Fig. 12.1: Gross anatomy of cornea [Courtesy: Allergan (India)]
3. Substantia propria or corneal stroma constitutes 90% of the entire thickness of the cornea and is composed of a modified connective tissue containing lamellae and cells. The lamellae, numbering 100 to 150, are ribbon-like bands of collagen fibers. They run parallel to each other and also to the surface of the cornea and become continuous with scleral lamellae at the limbus. Two types of corneal cells, keratocytes (fixed cells), and wandering cells are found between the lamellae.
4. Descemet’s membrane is a strong, homogeneous structureless layer. It is sharply defined from the corneal stroma and quite resistant to the inflammatory process of the cornea. Even when the entire cornea gives way, the mem- brane remains unimpaired. Unlike Bowman’s membrane, Descemet’s membrane can rege- nerate. It ends abruptly at the limbus as the ring of Schwalbe. The posterior surface of the membrane may present wart like bodies— Hassall-Henle bodies.
5. Endothelium is the most posterior layer of the cornea and consists of a single layer of flat hexagonal cells. On slit-lamp biomicroscopy, they appear as a brown mosaic of polygons. The cell population of endothelium varies considerably in individual eyes and decreases with advancing age.
Blood Supply of the Cornea
The cornea is an avascular tissue. However, it does get some nourishment from the superficial plexus formed by the episcleral branches of the anterior ciliary arteries. The veins follow a similar course. The lymphatics are absent from the cornea.
Nerve Supply of the Cornea
The cornea is richly supplied by the ophthalmic division of the trigeminal nerve through the long ciliary nerves which come from the suprachoroidal space and enter the sclera. They pass into the cornea as 60 to 80 myelinated trunks after forming a pericorneal plexus. They divide into anterior and
posterior groups, each comprising 40 to 50 twigs. The anterior group forms the subepithelial and intraepithelial plexuses, while the posterior supplies the posterior peripheral part of the cornea.
DISEASES OF THE CORNEA
Diseases of the cornea are serious as they often disturb the transparency of the cornea leading to visual impairment ranging from slight blurring to total blindness. The diseases of the cornea may be: 1. Inflammatory
2. Degenerative 3. Developmental, and 4. Symptomatic.
Inflammation of the Cornea
The inflammatory conditions of the cornea are frequent in occurrence and may arise from:
1. Exogenous infection: Cornea is often involved by direct invasion of an organism (corneal ulcer) which may or may not be preceded by trauma.
2. Endogenous infection: Cornea is involved in systemic, allergic and hypersensitivity reactions such as interstitial keratitis. 3. Secondary infection: Cornea is secondarily
involved in the diseases of conjunctiva, sclera and uvea as these structures are in direct anatomical continuity with the cornea.
Classification
The inflammation of the cornea is known as keratitis. It may be of two types:
1. Ulcerative keratitis wherein the corneal epithelium shows discontinuity, and
2. Non-ulcerative keratitis wherein epithelium is intact.
Ulcerative Keratitis
Clinically, ulcerative keratitis is divided into two categories: superficial and deep.
Topographically, the ulcerative lesion (corneal ulcer) may be central, paracentral or marginal. The ulcer can be suppurative (purulent) or non- suppurative (nonpurulent).
Deep corneal ulcers may cause sloughing of the corneal stroma (sloughing corneal ulcer) or are associated with pus in the anterior chamber (hypopyon corneal ulcer). The deep progressive corneal ulcer may undergo perforation.
A simplified classification of ulcerative keratitis is given in Table 12.1.
Bacterial Corneal Ulcer
Bacterial corneal ulcer is an infection of the cornea associated with discontinuity of the corneal epithelium often accompanied with pain and diminution of vision.
Etiology Corneal ulcer occurs usually due to exogenous infection by pyogenic organisms, viz. Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, Neisseria gonorrhoeae and Streptococcus hemolyticus. The ulcer is often associated with risk factors that disturb the integrity of the corneal epithelium. The common risk factors include trauma, foreign body, contact lens wear, prolonged use of corticosteroids and general disability or impaired defence mechanism. The intact corneal epithelium offers considerable resistance to the invasion by the microorganisms except Neisseria gonorrhoeae and Corynebacterium diphtheriae.
