Dissertation on

A RETROSPECTIVE AND PROSPECTIVE STUDY ON MOOREN’S ULCER

Submitted in partial fulfilment of requirements of

M.S. OPHTHALMOLOGY

BRANCH-III

REGIONAL INSTITUTE OF OPHTHALMOLOGY

MADRAS MEDICAL COLLEGE

CHENNAI-600003

THE TAMILNADU DR.M.G.R. MEDICAL UNIVERSITY

CHENNAI

APRIL 2015

CERTIFICATE

This is to certify that this dissertation entitled

“A RETROSPECTIVE AND PROSPECTIVE STUDY ON MOOREN’S

ULCER” is a bonafide record of the research work done by Dr. R.G.

RACHEL., Post graduate in Regional Institute of Ophthalmology,

Madras Medical College and, Government General Hospital, Chennai-03.

In partial fulfilment of the regulations laid down by The Tamil Nadu

Dr.M.G.R. Medical University for the award of M.S. Ophthalmology

Branch III, under my guidance and supervision during the academic

years 2012-2015.

Dr. K. NamithaBhuvaneshwari, M.S.,D.O Director and Superintendent, Chief, cornea and contact lens services, Regional Institute of Ophthalomology, Government Ophthalmic Hospital, Chennai-600008

Dr. K. NamithaBhuvaneshwari, M.S.,D.O Director and Superintendent, Chief, cornea and contact lens services, Regional Institute of Ophthalomology, Chennai-600008.

Dr. R. Vimala, M.D.,

Dean,

Madras MedicalCollege,

Chennai-600003.

DECLARATION BY THE CANDIDATE

I hereby declare that this dissertation entitled

“A RETROSPECTIVE AND PROSPECTIVE STUDY ON

MOOREN’S ULCER” is a bonafide and genuine research work carried

out by me under the guidance of Prof.Dr.K. NAMITHA

BHUVANESHWARI., M.S.,D.O.

DATE:

PLACE: Dr.R.G.RACHEL

ACKNOWLEDGEMENT

I express my sincere thanks and gratitude to

Prof. DR. R. VIMALA, M.D., Dean, Madras Medical College for

permitting me to conduct this study.

I have great pleasure in thanking Professor DR. K. NAMITHA

BHUVANESHWARI, M.S., D.O., Director and Superintendent

RIO- GOH, Madras Medical College, Chennai, for her valuable advice in

preparing this dissertation.

I am very grateful to my unit chief and assistant professor,

Prof.Dr. M.R.Chitra, M.S., Dr.K.S.T.Latha, M.S., for rendering their

valuable advice and guidance for this study.

I wish to express my sincere thanks to all my professors, assistant

professors and all my colleagues who had helped me in bringing out this

study.

Finally, I am indebted to all the patients for their sincere

co-operation for the completion of this study.

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INDEX

S. NO TITLE PAGE NO

PART I

1. INTRODUCTION 1

2. ANATOMY 3

3. MOOREN’S ULCER 9

4. DIFFERENTIAL DIAGNOSIS 14

5. OCULAR EXAMINATION AND LABORATORY INVESTIGATIONS

19

6. MANAGEMENT 20

7. REVIEW OF LITERATURE 30

PART II 41

1. AIMS AND OBJECTIVES 42

2. MATERIALS 44

3. METHODOLOGY 47

4. RESULTS 60

5. DISCUSSION 86

6. SUMMARY 97

7. CONCLUSION 101

PART III 103

1. BIBLIOGRAPHY 104

2. PROFORMA 111

3. MASTER CHART 117

PART 1

1

INTRODUCTION

2

INTRODUCTION

Mooren’s ulcer is a rare degenerative superficial ulcer which

occurs at corneal margin and its etiology is unknown. It is also as called

chronic serpiginous ulcer or ulcus serpens. It is an idiopathic, painful

relentlessly progressive,chronic ulcerative keratitis begins peripherally

and progresses circumferentially and centrally. It is not associated with

scleritis or systemic involvement.

It was first described by Bowman in 1849 and in 1854, Mckenzie

defined it as a clinical entity. The types of Mooren’s ulcer were described

by Wood and Kaufman.

3

ANATOMY

4

ANATOMY OF CONJUNCTIVA

The conjunctiva has three layers, the epithelial layer, the adenoid

layer and the fibrous layer. The latter two are together called the

substantia propria of conjunctiva. The epithelial layer is made of varying

layers of squamous epithelium along with goblet cells, few melanocytes

and Langerhan cells. The Langerhan cells are responsible for antigenic

presentation, lymphokine and prostaglandin production, T lymphocyte

stimulation and allograft rejection. The next layer is the adenoid layer,

otherwise called as lymphoid layer. It contains lymphocytes which

develops at 2-3months of age which is responsible for follicular reaction.

The fibrous layer has meshwork of collagen and elastin fibres.

ANATOMY OF CORNEA

Cornea is an avascular structure. Together with sclera it forms the

outermost wall of the eye constituting about 1/6th of the outer wall. It is

exposed to the external environment and allows the entry of light. It has

interwoven fibrous collagen that provides mechanical strength thereby

protecting the ocular contents from physical damage and maintaining the

ocular contour. The corneal epithelium has inter-digitation of cell

5

membranes and junctional complexes like tight junctions and

desmosomes and it forms an effective mechanical barrier.

The anterior corneal surface is aspheric and convex. It is covered

by tear film and the posterior corneal surface is lined by aqueous humour.

At the junction of cornea and sclera is the highly vascularised limbus

which has pluripotent stem cells. Cornea is transversely oval due to

scleralisation superiorly and inferiorly. Cornea derives nutrients from

blood components from both external and internal carotid artery. Anterior

ciliary artery from ophthalmic artery anastomosis with facial artery of

external carotid artery providing blood components. They also help in

wound healing and corneal metabolism.

The cornea has five layers, three cellular layers and two interfaces.

Epithelium, Bowman’s membrane, Stroma (subtantia propria),

Descemet’s membrane and Endothelium. The types of cells present in

cornea are epithelial cells, corneal fibroblasts(keratocytes) and

endothelial cells. The corneal epithelium is made of non-keratinised

stratified squamous epithelium. It has five to six layers and is made up of

superficial cells, wing cells and columnar basal cells. The basal cells

6

proliferate and migrate anteriorly. The tight junctions (zonula occludens)

between superficial cells and hemi-desmosomes (zonula adherens) and

desmosomes between cells in all layers provide effective barrier function

to cornea. Cornea is immune privileged. Dendritic langerhan cells are

present only in the peripheral corneal epithelium normally. In case of

injury to central cornea,they migrate centrally.

Between the epithelium and the stroma is the Bowman’s

membrane. It has a random arrangement of proteoglycans and collagen

types I and III. They are synthesized by stromal keratocytes. They do not

regenerate after injury.The stroma constitutes 90% of corneal thickness.

It is composed of collagen fibres (types I, III and V) and keratocytes.

These keratocytes are quiescent but can be readily activated by various

types of insults to myofibroblasts. They produce Extra Cellular Matrix,

collagen degrading enzymes, matrix metalloproteinases and cytokines

which help in tissue repair.

Descemet’s membrane is the basement membrane of endothelium

and is divided into anterior banded zone and posterior non-banded zone.

It mainly contains collagen type IV and VIII and fibronectin. A single

7

layer of endothelial cells line the Descemet’s membrane and is arranged

in a mosaic pattern. These cells are metabolically active.

ANATOMY OF LIMBUS

Limbus refers to circumcorneal transition zone of conjunctivo-

corneal and corneo-scleral junction. At conjunctivo-corneal junction, the

bulbar conjunctiva is firmly adherent to underlying structure. The

substantia propria of conjunctiva ends here but the epithelium of

conjunctiva continues with that of cornea. The epithelial layer here is

several layers thick,irregularly arranged, and has melanin. At sclero-

corneal junction, the corneal lamellae continues with that of sclera

lamellae.

IMMUNOLOGICAL CHARACTERISTICS OF OCULAR

SURFACE

The lymphocytes of conjunctiva are similar to the mucosa

associated lymphoid tissue (MALT) present in GIT and respiratory

system. Human mucosal lymphocyte-1 is present in conjunctiva, limbus

and the lacrimal gland. The epithelial layer of conjunctiva has

8

lymphocytes in interspersed manner which are usually cytotoxic T cells,

whereas the stroma has cytotoxic Tcells, helper T cells and small

population of B cells. These lymphoid tissues acquire and process the

antigens and they themselves become activated to lymphoblasts. These

lymphoblasts travel to local lymph nodes, preauricular and

submandibular nodes. They then travel back to ocular surface by

unknown mechanism where the local antibody production occurs.

From immunological point of view cornea has immunoglobulins

like IgG, IgA, complement components like C3, C4, C5 probably due to

diffusion from the limbal blood vessels. Near the limbus higher

concentration of Ig M, C19 and Langerhan cells are present.

9

MOOREN’S ULCER

10

MOOREN’S ULCER

CLINICAL FEATURES

Mooren’s ulcer is a localised disease of cornea characterised by

chronic ulceration. It is generally more common in males probably due to

higher incidence of trauma in males. It presents with pain, watering,

redness and photophobia. The pain is out of proportion to inflammation.

It initially presents with patchy peripheral stromal infiltrate in the

interpalpebral area in the medial and lateral quadrant which later

coalesce. This is followed by loss of epithelium and stromal thinning

which spreads deep up to the level of Descemet’s membrane and also

spreads circumferentially and centrally. The central margin is

overhanging, the undermined edge extending about 1-4mm inwards and

the periphery extends up to limbus. Some parts of the ulcer maybe active

and some maybe inactive. The active areas do not have epithelium over

them and stains with fluorescein. The stromal thinning may extend from

one-third to three-fourths depth and is associated with superficial

vascularisation. The affected cornea re-epithelises and scars. In severe

and rare cases it leads onto perforation. The natural course of ulcer is

from 3 months to 1 year.

11

ETIOLOGY

It is mainly idiopathic. There are certain hypothesis suggesting the

relationship between Mooren’s and corneal injury either due to surgery,

inflammation or trauma (physical or chemical) which alters the corneal

antigen and elicits an immunological response. Association with

Helminthic³ infection is noted where there is immunological reaction to

Helminth related antigen in cornea or corneal antigen altered by

Helminth infection may trigger an autoimmune response. Bilateral

Mooren’s found associated with Hepatitis C infection were found to

improve with interferon alpha therapy which maybe due to molecular

mimicry. Other associations reported are TB, Syphilis, Salmonella,

foreign body, burns, HSV, HZV.

