Immune disorders of cornea contains many systemic diseases and local disorders of the eye. In this powerpoint we will mainly discuss about the systemic disorders affecting the eye.

1. Immune disorders of cornea
Presenter-Dr Vaibhav
Moderator- Dr Shivanand

2. Left eyeRight eye
50 yr/F
C/o BE defective vision- 1 year, LE
pain
No H/o trauma
H/o RE cataract Sx 1 yr back
BCVA RE- 6/12, LE 6/12 p
LE microbiological workup- Negative
Raised ESR- 104mm/hr

3. Immune disorders affecting the eye
• Rheumatoid Arthritis
• Nonrheumatoid collagen vascular disease- SLE, Wegerner’s syndrome,
PAN
• Phlectenular conjunctivitis and keratitis

5. Rheumatoid arthritis(RA)
• Systemic autoimmune disease
• Affects primarily synovial joints and less
frequently extra-articular tissues (eye,
pleura, pericardium and nerve)
• Incidence-1%, Women>Men(3 times
higher)
• Onset: 4th-6th decade
Age distribution of ocular manifestation of RA patients

6. • Diagnosis of RA by American Rheumatism Association(ARA)

7. • Pathogenesis
• RF- Detected in 70-90% of RA patients- Extra-articular manifestations
• Positive anti-CCP(cyclic citrullinated protein) and RF – Highly
specific(99%)
Immunological reaction to unknown antigen
Imbalance b/w pro-inflammatory mediators
and their inhibitors
IL-1, TNF-alpha
Inflammation, Vasculitis

8. Ocular manifestations of RA

9. Keratoconjunctivitis sicca(15-25%)
• Presentation- Dry eye symptoms
• Pathogenesis-
Lacrimal gland hyposecretion (Neurosecretory block*)
*Inflammatory cytokines- IL-1beta, IL-6 and TNF- alpha, antibodies
Confluent positive staining
with rose bengal in
interpalpebral conjunctiva
and cornea- PEE’s/
Filamentary keratitis
High tear
osmolarity
Tear film
instability

10. Scleritis/Episcleritis(20%/11%)
• Medical therapy should be re-evaluated
• Diffuse anterior scleritis (m.c variant)
• Nodular scleritis- Diffuse or single nodule
• Necrotizing scleritis
• Secondary bacterial/fungal infection
• Scleromalacia perforans- Necrotizing scleritis
without inflammation

11. • Posterior scleritis – Concurrent anterior scleritis, ocular pain
worsening with eye movements, exudative RD
• CT/ MRI scan helps differentiate it with orbital pseudo-tumour or
orbital cellulitis
B scan- T sign CT scan- Diffuse sclera;
thickening

12. Keratitis
• Most often occurs in contiguous with adjacent scleritis(50%)
• Most common presentation- Sclerosing keratitis
Sclerosing keratitis Stromal keratitis +PUK
Limbal guttering, Intact
epithelium

13. • Pathogenesis of PUK
Immune complex deposition @limbal vessels
Vasculitis and leakage of inflammatory cells and proteins
Complement activation, increase in cytokines, neutrophils and
macrophages
Collagenases and proteases release causing corneal tissue destruction

14. Treatment:
• Goal: Aggressively treat, slow down and reduce the ongoing
inflammatory process
• Treatment options:
a) Oral NSAIDS
b) Oral Corticosteroids
c) Disease modifying antirheumatic drugs(DMARDs)
• Improve signs and symptoms and the quality of life for patients
• Initial therapy: NSAID, DMARD and sometimes oral prednisolone

15. Drug Name Mechanism Dosage Side effects
Methotrexate Antagonist of THFA, purine,
adenosine metabolism
7.5-20mg/week
+
Folic acid 1-2mg daily
Aphthous stomatitis, nausea,
diarrhoea, cytopenias*,
hepatic toxicity*
Sulfasalazine Unknown, preferred as initial
DMARD
500mg BD Gastrointestinal intolerance,
improved with enteric
coating
Leflunomide(Arava) Inhibits enzyme
dihydroorotate
dehydrogenase, blocking
pyrimidines in lymphocytes
10-20 mg OD Diarrhoea, rash and hair loss,
hepatic toxicity*
Cyclosporine Inhibits production of
cytokines involved in the
regulation of T-cell
activation
2-4mg/kg/day Renal toxicity
(close monitoring of serum
creatinine and BP control)
• Biological DMARD’s- Etanercept, Infliximab, Anakinra, Abatacept, Rituximab,
*-Periodic laboratory examination- CBC,ALT, AST

