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«Course outline There are some common external disease problems that affect children commonly. Among these are allergic conjunctivitis, ...»

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External Diseases for the Pediatric Ophthalmologist

Inez BY Wong Ms/ FRCSEd (Ophth), Ken K Nischal Mr/ FRCOphth

National University Hospital Singapore, Great Ormond Street Hospital for Children

United Kingdom

Course outline

There are some common external disease problems that affect children commonly.

Among these are allergic conjunctivitis, blepharokeratoconjunctivitis, persistent

punctate epithelial erosions and persistent epithelial defect.

Allergic conjunctivitis can range from simple allergic reaction to severe vernal keratoconjunctivitis with secondary glaucoma due to steroid therapy. Strategies will be discussed as to how to manage these conditions with emphasis on newer drugs and therapies available.

Blepharokeratoconjunctivitis can be extremely difficult to treat and may present with recurrent chalazia or marked photophobia with reduced vision. Treatment of the lid margin disease using topical and systemic treatments will be outlined as will management therapies for the functional drying of the eye that may follow.

Persistent epithelial erosions can result in marked rubbing of the eyes.Common etiologies and treatment modalities will be discussed. Types of lubrication and how they may best be utilised will also be outlined.

Persistent epithelial defects may occur due to a variety of reasons but in order to treat these efficiently one must look at the micro-environment of the ocular surface to improve them. Therapeutic modalities may include botulinum induced ptosis, lateral tarsorraphy, and if the cornea is thinning, amniotic membrane graft. Rare causes of corneal anesthesia will be discussed.

I. Allergic eye diseases Ocular allergy is a common problem affecting 20% of the population worldwide, including both adults and children. It encompasses a spectrum of disorders which range from relatively mild acute allergic reactions to more severe and potentially blinding forms such as vernal keratotconjunctivitis. Six main clinical forms have been described.

1. Acute allergic conjunctivitis (AAC)

2. Seasonal allergic conjunctivitis (SAC)

3. Perennial allergic conjunctivitis (PAC)

4. Vernal keratoconjunctivits (VKC)

5. Atopic keratoconjunctivitis (AKC)

6. Giant Papillary Conjunctivitis (GPC) The treatment has in the past focused on symptomatic relief, but with better understanding of the immunopathological mechanisms involved, newer therapeutic strategies interventions are being developed.

Immunopathology The allergic response results from exposure of the conjunctiva to an allergen. SAC and PAC are the only diseases to involve solely Type 1 hypersensitivity, in which the allergen binds to the sensitized IgE antibody on the mast cell, causing the mast cell to degranulate and releasing mediators such as histamine, prostaglandins, and leukotrienes. This early phase response is immediate but a late phase response involving eosinophils and T cells occurs 4-6 hours later.

The other forms of ocular allergies involve a more complex immunological basis and a chronic imflammatory component. In addition to a type 1 hypersensitivity reaction, a delayed type IV hypersensitiviy reaction induced by T lymphocytes and macrophages also play a pivotal role. VKC is thought to be a TH2 driven disease, and both T cells and eosinophils are markedly increased in the conjunctiva. Products of degranulation from eosinophils, such as eosinophil cationic protein (ECP), eosinophil granule major basic protein (MBP) are thought to contribute to the more serious corneal symptoms of VKC. AKC and GPC have similar mechanisms but a different chemokine profile.

Clinical features

–  –  –

1. Allergen avoidance and lubrication

2. Topical Antihistamines Relieve itching and redness, but short acting. Useful for SAC and PAC.

Second generation selective H1 antagonists

• levocabastine HCL suspension 0.05% (Livostin) qds

• emedastine difumarate solution 0.05% (Emadine) qds Topical antihistamines (usually 1st generation) combined with vasoconstrictors are usually available without a prescription, e.g. Opcon-A (B&L) which is a combination of naphazoline and pheniramine. Longterm use is not advised as rebound vasodilatation and inflammation may exacerbate the condition.

3. Systemic Antihistamines

Oral antihistamines are extensively used to control allergic rhinoconjunctivitis.

They may also be helpful in patients with severe AKC and VKC. The newer antihistamines are not associated with drowsiness.

• Loratidine (Claritin) 10mg od (6 years or above)

• Fexofenadine (Allergra) 60mg bd (30mg bd 6-11 years)

4. Mast Cell Stabilizers

The mechanism of action is unclear, but there is decrease in degranulation of mast cells in response to an antigen. Therefore they do not relieve existing symptoms and need to be used on a prophylactic basis, or combination with other drugs.

