peripheral ulcerative keratitis

1. DR. RESHMA PETER
PERIPHERAL
ULCERATIVE
KERATITIS

2. A group of
Destructive inflammatory diseases
involving the Peripheral cornea
Final common pathway  sloughing of corneal epithelium and
keratolysis (corneal melting)
• Begins with crescentic destructive inflammation at corneal periphery
• Ass w/ epithelial defects, stromal inflammatory cells, Progressive
stromal melting , degradation and necrosis perforation
• May be associated with Episcleritis, Necrotizing Scleritis, Iridocyclitis

3. PERIPHERAL CORNEA
• No clear-cut borders delineating peripheral cornea
• Portion located b/w central 50% of cornea and limbus.
• An arbitrary central limit beginning at 3.5–4.5 mm from the visual axis
extending to junction of ill-defined transition b/w limbus and conjunctiva.
• Directly adjacent to limbus and internal angle structures
• Highly vascular zone with associated lymphatic tissue, scleral collagen,
corneal collagen and limbal stem cells.
• Thus, vascular inflammatory disorders, limbal infections, collagen
vascular disorders, neoplastic disease, and local degenerations may
affect peripheral cornea in a distinctive way

4. Distinct anatomic differences of the peripheral cornea
• Thickest region of the cornea (up to 0.7 mm) with tight collagen bundle
packing
• A vascular arcade originating from the anterior ciliary arteries extends
approx. 0.5 mm into the clear cornea
• Unlike central avascular cornea , peripheral cornea derives part of its
blood supply from Ant conjunctiva and deep episcleral vessels which are
a source of immunocompetent cells
• The accompanying lymphatics, which drain to the regional lymph nodes.

5.  The adjacent conjunctival blood vessels and lymphatics provide the
peripheral cornea
• Access to afferent and efferent arc of the immune system
• Source of inflammatory effector cells and cytokines involved in the
production of collagenase and proteoglycanase, which contribute to
corneal degradation.
 Unique immunologic characteristics of the peripheral cornea
• presence of more Langerhans’ cells,
• higher concentrations of IgM and C1 (important in the activation of the
classic complement pathway), due to diffusion from limbal vessels due
to large size

6. ETIOLOGY
 Majority- local and systemic immunological processes
 Few cases - infectious
Ocular
Non-infectious Infectious
• Idiopathic
• Acne rosacea (ocular)
• Mooren’s ulcer
• Traumatic, post surgical
• Exposure/neuroparalytic keratopathy
• Marginal keratitis
• Contact lens use
• Nutritional deficiencies
• Bacterial (Staphylococcus,
Streptococcus, Gonococcus [rare]
• Viral (HSV,HZV)
• Amoebic (Acanthamoeba)
• Fungal

7. Systemic
Noninfectious Infectious
Collagen vascular
diseases/vasculitis
• Rheumatoid arthritis
• ANCA-associated vasculitides
• Wegener’s granulomatosis
• Polyarteritis nodosa
• Microscopic polyangiitis
• Churg–Strauss syndrome
• Relapsing polychondritis
• SLE
• Progressive systemic sclerosis
or scleroderma
• Giant cell arteritis
Other systemic autoimmune
• Sjögren’s syndrome
• Cicatricial pemphigoid
(especially with trichiasis)
• Inflammatory bowel
disease
• Sarcoidosis
• Leukemia/malignancy
• Giant cell arteritis
• Gonorrhea
• Bacillary dysentery-
Salmonella, Shigella
• Tuberculosis
• Syphilis
• Varicella zoster
• Helminthiasis
• Hep C
• HIV
• Borreliosis(Lyme
disease )

8. PATHOGENESIS
Exact pathophysiologic mechanisms - unclear.
PROPOSED MECHANISMS IN IMMUNOLOGICAL PATHOGENESIS
 Circulating immune complex deposition
 Autoimmune reactions to corneal antigens
 Hypersensitivity reactions to exogenous antigens
Evidence suggests that both humoral and cell-mediated mechanisms (T
cell and B cell) are involved.

9. Various Etiologies
Inflammatory reaction at corneal periphery
Immune complex deposition and Complement Activation (C1)
Immune vasculitis (damage to the vessel wall )
Further increase in vascular permeability causing leakage
Generates chemotactic factors for neutrophils,pro inflammatory cytokines (C3a, C5a)
Neutrophils recruited at peripheral cornea liberate proteolytic and collagenolytic
enzymes
Metalloproteinases production by local resident cells
Destruction of corneal stroma

10. INFECTIOUS PATHOGENESIS
Microorganisms produce proteases  disrupt the extracellular matrix
Local productions of cytokines and chemokines
diapedesis and migration of neutrophils into peripheral cornea from limbal vessels
Cornea inflammation
Enzymes released by neutrophils and corneal matrix metalloproteinases activation
exacerbate inflammatory necrosis corneal perforation
Antimicrobial control of bacterial replication wound healing processes
NV vs scarring

11. Superinfection
• Sta. aureus -Adhesins bind to collagen and other components of
exposed Bowman and stroma.
• Pseudomonas aeruginosa can bind to molecular receptors exposed
on injured epithelial cells.
Signs of resolution of active PUK
 Resolution of the conjunctival inflammation
 Epithelialization of the corneal surface with residual corneal thinning
and a vascularized scar.

12. OCULAR MANIFESTATIONS
Presenting symptoms of PUK -not specific.
Foreign body sensation, watering, pain, and photophobia - epithelial
erosion and ulceration.
Pain is severe - associated scleritis
Pain without scleral involvement- Mooren’s Ulcer
Decreased Vision - inflammatory process proceeds centrally.
• Photophobia with reduced visual acuity - Associated anterior uveitis

13. Slit lamp Examination
• Crescent shaped destructive lesion at juxta limbal corneal stroma
• W/in 2mm of limbus ,accompanied by varying degrees of vaso-occlusion of
adjacent limbal networks
• Epithelial defect
• Stromal thinning w/ yellow white infiltrates –inflammatory cells
• In early ds., patchy epithelial involvement;stroma –near normal thickness
• Varying degrees of corneal thinning
Thinning due to keratolysis (corneal melting), may occur at any clock hour of
the peripheral cornea, with or w/out an intervening clear zone from limbus

15. • Disease process may progress circumferentially, centrally, and
posteriorly  perforation.
• Corneal melting may progress very rapidly
• Amount of stromal loss underappreciated due to debris and necrotic
material deposited at the base of the ulcer.
• Becomes more apparent after scrapings

16. • Frequently limbal, conjunctival, and episcleral injection occurs.
• Concurrent scleritis denotes a higher likelihood of active vasculitis
• When PUK is ass w/ scleritis there exists worse ocular and systemic
outcome than when there is scleritis alone.
• Complications include Severe Astigmatism, Secondary bacterial infection ,
perforation, cataract ,glaucoma
• Cataract and glaucoma may occur as a result of the inflammatory process
or the use of corticosteroids

17. SYSTEMIC ASSOCIATIONS
50% of patients with PUK may have an associated systemic disease with
the large majority being the collagen vascular diseases (CVDs).
Rheumatoid arthritis (RA) is most common CVD ass w/ PUK, likely due
to its high prevalence in the population (affecting 2.5–3% of adults).
Wegener’s granulomatosis and other ANCA-associated vasculitides,
although relatively rare, are an important cause of PUK.

