notes/A K Khurana - Comprehensive Ophthalmology_4.txt

9. Vicarious bleeding associated with menstruation is an extremely rare cause of subconjunctival haemorrhage.
Clinical features
• Subconjunctival haemorrhage per se is sympt-omless. However, there may be symptoms of associated causative disease.
• On examination, subconjunctival haemorrhage looks as a flat sheet of homogeneous bright red colour with well-defined limits (Fig. 5.34).
• In traumatic subconjunctival haemorrhage, posterior limit is visible when it is due to local trauma to eyeball, and not visible when it is due to head injury or injury to the orbit.
• Most of the time it is absorbed completely within 7 to 21 days. During absorption colour changes are noted from bright red to orange and then yellow. In severe cases, some pigmentation may be left behind after absorption.
Chapter 5	Diseases of Conjunctiva	91















Fig. 5.34 Subconjunctival haemorrhage

Treatment
• Treat the cause when discovered.
• Placebo therapy with astringent eye drops.
• Psychotherapy and assurance to the patient is most important part of treatment.
• Cold compresses to check the bleeding in the initial stage and hot compresses may help in absorption of blood in late stages.
XEROSIS OF CONJUNCTIVA
Xerosis of the conjunctiva is a symptomatic condition in which conjunctiva becomes dry and lustreless. Normal conjunctiva is kept moist by its own secretions, mucin from goblet cells and aqueous solution from accessory lacrimal glands. Therefore, even if the main lacrimal gland is removed, xerosis does not occur. Depending upon the etiology, conjunctival xerosis can be divided into two groups, parenchymatous and epithelial xerosis.
1. Parenchymatous xerosis. It occurs following cicatricial disorganization of the conjunctiva due to local causes which can be in the form of:
• Destructive interstitial conjunctivitis as seen in trachoma, diphtheric membranous conjunctivitis, Steven-Johnsons syndrome, pemphigus or pemphigoid conjunctivitis, thermal, chemical or radiational burns of conjunctiva.
• Exposure of conjunctiva to air as seen in marked degree of proptosis, facial palsy, ectropion, lack of blinking (as in coma), and lagophthalmos due to symblepharon.
2. Epithelial xerosis.  It occurs due to hypo-vitaminosis-A. Epithelial xerosis may be seen in association with night blindness or as a part and parcel of the xerophthalmia (the term which is applied to all ocular manifestations of vitamin A deficiency) which range from night blindness to keratomalacia (see pages 467–470).

Clinical features. Epithelial xerosis typically occurs in children and is characterized by varying degree of conjunctical dryness, thickening, wrinkling and pigmentation.
Treatment. Treatment of conjunctival xerosis consists of:
• Treatment of the cause,
• Symptomatic local treatment with artificial tear preparations (0.7% methyl cellulose or 0.3% hypromellose or polyvinyl alcohol), which should be instilled frequently.
DISCOLORATION OF CONJUNCTIVA
Normal conjunctiva is a thin transparent structure. In the bulbar region, underlying sclera and a fine network of episcleral and conjunctival vessels can be easily visualized. In the palpebral region and fornices, it looks pinkish because of underlying fibrovascular tissue.
Causes. Conjunctiva may show discoloration in various local and systemic diseases given below:
1. Red discoloration. A bright red homogeneous discoloration  suggests  subconjunctival haemorrhage (Fig. 5.34).
2. Yellow discoloration. It may occur due to: (i) bile pigments in jaundice, (ii) blood pigments in malaria and yellow fever, (iii) conjunctival fat in elder and Negro patients.
3. Greyish discoloration. It may occur due to application of Kajal (surma or soot) and mascara in females.
4. Brownish grey discoloration. It is typically seen in argyrosis, following prolonged application of silver nitrate for treatment of chronic conjunctival inflammations. The discoloration is most marked in lower fornix.
5. Blue discoloration. It is usually due to ink tattoo from pens or effects of manganese dust. Blue discoloration play also be due to pseudopigmentation as occurs in patients with blue sclera and scleromalacia perforans.
6. Brown pigmentation. Its common causes can be grouped as under:
a. Non-melanocytic pigmentation
i.  Endogenous pigmentation. It is seen in patients with Addison’s disease and ochronosis.
ii. Exogenous pigmentation. It may follow long-term use of adrenaline for glaucoma. Argyrosis may also present as dark brown pigmentation.
b. Melanocytic pigmentation
i.  Conjunctival epithelial melanosis (Fig. 5.35). It develops in early childhood, and then remains stationary. It is found in 90% of the blacks. The
92	Section III   Diseases of Eye












Fig. 5.35 Conjunctival epithelial melanosis

pigmented spot freely moves with the movement of conjunctiva. It has got no malignant potential and hence no treatment is required.
ii. Subepithelial melanosis. It may occur as an isolated anomaly of conjunctiva (congenital melanosis oculi, Fig. 5.36) or in association with the ipsilateral hyperpigmentation of the face (oculodermal melanosis or Naevus of Ota). iii.Pigmented tumours. These can be benign naevi, precancerous melanosis or malignant
melanoma.

CYSTS AND TUMOURS

CYSTS OF CONJUNCTIVA
The common cystic lesions of the conjunctiva are: 1. Congenital cystic lesions. These are of rare
occurrence and include congenital corneoscleral cyst and cystic form of epibulbar dermoid.
2. Lymphatic cysts of conjunctiva. These are common and usually occur due to dilatation of lymph spaces in the bulbar conjunctiva. Lymphangiectasis is characterized by a row of small cysts. Rarely, lymphangioma may occur as a single multilocular cyst.
3. Retention cysts. These occur occasionally due to blockage of ducts of accessory lacrimal glands of Krause in chronic inflammatory conditions, viz.,












Fig. 5.36 Congenital melanosis oculi

trachoma and pemphigus. Retention cysts are more common in upper fornix.
4. Epithelial implantation cyst (traumatic cyst). It may develop following implantation of conjunctival epithelium in the deeper layers, due to surgical or non-surgical injuries of conjunctiva.
5. Epithelial cysts due to downgrowth of epithelium are rarely seen in chronic inflammatory or degenerative conditions, e.g., cystic change in pterygium.
6. Aqueous cyst. It may be due to healing by cystoid cicatrix formation, following surgical or non-surgical perforating limbal wounds.
7. Pigmented epithelial cyst. It may be formed sometimes following prolonged topical use of cocaine or epinephrine.
8. Parasitic cysts such as subconjunctival cysticercus (Fig. 5.37), hydatid cyst and filarial cyst are not infrequent in developing countries.
Treatment
Conjunctival cysts need a careful surgical excision. The excised cyst should always be subjected to histopathological examination.
TUMOURS OF CONJUNCTIVA Classification
Non-pigmented tumours
i.  Congenital:  Dermoid  and  lipodermoid (choristomas).
ii. Benign:Simple granuloma, papilloma, adenoma, fibroma and angiomas.
iii.Premalignant: Intraepithelial epithelioma (Bowen’s disease).
iv. Malignant: Epithelioma or squamous cell carcinoma, basal cell carcinoma.
Pigmented tumours
i.  Benign: Naevi or congenital moles.
ii. Precancerous melanosis: Superficial spreading melanoma and lentigo maligna (Hutchinson’s freckle).












Fig. 5.37 Cysticercosis of conjunctiva
Chapter 5	Diseases of Conjunctiva	93


iii. Malignant: primary melanoma (malignant melanoma).
A. Non-pigmented tumours
I. Congenital tumours
1. Dermoids. These are common congenital tumours which usually occur at the limbus. They appear as solid white masses, firmly fixed to the cornea (Fig. 5.38). Dermoid consists of collagenous connective tissue, sebaceous glands and hair, lined by epidermoid epithelium. Treatment is simple excision.
2. Lipodermoid (Fig. 5.39). It is a congenital tumour, usually found at the limbus or outer canthus. It appears as soft, yellowish white, movable subconjunctival mass. It consists of fatty tissue and the surrounding dermis-like connective tissue, hence the name lipodermoid.
Sometimes, the epibulbar dermoids or lipode-rmoids may be associated with accessory auricles and other congenital defects (Goldenhar’s syndrome).
II. Benign tumours
1. Simple granuloma. It consists of an extensive polypoid, cauliflower-like growth of granulation tissue. Simple granulomas are common following squint surgery, as foreign body granuloma and following inadequately scraped chalazion.











Fig. 5.38 Limbal dermoid














Fig. 5.39 Lipodermoid

■Treatment consists of complete surgical removal. 2. Papilloma. It is a benign polypoid tumour usually occurring at inner canthus, fornices or limbus. It may resemble the cocks comb type of conjunctival tubercular lesion. It has a tendency to undergo malignant change and hence needs complete excision. 3. Fibroma. It is a rare soft or hard polypoid growth usually occurring in lower fornix.
III. Premalignant tumours
Bowen’s intraepithelial epithelioma (carcinoma in situ). It is a rare, precancerous condition, now included in ocular surface squamous neoplasia (OSSN).
IV. Malignant tumours
1. Squamous cell carcinoma (epithelioma) (Fig. 5.40). It usually occurs at the transitional zones, i.e., at limbus and the lid margin. The tumour invades the stroma deeply and may be fixed to underlying tissues. Histologically, it is similar to squamous cell carcinomas occurring elsewhere (see page 385). Now it is also included in ocular surface squamous neoplasia (OSSN).
Ocular Surface Squamous Neoplasia Ocular surface squamous neoplasia (OSSN) is the term coined to denote the wide spectrum of dysplastic changes involving epithelium of conjunctiva, cornea and limbus. It includes squamous dysplasia, carcinoma-in-situ i.e. corneal and conjunctival intraepithelial neoplasia (CIN) and squamous cell carcinoma(SCC). CIN is characterised by partial to full thickness intraepithelial neoplasia with an intact basement membrane without involvement of the underlying substantia propria. While, SCC occurs when neoplastic cells penetrate the basement membrane and invade the underlying stroma. Very few CIN progress to SCC.















Fig. 5.40 Squamous cell carcinoma at the limbus
94	Section III   Diseases of Eye


Risk factors for OSSN include:
• Exposure to intense UV radiation, • Aadvanced age,
• Cigarette smoking,
• AIDS and conjunctival Human papilloma virus (HPV) infections,
• History of squamous cell carcinoma in head and neck,
• Xeroderma pigmentosa, and • Light complexion.
Pathogenesis. Since OSSN usually arise at the limbus, so it has been postulated that various predisposing factors probably act on the stem cells causing their abnormal maturation and proliferation resulting in OSSN (Stem cell theory).
Clinical features. Since, initially it is not possible to clinically differentiate between squamous dysplasia, carcinoma-in-situ and SCC; so that term OSSN is used. Three morphological patterns are described: • Leukoplakic form appears as a focal thickening
of the epithelium with overlying hyperkeratotic plaque,
• Papillomatous form appears as well-defined soft vascularised mass, and
• Gelatinous form appears as an ill-defined translucent thickening.
Over the period a nodular tumour involving the stroma deeply may occur as SCC (Fig 5.40). Treatment. Surgical excision with surrounding 2-4 mm of normal tissue is the treatment of choice. Measures to decrease recurrence include:
• Cryotherapy to surrounding tissue,
• Topical chemotherapy with mitomycin
Radical excision including enucleation and even exentration may be needed along with postoperative radiotherapy in advanced cases of SCC
2. Basal cell carcinoma. It may invade the conjunctiva from the lids or may arise pari-passu from the plica