• Sodium cromoglycate 4% (Cromolyn Sodium) qds

• Lodoxamide tromethamine 0.1% (Alomide) qds

• Pemirolast potassium ophthalmic solution 0.1% (Alamast) qds

5. Dual-acting Agents

Mast cell stabilizer with antihistamine effect (H1 antagonist) Also demonstrated to inhibit eosinophil chemotaxis/ activation.





Rapid relief, with longterm effect.

• Olopatadine HCL solution 0.1% (Patanol) bd, or 0.2% (Pataday) od

• Nedocromil sodium 2% (Alocril) bd

• Ketotifen fumarate solution 0.025% (Zaditor) tds

• Azelastine HCL solution 0.05% (Optivar) bd

6. NSAIDS Topical NSAIDS inhibits the cyclooxygenase enzyme that is essential in the synthesis of prostaglandins. They have been shown to relieve ocular itching in allergic conjunctivitis.

• ketorolac tromethamine 0.5% (Acular) qds

7. Steroids Topical corticosteroids are extremely effective in controlling inflammation and symptoms, but may be associated with localized ocular complications, including increased intraocular pressure, cataract formation and viral or fungal infections.

Short pulses are therefore recommended for acute flare-ups:

• prednisolone acetate ophthalmic suspension 1% (Pred forte), or 0.12% (Pred mild)

• dexamethasone suspension 0.1%(Maxidex)

• fluorometholone ophthalmic suspension 0.1% (FML) Studies show that weaker steroids such as FML has a lower propensity to increase intraocular pressure than dexamethasone.

Two modified steroids which are derivatives of prednisolone are rapidly inactivated once they enter the anterior chamber thus reducing the risk of raised intraocular pressure.

• Loteprednol etabonate ophthalmic suspension 0.2% (Alrex) or 0.5% (Lotemax)

• Rimexolone ophthalmic suspension 1% (Vexol)

Supratarsal steroid injection

Advanced VKC not responding to conventional therapy, especially those with cornea or limbal involvement, may be treated with supratarsal steroid injection.

Both short-acting (e.g. dexamethasone) and intermediate-acting steroids (e.g.

triamcinolone) appear to be equally effective, and have a similar recurrence rate.

Symptoms improve after 1 to 5 days, but signs such as giant papillae and shield ulcers may take 2 to 3 weeks to resolve.

Technique:

Under general anaesthesia, the upper eyelid is everted, and a mixture of triamcinolone 20mg/0.5ml & betnesol 2 mg/0.5ml is injected into the subconjunctiva 1mm above the superior tarsal border with a 27-gauge needle.

1. Holsclaw DS, Whitcer JP, Wong IG, Margolis TP. Supratarsal injection of corticosteroid in the treatment of refractory vernal keratoconjunctivitis. Am J Ophthalmol 1996 Mar;121(3):243-9.

2. Saini JS, Gupta A, Pandey SK, Gupta V, Gupta P. Efficacy of supratarsal dexamethasone versus triamcinolone injection in recalcitrant vernal keratoconjunctivitis. Acta Ophthalmol Scand. 1999 Oct;77(5):515-8.

3. Singh S, Pal V, Dhull CS. Supratarsal injection of corticosteroids in the treatment of refractory vernal keratocomjunctivitis. Indian J Ophthalmol 2001;49:241

8. Immunosuppressive agents Immunosuppressive agents can be considered in steroid-dependent cases. Topical cyclosporine A has been shown to be effective in treatment of AKC and VKC. It is an immunomodulator, and inhibits IL-2, T cells and eosinophils. The 2% formulation has been proven effective in many studies but lower concentrations (1%, 0.5%, 0.05%) have been tried and shown to be efficacious.

Tacrolimus is not available as an eyedrop, low dose systemic tacrolimus has been reported to be effective in severe AKC, and the ointment is licensed for use in atopic dermatitis.

• Cyclosporine A 0.05% (Restasis) to 2%

• Tacrolimus (FK-506)

9. Immunotherapy

Immunotherapy describes the immunizing process in which increasing doses of specific antigen are given to induce increased tolerance. Multiple delivery methods are available, including sublingual, local conjunctival, and subcutaneous injections. Results with sublingual immunotherapy (SLIT) documented the clinical efficacy and safety on allergic eye symptoms, but most studies referred to rhinoconjunctivitis, with ocular symptoms as a secondary outcome. Other studies did not show a long-lasting effect.