18. • Generally, patients with RA-associated PUK have an established
advanced systemic diagnosis
• However, in up to 25% patients, PUK may be the initial presenting
feature of a potentially lethal undiagnosed systemic vasculitis,
highlighting the importance of a thorough systemic evaluation.

19. General Examination 0f The Head And
Extremities In Peripheral Ulcerative
Keratitis
Clinical Finding Associated Systemic Diseases
Saddle Nose Deformity Relapsing Polychondritis, WG
Auricular Pinnae Deformity Relapsing Polychondritis
Nasal Mucosal Ulcers WG
Oral/Lip/Tongue Mucosal Ulcers SLE, Sjogrens Syndrome
Facial "Butterfly" Rash SLE
Alopecia
SLE, Progressive Systemic Sclerosis,
Relapsing Polychondritis
Hypo/Hyperpigmentation (Scalp, Face) PSS

20. Clinical Finding Associated Systemic Diseases
Loss Of Facial Expression Rosacea, PSS
Facial Telangiectasias Rosacea
Rhinophyma All Vasculitic Syndromes
Facial/Arms/Legs Rashes, Ulcers PSS
Facial/Arms/Legs Taught Skin GCA
Temporal Artery
Erythema/Tenderness
PSS, SLE, GCA, Sjogrens Syndrome
Raynaud’s Phenomenon (Fingers) All Vasulitic Syndromes
Ulcers In Fingertips RA, SLE, WG, Churg Strauss, PAN
Subcutaneous Nodules In Arms
And Legs
All Vasculitic Syndromes

21. DIAGNOSTIC WORK-UP
• A thorough ocular history, contact lens wear, current and previous
medication for any diseases, trauma, or surgery
• A comprehensive Systemic review to r/o systemic diseases ass w/ PUK
• A complete ophthalmic examination to exclude local pathologies is
critical.

22. Tests to exclude infectious etiologies
Corneal scrapings and subject to
1. Gram Stain , KOH
2. Culture
3. Limulus Lysate Assay
 Rapid and reliable method
 Detect minute amounts of Gram Negative endotoxin
 Prompt selection of appropriate anti microbial

23. LABORATORY INVESTIGATIONS
1. CBC , ESR
2. RF( +ve in 80 % patients with RA)
3. Angiotensin Converting Enzyme ( Sarcoidosis)
4. Anti Nuclear Antibody(ANA) (SLE ,RA)
5. Antibody to Double Strand DNA (anti –ds DNA)(SLE)
6. Antibody to small nuclear ribonucleoprotein (anti-RNP )(SLE)
7. Anti neutrophil cytoplasmic antibodies (ANCA ) c-ANCA in WG
8. Anti CCP
9. Urine Analysis
10. HBsAg
11. FTA –ABS
12. CXR
13. Sinus CT

24. 14 . Biopsy of the bulbar conjunctiva adjacent to the ulcerating cornea
should be considered, especially in suspected autoimmune associated PUK.
Available modalities for studying the specimens include
Light and electron microscopy
Immunoprobes
Polymerase chain reaction (PCR)

25. LABORATORY TESTS FOR SUSPECTED SYSTEMIC
DISEASES IN PUK
Systemic Diseases Laboratory Tests
Systemic lupus erythematosus
ESR, ANA (anti-dsDNA, anti-Sm) IgG, Complement,
Cryogl
Rheumatoid arthritis
ESR, RF, ANA(anti-RNP), CIC, Complement, Cryog,
joint X-rays
Progressive systemic sclerosis
ESR, ANA (anti-centromere, anti-Scl-70), RF, IgG,
CIC
Sjoren’s syndrome
ESR, ANA (anti-RO, anti-La), CIC, RF, Cryo, IgG,
IgA, IgM, sialography

26. Systemic Diseases Laboratory Tests
Polyarteritis nodosa
ESR, HbSAg, IgG, Cryog,complement, CIC,
angiography
Churg-Strauss
ESR, WBC/Eosinophil count, IgE, CIC, Chest
X-ray
Relapsing polychondritis CIC, Complement
Wegener’s
granulomatosis
ESR, IgA, IgE, RF, ANCA, CIC, sinus and chest
x-ray, BUN, creat
Giant cell arteritis ESR, CRP, CIC, IgG

27. • Infectious causes need to be excluded by the appropriate culture techniques
• If infections are suspected- Antimicrobial therapy administered
• Prophylactic topical antibiotics - prevent secondary infections
ENHANCED LUBRICATION
• Dilutes effect of inflammatory cytokines in preocular tear film
• Many rheumatoid patients have KCS as a manifest of 2◦ Sjogren syndrome
Melting stops or slows down if epithelium made to heal by Lubricants,
Pathching, Bandage Contact lens
Medical Treatment

28. Topical Collagenase Inhibitors
• Sodium citrate 10 %
• Acetylcysteine solution 20 %
• Medroxy progesterone 1%
Systemic Collagenase inhibitors
• Tetracycline

29. Topical corticosteroids
• considered as initial therapy in milder, u/l cases (typically when not
associated with a systemic CVD)
• Useful in mild cases of RA-associated PUK
• May be harmful in a subset of vasculitic PUK because they inhibit new
collagen production
• Not effective in WG, microscopic polyangiitis, Churg–Strauss
syndrome, and PAN
• In these cases, corticosteroids may promote progression and even
enhance perforation and thus must be used judiciously.

30. Systemic corticosteroids
• Oral prednisone 1 mg/kg/day- very commonly used for the a/c
management of more severe cases of PUK.
• If there is progression, pulsed methylprednisolone (0.5-1.0 g) for 3
consecutive days may be effective.
• Corticosteroids alone may be inadequate to control the progressive
ocular disease process
• Prolonged use of corticosteroids - significant systemic side-effects
necessitating alternative steroid-sparing immunosuppressive agents.

31. Systemic immunosuppressants
• Immunomodulatory agents, such as methotrexate, azathioprine, or
cyclosporin A, mycophenolate mofetyl and Cytotoxic agents like
cyclophosphamide have demonstrated clinical efficacy for inflammatory
eye disease
Indications for IMMUNOSUPPRESSION in PUK
1. ass w/ potentially lethal systemic vasculitic syndromes such as PAN, RA, SLE,
PSS, Sjogren’s syndrome,WG, allergic angiitis of Churg-Strauss,GCA
2. ass w/ necrotizing scleritis and vasculitis confirmed by histopathologic
analysis of ocular tissue.
3. B/l and /or progressive Mooren’s ulcer.
4. unresponsive to aggressive conventional medical and surgical therapy

32. • Studies suggest that cyclosporin A with dosages in the range of 2.5
mg/kg/day may be a reasonable initial choice for In idiopathic PUK,
(especially if nephrotoxicity is not a concern)
• In cases of PUK ass w/ WG , necrotizing scleritis or Severe or rapidly
progressive PUK associated with other CVDs
First-line therapy- Cytotoxic immunosuppressives, such as cyclophosphamide
(2 mg/kg/day), together with corticosteroids (oral or pulse intravenous)
Maintenance- oral or SC methotrexate(7.5 -12.5 mg /week)