Fig. 5.41 Conjunctival naevus


semilunaris or caruncle. Though it responds very favourably to radiotherapy, the complete surgical excision, if possible, should be preferred to avoid complications of radiotherapy.
B. Pigmented tumours
1. Naevi or congenital moles. These are common pigmented lesions, usually presenting as grey gelatinous, brown or black, flat or slightly raised nodules on the bulbar conjunctiva, mostly near the limbus (Fig. 5.41). They usually appear during early childhood and may increase in size at puberty or during pregnancy. Histologically, they resemble their cutaneous brethren. Malignant change is very rare and when occurs is indicated by sudden increase in size or increase in pigmentation or appearance of signs of inflammation. Therefore, excision is usually indicated for cosmetic reasons and rarely for medical reasons. Whatever may be the indication, excision should be complete.
2. Precancerous melanosis. Precancerous melanosis (intraepithelial melanoma) of conjunctiva occurs in adults as ‘superficial spreading melanoma’. It never arises from a congenital naevus.
■Clinically, a small pigmented tumour develops at any site on the bulbar or palpebral conjunctiva, which spreads as a diffuse, flat, asymptomatic pigmented patch. As long as it maintains its superficial spread, it does not metastasize. However, ultimately in about 20% cases it involves the subepithelial tissues and proceeds to frank malignant change.
■Treatment. In early stages local excision with postoperative radiotherapy may be sufficient. But in case of recurrence, it should be treated as malignant melanoma.
3. Malignant melanoma (primary melanoma). Malignant melanoma of the conjunctiva mostly arises de-novo, usually near the limbus, or rarely it may occur due to malignant change in pre-existing naevus. The condition usually occurs in elderly patients.
■Clinically, it may present as pigmented or nonpigmented mass near limbus or on any other part of the conjunctiva. It spreads over the surface of the globe and rarely penetrates it. Distant metastasis occurs elsewhere in the body, commonly in liver. ■Histologically, the neoplasm may be alveolar, round-celled or spindle-celled.
■Treatment. Once suspected, enucleation or exenteration is the treatment of choice, depending
upon the extent of growth.
6

Diseases of Cornea



CHAPTER OUTLINE

ANATOMY AND PHYSIOLOGY Applied anatomy
Applied physiology CONGENITAL ANOMALIES INFLAMMATIONS OF CORNEA Ulcerative keratitis
•
•
Infective keratitis Bacterial corneal ulcer Mycotic corneal ulcer Viral corneal ulcer Protozoal keratitis
•
•
•
•
Allergic keratitis Trophic corneal ulcer
•
•
Neurotrophic keratopathy Exposure keratopathy
Peripheral ulcerative keratopathies Non-ulcerative keratitis
•
•
Superficial Deep
CORNEAL DEGENERATIONS
•
Age-related corneal degenerations



ANATOMY AND PHYSIOLOGY

APPLIED ANATOMY
Cornea is a transparent, avascular, watch-glass like structure. It forms anterior one-sixth of the outer fibrous coat of the eyeball.
Dimensions
• Anterior surface of cornea is elliptical with an average horizontal diameter of 11.7 mm and vertical diameter of 11 mm.
• Posterior surface of cornea is circular with an average diameter of 11.5 mm.
• Thickness of cornea in the centre varies from 0.5 to 0.6 mm while at the periphery it varies from 1 to 1.2 mm.
• Radius of curvature. The central 5 mm area of the cornea forms the powerful refracting surface of the eye. The anterior and posterior radii of curvature of this central part of cornea are 7.8 mm and 6.5 mm, respectively.

• Pathological corneal degenerations CORNEAL DYSTROPHIES
Epithelial and subepithelial dystrophies Bowman layer dystrophies
•
•
•
•
Stromal corneal dystrophies
Descemet membrane and endothelial corneal dystrophies ECTATIC CONDITIONS OF CORNEA
•
•
•
Keratoconus Keratoglobus Keratoconus posterior
ABNORMALITIES OF CORNEAL TRANSPARENCY Corneal oedema
•
•
•
Corneal opacity Corneal vascularization
CORNEAL SURGERY Keratoplasty
•
•
•
•
Refractive corneal surgery Phototherapeutic keratectomy Keratoprosthesis



• Refractive index of the cornea is 1.376.
• Refractivepowerof the cornea is about 45dioptres, which is roughly three-fourth of the total refractive power of the eye (60 dioptres).
Histology
Histologically, the cornea consists of six layers. From anterior to posterior these are: epithelium, Bowman’s membrane, substantia propria (corneal stroma), Pre-Descemet’s membrane (Dua’s layer), Descemet’s membrane and endothelium (Fig. 6.1).
1. Epithelium. It is of stratified squamous type and becomes continuous with epithelium of bulbar conjunctiva at the limbus. It consists of 5–6 layers of cells. The deepest (basal) layer is made up of columnar cells, next 2–3 layers of wing or umbrella cells and the most superficial two layers are made of flattened cells. Tight junctions between superficial epithelial cells prevent penetration of tear fluid into the stroma. ■Limbal epithelium. The basal epithelial cells of the limbal area constitute the limbal stem cells which
96	Section III   Diseases of Eye




















Fig. 6.1 Microscopic structure of the cornea

amplify, proliferate, and differentiate into corneal epithelium. Damage to this area results in the invasion of conjunctival epithelium on to the cornea. 2. Bowman’s membrane. This layer consists of acellular mass of condensed collagen fibrils. It is about 12 mm in thickness and binds the corneal stroma anteriorly with basement membrane of the epithelium. It is not a true elastic membrane but simply a condensed superficial part of the stroma. It shows considerable resistance to infection. But once destroyed, it is unable to regenerate and, therefore, heals by scarring.
3. Stroma (substantia propria). This layer is about 0.5 mm in thickness and constitutes most of the cornea (90% of total thickness). It consists of collagen fibrils (type-I and type-V fibrillae interwined with filaments of type-VI collagen) embedded in hydrated matrix of proteoglycans (chondroitin sulphate and keratan sulphate). The lamellae are arranged in many layers. In each layer they are not only parallel to each other but also to the corneal plane and become continuous with scleral lamellae at the limbus. The alternating layers of lamellae are at right angle to each other. Among the lamellae are present keratocytes (modified fibroblasts), wandering macrophages, histiocytes and a few leucocytes.
4. Pre–Descemet’s  membrane, also known as Dua’s layer has been discovered in 2013 by Dr Harminder Dua, an Indian ophthalmologist working in Great Britain. Located anterior to   the Descemet’s membrane, it is about 15 micrometer thick acellular structure which is very strong and imprevious to air.

5. Descemet’s membrane (posterior elastic lamina). The Descemet’s membrane is a strong homogenous basement membrane of the corneal endothelium which is separated from the stroma by pre-Descemet’s membrane. It is very resistant to chemical agents, trauma and pathological processes. Therefore, ‘Descemetocele’can maintain the integrity of eyeball for long. Descemet’s membrane consists of collagen and glycoproteins. Unlike Bowman’s membrane it can regenerate. Normally, it remains in a state of tension and when torn, it curls inwards on itself. In the periphery it appears to end at the anterior limit of trabecular meshwork as Schwalbe’s line (ring). 6. Endothelium. It consists of a single layer of flat polygonal (mainly hexagonal) epithelial cells (misnamed as endothelium) which on slit-lamp biomicroscopy appear as a mosaic. The cell density of endothelium is around 3000 cells/mm2 in young adults, which decreases with the advancing age. The human endothelium cells do not proliferate in vivo and the cell loss with age is compensated by enlargement (polymegathism) and migration of neighbouring cells. There is a considerable functional reserve for the endothelium. Therefore, corneal decompensation occurs only after more than 75% of the cells are lost. The endothelial cells contain ‘active-pump’ mechanism which keeps cornea dehydrated.
Blood supply
Cornea is an avascular structure. Small loops derived from the anterior ciliary vessels invade its periphery for about 1 mm. Actually, these loops are not in the cornea but in the subconjunctival tissue which overlaps the cornea.
Nerve supply
Cornea is supplied by anterior ciliary nerves which are branches of ophthalmic division of the 5th cranial nerve (see page 5). After going about 2 mm in cornea the nerves lose their myelin sheath and divide dichotomously, and form three plexuses: the stromal, subepithelial and intraepithelial.
APPLIED PHYSIOLOGY
The two primary physiological functions of the cornea are (i) to act as a major refracting medium; and (ii) to protect the intraocular contents. Cornea performs these functions by maintaining its transparency and regular replacement of its tissues.
Corneal transparency
The corneal transparency is the result of:
• Peculiar arrangement of corneal lamellae (lattice theory of Maurice).
Chapter 6	Diseases of Cornea	97


• Peculiar refractive index of corneal lamellae with variation less than 200 mm (Goldmann and Benedek theory).
• Avascularity of cornea.
• Relative state of dehydration (78% water content), which is maintained by the barrier effects of epithelium and endothelium and the active Na+ K+ ATPase pump of the endothelium.
• Swellingpressure (SP) of the stroma which counters the imbibition effect of intraocular pressure (IOP).
• Corneal crystallins, i.e, water soluble proteins of keratocytes (transketolase and aldehyde dehydrogenase class IA1) also contribute to corneal transparency at the cellular level.
For these processes, cornea needs some energy.
Metabolism of cornea
Most actively metabolizing layers of the cornea are epithelium and endothelium, the former being 10 times thicker than the latter requires a proportionately larger supply of metabolic substrates.
Source of nutrients for cornea are:
1. Solutes (glucose and others) enter the cornea by either simple diffusion or active transport through aqueous humour and by diffusion from the perilimbal capillaries.
2. Oxygen is derived directly from air through the tear film. This is an active process undertaken by the epithelium. Therefore, corneal hypoxia may occur with over wear of contact lenses. Some oxygen may reach the superficial layers of cornea from the perilimbal capillaries (especially when eyelids are closed) and deeper corneal layers through the aqueous humour.
Endothelium requires oxygen and glucose for metabolic activities and proper functioning of Na+ - K+ATPase pump.
Like other tissues, the epithelium can metabolize glucose both aerobically and anaerobically into carbon dioxide and water and lactic acid, respectively. Thus, under anaerobic conditions lactic acid accumulates in the cornea.
Respiratory quotient of cornea is 1%.

CONGENITAL ANOMALIES

ANOMALIES OF SIZE AND SHAPE Megalocornea
Definition. Horizontal diameter of cornea at birth is about 10 mm and the adult size of about 11.7 mm is attained by the age of 2 years. Megalocornea is labelled when the horizontal diameter of cornea is of adult size at birth or 13 mm or greater after the age of 2 years.

Salient features. Cornea is usually clear with normal thickness and vision. The condition is not progressive. Systemic associations include Marfan’s, Apert, Ehlers Danlos and Down syndromes.
Differential diagnosis includes:
1.  Buphthalmos. In this condition IOP is raised and the eyeball is enlarged as a whole. The enlarged cornea is usually associated with central or peripheral clouding and Descemet’s tears (Haab’s striae).
2.  Keratoglobus. In this condition, there is thinning and excessive protrusion of cornea, which seems enlarged; but its diameter is usually normal.
Microcornea
In microcornea, the horizontal diameter is less than 10 mm since birth. The condition may occur as an isolated anomaly (rarely) or in association with nanophthalmos (normal small eyeball) or microphthalmos (abnormal small eyeball).
Cornea plana
This is a rare anomaly in which bilaterally cornea is comparatively flat since birth. It may be associated with microcornea. Cornea plana usually results in marked astigmatic refractive error.

ANOMALIES OF CORNEAL TRANSPARENCY Normal cornea is a transparent structure. A few congenital conditions in which corneal transparency is disturbed are as given below:
1.  Anterior embryotoxon. It is characterized by congenitally broad limbus superiorly.
2.  Posterior embryotoxon. It refers to thickening and anterior displacement of Schwalbe’s line.
3.  Congenital corneal opacity. Corneal opacity, i.e., scarring of corneal stroma, is often an acquired condition but has been reported to occur congenitally in isolation and also in association with Lowe’s syndrome, Axenfeld’s anomaly, Rieger’s syndrome and Peter’s anomaly.
4.  Sclerocornea refers to sclera like cloudy cornea, which may be peripheral or diffuse.
5.  Dermoidsusually occur at inferotemporal limbus and are round, dome shaped, and pink to white to yellow in colour (see page 93, Fig. 5.38). Rarely the dermoids may involve large area of cornea, the entire limbus, the entire cornea, or even the interior of the eye.
Differential diagnosis of neonatal cloudy cornea. The acronym ‘STUMPED’ helps to remember the common conditions to be included in differential diagnosis of neonatal cloudy cornea. The conditions
are as follows:
98	Section III   Diseases of Eye


• Sclerocornea
• Tears in Descemet’s membrane • Ulcer
• Metabolic conditions
• Posterior corneal defect • Endothelial dystrophy
• Dermoid.

