pannus. Filamentary keratitis. Shield ulcer. Pseudogerontoxon. Keratoconus.

VKC
Diagnostic approaches:

Clinically. Specific IgE maybe assayed in serum and tears. CBC for eosinophilia. Conj scraping and tear cytology:

Eosinophils. Basophils. Neutrophils.

Tears tryptase level .

VKC
Pathogenesis:
Type I hypersensitivity. Type IV hypersensitivity.

VKC
Histopathology:

Proliferative and degenerative changes in the epithelium:

Occur early with marked acanthosis, and intraepithelial pseudocysts.

Prominent cellular infiltration in the substantia propria:

Eosinophils, neutrophils, basophils, lymphocytes, and plasma cells. Resident plasma cells and fibroblasts are also increased.

Hyperplasia of the connective tissues:

Mainly type III collagen, they run parallel to the surface forming the fibrous structure for giant papillae.

Trantas dots. Shield ulcer.

VKC
Therapy:

Preventive measures:

Change of climate. Avoid exposure to nonspecific triggering factors such as sun, wind, and salt water.

Mucolytic agents 10% Acetylcysteine Tears/vasoconstrictors/ cold compresses. Mast cells stabilizers:

Should be used continuously throughout the season.

Antihistamines. NSAIDS: either locally or systemically. Steroids. Short pulses, topical/ tarsal injection. Cyclosporine.

VKC

Corneal ulcers.
Steroids-antibiotic/eye patching. Superficial keratectomy. PTK.

GPC..
Local steroid injection. papillae excision/cryotherapy/mucosal graft.

AKC
Atopy is hereditary condition that manifests in ocular diseases, skin abnormalities, and respiratory tract dysfunction. Atopy occurs in 5 to 20% of the general population. The term AKC is misleading, although ocular surface disease is most prominent, the disease usually involve the lid also.

AKC
Epidemiology:

AKC occur in up to 25% of patients with atopic dermatitis. A review of family history frequently reveals the presence of other diseases such as asthma, hay fever, and urticaria. AKC occurs more frequently in men. Typically begin in the late teens or early twenties, and they persist until the fourth or fifth decade of life. The peak incidence occurs between the ages of 30 and 50 years.

AKC
Clinical signs of the disease generally improve with age and may totally regress. Patients with severe cases don't follow this trend. AKC is often worse in the winter, but it usually has a perennial pattern of occurrence.

AKC
Clinical features:

Symptoms:
Bilateral itching Tearing Watery discharge Burning Photophobia Blurred vision.

AKC
Signs:

Lid:

Thickening of the eyelid margins (tylosis) Eyelid swelling. Scaly, indurated, and wrinkled appearance of the periocular skin With profound swelling, a dennie-morgan folds or Dennie line is seen. Chronic inflammation can give upper lid ptosis. Fissures can occur at the lateral canthus owing to excessive skin rubbing. An absence of lateral eyebrows, or Hertoghes sign can be seen in severe form. Marginal belpharitis caused by staphylococcal infection is common.

AKC

Conjunctiva:

The conjunctive can be hyperemic to milky edematous. Tarsal conjunctival papillary reaction is a common finding usually in small to medium size, both upper and lower conjunctive. Limbal papillae. Trantas dots. Rarely GPC in lower conjunctive. Conjunctival cicatrization and symblepharon most commonly in the inferior fornix.

AKC

Cornea:
PEE/PEK. Intraepithelial microcyst. Infecious and noninfecious corneal ulcer. Peripheral micropannus. Neovascularization extending to the central cornea. Keratoconus in 16% of patients with AKC. Pellucidal marginal degeneration, and keratoglobus.

AKC

Lens: ? In 5 to 25%

Anterior subcapsular cataract (shield cataract). Posterior subcapsular cataract ( related to steroid ) Retinal detachment. Hay fever. Asthma (? in 87%). Atopic dermatitis ( ? In 95%)- chronic pruritic inflammation of the skin mainly forehead, cheeks, and flexor surfaces of the arms and legs, atopic dermatitis usually begin in childhood.