Pathogenesis The pathogenesis of corneal ulcer may be described under 4 stages.
Stage of infiltration: Corneal inflammation begins with local production of cytokines and chemokines inducing diapedesis and migration of neutrophils into the cornea from the limbal vessels. Some organisms produce proteases that disturb the extracellular matrix. The superficial layers of cornea show focal infiltration with inflammatory cells predominantly polymorphonuclear. The epithelium is edematous and raised at the site of infiltration. It undergoes necrosis and ultimately desquamates. If the lesion is superficial and does not involve Bowman’s membrane it heals quickly without leaving any opacity. In case,the infil- tration extends into the deeper layers of the cornea and destroys Bowman’s membrane, it indicates the progression of lesion.
Stage of progression: The epithelium at the margins of the ulcer swells and overhangs. The corneal lamellae imbibe fluid and project above the surface giving a saucer-shaped appearance to the ulcer. The floor and the margin of the ulcer are packed with inflammatory cells and they appear gray. Enzymes released by neutrophils and activation of corneal metalloproteinases exacerbate necrosis. Bacterial toxins may diffuse in the anterior chamber and cause damage to the corneal endothelium, and induce iritis. Table 12.1: Classification of ulcerative keratitis
Location Depth Necrosis Uveal Etiology
reaction
Central Superficial Suppurative With hypopyon Infective: Bacterial, Viral, Fungal,
Paracentral Deep Nonsuppurative Without hypopyon Chamydial, Protozoal, Spirochetal Peripheral Allergic: Phlyctenular, Vernal,
Atopic
Traumatic Trophic
Associated with systemic disorders Idiopathic
Stage of regression: The sloughed corneal lamellae are cast off and the ulcer appears somewhat larger but clean with smooth floor and edges. Simulta- neously, the limbal vessels extend and invade the ulcer. The vessels help in the proliferation of granulation tissue, supply of antibodies and sliding of marginal epithelium to bridge the gap.
Stage of cicatrization: In this stage, the granulation tissue is formed which is composed of irregularly arranged fibroblasts. Thus after healing, cornea becomes opaque at the site of ulceration. At times, due to deficient cicatrization, a corneal facet is left behind. The opacity in the cornea, depending on its density, may be nebular, macular or leukomatous. Clinical features Pain, gritty sensation, redness, lacrimation, photophobia, blepharospasm and impairment of vision are the common symptoms of a corneal ulcer. Most corneal ulcers start as a gray or white localized infiltrate in the cornea causing loss of luster of the tissue. There is a discontinuity of the corneal surface which can be demonstrated by fluorescein staining. The ulcer takes a green stain (Fig. 12.3). The ulcer may be round, oval or irregular in shape.
The margin of the ulcer is edematous and overhanging with sloping edges. There occurs marked ciliary injection associated with slough (Fig. 12.4). Small superficial vessels grow in from the limbus towards the margin of the ulcer. Occasionally, an exuberant fibrofleshy growth may cover the ulcer and retard its healing. Complications Generally, the ulcer heals by granulation. However, in adverse circumstances (like debility state or microorganism not amenable to the treatment), the ulcer extends both in size and depth. The corneal lamellae are macerated and the necrotic tissue covers the floor. The loss of entire corneal stroma leads to exposure of Descemet’s membrane which may bulge as a transparent vesicle under the effect of normal intraocular pressure. The bulging of the Descemet’s membrane is called descemetocele or keratocele (Fig. 12.5). The ulcer may eventually perforate if not managed properly.
