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Year : 1994  |  Volume : 42  |  Issue : 4  |  Page : 171-192

Current perspectives in infectious keratitis

1 Bombay City Eye Institute, Bombay, L.V. Prasad Eye Institute, Hyderabad, India
2 Sankara Nethralaya, Madras, India
3 Postgraduate Institute of Medical Education and Research, Chandigarh, India
4 L.V. Prasad Eye Institute, Hyderabad, India
5 Aravind Eye Hospital, Madurai, India

Correspondence Address:
Madhukar K Reddy
L.V. Prasad Eye Institute, Road No. 2, Banjara Hills, Hyderabad 500 034
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Source of Support: None, Conflict of Interest: None

PMID: 10576995

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How to cite this article:
Agrawal V, Biswas J, Madhavan H N, Mangat G, Reddy MK, Saini JS, Sharma S, Srinivasan M. Current perspectives in infectious keratitis. Indian J Ophthalmol 1994;42:171-92

How to cite this URL:
Agrawal V, Biswas J, Madhavan H N, Mangat G, Reddy MK, Saini JS, Sharma S, Srinivasan M. Current perspectives in infectious keratitis. Indian J Ophthalmol [serial online] 1994 [cited 2023 Sep 30];42:171-92. Available from: https://journals.lww.com/ijo/pages/default.aspx/text.asp?1994/42/4/171/25566

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Corneal blindness is a major public health prob­lem in India and infections constitute the most pre­dominant cause. Infectious keratitis has for long been the Achille' heel of most ophthalmic surgeons. A wide spectrum of microbial organisms can produce corneal infections and consequently the therapeutic strategies may be variable [Figure - 1]. Proper public health initiatives can effectively prevent sight-threat­ening corneal infections and aggressive initial treat­ment for clinical cases of infectious keratitis can minimize the incidence of post-infectious corneal scars. One of the key elements in this effort is a proper understanding of the microbiological and clinical characteristics of this disease entity which will enable the ophthalmologist to initiate appropriate antimicro­bial therapy.

A recent survey carried out in Southern Califor­nia covering a representative population of ophthal­mologists had very revealing figures. A total of 47.8 percent of the patients with a clinical diagnosis of in­fectious keratitis were treated with antibiotics with­out any cultures being obtained. [1] If this is the case in countries with advanced care, a thought about the possible situation in developing countries like ours would indeed be revealing. It is time, however, that we stop using the excuse of limited resources to hide our sins of omission about the recommended steps in the approach to the treatment of any disease. More often than not, it is the lack of proper train­ing and outlook rather than the paucity of resources which is responsible for irregular treatment modali­ties.

This review is an attempt to provide the reader with a survey of all aspects of infectious keratitis. Emphasis is given to the most recent information. Although a lot of progress has been made in the medical therapy of bacterial keratitis, fungal keratitis still remains a therapeutic challenge.


This section will cover some salient features of infectious keratitis that may help in the initial diagnosis.

II. A. Bacterial Keratitis

Although the clinical characteristics of bacterial keratitis caused by specific individual organisms have been previously described, it is not generally possible to identify the causative agent by clinical examination alone. The microorganisms by virtue of their toxins, adherence capabilities, invasiveness and even strain differences within each species may produce different types of clinical picture. The clinical picture may also vary or alter in these patients using contact lenses or with a previous corneal scar due to viral infections, trauma, or surgery. However, some general clinical descriptions may be useful. For example, gram­positive organisms tend to produce discrete, small abscess like lesion and gram-negative bacteria are more likely to cause diffuse, rapidly spreading necrotic lesions, but exceptions do occur. The bacterial or fungal infection may strongly be suspected on the basis of clinical criteria, but confirmation by scrapings and culture is essential. Herpetic keratitis, non­infectious keratitis, fungal keratitis and even toxic keratitis can all be confused with bacterial keratitis without proper laboratory diagnostic studies.

Patients with infectious corneal ulceration complain of pain, watering, foreign body sensation, redness and decreased vision. Pain is a prominent symptom but it varies with the size of the ulcers and nature of the organism. Watering and pain are more severe in rapidly spreading ulcer caused by Pseudomonas and Streptococcus pneumoniae species. Indolent ulcers due to Moraxella and Staphylococcus may be quiet and less symptomatic [Figure - 2]. Marked lid oedema and conjunctival chemosis are commonly seen in corneal ulceration due to gram-negative organisms especially following trauma and gonococcal infection. However, one should remember that patients who had topical steroids will exhibit signs and symptoms in milder form.

Hypopyon, one of the most important clinical signs of any type of infectious keratitis could be considered as the most important sign in establish­ing the aetiological diagnosis. For example, a defini­tive diagnosis of pneumococcal ulcer was based on hypopyon. It was once called as central hypopyon corneal ulcer. Haemorrhagic hypopyon is attributed to either Pneumococcal or Herpes simplex viral ker­atitis. It is also seen in fungal ulcer. One should remember that hypopyon could form with viral, fungal and parasitic ulcers. Non-bacterial or non­fungal problems such as Bechet's syndrome, abuseof topical anaesthetic agents and severe bums may also give rise to hypopyon. In general, corneal ulceration associated with purulent or mucopurulent discharge from lacrimal sac of the same side gives diagnostic clue in favour of pneumococcal ulcer; whereas, greenish discharge makes one think of Pseudomonas ulcer. Gonococcal ulcer in infants which, is rare now, presents with lid oedema, marked che­mosis and purulent discharge.

One of the most dreaded corneal ulcers is that caused by Pseudomonas species. It is typically char­acterized by rapid evolution, primary involvement of corneal stroma and rapid spread to involve the entire cornea, unusual size of hypopyon and mucous consistency and often greenish colour of the pus [Figure - 3].