16. 3 Goals
local healing
Promote epithelial
healing- Dec stromal
thinning
• Lubricating drops,
gels
• Avoid epitheliotoxic
drugs
• No role of topical
antibiocs/ antifungals
unless secondary
infection
Control of inflammation
• Topical pred acetate
• Topical cyclosporin
0.5-1%
• Low dose steroids,
lid hygiene only in
marginal infiltrates
with blepharitis
Collagenase inhibition-
Dec stromal thinning
• Tetracycline 250 mg
QID
• Doxycycline 100mg
OD
• Systemic
steroids+cytotoxic
immunosuppresives

17. Keratoconjunctivitis sicca- Stepwise progressive therapy
Rx blepharitis, allergic conjunctivitis, environmental triggers,
abnormalities of eyelid position, ocular lubricants, dietary
modifications(essential FA supplements)
Topical corticosteroids, topical cyclosporinA, oral tetracycline,
topical secreatagougues(Diquafosol, Rebamipide), moisture
chamber, DO NOT USE PUNCTAL PLUGS*
Oral secreatagougues(Oral Pilocarpine, Cevimeline), autologous/
allogenic serum eye drops, soft BCL
Amniotic membrane graft, surgical approaches such as
tarsorrhaphy, chemical tarsorrhaphy

18. Keratitis
• Oral steroids- Rule out Tuberculosis
• Topical steroids and antibiotic combination
• Topical Cyclosporin A
• Oral tetracyclines- Inhibits protease activity and cytokine levels
• Contact lens therapy- Close follow-up for mechanical, hypoxic and
infectious complications
• Suture or chemical tarsorrhaphy- Persistent epithelial defect
Non-necrotizing scleritis
• Systemic medical therapy- Stepwise approach

19. • Oral NSAIDs + Topical steroid drops
• Subconjunctival corticosteroid injection- Non-infectious, non-
necrotizing anterior scleritis
Necrotizing scleritis and peripheral ulcerative keratitis(PUK)
• Should be managed with an internal medicine/rheumatologic opinion
• Rule out infectious etiology- Microbiological work-up
• Systemic immunosuppression
• Broad spectrum topical antibiotics+ potent topical steroids
• Cyclosporin A eye drops- Steroid sparing agents
• Tetracycline derivative- Protease inhibitor

20. Surgical management
• Conjunctival resection, conjunctival
flaps, annular lamellar corneoscleral
patch grafting(impending perforation)
• Adjunctive surgical procedures for
scleral melt - Tectonic support like CAG
with oversized BCL(temporary), scleral
graft, AMG
• Scleromalacia perforans- No need for
aggressive treatment
• Aggressive lubrication and
tarsorrhaphy enhances surgical
success

21. Systemic Lupus Erythematosus(SLE)
• Etiology- Unknown
• Women:men ratio is 9:1
• T cell and B cell hyper-reactivity
Auto-antibodies and immune
complex deposition Chronic
inflammation and organ damage
• ACR criteria- 4/11- Diagnostic
• Diagnosis- Clinical findings + Auto-
antibodies(ANA, anti-DNAs, Anti-ds
DNA)

22. Ocular manifestations
• Seen in minority of patients
• Most common manifestation- KCS
• Most common vision threatening- Retinal vascultis, choroidal involvement
• Eyelid- Lid erythema, scaling plaques, loss of lashes
• Anterior segment- Conjunctival scarring, symblepharon, periorbital edema,
orbital inflammation, corneal staining , PUK, corneal endothelitis with
bilateral corneal edema
• Recurrent episcleritis, scleritis(rare)
• Treatment
• NSAIDS
• Systemic corticosteroids

23. • Hydroxychloroquine- Dose: 6.5mg/kg, Side effects: Bulls eye
maculopathy* with paracentral scotoma
• Cytotoxic agents- Azathioprine, chlorambucil, cyclophosphamide
• Rituximab in combination with cyclophosphamide and
methylprednisolone
• Dry eye- Lubricants
• Retinal vasculitis- PRP
• Retinal neovascularisation- anti-VEGF, Intravitreal triamcininolone