Fig. 12.4: Central corneal ulcer
Fig. 12.5: Sloughing corneal ulcer with descemetocele Fig. 12.3: Fluorescein staining of corneal ulcer
Specific Types of Bacterial Corneal Ulcers
Hypopyon Corneal Ulcer
A disk-shaped central corneal ulcer with hypo- pyon (sterile pus in the anterior chamber) and violent iridocyclitis is called hypopyon corneal ulcer. Etiology The hypopyon ulcer is usually found in old, debilitated, malnourished patients who may be suffering from chronic dacryocystitis. There is always a risk of development of hypopyon ulcer following an injury by organic matters like leaf, twigs, coal, stone and finger-nail. Streptococcus pneumoniae, Streptococcus hemolyticus, Neisseria gonorrhoeae and Proteus vulgaris are common pyogenic organisms capable of producing the ulcer. Pseudomonas pyocyanea causes a fulminant slough- ing hypopyon corneal ulcer with a greenish look within a short time. Hypopyon is frequently found in mycotic corneal ulcers.
Clinical features A typical pneumococcal ulcer, also known as ulcus serpens, starts as a grayish- white disk with infiltrating edges near the central part of the cornea. The cornea becomes cloudy and lusterless. The toxins liberated by the offend- ing organisms diffuse into the anterior chamber and induce severe iridocyclitis associated with pouring of polymorphonuclear leukocytes in the anterior chamber known as hypopyon (Fig. 12.6A). The hypopyon remains sterile as long as Descemet’s membrane is intact, since the latter is impermeable to the organisms. The hypopyon gravitates to the bottom of the anterior chamber (Fig. 12.6B). The horizontal upper level of the fluid moves with the change in the position of the patient’s head. Hypopyon may be so small that the rim of sclera covers it and thus is hardly visible, or it may be so massive that it masks the entire iris. Large hypopyon tends to get organized owing to the presence of fibrinous network that traps the leukocytes.
The ulcer progresses on the edge of densest infiltration which appears as a yellowish crescent.
Fig. 12.6A: Hypopyon corneal ulcer
Fig. 12.6B: Schematic diagram of hypopyon corneal ulcer: b-d, Extent of ulcer; b, Actively progressive margin; b-c, Mass of leukocytes and fibrin adherent to the endothelial surface; e-f, Hypopyon
The superficial corneal stroma becomes necrotic and breaks down. An additional infiltration develops anterior to Descemet’s membrane at a spot just opposite to the floor of ulcer, while the intervening corneal lamellae are healthy. The progression of the ulcer from both the sides causes gross corneal necrosis. Massive hypopyon often causes rise in intraocular pressure (secondary glaucoma).
Sometimes the entire cornea sloughs off with the exception of a narrow rim at the margin causing a total prolapse of the iris. Such eyes go in phthisis. A pseudocornea is formed which ultimately tends to become ectatic. An anterior ectasia of the pseudocornea, in which the iris tissue is incarcerated, is called anterior staphyloma. The latter may be partial or total.
Staphylococcal Corneal Ulcer
Staphylococcal corneal ulcer is often found in compromised cornea, dry eyes and postherpetic keratitis. The ulcer remains localized with distinct borders and the surrounding stroma shows edema. Chronic ulcer tends to bore deep forming a stromal abscess which may cause perforation.
Pseudomonas Corneal Ulcer
Pseudomonas causes a rapidly spreading slough- ing corneal ulcer with greenish-yellow muco- purulent discharge adherent to the ulcer (Fig. 12.8). The ulcer presents a characteristic diffuse epithelial graying that occurs away from the main site of epithelial and stromal infiltration. It spreads Complications In severe cases, the entire cornea is
affected by the ulcerative process. A sudden exertion (coughing or sneezing) results in perforation of the ulcer which is marked by escape of aqueous humor, reduction in intraocular pressure and forward displacement of the iris and the lens.
Complications of a perforated ulcer are serious and may endanger the eyeball. The effect of perforation largely depends on its size and position. A small perforation in the peripheral or paracentral zone of the cornea is promptly plugged by the iris, which on healing leads to adherent leukoma. When the perforation is large, iris prolapse occurs through the site of perforation (Figs 12.7A and B). When perforation occurs in the center of the cornea, the pupillary margin fails to seal the gap. The lens comes in contact with the cornea and exudates fill the gap. There occurs repeated formation and collapse of the anterior chamber and subsequently corneal fistula develops associated with anterior capsular cataract. Sudden perforation of a large corneal ulcer may even cause extrusion of the lens from the eye, prolapse of the vitreous and intraocular hemorrhage.