II. B. Fungal Keratitis

Corneal infection of fungal aetiology is very common and may represent 30 to 40 percent of all cases of culture-positive infectious keratitis in South India. Of these, Aspergillus and Fusarium are responsible for 70 percent of cases. These affect young, immunocompetent healthy adults, more often from rural areas. A history of trauma with organic matter is elicited in a significant percentage of cases. The ulcer commences insidiously and runs an indolent course. It begins at the midperiphery of healthy cornea in the exposed areas. The epithelium may show defect at the site of infiltration or epithelial defect would have healed with deep stromal infiltrate or endothelial plaque. The ulcer spreads towards the centre of the cornea. Moderate hypopyon or cheesy hypopyon is frequently noticed. In rare cases one may see a haemorrhagic hypopyon. The ulcer base has a raised, wet, soft creamy to greyish-white or yellowish­-white infiltrate without mucous or exudate [Figure - 4]. It has feathery or hyphate borders. In the early stages a dendritic pattern may be seen leading to misdiagnosis and treatment with antiviral drugs. In advanced stages with involvement of the whole cornea, the typical clinical signs of fungal ulcer become obliterated. Satellite lesions and immune ring, which are infrequent, may assist in diagnosing fungal ulcer. Endothelial plaque and posterior corneal abscess are seen more frequently than described earlier. In pigmented ulcers (chromomycosis) the brown, dark brown or black pigment covering the ulcer base is the unique clinical sign caused by pigmented fungi (dematiaceous). In some of these eyes the slough is dry, tough and leathery and one usually needs a blade to remove it. These ulcers heal very slowly.

Keratitis caused by Candida is extremely rare in India and should be differentiated from staphylococcal and Moraxella ulcers. Stromal herpes and other low virulent bacterial ulcers should be considered in the differential diagnosis. All these clinical features mentioned earlier may be masked or altered by using native medicines, steroids or/and minor surgical procedures. Although fungal ulcers spread very slowly, corneal perforation can occur within 5 to 6 days from the onset as happens in Pseudomonas ulcer.

II. C. Acanthamoeba Keratitis

This parasitic infection is now reported with increasing frequency throughout the world. Of the 44 cases diagnosed by one of us (MS), only two were contact lens wearers. The experience of others in India has been similar (unpublished data). Trauma with organic matter, exposure to muddy or brack­ish water are the major predisposing factors. Delayed diagnosis is common. Even though severe pain is considered as the characteristic clinical symptom, we have not seen any marked difference in this symp­tom between Acanthamoeba keratitis and fungal ker­atitis. A history of unsuccessful treatment by several ophthalmologists with various ophthalmic topical preparations is more often the rule than an excep­tion. Acanthamoeba keratitis is usually never suspected or diagnosed during the first visit. Ring of stromal infiltration at midperiphery of the cornea without involving the pupillary area with intact gray or hazy epithelium is noticed in a high percent of cases [Figure - 5]. Superficial punctate keratitis, small dendrites, subepithelial keratopathy, satellite lesions could be other variants [Figure - 6]. Radial keratoneuritis is very rare. Usually there is no hypopyon but it may be seen in about 20 percent of patients. The ulcer remains superficial for several weeks [Figure - 7]. Typically the disorder evolves over several weeks as a gradually worsening keratitis with periods of temporary remis­sion. A higher index of suspicion is the key to diagnosing Acanthamoeba keratitis. Keratitis due to Herpes simplex, atypical Mycobacteria and fungi should be thought of in the differential diagnosis.

II. D. Viral Keratitis

Among the causative agents of viral keratitis, Herpes simplex virus (HSV) infection is the most important one as it often leads to blindness. [1]a Among the two types of HSV, type I is more commonly associated with this condition. [1]a Type II virus ker­atitis is found in 20 percent of infants born with HSV infection . [2] In adults the recurrence rates of Herpes simplex keratitis (HSK) are about 25 percent within 1 year and 33 percent within 2 years. [3] Vari­ous nonspecific stress factors, e.g., trauma, fever, menstruation, psychological stress, climatic changes are implicated as precipitating factors [Table - 1]. The type of treatment at the beginning of the disease has no apparent effect on recurrence. Recurrent HSV infec­tion manifests in the following varied forms [Table - 2].

II. D. 1. Corneal Epithelial Lesions

II. D. 1.a. Dendritic Keratitis

The most frequent manifestation of herpetic ocular infection is the branching linear epithelial ulcer re­ferred to as dendritic keratitis [Figure - 8]. Superficial herpetic infections of the cornea, appearing as first or recurrent attacks, are almost invariably accompa­nied by partial or complete loss of corneal sensation. Although this sensory loss can usually be detected within a day or two of the onset of the attack, it can be delayed for as long as 11 days. In antibiotic- or placebo-treated patients, most cases of dendritic keratitis last 7 to 14 days, although some may persist for 25 days or longer. Unfortunately, dendritic ker­atitis may usher in some of the more prolonged forms of the disease. Atypical and resistant forms of dendritic keratitis are seen in immunocompromised and AIDS victims.[ 4],[5],[6]

II. D. 1.b. Geographic or Amoeboid Herpetic Ulcers

Occasionally a linear dendritic figure progresses to a broad area of epithelial involvement with irregu­lar angulated borders ("geographic" or "amoeboid" ulcer). These lesions have a much longer clinical course, often of many months and often follow the injudicious use of topical corticosteroids for the treatment of dendritic keratitis.

II. D. 1.c. Marginal Herpetic Keratitis

Dendritic and geographic forms near the corneal limbus tend to run a longer course and to respond less readily to antiviral chemotherapy than other herpetic lesions. The marginal lesions- often have underlying corneal infiltration as well as epithelial staining, and thus are mistaken for bacterial or other marginal ("catarrhal") infiltrates. In India, marginal herpetic lesions are more frequently reported after penetrating keratoplasty and cataract surgery . [7]

II. D. 1.d. Indolent Keratitis

Necrotic stromal keratitis may be associated with relatively large epithelial defects or it may evolve from treated geographic ulcers. These indolent forms have a particularly prolonged course and usually have profound corneal anaesthesia, do not respond to therapy with topical antiviral drugs, and are not associated with infectious HSV. Along with the loss of the epithelium, there is marked swelling of the cornea, accompanied by folds in Descemet's membrane and marked discomfort. The term "trophic" ulcer is often applied to these indolent ulcers because of the marked loss of sensation.

