Childhood corneal neovascularization

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1 Miltos Balidis PhD, FEBOphth, ICOphth Sotiria Palioura MD,PhD Childhood corneal neovascularization

2 Opacities Cornea clarity is essential for optimal vision at any age. In childhood, loss of corneal transparency may also lead to amblyopia. Proper management of the conditions that lead to corneal scarring and neovascularization in children is of utmost importance

3 The most common causes of childhood keratitis with new vessel formation Primary infection or reactivation of the herpes simplex virus type 1 vernal keratoconjunctivitis blepharokeratoconjunctivitis.

4 CATEGORIES Superficial or pannus Midstromal deep overlying Descemet membrane. CAUSE Pannus is generally associated with ocular surface disorders Mid and deep stromal with inflammatory or infectious keratitis.

5 HERPES SIMPLEX KERATITIS It is the most common infectious cause of corneal blindness. 2 Subtypes: HSV-1 mostly transmits the infection to eyes HSV-2 Primary infection Childhood (until % seropositive) Droplet transmission or direct inoculation Mild fever, malaise and upper respiratory tract symptoms Blepheritis and follicular conjunctivitis Topical antiviral treatment

6 HSK-1 onset Outcomes of corneal HSV-1 infection in children are significantly worse than in adults for a variety of reasons. Children present with stromal keratitis, long-standing scarring and neovascularization Adult HSK presents in epithelial dendritic HSV may be bilateral in children with asthma and atopy Late diagnosis, poor topical compliance Recurrence rate of HSV is greater than 50% Estimated mean time to recurrence of 13 months

7 Topical EPITHELIAL KERATITIS TREATMENT Aciclovir 3% ointment or Ganciclovir 0.15% gel ( 5 times daily) Steroid Debridement Slow healing or frequent recurrence Combination of two topical agents with oral antiviral valaciclovir or famiciclovir Skin lesions acyclovir cream five times daily

8 10 years old girl with bilateral HSK1 on systemic treatment

9 Bilateral HSK ISK 6 years old girl with recurencies and neovascularization

10 Systemic antivirals Acyclovir dosing is 100 mg 3 times/day (0 18 months) 200 mg 3 times/day (18 months 3 years) 300 mg 3 times/day (3 6 years) 400 mg 3 times/day (>6 yrs) In acyclovir-resistant strains Valacyclovir, ganciclovir, and famciclovir, Trifluridine foscarnet, and cidofovir

11 RECURRENT INFECTION After primary infection : the virus is carried to the sensory ganglion for that dermatome periodically occur contagious Clinical reactivation A variety of stressors such as fever, hormonal change, uv radiation, trauma or trigeminal injury.

12 Childhood blepharitis Blepheritis is an acute subacute or chronic inflammatory process or infection of the lid margins. Globally it is one of the most common eye disorder and ophthalmologic complications which is difficult to treat. It may be associated with rosacea, seborrheic dermatitis, dry eye, chalazion, conjunctivitis and keratitis.

13 Anterior blepharitis Bacterial or Staphylococcal Chronic Seborrhoeic Parasitic Demodex Posterior blepharitis or meibomian gland dysfunction Mixed CLASSIFICATION

14 Inflamed meibomian glands. Rarely, corneal inflammation can extend centrally Secretions of inflamed glands Phlyctenules, sterile corneal infiltrates in the peripheral cornea (10,2,4,8). Inflammation of ocular surface

15 BACTERIAL SEBORRHEIC PARASITIC Gluing of yellow crust at the root of cilia Small ulcers on removal of crusts Red thickened lid Mild papillary conjunctivitis & conjunctival hyperemia White dandruff like scales on lid margins and lashes Hyperaemia of lids Falling of lashes and replacement Thickening of lid margins Redness & inflammation of lid margins Lice anchoring on lashes Demodex at the base of cilia Conjunctival hyperaemia

16 COMPLICATIONS SEQUEALE Lash abnormalities Recurrent chalazia Epiphora Marginal keratitis Tear film instability Dry eyes

17 TREATMENT OF ANTERIOR BLEPHERITIS Inflammation is controlled using topical (i.e. corticosteroids, cyclosporine, azithromycin) and oral (i.e. doxycycline, erythromycin). Doxycycline (effective for ocular rosacea in adults), it is contraindicated in young children (age <8) Doxycycline is a matrix metalloproteinase inhibitor, and thus it indirectly protects against new vessel formation by inhibiting enzymes responsible for creating space within the corneal stroma for the new vessels to grow into. Additional effects on the composition of the lipid meibomian gland secretions and on the local ocular microflora are thought to break the cycle of inflammation. In young children, the macrolides erythromycin (50 mg/kg/day twice daily) and azithromycin (5 15 mg/kg/day once daily)

18 STEROIDS Steroid-sparing agents, such as cyclosporine (0.2 2%), have shown promise in controlling inflammation due to BKC, topical corticosteroids still represent the preferred treatment regimen in the acute phase of the disease. High-potency topical steroids are usually used briefly to suppress the acute inflammatory phase and are tapered quickly or switched to lower potency ones, such as fluorometholone or loteprednol.

19 TREATMENT OF ANTERIOR BLEPHERITIS Alternative to the oral regimen in young children is topical azithromycin either in the form of eye drops (1 or 1.5%) In some reports, the effects of topical azithromycin instillation (1.5% eye drops) were as good as the oral dosing. Parents generally feel more comfortable with a chronic topical medication rather than a chronic systemic medication, though administration of eye drops is more challenging in children

20 TREATMENT OF PARASITIC BLEPHERITIS Mechanical removal of nits with forceps Tea tree oil scrub every 2 weeks for 2 months Nits cycle Lid hygiene with specific antiseptic foam with tea tree oil Delousing of the patient, other family members, clothing and bedding.

21 Corneal stromal inflammation due to blepharokeratoconjunctivitis will resolve with scarring and neovascularization. Unlike HSV keratitis, the scars are in most cases peripheral and do not involve the visual axis

22 Vernal keratoconjuctivitis Tarsal conjunctival disease process with giant papillae Mechanical injury from rough tarsal papillae damage corneal epithelium. Secretions from eosonophils and mast cells lead to inflammatory reaction in bare stroma Limbal stem cell deficiency (LSCD) presents due to prolonged relentless inflammation resulting in pannus formation and conjuctival epithelium invasion

23 Vernal keratoconjuctivitis Basic protein and eosonophil cationic protein, (cytotoxicity) IL-13 and tumor necrosis factor-a (fibroblast stimulation) topical corticosteroids and immunomodulators (e.g. cyclosporine 0.5 2% or tacrolimus %) The more severe the manifestations of VKC, the higher the concentrations of cyclosporine and tacrolimus that are needed

24 Neovascularization

25 Neovascularization VEGF Pre-angiogenic factors Space within extracellular matrix Proteases MMP-2, MMP-9 Topical steroids Anti VEGF subconj Not in chronic

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27 Athens September 2017