INFLAMMATIONS OF CORNEA

Inflammation of cornea (keratitis) is characterised by corneal oedema, cellular infiltration and ciliary congestion.
Classification
It is difficult to classify and assign a group to each and every case of keratitis; as overlapping or concurrent findings tend to obscure the picture. However, the following simplified topographical and etiological classifications provide a workable knowledge.
Topographical (morphological) classification

A. Ulcerative keratitis (corneal ulcer)
Corneal ulcer can be further classified variously: 1. Depending on location
• Central corneal ulcer
• Peripheral corneal ulcer 2. Depending on purulence
• Purulent corneal ulcer or suppurative corneal ulcer (most bacterial and fungal corneal ulcers are suppurative).
• Non-purulent corneal ulcers (most of viral, chlamydial and allergic corneal ulcers are non-suppurative).
3. Depending upon association of hypopyon
• Simple corneal ulcer (without hypopyon) • Hypopyon corneal ulcer
4. Depending upon depth of ulcer • Superficial corneal ulcer
• Deep corneal ulcer
• Corneal ulcer with impending perforation • Perforated corneal ulcer
5. Depending upon slough formation • Non-sloughing corneal ulcer
• Sloughing corneal ulcer

B. Non-ulcerative keratitis 1. Superficial keratitis
• Diffuse superficial keratitis
• Superficial punctate keratitis (SPK) 2. Deep keratitis
a. Non-suppurative • Interstitial keratitis
• Disciform keratitis

• Keratitis profunda • Sclerosing keratitis
b. Suppurative deep keratitis • Central corneal abscess
• Posterior corneal abscess.
Etiological classification 1. Infective keratitis
• Bacterial keratitis • Viral keratitis
• Fungal keratitis
• Chlamydial keratitis • Protozoal keratitis
• Spirochaetal keratitis 2. Allergic keratitis
• Phlyctenular keratitis • Vernal keratitis
• Atopic keratitis 3. Trophic keratitis
• Exposure keratitis
• Neurotrophic keratopathy • Keratomalacia
• Atheromatous ulcer
4. Keratitis associated with diseases of skin and mucous membrane.
5. Keratitisassociatedwithsystemiccollagenvascular disorders.
6. Traumatic keratitis which may be due to mechanical trauma, chemical trauma, thermal burns, radiations.
7. Idiopathic keratitis e.g.,
• Mooren’s corneal ulcer
• Superior limbic keratoconjunctivitis
• Superficial punctate keratitis of Thygeson.

ULCERATIVE KERATITIS

Corneal ulcer may be defined as discontinuation in normal epithelial surface of cornea associated with necrosis of the surrounding corneal tissue. Pathologically, it is characterised by oedema and cellular infiltration. Common types of corneal ulcers are described below.

INFECTIVE KERATITIS

BACTERIAL CORNEAL ULCER

Being the most anterior part of eyeball, the cornea is exposed to atmosphere and hence prone to get infected easily. At the same time cornea is protected from day-to-day minor infections by the normal defence mechanisms present in tears in the form of
Chapter 6	Diseases of Cornea	99


lysozyme, betalysin and other protective proteins. Therefore, infective corneal ulcer may develop when: • Either the local ocular defence mechanism is
jeopardised, or
• There is some local ocular predisposing disease, or • Host’s immunity is compromised, or
• The causative organism is very virulent.

Etiology
There are two main factors in the production of purulent corneal ulcer:
• Damage to corneal epithelium; and • Infection of the eroded area.
However, following three pathogens can invade theintactcornealepithelium and produce ulceration: Neisseriagonorrhoeae,Corynebacteriumdiphtheriae and Neisseria meningitidis.
1. Corneal epithelial damage. It is a pre-requisite for most of the infecting organisms to produce corneal ulceration. It may occur in following conditions:
• Corneal abrasion due to small foreign body, misdirected cilia, concretions and trivial trauma in contact lens wearers or otherwise.
• Epithelial drying as in xerosis and exposure keratitis.
• Necrosis of epithelium as in keratomalacia.
• Desquamation of epithelial cells as a result of corneal oedema as in bullous keratopathy.
• Epithelial damage due to trophic changes as in neuroparalytic keratitis.
2.  Sources of infection include:
• Exogenous infection. Most of the times corneal infection arises from exogenous source like conjunctival sac, lacrimal sac (dacryocystitis), infected foreign bodies, infected vegetative material and waterborne or airborne infections.
• Fromtheoculartissue.Owing to direct anatomical continuity, diseases of the conjunctiva readily spread to corneal epithelium, those of sclera to stroma, and of the uveal tract to the endothelium of cornea.
3. Causative organisms. Bacteria reported to be associated with keratitis can be classified as below: • Gram positive cocci: Staphylococcus aureus,
Staphylococcus epidermidis and Streptococcus pneumoniae.
• Gram negative cocci: Neisseria gonorrhoeae, Neisseria meningitidis.
• Grampositivebacilli:Corynebacteriumdiptheriae, C. xerosis, Bacilluscereus, Propionibacteriumacne, listeria and clostridium.
• Gram negative bacilli: Pseudomonas aeruginosa, Enterobacteriaceae (Klebsiella, Proteus, E. coli,

Serratia), Moraxella lacunata (diplobacillus), Haemophilus influenzae (cocobacillus).
• Grampositivefilamentousbacteria:Actinomyces, Nocardia.
• Mycobacteria:Non-tuberculous mycobacteria and M. tuberculosis.
Common bacteria associated with corneal ulceration include Staphylococci, Pseudomonas, Streptococcus pneumonia, Enterobacteriaceae and Neisseria.

Pathogenesis and pathology of corneal ulcer
1. Once the damaged corneal epithelium is invaded by the offending agents, the sequence of pathological changes which occur during development of corneal ulcer can be described under four stages:
• Stage of progressive infiltration, • Stage of active ulceration,
• Stage of regression, and • Stage of cicatrization.
2. Terminal course of corneal ulcer depends upon the virulence of infecting agent, host defence mechanism and the treatment received.
3. Depending upon the prevalent circumstances the course of corneal ulcer may take one of the three forms:
• Ulcer may become localised and heal,
• Penetrate deep leading to corneal perforation, and • Spread fast to involve the whole cornea as
sloughing corneal ulcer.
The salient pathological features of these are described below:
A. Pathology of localised corneal ulcer
1. Stage of progressive infiltration (Fig. 6.2A). It is characterised by the infiltration of polymor-phonuclear and/or lymphocytes into the epithelium from the peripheral circulation supplemented by similar cells from the underlying stroma if this tissue is also affected. Subsequently, necrosis of the involved tissue may occur, depending upon the virulence of offending agent and the strength of host defence mechanism.
2.Stage of active ulceration(Fig. 6.2B). Active ulceration results from necrosis and sloughing of the epithelium, Bowman’s membrane and the involved stroma. The walls of the active ulcer project owing to swelling of the lamellae by the imbibition of fluid and the packing of masses of leucocytes between them. This zone of infiltration may extend to a considerable distance both around and beneath the ulcer. At this stage, sides and floor of the ulcer may show grey infiltration and sloughing.
100	Section III   Diseases of Eye







A





B




C





D

Fig. 6.2 Pathology of corneal ulcer: A, stage of progressive infiltration; B, stage of active ulceration; C, stage of regression; D, stage of cicatrization

■  Duringthisstageofactiveulceration,thereoccurs: • Hyperaemia of circumcorneal network of vessels which results into accumulation of purulent
exudates on the cornea.
• There also occurs vascular congestion of the iris and ciliary body and some degree of iritis due to absorption of toxins from the ulcer. Exudation into the anterior chamber from the vessels of iris and ciliary body may lead to formation of hypopyon.
• Ulcerationmayfurtherprogress by lateral extension resulting in diffuse superficial ulceration or it may progress by deeper penetration of the infection leading to Descemetocele formation and possible corneal perforation. When the offending organism is highly virulent and/or host defence mechanism is jeopardised there occurs deeper penetration during stage of active ulceration.
3.Stage of regression (Fig. 6.2C). Regression is induced by the natural host defence mechanisms (humoral antibody production and cellular immune defences) and the treatment which augments the normal host response. A line of demarcation develops around the ulcer, which consists of leucocytes that neutralize and eventually phagocytose the offending organisms and necrotic cellular debris. The digestionof necrotic material may result in initial enlargement of the ulcer. This process may be accompanied by superficial

vascularization that increases the humoral and cellular immune response. The ulcer now begins to heal and epithelium starts growing over the edges. 4. Stage of cicatrization (Fig. 6.2D). In this stage healing continues by progressive epithelization which forms a permanent covering. Beneath the epithelium, fibrous tissue is laid down partly by the corneal fibroblasts and partly by the endothelial cells of the new vessels. The stroma thus thickens and fills in under the epithelium, pushing the epithelial surface anteriorly.
The degree of scarring from healing varies. If the ulcer is very superficial and involves epithelium only, it heals without leaving any opacity behind. When ulcer involves Bowman’s membrane and few superficial stromal lamellae, the resultant scar is called a ‘nebula’. Macula and leucoma result after healing of ulcers involving up to one-third and more than that of corneal stroma, respectively.
B. Pathology of perforated corneal ulcer
Perforation of corneal ulcer occurs when the ulcerative process deepens and reaches up to Descemet’s membrane. This membrane is tough and bulges out as Descemetocele (Fig. 6.3). At this stage,













A












B
Fig. 6.3 Descemetocele: A, Diagrammatic depiction; B,
Clinical photograph
Chapter 6	Diseases of Cornea	101


any exertion on the part of patient, such as coughing, sneezing, straining for stool etc., will perforate the corneal ulcer. Immediately after perforation, the aqueous escapes, intraocular pressure falls and the iris-lens diaphragm moves forward. The effects of perforation depend upon the position and size of perforation. When the perforation is small and opposite to iris tissue, it is usually plugged and healing by cicatrization proceeds rapidly (Fig. 6.4). Adherent leucoma is the commonest end result after such a catastrophe.
C. Pathology of sloughing corneal ulcer and formation of anterior staphyloma
When the infecting agent is highly virulent and/or body resistance is very low, the whole cornea sloughs with the exception of a narrow rim at the margin and total prolapse of iris occurs. The iris becomes inflamed and exudates block the pupil and cover the iris surface; thus a falsecorneais formed. Ultimately, these exudates organize and form a thin fibrous layer over which the conjunctival or corneal epithelium rapidly grows and thus a pseudocornea is formed. Since, the pseudocornea is thin and cannot withstand the intraocular pressure, so it usually bulges forward













A












B
Fig. 6.4 Perforated corneal ulcer with prolapse of iris: A,
Diagrammatic depiction; B, Clinical photograph

along with the plastered iris tissue. This ectatic cicatrix is called anteriorstaphylomawhich, depending upon its extent, may be either partial or total. The bands of scar tissue on the staphyloma vary in breadth and thickness, producing a lobulated surface often blackened with iris tissue which resembles a bunch of black grapes (hence the name staphyloma).
Clinical features
In bacterial infections the outcome depends upon the virulence of organism, its toxins and enzymes, and the response of host tissue.
Broadly bacterial corneal ulcers may manifest as: • Purulent corneal ulcer without hypopyon; or
• Hypopyon corneal ulcer.
In general, following symptoms and signs may be present:
Symptoms
1. Pain and foreign body sensation occurs due to mechanical effects of lids and chemical effects of toxins on the exposed nerve endings.
2. Watering from the eye occurs due to reflex hyperlacrimation.
3. Photophobia,i.e., intolerance to light results from stimulation of nerve endings.
4. Blurred vision results from corneal haze.
5. Redness of eyes occurs due to congestion of circumcorneal vessels.
Signs
1. Swelling of lids of varying degree is present. 2. Blepharospasm may be moderate to severe.
3. Conjunctiva is chemosed and shows conjunctival hyperaemia and ciliary congestion.
4. Corneal ulcer usually starts as an epithelial defect associated with greyish-white circumscribed infiltrate (seen in early stage). Soon the epithelial defect and infiltrate enlarges and stromal oedema develops. A well established bacterial ulcer is characterized by (Fig. 6.5):
• Yellowish-white area of ulcer which may be oval or irregular in shape.
• Margins of the ulcer are swollen and over hanging. • Floor of the ulcer is covered by necrotic material. • Stromal oedema is present surrounding the ulcer
area.
Characteristic features produced by some of the common causative bacteria are as follows:
• Staphylococcus aureus and Streptococcus pneumoniae usually produce an oval, yellowish white densely opaque ulcer which is surrounded by relatively clear cornea (Fig. 6.5A).
• Pseudomonasspeciesusually produce an irregular sharp ulcer with thick greenish mucopurulent
102	Section III   Diseases of Eye












