VKC.pptx

Vernal keratoconjunctivitis (VKC) is a chronic, bilateral, at times asymmetrical, seasonally exacerbated, allergic inflammation of the ocular surface, involving tarsal and⁄or bulbar conjunctiva

More common in children and young adults

Has an atopic background

First mentioned in the ophthalmic literature as conjunctiva lymphatica more than 150 years ago

More common in the summers than in the winters

1. VKC Presenter- DR SHAYRI PILLAI Liberia Eye Centre JFK Memorial Medical Centre L V Prasad Eye Institute November 13, 2019

2. VKC(Spring Catarrh)

3. Introduction Vernal keratoconjunctivitis (VKC) is a chronic, bilateral, at times asymmetrical, seasonally exacerbated, allergic inflammation of the ocular surface, involving tarsal and⁄or bulbar conjunctiva More common in children and young adults Has an atopic background First mentioned in the ophthalmic literature as conjunctiva lymphatica more than 150 years ago More common in the summers than in the winters It is more common in children and young adults having an atopic background. Kumar, Sunil Department of Ophthalmology, Mohammad Dossary Hospital, Al Khobar, Saudi Arabia, Acta Ophthalmologica 2009 Subsequently, most of the doyens of ophthalmology during that period ( Arlt , Dasmarres , von Graefe , Axenfeld , Trantas and Herbert) published about this interesting malady (Barney 1997) The most striking point in its presentation is the seasonal variation i.e. it is more common in the summers than in the winters.

4. The efficiency of school-aged children decreased profoundly because of the chronic and recurrent course Although this is not usually a blinding disease, visual impairment may occur if the cornea is involved

5. Geographical distribution VKC has a wide geographical distribution Young males in dry and hot climates are primarily affected It is more common in temperate zones of Mediterranean areas, central and west Africa, the Middle East, Japan, the Indian subcontinent and South America. VKC cases are also seen in Western Europe, Australia and North America Varying prevalence has been reported in different ethnic groups. Kumar, Sunil Department of Ophthalmology, Mohammad Dossary Hospital, Al Khobar, Saudi Arabia, Acta Ophthalmologica 2009

6. Demography VKC starts before the age of 10 years The earliest reported age of onset is 5 months ( Ukponmwan 2003) Resolves after puberty, usually around 4–10 years after onset ( Bielory 2000; Leonardi 2002a) The disease is more common among males, ratio varying from 4 : 1 to 2 : 1 ( Bonini et al. 2000) After the age of 20 years, the male and female ratio becomes almost equal ( Bielory 2000 Kumar, Sunil Department of Ophthalmology, Mohammad Dossary Hospital, Al Khobar, Saudi Arabia, Acta Ophthalmologica 2009 It generally resolves after puberty, usually around 4–10 years after onset ( Bielory 2000; Leonardi 2002a) The disease is more common among males, with the male to female ratio reported in the literature varying from 4 : 1 to 2 : 1 (Neumann et al. 1959; Beigelman 1965; Bonini et al. 2000).

7. Genetics and family history No genetic predisposing factor has been identified for VKC Predominance of VKC in Asia and Africa strengthens the possibility of a genetic predisposition VKC is more common among individuals of Asian and African origin living in Sweden ( Montan et al. 1999). So far, no genetic predisposing factor has been identified for VKC but the predominance of VKC in Asia and Africa, along with the persistence of this predilection in migrated African and Asian populations, strengthens the possibility of a genetic predisposition.

8. Relationship between VKC and a particular genotype is not confirmed Eosinophils in blood, tears and conjunctival scrapings Expression of mediators and cytokines Predominance of CD4 cells locally Although no genetic analysis has been performed to confirm a relationship between VKC and a particular genotype, the constant and increased presence of eosinophils in blood, tears and conjunctival scrapings, the expression of a multitude of mediators and cytokines, as well as the predominance of CD4 cells locally suggest that VKC may be a phenotypic model of upregulation of the cytokine gene cluster on chromosome 5q. suggest that VKC may be a phenotypic model of upregulation of the cytokine gene cluster on chromosome 5q. suggest that VKC may be a phenotypic model of upregulation of the cytokine gene cluster on chromosome 5q.

