Hypersensitivity, Giant papillary conjunctivitis, Vernal keratoconjunctivitis, perennial conjunctivitis, Phlyctenular conjunctivitis

1. ALLERGY AND HYPERSENSITIVITY:
PERRENIAL CONJUNCTIVITIS,
VERNAL CONJUNCTIVITIS,
GPC AND
PHLYCTENULAR CONJUNCTIVITIS.
RAJU KAITI
OPTOmETRIST
DHULIKHEL HOSPITAL, KU HOSPITAL

2. IMMUNITY
• Immune system is an interacting set of
specialized cells and proteins designed to
identify and destroy foreign invaders or
abnormal substances before they damage the
body
• Sequence of cellular and molecular events
designed to rid the host of an offending
stimulus

3. Failure of Immune system
Immune system
Hypersensitivity
(Overactive immune response)
Immunodeficiency
(ineffective immune
response)
Autoimmunity
(mistaken recognition of self
antigens)

4. Hypersensitivity
• Term used to describe immune responses
that cause host tissue damage
• Detrimental effect on hosts
– Fever
– shock
– Inflammatory nature
– Spasm of smooth muscle
– Gastrointestinal and pulmonary disorders
– Fatal circulatory collapse

5. Hypersensitivity
• State in which the introduction of an
antigen into the body elicits an unduly
severe immunological reaction.
• 4 types: -
1. Anaphylaxis, atopic or Type I reaction.
2. Cytotoxic or Type II
3. Immune complex, Arthus-Type III
4. Delayed hypersensitivity Type IV

6. Hypersensitivity
• Type I
– Exaggerated IgE response to relatively harmless
environmental antigens
– Genetic predisposition
– Manifests itself in tissue reactions occurring within
5mins after the antigen combines with the
matching antibody

7. • Results in release of several active substances
including histamine, slow reacting substance and an
eosinophils chemo tactic factor within minutes
• Also may be a second “late phase”
• TYPE 1 HYPERSENSITIVITY MEDIATORS
• Histamine
• Prostaglandin and thromboxanes
• cytokines

8. Type I
– E.g.:
• Hay fever, atopic dermatitis, systemic
anaphylaxis
• Atopic conjunctivitis
• Seasonal and perennial allergic conjunctivitis

9. Type II
– Antibody mediated hypersensitivity against self
cells or receptors or membranes
– Mediated by IgG or IgM antibodies against tissue
antigens, resulting in organ-specific antibody
production
– Antibody binds to cells or tissues and causes local
complement activation, influx of leukocytes, and
tissue destruction

10. Type II
• e.g.
Mooren’s ulcer
Hemolytic disease of the newborn
Good pasture syndrome
Hyper acute graft rejection

11. Type III
• Due to high levels of circulating, soluble immune
complexes overwhelming the ability of the
mononuclear phagocyte system to remove them
• Damage is caused by antigen-antibody complex.
• The excess complexes deposit in various tissues and
activate complement
• Subsequent attempt by neutrophils to remove them
results in degranulation and tissue damage.

12. Type III
• Can take one of two forms according to
whether the immune complex develops in
circulating blood or in tissues
• Arthus reaction
Local manifestation in tissue
• Serum sickness
 Systemic form of type III hypersensitivity

13. Type III
– E.g..
• Arthus reaction, serum sickness, Lupus,
Rheumatoid arthritis, etc.
• Immune ring formation in cornea in Herpes
simplex Keratitis
– Diagnosis:
• very low levels of complements in blood, esp. c3
and c4

14. Immune ring formation in herpes
simplex Keratitis

15. Type IV
– No role of antibody or complement
– One aspect of cell mediated immunity
– Antigen activates specifically macrophages and sensitized
T-lymphocytes leading to secretions of lymphokines
– Due to activity of thymus dependent lymphocytes and
clinically has a delayed onset
– Two types:
• Classical or Tuberculin type
• Contact hypersensitivity

16. • Example
– Corneal graft rejection
– Sympathetic ophthalamia
– Vogt Koyonagi Harada’s syndrome
– Optic neuritis
– Recurrent herpetic Keratitis
– Bacterial, fungal, viral, protozoal and parasitic infection.
– Allergic Dermatoconjunctivitis
– disciform Keratitis

22. Allergic conjunctivitis:
• Inflammation of conjunctiva due to allergic or
hypersensitive reaction which may be
immediate (humoral ) or delayed (cellular) to
specific antigens

23. Types
• SIMPLE ALLERGIC
• VERNAL KERATOCONJUNCTIVITIS
• ATOPIC KERATCONJUNCTIVITIS
• GIANT PAPILLARY CONJUNCTIVITIS
• PHLYCTENULAR CONJUNCTIVITIS
• CONTACT DERMATOCONJUNCTIVITIS

