This document discusses allergic conjunctivitis and its subtypes. It describes the signs, symptoms, pathogenesis, differential diagnosis, and management of various forms of allergic conjunctivitis including seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC), and shield ulcers which can complicate VKC. Treatment options discussed include lifestyle modifications, topical antihistamines, mast cell stabilizers, corticosteroids, cyclosporine, tacrolimus, and sublingual immunotherapy.

2. Introduction
 Allergic conjunctivitis is a group of ocular surface
diseases that are typically associated with type 1
hypersensitivity reactions .
 May be associated with rhinitis and asthma

3. Allergic conjunctivitis
Seasonal allergic conjunctivitivitis
coincides with regional seasonal increases in circulating allergens, such as
grass pollens
Perennial allergic conjunctivitivitis
symptoms throughout the year; however seasonal spikes can occur, Animal
dander, house dust, molds
Vernal keratoconjunctivitis associated with conjunctival scarring, ptosis,
corneal neovascularisation, ulceration, thinning, Keratoconus, vision loss
Atopic keratoconjunctivitis eyelid tightening, loss of eyelashes, and
cataracts

4. VKC
 Younger , 1st decade
 Not so
 Males more
 Resolves at puberty
 Upper tarsus
 Forniceal shortening rare
 Shield ulcer
 Corneal vascularization
not common
 Periocular skin normal
AKC
 Older 2nd to 5th decade
 Associated with atopic
dermatitis
 No predilection
 Chronic
 Lower tarsus
 Forniceal shortening and
subepithelial scarring
 Persistent epithelial
defect
 Corneal vascularization
common
 Periocular skin, scaly,
dry, lid thickened,
madarosis, cicatricial
ectropion

5. Sheild
Ulcer in
severe VKC
Cobblestone
papillae

6. Atopic
keratoconjunctivitis

7. OD

8. OS

9. Symptoms
 Itching (pruritus) and
 Redness
 Burning,
 Stinging, Photophobia
 Tearing (epiphora)
 watery or mucoid ropy discharge

10. Signs
 Conjunctiva pinkish or milky appearance
(obscuration of conjunctival vessels due
to chemosis)
 Papillary hypertrophy upper tarsus,
limbal
 Tarsal papillae 1mm or more,
cobblestone like (differentiate VKC from
SAC, PAC)
 Limbal papillae confluent, gelatinous

12. Signs
 Horner Trantas dots along the limbus
( white dots are a collection of eosinophils
and epithelial cells an indicator of active
allergy)
 Spotty pigmentation of interpalpebral
conjunctiva in brown individuals
 Punctate epithelial erosions on Cornea
 Peripheral cornea superficial stromal grey
white deposition Pseudogerontoxon

13. Limbal VKC
Horner trantas spots pseudogerontoxon
Subepithelial scarring
Corneal
scarring

14. Limbal VKC & cataract4 weeks post cataract surgery
6 months post op after stopping treatment
Shield ulcer
Limbal thickening
Limbal thickening
Steroid induced cataract
OS

15. Limbal VKC
6 weeks of medical management
6 months later after discontinuing treatment
Partial stem cell deficiency
OD

16. Limbal VKC
 Fulminant & long standing limbal VKC
can result in stem cell deficiency
 Under recognised and frequently missed
 In established limbal stem cell deficiency
limbal allograft- direct or cultivated
 Immunosuppression

17.  the greater the papillary size, the more
probable is the persistence or worsening
of symptoms in the long term follow up
period
Giant papillae in VKC

18. Giant papillae in VKC
Supratarsal Steroid injection
 Short acting dexamethasone 4mg
 Intermediate acting triamcinolone
acetonide 20mg
 Improvement in 2 weeks
 Both effective
 Recurrences less with triamcinolone
Holsclaw DS et al, Am J Ophthalmol 1996
Saini JS et al, Acta Ophthalmol Scand,1999 Oct

19. Giant papillae in VKC
After supratarsal steroid injection tricort

21. Differential features of allergic conjunctivitis

22. Pathophysiology
 type I (IgE-dependent) immediate
hypersensitivity reaction in VKC
 B lymphocytes from the lymphoid follicle of
the conjunctiva locally produce IgE.
 Mast cell degranulation results in the release
of a range of mediators such as histamine,
leading to the classical allergic reactions of
vasodilatation, oedema, hyperaemia,
 And recruitment of other inflammatory cells.