12

PATHOLOGY

It is mainly an autoimmune process which stimulates both cell

mediated and humoral immunity. In cell mediated immunity against

corneal antigens, there is decrease in suppressor T cells with unregulated

increase in helper T cells. This leads to increase in antibodies, immune

complex and increased complement activation. All these lead to

deposition of plasma cells, neutrophils, mast cells and eosinophils in the

adjacent conjunctiva with production of proteases and collagenases

which digests the collagen and proteoglycan which is responsible for

tissue destruction. There is increase in circulating antibodies against

corneal and conjunctival tissue, tissue fixated antibodies and complement

in conjunctiva. Recurrences are noted in corneal transplants due to a

phenomenon called anamnesis.

The histopathology of Mooren’s ulcer shows epithelium and

Bowman’s to be absent. The stroma exhibits three zone. The superficial

stroma has plasma cells, lymphocytes with vascularisation and

destruction of collagen matrix. The mid-stroma has hyperactive fibroblast

and disorganised corneal lamellae. The deep stroma has macrophages.

The Descemet’s membrane and endothelium are intact. The leading edge

13

has predominance of neutrophils. The adjacent conjunctiva has heavy

infiltration with plasma cells and lymphocytes

TYPES

Mooren’s ulcer is divided into two types as follows. The type I or

benign type is more common, 75% unilateral, occurs in patients >40yrs,

with mild to moderate symptoms, slowly progressive, good response to

treatment. Perforation is uncommon. Type II or malignant type is

relatively uncommon, occurs in young patients of 20-30yrs of age,75%

are bilateral and they have severe pain, rapid progression and poor

response to treatment. Perforation occurs in one-third of the patients with

association with trauma or Helminthiasis.

Type I or benign Type II or malignant

More common,typical; Uncommon

75% unilateral 75% bilateral

>40yrs 20- 30 yrs

Mild to moderate symptoms Severe symptoms

Slow progression Rapid progression

Responds well to treatment Response to treatment is poor

Perforation is uncommon Perforation in one-third of patients

14

DIFFERENTIAL DIAGNOSIS

15

DIFFERENTIAL DIAGNOSIS

Figure 1 differential diagnosis of Mooren's ulcer

Peripheral ulcerative keratitis(PUK) is associated with scleritis

and there is associated systemic involvement like rheumatoid arthritis,

polyarteritis nodosa, relapsing polychondritis, wegeners granulomatosis.

peripheral ulcer

non infectious

local

inflammed

immuneeg:mooren's

non immuneeg:chemical injury

staphhypersensitivity

non inflammed

terrien'spellucid

systemic

infectious

bacterialfungalviral

parasitic

16

Positivity of RF, ANA, ANCA, Hb S Ag, Chest X ray, ESR, CRP and

associated scleral involvement differentiates PUK from Mooren’s ulcer.

Staphylococcal marginal keratitis has associated blepharitis with

a lucid interval between the ulcer and limbus and there is no overhanging

edge or pain. It produces a peripheral corneal infiltrate with overlying

epithelial breakdown due to immune reaction to microbial antigen. It

occurs at point of contact of lid and cornea at 4, 7, 10 and 2 o clock

positions.

Terriens and pellucid marginal degeneration are non-

inflammatory conditions and are differentiated by their absence of pain

with intact epithelium, hence there is no staining with fluorescein. It

starts in superior or inferior quadrant of cornea unlike Mooren’s which

occurs in interpalpebral area.

17

Mooren’s ulcer Terrien’s

degeneration

Pellucid

degeneration

Pain Present Absent Absent

Visual loss Present Present or

absent

Present or

absent

Location Interpalpebral

area Superior Inferior

Progression Rapid Slow Slow

Central

involvement Present Absent Absent

Epithelial

defect Present Absent Absent

Stromal

thinning Present Present Present

Ulcer

vascularisation Present Present Absent

Inflammation Present Absent Absent

Visual threat Opacification Astigmatism Astigmatism

Ulcer

characteristics

Overhanging

central edge

Lipid

deposition

Central

flattening

18

Herpetic keratitis do not exhibit overhanging edge and there is

decreased corneal sensation. Previous history of herpetic infection is

elicited.

Bacterial keratitis has yellowish infiltrate, purulent discharge and

anterior chamber reaction.

Acanthamoeba keratitis has history of contact lens usage. Other

ulcers like dry eye / neuroparalytic ulcers has to be ruled out.

19

OCULAR EXAMINATION AND LABORATORY

INVESTIGATIONS

Ocular examination is done with slit lamp biomicroscopy and any

other associated illness is ruled out. Mooren’s ulcer is a diagnosis of

exclusion. Lids are examined for discharge and matting of eyelashes and

associated blepharitis. Any lacrimal sac pathology and lid malformations

are looked for. Adequate lid closure is ensured and blink frequency is

noted. Intact Bell’s phenomenon is checked. Dry eye and lagophthalmos

are looked for and ruled out. Dry eye can also be checked for using

Schirmer’s test. Corneal sensation is checked to rule out viral etiology.

Associated scleritis and episcleritis are looked for to rule out connective

tissue disorders. Scraping, culture and sensitivity are done to rule out

bacterial, fungal and acanthamoeba infections.

Immunology and dermatological workup is done. Hemogram,

Total Count, Differential Count, Eryhtrocyte Sedimentation Rate,

CReactive Protein, Mantoux, chest X-ray, Rheumatoid Factor, Anti

Nuclear Antibody, Anti Nuclear Cytoplasmic Antibody, serum ACE

levels, VDRL, Hep B and C Ag, ELISA, LFT, RFT are done.

20

MANAGEMENT

21

MANAGEMENT

Unilateral cases are treated initially with 1%prednisolone acetate

e/d 6tid. If superadded infection are present topical antibiotics like

flouroquinolones are used. After 4 -5 days if there is no response to

treatment, conjunctival peritomy with excision is done. About 4 mm of

conjunctiva adjacent to limbus and 2 clock hours on either side are

excised. It helps remove the collagenase and proteoglycans and is

temporary and can be repeated several times. Cryotherapy of perilimbal

conjunctiva can also be done.

Ulcer debridement with cyanoacrylate glue is used along with

bandage contact lens for non-responsive cases or small perforation.

Topical tetracycline or medroxyprogesterone can be used as they have

anti collagenolytic effect. Treatment of associated blepharitis and dry eye

should be started.

BANDAGE CONTACT LENS

This otherwise called as therapeutic contact lens. Its functions are

as follows

22

i. Mechanical protection

ii. Relief of symptoms e.g. ocular surface pain (Secondary to erosion,

edema)

iii. Facilitates corneal epithelial healing & adhesion

iv. Prevention of desiccation

v. Drug delivery

vi. Helps seal small corneal perforation

vii. Cover irregular surface of tissue adhesive

The decision to use a TCL should be carefully considered,as the

risks, particularly microbial infections are substantial.Therapeutic contact

lens wear can be a long-term therapy, so chronic edema and corneal

vascularization can be a consequence of such lenses. The range of the

radius of curvature of these lenses is 7.80 – 9.50 mm. The overall

diameter of the contact lens varies between 13.5 to 16.5 mm (mostly

14mm). These lenses derive their oxygen permeability from their water

content, which can be somewhere from 37.5 to 85%. Central thickness

varies from 0.10 to 0.25 mm, the lowerwater content being thinner.

23

The complications of bandage contact lens are corneal oedema,

microcyst formation, decrease corneal sensation, neovascularization,

giant papillary conjunctivitis, bacterial keratitis, pannus formation and

tight lens syndrome. Hence the following precautions has to be made.

Topical antibiotics are prescribed as the risk of infection is high,

especially in diabetics and patients with dry eye. A new lens is always

better than a lens that has to becleaned and reinserted. It is advisable to

change BCL after 5 nights of wear.

Patient education is an essential in therapeutic lens practice as it is

in all forms of contact lens fitting. The education may often have to

include other members of the patient’s family. BCL practice can be

rewarding as it can lead to dramatic improvements for the patient in

reducing discomfort and aiding the healing process. However, in patients

with bad ocular hygiene, it should be avoided in order to prevent corneal

infection.

In bilateral severe cases or unilateral progressive cases

immunosuppressive drugs like cyclophosphamide (3mg/kg/day),

methotrexate (7.5-25 mg/day), azathioprine (3mg/kg/day) can be started.

24

The WBC count before starting should be >3500/dl. Topical cyclosporine

A (0.5-2%) are tried in few patients. Cyclophosphamide mainly inhibits

the B cells and cyclosporine inhibits the T cells. Methotrexate are to be

given along with folic acid 1-5mg/day for 6days per week. Side effects of

immunosuppressants are nephrotoxicity, hepatotoxicity, anemia,

alopecia, nausea etc.

Surgical intervention is done when there is perforation or severe

thinning with impending perforation. In keratoepithelioplasty several

fresh donor corneal lenticules with intact epithelium is placed near the

ulcerated area and sutured. This acts as a barrier between conjunctiva and

cornea and prevents the inflammatory cells from reaching the ulcerated

site. Amniotic membrane grafting⁴ and conjunctival hooding is resorted

to at last for perforated ulcer to maintain integrity.

PENETRATING KERTOPLASTY

The procedure of penetrating keratoplasty involves trephination of

donor cornea, trephination of recipient cornea, suturing of donor corneal

button onto the recipient rim of cornea and formation of anterior

chamber. Trephination of donor cornea: most of the eye banks provide

25

the donor cornea in the form of sclerocorneal button which has a 2-3mm

of sclera rim surrounding the entire cornea. The donor corneal button is

placed over a Teflon block with epithelial side down bathed in

viscoelastic substance above and below. A disposable trephine blade is

placed over mechanical punch and secured in place. It should be made

sure that the trephine is placed vertical onto the punch and there should

be no tilting. A vertical placement ensures a vertical uniform edge of

corneal button. The donor corneal button is centred visually onto Teflon

block. Curvature of the Teflon should be approximately similar to the

curvature of the epithelial side of the donor. This will avoid slipping of

the donor while punching. After proper placement, the trephine is

lowered with a single, purposeful punch that will produce a uniformly

perpendicular wound edge around the circumference of the donor button.

Trephination of recipient eye:

During trephination of recipient eye, it is necessary to prevent

rotatory motion of the globe. This is obtained by three points of fixation.

Superior and inferior rectus bridle sutures or a scleral ring with sutures in

superior and inferior pole can act as two points of fixation. Third point of

fixation is by grasping the horizontal rectus muscle by toothed forceps.

26

The size of the recipient bed is determined by the location and the extent

of corneal ulcer. The most commonly used trephine are from 7.5 to 8.5

mm in diameter. The radial marker stained with a marking pen can be

used to locate the sutures. The trephine is centred over corneal

abnormality and the marks are made over the epithelium. The anterior

chamber is entered along the mark at the point using a 15 degree side

port. Anterior chamber is formed with visco and the incision is extended

using corneo scleral scissors. The trephined corneal button is removed.