A	B
Fig. 6.5 Bacterial corneal ulcer: A, Oval ulcer; B, Ring-shaped ulcer


exudate, diffuse liquefactive necrosis and semiopaque (ground glass) surrounding cornea. Such ulcers are usually associated with hypopyon, spread very rapidly and may even perforate within 48 to 72 hours.
• Enterobacteriae(E.coli,Proteussp.,and Klebsiella sp.) usually produce a shallow ulcer with greyish white pleomorphic suppuration and diffuse stromal opalescence. The endotoxins produced by these Gram -ve bacilli may produce ring-shaped corneal infiltrate (Fig. 6.5B).
5. Anterior chambermay or may not show pus (hypopyon). In bacterial corneal ulcers the hypopyon remains sterile so long as the Descemet’s membrane is intact.
6. Iris may be slightly muddy in colour.
7.Pupil may be small due to associated toxin induced iritis.
8. Intraocular pressure may sometimes be raised (inflammatory glaucoma).
HYPOPYON CORNEAL ULCER
Etiopathogenesis
Causative organisms. It is customary to reserve the term ‘hypopyon corneal ulcer’ for the characteristic ulcer caused by Pneumococcus and the term ‘corneal ulcer with hypopyon’ for the ulcers associated with hypopyonduetootherorganismssuchasStaphylococci, Streptococci, Gonococci, Moraxella and Pseudomonas pyocyanea.The characteristic hypopyon corneal ulcer caused by Pneumococcusis called ulcusserpens. Source of infection for pneumococcal infection is usually the chronic dacryocystitis.
Factors predisposing to development of hypopyon. Two main factors which predispose to development of hypopyon in a patient with corneal ulcer are the virulence of the infecting organism and the resistance of the tissues. Hence, hypopyon ulcers are much more common in old debilitated or alcoholic subjects. Mechanism of development of hypopyon. Corneal ulcer is often associated with some iritis owing to diffusion

of bacterial toxins. When the iritis is severe the outpouring of leucocytes from the vessels is so great that these cells gravitate to the bottom of the anterior chamber to form a hypopyon. Thus, it is important to note that the hypopyon is sterile since the outpouring of polymorphonuclear cells is due to the toxins and not due to actual invasion by bacteria. Once the ulcerative process is controlled, the hypopyon is absorbed.

Clinical features
Symptoms are same as described above for bacterial corneal ulcer. However, it is important to note that during initial stage of ulcus serpens there is remarkably little pain. As a result, the treatment is often unduly delayed.
Signs. In general, the signs are same as described above for the bacterial ulcer.
Characteristic features of ulcus serpens are:
• Ulcus serpens is a greyish white or yellowish disc-shaped ulcer occurring near the centre of cornea (Fig. 6.6).
• Theulcer has a tendency to creep over the cornea in a serpiginous fashion. One edge of the ulcer, along which the ulcer spreads, shows more infiltration. The other side of the ulcer may be undergoing simultaneous cicatrization and the edges may be covered with fresh epithelium.
• Violent iridocyclitis is commonly associated with a definite hypopyon.
• Hypopyon increases in size very rapidly and often results in secondary glaucoma.
• Ulcer spreads rapidly and has a great tendency for early perforation.

Management
Management of hypopyon corneal ulcer is same as for other bacterial corneal ulcer.
Chapter 6	Diseases of Cornea	103

















A












B
Fig. 6.6 Hypopyon corneal ulcer: A, Diagrammatic
depiction; B, Clinical photograph

4. Perforation of corneal ulcer. Sudden strain due to cough, sneeze or spasm of orbicularis muscle may convert impending perforation into actual perforation (Fig. 6.4). Following perforation, immediately pain is decreased and the patient feels some hot fluid (aqueous) coming out of eyes. Sequelae of corneal perforation include:
• Prolapse of iris. It occurs immediately following perforation in a bid to plug it.
• Subluxation or anterior dislocation of lens may occur due to sudden stretching and rupture of zonules.
• Anterior capsular cataract. It is formed when the lens comes in contact with the ulcer following a perforation in the pupillary area.
• Corneal fistula. It is formed when the perforation in the pupillary area is not plugged by iris and is lined by epithelium which gives way repeatedly. There occurs continuous leak of aqueous through the fistula.
• Purulent uveitis, endophthalmitis or even panophthalmitis may develop due to spread of intraocular infection.
• Intraocular haemorrhage in the form of either vitreous haemorrhage or expulsive choroidal haemorrhage may occur in some patients due to sudden lowering of intraocular pressure.
5.Corneal scarring. It is the usual end result of healed corneal ulcer. Corneal scarring leads to permanent visual impairment ranging from slight blurring to total blindness. Depending upon the clinical course

Special points which need to be considered are:
• Secondary glaucoma should be anticipated and treated with 0.5% timolol maleate, B.I.D. eye drops and oral acetazolamide.
• Source of infection, i.e., chronic dacryocystitis if detected, should be treated by dacryocystectomy.

Complications of Corneal Ulcer
1.Toxic iridocyclitis. It is usually associated with cases of purulent corneal ulcer due to absorption of toxins in the anterior chamber.
2. Secondary glaucoma. It occurs due to fibrinous exudates blocking the angle of anterior chamber (inflammatory glaucoma).
3. Descemetocele. Some ulcers caused by virulent organisms extend rapidly up to Descemet’s membrane, which gives a great resistance, but due to the effect of intraocular pressure it herniates as a transparent vesicle called the descemetocele or keratocele (Fig. 6.3). This is a sign of impending perforation and is usually associated with severe pain.

of ulcer, corneal scar noted may be nebula, macula, leucoma, ectatic cicatrix or kerectasia, adherent leucoma or anterior staphyloma (for details see page 135).
MANAGEMENT OF A CASE OF CORNEAL ULCER
Since corneal ulcer is sight threatening, it needs urgent treatment by identification and eradication of causative bacteria. Preferably such patients should be hospitalized. The management includes:
• Clinical evaluation,
• Laboratory investigations, and • Treatment.
A. Clinical evaluation
Each case with corneal ulcer should be subjected to:
1. Thorough history taking to elicit mode of onset.
2. General physical examination, especially for built, nourishment, anaemia and any immuno-compromising disease.
104	Section III   Diseases of Eye


3. Ocular examination should include:
• Diffuse light examination for gross lesions of lids, conjunctiva and cornea including testing for sensations.
• Regurgitationtestand syringingto rule out lacrimal sac infection.
• Biomicroscopic examination after staining of corneal ulcer with 2% freshly prepared aqueous solution of fluorescein dye or sterilised fluorescein impregnated filter paper strip. Ulcer area stains as brilliant green, which looks opaque green when seen with blue filter. Note site, size, shape, depth, margin, floor and vascularization of corneal ulcer. On biomicroscopy also note presence of keratic precipitates at the back of cornea, depth and contents of anterior chamber, colour and pattern of iris and condition of crystalline lens.
B. Laboratory Investigations
1. Routine laboratory investigations such  as haemoglobin, TLC, DLC, ESR, blood sugar, complete urine and stool examination should be carried out in each case.
2. Microbiological investigations. These studies are essential to identify causative organism, confirm the diagnosis and guide the treatment to be instituted. Material for such investigations is obtained by scraping the base and margins of the corneal ulcer (under local anaesthesia, using 2% xylocaine or preferably paracain) with the help of a modified Kimura spatula or by simply using the bent tip of a 20 gauge hypodermic needle. The material obtained is used for the following investigations:
• Gram and Giemsa stained smears for possible identification of infecting organisms.
• 10% KOH wet preparation for identification of fungal hyphae.
• Calcofluor white (CFW) stain preparation is viewed under fluorescence microscope for fungal filaments, the walls of which appear bright apple green.
• Culture on blood agar medium for aerobic organisms.
• Culture on Sabouraud’s dextrose agar medium for fungi.
C. Treatment
I. Treatment of uncomplicated corneal ulcer
Treatment of corneal ulcer can be discussed under three headings:
• Specific treatment of the cause. • Nonspecific supportive therapy. • Physical and general measures.


1. Specific treatment
a. Topical antibiotics
• Initial therapy (before results of culture and sensitivity  are  available)  should  be  with combination therapy to cover both gram-negative and gram-positive organisms. To begin with any of the following two drugs may be instilled:
• Fortified Cefazoline, 5% i.e., 50 mg/ml freshly prepared by adding sterile water to 500 mg powder to make 10 ml solution, and
• Fortified tobramycin, 1.3%, i.e., 13.6 mg/ml prepared by adding 2 ml of tobramycin injection (40 mg/ml in 5 ml bottle of commercially available 0.3% tobramycin drops).
or
• Freshly prepared fortified vancomycin 5%, i.e., 50 mg/ml (prepared by adding sterile water to 500 mg vancomycin powder to form 10 ml solution) and one of commercially available fluoroquinolones eye drops (0.3% ciprofloxacin, or 0.3% ofloxacin or 0.3% gatifloxacin or 0.5% moxifloxacin).
■Frequency of instillation. The chosen two drugs should be instilled alternately as below:
• Every 5 minutes for 30 minutes, • Every 15 minutes for 2 hours,
• 1 hourly round the clock for first 48 hours,
• 2 hourly during day and 4 hourly at night till healing is ensured, and then
• 4–6 hourly till healing occurs.
• Once the favourable response is obtained, the fortified drops can be substituted by the commercially available eye drops.
■Subsequent therapy. There is no need to change initial antibiotics, if the response is good. However, if the response is poor, immediately change the antibiotics as per culture and sensitivity report.
b. Systemic antibiotics
Systemic antibiotics are usually not required. However, a cephalosporine and an aminoglycoside or oral ciprofloxacin (750 mg twice daily) may be given in fulminating cases with perforation or when sclera is also involved.
2. Nonspecific treatment
a. Cycloplegic drugs. Preferably 1% atropine eye ointment or drops should be used:
• To reduce pain from ciliary spasm and
• To prevent the formation of posterior synechiae from secondary iridocyclitis.
• Atropine also increases the blood supply to anterior uvea by relieving pressure on the anterior ciliary arteries and so brings more antibodies in the aqueous humour.
Chapter 6	Diseases of Cornea	105


• It also reduces exudation by decreasing hyperaemia and vascular permeability.
• Other cycloplegic which can be used is 2% homatropine eye drops.
b. Systemic analgesics and anti-inflammatory drugs such as paracetamol and ibuprofen relieve the pain and decrease oedema.
c. Vitamins (A, B-complex and C) help in early healing of ulcer.
3. Physical and general measures
• Hot fomentation. Local application of heat (preferably dry) gives comfort, reduces pain and causes vasodilatation.
• Darkgogglesmay be used to prevent photophobia. • Rest, good diet and fresh air may have a soothing
effect.
II. Treatment of non-healing corneal ulcer
If the ulcer progresses despite the above therapy the following additional measures should be taken:
1. Removal of any known cause of non-healing ulcer. A thorough search for any already missed cause not allowing healing should be made and when found, such factors should be eliminated. Common causes of non-healing ulcers are as under:
• Local causes. Associated raised intraocular pressure, concretions, misdirected cilia, impacted foreign body, dacryocystitis, inadequate therapy, wrong diagnosis, lagophthalmos and excessive vascularization of ulcer.
• Systemiccauses:Diabetes mellitus, severe anaemia, malnutrition, chronic debilitating diseases and patients on systemic steroids.
2. Mechanical debridement of ulcer to remove necrosed material by scraping floor of the ulcer with a spatula under local anaesthesia may hasten the healing.
3. Cauterisation of the ulcer may also be considered in non-responding cases. Cauterisation may be performed with pure carbolic acid or 10–20% trichloracetic acid. 4. Bandage soft contact lens may also help in healing. 5. Peritomy, i.e., severing of perilimbal conjunctival vessels may be performed when excessive corneal vascularization is hindering healing.
III. Treatment of impending perforation
When ulcer progresses and perforation seems imminent, the following additional measures may help to prevent perforation and its complications: 1. Nostrain.The patient should be advised to avoid
sneezing, coughing and straining during stool, etc. He should be advised strict bed rest.
2. Pressurebandageshould be applied to give some external support.