24. Wegener’s granulomatosis
• Known as Granulomatosis with polyangitis(GPA)
• Systemic vasculitis characterised with necrotising and granulomatous
inflammation of the upper and lower respiratory tract, glomerulonephritis,
and other organ involvement with small vessel inflammation
• Etiology- Unknown
• American college of Rheumatology
• >=2 of the four criteria
• Sensitivity- 88%; Specificity- 92%
• Onset in mid 40s
• Male: Female(2:1)

25. • Presentation- Non-specific- fever, malaise, joint and muscle pain, and
weight loss, sinusitis with discharge, rhinorrhea, epistaxis and otitis,
pulmonary infiltrates, haemoptysis, renal failure, ocular inflammation
• Lab findings- Normocytic normochromic anaemia, high ESR, positive
RF, C-ANCA(most sensitive, specific)
• Ocular features
Proptosis with pseudotumour or orbital inflammation(40-50%)
Scleritis(16-38%)
PUK
Nasolacrimal duct obstruction secondary to nasopharyngeal disease

26. • Other anterior segment- Secondary sjogrens with dry eye, tarsal
conjunctival necrosis- entropion, trichiasis,
• Retinal vasculitis, ischaemic optic neuropathy, retinal artery or vein
occlusion, cotton wool spots
Focal necrotizing scleritis
with peripheral keratitis
Peripheral anterior stromal
and subepithelial infiltrates
Necrotizing scleritis

27. Treatment
• Systemic disorder- systemic corticosteroids(oral prednisolone
1mg/kg) and cytotoxic agents(oral cyclophosphamide-2mg/kg)
• Pulsed therapy of oral prednisolone 500mg and oral
cyclophosphamide *500mg
• ANCA levels(monitor disease activity)
• Other drugs- Trimethoprim-sulfamethoxazole and methotrexate,
infliximab, etanercept(Anti-TNF alpha)
• Ocular- Artificial tears for dry eyes, topical corticisteroids for
episcleritis, scleritis

28. Polyarteritis nodosa
• Vasculitis of small and medium size arteries
• Multiple organ failure
• Males>Females; Age -40-60 years
American college of rheumatology >=3

29. Ocular findings(10-20%)
• Retinal vessel involvement secondary to hypertension or vasculitis,
retinal arteriolar occlusive disease, choroidal infarcts, exudative RD
• CNS or direct nerve involvement causing EOM palsy, optic nerve
infarction
• Orbit- Pseudotumour-like lesion
• Conjunctival nodules caused by edema and necrosis of conjunctival
vessels as well as uveitis
• Scleritis
• Peripheral ulcerative keratitis

30. Diagnosis-
ARA criteria+ raised ANCA levels
Treatment-
Focuses on systemic disease- Corticosteroids, cytotoxic agents
Improves 5 year survival rate to 80%
• Five year mortality with no treatment is 90%

32. Phlyctenular Keratoconjunctivitis
• Phlyctenule derived from a greek word phlyctena meaning blister
• Was classically described as a disease of sickly children in areas of
endemic tuberculosis
• Common pathophysiological mechanism with marginal keratitis
• Bacterial allergy- most common is tuberculoprotein and staphylococcal
antigen

33. Pathogenesis- Type 4 hypersensitivity reaction
• Staphylococcal PKC- Eyelids
• Tubercular PKC- Pas pulmonary infection
Sensitization of conea/conjunctiva to
a microbial antigen
Repeated exposure to the antigen
via exogenous or endogenous route
Phlyctenular keratoconjunctivitis
Type 4 hypersenstivity reaction

34. Presentation- Conjunctival lesion: Mild tearing and foreign body
sensation; Corneal lesion: Associated with photophobia
Signs- Phlyctenule at the limbus, but can occur anywhere in the bulbar
conjunctiva, rarely in palpebral conjunctiva
Nodular Lesion 1-2 mm in diameter
after few days
Central superficial portion turns
yellow/gray or soft
Ulcer formation, later re-epitheliases
This cycle takes 1-2 weeks, no scarring

35. • Corneal phlyctenules appear at the limbus, small white nodule with
adjacent intense conjunctival inflammation
This nodule undergoes necrosis
forming a marginal ulcer,
resulting an anterior stromal
scarring, triangular in shape.
Pannus formation- Fascicular or
broader, subsequent pannus can
form the central edge of a
pannus