The donor corneal button is placed over the recipient bed and sutured

using 10-0 nylon sutures. A double –pronged forceps is used to place the

four cardinal sutures at 12-, 6-, 3- and 9- 0 clock meridians. The bite in

the donor and recipient cornea ideally should be 1mm long, equally

placed and radially arranged. The sutures should be incorporated into

95% of corneal thickness up to the level of Descemet’s membrane. After

placing four cardinal sutures 12 interrupted sutures are placed

sequentially on opposite sides. Before placing the last suture, the anterior

chamber is washed using a simcoe cannula and anterior chamber is

deepened using balanced salt solution. The final suture is then tightened.

All the sutures are buried by holding the sutures using non-toothed

forceps and pushing the knot along the needle track into the donor

27

cornea. 0.5 cc of sub conjunctival dexamethasone is given and pad and

bandage applied.

Conjunctival hooding:

Trygve Gundersen described the technique for creating a

conjuctival flap and placing it over the abnormal corneal surface. This

procedure is indicated only if all medical measures fail and is used for

promoting healing in recalcitrant ulcers with impending perforation.

Under local anaesthesia, a traction suture is placed in clear cornea

adjacent to 12 o clock limbus and is used to rotate the eye downwards.

The conjunctival resection is done as superiorly as possible near superior

fornix. An extensive superior limbus based flap is dissected from bulbar

conjunctiva. A 360 degree peritomy is made as close to limbus as

possible. The conjunctival flap is spread onto the corneal surface until it

covers the entire cornea without tension. The superior and inferior edges

of the flap are sutured onto perilimbal episclera.

28

AMINOTIC MEMBRANE GRAFTING:

Amniotic membrane is commercially available in two main forms:

preserved amniotic membrane that is wet; and a dry form (AmbioDry),

which can be reconstituted and applied to the ocular surface.

Amniotic membrane is obtained from prospective donors

undergoing elective Caesarean section, who are screened for HIV,

hepatitis and syphilis. The placenta is cleaned with balanced salt solution

containing a cocktail of antibiotics (50 mg/ml penicillin, 50 µg/ml

streptomycin, 100 mg/ml of neomycin as well as 2.5 mg/ml of

amphotericin B) under sterile conditions. The amnion is separated from

the chorion by blunt dissection. The separated membranes are cut in

different sizes placed on nitrocellulose paper strips with the epithelial

side up. Dulbecco Modified Eagles Medium/glycerol (1:1) is used for

cryopreservation and the tissues are frozen at -80 degrees until further

use. Amnion stored in 50-85% glycerol is reliable and effective for over

a year, with the added advantage of antibacterial properties.

The preferred surgical orientation of the AM on the ocular surface

is with the epithelial side up. The stromal surface can be identified by the

presence of vitreous-like strands that can be raised with a sponge.

29

Inlay or graft technique: When the AMG is tailored to the size of

the defect and is meant to act as a scaffold for the epithelial cells, which

then merges with the host tissue, it is referred to as a graft. The amniotic

membrane is secured with its basement membrane or epithelial side up to

allow migration of the surrounding epithelial cells on the membrane.

Overlay or patch technique : When the AM is used akin to a

biological contact lens in order to protect the healing surface defect

beneath, it is referred to as a patch. The overlay technique involves the

entire corneal surface including the limbus being covered with the

amniotic membrane graft. A patch also reduces inflammation by its

barrier effect against the chemical mediators from the tear film. When

used as patch the membrane is secured with its epithelial side up and it

either falls off or is removed. AM transplantation is useful only when

there is some reserve of stem cells present, as the amniotic membrane

itself is not a source of stem cells.

Superficial lamellar keratectomy can be done with anterior stroma

removal. It removes the antigenic targets, prevents immunological

reaction, reconstructs the anatomical structure and prevents perforation.

Later a central PKP can be done over it.

30

REVIEW OF

LITERATURE

31

REVIEW OF LITERATURE

Regarding epidemiology of Mooren’s ulcer, it was found to be

more common in southern and central Africa, China and the Indian

subcontinent¹. The prevalence of Mooren’s and the blindness caused by it

worldwide is unknown. It is found to be very rare in children¹ and the

range of age based on a retrospective review in Nigeria was found to be

12 to 42 years². The incidence of the disease varies widely. It ranges from

one case per year in Europe and North America to about one in 350 and

1 in 2200 in countries like India and Nigeria³. A large study from china

showed incidence of 0.03%⁴.

The risk factor of Mooren’s ulcer is still unknown and certain

associations have been reported. Genetic and environmental basis for the

disease has been suggested. The environmental factors which might

contribute were found to be history of accidental trauma or history of

surgery and exposure to parasitic and viral infections. In India, an

increase in Helminthiasis is not reported in patients with Mooren’s ulcer¹.

There has been reports of association with Mooren’s ulcer but even in the

absence of the disease, Mooren’s ulcer can develop. Even in places

where Helminthiasis is endemic, Mooren’s is found to be rare¹. HLA

32

(Human Leukocyte Antigens) offer susceptibility to diseases of

autoimmune origin especially in Asian and black African patients. In

these groups of races, the presence of HLA-DR17 or HLA-

DR2(histocompatibility antigens)offer susceptibility to Mooren’s ulcer⁵.

HLA-DR was found to be expressed more in patients with Mooren’s by

Zhao⁶ in 1993.

The clinical characteristics of Mooren’s were described over the

years by many authors. The characteristic overhanging edge of the ulcer

was described by Young⁷ 1982, Bouchard⁸ 1998, Foster٩ 1999,

Wilhelmus¹° 2001 and Kanski¹¹ 2003. The ulcer progresses from an

initial stromal infiltrate to epithelial breakdown in the interpalpebral

region by Tuft¹² in 2003 and Kanski in 2003.

The clinical grading of Mooren’s ulcer is given in 2005 by

Sharma¹³ as follows,

Based on the extent of corneal thinning in one or more quadrants

as mild, moderate and severe. Where mild is thinning which affects less

than 25%of corneal circumference, moderate is thinning which affects

25%-50% of circumference and severe is thinning affecting >50% of

33

circumference.Impending corneal perforation and perforation greater

than 2mm is also taken into account for grading.

The treatment of Mooren’s ulcer can be medical and

surgical,medical being local and systemic.The most widely suggested

treatment is the use of topical corticosteroids as a first line of therapy

followed by conjunctival resection. The use of topical cyclosporine A

1 % e/d⁶ has been suggested by few in their studies. In addition to these,

Bandage contact lens has been described which helps by reducing

discomfort, promoting epithelial healing. Also used were tissue

adhesives, subconjunctival heparin injections, artificial tear drops, topical

collagenase inhibitors like L-cysteine 0.2 molar and acetylcysteine eg:

Mucomyst 10%. Shimmura²⁷ in 2003 described the use of Lecithinase

superoxide dismutase for Mooren’s ulcer.

The use of systemic immunosuppressants were considered in

special situations like in extensive corneal thinning, in cases where the

ulcer is advanced at initial examination, where conjunctival resection

fails or when the disease is bilateral and extensive. In these cases the use

34

of cyclophosphamide followed by azathioprine٩ were reported to be

initiated.

In 1984 Brown described the use of oral corticosteroid,

cyclosporine A and methotrexate as a treatment for more aggressive and

bilateral cases. The use of high dose cyclosporine A was described by

Foster in 1985. In patients with hepatitis C virus association with

Mooren’s ulcer, the use of plasma exchange has been described. Also use

of interferon alpha-2b has been described by Moazami²⁸ in 1995 and also

by Wilson²٩ in 1994. There are also results of use of monoclonal

antibodies campath- 1H and infliximab by Fontana and Van der Hoek.

The types of surgical treatment include conjunctival resection,

lamellar keratoplasty, delimiting keratotomy, conjunctival flap,

epikeratoplasty and patch grafts of fascia lata and periosteum described

by Kinoshita in 1991.Some investigators advocate “removal of the

presumed antigenic corneal source (central lamellar keratectomy)” in an

attempt to mediate a more rapid resolution of the inflammation (Brown

1984). Although initial corneal surgery is usually contra-indicated, some

authors have reported good results with a primary lamellar keratoplasty

combined with topical cyclosporine A. Using this regimen Chen 2000

35

achieved a cure of 74% for the first procedure, and a final cure rate of

95%.

Chen (2000) used a combination of conjunctival excision, lamellar

keratoplasty and topical 1% cyclosporine A with some success. This is

the largest case series reported. Sharma 2005 used a step ladder

approach, selecting the type ofintervention for each case of Mooren’s

ulcer. The classification isbased on the degree of cornea thinning at time

of commencement of treatment. Definition of success also seems to vary

in the literature. Some studies used ‘healed’ (Brown 1975; Chen 2000;

Erdem2007; Tiev2003; Zhao 1993) while others used ’visual acuity’

(Chen 2004; Hill 1987). Failure was defined as progression of corneal

melting leading to perforation and loss of the eye.

A clinical study conducted by Yan Ke Xue Bao¹⁴ in 1998 studied

the clinical characteristics and treatment of Mooren’s ulcer. The average

age of onset was reported to be 48.4 yrs old. A male preponderance was

reported by male to female ratio of 1:0.74. Among the total 550 cases

studied, 30 % were bilateral and among these 31.5% were young and

68.5% were old. They also studied the rate of perforation which was

36

found to be 13.3% and of these 43.2% were in young and 68.5% in old.

This study provided clinical characteristics in terms of young and old

patients of Mooren’s ulcer in China and did not support the major

classification of Mooren’s into benign and malignant type.

Mooren’s ulcer is a potentially blinding eye condition which is rare

and infrequent in occurrence. Generally males are more affected than

females and can occur either unilaterally or bilaterally. The study

performed by Srinivasan M¹⁵ showed the characteristics of Mooren’s

ulcer in southern parts of India. Male preponderance was noted by the

male female ratio of 4.7:1. The mean age of presentation was observed to

be 61 years with range of 13-95 years. 54% were unilateral. Of the 242

eyes studied, 14% had 6/12 and better vision, 69% had vision between

6/12 and 3/60, 17% had vision less than 3/60. They identified risk factors

for Mooren’s ulcer as corneal surgery in 22%, corneal trauma in 17% and

corneal infection in 2%. This supports the theory of autoimmunity with

reaction to corneal antigen which gets exposed to above said conditions.

Perforation was seen in 1 in 10 eyes with more tendency to perforate in

peripheral ulcer compared to total ulceration.

37

A step ladder approach of immunosuppressives was evaluated in a

study conducted by Ashar JN¹⁶ et al. This study shows a retrospective

analysis of Mooren’s ulcer from 1987 to 2010. Topical steroids when

used as a single mode of therapy had a resolution rate of 76%, oral

steroids has a resolution rate of 86%, oral methotrexate 78.5% , iv methyl

prednisolone 71.4%. This study gave us a conclusion that when a tailor

made immunosuppression based on severity of ulcer is considered there

is an increased chance of disease control even in aggressive Mooren’s

ulcer.