Figs 12.7A and B: (A) Perforated corneal ulcer with prolapse of iris, (B) Diagrammatic representation of prolapse of the iris
symmetrically and concentrically involving whole width and depth of the cornea associated with severe anterior chamber reaction and hypopyon formation. Pseudomonas strains produce protease, lipase and exotoxin-A that cause melting of the cornea resulting in perforation.
Moraxella Corneal Ulcer
Moraxella corneal ulcer occurs after trauma in diabetic or malnourished patients. The ulcer is usually oval in shape and located in the inferior half of the cornea. It is indolent and spreads deep into the stroma causing mild to moderate anterior chamber reaction.
Diagnosis A definitive diagnosis of corneal ulcer can only be made by organismal culture and sensitivity. The microbiologic work-up of an infective corneal ulcer must be done before the start of therapy. Smear and culture examinations should be carried out. The Kimura spatula or sterile disposable blade is used to take scrapings from the floor of the ulcer after anesthetizing the surface. The material is innoculated on blood agar, chocolate agar, and Sabouraud agar for culture and spread over slides for gram and Giemsa stains for bacteria, and KOH preparation for fungi. The
Fig. 12.8: Pseudomonas corneal ulcer
Figs 12.9A to C: Corneal scrapings stained by gram stain showing: (A) gram-positive cocci, (B) gram-negative bacteria, (C) septate fungal filaments (Courtesy: Dr Savitri Sharma, LVPEI, Hyderabad)
calcofluor white stained corneal scrapings are seen under fluorescent microscope for the fungal filaments (Figs 12.9A to C). Cultures are more sensitive than smears in identifying the causative organism.
Treatment
Prophylaxis: In majority of cases, development of corneal ulceration can be prevented by wearing protective glasses against foreign body and mechanical or chemical injuries, and proper and timely treatment of acute conjunctivitis, dacryo- cystitis and trichiasis. Exposure of the cornea should be prevented during unconsciousness or moribund conditions.
Once corneal ulcer develops, it requires prompt and adequate treatment. Surgical cleanliness, specific treatment of the infection, rest and protection to the eye are the basic principles of management of corneal ulcer.
Irrigation: Eye is irrigated with warm saline 2 to 3 times a day. It removes the discharge and necrotic materials along with organisms and their toxins. Warmth of the saline employed prevents vascular stasis and encourages flow of antibodies. Antibiotics: The infection is controlled by the topical use of specific bactericidal or bacteriostatic antibiotics selected after the sensitivity test. However, testing facilities are not available in all the hospitals and the procedure is time consuming. It is, therefore, necessary to start a broad-spectrum antibiotic without waiting for the culture and sensitivity report. Instillations of fluoroquinolone (moxifloxacin, gatifloxacin or ciprofloxacin) and cefalosporin (cefazolin 5%) drops are effective in controlling the corneal infection caused by both gram-positive and gram-negative organisms. Fortified antibiotics: In severe infection, fortified antibiotics are preferred to their commercially available concentrations. The fortified antibiotics used for the treatment of corneal ulcer are freshly prepared from their injectable preparations (Table 12.2).
To achieve therapeutic corneal concentration of the drug one of the antibiotics should be instilled every 5 or 10 minutes, then one drop every 30 or 60 minutes for 24 to 48 hours in day time. The antibiotic ointment can be applied at bed time.
The therapy should be reviewed or modified after receiving the culture-sensitivity report. The frequency of instillation of an antibiotic drop is gradually reduced if the condition improves. Cycloplegics: Rest to the eye can be provided by the use of a cycloplegic, homatropine (2%) eye drop or atropine sulphate (1% drop or ointment) at least twice a day. Atropine prevents or relieves the ciliary spasm and minimizes the complications of accompanying anterior uveitis. Corticosteroid preparation must not be applied in a corneal ulcer (with rare exceptions) as it retards the epithelial healing and promotes secondary viral and fungal infections.