In patients with severe localized stromal kerati­tis, necrosis of the deep tissues leads to loss of the overlying epithelium. These round or oval, relatively deep ulcers tend to have straight borders and were referred to by Gunderson as "metaherpetic ulcers." They are usually accompanied by marked corneal anaesthesia and run a prolonged course.

All these indolent ulcers bear some resemblance to recurrent epithelial erosions of the cornea in which there is a failure of the epithelium to attach to underlying basement membrane. Some of these in­dolent ulcers are complicated by microperforation. [8]

II. D. 2. Herpetic Stromal Keratitis

II. D. 2.a. Superficial Keratitis With Epithelial Lesions

It is not uncommon to see opacification of the anterior corneal stroma directly beneath the site of dendritic lesion. This superficial opacity has the same form as the ulcer and persists long after the epithe­lial lesion has healed, particularly in cases treated with antiviral agents.

II. D. 2.b. Disciform Keratitis

This is a central round (Disciform) lesion of the cornea, with opacity and swelling of the corneal stroma. It may follow an epithelial lesion immedi­ately or may appear long after the original epithe­lial lesions have healed. Disciform keratitis due to HSV is associated with marked anaesthesia and with keratic precipitates immediately beneath the lesion on the corneal endothelium. It may also follow infections with vaccinia, herpes zoster, mumps and varicella but is most frequently associated with HSV ocular infec­tions. It may run a course of a few weeks to sev­eral months. The milder cases tend to heal without sequel, but severe cases sometimes progress to per­manent stromal scarring.

II. D. 2.c. Diffuse Stromal Keratitis

In patients with previous ocular herpetic infection, the deep layers of the corneal stroma may be diffusely affected, often without any typical epithelial herpetic lesions. This is most likely to occur after the use of corticosteroids, and the lesion may have a prolonged course.

II. D. 3. Endothelial Involvement

Herpes simplex endothelitis is a recently recog­nized clinical entity. Clinically endothelitis presents with mild stromal oedema, few medium sized ker­atic precipitates, aqueous flare and cells. [9] The con­dition is usually associated with secondary glaucoma due to trabeculitis. Herpes simplex virus antigens have been demonstrated in human endothelial cells in patient suffering from endothelitis, disciform kerati­tis and anterior uveitis.

II. D. 4. Herpetic Limbitis

This is characterized by the presence of localized inflammation of the deep corneal stroma at the limbus with an adjacent sector involved by scleritis. The corneal lesion often has a wide base at the limbus and narrows towards the centre of the cornea. These lesions may represent sclerokeratitis or may evolve from marginal epithelial herpetic lesion.

II. D. 5. Herpes Zoster Ophthalmicus (HZO)

It occurs due to activation of latent varicella zoster virus infection which persists after primary varicella infection. Corneal complications occur in 40 percent of cases of HZO. The most common findings are dendrites and punctate keratitis [10] [Figure - 9]. The den­dritiform figures are not excavated, but are made of swollen, heaped cells and have a gray plaque-like appearance; unlike the delicate pattern of HSV dendrites, the zoster dendrite is more coarse, ropy and stellate, also the terminal bulbs seen in simplex dendrites are absent. They resolve without treatment within one month.

Other findings in cases with corneal involvement in HZO are punctate keratitis, disciform keratitis and mucous plaques.


The pathology of corneal ulcer can be divided into three stages: (A) stage of infiltration (B) stage of ulceration (C) stage of healing.

III. A. Stage of Infiltration

Normally tear film and intact corneal epithelium act as effective barriers against invasion by organ­isms. However, this barrier can sometimes get dis­rupted, leading to invasion of organisms. Initially the organisms adhere to the defective epithelial surface. Exceptions to this rule are Neisseria gonorrhoeae, Co­rynebacterium diptheriae and Acanthamoebae which can invade the intact corneal epithelium directly. Invasion of the organism even in the presence of a damaged epithelium depends on the amount of inoculum and virulence of the organism. The most common corneal pathogens like Staphylococcus aureus, Staphylococcus ep­idermidis, or Psuedomonas aeruginosa are known to possess adhesiveness to a breached epithelium. The glycocalyx (the slimy envelope) assists in the adhe­sion of the organism to the epithelium. [11]sub Scraping of the cornea at this stage is often helpful in demonstrating the pathogenic organism. Once the organisms gain entry, they proliferate in the epithe­lium and superficial stroma leading to swelling and necrosis which clinically cause a white or yellowish lesion in the cornea. Infiltration of acute inflamma­tory cells (mostly polymorphs) occurs following invasion of the organism in the tissue. Necrosis of the tissue occurs due to the toxins and enzymes liberated by the organism. Even after the microorgan­isms die or are killed, their residues release endotox­ins which can perpetuate inflammation. Toxins lib­erated by most of the bacteria do not have col­lagenolytic activity except in the case of Pseudomonas which produces a protease which can destroy the collagen. Polymorphonuclear (PMN) leucocytes liberate several toxins causing tissue damage. Com­plement components (C3 & C5) help in chemotaxis of polymorphonuclear leucocytes, their adherence and activation. [12]

III. B. Stage of Ulceration

If the infection is not controlled, the inflamma­tory reaction progresses relentlessly leading to deeper stromal invasion and perpetuation of ulcer. There is sloughing of the epithelium and stroma leading to tissue loss thereby causing a crater. The margin of the crater is surrounded by oedematous corneal epithelium and the stroma is infiltrated by acute and chronic inflammatory cells. There can be an outpour­ing of acute inflammatory cells (hypopyon) into the anterior chamber. In the case of a bacterial corneal ulcer the hypopyon is usually sterile as the organ­ism does not ordinarily penetrate an intact Descemet's membrane. However, fungi can often penetrate such a barrier and can be demonstrated in the hypopyon material. Progression of such ulcerative processes can lead to perforation of the cornea.