A study conducted by Seino JY¹⁷ et al in 1998 studied three

patients. In one patient they elicited a history of chemical trauma. They

treated this patient with oral steroids. The second patient was positive for

hepatitis C who responded to aggressive topical steroid therapy. The third

patient was 68yrs old who progressed rapidly and developed corneal

melting. A penetrating keratoplasty was done after a patch graft failed.

They concluded that Mooren’s ulcer is progressive, painful, idiopathic

ulceration of cornea which usually respond very poorly to conventional

therapy as the pathology behind the condition is poorly understood. Use

of steroids and immunosuppressants were justified as there is evidence of

autoimmune component.

38

Use of topical cyclosporine A 2% was studied by Tandon R¹⁸ et al.

It shows that topical cyclosporine A 2% can be used as a safe and adjunct

to standard medical therapy in recalcitrant Mooren’s ulcer. In 12 eyes it

was started as an adjunct to standard medical therapy and all resolved

completely with vascularisation with mean healing time of 34.4 +/-13.1

days. Of this 1 case showed recurrence. In 5 cases,topical cyclosporine

was started after tectonic keratoplasty and no recurrence was noted.

Adverse effects were found to be nil due to topical cyclosporine.

In case of progressive bilateral Mooren’s ulcer, the use of systemic

immunosuppressive therapy was suggested by Foster CS¹٩ in his study.

He studied nine patients which was bilateral relentlessly progressive

which did not respond to conventional ocular and systemic therapy.

These patients were started on methotrexate or cyclophosphamide. There

was an arrest in the progressively destructive inflammatory disease

process and preservation of ocular anatomy and function was observed in

eight patients started on systemic immunosuppression for 6 to 24 months.

One patient who did not come for follow up and did not receive adequate

medical therapy developed destruction of both eyes due to inflammatory

process. This study came to a conclusion that immunosuppressive drugs

like methotrexate or cyclophosphamide when used properly may offer

reasonable cure for patients with progressive bilateral Mooren’s ulcer.

39

A study by Brown SI²° on therapy of Mooren’s ulcer studied the

use of topical steroids, conjunctival resection and immunosuppression for

treatment of Mooren’s ulcer. Of the 37 eyes studied, 12 healed with only

topical steroids alone. Eight eyes needed an additional conjunctival

resection as topical steroids alone failed to heal. Those who did not

respond to both were started on immunosuppression. By this four healed.

The overall healing in this study was 65%. Of the unilateral cases eight of

nine healed and of the bilateral cases which were non simultaneous, six

of six cases healed with topical steroids and conjunctival resection. Of

the bilateral simultaneous cases, ten of twenty two only responded to

topical steroids, conjunctival resection and immunosuppression. They

came to a conclusion that if a bilateral Mooren’s ulcer occurs

simultaneously, and if it is active, it is severe and relentlessly progressive

and no satisfactory treatment exists.

The study conducted by Erdem U et al²¹ used topical interferon

alpha 2a for treatment of Mooren’s ulcer. Interferon alpha2a was used as

a single mode of therapy and two patients were treated. Signs and

symptoms improved in the first week of treatment and in seven and ten

days reepithelialisation was achieved in two cases. Visual acuity also

improved at the end of one month. There was no recurrence observed

during follow up done at 6 months and 1 year. So interferon alpha 2a

when used as a single therapeutic agent was concluded to be an effective

40

treatment for Mooren’s ulcer. It avoids the surgical complications that

leads to stem cell deficiency.

There was a study conducted by Mathur A et al²² which studied the

occurrence of Mooren’s ulcer in children. Average age of presentation

observed in this study was 12.45+-2.25 years. Unilateral cases were eight

and bilateral cases were three. More severe symptoms were noted

compared to adults. The commonest predisposing factor was found to be

trauma. There was severe corneal involvement in eight cases. They were

treated with topical steroids, oral steroids, immunosuppressives, tissue

adhesives, bandage contact lens, amniotic membrane transplantation,

optical penetrating keratoplasty and limbal stem cell transplantation. The

data collected by this study suggest that clinical features and demography

differs from that available for adults. Steroids and immunosuppressants

in children is to be used cautiously and judiciously with close monitoring.

Good visual outcome and stable anatomical integrity can be achieved if

appropriate medical and surgical therapy is used.

41

PART II

42

AIMS AND OBJECTIVES

43

AIMS AND OBJECTIVES

The aim of the study is to

1. Study the natural history of the disease

2. Evaluate and to classify based on laterality, no of clock hours of

involvement, depth of stromal involvement and presence and

absence of corneal perforation

3. Start a step ladder approach of immunosuppressives after systemic

evaluation

4. Assess the visual outcome and progression of Mooren’s ulcer.

44

MATERIALS

45

PATIENT SELECTION

SUBJECT SELECTION

All cases attending Ophthalmology OPD with typical signs and

symptoms of Mooren’s ulcer in the period of 1year by method of random

sampling. Age of inclusion is 20 -90 yrs. Both genders are included.

INCLUSION CRITERIA

Patients with typical symptoms and signs of Mooren’s Ulcer

(peripheral ulcer with overhanging edge progressing circumferentially

extending up to limbus, starting in the interpalpebral region with

excruciating pain, watering with no lucid interval. There should be no

associated scleritis or blepharitis)

There should be no systemic associations.

EXCLUSION CRITERIA

1. Patients with Terrien marginal degeneration ,

2. Pellucid marginal degeneration(starting in superior or inferior

cornea with intact epithelium and no pain)

3. Peripheral ulcerative keratitis associated with scleritis due to

Rheumatoid Arthritis, Wegener’s, PAN, Relapsing polychondritis

(positive for ANA, ANCA, RF, CRP, ESR)

46

4. Staphylococcal marginal keratitis (has a lucid interval between

lesion and limbus with associated blepharitis)

5. Infectious ulcer secondary to Herpes (decreased corneal sensation)

or Acanthamoeba (h/o contact lens wear)

6. Other causes of ulceration like neuroparalytic ulcer/dry eye

And all patients with renal failure, liver failure were excluded from

the study. Those who were not compliant with therapy were not included.

47

METHODOLOGY

48

SCREENING PROCEDURES/ VISITS

For all patients included in the study a thorough history of past and

presentcomplaints, history of connective disorders,joint involvement,

other system involvement (upper/lower respiratory tract involvement,

renal involvement), history of any dermatological illness is obtained.

Clinical examination under slit lamp biomicroscopy, fluorescein staining

of cornea, Corneal sensation, Corneal smear, culture and sensitivity,

Intraocular pressure measurement using noncontact tonometer, Dilated

fundus examination were done. Systemic investigations like complete

blood count,TC,DC, ESR, CRP,RF, ANA, Mantoux, Chest X ray were

done. Also a Rheumatologist’s opinion was obtained for all patients and

connective tissue involvement ruled out.

FOLLOW UP PROCEDURES / VISITS:

The follow up visits were done at 1,2,3,4,6,8,12 and 16 weeks.

49

METHODS

All patients included in the study are evaluated first by measuring

the visual acuity using Snellens chart done at 6 meter distance. History

regarding duration of illness and history of trauma if any (whether

mechanical or chemical) is obtained. A thorough slit lamp

biomicroscopic examination is done and the ulcer characteristics are

noted with respect to location, laterality, no of clock hours of stromal

involvement,depth of ulceration. A frontal and a slit diagram is drawn

and slit lamp photograph taken at the time of presentation for

documentation and future reference. Intraocular pressure measurement is

done using non-contact tonometry.

Fluorescein staining of cornea is done using commercially

available sodium fluorescein strips. It is used to detect epithelial defects

and surface irregularities, as in this case to see if the ulcer is active or not

by the presence of epithelial defect which is noted by staining. There can

also be pooling due to depression and thinning in the area of ulceration.

Pooling is differentiated from staining by irrigation with sterile

ophthalmic solution where pooling disappears and staining retains. The

strips are wetted using normal saline and applied over the inferior cul de

sac of conjunctiva or over the bulbar conjunctiva. The patient is asked to

50

blink in order to spread the fluorescein and examined using cobalt blue

filter under slit lamp. Any staining of cornea is noted as bright green

coloured spot and taken as positive. Pooling is not taken into account.

Corneal sensation should be checked after fluorescein staining as

testing for sensation produces linear and punctate staining. Prior

application of anaesthetic drops is to be avoided. The normal non-

infected eye is checked first followed by the affected eye to avoid cross

contamination. Corneal sensation is checked in the normal area of the

cornea of both eyes using a wisp of cotton. This is created by stretching

and pulling from a cotton tipped applicator which is twisted onto itself.

Sensation is tested approaching the eye temporally from behind the

patient. The patient is asked to fixate on a distant target during the test.

Corneal sensation is checked in four quadrants, superior, inferior, medial

and lateral. A blink reflex is noted for objective response which is graded

as normal, reduced or absent. The patient is questioned whether he can

feel the touch for a subjective response

Dilated fundus examination is done using direct and indirect

ophthalmoscopy.

51

Corneal smear is obtained using 15-blade mounted on Bard Parker

handle and scrapings obtained from the edge and the base of the ulcer.

The scrapings are stained using grams stain to rule out bacterial

infections. If the gram stain is positive the scraping is cultured using

blood agar. A 10% KOH wet mount is done to rule out fungal infections,

and if it is positive, a culture is done using Sabourard’s dextrose agar

medium.

Blood investigations like Complete blood count, Total Count,

Differential Count, Erythrocyte Sedimentation Rate, CReactive Protein,

Rheumatoid factor, Anti-Nuclear antibody are done. Mantoux test and

Chest X ray are obtained.

52

Mooren's ulcer

start on topical steroids. Follow up

after 2 weeks

healing

continue topical steroid for 2 weeks then taper and stop

progressed

conjunctival resectionfollow up after 2 weeks

healing

continue topical steroids for two

weeks, then taper and stop

progressive

oral steroids.follow up after 2 weeks

healing

continue topical and oral steroids for 2

weeks taper and then stop

progressive

add topical cycloimmune

follow up after 2 weeks

healing

continue all drugs for 4 weeks and taper steroids and stop

progressive

oral methotrexate (stop steroids)

continue for 6 months

stationary

stationary

stationary

each drug in stationary stage is maintained for 4

weeks to look for status. If no improvement next

drug started

stationary

continue topical steroids for 2 weeks,if still

stationary go to next level of managemant

Figure 2treatment protocol for Mooren's ulcer

53

GRADING OF ULCER

In order to divide the ulcer into mild, moderate and severe, three

parameters are taken into account and each parameter is given an

arbitrary grading and the final score helps in classifying the severity. The

parameters considered are total number of clock hours of involvement,

depth of stroma and fluorescein stain result.