23.  Role of eosinophil in ocular allergy
important their consistent presence in
conjunctival biopsy tissues affected by
ocular allergy and by eosinophilic
cationic protein levels in tears.
 Activated eosinophils elicit ocular
surface inflammation by their soluble
mediators (EMBP, ECP) can lead to
corneal epithelial breakdown
Pathophysiology

24.  There is also growing evidence for the
involvement of a CD4T helper 2 (Th2)-
driven type IV (delayed or cell-
mediated)hypersensitivity reaction as
well.
 Once activated, these Th2 lymphocytes
play a role in recruitment and activation
of mast cells and eosinophils, and in B
cell switching to the production of IgE.
Pathophysiology

25. Antigen presentation to T lymphocytes
Naïve T cell
Interaction between T Helper Lymphocytes
and antibody producing cells

27. Interleukins, 1,3,4,5,6, TNF
over hours
In minutesimmediate

28. Differential diagnosis
 Bacterial / viral conjunctivitis,
 rhinitis, dry eye,
 meibomian gland disease (resulting in
tear film abnormality or insufficiency),
 blepharitis
 Contact lens wear
 A medical history and assessment of
environmental risk factors

29.  Signs and symptoms (itching, redness,
and chemosis)
 Symptom duration
 Discharge
 Unilateral or bilateral presentation
 Allergy, asthma, or eczema
 Topical and systemic medication use
(i.e. overthe-counter eyedrops and
systemic allergy medications)
Differential diagnosis

30. Severe VKC
 23 % have perennial form
 16% seasonal form becomes perennial
after 3years from disease onset
 9.7% develop shield ulcers
 6% develop visual impairment –due to
corneal damage, cataract, glaucoma
Bonnini S et al Ophthalmology June 2000

31. Shield ulcer
 Sight threatening complication of VKC
 Superficial Epithelial erosions
Macroerosion
Collected cellular debris & mucus- vernal
plaque or shield ulcer

32. Pathogenesis
 Mechanical Hypothesis
Abrasion of cornea by giant papillae on upper
tarsal conjunctiva
 Hence superior location of shield ulcer

33. Pathogenesis
 Toxin Hypothesis
Eosinophil granule major basic protein
Cytotoxic, inhibits epithelial healing
 Hence removal of inflammatory debris
promotes epithelisation

34. Grades
Grade I
 Transparent clear base
 Respond to medical management
 Minimal scarring, no vascularisation
 Good outcome

35. Shield ulcer
 Grade I-II
Central base clear Peripheral translucency

36. Grades
Grade II
 Inflammatory debris in Ulcer base
 Respond poorly to medical management
 Surgical debridement of ulcer base
required
 Re-epithelisation in a week
Cameroon JA, Ophthalmology 1995
Ozbek Z, Rapuano CJ, Cornea. 2006 May

37. Shield ulcer
 Grade II
After amniotic membrane transplantation
Translucent base

38. Grades
Grade III
 Elevated plaque above surrounding
epithelium
 Responds best to surgical treatment

39. Shield ulcer
 Grade III
Giant papillae
Shield ulcer with plaque
After AMG

40. Shield ulcer Complications
 Secondary infection
 Corneal vascularisation
 Corneal scarring
 Amblyopia
 Strabismus
Cameroon JA, Ophthalmology 1995
Cameroon JA et al,J Pediatr Ophthalmol
Strabismus 1997

41. Management
 No improvement or evidence of
epithelisation after 1 week of medical
treatment – surgical debridement for
grade I & II.
 Surgical debridement needed for grade
III

42. Amniotic membrane for Shield
Ulcer
 For nonresponsive cases –AMG
 Promotes epithelisation
 Antiscarring
 Antivascularisation
 Anti inflammatory
 Acts like a BCL
M.S.Sridhar et al, Ophthalmology July 2001