33. Drug MOA Disease Dosage SIDE EFFECTS MONITOR
Azathioprine Prodrug: 6
Mercaptopurine
,Purine
nucleotide
analog
Blocks RNA ,DNA
&protein
synthesis, S
phase specific
Rheumatoid arthritis,
WG, and Relapsing
polychondritis (2nd
Choice)
1-3 mg/kg/day ORAL Bone marrow
suppression
(reversible),
increased risk
of
malignancies(
NHL)
LFT,Absolute
platelet count
Cyclophospha
mide
Alkylating agent ,
DNA to DNA
cross linking ,
DNA miscoding
WG and PAN (1st
Choice), Rheumatoid
arthritis
2 mg/kg/day ORAL/IM Bone Marrow
Depression
Blood
Counts,LFT
Methotrexate Inhibits DHFR,
Bloocks DNA
&RNA synthesis
&repair , S phase
specific
Rheumatoid arthritis
(1st choice),
Maintenance
for WG
7.5-12.5 mg/wk p.o. or IM Hepatotoxicity,
cytopenia,int
erstitial
pneumonia
CBC, LFT every
2 weeks for
1st month
,then every 4-
6 weeks, RFT
Cyclosporine Inhibits IL 2 and
othe
rproinflammator
y cytokines by
inhibiting NF –AT
transcription
factor for
signalling
Idiopathic (1st
Choice), Rheumatoid
arthritis,
Relapsing
polychondritis (2nd
Choice)
2–2.5 mg/kg Twice Daily Transient
increase in
creatinine (50
),gingival
hyperplasia
(40
%),hirsuitism,
nephrotoxicit
y, HTN
RFT, LFT, BP
every 2
weeks
Mycophenolate
mofetil
Selectove inhibitor
of IMP
Dehydrogenae ,
inhibits de novo
synthesis ,
decreasing DNA
synthesis
Alternative to
Azathioprine
1 g Twice Daily, with Max of 1.5
g
Twice Daily
Hepatotoxicity
, leukopenia
CBC, LFT

34. Biological agents
• The efficacy of Biologic agents such as the anti-tissue necrosis factor
(TNF) and anti-B cell monoclonal antibodies in the treatment of RA,
WG, spondylo-arthropathies, inflammatory bowel disease as well as
other systemic vasculitis suggest that they have a role.
• Systemic therapy should be continued for a period of 6 months to 1 year
after initial control of inflammation has been achieved

35. Drug Disease Dosage
Biologic agents
Anti-TNF
Inflixamab RA, Crohn’s disease RA: 3 mg/kg IV infusion at 0, 2, 6 wk then every 8 wk.
Crohn’s diseases 5 mg/kg 0, 2 and 6 wk then every 8 wk.
Dosage may be increased interval of treatment reduced
Adalimumab Wegener’s
granulomatosis,
RA
40 mg s.c. every 4 wk
Anti CD22 (B cell)
Rituximab
WG: 375 mg/m2 once weekly for 4 wk.
RA: Two 1000 mg IV infusion separated by 2 wk,
preceeded by 30 min with 100 mg of IV prednisolone
Dosage maybe increased interval of
treatment reduced

36. Surgical Treatment
Surgical treatments mainly to maintain the integrity of the globe and are
typically palliative.
Conjunctival resection
• Temporarily remove the limbal source of local cellular mediators and
collagenases important in progression of the disease process
• May be of great diagnostic help
Patch graft
• When a perforation is too large for tissue adhesive to seal the leak, some
type of patch graft will be necessary.
• This may range from a small tapered plug of corneal tissue to a
penetrating keratoplasty
Tissue adhesive
Application of Isobutyl cyanoacrylate glue , forms a biological barrier b/w
host cornea and the reepithelializing conjunctiva and the immune

37. Superficial lamellar keratectomy
• arrest the inflammatory process and allow healing
Rehabilitative surgical therapy
• Initial lamellar tectonic grafting followed by central penetrating
keratoplasty
• In advanced cases
• LKP is the most widely practiced surgery – in 2 stages
• For an ulcer < 1/2 circle of limbus and the central 7-8 mm of cornea
uninvolved, crescent shaped lamellar graft can be used.
• For an ulcer > 2/3 of a circle of limbus where the central 7-8 mm of cornea
is intact, a doughnut shaped lamellar graft is recommended.

38. 1st stage
• Lamellar flap that encloses corneal pathology –microkeratome
• Flap lifted to ensure underlying stroma clear, replaced
4-6 week interval
• Flap stabilizes and partially adhere
2nd stage
• Trephine over previously made flap to a depth slightly below initial lamellar
dissection
• 1mm flap rim left behind, Flap removed
• Donor tissue transferred to host bed
 Spontaneously adhere
 10-0’nylon sutures
 Bandage Contact Lens
Femto second laser can be used for making the flap

39. • Amniotic Membrane transplantation- preserve the integrity of the globe
• Cyanoacrylate adhesive in conjunction with immunosuppressive therapy may be
used in patients with impending perforation and may delay the need for tectonic
corneal surgery.
• Conjunctival flaps
 control corneal melting in difficult to manage microbial keratitis,
 but best avoided in immune mediated disease
 Bringing conjunctival vasculature closer to area of corneal disease accelerate
melting

40. COURSE AND OUTCOME
• The course, duration, and outcome are variable and dependent on the
underlying cause of the PUK and on prompt and appropriate
management.
• Many patients with mild or moderate PUK may maintain good vision if the
inflammatory process is rapidly controlled.
• The prognosis is more guarded when PUK is ass with a systemic CVD.
• Significant visual loss and ocular morbidity may develop with corneal
perforation.
• Both ocular and systemic prognosis is more guarded when there is
concomitant scleritis, especially necrotizing scleritis

41. Mooren’s ulcer
• strictly a PUK, with no associated scleritis.
• Bowman published the first report of Mooren’s ulcer in 1849.
• In 1854, McKenzie described it as ‘c/c serpiginous ulcer of the cornea or
ulcus roden.’
• The disorder was named as Mooren’s ulcer after Dr Mooren, who was the
first to clearly describe this insidious corneal problem and define it as a
clinical entity

42. • Mooren’s ulcer can occur in all age groups, but the vast majority present
b/w 40 and 70 years.
• Disease can occur in either sex, but men outnumber women.
• U/l involvement is more common
• Interpalpabral limbus is involved most often, followed by the inferior and
then the superior limbus.
• occurs in complete absence of any diagnosable systemic disorder that
could be responsible for progressive destruction of the cornea.

43. • rare, degenerative, superficial ,idiopathic disease
• painful, rapidly progressive, chronic ulcerative keratitis that begin
peripherally and progresses circumferentially , then centripetally
• single or multi-centric crescent shaped peripheral corneal ulcer with a
characteristic steep, infiltrated, undermined, or overhanging edges

44. Healing: Corneal epithelialization and vascularization associated with
scarring and thinning.
Advanced cases: most of the cornea is lost leaving behind a central island
surrounded by area of grossly thinned, scarred, and vascularized
tissue.Corneal perforation is uncommon.

45. Epidemiology
Wood and Kaufman described two clinical types of Mooren’s ulcer.
Limited type(typical or benign Mooren’s ulcer)
• U/l with mild to moderate symptoms,
• generally responds well to medical and surgical treatment.
• occur in older patients
Atypical or malignant Mooren’s ulcer
• B/l although both eyes may not be affected simultaneously
• relatively more pain and generally a poor response to therapy.
• younger patients
• progresses relentlessly and is more likely to result in corneal perforation.