No. Of clock hours of involvement

Clock hours Score

<3 1

4-6 2

7-9 3

10-12 4

54

Depth of stromal involvement

Depth of stroma Score

<1/4th 1

1/4th-1/2 2

½-3/4th 3

Perforation 4

Fluorescein staining

Fluorescein stain Score

Negative 0

Positive 1

Total =9

55

Severity Score

Mild ≤3

Moderate 4-6

Severe 7-9

All patients with Mooren’s ulcer are started on topical

1%prednisolone acetate e/d 6tid. If any associated secondary infection is

present they are also started on topical 0.5%moxifloxacin e/d 6tid. All

patients are followed up after 2 weeks and stage of ulcer analysed.

The ulcer stages are divided into healing, stationary or progressive

based on following criteria

1. Healing stage is defined by decrease in No. Of clock hour of

involvement or decrease in depth of ulcer or conversion of fluorescein

stain from positive to negative.

2. Stationary stage is defined as same depth of ulcer and clock hours and

fluorescein staining pattern as at the beginning of the study or at previous

follow up.

56

3. Progressive stage is defined as increase in no. of clock hours of

involvement or increase in depth of ulcer or conversion of fluorescein

stain pattern from negative to positive.

After the first two weeks into the study, the ulcer is graded as

healing, stationary or progressive. The healing stages are treated with

continual of topical steroids for two weeks followed by taper and stop.

Those in the stationary are maintained on topical steroids for 2 more

weeks and looked for response. If no response or worsens, next line of

management is started. All patients in stationary group at any point of

time is maintained in a particular drug or therapy for 4 weeks and looked

for improvement. If there is no improvement at 4 weeks, next drug is

started. Those in the progressive group underwent conjunctival resection.

All cases are followed up after 2 weeks.

After two weeks all cases are divided into healing, stationary and

progressive. Those in healing stage are continued on topical steroids for 2

weeks then tapered and stopped. Those in progressive are treated with

oral steroids 1mg/kg/day, if no systemic contraindication. A blood sugar

level is checked before starting steroids and then once in two weeks

thereafter. The next review was two weeks later.

57

After 2 weeks, healing, stationary and progressive are identified.

Those in healing stage are continued on topical and oral steroids for 2

weeks and then tapered and stopped. Those in progressive group are

started on topical 0.5%cycloimmune e/d add on to topical and oral

steroids and reviewed after 2 weeks. Those which entered healing stage

are maintained on all drugs for 4 weeks and then tapered and stopped. If

it still is progressive at the end of 2 weeks, they are started on oral

methotrexate 7.5mg once weekly (3 x 2.5 mg tablets) along with T. Folic

acid5 mg 6 days per week excluding the day of methotrexate intake.

Liver Function Tests and Renal Function Tests are measured before

staring treatment and repeated once in two weeks. Once started on

methotrexate, the patient is maintained on it for at least 6 months.

Perforation at any point of study is taken up for penetrating keratoplasty

along with topical steroids, topical cycloimmune and oral methotrexate.

Conjunctival resection:

The procedure is undertaken at an operating theatre, under strict

aseptic precautions. Under local sub-conjunctival anaesthesia,

conjunctiva is resected adjacent to the ulcer near limbus using

conjunctival scissors and Lims forceps. The amount of resection is 4 mm

58

from limbus and 2 clock hours on either side of the ulcer. Excessive

bleeding is controlled using minimal wet field cautery applied directly to

the bleeders. At the end of the procedure, 0.5cc of sub-conjunctival

dexamethosone is given and pad and bandage applied for one day. The

pad is removed the next day and steroid eye drops are continued.

Penetrating keratoplasty:

If perforation occurs patch grafting /PKP is done immediately to

maintain ocular integrity along with T.Methotrexate. The surgery is done

under strict aseptic precautions under peribulbar anaesthesia. The donor

corneal button is made and the correct size according to the area of

ulceration is trephined. The recipient bed is made ready to appropriate

size by excising the infiltrates and debris. The donor corneal button is

placed over the recipient bed and is sutured using 10-0 nylon interrupted

sutures. The sutures are taken from the graft towards the host side always

and not otherwise. The sutures are radial , equidistant 1 mm from the

edge and partial thickness 2/3rd stromal thickness and tied using 3-1-1

sutures. The knots are cut very short and the sutures buried in the graft

side. Conjunctival peritomy and excision is also done along with this.

Anterior chamber wash is given and it is formed with saline. 0.5cc

59

subconjunctival dexamethosone given and pad and bandage applied. The

pad was removed the next day and patient started back on topical and

oral steroids with methotrexate.

60

RESULTS

61

RESULTS

Total number of patients included in the study were 30 and the

total number of eyes observed were 42. All the data included in the study

were analysed using SPSS software and the comparisons analysed using

Pearson Chi-Square test.

AGE

The age group was divided into young <40 yrs and old >40 yrs. 10

patients were under 40 yrs of age which constituted 33.3% and 20

patients were over 40 years of age which constituted 66.7% . The mean

age of presentation was found to be 58 yrs.

AGE IN YRS NO. OF PATIENTS

(n=30)

LESS THAN 40 10 (33.3%)

MORE THAN 40 20 (66.7%)

62

1033%

2067%

AGE

< 40 YRS

>40 YRS

63

SEX

Regarding sex distribution, among the total 30 patients included in

the study, 27 patients were male constituting 90% and only 3 were

female which was 10 % of total.

SEX NO. OF PATIENTS

( n=30 )

MALE 27 (90%)

FEMALE 3 (10%)

2790%

310%

SEX

MALE

FEMALE

64

LATERALITY

Based on either one eye or both eyes involved they are further

divided into unilateral and bilateral. Unilateral cases were 18 cases.

11(36.7%) patients had right eye involvement and 7(23.3%) had left eye

involvement. 12 patients had bilateral involvement. Of the 18 unilateral

patients 61.1% had right eye involvement and 38.9% had left eye

involvement.

LATERALITY NO. OF PATIENTS

(n=30)

UNILATERAL 18 (60%)

BILATERAL 12 (40%)

Laterality with respect to age, among young patients all 10 patients

were unilateral (100%) and among 20 old patients 8 had unilateral

involvement i.e. 40% and 12 had bilateral involvement(60%) , i.e. among

unilateral patients , 10 were young and 8 were old. Hence 55.6% among

unilateral were young and 44.4% were old.

65

<40 YRS >40 YRS

UNILATERAL 10 8

BILATERAL 0 12

p= 0.002

Hence all young patients had unilateral involvement, i.e. in other

words all bilateral patients were old.

0

2

4

6

8

10

12

14

16

18

20

YOUNG OLD

108

0

12

BILATERAL

UNILATERAL

66

DURATION OF ILLNESS

10 patients presented with less than 2 months history, 9 with a

history of 2- 4 months,8 with history of 4 -6 months and only 3 patients

had a history of 6months -1 year.

DURATION NO. OF PATEINTS

(n=30)

<2 months 10 (33.3%)

2-4 months 9 (30%)

4-6 months 8 (26.7%)

6months – 1 year 3 (10%)

0

1

2

3

4

5

6

7

8

9

10

duration of illness

10

9

8

3

<2months

2-4months

4-6months

6months-1yr

67

HISTORY OF TRAUMA

Totally 9 patients have history of trauma which constitutes 30%.

All these 9 patients were found to be young and none of the old patients

had any history of trauma. Hence among the 10 young patients 9 had a

history of trauma and only one patient did not have i.e. 90% of young had

history of trauma and 10 % did not give a history of trauma.

History of

trauma

No history of

trauma

<40 yrs 9 1

>40 yrs 0 20

0

2

4

6

8

10

12

14

16

18

20

<40 yrs > 40 yrs

9

0

1 20

Chart Title

history of trauma

no history of trauma

68

SUPERADDED INFECTIONS

Superadded infections with gram positive cocci were present in 24

eyes of which 6 were young and 18 were old. Of those who did not have

infection, 4 were young and 14 were old. Hence 57.1% of the total 42

eyes were positive for infection and 42.9% were negative. Among the

positives, 25% were young and 75 % were old. Among negatives 22.2%

were young and 77.8% were old. In other words among the eyes in

younger age group 6 eyes had infection (60%) and 4 were non infected

(40%). Among older age group.18 eyes showed secondary infection

(56.3%) and 14 were non infected (43.8%).

Secondary infection

Present Absent

<40yrs 6 4

>40yrs 18 14

69

VISUAL ACUITY

Based on the visual acuity at the time of presentation, they are

roughly divided into 3 broad groups. 17 eyes had vision between 6/6 to

6/18 i.e. 40.5%, of this 8(47.1%) were young and 9(52.9%) were old. 15

had a vision between 6/24 to 6/60 i.e.35.7%, of this 2(13.3%) were young

and 13(86.7%) were old. 10 had a vision between 5/60 to 1/60, i.e.

23.8%, of this none were young and all 10 were old. Among young, 8

had a vision between 6/6 to 6/18, i.e. 80% and 2 had a vision between

6/24-6/60, i.e. 20%. Among old, 9 had a vision between 6/6 to 6/18, i.e.

28.1% and 13 had a vision between 6/24-6/60, i.e. 40.6%, 10 had a vision

between 5/60-1/60, i.e. 31.3%.

6

18

4

14

0

2

4

6

8

10

12

14

16

18

20

< 40 yrs > 40 yrs

superadded infection present

superadded infection absent

70

Visual acuity <40yrs >40yrs

6/6-6/18 8 9

6/24-6/60 2 13

5/60-1/60 0 10

0

2

4

6

8

10

12

14

16

18

6/6-6/18 6/24-6/60 5/60-1/60

8

20

9

13

10

>40yrs

<40 yrs

71

SEVERITY OF ULCER

Based on this arbitrary scoring system to help in further analysis of

data, the severity of ulcer is graded. Of the 42 eyes studied, 15 eyes had

mild disease, i.e.35.7%, 22 eyes had moderate disease, i.e.52.4% and 5

had severe disease ,i.e.11.9%. In the mild disease, 3 were found to be

young and 12 were found to be old, constituting 20% young and 80% old

. In the moderate disease 7 were young constituting 31.8%, 15 were old

constituting 68.2%. All eyes in severe category were old.

In the younger age group 3 eyes had milder form constituting 30%

and 7 had moderate form constituting 70%. None of them had severe

disease. In the older age group 12 (37.5%) had mild disease and

15(46.9%) had moderate disease and 5(15.6%) had severe disease.

<40yrs >40 yrs

Mild 3 12

Moderate 7 15

Severe 0 5

72

PERFORATION

6 eyes had perforation either at the time of presentation or during

the course of treatment. 14.3% had perforation of which 2 (33.3%) were

young and 4 (66.7%) were old.

AGE

No of eyes with

perforation

(n=6)

<40yrs 2(33.3%)

>40yrs 4(66.7%)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

mild moderate severe

> 40 yrs

< 40 yrs

73

TREATMENT OUTCOMES

IN MILD DISEASE

Of the total 15 eyes with mild disease, 8(53.3%) were treated with

topical steroids alone, 2 (13.3%) were treated with topical steroids with

conjunctival resection and 5(33.3%) with added on oral steroids. Of this

12 (80%) were in healing stage, 2(13.3%) remained stationary, and only

one progressed (6.7%). Of the 12 in healing stage, 9 were treated with

topical steroids that constitutes 75%, 2 were treated with topical steroids

and conjunctival resection which constitutes 16.67%, and 1 needed oral

steroids (13.33%). Both progressed and stationary were treated upto level

oral steroids.