III. C. Stage of Repair

In this stage, both humoral and cellular immu­nity result in neutralization of the organisms by phagocytosing them as well as the cellular debris. The corneal epithelium grows over the crater of the ulcer from its margin. A leash of blood vessels as well as fibroblasts and macrophages encroach the subepithe­lial space, laying down collagen tissue, resulting in scar formation. Histopathologically, fibrocytes with characteristic deep staining nuclei and cytoplasm, with dense collagen fibres and absence of normal lamel­lar clefts indicate past inflammation. Since Bowman's membrane is not capable of regeneration, it is often found replaced by fibrous tissue. The stage of heal­ing is often complicated by keratectasia (bulging forward of the Descemet's membrane and adherent leucoma (adherence of intraocular tissue, e.g., iris on the posterior surface of the cornea). Histopathologic changes in keratitis due to various organisms differ and are discussed below.

III. D. Histopathology of Corneal Ulcers III.

D. 1. Bacterial Corneal Ulcer

Common bacterial organisms which cause keratitis usually affect the central two-thirds of the cornea. The extent of damage by the organism depends on the virulence of the organism, e.g., Pseudomonas causes a rapid and nonreactive necrosis. [13] In 50 percent of cases, histopathological demonstration of the bacteria is possible from the specimen. [14] There is more likelihood of demonstration of the organism if it is removed in the early stage. Bacteria are seen as colonies and appear as clumps of basophilic material [Figure - 10]. Infiltration of acute and chronic inflammatory cells is usually seen within the stroma. In the case of crystalline keratopathy there is a characteristic absence of inflammatory cells. Gram­positive cocci are seen as clumps by special stain or transmission electron microscopic study. The organisms identified are usually Streptococcus viridans or Peptostreptococcus. [15],[16]

III. D. 2. Fungal Corneal Ulcer

The pathologic study of fungal keratitis in contrast to bacterial keratitis exhibits less marked purulent inflammatory cellular reaction. [17] The peripheral cornea is rarely involved. The filamentous fungus is seen mostly lying parallel to the corneal stromal lamellae [Figure - 11]. They may be found in areas without inflammation and can be seen in the deeper stroma skipping the superficial portion. Inflammatory cells seen are often lymphocytes and plasma cells with variable degree of polymorphonuclear leucocytes. There is coagulative necrosis of the stroma resulting in stromal abscess. Satellite microabscesses are also seen with focal necrosis of corneal stroma with clusters of acute inflammatory cells. Healing of the epithelium is seen with the active proliferation of the fungus in the deeper stroma. [18] Corneal scrapings at this stage often fail to demonstrate the organisms. Corneal biopsy is recommended in cases of suspected fungal keratitis with negative results from scrapings. The destruction of the stroma is caused not only by the fungus but also by the toxins, enzymes and antigens liberated from it. An intact Descemet's membrane often prevents the spread of the fungus to the anterior chamber. However, some fungi, especially Fusarium solani can penetrate such a barrier and can be seen in the anterior chamber. In the tissue specimens (corneal biopsy, corneal button) fungus is well demonstrated by PAS, GMS stain or Gram's stain. One can use fluorescent dyes like calcofluor white or fluorescein conjugated lectins. Selective screening of several fungal species has been demonstrated when a panel of commercially available lectins were used. [19]

III. D. 3. Acanthamoeba Keratitis

This organism has been demonstrated in both contact lens wearers and others [20],[21] The diagnosis is made from corneal scrapings in initial stages, but in some cases a corneal biopsy is needed. The organism can be seen in haematoxylin-eosin stain, but special stains like PAS, GMS, calcoflour [22] and fluorescein conjugated lectins [23] can also help in their identification . [20] Ultrastructural studies reveal that the cyst measured 10 to 25 urn in size and has a characteristic double-layered cell wall, outer wall of which is wrinkled (ectocyst) and the inner wall is round, polygonal or stellate (endocyst) [Figure - 12]. The nucleus is large with centrally located densely staining nucleolus. Trophozoites are difficult to identify by light microscopy alone, as they are of irregular outline, their sizes and shapes vary and they resemble histiocytes and keratocytes. The surrounding corneal tissue shows variable degree of inflammatory cellular infiltration, comprising of neutrophils and lymphocytes. The epithelium is often absent or detached. Immunohistochemical studies done in two cases of Acanthamoeba keratitis showed majority of inflammatory cells to be neutrophils and HLA-DR positive macrophages [24]


III. D. 4. Viral Keratitis

In epithelial disease caused by Herpes simplex virus, active viral replication occurs in the ulcer mar­gin. [25] In the early stages, polymorphonuclear leu­cocytes form the main inflammatory reaction later replaced by lymphocytes, macrophages and multinu­cleated giant cells with intranuclear acidophilic inclu­sions. The titre of virus is highest before the devel­opment of dendritic lesion and progressively falls as the lesion progresses . [25] Stromal involvement occurs in recurrent attacks and is often referred to as disciform keratitis. This is an immune-mediated disease as evi­denced by the presence of empty viral capsids and incomplete virions in stromal cells, activity of lym­phokines and a favourable outcome of steroid ther­apy. [26],[27] These immunopathologic lesions have also been demonstrated in experimental animals and have been shown to be due to CD4+ T lymphocytes. [28] Re­current HSV keratitis occurs when latent virus in trigeminal ganglion is reactivated, replicates and travels along the trigeminal nerve to the eye.

Latency of HSV in cornea is proposed. Demon­stration of HSV-DNA in human cornea without any apparent active disease has been made using polym­erase chain reaction. [29]Recovery of HSV from human cornea by co-cultivation techniques has also been re­ported. [30] Latency of HSV in cornea of rabbit [31] and mice [32] has been experimentally demonstrated. Further studies are needed for final acceptance of HSV in cornea.

Adenovirus is the most common cause of acute viral keratitis. Several serotypes (frequently 8, 19 and 37 and infrequently 3, 4, 7, 10, 11, 21) cause epidemic keratoconjunctivitis. Viral replication occurs in the corneal epithelial cells and later with the development of delayed hypersensitivity, subepithe­lial infiltration appear which persists for an extended period of time.


Owing to the considerable overlap in the clinical appearances of corneal ulcers due to various micro organisms, a standard basic laboratory methodology should encompass techniques that allow for the recognition of as large a number of offending organ­isms as possible. There are now enough studies available to justify a mandatory decision to perform proper laboratory studies in every patient seen with corneal ulcer or infiltrate [33],[34] [Figure - 13] depicts a pro­cedural flowchart to isolate the causative organism.