3. Loweringofintraocularpressureby simultaneous use of acetazolamide 250 mg QID orally, intravenous mannitol (20%) drip stat, oral glycerol twice a day, 0.5% timolol eye drops twice a day, and even paracentesis with slow evacuation of aqueous from the anterior chamber may be performed if required.
4. Tissue adhesive glue such as cyanoacrylate is helpful in preventing perforation.
5. Bandage soft contact lens may also be used.
6. Conjunctival flap. The cornea may be covered completely or partly by a conjunctival flap to give support to the weak tissue.
7. Amniotic membrane transplantation may also be considered as an option.
8. Penetrating therapeutic keratoplasty (tectonic graft) may be undertaken in suitable cases, when available.
IV. Treatment of perforated corneal ulcer
Best is to prevent perforation. However, if perforation has occurred, immediate measures should be taken to restore the integrity of perforated cornea. Depending upon the size of perforation and availability, measures like use of tissue adhesive glues, covering with conjunctival flap, use of bandage soft contact lens or therapeutic keratoplasty should be undertaken. Best option is an urgent tectonic keratoplasty.
MARGINAL CATARRHAL ULCER
These superificial ulcers situated near the limbus are frequently seen especially in old people.
Etiology
Marginal catarrhal ulcer is thought to be caused by a hypersensitivity reaction to Staphylococcal toxins. It occurs in association with chronic Staphylococcal blepharoconjunctivitis. Moraxella and Haemophilus are also known to cause such ulcers.
Clinical features
• Patientusuallypresentswithmild ocular irritation, pain, photophobia and watering.
• Ulcer is shallow, slightly infiltrated and often multiple, usually associated with Staphylococcal conjunctivitis (Fig. 6.7).
• Vascularization occurs soon and is followed by resolution.
• Recurrences are very common.

Treatment
• Ashortcourseoftopicalcorticosteroiddropsalong with adequate antibiotic therapy often heals the condition.
106	Section III   Diseases of Eye















Fig. 6.7 Marginal corneal ulcer in a patient with acute conjunctivitis

• Adequate treatment of associated blepharitis and chronic conjunctivitis is important to prevent recurrences.

MYCOTIC CORNEAL ULCER

The incidence of suppurative corneal ulcers caused by fungi has increased in the recent years due to injudicious use of antibiotics and steroids.
Etiology
1.  Fungi. The fungi can be classified as below:
i.  Filamentous fungi e.g., Aspergillus, Fusarium, Alternaria, Cephalosporium, Curvularia and Penicillium are septate multicellular fungi. Mucor and rhizopus are non- septate organisms.
ii. Yeasts e.g., Candida and Cryptococcus are unicellular fungi that reproduce by budding.
iii Dimorphicfungisuch as histoplasma, coccidioides and blastomyces demonstrate both yeast phase that occurs in the tissues and a mycelia phase that appears in culture media and on saprophytic surfaces.
Fungi commonly responsible for mycotic corneal ulcers are Aspergillus(most common), Candidaand Fusarium.
2.  Modes of infection
i.  Injury by vegetative material such as crop leaf, branch of a tree, straw, hay or decaying vegetable matter. Common sufferers are field workers especially during harvesting season.
ii. Injurybyanimaltailis another mode of infection. iii.Secondary fungal ulcers are common in patients who are immunosuppressed systemically or locally such as patients suffering from dry eye, herpetic keratitis, bullous keratopathy or
postoperative cases of keratoplasty.

3. Role of antibiotics and steroids. Antibiotics disturb the symbiosis between bacteria and fungi; and the steroids make the fungi facultative pathogens which are otherwise symbiotic saprophytes. Therefore, excessive use of these drugs predisposes the patients to fungal infections.

Clinical features
Symptoms are similar to the central bacterial corneal ulcer (see page 101), but in general they are less marked than the equal-sized bacterial ulcer and the overall course is slow and torpid.
Signs. A typical fungal corneal ulcer has following salient features (Fig. 6.8):
• Corneal ulcer is dry-looking, greyish white, with elevated rolled out margins.
• Pigmented ulcer (brownish) may be caused by some species of fungi, e.g., dermatiaceous fungi.
• Delicate featheryfinger-likeextensionsare present into the surrounding stroma under the intact epithelium.
• A sterileimmunering(yellow line of demarcation) may be present where fungal antigen and host antibodies meet.
• Multiple, small satellite lesions may be present around the ulcer.
• Usually a bighypopyonis present even if the ulcer is very small. Unlike bacterial ulcer, the hypopyon may not be sterile as the fungi can penetrate into the anterior chamber without perforation.
• Endothelial plaque, composed of fibrin and leucocytes, may be located under the stromal lesion. It may be present in the absence of hypopyon.
• Perforation in mycotic ulcer is rare but can occur. • Corneal vascularization is conspicuously absent
in pure mycotic ulcer.














Fig. 6.8 Fungal corneal ulcer
Chapter 6	Diseases of Cornea	107


Diagnosis
1. Typical clinical manifestations associated with history of injury by vegetative material are highly suspicious of a mycotic corneal ulcer.
2. Chronic ulcer worsening inspite of most efficient treatment should arouse suspicion of mycotic involvement.
3. Laboratoryinvestigationsrequired for confirmation, include examination of wet KOH, Calcofluor white, Gram’s and Giemsa-stained films for fungal hyphae and culture on Sabouraud’s agar medium. Methods of sample collection for microbiological evaluation are as below:
• Corneal scrapings should be performed from the base and leading edge of ulcer.
• Anterior chamber paracentesis may be carried out in cases with intraocular extension.
• Corneal biopsy is indicated in cases with deep stromal abscess or in cases where repeated cultures from scrapings are negative.
4. Confocal microscopic examination of cornea is reported to identify actual fungi.
5. Polymerase chain reaction (PCR) is also being recommended for its rapid results.
Treatment
A. Specific treatment includes antifungal drugs:
1. Topical antifungal eyedrops should be used for a long period (6 to 8 weeks). These include:
• Natamycin(5%), AmphotericinB (0.1 to 0.3%), and either Fluconalzole(0.2%), or miconazole (10 mg/ ml) or voriconazole (10%) eyedrops to be instilled initially one hourly around the clock, then taper slowly over 6 to 8 weeks. These are effective against Aspergillus and Fusarium.
• Nystatin (3.5%) eye ointment, five times a day is effective against Candida. (For details see page 448).
2. Intracameral and intracorneal/intrastromal administration of voriconazole may be considered in cases with intraocular extension or anterior chamber involvement.
3. Systemic antifungal drugs may be required for severe cases of deeper fungal keratitis. Tablet fluconazole or ketoconazole or voriconazole may be given for 2–3 weeks.
B. Non-specific treatment. Non-specific treatment and general measures are similar to that of bacterial corneal ulcer (see page 104).
C. Therapeutic penetrating keratoplasty may be required for nonresponsive cases.

VIRAL CORNEAL ULCER

Incidence of viral corneal ulcers has become much greater especially because of the role of antibiotics in eliminating the pathogenic bacterial flora. Most of the viruses tend to affect the epithelium of both the conjunctiva and cornea, hence the typical viral lesions constitute the viral keratoconjunctivitis. Common viral infections include herpes simplex keratitis, herpes zoster ophthalmicus and adenovirus keratitis.
HERPES SIMPLEX KERATITIS
Ocular infections with herpes simplex virus (HSV) are extremely common and constitute herpetic keratoconjunctivitis and iritis.
Etiology
Herpes simplex virus (HSV). It is a DNA virus. Its only natural host is man. Basically, HSV is epitheliotropic but may become neurotropic. According to different clinical and immunological properties, HSV is of two types: HSV type I typically causes infection above the waist and HSV type II below the waist (herpes genitalis). HSV-II has also been reported to cause ocular lesions.
Mode of infection are as below:
• HSV-Iinfection.It is acquired by kissing or coming in close contact with a patient suffering from herpes labialis.
• HSV-II infection. It is transmitted to eyes of neonates through infected genitalia of the mother.
Ocular lesions of herpes simplex
Ocular involvement by HSV occurs in two forms, primary and recurrent; with following lesions:
A. Primary herpes 1.Skin lesions
2.Conjunctiva-acute follicular conjunctivitis 3.Cornea
• Fine epithelial punctate keratitis
• Coarse epithelial punctate keratitis • Dendritic ulcer
B. Recurrent herpes 1.Active epithelial keratitis
• Punctate epithelial keratitis • Dendritic ulcer
• Geographical ulcer 2.Stromal keratitis
i.  Disciform keratitis;
ii. Diffuse stromal necrotic keratitis 3. Trophic keratitis (meta-herpetic) 4. Herpetic iridocyclitis
108	Section III   Diseases of Eye


A. Primary Ocular Herpes
Primary infection (first attack) involves a nonimmune person. It typically occurs in children of 6 months till 5 years of age and in teenagers. Initial infection occurs by direct contact of mucous membranes with infected secretions.
Clinical features
1. Systemic features include mild fever, malaise and non-suppurative lymphadenopathy. Rarely, severe morbidity can result from multi-system failure. Disease may be fatal when encephalitis develops. 2. Skin lesions. Vesicular lesions may occur involving skin of face, lips, lids, periorbital region and the lid margin (vesicular blepharitis).
3. Ocular lesion includes:
•  Acute  follicular  conjunctivitis with regional lymphadenitis is the usual and sometimes the only manifestation of the primary infection.
•  Keratitis. Cornea is involved in about 50% of the cases. The keratitis can occur as a coarse punctate or diffuse branching epithelial keratitis that does not usually involve the stroma.
Note. Primary infection is usually self-limiting but virus travels up to the trigeminal ganglion and establishes the latent infection.

