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).

 4) the presence of lymphocytes with a Th2 profile of cytokines production .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.

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

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  antigen is presented to native Th0 cells expressing antigen – specific T cell receptors recognize the antigenic peptide.


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


Mast cells     Mast cells particularly abundant in the conjunctival stroma especially at the limbus. differentiated by their content of tryptase alone ( mucosal mast cell or MCT) or both tryptase and chymase ( connective tissue type mast cell or MCTC) . 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.

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

.Mast cells Mast cells mediators:  Histamine.  Itching..  Potentiates histamine.  Tryptase.redness.activates eosinophils and mast cells .smooth muscle constriction.  Anti-inflammatory.  Vasodilatation….  Prevent blood coagulation.  Heparin.

.platelet aggregation.smooth muscle contraction...  Airway hyperresponsiveness…asthma.Mast cells  Prostaglandins and leukotrienes  Capillary leakage.increase granulocyte action..

neutrophil chemotaxis.  . Bronchoconstriction…hypotension…hyperemia..  Attract eosinophils.Mast cells  Eosinophil chemotactic factor-alpha (ECFalpha). Platelet aggregation….   Platelet activating factor (PAF). Chemosis.

Eosinophil derived neurotoxin (EPX). Activated eosinophils release very basic highly charged polypeptide including:     Major basic protein (MBP). Eosinophil cationic protein (ECP). Eosinophils are activated by interaction with other inflammatory cells such as platelet activating factors.Eosinphils    Influx of eosinphils is essential in allergic inflammation and profound changes in conjuncatival mucosa. eosinophil peroxidase (EPO). .


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

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

IL4. . T cells have been subdivided into two functionally distinct subset on the basis of their cytokine profile:  Th1 and Th2 . CD4-T cells are the predominant population in conjunctival inflamed tissues.   Th1 is known to produce IL2 and interferon gamma(INFg).IL5. Th2 is known to produce IL3.Lymphocytes    One of the most important process responsible for orchestrating and regulating allergic inflammation is the production of cytokines by T cells lymphocytes.

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


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. such as pollens. or trees. SAC can develop suddenly when patient comes in contact with an appropriate antigen. SAC is often associated by rhinitis and even sinusitis. grasses. 70% of patients provide either a personal of familial allergic history.

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

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



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

or chemical response to an antigen that occurs 3 to 12 hours after the initial acute (early phase) mast cell-mediated allergic reaction.SAC Pathophysiology: Type I hypersenstivity.  Late phase reaction (LPR):   Clinical. histological. .

NSAIDs. Drive car with windows closed. Mast cell stabilizers.SAC Treatment:  Avoidance of allergen:     Limit outdoor activities. Immunotherapy. Use protective eyegear when outdoor. . Steroids. Antihistamines. Use air conditioning or air filter system.       Washing allergen.

. Antiviral agents... Epinephrine. tearing. contact lens solution..  Itching. and preservatives. eyelid erythema and swelling.Acute allergic toxic induced conjunctivitis    Usually triggered by external non.      Bactriacin. Type I medicated..airborne antigens such as drugs. Typically occur within minutes after application of an allergen. and conjunctival redness and chemosis.apraclonidine.tetracycline Atropine…homatropine. Thimerosal..cephalosporins.chlorhexidine…bezalkonium chloride. Symptoms are similar to SAC but no seasonal component.. irritants.pilocarpine.sulfacetamide.




Offending agents. Steroid Treatment:       . Conj scrapings... NSAIDs. Tears. Antihistamines. Cold compresses..Acute allergic toxic induced conjunctivitis Diagnosis:    Clinical presentation. Discontinue the offending agents.

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

Eliminate animals from house.       Washing allergen. NSAIDs. Immunotherapy . Washing bedding regularly.PAC Treatment:  Avoidance of allergen:      Cover for mattress and pillows. Antihistamines. Reduce humidity. Steroids. Vaccum and damp dust. Mast cell stabilizers.

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


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

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

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

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.

Itching.  Tearing.  Mucus secretion.  Photophobia.  Pain.  Blepharospasm.  Decreased visual acuity.








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

. Keratoconus. Pannus. Pseudogerontoxon.VKC Corneal involvement:        SPK (Togby – Dusting of flour…uppper 1/3) PEE. Shield ulcer. Filamentary keratitis.