IV. A.

Collection and Processing of Clinical Samples

IV. A.1. Conjunctival and Lid Swabs

It has generally been recommended to collect conjunctival and lid cultures from the ipsilateral and contralateral eyes before the corneal material is ob­tained. [35] The utility of these cultures is, however, controversial. In a recent study, designed to determine if the organism isolated from conjunctiva reflects the causative organism of infectious keratitis, it was found that a correlation existed only in 3 percent of cases. [36] Based on this, it is our feeling that microbiologic evaluation of scrapings from the ulcer is mandatory.

IV. A.2. Corneal Scrapings

Kimura's spatula is traditionally used to collect scrapings from a corneal ulcer though Bard-Parker blade no. 15 is equally popular. Cotton swabs are not recommended for collection of corneal material. [35] Multiple scraping of the ulcer bed and margins is done under topical anaesthesia (0.5% proparcaine hydrochloride or 4% lignocaine hydrochloride) with the aid of a slit-lamp or operating microscope after removal of debris or discharge in the vicinity. Several scrapings are collected and used in a sequence to prepare smears and inoculate culture media [Table - 3]. The blade or spatula may be reused when a sterile medium has been streaked. However, a blade must be changed (spatula should be flamed) when a smear has been made on a slide which may not be sterile.

Solid agar media are inoculated on the surface making multiple "C" shaped marks without cutting the agar. In the liquid media the spatula or blade is swirled to allow the sample to be transferred. In the case of thioglycolate broth deep inoculation of the medium is ensured by transferring the sample to a swab tip and dropping the swab in the tube allow­ing it to settle at the bottom. The incubation period and conditions of growth for various culture media are presented in [Table - 4].

Techniques of Gram stain, Kinyoun stain (Cold carbol Fuchsin) or Giemsa stain are employed to study the corneal material which is spread as a thin layer on several clean glass slides within an area defined with a wax pencil on the reverse. In the preparation of wet mounts such as potassium hydrox­ide, lactophenol cotton blue or calcoflour white, the scrapings can be placed on the slide in a demarcated area and covered with a drop of the solution followed by a coverslip. Special stains and media may be in­cluded whenever usual procedures have yielded negative results.

IV. A.3. Corneal Biopsy

If infectious keratitis is suspected clinically and twice repeated microscopic evaluation of smears and culture results are negative and no clinical improvement is noted on the initial broad spectrum antibiotic therapy, we recommend corneal biopsy. A partial-thickness trephination employing a trephine of sufficient size, to guarantee adequate material for the laboratory, is required. Harvesting the material for diagnosis should include an adequate area of cornea affected clinically by the inflammatory or ulcerative process. Corneal scrapings for microbiological evaluation from the site of biopsy may help in isolating the organism.

The biopsied tissue is preferably removed enbloc. It is bisected, half being sent to microbiology laboratory for homogenization and culture, and the remaining half placed in 10% buffered formalin to be transported to a pathology laboratory.

IV. A.4. Anterior Chamber Paracentesis

This procedure is rarely indicated in the diagnos­tic evaluation of a patient with a corneal ulcer. However, this procedure may be indicated in the instance where keratomycosis is strongly suspected clinically, yet corneal scrapings and biopsy have been negative, the damage to the cornea is progressive and a hypopyon is present or increasing.

IV. B. Interpretation of Smears and Cultures IV. B.1. Smears

These methods yield a rapid result and form the basis for a provisional diagnosis and therefore determine the initial choice of an antimicrobial agent to be instituted for therapy.

IV. B.1.a. Potassium Hydroxide (KOH) Wet Preparation

A 10 to 20% solution of KOH has been used to visualize fungal elements in corneal scrapes. [37] Though later reports [38]sub have discounted the value of KOH mount it has been found to be an useful diagnostic aid for both fungi and Acanthamoeba. [21]sub Owing to the chitin in their cell wall, fungal filaments [Figure - 14] and cysts of Acanthamoeba are clearly delineated in a homogenous background of corneal tissue digested by KOH. Addition of 10% glycerol to the KOH acts as a mordant and serves to preserve the smear for as long as six months.

IV. B.1.b. Gram Stain

The Gram stain is utilized to identify bacteria, fungi as well as Acanthamoeba. It has been reported to yield an accuracy of 60 to 75 percent in identify­ing the responsible organisms. [39] However, one should be aware that indigenous bacterial flora in the tear film can occasionally be detected in the corneal smear.

Fungal filaments exhibit variability in their stain­ing pattern in Gram stain with the cell wall and septae remaining unstained and only the protoplasm being stained or an empty protoplasm with faint outline of fungus. Yeasts, on the other hand, stain typically blue.

The Giemsa technique renders all bacteria dark blue. Acanthamoeba cyst wall stains dark blue, and the cytoplasm stains blue. The value of the Giemsa stain for distinguishing infectious from non-infectious keratitis by type of inflammatory cells has not been established.

IV. B.1.c. Calcofluor White (CFW) Stain

CFW is a fluorescent brightener with great affin­ity for certain polysaccharides such as cellulose and chitin, thus providing the basis for demonstration of fungal cell walls as well as cysts of Acanthamoeba spe­ cies. [40]sub The preparation is viewed under fluorescence microscope using exciter and barrier filters. The cysts of Acanthamoeba and fungal filaments appear bright apple green in a corneal scraping stained with CFW. Acanthamoeba trophozoites and bacteria such as Nocar­dia and Actinomyces do not stain with CFW . [40]

IV. B.1.d. Other Stains

A modification of Gomori methenamine silver stain may be helpful for the identification of fun­gal elements and Acanthamoeba cysts in corneal scrap­ings. Fungi and Acanthamoeba cysts stain black on a light green background.

The periodic acid-schiff (PAS) stain may also be used to visualize fungal elements as well as Acan­thamoeba especially in tissue sections.

Bacteria, fungi as well as Acanthamoeba have been demonstrated in smears and tissues using lectins conjugated with fluorescein or peroxidase. [41]

Nonspecific fluorescent stains like blankophor and uvitex 2B have been introduced for the rapid detec­tion of fungal elements in corneal scrapings.