Retina:

Systemic disorders:

VKC Vs AKC
VKC Age of onset Duration Seasonal variation Childhood, teens Resolved in mid to late teens Markedly worse in spring AKC age 20 to 50 Resolved by age 50 variable

Conjunctival papillae
Conjunctival scarring skin

GPC.upper lid
Uncommon Uncommon

Small or medium size..upper and lower

Can give symblepharon Often

Eosinophils
Corenal vascularization and scarring lens

Numerous
Less extensive No

Less munerous and less often degranulated

More extensive ASCC/PSCC

AKC
Etiology and histopathology:

Type I hypersenstivity reaction.

Elevated levels of tear and serum IgE are charactristic of exacerbated AKC. Conj scraping showed approximately 50 million mast cells, also an excess of eosinophils ( less than VKC)

Type IV hypersenstivity Diminished cell medicated immunity is common.

Staph aureus..HSVresponse to PPD.

AKC
Diagnosis:

Family history. Some level of disease activity is always present with variable exacerbations. Atopic dermatitis. Papillary reaction more inferiorly than superiorly. Rarely GPC inferiorly. Usually begin in late teenage or more commonly later. Most severe type of ocular allergy.

AKC
In Vivo Tests:

Positive intradermal skin tests Conjunctival challenge Prausnitz-Kustner test In Vitro Tests: Basophil histamine release Radioallergosorbent test (RAST)

AKC

Conjunctival cytology - eosinophils Tear histamine level 10 ng/ml normal Tear IgE, Serum IgE Eosinophilia > 500 cells/ml

AKC
Managemant:

Tears. Vasoconstrictors. Cold compresses Antihistamines NSAID. Mast cell stabilizers. Steroid. Cyclosporine. Antibiotics. Surgical: lid procedures/ PKP.

GPC
Characterized by the presence of abnormally large papillae ( more than 0.3 mm in diameter) on the upper tarsal conjunctiva, conjunctival hyperemia, excess mucus secretion, foreign body sensation, and itching. First reported in 1970 in patients wearing contact lenses.

GPC
Epidemiology:
Incidence among RCL user with average period of 10 months is 10.5%. History of atopy plays a major role in predisposition of GPC. Patients with GPC report higher incidence of allergy to pollens as well as to medications.

GPC
Etiology:

Contact lenses:

Soft..any time between 3 weeks to 31/2 yrs after wearing CL. Rigidmay appear even after 11 ys.

Sutures..nylon/prolene. Prosthesis. Cyanoacrylate glue. Scleral buckle. Bleb/valve.. Vernal. Atopy. Epibulbar dermolipoma.

GPC
Symptoms:
Foreign body sensation. Intolerance to CLW. Itching. Irritation. Mucus secretion.

GPC
Signs:
Enlarged papillae ( > 0.3 mm in diameter), variable in numbers, and almost always in the upper tarsal conjunctive. Mucus strands. Mild to severe hyperemia. Trantas dots and limbal inflammation.. Ptosis.

GPC
Stages:

Stage I:

Initial symptoms including mucus in the nasal corner of the eye after sleep and mild itching after lens removal. No papillae detected usually. Increased severity of mucus and itching and mild blurring of the vision, which occur toward the end of the usual lens wearing time. Small, round papillae, conj is thickened, edematous and hyperemic.

Stage II:

GPC

Stage III:

Increased severity of mucus and itching, accompanied by excessive lens movement associated with blinking. CL surface become coated with mucus and debris. GPC..increased in numbers and size.

Stage IV:

Exacerbation of stage III. CL intolerance. CL are coated and cloudy soon after insertion.

GPC
Pathogenesis:

Mechanical traumaresult in degranulation of mast cells and disruption of the epithelial surface.