43. Excimer PTK for Shield ulcer
 After removal of the plaque & control of
inflammation
 Excimer laser PTK beneficial in certain
cases
 Produces smooth surface
 Removes toxic inflammatory products
 Allows epithelisation
 Reduces scarring
Cameron JA, et al J Refract Surg 1995

45. Corneal edema, small infiltrate
Healed with scarring and resolution of edema

46. 26 % on topography
7% on slit lamp and keratometry
Ophthalomology 2001

47. Treatment
 Topical Antihistamines
 Mast cell stabiliser
 Antihistamine and mast cell stabiliser
combination
 Topical steroids
 Immunomodulators

48. Severity of Allergic conjunctivitis

50. Lifestyle modification
 Allergen avoidance – avoid being outdoors
 Avoidance of animal exposure for sensitive
individuals
 Hypoallergenic bedding
 Washing sheets in hot water, which denatures
allergenic proteins (i.e. those from dust mites)
 Showering and shampooing at bedtime to remove
allergens
 Sunglasses, which serve as a barrier to airborne
allergens
 Avoidance of eye rubbing –release of more
inflammatory mediators
 Cool compresses – help to alleviate ocular itching

51. Topical antihistamine
 The benefits of these agents are that
 they block histamine, stabilize the mast
cell, and inhibit eosinophil activation and
migration .
 antihistamines address the signs and
symptoms of ocular allergy, particularly
itching
 Onset of action quick but duration short up
to 4 times daily

52.  Levocabastine
 Chlorpheniramine
 Antazoline
 Systemic antihistamines increase
dryness can be given for rhinitis
Topical antihistamine

53. Mast cell stabiliser
 Mast cell stabilizers (inhibitors) prevent
degranulation of mast cells.
 These agents are particularly effective in
SAC and PAC in which the predominant
cell types are the mast cell and eosinophil.
 Mast cell stabilizers address both the early
and late phases of the allergic response
 clinically effect takes 1-2 weeks

54.  Disodium cromoglycate (Cromolyn) 4%
twice a day
 Lodoxamide (Alomide 0.1 %) twice a
day
 Nedocromil 2% twice a day
Mast cell stabiliser

55. Antihistamine and mast cell
stabiliser combination
 These dual-acting medications relieve
redness, itching, and irritation.
 They have a quick onset of action, which is
likely to improve patient adherence
compared with the pure mast cell stabilizers
 require only once-a-day or twice-a-day
dosing.
 Side-effects, which tend to be transient and
mild, include: stinging, burning, bitter taste,
and sedation.

56.  Ketotifen 0.025%
 Epinastine 0.05% b.d is a multi-action agent
 potent H1 and H2-receptor antagonist, mast
cell-stabilizing properties and anti-
inflammatory actions
 Epinastine not only inhibits activation of
neutrophils and eosinophils but also
interferes with CD4+ T-cell signaling, and
thus decrease of TH2 cytokine production
 Onset of action 3 minutes, duration 8 hours
Antihistamine and mast cell
stabiliser combination

57.  Olopatadine
 It also has anti-inflammatory properties such as
inhibition of cytokine secretion , inhibition of
TNF-α release from human conjunctival mast
cell , with a subsequent decrease in ICAM-1
expression and thereby a decrease in
chemotaxis of inflammatory cells such as
eosinophils.
 rapid onset (within 20 min), with at least 8h
duration of action .
 The 0.1% b.d / 0.2% o.d (24 hours action) .
Antihistamine and mast cell
stabiliser combination

58. NSAIDS
 NSAIDs can address the itching associated
with allergic conjunctivitis
 These agents can cause discomfort upon
instillation, which can in turn lead
to reduced patient adherence, not ideal in
presence of epithelial erosions

59. Corticosteroids
 Corticosteroids are the most effective anti-
inflammatory drugs available
 Productions of several pro-inflammatory cytokines
such as IL-1, IL-4, IL-5and TNF-a are directly
‘repressed’ by corticosteroids
 decrease expression of adhesion molecules
 decrease in numbers of eosinophils neutrophils,
mast cells and lymphocytes at the site of
inflammation
 Topical application high local tissue concentration