Lactophenol cotton blue stain, which is generally used for the microscopic examination of fungal cultures, has been effectively used for the demon­stration of fungal elements and Acanthamoeba cysts in corneal scrapings . [42],[43] Ziehl-Neelsen stain or its modification (Kinyoun's stain) are indicated for the detection of Mycobacteria and Nocardia species, respec­tively.

IV. B.2. Cultures

A daily monitoring of all culture media is essen­tial, coupled with standard procedures for descrip­tion of colony morphology, selection of colonies for processing and antibiotic susceptibility testing. The use of solid media has definite advantages. Growth away from a streak is assumed to be a contaminant. A rough quantitation is also possible on a solid medium.

The amount of growth depends on many factors. Ophthalmologists can vary in their enthusiasm when collecting material to inoculate plates. Occasionally, many bacteria may be seen in a smear of the scrap­ing, but very little is grown on culture. This may be due to previous antimicrobial treatment or most of the infected corneal tissue being used for preparing the smears.

An isolate is more likely to be considered significant if:

1. it is consistent with the clinical signs

2. smear results are consistent with culture

3. the same organism is grown on more than one media

4. the same organism is grown from repeated scrapings

Identification of bacteria may be accomplished within 48 hours along with its antibiotic susceptibility pattern. Standardized disk diffusion or dilution techniques should be utilized for antibiotic susceptibility testing of bacteria. One should be aware, however, that results of disk diffusion susceptibility tests relates to levels of drug achievable in serum and do not relate directly to concentration of drug produced in the preocular tear film and ocular tissues.

Bacterial contamination of fungus cultivating media (e.g., Sabourand's dextrose agar, potato dextrose agar) can be avoided by incorporating chloramphenicol in a concentration of 50 ug/ml. Cycloheximide, an inhibitor of saprophytic fungal growth, is a frequent component of some fungal media. It should not be added to SDA used in ocular microbiology laboratory since most cases are due to so-called saprophytes. The majority of fungi causing keratitis can be detected on SDA within 72 hours. Aspergillus and Fusarium species grow on blood agar, SDA and brain-heart infusion broth within 48 hours. However, appreciably characterisitic colonies develop after 1 to 2 weeks. Culture media should be observed for at least 2 weeks before they are considered negative. [44] It is not unusual to come across strains of fungus that do not show spores and thus are unidentifiable. Such cultures should be sent to reference centres for identification. The value of antifungal susceptibility testing for treatment of mycotic keratitis is not yet established.

Non-nutrient agar (NNA) is the standard medium used with an overlay of Escherichia coli for the growth of Acanthamoeba [45]The specimen is simply touched to the surface of the plate without streaking or breaking the surface. Two plates may be inoculated for incubation at 25 and 37 o C since some species do not grow at the higher temperature [46] and the plates are examined for trophozoites and cysts directly under the microscope (100 X). Trophozoites may be seen in 24 to 48 hours. They move and cover the entire plate surface on further incubation and turn into cysts. The plates should be observed for at least 7 days.

Special media, selective and non-selective, may be indicated in certain clinical situations. Lowenstein-Jensen medium is used when mycobacterial infection is suspected. Nocardia organisms can grow, though slowly, on blood agar as well as other bacterial media.

IV. C. Diagnosis of Contact Lens-associated Keratitis

A variety of organisms have been reported from keratitis associated with contact lens wear, most notable of them being Pseudomonas aeruginosa and Acanthamoeba species. Contact lenses, lens cases and lens solutions should be collected for culture apart from the corneal scrapings. Contact lenses, if pres­ent on the eye, should be removed aseptically and placed in sterile saline or buffered saline and sent to the laboratory, where they can be cultured by agar-sandwich method . [47] Fluid from the lens cases can be cultured on standard media such as blood agar, MacConkey agar, NNA and SDA. Microscopy of the lens deposit, centrifuged deposit of the lens care solutions may help detect the offending organism.

IV. D. Newer Methods in the Diagnosis of Infectious Keratitis

The need for rapid diagnosis has led to modifi­cation of various conventional techniques and intro­duction of new techniques such as immunohistochem­istry, fluorescent microscopy, enzyme immunoassays, radioimmunossay and molecular biology. Most ocular infections can now be diagnosed by these modern techniques within 1 to 6 hours. [48]

Most immunoassays are based on the availability of specific antisera against infectious agents. Highly specific antibodies have been made available by hybridoma technology. Such monoclonal antibodies have been used in the diagnosis of viral, chlamydial and bacterial infections.

Recent introduction of nucleic acid hybridisation technique has revolutionized the field of diagnostic microbiology. This technique utilizes the methods of molecular biology and is now being marketed for various diseases as diagnostic test kits. They are highly sensitive and specific. Some of these test kits use non-radioactive DNA probes and are easy to perform. This method not only detects the species of microorganisms but also the strain of the organism, thus providing information on antibiotic susceptibility of the organism. Presently, probes are available for limited organisms such as viruses, Chlamydiae and Mycobacteria. The availability of probes is increasing with time and this technique is going to have a tremendous impact on the rapid diagnosis of infectious keratitis and many other ocular diseases.

IV. E. Laboratory Diagnosis of Viral Keratitis

Basic approaches to laboratory diagnosis of viral keratitis are proper collection and transport of clini­cal specimens (corneal scrapings), rapid methods for detection of viral antigens or viral products in the clinical material with isolation and identification of the virus. Direct demonstration of viral antigens or viral products are possible by Giemsa stain cytology, electron microscopy, immunodiagnostic methods such as enzyme immune assay (EIA) or immunofluores­cence (IF) and nucleic acid hybridisation. Scraped material in adequate amount is placed in one ml of Hank's balanced salt solution (HBSS) containing 3% foetal calf serum (FCS) and material collected later is used for preparing 4 to 5 smears on clean micro­scopic slides. If conjunctivitis co-exists, as in adeno­virus infections, smears of conjunctival scrapings and conjunctival swab in HBSS with 3% FCS are col­lected. Smears are fixed in cold acetone or methyl alcohol. The specimens in HBSS are transported in an ice chest to the laboratory.