Conj scraping and tear cytology:    Eosinophils.  Tears tryptase level . Neutrophils.VKC Diagnostic approaches:     Clinically. . Basophils. CBC for eosinophilia. Specific IgE maybe assayed in serum and tears.

 .  Type IV hypersensitivity.VKC Pathogenesis: Type I hypersensitivity.

. Shield ulcer.VKC Histopathology:  Proliferative and degenerative changes in the epithelium:  Occur early with marked acanthosis. lymphocytes. basophils. neutrophils.   Trantas dots.   Hyperplasia of the connective tissues: Mainly type III collagen. and plasma cells. and intraepithelial pseudocysts. Resident plasma cells and fibroblasts are also increased.  Prominent cellular infiltration in the substantia propria:  Eosinophils. they run parallel to the surface forming the fibrous structure for giant papillae.

VKC Therapy:  Preventive measures:   Change of climate. Short pulses.    Mucolytic agents 10% Acetylcysteine Tears/vasoconstrictors/ cold compresses. wind. and salt water.     Antihistamines. NSAIDS: either locally or systemically. topical/ tarsal injection. . Cyclosporine. Steroids. Mast cells stabilizers:  Should be used continuously throughout the season. Avoid exposure to nonspecific triggering factors such as sun.

  GPC….  . Steroids-antibiotic/eye patching.  PTK.  Superficial keratectomy. Local steroid injection..VKC  Corneal ulcers….  papillae excision/cryotherapy/mucosal graft.

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

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

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

 .AKC Clinical features:  Symptoms: Bilateral itching  Tearing  Watery discharge  Burning  Photophobia  Blurred vision.

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


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

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


Hay fever.AKC  Lens: ? In 5 to 25%   Anterior subcapsular cataract (shield cataract).   Retina:  Systemic disorders:    . and flexor surfaces of the arms and legs. cheeks. Posterior subcapsular cataract ( related to steroid ) Retinal detachment. Atopic dermatitis ( ? In 95%). atopic dermatitis usually begin in childhood.chronic pruritic inflammation of the skin mainly forehead. Asthma (? in 87%).

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 .VKC Vs AKC VKC Age of onset Duration Seasonal variation Childhood.

.HSV……response to PPD.   Elevated levels of tear and serum IgE are charactristic of exacerbated AKC.  Staph aureus….AKC Etiology and histopathology:  Type I hypersenstivity reaction. . 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.

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

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 .

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

conjunctival hyperemia. First reported in 1970 in patients wearing contact lenses. excess mucus secretion. .3 mm in diameter) on the upper tarsal conjunctiva. and itching. foreign body sensation.GPC Characterized by the presence of abnormally large papillae ( more than 0.

 .5%.  History of atopy plays a major role in predisposition of GPC.GPC Epidemiology: Incidence among RCL user with average period of 10 months is 10.  Patients with GPC report higher incidence of allergy to pollens as well as to medications.

Atopy. Rigid…may appear even after 11 ys. Cyanoacrylate glue. Vernal.nylon/prolene.GPC Etiology:  Contact lenses:   Soft. Prosthesis.         Sutures.any time between 3 weeks to 31/2 yrs after wearing CL. Epibulbar dermolipoma. Bleb/valve.. .. Scleral buckle..

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

 Ptosis. and almost always in the upper tarsal conjunctive.GPC Signs: Enlarged papillae ( > 0.  .  Mucus strands.  Trantas dots and limbal inflammation. variable in numbers.3 mm in diameter)..  Mild to severe hyperemia.


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

.increased in numbers and size. GPC. CL surface become coated with mucus and debris.  Stage IV:    Exacerbation of stage III..GPC  Stage III:    Increased severity of mucus and itching. accompanied by excessive lens movement associated with blinking. CL are coated and cloudy soon after insertion. CL intolerance.

Mediators in tear fluid:      Increase tryptase.MBP. Increase histamine.M.ECP.E.  Stimulate production of neutrophil chemotactic factors and inflammatory mediators. Decrease lactoferin.   Immunological response consisting of both humoral and cell mediated immunity. Increase eosinophil . . increase Ig G.GPC Pathogenesis:  Mechanical trauma…result in degranulation of mast cells and disruption of the epithelial surface...

wearing times…hygiene.. Steroid….for moderate to severe cases.  Prevention:   Lens design/hygiene. prosthesis. yet these patients remain a symptomatic CLW.  Relieving the symptoms:  Removal of the CL. Change CL design.   Symptoms usually dissipate within 48 hrs after d/c CL. in some patients. the papillae have not disappeared in more than 20 years.   Mast cell stabilizers…mainly in mild cases. suture. Burying sutur knots.  It may take months or even years for GPC to disappear. .GPC treatment..