60.  Important side effect of ocular steroids is
increase in ocular pressure (IOP)
 Cataract, secondary infection
 newer ‘soft’ corticosteroids with the alteration
of the ketone structure to ester at carbonC20
of the corticosteroid structure has led to a
marked decrease in this side effect in both
IOP and cataract formation
 Loteprednol etabonate
 is thus a preferred topical steroid 0.2%
Corticosteroids

61. Topical cyclosporin and
Tacrolimus
 Moderate to severe AKC and VKC
 Topical Cyclosporin or Tacrolimus
 actions of both agents are inhibition of T-cell
activation and inhibition of release of IgE-
dependent mediators and cytokines from mast
cells and other related cells
 cyclosporine A (CsA) inhibits proliferation and
cytokine production from conjunctival
fibroblasts thus suppressing the inflammatory
cascade

62. Topical cyclosporin
 1% - 2% in olive oil, castor oil, lubricants
 Burning sensation on topical application
 Can affect compliance
 0.1 % - 0.05% less burning, not so
effective
 Aurosporin 2% cyclosporin from Aurolab

63. Topical Tacrolimus
 0.1% - 0.03% ointment
 0.03% can be applied in lower fornix 2
times a day
 Minimal stinging on topical application
 Tacliment 0.03% from Aurolab
 Beneficial effects reported in VKC, AKC,
GPC in 4 weeks

64.  No systemic adverse effects reported
with both Cyclosporin and Tacrolimus on
topical use.
 Burning and stinging less with
Tacrolimus ointment
 HSV keratitis reported by some on
tacrolimus use.
Topical cyclosporin and
Tacrolimus

65.  Because allergic conjunctivitis usually
accompanies allergic rhinitis, most of the
studies of allergen immunotherapy were
conducted in patients with symptoms of
both organ systems.
 As a consequence, ocular symptoms
were shown to be improved together
with rhinitis symptoms
 Needs to be given for atleast a year.
Sublingual immunotherapy

66. Sublingual immunotherapy
 Sublingual immunotherapy is taken as drops or
tablets, containing specific allergen extracts which
interact with the immune system to decrease
allergic sensitivity.
 Increasing doses of the allergen are administered
by sublingual immunotherapy route to achieve
hyposensitization and creating immune tolerance
to antigens.
 Long term changes that occur with immunotherapy
include a decrease in mast cell sensitivity and a
decrease in IgE production by mucosal B-cells.
 There is a decrease in the IgE/IgG4 and a
decrease in the TH1/TH2 ratio.

67.  recently published metaanalysis results
of SLIT for allergic conjunctivitis.
 not only improved patients’ eye
symptoms (red eyes, itching, watery
eyes) but also increased allergen
threshold
 May benefit VKC , AKC
Sublingual immunotherapy

68. Conclusion
 a proactive, multifaceted approach
based on severity of the disease.
 Co management with an allergy
specialist in severe cases
 Immunomodulators for severe VKC,
AKC
 Patients going for elective laser vision
correction or cataract surgery should be
well controlled

69. October 2013

71. Giant papillae in VKC
 Surgical resection of giant papillae and
autologous conjunctival graft in
refractory cases
 No recurrence over 9-27 months
Nishiwaki-Dantas MC, et al Ophthal Plast Reconstr
Surg. 2000 Nov

72. Giant papillae in VKC
 Surgical Resection and cryotherapy
Drawback
 Irregular conjunctival scarring can
produce palpebral deformity & surface
irregularity of superior palpebral
conjunctiva

73. Giant papillae in VKC
 Superficial tarsectomy
Compromises accessory lacrimal and
meibomian gland function
 Surgical resection & Buccal mucous
membrane graft

74. Giant papillae in VKC
 Removal of giant vernal papillae by CO2
laser.
Belfair N et al Can J Ophthalmol. 2005 Aug
 Only mechanical trauma eliminated,
immunologic process controlled
medically