10. Experimental interventions

Montelukast, a leukotriene receptor antagonist, has been shown to improve • VKC symptoms in children treated for asthma.

Lambiase A et al. Montelukast, a leukotriene receptor antagonist, in vernal keratoconjunctivitis associated with asthma. Arch Ophthalmol. 2003 May;121(5):615-20.

Anti-IgE therapy – Omalizumab administered subcutaneously is currently • approved for treatment of asthma. A study using this drug in seasonal allergic rhinitis reported improvement in ocular symptoms.

Okubo K, Ogino S, Nagakura T, Ishikawa T. Omalizumab is effective and safe in the treatment of Japanese cedar pollen-induced seasonal allergic rhinitis. Allergol Int 2006; 55:379–386.

Williams PB, Sheppard JD Jr. omalizumab; a future innovation for treatment of severe ocular allergy? Expert Opion Biol Ther. 2005 Dsc;5(12);1603-9.

Others have been used in animal models and found to have an inhibitory effect • on antigen-induced conjunctivitis

–  –  –

BKC is a common but under-recognized problem in children. The condition is similar to that seen in adults but there are important differences in terms of clinical presentation and treatment.

BKC is primarily an eyelid margin disease with secondary corneal and conjunctival involvement. It is traditionally divided into anterior and posterior blepharitis although the conditions often coexist. Anterior disease involves the anterior lid margin, hair follicles and associated oil glands, whereas posterior disease is associated with meibomian gland dysfunction.

–  –  –

In addition to the above signs, chronic BKC are often associated with mild papillary or follicular hypertrophy of the palpebral conjunctiva. Acute exacerbations present with episodes of conjunctivitis, and may be accompanied by a variety of secondary corneal changes such as punctate epithelial erosions, subepithelial infiltrates, phylctenules, marginal keratitis and ulceration. Cornea scarring and vascularization may develop. Recurrent chalazia or styes may be another presenting feature.

Important features in children:

Age of presentation is around 6-7 years (mean 6.9 years1, 7 years2, 6.5 years3, • median 5.4 years4), although there is usually a delay of 1 to 2 years between the onset of symptoms and diagnosis.

Cornea involvement is common 81%1, 65%2, 64%3. However, there may be a • selection bias as all the quoted studies are from tertiary referral centers which tend to see more severe disease.

Location of cornea involvement tends to be central or paracentral rather than the • classical peripheral or marginal inflammation seen in adults1.

Visual impairment is common. Superimposed amblyopia due to prolonged corneal • opacification and/ or refractive changes (in particular astigmatism due to cornea scarring) is frequently present.

There may be frequent exacerbations requiring prolonged steroid treatment.

Treatment strategies:

1. Lid hygiene/ warm compresses – using cotton wool tipped swab sticks warm water, diluted baby shampoo or special products like Blephagel or Lid Care.

Modified lid hygiene using a clean fingertip or warm damp flannel to rub the eyelids at the base of lashes during showering may be more easily implemented in small children1.

2. Topical antibiotics - A variety of topical antibiotics have been used including chloramphenicol 0.5%, ciprofloxacin, gentamicin, fusidic acid. Staphylococcus aureus or Staphylococcus epidermis are the most common organisms cultured form conjunctival or lid swabs taken.

3. Topical steroids – prednisolone acetate 1%, prednisolone 0.5%, or fluoromethaolone (FML) 0.1% depending on severity. Patients should be converted to FML once the disease comes under control as it is less likely to induce secondary glaucoma.

4. Systemic antibiotics – Oral tetracycline has been reported to be successful, but is contraindicated in children under the age of 8 years because of its effect on dental enamel. Oral erythrymycin has also been found to be effective and well tolerated, although it is unclear whether the mechanism of action is a direct effect on lipid synthesis or influence on the microflora. Recommended dosage ranged from 25% to 80% of the recommended dose for treatment of moderate infections in children (50mg/kg per day in divided doses). Treatment is usually required in the longterm but should be reduced quickly to the minimum dose required to control lid margin disease.

5. Flaxseed oil (α-linolenic acid) – can be considered for children who unable to tolerate or reluctant to use longterm systemic antibiotics. It is a source of omega-3 essential fatty acids which have been found to have anti-inflammatory effects and improve dry eye syndrome. In addition, they appear to have a thinning effect on meibomian secretions. The dosage recommended is 2.5ml once a day reducing to alternate days for up to 6 months1.



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