46. Watson, based on clinical presentation and anterior segment fluorescein
angiographic findings, divided Mooren’s ulcer into three distinct varieties.
U/l Mooren’s ulceration
• painful progressive corneal ulceration in elderly
• Ass w/ nonperfusion of the superficial vascular plexus of the ant segment
B/l aggressive Mooren’s ulceration
• occurs in young patients
• progresses circumferentially, then centrally in the cornea.
• Vascular leakage and new vessel formation, extending into base of ulcer.
B/l indolent Mooren’s ulceration
• usually in middle-aged patients
• presenting with progressive peripheral corneal guttering in both eyes,
with little inflammatory response

48. Pathogenesis
• Although etiology unknown, precipitating factors include accidental
trauma or surgery and exposure to parasitic infection(incidence is higher
in areas of endemic infection)
• Ass w/ infections- helminthiasis, hep C, herpes simplex and zoster.
• Characteristics of an autoimmune process
• decrease in number of suppressor T cells relative to no of helper T cells
• elevated IgA levels
• Higher circulating IgG antibodies and immune complexes to human
corneal and conjunctival epithelium.
• Ratio of CD4/CD8 cells and B7-2/antigen-presenting cells higher
• Ass w/ HLA-DR17

49. • Antibodies to an auto-antigen that exists in corneal stroma.
• The antigen, known as ‘cornea-associated antigen’, has an amino acid
sequence identical to that of calgranulin C of neutrophils.
• No change from normal vascular architecture except an extension of new
vessels into the ulcer.
• Trauma or infection alter normal corneal antigenautoimmune response
• Altered antigen taken up by macrophages(APC),  T-cell activation,
differentiation, and proliferation.
• Lymphocytes return to the conjunctival vesselsocular inflammation.

50. • Corneal edema from inflammation  easier diffusion of immune
components into pericentral and central cornea from the limbal vessels
• Thus cornea is damaged, liberating more altered corneal antigens that
aggravate and perpetuate the process until the corneal stroma is
completely destroyed
• Molecular mimicry may be involved, stimulating an auto immune response.
• Deposition of immune complex over peripheral cornea
• Auto immune lysis of epithelium with release of collagenolytic enzymes.

51. • Grey infiltrates , which break down, forming small ulcers that spread and
coalesce.
• It destroys the epithelium and superficial stromal lamellae, forming a whitish
overhanging edge, while the base quickly becomes vascularised.

52. SYMPTOMS
• severe and persistent neuralgic pain.
• Redness Photophobia Lacrimation
• Decrease in visual acuity due to associated iritis, central corneal
involvement and irregular astigmatism.

53. • The following stepwise approach to management is recommended
1.Topical steroids and antibiotics-Unilateral, mild-moderate cases
2. Conjunctival resection
Conjunctiva is resected up to 2 clock hours on either side to bare sclera
and extend 3–4 mm from the limbus.
Excision of a 4-7 mm strip of adjacent conjunctiva may prove successful by
eliminating conjunctival sources of collagenase , proteoglycanase and other
inflammatory mediators.
3. Topical acetylcysteine 10% and L-cysteine (0 .2 molar), topical
cyclosporine

54. 4. In case of Perforation:
• ulcer debridement with cyanoacrylate adhesive and soft contact lenses.
• Lamellar keratoplasty with IV methotrexate– halt the process
5.Topical IF 2 alpha, Infliximab
6. Systemic immunosuppression-Bilateral or progressive Mooren's ulcer that
fail w/therapeutic steroids and conjunctival resection will require systemic
cytotoxic chemotherapy
5.Additional surgery:
Keratoepithelioplasty
Lamellar keratectomy

55. • A stepwise approach to treatment of Mooren's ulcer is used.
• Treatment proceeds from topical corticosteroids to conjunctival
excision with or without lamellar keratectomy and, finally, to systemic
immunosuppression.
• However, if a patient presents with b/l simultaneous ulcer or
advanced disease or progresses rapidly, little time is spent waiting for
a therapeutic response to topical therapy, and treatment consisting of
conjunctival excision with systemic immunosuppression is undertaken.

56. ROSACEA KERATITIS(acne rosacea)
• c/c acneiform inflammatory disorder chiefly affecting skin and eyes
• unknown etiology but may be related to overexpression of cathelicidin
antimicrobial peptides.
• Cathelicidins cause neutrophil recruitment, angiogenesis, and cytokine
release, which may contribute to the inflammatory skin changes
• sebaceous gland dysfunction of the face, neck, and shoulders
• More common in women in 4th decade
• More severe manifestations occur in men
• Alcohol can contribute to a worsening of this disorder because of its effect
on vasomotor stability

57. CLINICAL PRESENTATION
• More common in fair-skinned individuals, it may simply be more difficult to
diagnose in people with dark skin.
• Skin manifestations precede Corneal manifestations except in 10% of cases
• Facial lesions consist of telangiectasias, recurrent papules and pustules,
and midfacial erythema
• Characteristic malar rash with unpredictable
flushing episodes, ass w/ consumption
of alcohol, coffee, or other foods
• Hypertrophic cutaneous changes occur late in
the disease process-Rhinophyma

58. • Excessive sebum secretion with frequently recalcitrant c/c blepharitis.
• Eyelid margin telangiectasia
• Meibomian gland distortion, disruption, and dysfunction, which can lead to
recurrent chalazia.
• c/c conjunctivitis, marginal corneal infiltrates ,sterile ulceration,
episcleritis, or iridocyclitis.
• If properly treated, these lesions can resolve with few sequelae.
• Repeated bouts of ocular surface inflammation can cause corneal
neovascularization and scarring

59. CORNEA
 Affects inferior quadrant of cornea
 Punctate epithelial erosions
 Vascular invasion of the peripheral cornea with subepithelial infiltrates
 Progresses centrally and circumferentially –ulceration ,scarring and
perforation
• Limbal involvement – Nodular conjunctivits, Nodular scleritis

61. MANAGEMENT
• Systemic tetracyclines as the mainstay of therapy.
• Tetracyclines have anti-inflammatory properties that include suppression of
leukocyte migration, reduced production of NO and ROS, inhibition of
MMPs, and inhibition of phospholipase A2 and reduce irritative FFA and
diglycerides by suppressing bacteriallipases.
• With time, oral therapy with doxycycline or minocycline can be tapered.
• Oral tetracycline 250 mg QID for 6 – 8 weeks
• After that dosage to be tapered by 250 mg per week
• Tetracycline 250mg OD for a year before discontinuing

62. • Topical metronidazole 0.75% gel, metronidazole 1% cream, or azelaic acid
gel 15% to the affected facial areas reduce facial erythema.
• PUK can be ass w/ infectious agents in rosacea, or it may have a sterile
inflammatory etiology.
• Once it is ascertained that PUK is noninfectious, topical corticosteroids, used
in reducing sterile inflammation and enhancing epithelialization of the
cornea.
• In advanced cases with scarring and neovascularization, conservative
therapy is generally recommended.
• Penetrating keratoplasty is a high-risk procedure in rosacea patients; it may
result in a poor prognosis if the ocular surface is severely compromised.
• Light-pulse treatment may help reduce eyelid erythema.