9. Family history of allergic disorders such as asthma rhinitis eczema urticaria and multiple atopic diseases The cytokine gene cluster, throughits products like Interleukin (IL)-3, -4, -5 and granulocyte⁄macrophagecolony-stimulating factor (GM-CSF), regulate the prevalence of T helper cell type 2 (Th2), the growth and function of mast cells and eosinophils as well as the production of immunoglobulin (Ig) E in VKC ( Bonini et al. 1995a). reported in 49% of patients suffering from VKC ( Bonini et al. 2000). Kumar, Sunil Department of Ophthalmology, Mohammad Dossary Hospital, Al Khobar, Saudi Arabia, Acta Ophthalmologica 2009

10. Associated conditions Atopy is common among VKC patients Asthma is the most common atopic disease seen among VKC patients Keratoconus and acute hydrops Due to excessive eye rubbing Sex-hormone-related diseases such as Gynaecomastia Polycystic ovary syndrome Mammary fibroadenoma Adiposogenital dystrophy and Autoimmune diseases Atopy, defined as the presence of allergen-specific IgE antibodies, is common among VKC patients. One third of VKC patients have multiple atopic diseases ( Bonini et al. 2000) Atopy is less common in limbal compared to tarsal VKC (Tuft et al. 1989) were reported by 2% of patients suffering with VKC ( Bonini et al. 2000)

11. Pathophysiology VKC is characterized by infiltration of the conjunctiva by a variety of inflammatory cell types, especially eosinophils Increased number of activated CD4+ T-lymphocytes, predominantly Th2, indicating that there is a hypersensitivity reaction to an unknown pathogen Increased levels of inflammatory cytokines IL-3, IL-4, and IL-5 have also been demonstrated Conjunctival papillae formation is related to fibroblast activation and production Limbal conjunctival nodules are related to infiltration of inflammatory cells Although VKC has previously been thought of as an IgE -mediated disease,5 several other immunologic pathways have also been implicated. Patients with VKC have been shown to have an increased number of activated CD4+ T-lymphocytes, predominantly Th2, indicating that there is a hypersensitivity reaction to an unknown pathogen.6 Hampton, Addis et Bennie H Jeng . Vernal keratoconjunctivitis,Clinical Ophthalmology 2018:12 119–123

12. Cellular irregularities in patients with VKC Injury to the superficial corneal epithelial layer and the basal epithelium and anterior stroma Corneal nerves may be affected decreased density increased concentration of adjacent inflammatory cells Studies using in vivo confocal microscopy have shown cellular irregularities in patients with VKC. Patients have been shown to have not only injury to the superficial corneal epithelial layer but also involvement of the basal epithelium and anterior stroma. Corneal nerves may be affected in VKC, and they have been shown to have decreased density as well as increased concentration of adjacent inflammatory cells Hampton, Addis et Bennie H Jeng . Vernal keratoconjunctivitis,Clinical Ophthalmology 2018:12 119–123

13. Aberrations in the normal ocular surface microbiome may play a role in VKC In a recent study, Staphylococcus aureus was more frequently isolated from the conjunctival specimens from patients with VKC, and may be a significant cause of exacerbations, while S. epidermidis was more frequently found in normal control patients. It is also thought that aberrations in the normal ocular surface microbiome may play a role in VKC Hampton, Addis et Bennie H Jeng . Vernal keratoconjunctivitis,Clinical Ophthalmology 2018:12 119–123

14. Classification Palpebral VKC involves the upper tarsal conjunctiva. Associated with significant corneal disease as a result of the close apposition between the inflamed conjunctiva and the corneal epithelium Limbal disease typically affects black and Asian patients Mixed VKC has features of both palpebral and limbal disease. Aassociated with significant corneal disease as a result of the close apposition between the inflamed conjunctiva and the corneal epithelium Bowling , B. Kanski’s Clinical Ophthalmology: A Systemic Approach, 8 th Ed. 2016. Australia.P.145

15. Clinical features Symptoms Intense itching Lacrimation Photophobia Foreign body sensation Burning and thick mucoid discharge Increased blinking is common Bowling , B. Kanski’s Clinical Ophthalmology: A Systemic Approach, 8 th Ed. 2016. Australia.P.145

16. Signs Palpebral disease Early-mild disease is characterized by Conjunctival hyperaemia and Diffuse fine papillary hypertrophy on the superior tarsal plate  (A) Diffuse fine papillary hypertrophy; (B)  macropapillae  with focal inflammatory infiltrates;  (C)  macropapillae  with diffuse infiltrate; (D) giant papillae; (E) intense disease with mucus; (F) milder disease; note mucous  discharge 