B. Recurrent Ocular Herpes
The virus which lies dormant in the trigeminal ganglion, periodically reactivates and replicates. The reactivated virus in enveloped infectious form travels down along the trigeminal nerve to cause recurrent infection. The recurrent herpatic ocular infection is not associated with systemic features and typically is a unilateral disease.
Predisposing stress stimuli which trigger an attack of herpetic keratitis include fever such as malaria, flu, exposure to ultraviolet rays, general ill health, emotional or physical exhaustion, mild trauma, menstrual stress following administration of topical or systemic steroids and immunosuppressive agents.
1. Epithelial keratitis
Symptoms
Symptoms of epithelial HSV keratitis include redness, pain, photophobia, tearing and decreased vision.
Signs
Three distinct patterns of epithelial keratitis seen are: punctate epithelial keratitis, dendritic ulcer and geographical ulcer.
1. Punctate epithelial keratitis (Figs. 6.9A and B). The initial epithelial lesions of recurrent herpes resemble


those seen in primary herpes and may be either in the form of fine or coarse superficial punctate lesions. 2. Dendritic ulcer (Figs. 6.9C and D). Dendritic ulcer is a typical lesion of recurrent epithelial keratitis. The ulcer is of an irregular, zigzag linear branching shape. The branches are generally knobbed at the ends. Floor of the ulcer stains with fluorescein and the virus-laden cells at the margin take up rose bengal. There is an associated marked diminution of corneal sensations.
3. Geographical ulcer (Figs. 6.9E and F). Sometimes, the branches of dendritic ulcer enlarge and coalesce to form a large epithelial ulcer with a ‘geographical’ or ‘amoeboid’ configuration, hence the name. The use of steroids in dendritic ulcer hastens the formation of geographical ulcer.
Treatment
A. Specific treatment
1. Antiviral drugs are the first choice presently. Any one of the following drugs may be given:
• Acycloguanosine(Aciclovir) 3% ointment: 5 times a day for 14–21 days. It is least toxic and most commonly used antiviral drug. It penetrates intact corneal epithelium and stroma, achieving therapeutic levels in aqueous humour, and can therefore be used to treat herpetic keratitis.
• Ganciclovir (0.15% gel), 5 times a day until ulcer heals and then 3 times a day for 5 days. It is more toxic than aciclovir.
• Triflurothymidine1% drops: Two hourly until ulcer heals and then 4 times a day for 5 days.
• Adenine arabinoside (Vidarabine) 3% ointment: 5 times a day until ulcer heals and then 3 times a day for 5 days.
2. Mechanical debridement of the involved area along with a rim of surrounding healthy epithelium with the help of sterile cotton applicator under magnification helps by removing the virus-laden cells.
Before the advent of antiviral drugs, it was the treatment of choice. Now it is reserved for resistant cases, cases with noncompliance and those allergic to antiviral drugs.
3. Systemic antiviral drugs for a period of 10 to 21 days are increasingly being considered for recurrent and even acute cases in following doses:
• Acyclovir 400 mg p.o. tid to bid, or • Famcyclovir 250 mg p.o. bid, or
• Valacyclovir 500 mg p.o.bid.
B. Non-specific supportive therapy and physical and general measures are same as for bacterial corneal
ulcer (see page 104).
Chapter 6	Diseases of Cornea	109










































Fig. 6.9 Lesions of recurrent herpes simplex keratitis; diagrammatic depiction and Clinical photograph; A and B, Punctate epithelial keratitis; C and D, Dendritic ulcer; E and F, Geographical ulcer; and G and H, Disciform keratitis


2. Stromal keratitis a. Disciform keratitis
Pathogenesis.It occurs due to delayed hypersensitivity reaction to the HSV antigen. Primarily, there occurs endothelitis. Endothelial damage results in disciform corneal stromal oedema due to imbibition of aqueous
humour.

Symptoms include photophobia, mild to moderate ocular discomfort, and a reduction in visual acuity. Signs. Disciform keratitis is characterized by (Figs. 6.9 G and H):
• Focaldisc-shapedpatchof stromal oedema without necrosis, usually with an intact epithelium.
• Folds in Descemet’s membrane.
• Keraticprecipitatesunder the round area of stromal edema.
• Ring of stromal infiltrate (Wessley immune ring) may be present surrounding the stromal oedema. It signifies the junction between viral antigen and host antibody.
• Corneal sensations are diminished.
• Intraocular pressure (IOP) may be raised despite only mild anterior uveitis due to trabeculitis. In severe cases, anterior uveitis may be marked.
Important note. During active stage diminished corneal sensations and keratic precipitates are the differentiating points from other causes of stromal oedema.
Treatment consists of:
• Diluted steroid eye drops instilled 4–5 times a day with an antiviral cover (aciclovir 3%) twice a day. Steroids should be tapered over a period of several weeks. When disciform keratitis is present with an infected epithelial ulcer, antiviral drugs should be started 5–7 days before the steroids.
• Non-specific and supportive treatment (see page 104).
b. Stromal necrotic keratitis
It is a type of interstitial keratitis (IK) caused by active viral invasion and tissue destruction.
Symptoms. Pain, photophobia and redness are common symptoms.
Signs are as below:
• Corneal lesions include necrotic, blotchy, cheesy white infiltrates that may lie under the epithelial ulcer or may present independently under the intact epithelium.
• Mild iritis and keratic precipitates are usually associated (herpetic keratouveitis).
• Stromal vascularization may occur.
Treatment is similar to disciform keratitis but frequently the results are unsatisfactory.
• Systemicantiviraldrugsfor 10 to 21 days are being considered in recurrent cases and in those with associated herpetic uveitis.
110	Section III   Diseases of Eye


• Keratoplasty should be deferred until the eye has been quiet with little or no steroidal treatment for several months; because viral interstitial keratitis is the form of herpes which is most likely to recur in a new graft.
3. Metaherpetic keratitis
Metaherpetic keratitis (epithelial sterile trophic ulceration) is not an active viral disease, but is a mechanical healing problem due to persistent defects in the basement membrane of corneal epithelium (similar to recurrent traumatic erosions) which occurs at the site of a previous herpetic ulcer. Clinical features. It presents as an indolent linear or ovoid epithelial detect. Margin of the ulcer is grey and thickened due to heaped up epithelium.
Treatment is aimed to promote healing by use of lubricants (artificial tears), bandage soft contact lens and lid closure (tarsorrhaphy).
HERPES ZOSTER OPHTHALMICUS
Herpes zoster ophthalmicus is an acute infection of Gasserian ganglion of the fifth cranial nerve by the varicella-zoster virus (VZV). It constitutes approximately 10% of all cases of herpes zoster. Herpes zoster occurs more commonly in immuno-compromised individuals.

Etiology
Varicella-zoster virus. It is a DNA virus and produces acidophilic intranuclear inclusion bodies. It is neurotropic in nature.
Pathogenesis. The infection is contracted in childhood, which manifests as chickenpox and the child develops immunity. The virus then remains dormant in the sensory ganglion of trigeminal nerve. It is thought that, usually in elderly people (can occur at any age) with depressed cellular immunity, the virus reactivates, replicates and travels down along one or more of the branches of the ophthalmic division of the fifth nerve to produce cutaneous and ocular lesions.
Clinical Features
• Frontalnerve is more frequently affected than the lacrimal and nasociliary nerves in herpes zoster ophthalmicus.
• Ocularcomplicationsoccurs in about 50% cases of herpes zoster ophthalmicus.
• Hutchinson’s rule, which implies that ocular involvement is frequent if the side or tip of nose presents vesicles (cutaneous involvement of nasociliary nerve), is useful but not infallible.

• Lesionsarestrictlylimitedto one side of the midline of head.
Clinical phases of H. zoster ophthalmicus are:
I.	Acute phase lesions, which may totally resolve within few weeks.
II.  Chronic phase lesions, which may persist for years.
III. Relapsing phase lesions, where acute or chronic lesions reappear sometimes years later.
I. Acute phase lesions
A. General features. The onset of illness is sudden with fever, malaise and severe neuralgic pain along the course of the affected nerve. The distribution of pain is so characteristic of zoster that it usually arouses suspicion of the nature of the disease before appearance of vesicles.
B. Cutaneous lesions. Cutaneous lesions (Fig. 6.10) in the area of distribution of the involved nerve appear usually after 3 to 4 days of the onset of disease. To begin with, the skin of lids and other affected areas become red and oedematous (mimicking erysipelas), followed by vesicle formation. In due course of time vesicles are converted into pustules, which subsequently burst to become crusting ulcers. When crusts are shed, permanent pitted scars are left. The active eruptive phase lasts for about 3 weeks. Main symptom is severe neuralgic pain which usually diminishes with the subsidence of eruptive phase. C.Ocular lesions.Ocular complications usually appear at the subsidence of skin eruptions and may present as a combination of two or more of the following lesions: 1. Conjunctivitis is one of the most common complication of herpes zoster. It may occur as mucopurulent conjunctivitis with petechial haemorrhages or acute follicular conjunctivitis














Fig. 6.10 Cutaneous lesions of herpes zoster ophthalmicus
Chapter 6	Diseases of Cornea	111


with regional lymphadenopathy. Sometimes, severe necrotizing membranous inflammation may be seen.
2. Zoster keratitis occurs in 40% of all patients and sometimes may precede the neuralgia or skin lesions. It may occur in several forms (Fig. 6.11):
• Epithelial keratitis. To begin with there occurs fine or coarse punctate epithelial keratitis (Figs. 6.11A and B). It is followed by microdendritic epithelialulcers(Figs. 6.11C and D) which unlike dendritic ulcers of herpes simplex are usually peripheral and stellate rather than exactly dendritic in shape. In contrast to Herpes simplex dendrites, they have tapered ends which lack bulbs.
• Nummular  keratitis  (Figs.  6.11E  and  F) characterised by anterior stromal infiltrates is seen in about one-third number of total cases. It typically occurs as multiple tiny granular deposits surrounded by a halo of stromal haze. After healing ‘nummular scars’ are left behind.
• Disciform keratitis (Figs. 6.11G and H) occurs in about 50% of cases and is always preceded by nummular keratitis.
3. Episcleritis and scleritis occur in about one-half of the cases. These usually appear at the onset of the rash but are frequently concealed by the overlying conjunctivitis.
4. Iridocyclitis is of a frequent occurrence and may or may not be associated with keratitis. There may be associated hypopyon and hyphaema (acute haemorrhagic uveitis).
5. Acute retinal necrosis may occur in some cases.
6. Secondary glaucoma. It may occur due to trabeculitis in early stages and synechial angle closure in late stages.
7. Anterior segment necrosis and phthisis bulbi, may occur rarely as a  result from zoster vasculitis and ischemia.
D. Associated neurological complications. Herpes zoster ophthalmicus may also be associated with other neurological complications such as:
1. Motornervepalsiesespecially involving the third, fourth, sixth or seventh nerve.
2. Optic neuritis occurs in about 1% of cases.
3. Encephalitis occurs rarely with severe infection.
II. Chronic phase lesions
Chronic phase lesions are basically sequelae of acute phase, which may persist for up to 10 years.
1. Post-herpetic neuralgia refers to persistence of pain even after subsidence of eruptive phase of zoster which occurs in about 10% cases. Pain is mild









































Fig. 6.11 Types of zoster keratitis. Diagrammatic depictions and clinical photographs of: A and B, Punctate epithelial keratitis; C and D, Microdendritic epithelial ulcer; E and F, Nummular keratitis; G and H, Disciform keratitis

to moderate in intensity, worsens at night and is aggravated by touch and heat. But sometimes it may persist for years with little diminution of intensity. There occurs some anaesthesia of the affected skin which when associated with continued postherpetic neuralgia is called anaesthesia dolorosa.
2. Lid lesions which occur as sequelae of scarring include ptosis, trichiasis, entropion and notching.
112	Section III   Diseases of Eye


3. Conjunctival lesions include chronic mucous secreting conjunctivitis.
4. Corneal lesions are as below:
• Neuroparalyticulcerationmay occur as a sequelae of acute infection and Gasserian ganglion destruction.
• Exposure keratitis may supervene in some cases due to associated facial palsy.
• Mucous plaque keratitis develops in 5% of cases between 3rd and 5th months and is characterised by sudden development of elevated mucous plaque which stain brilliantly with rose bengal.
5. Scleritis and Uveitis may persist in chronic form.

III. Relapsing phase lesions
Relapsing phase lesions, which may recur even after ten years of acute phase include nummular keratitis, mucous plaque keratitis, episcleritis, scleritis and secondary glaucoma.