63. RHEUMATOID ARTHRITIS
• Commonest systemic association
• Involves both eyes in 30% cases
• Tends to affect during late and advanced vasculitic phase
• Ass w/ all types of anterior scleritis including Diffuse, nodular, necrotizing
scleritis with inflammation and necrotizing scleritis without inflammation
(scleromalacia perforans), as well as posterior scleritis

64. • Corneal findings
 PUK
 Sclerosing keratitis(gradual thickening and opacification of corneal stroma
adjacent to site of scleritis)
 Acute stromal keratitis
 Limbal guttering
 Keratolysis
 Keratoconjunctivitis sicca

65. PATHOGENESIS
• Immune complex deposition in peripheral cornea and limbal vessels
• Chemotaxis of inflammatory cells
There are 2 types of PUK in RA
1)Paracentral
2)Peripheral
Paracentral keratolysis
• In patients with severe dry eye
• Mechanism – Altered epitheliumInflammatory mediators enter the
stromaStimulate a sterile keratolysis and a T cell infiltrate
• Progresses both centrally and circumferentially
• Unresponsive to topical therapy

66. 2.Peripheral keratolysis
• There is an obliterative Microangiitis at the level of limbal vascular arcades
• Deposition of Immune complexes in limbal vessels
• Causes an immune microangiopathy and obliterative microangiitis
• leakage of inflammatory cells and proteins
• collagenases and proteases are released by neutrophils
• corneal melting

68. Rheumatoid polyarthritis suspected in an HIV patient with scleritis
,peripheral ulcerative keratitis, and anterior uveitis by Domngang Noche
C1, Singwé-Ngandeu M2, Bella AL2
• 37/F
• K/c/o AIDS on ART for 3 years
• H/o c/c polyarthropathies x past 6 months
• Presented with RE- nodular scleritis
LE-PUK,necrotizing scleritis,granulomatous ant uveitis
• Ophthalmic workup- negative for opportunistic infections and potential
causes of scleritis and PUK
• Patient unresponsive to topical antibacterial and anti-inflammatory
treatment

69. • Sulfasalazine started
• Ocular lesion resolution and articular swelling improvement observed
in <6 weeks
• Based on American College of Rheumatology classification criteria,
and considering the good response to the treatment (sulfasalazine),
diagnosis of Rheumatoid Arthritis with ocular involvement was made
in the absence of confirmatory lab tests result.

70. Necrotising Scleritis and Peripheral Ulcerative Keratitis Associated with
Rheumatoid Arthritis Treated with Rituximab. By Hardy S1, Hashemi K1, Catanese
M1, Candil M2, Zufferey P2, Gabison E1, Guex-Crosier Y1.
• 3 cases of PUK ass/ w/ RA
• 2 patients - necrotising scleritis
• In the 2 patients who received the induction therapy with rituximab ,
good initial therapeutic response observed - stabilized from an ocular
standpoint as compared to patient on only high dose corticosteroid
• The patient who received only corticosteroid developed massive colon
perforation as well as acute renal insufficiency early on in the Rx course
• In patients receiving rituximab, eventually the drug had to be switched
to other molecules, either due to other systemic symptoms from the
disease itself or due to adverse effect of this treatment.
• This study contributes to other reports stating that rituximab can be an
effective treatment for refractory ocular complications in RA, at least as
an induction therapy.

71. WEGENER’S GRANULOMATOSIS(Granulomatosis with Polyangiitis)
• Multisystem necrotizing granulomatous vasculitic disease
• Common ophthalmic manifestations-Usually bilateral
 Orbital involvement with proptosis
 PUK
 adjacent necrotizing scleritis
 Sometimes conjunctivitis or episcleritis
PUK
• can be the initial clinical manifestation
• May be the presenting or only sign of the disease.
• Crescentic peripheral corneal ulcer that resembles Mooren’s ulcer
• Scleral involvement is invariably present C/F from Moorens

72. HISTOPATHOLOGY
• Lymphocytes and plasma cells predominate the substantia propria
• Sclera and episclera may show a Granulomatous reaction with epithelioid
cell and giant cells
• Areas of active collagen degradation can be seen
p ANCA testing is positive
MANAGEMENT
Systemic immunosuppression with cyclophosphamide and steroids

73. Peripheral Ulcerative Keratitis Associated with Granulomatosis with
Polyangiitis Emerging Despite Cyclophosphamide, Successfully Treated with
Rituximab. By Fujita Y1, Fukui S1,2, Endo Y1, Tsuji S1, Takatani A1, Shimizu T1, Umeda M1,3, Nishino A1,4, Koga
T1,5, Kawashiri SY1,2, Iwamoto N1, Ichinose K1, Tamai M1, Nakamura H1, Origuchi T1,6, Ueki R7, Uematsu M7, Ishida K8, Abe
K8, Kawakami A1.
• 67/M
• K/c/o GPA (right maxillary sinusitis, proteinase 3 ANCA positivity)
• RE scleritis
• A conjunctival biopsy specimen -neutrophil-predominant infiltration around
the vessels without granuloma
• Pulsed methylprednisolone and IV cyclophosphamide pulse therapy
started.

74. • However, it was ineffective, and PUK newly emerged.
• Promptly switched the patient from IVCY to rituximab, which controlled
ocular disease
• Amniotic membrane transplantation.

75. A case report of the orbit, ocular association and the lung in granulomatosis
with polyangiitis: A diagnostic challenge. By Lu CW1, Liu XF1, Luan Y1, Lu CB2, Zhou
DD3, Guo LM1, Sun YB1, Chen SN1, Wu YL1, Hao JL1.
• 40/F
• Progressive worsening pain, redness and gradual decrease in VA in the BE x
7 years
• Previous therapeutic interventions - noncompliant topical and IV
dexamethasone x 6 years.
• H/o asymptomatic space-occupying lesion in the right middle lung, which
was surgically removed 4 months back
• 1 month later,h/o surgical removal of Left orbital mass
• Diagnosed as PUK ass w/ GPA

76. • Corneal lesions were then treated bilaterally with cryotherapy and oral
prednisone and cyclophosphamide were administered.
• Following surgery, Condition of the eyes appeared to be stable.
• 7 months later, the redness and pain of the right eye recurred, followed by a
deep lamellar keratoplasty for the treatment of necrotizing scleritis.
• The condition of 2 eyes was subsequently observed to be stable during the 9
month follow-up.
• Thus,GPA must be considered in D/d of inflammatory conditions and tumors
• Early diagnosis and an appropriate interdisciplinary approach to
management, are required to decrease recurrence and morbidity in patients
with GPA-mediated inflammatory ocular disease.

77. Successful Treatment Strategies in Granulomatosis With Polyangiitis-
Associated Peripheral Ulcerative Keratitis. BYEbrahimiadib N1, Modjtahedi
BS, Roohipoor R, Anesi SD, Foster CS.
• Patient database of Massachusetts Eye Research and Surgery Institution
was searched from 2005 to 2015 to identify patients of PUK w/ GPA.
• 16 patients mean follow-up of 64 months duration
• Rituximab and cyclophosphamide, either alone or in combination with other
agents- most successful agents in controlling inflammation.
• Rituximab in 11 patients with remission being achieved in all (100%)
• Cyclophosphamide successfully controlled inflammation in 50% (5/10).

78. • 2 patients (2/5, 40%) who had achieved initial control on cyclophosphamide
had flares of their PUK.
• 2 patients (2/11, 18%) patients on rituximab had flares of scleritis and
orbital inflammation but not PUK.
• 2 patients, 1 in each treatment group, stopped treatment after achieving
remission after 6 months of therapy but suffered disease recurrence within
2 months of treatment cessation.
• Rituximab achieved a high rate of disease control in PUK patients with GPA
and is the preferred agent in halting disease progression.