17. Macropapillae (<1 mm) have a flat-topped polygonal appearance (B)  macropapillae  with focal inflammatory infiltrates; focal inflammatory infiltrates diffuse whitish inflammatory infiltrates

18. Giant papillae (>1 mm) Progression to giant papillae (>1 mm) can occur, as adjacent smaller lesions amalgamate when dividing septa rupture Mucus deposition between giant papillae Decreased disease activity is characterized by milder conjunctival injection and decreased mucus production Thick mucus hyper-secretion with sticky mucous filaments, called ‘ropy discharge’, is a characteristic of VKC. Transient limbal or conjunctival yellow-white points or deposits, known as Horner– Trantas’s dotsare degenerating eosinophils and epithelial cell debris.

19. Large (> 1 mm) papillae in VKC occur predominantly at the upper tarsus Papillae that may attain a size of 7–8 mm are known as cobblestone papillae Papillae size correlate positively with the persistence or worsening of symptoms over long-term follow-up (Bonini et al. 2000). These papillae become quite swollen during the active stage but persist even during the quiescent

20. Limbal disease Gelatinous limbal conjunctival papillae that may be associated with transient apically located white cellular collections (Horner– Trantas dots) In tropical regions, limbal disease may be severe Thick mucus hyper-secretion with sticky mucous filaments, called ‘ropy discharge’, is a characteristic of VKC. Transient limbal or conjunctival yellow-white points or deposits, known as Horner– Trantas’s dots are degenerating eosinophils and epithelial cell debris.

21. Keratopathy is more frequent in palpebral disease and may take the following forms: Superior punctate epithelial erosions associated with layers of mucus on the superior cornea

22. Plaques and ‘shield’ ulcers Plaques and ‘shield’ ulcers (Fig. 5.15A and B) Fig. 5.15 Keratopathy in vernal disease. (A) Early plaque; (B) plaque and shield ulcer; (C) subepithelial scarring following  ulceration; (D)  pseudogerontoxon  and limbal papillae

23. subepithelial scarring  following  ulceration

24. Grading of papillae Bonini et al. (2000) graded the papillae on the upper tarsal conjunctiva or at the corneoscleral limbus as follows: Grade 0: no papillary reaction Grade 1+: few papillae, 0.2 mm widespread over the tarsal conjunctiva or around the limbus Grade 2+: papillae of 0.3–1 mm over the tarsal conjunctiva or at the limbus Grade 3+: papillae of 1–3 mm all over the tarsal conjunctiva or for 360o around the limbus Grade 4+: papillae of more than 3 mm over the tarsal conjunctiva or gelatinous appearance at the limbus covering the peripheral cornea

25. Diagnosis The diagnosis is clinical Investigations are generally not indicated Eosinophils may be abundant in conjunctival scrapings

26. Periodicity of disease Important parameter to consideration while planning treatment Two or three episodes in a year may be safely given short courses of mild steroids but in a child with chronic all year long disease, it may not be a good option to give chronic continuous steroid therapy. The periodicity of disease is an important parameter to be taken into consideration while planning treatment.

27. Intermittent disease periodicity is defined as inflammation free intervals of >2–3 months during which the patient is off medications maximum of 3–4 episodes in a year, which remit on therapy Chronic disease periodicity is defined as inflammation free intervals of <1 month during which the patient is off medications. Patient has continuous ongoing inflammation, which possibly recurs on attempting to stop or taper therapy Patient has chronic disease all throughout the year

28. Treatment Algorithm Classify the disease severity into mild, moderate-intermittent, moderate-chronic, severe, and blinding subtypes for treatment It is usually possible to classify the disease severity into mild, moderate-intermittent, moderate-chronic, severe, and blinding subtypes Gokhale, Nikhil S Gokhale Eye Hospital, Mumbai, Maharashtra, India, Volume : 64 Issue : 2 Page : 145-148 IJO 2016

29. Mild disease Redness and itching Congestion Fine velvety papillae No corneal involvement Steroids should be avoided in the absence of any corneal involvement Rx Allergen avoidance (A) Lubricants (L) Antihistaminics (H) Mast cell stabilizers (M) Gokhale, Nikhil S Gokhale Eye Hospital, Mumbai, Maharashtra, India, Volume : 64 Issue : 2 Page : 145-148 IJO 2016