24. Simple allergic conjunctivitis
• Hay fever conjunctivitis
• Seasonal allergic conjunctivitis
• Perennial allergic conjunctivitis
• Acute allergic conjunctivitis

25. Perennial allergic conjunctivitis(PAC)
• Occurs at any age
• History of personal and/or familial allergies
• Seen all year- round
• Causes can include animal dander, insects and dust
mites

26. Pathogenesis
Allergen enters tear film
Comes in contact with conjunctival mast cells that bear
lgE antibodies.
Degranulation of mast cells releases histamine
Histamine promotes vasodilatation & edema

27. • Symptoms and signs
– Itchy and watery eyes
– Burning sensation and mild photophobia
– Mild to moderate conjunctival injection and chemo
sis, mild hyperemia
– Mild papillary reaction
– Mild oedema of lids

28. • Treatment (severity dependent)
– Elimination of allergens if possible
– cold compresses
– NSAIDS
– antihistamines oral/ topical
– mast cell stabilizers (sodium cromoglycate)
– topical corticosteroids
– Immunosuppressant's (cyclosporin) for steroid
resistant cases

31. Vernal keratoconjunctivitis or spring catarrh
– Recurrent, Bilateral , self limiting allergic inflammation
of the conjunctiva affecting children and young adults
– more common in males
– allergic disorder in which IgE and cell mediated immune
mechanism play an important role

32. • Clinical features :
– 98% bilateral, can be asymmetric
– Intense ocular itching, Lacrimation, Photophobia,
blepharospasm, blurred vision, FB sensation , burning
and difficulty opening eyes in the morning.
– Thick mucous ropy discharge , Psudoptosis due to large
papillae.
– Giant papillae on the superior Palpebral conjunctiva are
the clinical hallmark.

33. • Papillae in limbal area have a white, chalky area at
apex(Tranta’s dot or Horner's points)
• Peripheral neovascularisation may occur.
• Tarsal papillae in 83-84% of VKC patients.
• Bulbar papillae in 7%. of VKC patients.
• Both forms in 9-17% of VKC patients.
• Cobblestone papillae in 16%(approx).
» Ref: illustrated ophthalmic pathologies-Dr. C. S. Miranda

34. • Pain if corneal involvement.
• Corneal complications-common; include-Punctate
erosions which coalesce to form painful macroerosions.
• Accumulations of inflammatory debris in
macroerosions prevents epithelization of cornea.
• Non-healed epithelial defects-shield ulcers

35. Progression of vernal Keratopathy
Punctate epithelopathy Epithelial macroerosions
Plaque formation (shield ulcer) Sub epithelial scarring

36. Papillae vs. follicles
• Papillae
• Vascular reaction consisting of
fibro vascular mounds with central
vascular tuft. Can be large-
cobblestone or giant papillae-
allergic conjunctivitis
• Follicles
• Small translucent, avascular
mounds of plasma cells and
lymphocytes seen in
keratoconjunctivitis, herpes
simplex virus, Chlamydia, drug
reactions

37. GRADING OF PAPILLAE
• Grade 0:no papillae are present
• Grade 1:a few widespread papillae<0.3mm in diameter on
Palpebral conjunctiva or limbus.
• Grade 2: tarsal or limbal papillae between 0.3-1.0mm in
diameter.
• Grade 3:tarsal papillae between 1.0-3.0mm in diameter or
limbal papillae present.
• Grade 4:papillae are >3.0mm in diameter and/or a gelatinous
limbal appearance of the peripheral cornea.
» Ref: illustrated ophthalmic pathologies-Dr. C. S. Miranda

38. • Predisposing factors :
• Age -
– Onset usually after 4 years .
– Resolves around puberty .
• Season -
– More common in dry and warm climate .
– Peak incidence - April and August.
– But can occur year around .

39. • Clinical types :
– Palpebral, Limbal and Mixed .
• Palpebral VKC :
– Conjunctival hyperemia followed by diffuse papillary
hypertrophy ( superior tarsus )
– Papillae enlarged and have flat topped polygonal
appearance ( cobblestone ).
– Formation of giant septa.
– Active disease - Redness, swelling , tightly packed papillae.