79. Surgical treatment of peripheral ulcerative keratitis and necrotizing scleritis
in granulomatosis with polyangiitis. By Lu CW1, Zhou DD, Wang J, Hao JL
• 70/M
• progressively worsening pain and redness RE x 6 months, and decreasing VA
x 1 month
• Was misdiagnosed and treated as keratitis elsewhere, but pain had not
decreased.
• Diagnosis of necrotizing scleritis with PUK in GPA made
• Surgery was performed with necrotic tissue removal, combined with
cryotherapy and a conjunctival flap covering surgery.
• Symptoms relieved after surgery, and the patient's ocular condition
remained stable thereafter.
• This case first demonstrates limited ophthalmic GPA (such as, PUK and
necrotizing scleritis) that was not aggravated can be successfully treated by
combined surgical interventions.

80. POLYARTHRITIS NODOSA
 PUK morphologically similar to Mooren’s ulcer with the central overha
nging edge may be present.
 Usually associated adjacent necrotizing scleritis is present.

81. Rapid corneal thinning and perforated ulcerative keratitis in a patient
with relapsing polychondritis by Lai THT1, Far N2, Young AL1,2, Jhanji V2,3.
• 43 Male
• K/c/o relapsing polychondritis w/ b/l scleritis, b/l swelling of pinna,
saddle nose and tracheal stenosis.
• Right eye pain and redness x 1 month.
• O/E- 80% peripheral corneal thinning b/w 3 and 7 o'clock in RE
• 1 week of oral corticosteroid use
• The degree of corneal thinning worsened to 90%
• Subsequently,
topical cyclosporine 2% eye drops QID,
oral doxycycline 100 mg BD
oral vitamin C 2 g OD added
• Corneal thinning improved to 60%.

82. • Patient rapidly tapered oral prednisolone against medical advice-
returned with an a/c drop in vision in RE.
• On Slit lamp -peripheral corneal perforation with iris prolapse.
• Emergency repair with cyanoacrylate glue.
• IV methylprednisolone 1 mg/kg body weight x3 days and 1 g/day and
IVIG every 4 weeks.
• 3 months postop, a well-formed anterior chamber with glue in situ.

83. Gout Keratitis: A Case of Peripheral Ulcerative Keratitis Secondary to Gout
With a Review of the Literature. byYazdanyar A1, Rizzuti AE, Mechel E, Denisova
K, Lazzaro DR.
• 41/ M / k/c/o severe gout disease
• Pain and redness of RE
• O/E-2 areas of peripheral corneal thinning with overlying epithelial defects.
Adjacent to these areas, reflective crystals identified in the corneal stroma.
• AS-OCT demonstrated stromal corneal deposits.
• Systemic workup was negative aside from an elevated serum uric acid level.
• The patient was administered oral prednisone, allopurinol, and colchicine.
• 2-month follow-up visit, the patient was asymptomatic and
his corneal thinning had significantly improved.
• Crystal deposition in the cornea is extremely rare and may be a cause
of peripheral ulcerative keratitis.

84. Peripheral ulcerative keratitis associated with chronic malabsorption
syndrome and miliary tuberculosis in a child byTarun Arora, Namrata
Sharma,1 Adarsh Shashni, and Jeewan S. Titiyal
• 16/F
• Pain, redness, watering, and blurring of vision RE
• O/E RE PUK and nodular scleritis.
• Systemic examination-stunted growth, low BMI, enlarged axillary nodes.
• Giardia cysts in the stool sample
• Histopathology of axillary lymph nodes showed caseating necrosis s/o TB
• Diagnosed as PUK with c/c malabsorption syndrome secondary to
giardiasis and miliary TB
• Oral metronidazole, anti-tubercular treatment, high protein diet and
vitamin supplements were started.
• Topical steroids were started for peripheral ulcerative lesions following,
which the PUK resolved.

85. Peripheral Ulcerative Keratitis Secondary to Chronic Hepatitis B Infection. By
Wei DW1, Pagnoux C, Chan CC.
• 52/Female
• RE eye pain and photophobia
• Arthralgia, remnants of a maculopapular rash, subsequently facial numbness
several weeks later.
• BCVA in RE 20/80.
• Slit-lamp examination -severe superior corneal thinning without infiltrate.
• Corneal ulceration worsened until 10% of the cornea remained.
• Laboratory workup was positive for rheumatoid factor and revealed
significantly decreased C4 complement, and HBV serology was positive.

86. • Clinical history, examinations, and laboratory results suggest HBV-associated
cryoglobulinemia and vasculitis.
• Management included prednisone, cyclophosphamide, and mycophenolate
mofetil for immunosuppression and tenofovir for HBV treatment.
• Conjunctival resection and a glue patch were used to reduce inflammation
and stabilize corneal melt.
• BCVA improved after treatment was initiated.
• Two years after initial presentation, her BCVA is 20/30, significantly improved
from her vision at presentation.

87. Peripheral Ulcerative Keratitis Associated with HCV-Related
Cryoglobulinemia. By Coelho P1, Menezes C2, Gonçalves R1, Rodrigues P1, Seara E1.
• 36/M
• H/o Hepatitis C and IV illicit drug abuse
• moderate pain ,redness and photophobia in RE.
• O/E BCVA RE - 20/30
• slight discomfort with eye movement.
• Ring shaped peripheral corneal ulcer, with a dense white stromal
infiltrate sparing the limbus, plus an adjacent area of mild anterior
diffuse nonnecrotizing scleritis.
• No intraocular inflammation was present.
• Posterior segment was normal.

88. • oral prednisolone (1 mg/Kg/day) with gradual tapering.
• A dramatic clinical response occurred, with complete resolution of the
clinical condition
• Systemic analytic workup aiming at autoimmune and infectious diseases
was negative, except for high HCV-viral load and the presence of type 2
cryoglobulins.

89. Contact lens wear
• reduces the amount of O2 available to the cellular components of cornea
• Less tear flow under contact lens than which will normally pass over
cornea
• may increase the temperature of the cornea
• the insertion and removal of lenses may produce regions of microtrauma
to the corneal surface, limbus, and adjacent conjunctiva.
• Soft contact lenses worn overnight,risk of a corneal infection is increased.
• Fequently, patients will not change or clean their contact lens storage
cases, which can harbor bacteria and other microorganisms.
• certain systemic diseases, such as diabetes and other diseases that slow
tissue healing, can increasthe risk of ocular infections.
• Dry eye and lagophthalmos serve to compromise the ocular surface.
When these conditions are present in an individual who also wears contact
lenses, the risk of microbial keratitis increases significantly.

90. Mooren Ulcer in a Child Wearing Orthokeratology Contact Lenses. BY Kim
J1, Kim MK, Wee WR, Oh JY.
• 10/M
• Referred for progressive peripheral corneal ulcer RE, despite intensive
use of fortified antibiotic eye drops.
• H/o overnight orthokeratology lenses x 4 months before presentation
of corneal ulcer.
• No other history of ocular or systemic trauma and disorders.
• Microbiological tests of the lesion were negative.
• Systemic evaluation showed no sign of rheumatologic disease.
• Under a diagnosis of Mooren ulcer, the patient was treated with topical
and systemic corticosteroids.
• After four weeks of treatment, the patient's symptoms rapidly
disappeared, and corneal ulcer was healed.
• Vision recovered to normal with the correction of with-the-rule
astigmatism.