33%

67%

perforation

< 40 yrs

> 40 yrs

74

Mild No. of patients (n=15)

Healing 12(80%)

Stationary 2(13.3%)

Progressed 1(6.7%)

N=15 Topical

steroids

Topical steroid

+ conjunctival

resection

Topical steroids+

conjunctival

resection+oral steroids

Healed 9 2 1

Stationary 0 0 2

Progressed 0 0 1

0

2

4

6

8

10

12

healing stage stationary progressive

9

0 0

2

0 0

1

2 3

top st with conj resection with oral steroids

top st with conj resection

topical steroids

75

MODERATE

Among 22 moderate cases 7 were in healing stage (31.8%), 5 in

stationary stage (22.7%), 10 in progressive stage (45.5%) .

No. Of patients (n=22)

Healing 7(31.8%)

Stationary 5(22.7%)

progressive 10(45.5%)

Of those 7 in healing stage, 5(71.4%) were treated with topical

steroid with conjunctival resection, 2(28.6%) were treated with topical

and oral steroids along with conjunctival resection of the 5 that remained

stationary, 1(20%) was treated upto oral steroids, 4 (80%) were treated

upto cycloimune. Of the 10 that progressed, 4(40%) treated upto oral

steroids, 2(20%) upto cycloimmune, 2(20%)were started on methotrexate

and 2 (20%) underwent keratoplasty.

76

Top

.st+c

onj

rese

ctio

n

+ora

l ste

roid

s

+Cyc

lo im

mun

e

+Met

hotr

exat

e

Ker

atop

last

y

Healing 5 2 0 0 0

Stationary 0 1 4 0 0

Progressive 0 4 2 2 2

0

1

2

3

4

5

6

7

8

9

10

healing stationary progressive

5

0 0

2

1

4

0

4

2

0

0

20

0

2

keratoplasty

methotrexate

cycloimmune

oral steroids

upto conj resection

77

SEVERE DISEASE

Among the 5 severe cases, only 1 was in healing stage (20%),

which had treatment till oral steroids, 2 were in stationary stage(40%)

whose treatment went upto keratoplasty, 2 were in progressive

stage(40%).and both were treated upto cycloimmune.

Severity of ulcer No. of patients (n=5)

Healing stage 1(20%)

Stationary 2(40%)

Progressive 2(40%)

+oral steroids +Cycloimmune +Keratoplasty

Healing 1 0 0

Stationary 0 0 2

Progressive 0 2 0

78

TREATMENT OUTCOME

Of the 42 eyes studied, 20 were in healing stage at the end of the

study, 9 were in stationary stage and 13 were in progressive stage. i.e.

47.6% entered healing stage at the end of study and 21.4% were in

progressive stage and 31% were in stationary stage. So majority of

patients entered healing stage due to this step ladder approach of

treatment with immunosuppressants.

0

0.5

1

1.5

2

healing stationary progressive

keratoplasty

cycloimmune

oral steroids

79

Stage of ulcer No. of patients (n=42)

Healing 20(47.6%)

Progressive 9(21.4%)

Stationary 13(31%)

2048%

921%

1331%

treatment outcome of eyes

healing

stationary

progressive

80

SEVERITY OF ULCER IN RELATION TO AGE AND

LATERALITY

IN RELATION TO AGE

Of the 10 eyes in younger age group <40 years, 40 % entered

healing stage, 30 %were in progressive stage and 30 % were stationary.

Of the 32 eyes in older age group, 50% entered healing stage, 31.3%

entered progressive stage and 18.8% were in stationary stage.

<40yrs >40yrs

Healing 4 16

Stationary 3 6

Progressive 3 10

4, 40%

3, 30%

3, 30%

<40 yrs

healing

stationary

progression

81

Among the 20 healing eyes, 20% were young and 80% were old.

Among the 9 stationary eyes 33.3%were young and 66.7% were old.

Among the 13 progressive eyes 23.1%were young and 76.9% were old.

1650%

619%

1031%

> 40 yrs

healing

stationary

progressive

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

healing stationary progressive

43

3

166

10> 40 yrs

< 40 yrs

82

WITH RESPECT TO LATERALITY

Of the 18 unilateral eyes, 61.1% were in healing stage, 16.7% were

in stationary stage and 22.2% were in progressive stage. Of the 24

bilateral eyes, 37.5%were in healing stage, 25% were in stationary stage

and 25 % were in progressive stage.

Unilateral Bilateral

Healing 11 9

Stationary 3 6

Progressive 4 9

p =0.071

1161%

317%

422%

unilateral

healing

stationary

progressive

83

Of the 20 eyes which were in healing stage 55%were unilateral and

45%were bilateral. Of the 9 eyes which were in stationary, 33.3% were

unilateral and 66.7% were bilateral. Of the 13 eyes which were in

progressive stage, 30.5%were unilateral ,69.2% were bilateral.

937%

938%

625%

bilateral

healing

stationary

progressive

0%

20%

40%

60%

80%

100%

healing stationary progressive

bilateral

unilateral

84

ON COMPARING SEVERITY OF ULCER WITH

PROGRESSION OF ULCER

Among the 20 healing eyes, 12 (60%) were mild cases, 7 (35%)

were moderate cases and 1(5%) was severe case. Among the 9 stationary

eyes, 2 (22.2%) were mild cases,5(55.6%)were moderate cases,

2(22.2%)were severe cases. Among the 13 progressive eyes, 1 was mild

(7.69%), 10(76.9%) were moderate and 2(15.38%) were severe.

Healing

(n=20)

Stationary

(n=9)

Progressive

(n=13)

Mild

(n=15) 12 2 1

Moderate

(n=22) 7 5 10

Severe

(n=5) 1 2 2

p = 0.026

85

0

2

4

6

8

10

12

14

16

18

20

healing stationary progressive

severe

moderate

mild

0

5

10

15

20

25

mild moderate severe

progressive

stationary

healing

Stage-mild, 2 clock hour, 1/3rd depth, fluorescein negative

Stage-mild with 2 clock hour, 1/3rd depth, fluorescein positive

Stage moderate- 5 clock hour, ½ depth, fluorescein positive

Stage-severe- 10 clock hours, 3/4th depth, fluorescein positive

Mild ulcer in healing stage with epithelisation and decrease in depth of ulcer

Conjunctival resection

Severe ulcer – before and after penetrating keratoplasty

Post penetrating keratoplasty status

86

DISCUSSION

87

DISCUSSION

The study was conducted in a tertiary eye care hospital in South

India for a period of one year. 42 eyes of 30 patients were included in the

study.

AGE

The mean age of presentation in our study was found to be 58.8

yrs.33.3% of cases occurred in age group<40 yrs and 66.7% occurred in

>40 yrs of age. Hence occurrence was found to be more common in older

age group more than 40 years.This was supported by a clinical study

conducted by Yan Ke Xue Bao in 1998 wherethe average age of onset

was reported to be 48.4 yrs old and 31.5% were young and 68.5% were

old. This is comparable to our study. The mean age of presentation was

observed to be 61 years in another study conducted by Srinivasan M et al.

SEX

Of the 30 patients included in the study, 90% were males and only 10%

were females with male female ratio of 9:1 which shows male

preponderance which is in congruous with the widely reported higher

88

incidence of this disease in this gender. A study by Srinivasan M et al

also reports a male preponderance with male female ratio of 4.7:1.

LATERALITY

In our study, 60% of patients were found to have unilateral disease

and 40 % were bilateral. All young people presented with unilateral

disease and among old, 40% were unilateral and 60%were bilateral. This

correlation was studied using Pearson Chi-Square test and p value was

found to be 0.002 which was statistically significant.

The two types of Mooren’s ulcer described by Wood and

Kaufmann shows that 75% of cases reported in young people were

bilateral and only 25 % of cases reported in old were bilateral.But a study

conducted byYan Ke Xue Bao¹ in 1998 shows that 30 % were bilateral

and among these 31.5% were young and 68.5% were old which is in

accordance to our study.

89

HISTORY OF TRAUMA

Totally 9 patients presented with history of trauma which

contributes to 30%. Of this, all were found to be young. This is supported

by Srinivasan M et al.

SUPERADDED INFECTION

Of the 42 eyes studied, 57.1% had superadded infections of which

25% were young and 75% were old.

VISUAL ACUITY

At the time of presentation, the visual acuity of 6/6-6/18 was found

in 40.5%, 6/24-6/60 was found in 35.7% and 5/60-1/60 was found in

23.81% of this majority of young patients presented with a good vision,

i.e., 6/6-6/18, about 80%. The vision in older age group varied almost

equally from6/6 to 1/60. This may be because of other coexistent causes

of defective vision in older age group like cataract.Of the 242 eyes

studied by Srinivasan M et al, 14% had 6/12 and better vision , 69% had

vision between 6/12 and 3/60, 17% had vision less than 3/60. Since we

had a smaller sample of 42 eyes our results are not comparable to theirs.

90

SEVERITY OF ULCER

The ulcer is divided into mild, moderate and severe. Mild ulcers

were 35.7% of which 20 % were young and 80%old. Moderate ulcers

were 52.38%of which 31.8% were young and 68.1% were old. Severe

ulcers were 11.9% of which all were old and none were young. Of the

younger population, 30%were mild and 70 %were moderate ulcers and of

the old, 37.5%were mild, 46.9%were moderate and 15.6% severe. Hence

severe ulcer was found only in older age group and in the young

moderate ulcers were more common. This result does not support the

classification of Mooren’s where younger people presented with severe

ulcer and older age group presented with mil and moderate type of ulcer.

PERFORATION RATE

The rate of perforation was 14.3% and of this 33.3%were young

and 66.7% were old. Again this data shows that old to have severe

manifestation.The study by Yan Ke Xue Bao¹ et al shows that the rate of

perforation as 13.3% and of these 43.2% were in young and 68.5% in

old. Our study results are similar to this.

91

MILD DISEASE

Of the 15 eyes with mild disease, 12(80%) were in healing stage,

2(13.3%) were in stationary stage and 1(6.7%) were in progressive stage.

Among the healing stage in mild disease, 75%were treated with topical

steroids, 16.7% with topical steroids and conjunctival resection and 8.3%

was treated with topical and systemic steroids along with conjunctival

resection. Thus majority of patients in mild disease was treated with

topical steroids alone and healing stage was achieved. Both progressive

and stationary were treated till oral steroids in the hierarchy.A study

conducted by Ashar JN⁵ et al evaluateda step ladder approach of

immunosuppressives in which topical steroids when used as a single

mode of therapy had a resolution rate of 76%and oral steroids has a

resolution rate of 86%. In another studyby Brown SI on therapy of

Mooren’s ulcer, of the 37 eyes studied, 12 healed with only topical

steroids alone. Eight eyes needed an additional conjunctival resection as

topical steroids alone failed to heal.