Treatment
Therapeutic approach to herpes zoster ophthalmicus should be vigorous and aimed at preventing severe devastating ocular complications and promoting rapid healing of the skin lesions without the formation of massive crusts which result in scarring of the nerves and postherpetic neuralgia. The following regime may be followed:
I. Systemic therapy for herpes zoster
1. Oral antiviral drugs. These significantly decrease pain, curtail vesiculation, stop viral progression and reduce the incidence as well as severity of keratitis and iritis. In order to be effective, the treatment should be started immediately after the onset of rash. It has no effect on post herpetic neuralgia.
• Acyclovir in a dose of 800 mg 5 times a day for 10 days, or
• Valaciclovir in a dose of 500 mg TDS.
2. Analgesics. Pain during the first 2weeks of an attack is very severe and should be treated by analgesics such as combination of mephenamic acid and paracetamol or pentazocin or even pethidine (when very severe).
3. Systemic steroids. They appear to inhibit development of postherpetic neuralgia when given in high doses. However, the risk of high doses of steroids in elders should always be taken into consideration. Steroids are commonly recommended in cases developing neurological complications such as third nerve palsy and optic neuritis.
4. Cimetidine in a dose of 300 mg QID for 2–3 weeks starting within 48–72 hours of onset has also been

shown to reduce pain and pruritis in acute zoster— presumably by histamine blockade.
5. Amitriptyline should be used to relieve the accompanying depression in acute phase.
II. Local therapy for skin lesions
1. Antibiotic-corticosteroid skin ointment or lotions. These should be used three times a day till skin lesions heal.
2. No calamine lotion. Cool zinc calamine application, as advocated earlier, is better avoided, as it promotes crust formation.
III. Local therapy for ocular lesions
1. For zoster keratitis, iridocyclitis and scleritis • Topical steroid eyedrops 4 times a day.
• Cycloplegics such as cyclopentolate eyedrops BD or atropine eye ointment OD.
• Topical acyclovir 3% eye ointment should be instilled 5 times a day for about 2 weeks.
2. Topreventsecondaryinfectionstopical antibiotics are used.
3. For secondary glaucoma
• 0.5% timolol or 0.5% betaxolol drops, BD. • Acetazolamide 250 mg, QID.
4. For mucous plaques, add topical mucolytics e.g. acetyl cysteine 5 to 10%, three times a day.
5. For persistent epithelial defects use: • Lubricating artificial tear drops, and • Bandage soft contact lens.
IV. Surgical treatment
For neuroparalytic corneal ulcer caused by herpes zoster:
1. Lateral tarsorrhaphy should be performed.
2. Amniotic membrane transplantation (AMT) or conjunctival flap should be considered for non-healing cases.
3. Tissue adhesive with bandage contact lens for corneal perforation.
4. Keratoplasty. It may be required for visual rehabilitation of zoster patients with dense scarring. However, these are high risk patients.

PROTOZOAL KERATITIS

ACANTHAMOEBA KERATITIS
Acanthamoeba keratitis has recently gained importance because of its increasing incidence, difficulty in diagnosis and unsatisfactory treatment.
Etiology
Acanthamoeba castellani, the causative organism is a free lying amoeba found in soil, fresh water,
Chapter 6	Diseases of Cornea	113


well water, sea water, sewage and air. It exists in trophozoite and encysted forms.
Mode of infection. Corneal infection with acanth-amoeba results from direct corneal contact with any material or water contaminated with the organism. Following situations of contamination have been described:
1. Contact lens wearers using home-made saline (from contaminated tap water and saline tablets) is the commonest situation recognised for acanthamoeba infection in western countries.
2. Non-contact lens related situations include mild trauma associated with contaminated vegetable matter, salt water diving, wind blown contaminant and hot tub use. Trauma with organic matter and exposure to muddy water are the major (90% cases) predisposing factors in developing countries.
3. Opportunistic infection. Acanthamoeba keratitis can also occur as opportunistic infection in patients with herpetic keratitis, bacterial keratitis, bullous keratopathy and neuroparalytic keratitis.

Clinical features
Symptoms
These vary from asymptomatic to foreign body sensation, mild pain to severe pain (out of proportion to the degree of inflammation), watering, photophobia, blepharospasm and blurred vision.
Signs
Acanthamoeba keratitis evolves over several months as a gradual worsening keratitis with periods of temporary remission. Presentation is markedly variable, making the diagnosis difficult.
Reported lesions of acanthamoeba keratitis are as below:
1.  Epithelial lesions include:
• Epithelial roughening and irregularities, often mistaken for punctate epitheliopathy,
• Epithelial ridges,i.e., raised epithelial lines, • Pseudodendrites formation, and
• Epithelial and subepithelial curvilinear opacities (usually fine).
2.  Stromal lesions include:
• Radial keratoneuritis (Fig. 6.12A), reported in 50% cases, seems to be pathognomonic early sign. It is thought to be the cause of severe pain disproportionate to inflammation.
• Patchy and satellite stromal infiltrates.
• Ring infiltrates, central or paracentral, with overlying epithelial defects and underlying keratic precipitates (Fig. 6.12B).

• Ring abscess (Fig. 6.12C) associated with stromal necrosis and hypopyon may occur in late stages and mimics any suppurative keratitis.
3.  Limbal and scleral lesions include:
• Limbitis is reported in majority of cases in early stages of infection.
• Scleritis, usually anterior diffuse or nodular, can be contiguous with keratitis. Rarely posterior scleritis with optic neuritis is also reported.














A













B













C
Fig. 6.12 Acanthamoeba keratitis: A, Radial
keratoneuritis; B, Ring infiltrate; and C, Ring abscess
114	Section III   Diseases of Eye


Differential diagnosis
1. Viral keratitis. In early stages both epithelial lesions and early infiltrates are often mistaken for viral keratitis.
2. Fungal keratitis can also be misdiagnosed when ring infiltrates are associated with hypopyon.
3. Suppurative keratitis due to bacterial or other causes may be misdiagnosed in stage of stromal necrosis, and ring abscess formation.
Diagnosis
1. Clinical diagnosis. It is difficult and usually made by exclusion with strong clinical suspicion out of the non-responsive patients being treated for herpetic, bacterial or fungal keratitis.
2. Confocal microscopy, when available allows direct visualization of the cysts, which is diagnostic.
3. Laboratory diagnosis. Corneal scrapings may be helpful in some cases as under:
a. Potassium hydroxide (KOH) mount is reliable in experienced hands for recognition of acanthamoeba cysts.
b. Calcofluor white stain is a fluorescent brightener which stains the cysts of acanthamoeba bright apple green under fluorescence microscope.
c. Lactophenol cotton blue stained film is also useful for demonstration of acanthamoeba cysts in the corneal scrapings.
d. Culture on non-nutrient agar (E.coli enriched) may show trophozoites within 48 hours, which gradually turn into cysts.
e. Polymerase chain reaction (PCR) for amoebic DNA is reported to be useful.
f.Corneal biopsy,may be required in non-conclusive cases, may be positive for amoebic cyst.
Treatment
It is usually unsatisfactory.
1. Non-specific treatment is on the general lines for corneal ulcer (see page 104).
2. Specific treatment
a. Topical antiamoebic agents include:
• Diamidines:Propamidine isethionate (0.1 %), and hexamidine (0.1%).
• Biguanides: Polyhexamethylene biguanide (PHMB), 0.02% and chlorhexidine, 0.02%.
• Aminoglycosides: Neomycin and Paromycin Imidazoles: Clotrimazole and miconazole.
■Multipledrugtherapyisneeded for a long time (3–4 months) for early epithelial lesions and 6–12 months for stromal lesions. Any of the following combination may be choosen:
• Propamidine or hexamidine + PHMB or


• Chlorhexidine + Neomycin or
• Paromycin + clotrimazole or miconazole or itraconazole.
• Frequency of instillation: hourly for a week, then taper slowly over 3–4 months for epithelial lesions and 6–12 months for stromal lesions.
b. Oral ketoconazole 200 mg BID, or itraconazole 100 mg BD may be added in advanced cases.
3. Long-term prophylactic therapy with PHMB, twice a day for a year is recommended.
4. Penetrating keratoplasty is frequently required in non-responsive cases. Surgery should be performed after a full course of maximum medical therapy and a quiescent phase of at least six months.

ALLERGIC KERATITIS

1. Phlyctenular keratitis (see page 83) 2. Vernal keratitis (see page 79)
3. Atopic keratitis (see page 82)

TROPHIC CORNEAL ULCERS

Trophic corneal ulcers develop due to disturbance in metabolic activity of epithelial cells. This group includes: Neurotrophic keratopathy and Exposure keratopathy.
NEUROTROPHIC KERATOPATHY
Neurotrophic keratopathy occurs due to decreased corneal sensations owing to damage of sensory nerve supply of the cornea.
Causes
A. Congenital
1. Familial dysautonomia (Riley-Day syndrome). 2. Congenital insensitivity to pain.
3. Anhidrotic ectodermal dysplasia.
B. Acquired
1. Following alcohol-block or electrocoagulation of Gasserian ganglion or section of the sensory root of trigeminal nerve for trigeminal neuralgia.
2. A neoplasm pressing on Gasserian ganglion.
3. Gasserian ganglion destruction due to acute infection in herpes zoster ophthalmicus.
4. Acute infection of Gasserian ganglion by herpes simplex virus.
5. Syphilitic (luetic) neuropathy.
6. Involvement of corneal nerves in leprosy, diabetes.
7. Injury to Gasserian ganglion.
Pathogenesis
Exact pathogenesis is not clear; presumably, the disturbances in the corneal sensations occur due to
Chapter 6	Diseases of Cornea	115


damage to sensory nerves. As a consequence, metabolic activity of corneal epithelium is disturbed, leading to accumulation of metabolites; which in turn cause oedema and exfoliation of epithelial cells followed by ulceration. Corneal changes can occur in the presence of a normal blink reflexand normal lacrimal secretions.
Clinical features
Symptoms
• Red eye, swollen eyelids and defective vision are common complaints.
• No pain, and no tearing are characteristic features.
Signs
1.  Ciliary congestion is marked, 2.  Corneal signs include:
• Sensations are decreased, • Sheen is lost (dull sheen),
• Punctate epithelial erosions involving the inter-palpebral area are initial lesions, which soon converts into,
• Frankepithelialdefects due to exfoliation of corneal epithelium, later followed by,
• Corneal ulcer formation, which is typically horizontally oval, located in the lower one-half of the cornea and have grey heaped-up epithelial borders (Fig 6.13A).
Note. Relapses are very common, even the healed scars quickly breakdown again.
Treatment
■Conventional  treatment  with  antibiotics, cycloplegics, lubricating drops and patching should be started immediately.
■Special treatment recommended is topical nerve growth factor drops and autologous serum drops. ■Amnioticmembranetransplantationisrecommended when patients present with large non-healing ulcers. ■Lateraltarsorrhaphyis usually required to promote healing and prevent relapses. It should be kept at least for one year alongwith and prolonged use of artificial tears is also recommended.
EXPOSURE KERATOPATHY
Normally cornea is covered by eyelidsduring sleep and is constantly kept moist by blinking movements during awakening. When eyes are covered insufficiently by the lids and there is loss of protective mechanism of blinking, the condition of exposure keratopathy (keratitis lagophthalmos) develops.
Causes
Following factors which produce lagophthalmos may lead to exposure keratopathy:

1. Extreme proptosis due to any cause will allow inadequate closure of lids.
2. Bell’s palsy or any other cause of facial palsy. 3. Ectropion of severe degree.
4. Symblepharon causing lagophthalmos.
5. Deepcomaassociated with inadequate closure of lids.
6. Physiological lagophthalmos. Occasionally, lagophthalmos during sleep may occur in healthy individuals.

Pathogenesis
Due to exposure the corneal epithelium dries up followed by dessication. After the epithelium is cast off, invasion by infective organisms may occur.
Clinical features
Symptoms and signsof the causative disease are evident. Symptoms of exposure keratopathy include ocular irritation, burning, foreign body sensation and redness. Symptoms are usually worse in the morning. Signs of exposure keratopathy are:
■Drying of cornea occurs to begin with due to inadequate blinking or closure of the lids.
■Punctateepithelialdefectsdevelop in the lower third of cornea or as a horizontal band in the region of palpebral fissure (Fig. 6.13).
■Corneal ulceration may develop soon due to necrosis followed by bacterial superinfection. If neglected, corneal ulcer may even perforate soon.
Treatment
1. Prophylaxis. Once lagophthalmos is diagnosed following measures should be taken to prevent exposure keratitis.
• Artificial tears should be instilled frequently.
• Instillationofointmentand closure of lids by a tape or bandage during sleep.
• Softbandagecontactlenswith frequent instillation of artificial tears is required in cases of moderate exposure.
• Treatment of the cause of exposure: e.g., proptosis, ectropion, symblepharon should be taken up.
2. Treatment of the corneal ulcer once developed is on the general lines (see page 104). Tarsorrhaphy is invariably required when it is not possible to treat the cause or when recovery of the cause (e.g., facial palsy) is not anticipated.