91. Case-Control Pilot Study of Soft Contact Lens Wearers
With Corneal Infiltrative Events and Healthy Controls. By Richdale K1, Lam
DY2, Wagner H3, Zimmerman AB4, Kinoshita BT5, Chalmers R6, Sorbara L7, Szczotka-Flynn
L8, Govindarajulu U1, Mitchell GL4.
• Purpose :To assess risk factors associated with soft contact lens (SCL)-
related corneal infiltrative events (CIEs).
• Single-visit, case-control study
• 30 Cases defined as current SCL wearers w/ a symptomatic CIE.
• For each case, 3 age- and sex-matched controls were enrolled(90 controls )
• 13 to 31 years of age
• Subjects supplied a recent health history ,completed the Contact Lens
Risk Survey , a standardized scripted medical interview,, and underwent
an ocular examination.
• Microbial culturing of the ocular surface, SCL, and lens storage case was
conducted for all cases.

92. • CIE diagnosis included contact lens-associated red eye,
infiltrative keratitis, and contact lens peripheral ulcer.
• Subjects with symptomatic CIEs more likely to harbor substantial levels
of gram-negative bioburden on the ocular surface and contact lens.
• Significant risk factors for developing a CIE were overnight wear of
SCLs, use of multipurpose solution, rinsing SCLs with water, lens
storage case older than 6 months, previous "red eye" event, use of
ocular drops in the past week, and illness during the past week.
• A larger sample size is needed to determine relationships between
patient-reported behaviors and exposures, microbial bioburden, and
CIE development.

93. Peripheral Ulcerative Keratitis following Laser in situ Keratomileusis. By
Burkholder BM1, Kuo IC1.
• 28/M underwent LASIK
• h/o glomerulonephropathy, not disclosed prior
• Developed severe postop PUK soon after surgery
• Within a week of surgery developed diffuse lamellar keratitis (DLK) not
contiguous with PUK
• Microbiologic evaluation of the flap interface disclosed no organisms, and
no epithelial ingrowth was found.
• Both PUK and DLK resolved with topical and oral steroid therapy, and the
patient's induced refractive error improved over the 12 months following
LASIK.
• This case demonstrates importance of diligent history taking to exclude
autoimmune disorders or atypical postinfectious sequelae prior to
proceeding with keratorefractive intervention.

94. GIANT CELL ARTERITIS

95. Infectious Disorders of the Peripheral Cornea
• As peripheral cornea is adjacent to the rich vascular supply of the limbus, the
limbal lymphatic tissue, and inflammatory cells, microbial keratitis maybe
thought to be less frequent than in the central cornea.
• However, other factors increase the likelihood of a peripheral corneal infection.
Bacterial keratitis
• occurs in the inf third of the cornea, could be secondary to corneal exposure.
• This should especially be considered in an individual who has suffered multiple
ocular infections.
• Significant pain
• Markedly hyperemic bulbar conjunctiva
• Quicly progress to perforation –w/in 24-48 hours
• May be Ass w/ uveitis- dense flare and cells , hypopyon

96. Common organisms
• St aureus ,St epidermidis
• Streptococcus pneumoniae and other strs
• Pseudomonas aeruginosa (soft contact lens
wearers)
• Enterobacteriaceae(proteus, Enterobacter)
• Moraxella spp
Uncommon organisms
– Neisseria spp
– Listeria
– Mycobacterium spp
– Nocardia spp
– Non-spore-forming anaerobes
– Corynebacterium spp
– Haemophilus influenzea
– Chlamydia trachomatis
Intact coneal Keratitis
• N. gonorrhoeae
• N. meningitidis
• C. diphtheriae
• H. influenzae
• Shigella

97. Staphylococcal ulcer
• Well defined
• Gray-white stromal infiltrate
Streptococcal
• Infiltrate purulent
• Severe AC reaction
• Hypopyon formation
Pseudomonas
• Rapidly progressive
• Suppurative
• Necrotic infiltrate
• Ass w/ a hypopyon and mucopurulent discharge

98. Presentations:
• Rapid onset of pain
• Decreased vision
• Photophobia
• Discharge
• Eyelid edema
Signs:
• Conjunctival injection
• White stromal infiltrate associated with an overlying epithelial defect and
secondary anterior uveitis
• Enlargement of stromal infiltration associated with stromal oedema
• Severe infiltration and hypopyon formation
• Corneal perforation and endophthalmitis in neglected cases

99. Investigations
Corneal scraping and culture
• Blood agar : most bacteria & fungi except Neisseria, Hemophilus & Moraxella
• Chocolate agar : Neisseria, Hemophilus, Moraxella
• Sabouraud dextrose agar : fungi
• Non nutrient agar : Acanthamoeba
• Brain Heart Infusion : Streptococci and Meningococus
• Löwenstein-Jensen : Mycobacteria and Nocardia
Staining
• Gram : Bacteria, fungi, Microsporidia
• Giemsa : Bacteria, fungi, Acanthamoeba, Microsporidia
• Calcofluor white : Acanthamoeba, fungi, Microsporidia
• Acid-fast stain : Mycobacterium, Nocardia
Conjunctival swabs : Severe cases and corneal scraping is negative
Contact lens cases

100. • Rx
1.Fortified topical /periocular injection of antibiotics
 GRAM POSITIVE (Staphyloccus, Strep. Pneumoniae)-semi synthetic Penicillin,
Vancomycin,Cephalosporin,Bacitracin
 GRAM NEGATIVE (Pseudomonas aeruginosa)-Gentamicin, Tobramycin,
Carbenicillin, Colistin, Polymyxin B
Monotherapy;
– Fluoroquinolone (Ciprofloxacin 0.3% or ofloxacin 0.3%
2.Mydriatic –Cycloplegic Prevent synechiae due to accompanying Seveere uveitis
3.Anti-Collagenase compounds- decrease corneal melting
4. Lateral, medial, or both types of tarsorrhaphy may be required to protect the
ocular surface and prevent subsequent episodes of infectious keratitis.

101. • Microbial keratitis from syphilis or TB can produce peripheral corneal
changes
• Syphilis ass w/ a deep corneal inflammation with deep vessels in the
peripheral cornea.
• TB produces an a/c inflammation that is more commonly u/l and involves
peripheral sectoral portions of the anterior cornea.

102. Ocular syphilis masquerading as bilateral peripheral ulcerative keratitis. By
Vignesh AP1, Srinivasan R1, Vijitha S1.
• 55/M
• recurrent pain and redness BE X 2 months.
• BE had b/l peripheral crescent-shaped corneal ulcers suggestive of PUK.
• The patient was started on topical steroids elsewhere, but lesion was not
showing any signs of healing.
• A series of investigations performed- positive VDRL and fluorescent
treponemal antibody absorption tests.
• Started on systemic penicillin, as well as topical steroids.
• The response to the treatment was good and the ulcer began to heal.

103. Fungal Keratitis
• Less common than BK
• 5%-10% of corneal infections
• May have devastating effects
• severe stromal necrosis
• may enter AC by penetrating intact Descemet membrane
• difficult control because poor penetration of antimycotic agents.
• Filamentous fungal : Asprgillus vs Fasarium
• Non Filamentous or Yeast : Candida
Predisposing factors :
c/c ocular surface disease, long-term use of topical steroids,Contact
lens wear, systemic immunosuppression, diabetes,vegetable matter

104. Presentation
Gradual onset of FB sensation, Photophobia,Blurred vision,Discharge
Signs
Filamentous keratitis
• Greyish-white infiltrate with indistinct feathery margins.
• Often surrounded by finger-like satellite stromal infiltrates
Candida keratitis
•Yellow-white infiltrate
• dense suppuration
• similar to bacterial keratitis

105. Investigations
• Staining
- Gram and Giemsa staining
- Periodic acid-Schiff (PAS)
• Culture
- Sabouraud dextrose agar
- on blood agar or in enrichment media.
- contact lenses
• Corneal biopsy
- is indicated in the absence of clinical improvement after 3–4 days
- if no growth develops from scrapings after a week.