MODERATE CASES

Among the 22 eyes with moderate disease, 31.8% were in healing

stage, 22.7% were in stationary stage and 45.5% in progressive stage. Of

92

this, 71.4% healed with conjunctival resection and topical steroids,

28.6% with topical and oral steroids with conjunctival resection. Of the

stationary, 80%were treated till topical cycloimmune, 20%till oral

steroids. Of those in progressive stage, 40%with upto oral steroids, 20%

till cycloimmune, 20% with methotrexate and 20% needed Therapeutic

keratoplasty.

SEVERE CASES

Only 20% entered healing stage and this was treated upto oral

steroids.40% were stationary even with therapeutic keratoplasty and

methotrexate and 40% were progressive even with topical cycloimmune.

Hence severe cases were very difficult to treat and even with

immunosuppression and therapeutic keratoplasty most of them did not

enter the healing stage.In a study by Brown SI,of the bilateral

simultaneous cases, ten of twenty two only responded to topical steroids,

conjunctival resection and immunosuppression. They came to a

conclusion that if a bilateral Mooren’s ulcer occurs simultaneously, and if

it is active, it is severe and relentlessly progressive and no satisfactory

treatment exists. This is similar to our study results. In a study by Foster

CS, there was an arrest in the progressively destructive inflammatory

93

disease process and preservation of ocular anatomy and function was

observed in eight patients started on systemic immunosuppression for 6

to 24 months. They came to a conclusion that came to a conclusion that

immunosuppressive drugs like methotrexate or cyclophosphamide when

used properly may offer reasonable care for patients with progressive

bilateral Mooren’s ulcer.

HEALING IN RELATION TO GRADE OF ULCER

In our study, of the 42 eyes observed, 47.6% were in healing stage,

21.4%in stationary stage, 31% in progressive stage. Of the 20 healing

eyes, 60% were mild, 35% were moderate and 5 % were severe. Hence if

the disease is presented early and identified early, it has high chance of

healing and whereas if the patient first reports with severe disease, it is

very difficult to treat and only very few cases enter healing stage and that

too with maximum possible medication available. Of the stationary eyes,

22.2%were mild, 55.6% were moderate and 22.2% were severe.

Of the progressives, 7.7% were mild, 76.9%were moderate and

15.4% were severe. Hence most of the moderate eyes were still in

progressive stage. Majority of healing were in mild cases and severe were

in either progressive or stationary and only a few healed. This associated

94

was studied using Pearson Chi-Square test and p value was found to be

0.026 suggesting a significant association between the variables.

HEALING IN RELATION TO AGE AND LATERALITY

In our study, 20% of young and 80 % of old entered healing stage.

Hence if age is considered, older people seem to have a higher chance of

entering healing stage compared to young people. This is supported by

the broad classification of Mooren’s ulcer where young people had

severe disease and there was poor response to therapy whereas older age

group responded better to treatment.

Of the healing eyes, 55% were unilateral and 45% were bilateral.

Hence laterality doesn’t seem to affect the healing in our study.

STATIONARY IN RELATION TO AGE AND

LATERALITY

In our study 9 eyes were in stationary stage. In this 33.3% were

young and 66.7% were old. Regarding laterality, 33.3% were unilateral

and 66.7% were bilateral.

95

PROGRESSION IN RELATION TO AGE AND

LATERALITY

In our study, 13 eyes were in progressive stage. Of this, 23.1%

were young and 76.9% were old. And regarding laterality, 30.5% were

unilateral and 69.2% were bilateral. Hence bilateral disease is in

progressive stage more than the unilateral disease.

Among the younger age group, 40% were in healing stage, 30%

were in stationary and 30 % were in progressive stage. Hence the

distribution of response to treatment is equivocal in younger age group.

In the older age group, 50% were in healing stage, 18.8% were in

stationary stage and 31.3% were in progressive stage. Hence in older age

group, majority of eyes were in healing stage whereas in young, age

doesn’t appear to play a role in healing. Hence if age is taken into

consideration, older age group appear to have a better prognosis.

Among laterality, in unilateral cases, 61.1% were in healing stage,

22.2% were in progressive stage and 16.7% in stationary stage. Hence

according to our study, if the disease is unilateral it has higher chance of

entering healing stage which is a sign of good prognosis. In bilateral

96

cases, 37.5% were in healing stage, 25% were in stationary stage and

37.5% were in progressive stage. No conclusion could be obtained

regarding bilateral cases.

97

SUMMARY

98

SUMMARY

· The mean age of presentation in our study was found to be 58.8

yrs. Occurrence was found to be more common in older age group

more than 40 years (66.7%).

· 90% were males and only 10% were females with male female

ratio of 9:1 which shows male preponderance.

· Unilateral disease was more common compared to bilateral disease

and all young people reported with unilateral disease. This might

probably be due to higher health seeking behaviour in young

compared to old. Hence they report as soon as the disease starts in

one eye.

· History of trauma was found in 30% of this all were young.

· 80% of young people had good vision (6/6- 6/18) at the time of

presentation. Again due to earlier presentation and absence of

associated confounding factors like cataract.

· Visual acuity in older individuals varies equally from 6/6-1/60

· Severe type of ulcer did not occur in young. In this age group,

moderate ulcers were common (70%).

· 15.6% of ulcers in old were severe and moderate type

predominated in this age group too (46.9%).

99

· Perforation rate is 14.3% and it is more common in older age

group.

· Of the mild ulcers, majority were in healing stage (80%) denoting

that it is easier to treat if the patient presented earlier in the mild

disease itself. Also in the mild disease, 75% were treated with

topical steroids alone and still healing stage was achieved in a

maximum number of patients.

· Moderate cases are equally dispersed among the healing, stationary

and progressive stage and of those which healed 71.4% needed

topical steroids and conjunctival resection. Whereas 20%of those

in progressive stage even with therapeutic keratoplasty still

remained progressive at the end of the study

· In severe ulcers, even with therapeutic keratoplasty and

methotrexate 40% remained stationary. Hence severe ulcers were

difficult to treat.

· Of the healing eyes majority were mild cases (60%)

· On comparing age with laterality, only older people had bilateral

disease and all young had unilateral disease. This correlation was

studied using Pearson Chi-Square test and p value was found to

be 0.002 which was statistically significant

100

· On comparison between the stage of ulcer at presentation and the

treatment outcome at the end of 4 months, majority of healing

were in mild cases and severe were in either progressive or

stationary and only a few healed. This associated was studied using

Pearson Chi-Square test and p value was found to be 0.026

suggesting a significant association between the variables.

· On comparing the laterality and stage of ulcer after treatment, the

progressive and stationary cases had more of the bilateral ulcer

type than the unilateral ones. Hence bilaterality is associated with

poor prognosis and this comparison is studied using Pearson Chi-

Square test and the p value was found to be 0.071. This shows a

significant association between the variables.

101

CONCLUSION

102

Mooren’s ulcer is a relentlessly progressive painful ulceration of

cornea with autoimmune aetiology. Steroids and immunosuppressants

form the main stay of medical therapy and when it fails surgical

interventions like conjunctival resection and in extreme cases with

perforation keratoplasty is opted.

In our study the young people mostly presented earlier with

unilateral disease with good visual acuity and milder form and healed

better with one or two medications. The bilateral disease which occurred

in older people were more severe and more difficult to treat and even

with maximal therapy only stationary stage is achieved.

Hence earlier recognition and prompt treatment with steroids and

immunosuppressants is the modality of treatment for Mooren’s ulcer

depending upon the stage of ulcer at the time of presentation.

103

PART III

104

BIBLIOGRAPHY

105

BIBLIOGRAPHY

1. Tuft 2003: Tuft S. Mooren’s Ulcer. In: Johnson GJ, Minassian DC,

Weale RA, West SK editor(s). Epidemiology of Eye Disease.

London: Arnold, 2003:209–11.

2. Alhassan 1999; Alhassan MB. Mooren’s ulcer: clinical types and

treatmentoutcome. Ophthalmological Society of Nigeria Annual

Conference; Abuja, Nigeria. 1999

3. Zegans1998 {published data only}Zegans ME, Srinivasan M.

Mooren’s ulcer. International Opthalmology Clinics

1998;38(4):81–8.

4. Chen 2000 {published data only}Chen J, Xie H, Wang Z, Yang B,

Liu Z, Chen L, et al. Mooren’s ulcer in China: a study of clinical

characteristics and treatment. British Journal of Ophthalmology

2000; 84 (11):1244–9.

5. Taylor 2000: Taylor CJ, Smith SI, Morgan CH, Stephenson SF,

Key T, Srinivasan M, et al.HLA and Mooren’s ulceration. British

Journal of Ophthalmology 2000;84(1):72–5.

6. Zhao 1993 {published data only}Zhao JC, Jin XY. Immunological

analysis and treatment of Mooren’s ulcer with cyclosporin A

applied topically. Cornea 1993; 12(6):481–8.

106

7. Young 1982: Young RG, Watson PG. Light and electron

microscopy of corneal melting syndrome (Mooren’s ulcer). British

Journal of Ophthalmology 1982; 66(6):341–56.

8. . Bouchard 1998: Bouchard CS. Mooren’s Ulcer. In: Yannoff M,

Duker JS editor(s). Ophthalmology. St Louis: Mosby, 1998.

9. Foster 1999: Foster CS. Immunologic disorders of the conjunctiva,

cornea and sclera. In: Albert DM, Jakobiec FA editor(s). Principles

and Practice of Ophthalmology. 2nd Edition. Philadelphia: WB

Saunders, 1999:803–28.

10. Wilhelmus 2001: Wilhelmus KR, Huang AJ, Hwang DG, Parrish

CM, Sutphin JE, Whitsett JC. External disease and cornea. In:

Liesegang TJ, Deutsch TA, Grand MG editor(s). Basic and

Clinical Science Course for Ophthalmologists Section 8. San

Francisco, CA: American Academy of Ophthalmology,

2001:217–8.

11. Kanski 2003: Kanski JJ. Clinical Ophthalmology: A Systematic

Approach. 5th Edition. Philadelphia: Butterworth-Heinemann,

2003: 117–9.

12. Kalogeropulous 2004 {published data only}Kalogeropulous CD,

Malamou-Mitsi VD, Aspiotis MB, Psilas KG. Bilateral Mooren’s

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ulcer in six patients: diagnosis, surgery and histopathology.

International Ophthalmology 2004;25(1):1–8.

13. Sharma 2005 {published data only}Sharma A, Vishawanath KB,

Mohan K. Critical analysis of management options in Mooren’s

ulcer. All India Ophthalmological Society. Jan 2005.