41. Progression of vernal conjunctivitis
Diffuse papillary hypertrophy, most marked on superior tarsus
Formation of cobblestone papillae Rupture of septae - giant papillae

42. • Limbal VKC :( Better prognosis)
– Mucoid nodules with smooth round surface .
– Discrete site superficial spots ( Tranta's dots )
– composed predominantly of eosinophils .
• Keratopathy :
– Punctate epithelopathy ,
– Macro erosion ,
– Plaque ,
– Sub-epithelial scarring ,
– Pseudogerontoxon ( resembles an arcus senilis )characterized
by cupid's bow out line.
• Mixed form

43. Limbal vernal
Tranta's dotsMucoid nodule

45. Management
• Therapy should be based on the severity of the
symptoms.
• For mild cases
– Cold compression
– Photo chromic glasses
– Topical antihistaminic
– NSAIDs such as ketorolac 0.5%

46. For severe cases
• Topical corticosteroids or topical
immunomodulatory agents such as
cyclosporine
• Intermittent or pulse therapy of corticosteroid
is very effective
– Topical steroids used at high frequency & tapered
slowly.
• Less potent soluble steroids are frequently
used.

47. • Patient & family member should be informed
of potential dangers of chronic steroid
therapy.
• Supratarsal injection of 0.5-1.0 ml of short
acting steroid can be given for co-operative
patients.

48. For most severe cases
• Topical cyclosporine 2% twice daily.
• Cyclosporine exerts immunomodulatory
effects on both afferent & efferent limbs of the
cellular immune response.
• Side effects
– Punctate epithelial Keratopathy
– Ocular surface irritation.

49. Phlyctenular conjunctivitis :
• Nodular affection occurring as an allergic response by
conjunctiva and corneal epithelium to some
endogenous allergens .
• Etiology -
– Delayed hypersensitivity ( type I ) response to
endogenous microbial proteins : Tuberculous protein
Staphylococcal protein , parasitic protein .

50. • Predisposing factors -
– Age (3 to 15 yrs.) , Sex(girls ), Undernourished one .
– Under hygienic and overcrowded living condition .
– More common in summer and spring .
• Pathology -
– Stage of nodule formation : exudation and infiltration
of lymphocytes
– Stage of ulceration : Necrosis of apex of nodule
leading to ulcer formation ,
– Stage of granulation
– Stage of healing .

51. • Clinical presentation -
– Simple Phlyctenular conjunctivitis
– Nercotizing Phlyctenular conjunctivitis
– Miliary Phlyctenular conjunctivitis .
• Symptoms -
– Lacrimation , discomfort , watering
– Mucopurulent conjunctivitis due to secondary
bacterial infection .

52. • Signs -
– Typical pinkish nodule surrounded by hyperemia on
bulbar conjunctiva near the limbus .
– Single or multiple phlycten.
• Phlyctenular Keratitis - may occur secondarily.
• Clinical course -
– Self limiting disease
– phlycten disappear in 8 to 10 days
– Recurrence are common.

53. • Treatment -
– steroid eye drops ,
– Antibiotic drops ( secondary infection )
– specific therapy
• Tuberculosis
• septic focus should be treated
• parasitic infestation - stool examination .
– General measures - improve health of child .

54. Giant papillary conjunctivitis
• GPC most commonly develops after prolonged conjunctival
contact with a foreign substance such as contact lens
• Also reported with exposure to ocular sutures or prosthesis
• Often it is not contact lens itself that causes GPC, but it is
deposits or allergens
• Soft contact lens cause GPC more commonly

55. Papillary conjunctivitis-cobblestone-grade-2(flour)

56. Papillary conjunctivitis-cobblestone-grade 3

57. Papillary conjunctivitis-cobblestone-grade-4(flour)

58. • SYMPTOMS AND SIGNS
– Thick mucous discharge, inflamed superior papillae and blurry
vision
– GPC staging
• Stage 1:itching and decreased lens tolerance
• Stage 2:blurred vision
• Stage 3:excessive contact lens movement because tarsal
papillae don’t allow smooth movement of lid over CL
• Stage 4:similar appearance to mild VKC
» Ref: illustrated ophthalmic pathologies-Dr. C. S. Miranda

59. • Treatment
– Offending causes should be removed
– Disodium cromoglycate-relieve symptoms and
enhance the rate of resolution
– Steroids not of much use

60. REFERENCES
• Illustrated ophthalmic pathologies-Dr.C.S.Miranda
• Ophthalmology-A.K.Khurana
• Clinical ophthalmology-Jack.J.Kanski
• Medical microbiology-Geo.F. Brooks,Janet.S.Butel,Stephen A.
Morse
• Short text book of medical microbiology, 6th
edition, Satish
Gupte
• Lippincott’s microbiology
• Robbin’s pathology
• Ocular Pathology by Myron Yanoff and Ben S. Fine
• Internet
• Class notes

61. …THANK YOU !!!