IV. E.1. Methods for Detection of HSV and Adenoviruses

Rapid presumptive diagnosis of the viral aetiology is possible by Giemsa stain cytology on the smears. Cytopathologic changes such as syncytial giant cells with Cowdry type A intranuclear acidophilic inclusions in HSV and VZV infections and intranuclear inclusions in adenovirus infections are demonstrable. Giemsa stain cytology is an useful screening procedure to arrive at an aetiological diagnosis taking into account the type of inflammatory cells seen in the smear . [48]

With the availability of specific monoclonal and polyclonal antibodies against viruses and their antigens, immunodiagnostic methods allow detection of virus in the direct smears. Enzyme Immune Assay (EIA) and immunofluorescence are commonly used for examination of smears and they are rapid, specific and sensitive. Monoclonal antibodies to differentiate HSV type 1 and type 2 have been developed. [49]

Exudates collected in buffers and smears are used for EIA. Several EIA formats have been described for detection of adenoviruses which can be applied for detection of this virus in specimens from cornea. Immunofluorescence (IF) has gained wide acceptance as a highly sensitive, specific and rapid diagnostic procedure for detection of viral antigen in direct smears from clinical material. For detection of HSV in corneal ulcer, IF is found to be highly reliable but results have to be considered with caution when patient is on antiviral therapy. [50] IF on direct smears has been found to be more sensitive than culture for detection of HSV in corneal ulcers particularly in those which are on treatment with acyclovir. This is likely to be due to the presence of HSV antigens rather than replicating virus in the lesions.

Electron microscopy is not a common diagnostic procedure for rapid detection of viruses causing keratitis. Polymerase chain reaction (PCR) for detection of HSV has recently been used by several workers. [51]sub Kowalski et al found that PCR was not significantly more sensitive than slit-lamp examination. Hayashi et a1 [52] found that PCR amplification technique provided a quick, sensitive method for the detection of the specific herpes virus in keratitis of unknown aetiology.

The most sensitive and specific method for diag­nosis of HSV and adenovirus infection is the conven­tional method of isolation and identification of viruses in cell cultures, which usually requires upto 2 to 4 weeks. This is more sensitive than direct methods described above for their detection because the virus content is amplified by growth in susceptible host system such as cell cultures [Figure - 15]. Both primary and established cell lines are extensively used for isolation and identification of HSV and adenoviruses.

Application of immune assays such as EIA, IF and immune electron microscopy (IEM) has made a significant advance in rapid identification of isolated viruses though neutralisation tests may be used for final typing of the isolate. PCR can also be applied to the virus isolate in cell cultures for rapid identi­fication. An isolate can be specifically identified in 48 to 96 hours by shell vial culture method which has been widely applied for detection of HSV [53] and adenoviruses. [54]

IV. E.2. Serological Methods of Diagnosis

The traditional serological methods for diagnosis HSV infection are generally of little value, since most viral infections of cornea are secondary to a primary infection elsewhere in the body. For diagnosis of adenovirus infection, neutralisation test, complement fixation test and ELISA test are useful serological tests.

IV. E.3. Other Viruses

Mumps virus keratitis is almost always one of the ocular complications of the systemic disease. Virus antigen can be detected in conjunctival epithelial cells by immunofluorescence. [54] Chick embryo and chick embryo fibroblast cell line are used for primary isolation of the virus. Being a generalised disease, serological responses to mumps and measles viruses are excellent for demonstration of four-fold rise in virus specific antibody titre in paired sera of the patients.


V. A. Bacterial Keratitis

Once a provisional diagnosis of bacterial keratitis is made, one should institute therapy with appropriate antibiotics. The selection of antibiotics can be in the form of specific agents [55] or a combination therapy. [56],[57] This latter strategy aims at using antibiotics that can be effective against both gram-positive and gram­negative bacteria. One guideline that may be helpful is the epidemiologic information on the microbiologic basis for infectious keratitis in a given geographic region.

Amongst the currently available antibiotics the most commonly employed is a combination of a cephalosporin with an aminoglycoside. The critical factor to enhance the efficacy of these drugs are the concentration of the drug and frequency of application. These drugs have to be made as fortified preparations and applied as frequently as every 30 minutes to 1 hour. The details of the actual drug regimen that we recommend are given in [Table - 5]. Alternatively, the newer fluoroquinolone drugs are often employed; the most popular being ciprofloxacillin. The major advantages claimed for its usage include ready availability as a commercial preparation, efficacy against broad spectrum of bacteria and relatively low toxicity and resistance.

V.A.1. Drug Delivery

At the concentration and frequency recommended, the antibiotics used topically reach the cornea in adequate concentration, and so other routes of admini­stration are rarely required. The usage of painful subconjuctival injections is almost eliminated except in situations where administration of drugs cannot be assured round-the-clock.

Systemic antibiotics are indicated only if there is a perforation and/or if there is any indication of endophthalmitis.

A grading of the severity of the keratitis is an useful adjunct in estimating the urgency of treatment and risk of perforation [Table - 6]. In a mild infection standard strength antibiotics used topically are proba­bly as effective as the fortified versions.

V. A.2. Assessment of Progress

A careful slit-lamp examination at each visit [Table - 7] is an essential feature. Early signs suggest­ing an improvement are:

1. increased comfort

2. decreased discharge

3. reduced "fluffiness" of the infiltrate

4. blunting of the edges of the ulcer

5. reduced oedema in adjacent stroma

6. reduced anterior chamber inflammation

Most often a lack of progression in the first 24 to 48 hours is an indication of effective treatment. In some cases, especially Pseudomonas infections, early progression can occur inspite of appropriate antibi­otic therapy.

The initial therapy should be reviewed at the end of 24 to 48 hours based on the progression of the keratitis and culture results. If there is an improve­ment, the initial therapy should be continued regard­less of the culture reports. This is so because it often happens that the organisms may not be sensitive to an agent in vitro but are sensitive at the high stromal levels achieved with topical administration of forti­fied antibiotics. If a combination of drugs has been commenced and the organism is sensitive to only one of them, the second drug may be discontinued or replaced with a more appropriate one. The whole plan can be designed as shown in [Figure - 16].