14. Yan Ke Xue Bao. 1998 Sep;14(3):164-9.A study of clinical

characteristics and treatment of Mooren's ulcer. Xie H, Chen J,

Gong X, Feng C, Chen L.

15. Br J Ophthalmol. 2007 May;91(5):570-5. Epub 2006 Oct 11.

Clinical characteristics of Mooren's ulcer in South India.

Srinivasan M1, ZegansME, Zelefsky JR, Kundu A, Lietman T,

Whitcher JP, Cunningham ET Jr.

16. Br J Ophthalmol. 2013 Nov;97(11):1391-4. doi: 10.1136/

bjophthalmol 2012-302627. Epub 2013 Mar 27.

Immunosuppression for Mooren's ulcer: evaluation of the

stepladder approach--topical, oral and intravenous

immunosuppressive agents. Ashar JN1, Mathur A, Sangwan VS.

17. Optom Vis Sci. 1998 Nov;75(11):783-90. Mooren's ulcer. Seino

JY1, Anderson SF.

18. Cornea. 2008 Sep;27(8):859-61. doi: 10.1097/ICO.

0b013e3181702d0c. Outcome of treatment of mooren ulcer with

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topical cyclosporine a 2%. Tandon R1, Chawla B, Verma K,

Sharma N, Titiyal JS.

19. Ophthalmology. 1985 Oct;92(10):1436-9. Systemic

immunosuppressive therapy for progressive bilateral Mooren's

ulcer. Foster CS.

20. Am J Ophthalmol. 1984 Jul 15;98(1):1-6. Therapy of Mooren's

ulcer. Brown SI, Mondino BJ.

21. Ophthalmology. 2007 Mar;114(3):446-9. Epub 2007 Jan

2.Treatment of Mooren's ulcer with topical administration of

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Dagli S.

22. Br J Ophthalmol. 2012 Jun;96(6):796-800. doi: 10.1136/

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23. Ophthalmology. 2007 Mar;114(3):450-3. Epub 2006 Nov

21.Hookworm infestation as a risk factor for Mooren's ulcer in

South India. Zelefsky JR1, Srinivasan M, Kundu A, Lietman T,

Whitcher JP, Wang K, Buyse M, Cunningham ET Jr.

24. Clin Experiment Ophthalmol. 2011 Jul;39(5):386-92. doi:

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membrane transplantation for Mooren's ulcer. Ngan ND1, Chau

HT.

25. Fontana 2007 {published data only}Fontana L, Parente G, Neri P,

Reta M, Tassinari G. Favourable response to infliximab in a case

of bilateral Mooren’s ulcer. Clinical & Experimental

Ophthalmology 2007;35(9):871–3.

26. Hill 1987 {published data only}Hill JC, Potter P. Treatment of

Mooren’s ulcer with cyclosporin A: a report of three cases. British

Journal of Ophthalmology 1987;71(1):11–5.

27. Shimmura 2003 {published data only}Shimmura S, Igarashi R,

Yaguchi H, Ohashi Y, Shimazaki J, Tsubota K. Lecithin-bound

superoxide dismutase in the treatment of non-infectious corneal

ulcers. American Journal of Ophthalmology 2003;135(5):613–9.

28. Moazami 1995; Moazami G, Auran JD, Florakis GJ, Wilson SE,

Srinivasan DB. Interferon treatment of Mooren’s ulcers associated

with hepatitis C. American Journal of Ophthalmology 1995;119

(3):365–6.

29. Wilson 1994; Wilson SE, LeeWM, Murakami C, Weng J,

Moninger GA. Mooren-type hepatitis C virus-associated corneal

ulceration. Ophthalmology 1994;101(4):736–45.

110

30. Erdem 2007 {published data only}Erdem U, Kerimoglu H,

Gundogan FC, Dagli S. Treatment of Mooren’s ulcer with topical

administration of interferon alfa 2a. Ophthalmology

2007;114(3):446–9.

31. Van der Gaag 1983; Van der Gaag R, Abdillahi H, Stilma JS,

Vetter JCM. Circulating antibodies against cornea epithelium

andhookworm in patients with Mooren’s ulcer in Sierra

Leone.British Journal of Ophthalmology 1983;67(9):623–8.

111

PROFORMA

112

PROFORMA

S.NO.

NAME

AGE

SEX

LATERALITY

DURATION OF ILLNESS

HISTORY OF TRAUMA

HISTORY OF CONNECTIVE TISSUE INVOLVEMENT/JOINT

INVOLVEMENT/ SKIN INVOLVEMENT

HISTORY OF RECURRENT RESPIRATORY TRACT INFECTIONS

AND RENAL INVOLVEMENT

CLINICAL FEATURES

VISION

TENSION BY NCT

113

ULCER DESCRIPTION

-LOCATION

-NO OF CLOCK HOURS OF INVOLVEMENT

-DEPTH OF STROMAL INVOLVEMENT

-PERFORATION + /-

-FLUORESCEIN STAIN +/-

DIAGRAM OF THE ULCER

FRONTAL VIEW OF CORNEA SLIT VIEW

CORNEAL SENSATION

SCHIRMERS TEST 1

FUNDUS

CORNEAL SMEAR

114

CULTURE AND SENSITIVITY

INVESTIGATIONS

COMPLETE BLOOD COUNT

TOTAL COUNT

DIFFERNTIAL COUNT

ERYTHROCYTE SEDIMENT RATE

C REACTIVE PROTEIN

RHEUMATOID FACTOR

ANTI NUCLEAR ANTIBODY

MANTOUX TEST

CHEST X-RAY

BLOOD SUGAR

LIVER FUNCTION TEST

RENAL FUNCTION TEST

TREATMENT GIVEN

MEDICAL

SURGICAL

115

FOLLOW UP AT 1, 2, 3, 4, 6, 8, 12 AND 16 WEEKS

VISION

ULCER DESCRIPTION-NO OF CLOCK HOURS OF

INVOLVEMENT

-DEPTH OF STROMAL INVOLVEMENT

-PERFORATION + /-

-FLUORESCEIN STAIN +/-

116

KEY TO MASTER CHART

AGE IN YEARS

M- MALE

F- FEMALE

DURATION OF ILLNESS - IN MONTHS

RE- RIGHT EYE

LE- LEFT EYE

+ PRESENT

- ABSENT

CR- CONJUNCTIVAL RESECTION

MTX- METHOTREXATE

TKP- THERAPEUTIC KERATOPLASTY

117

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+m

oder

ate

++

++

-+

prog

ress

ion

570

Mbi

late

ral

6-

RE-

1/6

06

1/2

+-

mod

erat

e+

++

--

-pr

ogre

ssio

n -

LE-

6/1

82

1/4

--

mild

+ -

+-

--

heal

ng6

70M

unila

tera

l1

-LE

- 6

/12

2 1

/4-

-m

ild+

--

--

-he

alin

g7

73M

bila

tera

l5

-RE

- 3

/60

2 1

/4-

-m

ild+

-+

--

-pr

ogre

ssio

n -

LE-

1/6

04

1/4

+-

mod

erat

e+

++

--

-pr

ogre

ssio

n8

65M

unila

tera

l2

-RE

+ 6

/60

2 1

/2-

-m

ild+

+-

--

-he

alin

g9

24M

unila

tera

l2

+RE

+ 6

/63

1/2

+-

mod

erat

e+

++

+-

_st

atio

nary

1060

Mbi

late

ral

12-

RE+

6/6

010

3/4

++

seve

re+

++

+-

-pr

ogre

ssio

n -

LE+

1/6

08

1/2

++

seve

re+

++

+-

-pr

ogre

ssio

n11

33F

unila

tera

l2

+LE

+ 6

/93

1/2

+-

mod

erat

e+

+-

--

-he

alin

g12

35M

unila

tera

l1

+RE

+ 6

/12

3 1

/2+

-m

oder

ate

++

--

--

heal

ing

1363

Mun

ilate

ral

3-

RE+

6/1

22

1/4

--

mild

+-

--

--

heal

ing

1478

Mun

ilate

ral

6-

LE+

6/6

02

1/2

+-

mod

erat

e+

++

--

-pr

ogre

ssio

n15

35M

unila

tera

l2

-RE

- 6

/64

1/2

+-

mod

erat

e+

++

+-

-pr

ogre

ssio

n16

84M

unila

tera

l3

-LE

+ 6

/36

3 1

/4+

-m

oder

ate

++

--

--

heal

ing

1788

Mbi

late

ral

4-

RE-

6/6

01

1/4

--

mild

+-

--

--

heal

ing

-LE

- 6

/60

5 1

/4+

-m

oder

ate

++

--

--

heal

ing

1861

Mbi

late

ral

6-

RE+

6/2

44

1/2

+-

mod

erat

e+

++

+-

-st

atio

nary

-LE

+ 6

/18

2 1

/4-

-m

ild+

-+

--

-st

atio

nary

1928

Fun

ilate

ral

2+

LE-

6/1

23

1/4

+-

mild

++

+-

--

stat

iona

ry20

85M

unila

tera

l3

-RE

- 6

/18

1 1

/4+

-m

ild+

--

--

-he

alin

g21

62M

bila

tera

l6

-RE

+ 5

/60

6 1

/2+

-m

oder

ate

++

+-

--

prog

ress

ion

-LE

+ 4

/60

9 1

/2+

_m

oder

ate

++

++

--

prog

ress

ion

2273

Mun

ilate

ral

2-

RE-

6/1

83

1/2

+-

mod

erat

e+

+-

--

-he

alin

g23

37M

unila

tera

l2

+RE

+ 6

/62

1/4

--

mild

+-

--

--

heal

ing

2431

Mun

ilate

ral

3+

RE+

6/9

5 1

/2+

+m

oder

ate

++

++

-+

prog

ress

ion

2580

Mbi

late

ral

12-

RE+

1/6

06

1/2

+-

mod

erat

e+

++

++

-pr

ogre

ssio

n -

LE+

2/6

08

1/2

+-

mod

erat

e+

++

++

-pr

ogre

ssio

n26

68M

unila

tera

l3

-RE

- 6

/60

3 1

/2-

-m

ild+

+-

--

-he

alin

g27

30F

unila

tera

l2

+LE

- 6

/18

2 1

/4-

-m

ild+

--

--

-he

alin

g28

75M

bila

tera

l6

-RE

+ 6

/36

5 1

/4+

-m

oder

ate

++

++

--

stat

iona

ry -

LE+

6/6

07

1/2

+-

mod

erat

e+

++

+-

-st

atio

nary

2979

Mbi

late

ral

4-

RE-

6/6

02

1/4

--

mild

+-

+-

--

heal

ing

-LE

- 6

/60

6 1

/2+

-m

oder

ate

++

+-

--

heal

ing

3025

Mun

ilate

ral

4+

RE+

6/3

64

1/4

+-

mod

erat

e+

++

--

-st

atio

nary

MA

STE

R C

HA

RT