Stimulate production of neutrophil chemotactic factors and inflammatory mediators.

Immunological response consisting of both humoral and cell mediated immunity. Mediators in tear fluid:

Increase tryptase. increase Ig G,M,E. Increase eosinophil ..MBP..ECP. Increase histamine. Decrease lactoferin.

GPC
treatment;

Prevention:

Lens design/hygiene. Burying sutur knots.

Relieving the symptoms:

Removal of the CL, prosthesis, suture.

Symptoms usually dissipate within 48 hrs after d/c CL. Change CL design..wearing timeshygiene.

Mast cell stabilizersmainly in mild cases. Steroid..for moderate to severe cases.

It may take months or even years for GPC to disappear, in some patients, the papillae have not disappeared in more than 20 years, yet these patients remain a symptomatic CLW.

Microbial Allergic Conjunctivitis

Staphylococcal blepharoconjunctivitis. Phlyctenular keratoconjunctivitis. Splendore-Hoeppli phenomena

Allergic granulomatous nodules

Ocular allergy treatment approach

Elimination of allergen. Eliminate eye rubbing. Cool compresses/ tears/ vasoconstrictors. Anithistamines for acute attack. Mast cell stabilizer as prophylactic. NSAIDs fro acute attack Steroid mainly for AKC/ VKC / GPC in short pulses.. Cyclosporine in VKC / AKC. Immunotherapy.

Drug therapy
Antihistamines. Vasoconstrictors. Mast cell stabilizers. NSAIDs. Steroids. Cyclosporine.

Topical antihistamine/vasoconstrictorw Topical antihistamine

Vascon-A.Naphcon-A. AK-Con-A.Opcon-A. Livostin. Emadine. Alocril Patanol. Alamast Optivar Zaditor.

Systemic antihistamine Mast cell stabilizers

Claritin .Allegra. Benadryl . Opticrom Alamast Alomide Zaditor Alamast Optivar Acular Ocufen Crolom Alocril Patanol Optivar Alocril Zaditor Voltaren Aspirin

Antihistamine+Mast cell stabilizer+ NSAID NSAIDs Steroids

FML inflammase mild/forte Pred mild/forte vexol Alrex Lotemax

Cyclosporine

Antihistamines
H1 receptor
-Found throughout
the body. -Vasodilation / increase capillary permeability. -Smooth muscle contraction. -Selective H1 stimulation in conj..produce itching without vasodilation.

H2 receptor
-Predominantly gut. -Found on ocular surface. -Vasodilation. -Smooth muscle relaxation. -Systemic H2 antagonist produce decrease in gastric acid production -Selective H2 stimulation in conjproduce vasodilation (redness).

H3 receptor
-Responsible for negative feedback regulation of anaphylactic histamine release. -located on histaminergic terminals of nerves. -Not been identified on ocular tissue. -no selective therapeutic agent yet.

Antihistamines
Topical antihistamine:

All H1 antagonist. Antihistamine/vasoconstrictor.

Vascon-A (antazoline 0.5/naphazoline HCl 0.05). $10.99 Naphcon-A ( pheniramine maleate 0.3/ naphazoline 0.025). US $10.69 AK-Con-A ( pheniramine maleate 0.3/ naphazoline HCl 0.025). Opcon-A (pheniramine maleate 0.315/ naphazoline HCl 0.027). US $14.49

Antihistamines

Livostin (CIBA Visio,n) (levocabastine HCl 0.05%). $53.47 15000x more potent than pheniramine.

Onst approx 10 mins.last 4 hours.

Emadine (Alcon), (emedastine difumarate 0.05%). $53.84

4x/day. Has dual action..antihistamine + mast cell stabilizer. 1 to 2 drops twice a day.

Patanol (Alcon),(Olopatadine HCl 0.1%). $42.12

Alocril Zaditor Alamast Optivar

Antihistamines
Systemic antihistamines:

Rarely prescribed by ophthalmologist. Useful in patients with rhinitis. Peak action within 1 to 2 hours. Last 4 to 6 hours.