Microbial Allergic Conjunctivitis Staphylococcal blepharoconjunctivitis. • Phlyctenular keratoconjunctivitis. • Splendore-Hoeppli phenomena  Allergic granulomatous nodules .




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

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

AK-Con-A.Opcon-A. 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 . Systemic antihistamine Mast cell stabilizers Claritin . Alocril Patanol. Livostin.Allegra.Topical antihistamine/vasoconstrictorw Topical antihistamine Vascon-A. Alamast Optivar Zaditor. Emadine.Naphcon-A. Benadryl .

-Vasodilation / increase capillary permeability.produce itching without vasodilation. -Smooth muscle relaxation. -Found on ocular surface. H3 receptor -Responsible for negative feedback regulation of anaphylactic histamine release. -no selective therapeutic agent yet. -Smooth muscle contraction. -Selective H1 stimulation in conj…. -Not been identified on ocular tissue.Antihistamines H1 receptor -Found throughout the body.. -Vasodilation. -located on histaminergic terminals of nerves. H2 receptor -Predominantly gut. -Systemic H2 antagonist produce decrease in gastric acid production -Selective H2 stimulation in conj…produce vasodilation (redness). .

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

 

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

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

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

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

US $59. Alomide (Alcon).1%).(Lodoxamide 0.54        Patanol Alocril Zaditor Alamast Optivar .$23.59  QID QID.79 Crolom (Bausch and Lomb) (cromolyn sodium 4%). Found to be superior to cromolyn in VKC.$15.Mast cell stabilizer    Opticrom (Akron) (Cromolyn sodium 4%).

H1 anatagonists+ mast cell stabilizer+NSAID  Alocril (Allergan) .025%). (Pemirolast potassium 0.59   Optivar  .(Nedocromil sodium 2%).59  BID. (ketotifen fumarate 0. $41.59 BID  Zaditor (CIBA Vision). BID (azelastine HCI) US $61.US $65.70   Alamast (Santen). TID to QID doses.1%).$36.

Stromal infiltration. Perforation.$50.        S/E: PEE. . Analgesic. limiting production of prostaglandins and thromboxanes.1%) Ocufen (Allergan). Thinning.5%). Ulceration. ( flurbiprofen sodium 0.(diclofenac sodium 0. Persistent epithelial defect.15 Voltaren (CIBA).03%)   All act by:  Block the cyclo-oxygenase pathway.NSAIDs Topical:    Acular ( Allergan).(ketorolac tromethamine 0.

.NSAIDs Systemic NSAIDs:  Aspirin:  1g /day for 6 weeks found to be useful in treating VKC.

69. US $38. Vexol (Alcon). . Ptosis Mydriasis. $ 30 Inflamase Forte (CIBA). (prednisone phosphate1/8%).2%). (loteprednol etabonate 0. PSCC.1%).  S/E:        Ocular descomfort.12%).(loteprednol etabonate 0. (fluorometholone 0.(prednisolone acetate 0. (prednisolone acetate 1%). $ 18 Inflamase Mild (CIBA).$ 54 Ophtho-Tate (Kenral). (prednisone phosphate 1%). Alrex (Bausch and Lomb). $ 28   Lotemax (Bausch and Lomb) .74 FML-F (Allergan). Increase IOP. US $33. HSV flare up.01 Pred Mild (Allergan). $52. (prednisone acetate 1%). Delayed epithelial healing. (fluorometholone 0.Steroids(topical)         FML (Allergan).25%).09.$ 35.5%).$ 29 Pred Forte (Allergan). (rimexolone 1%).

.  Oral.Steroids Local injection. VKC.  AKC.  For severe cases as in AKC.

Its effect is usually transient. It also has an inhibitory effect on eosinophils activation. .Cyclosporine • • • Cyclosporine (cyclosporine A.  S/E: • • Intense stinging. Keratitis. Topical CsA 2% was effective as steroid sparing drug in severe VKC and AKC. • Systemic CsA has been used in patients with AKC. CsA) is a selective immunosuppressant that inhibits IL2 and T-cell activation.

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