PERIPHERAL ULCERATIVE KERATOPATHIES

Peripheral ulcerative keratopathies (PUKs), characterized by peripheral corneal thinning, infiltrates
116	Section III   Diseases of Eye












A	B
Fig. 6.13 Trophic corneal ulcers: A, Neurotrophic; B, Exposure keratitis (Note punctate epithelial defects in the lower third of cornea)


and ulceration, includes various conditions with different etiologies. Some of the PUKs are as follows: • Peripheral ulcerative keratitis associated with
connective tissue disorders, • Mooren’s ulcer,
• Rosacea keratitis,
• Marginal keratitis (catarrhal ulcer) of Staphy-lococcal hypersensitivity (see page 105),
• Terrien marginal degeneration (see page 124), • Pellucid marginal degeneration (see page 124), • Phlyctenular keratitis (see page 84), and
• Dellen.

PERIPHERAL ULCERATIVE KERATITIS ASSOCIATED WITH CONNECTIVE TISSUE DISEASES (MARGINAL KERATOLYSIS)
Causes
Peripheral corneal ulceration and/or melting of corneal tissue is not of infrequent occurrence in patients suffering from connective tissue diseases such as:
• Rheumatoid arthritis,
• Systemic lupus erythematosus (SLE), • Polyarteritis nodosa, and
• Wegener’s granulomatosis.
Clinical features
• Peripheral acute corneal ulceration with rapid progression, usually in one sector, associated with inflammation at the limbus in one or both eyes.
• Peripheralcornealguttering or thinning may involve entire corneal periphery (contact lens cornea).
• Peripheral  corneal  melting may result in descemetocele formation or even perforation.
• Cornealulceration may be the first manifestation of the systemic disease and there may be associated systemic features of any of the causative disease.
Treatment
Such corneal ulcers are usually indolent and difficult to treat.

1. Topical medication include, antibiotics, cyclop-legics and frequent instillation of lubricating drops. Topical steroids may be used with great caution, but not in the presence of significant thinning.
2. Systemic medication includes immunosupp-ressants (corticosteroids, or methotrexate, cycloph-osphamide), doxycycline and oral vitamin C (to promote a healing stromal environment).
3. Surgical measures needed include:
• Excision of adjacent inflamed conjunctiva,
• Bandage contact lens or conjunctival flap for impending perforation,
•		tissue adhesive or peripheral tectonic keratoplasty for actual perforation.
MOOREN’S ULCER
Mooren’s ulcer (chronic serpiginous or rodent ulcer) is a severe inflammatory peripheral ulcerative keratitis.

Etiology
Exact etiology is not known. Most probably it is an autoimmune disease (antibodies against corneal epithelium have been demonstrated in serum).
Clinical features
Two clinical varieties of Mooren’s ulcer have been recognised.
1. Benignorlimitedformwhich is usually unilateral, affects the elderly Caucasians and is characterised by a relative slow progress.
2. Virulent type also called the progressive form  is bilateral, more often occurs in young African patients. The ulcer is rapidly progressive with a high incidence of scleral involvement.
Symptoms. These include severe pain, photophobia, lacrimation and defective vision.
Signs. Features of Mooren’s ulcer are shown in Fig. 6.14. • It is a superficial ulcer which starts at the corneal margin as patches of grey infiltrates which coalesce
to form a shallow furrow over the whole cornea.
Chapter 6	Diseases of Cornea	117















A













B
Fig. 6.14 Mooren’s ulcer: A, Diagrammatic depiction; B, Clinical photograph

• Peripheral ulcer is associated with undermining of the epithelium and superficial stromal lamellae at the advancing border which forms a characteristic whitish overhanging edge. Base of the ulcer soon becomes vascularized. The spread may be self-limiting or progressive.
• At the end-stage, the cornea is thinned and conjunctivalised.
• Ulcer rarely perforates and the sclera remains uninvolved.
Treatment
Since exact etiology is still unknown, its treatment is highly unsatisfactory. Following measures may be tried:
1. Topical corticosteroids instilled every 2–3 hours are tried as initial therapy with limited success.
2. Immunosuppressive therapy with systemic steroids may be of help. Immunosuppression with cyclosporinor other cytotoxic agents may be quite useful in virulent type of disease.
3. Softcontactlenseshave also been used with some relief in pain.

4. Lamellarorfullthicknesscornealgraftsoften melt or vascularize.
ROSACEA KERATITIS
Corneal ulceration is seen in about 10% cases of acne rosacea, which is primarily a disease of the sebaceous glands of the skin.
Clinical features
1. Facial  eruptions  presenting  in  butterfly configuration, predominantly involving the malar and nasal area of face typically occurs in elderly women.
2. Ocular  lesions  include  chronic  blepha-roconjunctivitis and keratitis. Rosacea keratitis occurs as yellowish white marginal infiltrates, and small ulcers that progressively advance across the cornea and almost always become heavily vascularised.
Treatment
1. Local treatment. Rosacea keratitis responds to topical steroids, but recurrences are very common.
2. Systemic treatment. The essential and most effective treatment of rosacea keratitis is a long course of systemic tetracycline (250 mg QID × 3 weeks, TDS × 3 weeks, BID × 3 weeks, and once a day for 3 months).

NON-ULCERATIVE KERATITIS

Non-ulcerative keratitis can be divided into two groups: Non-ulcerative superficial keratitis and Non-ulcerative deep keratitis.

NON-ULCERATIVE SUPERFICIAL KERATITIS

This group includes a number of conditions of varied etiology. Here, the inflammatory reaction is confined to epithelium, Bowman’s membrane and superficial stromal lamellae. Non-ulcerative superficial keratitis may present in two forms:
• Diffuse superficial keratitis and • Superficial punctate keratitis.

DIFFUSE SUPERFICIAL KERATITIS

Diffuse inflammation of superficial layers of cornea occurs in two forms, acute and chronic.
1. Acute diffuse superficial keratitis
Etiology. Mostly of infective origin, may be associated with Staphylococcal or gonococcal infections. Clinical features. It is characterised by faint diffuse epithelial oedema associated with grey farinaceous
118	Section III   Diseases of Eye

appearance being interspersed with relatively clear area. Epithelial erosions may be formed at places. If uncontrolled, it usually converts into ulcerative keratitis.
Treatment. It consists of frequent instillation of antibiotic eyedrops such as tobramycin or gentamycin 2–4 hourly.
2. Chronic diffuse superficial keratitis
It may be seen in rosacea, phlyctenulosis and is typically associated with pannus formation.


SUPERFICIAL PUNCTATE KERATITIS (SPK)

Superficial punctate keratitis is characterised by occurrence of multiple, spotty lesions in the superficial layers of cornea. It may result from a number of conditions, identification of which (causative condition) might not be possible most of the times.
Causes
Some important causes of superficial punctate keratitis are listed here.
1. Viral infections are the chief cause. Of these more common are: herpes zoster, adenovirus infections, epidemic keratoconjunctivitis, pharyngoconjunctival fever and herpes simplex.
2. Chlamydial infections include trachoma and inclusion conjunctivitis.
3. Toxic lesions e.g., due to Staphylococcal toxin in association with blepharoconjunctivitis.
4. Trophic lesions e.g., exposure keratitis and neuroparalytic keratitis.
5. Allergic lesions e.g., vernal keratoconjunctivitis. 6. Irritativelesions e.g., effect of some drugs such as
idoxuridine.
7. Disordersofskinandmucousmembrane, such as acne rosacea and pemphigoid.
8. Dryeyesyndrome, i.e., keratoconjunctivitis sicca. 9. Specific type of idiopathic SPK e.g., Thygeson’s superficial punctate keratitis and Theodore’s
superior limbic keratoconjunctivitis. 10. Photo-ophthalmia.
Morphological types
1. Punctate epithelial erosions (multiple superficial erosions).
2. Punctate epithelial keratitis (Figs. 6.15A and B). 3. Punctate subepithelial keratitis (Figs. 6.15C and D). 4. Punctate combined epithelial and subepithelial
keratitis (Figs. 6.15E and F).
5. Filamentary keratitis (Figs. 6.15G and H).






















Fig. 6.15  Morphological types of superficial punctate keratitis. diagrammatic depictions and clinical photographs of: A and B, Punctate epithelial; C and D, Punctate sub-epithelial keratitis; E and F, Punctate combined epithelial and subepithelial keratitis; G and H, Filamentary keratitis


Clinical features
Superficial punctate keratitis may present as different morphological types as enumerated above. Punctate epithelial lesions usually stain with fluorescein, rose bengal and other vital dyes. The condition mostly presents with acute pain, photophobia and lacrimation; and is usually associated with conjunctivitis.
Treatment
Treatment of most of these conditions is symptomatic. 1. Topicalsteroidshave a marked suppressive effect. 2. Artificial tears have soothing effect.
3. Specific treatment of cause should be instituted
Chapter 6	Diseases of Cornea	119


whenever possible e.g., antiviral drugs in cases of herpes simplex.
PHOTO-OPHTHALMIA
Photo-ophthalmia refers to occurrence of multiple epithelial erosions due to the effect of ultraviolet rays especially from 311 to 290 m.
Causes
• Exposure to bright light of a short circuit.
• Naked arc light exposure as in industrial welding and cinema operators.
• Snow blindness due to reflected ultraviolet rays from snow surface.
Pathogenesis
After an interval of 4–5 hours (latent period) of exposure to ultraviolet rays, there occurs desqua-mation of corneal epithelium leading to formation of multiple epithelial erosions.
Clinical features
• Typically,patientpresentswith severe burning pain, lacrimation, photophobia, blepharospasm, swelling of palpebral conjunctiva and retrotarsal folds.
• History of exposure to ultraviolet rays 4–5 hours earlier is positive.
• On fluorescein staining multiple spots are demonstrated on both corneas.
Prophylaxis
• Crooker’s glass which cuts off all infrared and ultraviolet rays should be used by those who are prone to exposure e.g., welding workers, cinema operators, etc.
Treatment
• Cold compresses.
• Patching with antibiotic ointment for 24 hours, heals most of the cases.
• Oralanalgesicsmay be given if pain is intolerable. • Single dose of tranquilizer may be given to
apprehensive patients.

SUPERIOR LIMBIC KERATOCONJUNCTIVITIS Superior limbic keratoconjunctivitis of Theodore is the name given to inflammation of superior limbic, bulbar and tarsal conjunctiva associated with punctate keratitis of the superior part of cornea.
Etiology
Exact etiology is not known. It occurs with greater frequency in patients with hyperthyroidism and is more common in females.

Symptoms include:
• Bilateral ocular irritation.
• Mild photophobia, and redness in superior bulbar conjunctiva.
Signs include (Fig. 6.16):
• Congestion of superior limbic, bulbar and tarsal conjunctiva.
• Punctate keratitis which stains with fluorescein and rose Bengal stain is seen in superior part of cornea.
• Corneal filaments are also frequently seen in the involved area.
Treatment
• Artificial tears provide soothing effect.
• Topicalcorticosteroidsin low doses may reduce the symptoms temporarily.
• Faint diathermy of superior bulbar conjunctiva in a checker board pattern gives acceptable results.
• Recessionorresection of a 3–4 mm wide perilimbal strip of conjunctiva from the superior limbus (from 10.30 to 1.30 O’clock position) may be helpful, if other measures fail.
• Therapeutic soft contact lenses for a longer period may be helpful in healing the keratitis.













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Clinical features
Clinical course is chronic with remissions and exacerbations.