30. Moderate disease (intermittent and chronic) Corneal involvement: Fine punctate erosions Horner– Trantas dots Limbal inflammation and thickening of <6 clock hours They require add-on therapy (in addition to ALHM) based on the periodicity of disease. In addition to ALHM Rx: intermittent Mild surface steroids (Loteprednol) Rx Chronic Cyclosporine 0.5% Gokhale, Nikhil S Gokhale Eye Hospital, Mumbai, Maharashtra, India, Volume : 64 Issue : 2 Page : 145-148 IJO 2016

31. Severe disease Large active cobblestones Coarse erosions or keratitis Macroerosions Severe limbal inflammation >6 clock hours Pannus Postinflammatory scarring limbal deficiency in the form of pannus and postinflammatory scarring. Rx Potent topical steroids + ALHM + 1% cyclosporine therapy Gokhale, Nikhil S Gokhale Eye Hospital, Mumbai, Maharashtra, India, Volume : 64 Issue : 2 Page : 145-148 IJO 2016

32. Blinding disease Extremely active large cobblestones Active shield ulcers, Severe annular limbal inflammation, Limbal stem cell deficiency extensive conjunctivalization limbal scarring extensive corneal scarring Patients with extremely active large cobblestones, active shield ulcers, severe annular limbal inflammation, limbal stem cell deficiency manifesting as extensive conjunctivalization , limbal scarring, and extensive corneal scarring and are the most difficult to treat. Rx Potent steroids + ALHMC Cyclosporine 2% e/d + tacrolimus 0.03% . A log book of daily steroid usage may be useful in these patients. These patients need to be more closely monitored for complications such as infection, cataract, and glaucoma. Cyclosporine 2% drops and tacrolimus 0.03% ointment can be used in combination Gokhale, Nikhil S Gokhale Eye Hospital, Mumbai, Maharashtra, India, Volume : 64 Issue : 2 Page : 145-148 IJO 2016

33. Patients with severe and blinding disease may also require surgical interventions: Superficial keratectomy for shield ulcer plaques Cryotherapy for refractory cobblestones Cobblestone excision with or without mitomycin C Amniotic membrane grafts Reconstructive surgery ( limbal stem cell transplants) Gokhale, Nikhil S Gokhale Eye Hospital, Mumbai, Maharashtra, India, Volume : 64 Issue : 2 Page : 145-148 IJO 2016

34. Differential diagnosis Seasonal allergic conjunctivitis Perennial allergic conjunctivitis Atopic keratoconjunctivitis Giant papillary conjunctivitis Chlamydial infection VKC may be differentiated from the above disorders by hypertrophic papillae in the tarsal form of VKC or Horner Trantas dots in the limbal form, or a combination of the two, along with no involvement of the eyelids. Differential diagnosis of VKC includes any of the chronic allergic conjunctivitis’s including Currently there is limited utility in testing for the diagnosis of VKC. Skin tests and IgE levels are rarely useful and may be negative in 50% of patients with VKC. In cases where the diagnosis is unclear, conjunctival scrapings showing eosinophilic infiltration may be beneficial in aiding the diagnosis.5

35. Complications Shield ulcers and plaques Plaques form when inflammatory debris accumulates at the base of a shield ulcer Limbal stem cell deficiency due to longstanding inflammation Keratoconus and irregular astigmatism due to frequent eye rubbing Steroid-induced glaucoma from frequent use of topical corticosteroid Hampton, Addis et Bennie H Jeng . Vernal keratoconjunctivitis,Clinical Ophthalmology 2018:12 119–123

36. Prognosis Generally good and the disease is self-limiting with appropriate treatment Despite an overall good prognosis, up to 6% of patients will develop vision loss due to complications associated with VKC In patients studied, over half will continue to have symptoms after 5 years and the presence of giant papilla may indicate a worse prognosis Hampton, Addis et Bennie H Jeng . Vernal keratoconjunctivitis,Clinical Ophthalmology 2018:12 119–123

37. Take home message VKC is a bilateral inflammatory disease that can cause visual loss The diagnosis of VKC is largely clinical Grading of the severity of disease and periodicity of disease can be very useful for deciding the appropriate line of management Topical cyclosporine in higher concentrations and tacrolimus ointment are useful steroid-sparing agents Severe, protracted cases of VKC remain a challenge to treat Continue research is necessary to better understand the complex nature of VKC and to develop more effective therapies.

38. Thank you! Excellence Equity Efficiency L V Prasad Eye Institute