Claritin (loratadine) 10 mg daily.$26.99 Allegra (fexofentadine) 60 mg twice daily.$21.19 Benadryl (diphenhydramine). Zytrec (cetirizine). $1/pill

Antihistamines
Side effect:

Topical:
Irritation. PEE due to preservatives. Dry eye symptoms. Vasoconstrictors should be used with caution in patient with narrow angle/ HTN/ CVD/ arrhythmias.

Antihistamines

Systemic:
Sedation. Dizziness. Fatigue. Nausea. Vomiting. Diarrhea. Constipation. Dry eye.

Mast cell stabilizer

Opticrom (Akron) (Cromolyn sodium 4%).$15.79 Crolom (Bausch and Lomb) (cromolyn sodium 4%).US $59.59

QID QID. Found to be superior to cromolyn in VKC.

Alomide (Alcon),(Lodoxamide 0.1%).$23.54

Patanol Alocril Zaditor Alamast Optivar

H1 anatagonists+ mast cell stabilizer+NSAID

Alocril (Allergan) ,(Nedocromil sodium 2%). $41.59

BID. TID to QID doses. BID (azelastine HCI) US $61.59 BID

Zaditor (CIBA Vision), (ketotifen fumarate 0.025%).$36.70

Alamast (Santen), (Pemirolast potassium 0.1%).US $65.59

Optivar

NSAIDs
Topical:

Acular ( Allergan),(ketorolac tromethamine 0.5%).$50.15 Voltaren (CIBA),(diclofenac sodium 0.1%) Ocufen (Allergan), ( flurbiprofen sodium 0.03%)

All act by:

Block the cyclo-oxygenase pathway, limiting production of prostaglandins and thromboxanes. Analgesic.

S/E:
PEE. Persistent epithelial defect. Stromal infiltration. Ulceration. Thinning. Perforation.

NSAIDs
Systemic NSAIDs:

Aspirin:

1g /day for 6 weeks found to be useful in treating VKC.

Steroids(topical)

FML (Allergan), (fluorometholone 0.1%).$ 35.74 FML-F (Allergan), (fluorometholone 0.25%). Vexol (Alcon), (rimexolone 1%). $52.01 Pred Mild (Allergan),(prednisolone acetate 0.12%).$ 29 Pred Forte (Allergan), (prednisolone acetate 1%),$ 54 Ophtho-Tate (Kenral), (prednisone acetate 1%). $ 18 Inflamase Mild (CIBA), (prednisone phosphate1/8%). $ 30 Inflamase Forte (CIBA), (prednisone phosphate 1%). Alrex (Bausch and Lomb), (loteprednol etabonate 0.2%). US
$38.09.

$ 28

Lotemax (Bausch and Lomb) ,(loteprednol etabonate 0.5%). US

$33.69.

S/E:

Ocular descomfort. Delayed epithelial healing. HSV flare up. Increase IOP. PSCC. Ptosis Mydriasis.

Steroids
Local injection.
VKC. AKC.

Oral.

For severe cases as in AKC.

Cyclosporine

Cyclosporine (cyclosporine A, CsA) is a selective immunosuppressant that inhibits IL2 and T-cell activation. It also has an inhibitory effect on eosinophils activation. Topical CsA 2% was effective as steroid sparing drug in severe VKC and AKC. Its effect is usually transient.

S/E:

Intense stinging. Keratitis.

Systemic CsA has been used in patients with AKC.

Immunotherapy
Immunotherapy (also called Desensitization or hyposensitization). Long term administration of low but progressively increasing doses of the offending allergen until the evoked clinical reaction is reduced or eliminated. It has been attempted sublingually, nasally, bronchially, ocularly, and subcutaneously (usual route). It takes 3 to 5 years. Recent meta-analysis showed that it is useful for allergic rhinitis and conjunctivitis.