106. Management
• Removal of the epithelium
• Topical treatment : hourly for 48 hours
- Candida : amphotericin B 0.15% or econazole 1%;or natamycin 5%, or
fluconazole 2%, or clotrimazole 1%
- Filamentous infection : natamycin 5% or econazole 1%; or
amphotericin B 0.15% or miconazole 1%.
• A broad-spectrum antibiotic
• Cycloplegia
• Subconjunctival fluconazole
• Systemic antifungals lesions are near the limbus, or for suspected
endophthalmitis
• Superficial keratectomy
• Therapeutic keratoplasty

107. Herpes simplex and zoster
• can develop peripheral corneal ulcers that do not exhibit typical dendrite
formation.
• Instead, they develop an irregular epithelium or epithelial defect over the
affected area, followed by a region of stromal haze that assumes a
crescent shape adjacent to the limbus.
• The associated limbus is typically hyperemic and the eye is painful.
• Herpes simplex and zoster may also produce a sterile or an infected
neurotropic ulcer
• Therefore, corneal sensation should always be tested in patients who
experience little pain in association with a corneal ulcer.
• Treatment is directed at healing the ulcer and protecting the ocular
surface with a tarsorrhaphy.
• A scleral contact lens may protect the corneal surface once the ulcer is
healed.

112. Actinobacillus actinomycetemcomitans Keratitis After Glaucoma Infiltration
Surgery: A Clinical Report and Literature Review. BY Hong J1, Xu J, Cao W, Ji J, Sun X
• 56/M / Long-standing h/o open-angle glaucoma BE
• h/o ocular pain, redness, blurred vision RE x 12 weeks
• h/o Glaucoma infiltration surgery RE x 6 months ago.
• 3 months postop, developed peripheral corneal stromal opacities ass w/ a
white, thin, cystic bleb, conjunctival injection.
• These opacities grew despite topical treatment w/ topical tobramycin,
levofloxacin, natamycin, amikacin, metronidazole eye drops.
• Multiple corneal scrapings revealed no organisms
• Aerobic, anaerobic, fungal, or mycobacterial cultures negative

113. • RE developed a severe purulent corneal ulcer with a dense hypopyon and
required corneal transplantation.
• Histopathologic analysis and 16S ribosomal RNA PCR sequencing revealed A
actinomycetemcomitans as the causative organism.
• Postop, treatment was initiated with topical levofloxacin and cyclosporine,
as well as oral levofloxacin and cyclosporine.
• Graft and host corneal transparency were maintained at the checkup 1
month after surgery.
• Although it is a rare cause of cornealdisease, A actinomycetemcomitans
should be suspected in patients with keratitis refractory to topical antibiotic
therapy
• Delay in diagnosis and appropriate treatment can result in vision loss.

114. Differential Diagnosis
1.Marginal keratitis ass w/ blepharitis
2.Pellucid marginal degeneration
3. Terrien’s marginal degeneration
4.Furrow degeneration

115. Local inflammatory causes
• Staphylococcus marginal ulcers, which begin with an infiltrate adjacent
to the limbus separated by a characteristic clear zone with progression to
ulceration
• Rosacea-associated blepharo-conjunctivitis which may result in a
peripheral keratitis with or without a clear zone.
Non inflammatory cause of thinning of the peripheral cornea
Terrien’s marginal degeneration, pellucid marginal degeneration, and
marginal furrow
can be distinguished from PUK due to lack of inflammation and typically an
intact epithelium

116. Pellucid marginal corneal degeneration
Unknown etiology
 Inferior peripheral corneal thinning and protrusion
Point of greatest protrusion is just above the area of maximal thinning
Absence of inflammation
The involved area is clear, and usually no iron line occurs central to it.
Marked against-the-rule astigmatism-Decreased vision
Rx-
 Contact lenses
 Penetrating Keratoplasty
 Wedge resection
 Lamellar Tectonic grafts
 Collagen Cross linking

117. Terrien’s degeneration
• Uncommon idiopathic thinning and ectasia of superior peripheral cornea
• Arcuate lipid deposition and vascularisation in pts aged >40 yrs
• 75% Male After 4th decade ,Usually B/l
• Initially asymptomatic
• Lack of inflammation or epithelial defect
• Presence of sup vascularization and advancing linear deposition of lipid
• Slow progressive course
• No known systemic disorders occur with terrien’s marginal degeneration
• Associated with VKC

118. • Mild, fine yellow white ,punctate, sub-epithelial or anterior stromal
opacities
• Peripheral, superficial, fine vascular pannus which start superiorly, spread
circumferentially and progresses over years
• Linear sub-epithelial opacity at the advancing edge
• The thinning slowly begins between the limbus and the line of lipid
deposition and is separated from limbus by clear zone
• Typically, a steeper sloping of the cornea occurs at the advancing edge.
• Gradual vision disturbance due to increasing corneal astigmatism
• Pseudopterygia in long standing cases
With increased corneal thinning -> ectasia
Can perforate after trauma

119. HISTOPATHOLOGY
• Fibrillar degeneration -Bowman’s Layer and stromal lamellae
• Cornea thinner with appearance of a subepithelial pannus
Rx
• Spectacles
• Contact lens-scleral lenses or soft lenses with RGP piggybacking
• Tectonic corneal grafting
• Topical lubricants and mild topical steroids

121. Blood derived eye drops for the treatment of cornea and ocular surface diseases. By
Giannaccare G1, Versura P2, Buzzi M3, Primavera L2, Pellegrini M2, Campos EC2.
• Use of blood derived eye drops for the Rx of ocular surface disorders, mainly dry eye
disease, persistent corneal epithelial defect, corneal ulcer, ocular surface burn,
recurrent corneal erosion and limbal stem-cell deficiency has become increasingly
popular in recent years.
• MOA -stimulation of cellular proliferation and migration by supplying an active mixture
of growth factors and cytokines at the ocular surface, thus mimicking function of the
lacking natural tears
• Autologous serum (from the patient’s own peripheral blood) is the first introduced and
most commonly used product. Despite several RCT showed its safety and efficacy, a
recent Cochraine meta-analysis failed to show significant results due to low evidence.
• Homologous serum sources including allogeneic serum obtained from healthy donors,
and umbilical cord blood serum collected at the time of delivery, are efficient
alternatives, especially when autologous serum therapy is C/I or not appropriate.
• Platelet-derived eye drops are prepared and used in various standardized preparations
like platelet-rich plasma, plasma rich in growth factors, and platelet lysate.
• Future perspectives include the introduction of tailored eye drops, screened for the
proper content of growth factors and cytokines according to each patient and ocular
surface disease.

122. CONCLUSIONS
• Diagnosis of peripheral ulcerative keratitis requires thorough history
and physical examinations given the numerous causes.
• Prompt treatment including immunosuppressive medication and
sometimes antimicrobial medication is crucial to preventing serious
visual consequences including corneal perforation and blindness

123. References:
1. Cornea- fundamentals, diagnosis and management by Krachmer
2. Myron Yanoff and Jay S. Duker
3. Post-graduate ophthalmology by Zia Chaudhari
4. Corneal disorder by Leibowitz
5. External Diseases and Cornea –AAO Series