36. • In recurrences phlyctenule can appear to wander across the cornea
Less commonly multiple phlyctenular
lesions may be distributed over the
entire corneal surface- Miliary
phlyctenulosis
Corneal perforation can rarely occur
Differential diagnosis
1. Nodular lesion- Salzmann’s corneal
nodules, limbal papillae in VKC,
inflamed pinguecula, nodular
episcleritis
Salzmann corneal nodule PKC
Not inflamed Inflamed
No rapid progession Rapidly progressive

37. VKC PKC
Bilateral Unilateral
Itching No itching
Diffuse lesions Well circumscribed
Cobble stone papillae -
Pinguicula PKC
Do not ulcerate or migrate onto the
cornea
Ulcerate and migrate
Present at 3 or 9 ’0’ clock limbus Anywhere in the bulbar conjunctiva,
but mostly in the limbal area
2.Ulcerative stage- HSV keratitis, Marginal ulcers, other ulcer associated with
collagen vascular diseases
Marginal ulcer PKC
Clear intervening space b/w
lesion and limbus
No clear intervening space
Long axis of infiltrate is parallel
to limbus
Long axis of infiltrate is
perpendicular to limbus

38. 3. Healing stage-
a) Trachoma- Herbert’s pits, tarsal conjunctiva scarring(Arlt’s line),
superior pannus (PKC pannus -Inferior); chlamydia infection
associated with PKC
b) Interstitial keratitis- Deep cornea with ghost vessels, evidence of
past iritis i.e. synechiae
c) Acne rosacea- Rosacea affects adults (30-40 years), remissions does
not occur post prolonged oral antibiotic therapy
• Diagnosis- History and examination
• History of travel- Endemic areas of TB

39. • Mantoux test, chest radiograph
• Test household members also, if positive
• Chlamydia- Young adults with H/o sexual risk factors or with
suspicious examination findings
Treatment- Topical corticosteroids- a)Prednisolone acetate 1%
b) Topical antibiotic- Cornea epithelial defect
c) Lid scrubs + Antibiotic ointments + oral tetracycline*
d) Cycloplegic agents
e) Dark sunglasses

40. • Oral tetracycline- 250 mg TID for 3 weeks, tapered slowly
• Side effect- Deposit in developing teeth- discoloration, hence
contraindicated <8 years, pregnant women, nursing mothers
• Alternative- Erythromycin
• Significant corneal scarring- Penetrating keratoplasty

41. Staphylococcal Marginal Keratitis
• Also referred as catarrhal infiltrates or ulcers
• It is the most common disorder of the peripheral cornea
Pathogenesis-
Chronic staphylococcal colonisation in the eyelids -Type 3
hypersensitivity reaction- immune complex deposition in the peripheral
cornea
Activation of the complement pathway ;forming catarrhal infiltrates
Gram and Giemsa staining of the corneal scrapings shows no organism

42. • Size of the immune complex :Ratio of antigen to antibody locally. Area
2mm away from limbus- zone of optimal proportions
• Association with staphylococcal
blepharoconjunctivitis (90%)
• Others include: B-Haemolytic streptococci,
Moraxella, Haemophilus
• Clinical features- Pain , photophobia, foreign
body sensation, conjunctival injection

43. • Round infiltrates position 2,4,8,10 o clock positions parallel to limbus;
separated from the limbus by 1-2mm of clear cornea
• Infiltrates coalesce to form broader lesions
• Epithelium overlying can break down- Ulcers
• Spontaneous resolution in 2-3 weeks, few
long term sequelae in blepharitis

44. • Differential diagnosis-
Infectious Ulcer Marginal Ulcer
More painful Painful
Central in location Peripheral 2,4,8,10 o
clock limbus
Anterior chamber
reaction
Not seen
History of trauma No such history
Herpes simplex virus Marginal ulcer
Epithelial defect Infiltrate Infiltrate Epithelial defect
Hypoaesthesia Normal sensation
PUK Marginal ulcer
More severe and progressive Self limiting and responds rapidly to
treatment
Deteriorates with topical steroids,
often need systemic
immunosuppression
Improve with topical steroids

45. Treatment
Goal- Suppressing the acute immune response and reducing the
stimulus for future attacks(bacterial antigens)
Topical steroids(FML, Loteprednol and prednisolone acetate)
Broad spectrum topical antibiotics- In case epithelial breakdown and
stromal ulceration; should be used briefly before initiating topical
steroid
Lid hygiene
Systemic antibiotics such as tetracycline, doxycycline, erythromycin

46. THANK YOU