Protection to eye: The eye may be protected by pad and bandage unless there is a copious discharge. Eyes with discharge can be protected with dark glasses.
General measures: Systemic analgesics and anti- inflammatory agents (diclofenac sodium, ibuprofen, etc.) relieve pain from inflammatory reaction. General health of the patient must not be ignored. Malnutrition should be taken care of and diabetes, if present, be controlled.
Non-healing ulcer: In case, the ulcer does not respond favorably to the above therapeutic regimen and continues to progress, a thorough Table 12.2: Fortified concentration of topical antibiotics
and dosage of antibiotics for subconjunctival injection Antibiotics Fortified Subconjunctival
concentration dose 1. Amikacin 50 mg/ml 25 mg/0.5 ml sulphate 2. Cefaloridine 50 mg/ml 100 mg/0.5 ml 3. Cefamandole 50 mg/ml 100 mg/0.5 ml 4. Cefazolin 50 mg/ml 100 mg/0.75 ml 5. Ceftriaxone 50 mg/ml 100 mg/0.5 ml 6. Gentamicin 10-20 mg/ml 20 mg/0.5 ml 7. Tobramycin 10-20 mg/ml 20 mg/0.5 ml 8. Ciprofloxacin 3 mg/ml — 9. Moxifloxacin 3.5 mg/ml — 10. Gatfloxacin 3.5 mg/ml —
search must be made for the presence of trichiasis, dacryocystitis, intracorneal foreign body and raised intraocular pressure. If found, corrective measures must be taken to hasten the healing. Subconjunctival injections: Additionally, sub- conjunctival and intravenous (IV) injections of antibiotics are recommended as adjunctive therapy to topical fortified antibiotics (Table 12.2). Specific indications for subconjunctival injection are: (i) non-healing ulcers with deep infiltrates, (ii) impending corneal perforation, and (iii) hypopyon corneal ulcer. Depending upon the culture-sensitivity test, subconjunctival injections of amikacin, gentamicin or cefalosporin may be given daily or on alternate day basis. However, injections are painful, anxiety provoking and may cause subconjunctival hemorrhage.
Surgical measures: To hasten healing, surgical measures may have to be adopted. These include: (i) mechanical debridement of the ulcer floor, (ii) cauterization of the ulcer floor with pure carbolic acid or 10% trichloracetic acid, and (iii) excision of 2 mm strip of limbal conjunctiva (peritomy) to regress exuberent corneal vascularization impe- ding healing.
Prevention of perforation: In case there is an imminent danger of corneal perforation, imme- diate measures should be taken to prevent perforation by lowering the intraocular pressure and by supporting the thin cornea. The intraocular pressure is reduced by oral acetazolamide and/ or IV mannitol and topical aqueous suppressants. The procedure not only checks perforation, but also improves nutrition of the diseased cornea. Bandage contact lens, conjunctival flapping and tectonic corneal grafting can support the weak cornea.
Management of perforated corneal ulcer: In spite of these measures if cornea perforates, attempts should be made to restore the integrity of the
anterior chamber as quickly as possible. Conjunc- tival flapping, penetrating therapeutic kerato- plasty, cynoacrylate glue and collagen plug or shield may be helpful to save the eye.
Viral Corneal Ulcers
Both DNA and RNA viruses may cause eye diseases. However, DNA viruses such as herpes, vaccinia and adenovirus quite often infect the cornea. The corneal involvement in viral infections is described under the nonulcerative keratitis. Fungal Corneal Ulcer
Etiology Fungal corneal ulcer occurs more frequently in warm and humid climate. Trauma to the cornea by vegetable material, indiscriminate use of corticosteroid, trauma related to contact lens wear, chronic keratitis and corneal surgery are important risk factors for fungal corneal ulcer. Aspergillus fumigatus, Candida albicans, Fusarium, and a few species of dermatophytes can cause fungal corneal ulcer.
Clinical Features Classically, most mycotic ulcers are gray, indolent and slowly progressive with relatively minimal symptoms. The clinical signs