Infections with gram-negative bacteria, especially Pseudomonas can lead to formation of ring-shaped infiltrates . [58] ]These appear to be an immunologic reaction to bacterial endotoxin, and respond to corticosteriods. They are usually seen about 10 to 14 days after the onset of the infection and it is critical to differentiate them from recurrence or worsening of the infection. [59]

V. A.3. Altering the Frequency of Drug Administration

It is a good policy to commence the antibiotic therapy in the dose of 1 drop every minute for 5 minutes and then every half hourly. This helps in achieving high concentrations of the antibiotic drops in the corneal stroma. The tapering of the antibiotics is based on the response in each individual case. Duration and severity of infection, depth of invasion and causative bacteria are some of the determining factors. Epithelialization alone is not a good criterion to suggest resolution of infection as any of the antibiotics may deter epithelial healing due to toxic or allergic reactions.

V. B. Fungal Keratitis

The antimicrobial agents available today to com­bat fungal keratitis are not as well developed as those available against bacterial infections. All the available agents only inhibit growth of the fungus, the host defence mechanisms must eradicate the infection. Most of these drugs are irritant and toxic to the ocular surface and have a limited penetration of the cornea. The main drugs in use currently are: (1) amphotericin B, (2) natamycin, (3) imidazole compounds (ketoconazole, miconazole, clotrimazole), (4) flucytosine.

In the warmer countries like India it is the fil­amentous fungi which are a major source of infec­tion. The mainstay of therapy have been the polyene group (amphotericin B, natamycin and nystatin).

Natamycin 5% suspension is the drug of choice for filamentous fungi. [60] It alters the permeability of the fungal cell elements, is unstable, but less toxic than amphotericin B. [61] A 5% solution of natamycin when applied topically usually "adheres" to the ulcer bed and forms a rope like strand in the inferior fornix which may serve as a reservoir. Therapy with na­tamycin should be initiated as 1 drop every half hourly for the first 3 to 4 days and then decreased to 6 to 8 times daily . [62] Like all other antifungal drugs it penetrates the deepithelialized cornea well. Unlike amphotericin B which cannot penetrate the intact epithelium, natamycin can penetrate intact epithelium,to a small extent . [63]

Imidazole compounds available to us are ketocon­azole and clotrimazole. Ketoconazole as a 1-2% solution is well tolerated as is systemic administra­tion. An oral dosage of 200 to 600 mg per day may be given. It has been shown to be an effective agent in limited trials. It is active against most yeasts and many filamentous fungi. Systemic usage requires careful monitoring of liver status.

Clotrimazole is most significant in treatment of Aspergillus group of fungi. Topical 1% concentration in arachis oil or the dermatologic cream are well tol­erated.

Antifungal therapy should not be initiated with­out laboratory evidence of fungal keratitis since clini­cal history and appearance alone are not diagnostic, therapy is prolonged, response is slow and agents are often toxic.

The selection of antifungal agents is based mainly on clinical response. There are no standardized sensitivity determinants for antifungal drugs. If the patient is doing well on a drug, treatment should not be changed unless toxicity to the drugs is seen. Improvement is often not visible till weeks after initiating treatment. One should look for reduced size of the central corneal infiltrate, disappearance of the satellite lesions and rounding off of the feathery margins. The conjunctiva usually reacts to the anti­fungal agents and shows chemosis and injection. The presence or absence of these features should not be used as an indication of the success of therapy. Per­sistent epithelial staining may be noticed. Similar to the conjunctival reaction, this too, often indicates tox­icity of the medication.

The duration of treatment should be long enough to allow the body defence mechanisms to eradicate the organisms. Long-term therapy of at least 6 weeks is usual. Negative cultures are not a guide to eradi­cation of the fungus. A close watch after discontinu­ing treatment is essential to look for any signs of re­currence. An important point usually not highlighted but which needs to be stressed upon is the need to scrape the corneal epithelium to within 2 to 3 mm of the limbus everyday, especially in case of stromal fungal infiltrates. This not only acts as a debulking procedure by removing the necrotic tissue but more importantly it enhances the penetration of the anti­fungal drugs . [64]

V. C. Acanthamoeba Keratitis

The current approach to treatment of Acanthamoeba keratitis lacks consistent efficacy. Some cases may progress despite medical therapy. Recurrence of infection in grafts after penetrating keratoplasty has been demonstrated .[65]

A host of drugs have been cited as being useful in treatment of Acanthamoeba keratitis. The most ex­tensive experience has been with propamidine isethionate and some medical -cures have been re­ported in combination with neomycin - polymyxin B - gramicidin (neosporin) drops. Propamidine is freely available in the United Kingdom. The recom­mended treatment regime is outlined in [Table - 8]. The duration of treatment should be up to one year in most cases. In the case of lack of response or stromal involvement 1% clotrimazole may be added .[66]

Recent additions to the armamentarium are benzethonium chloride and polyhexamethylene biguanide. [67] Other drugs which may be useful are: ketoconazole, miconazole, paromomycin, natamycin, amphotericin B, polymyxin B and metronidazole.

V. D. Viral Diseases

We shall restrict our discussion to the treatment of Herpes simplex (HSV) and Herpes zoster infections.

V. D.1. Herpes Simplex Virus (HSV) Keratitis

Of the various agents used to treat HSV kerati­tis (idoxuridine, trifluorothymidine, adenine arabi­noside, acyclovir) only idoxuridine and acyclovir are available locally. Idoxuridine was the first agent to be made available as an antiviral agent. It is used as a 0.1% solution and 0.5% ointment and is useful primarily in corneal epithelial disease due to poor topical penetration. The use of this drug as a first line drug has declined considerably due to its high incidence of toxicity [Table - 9], need for higher fre­quency of instillation and the availability of safer drugs like acyclovir. Acyclovir (acycloguanosine) has specific activity against HSV types I and II. After topical application it penetrates the stroma and reaches the aqueous. It is least toxic to the ocular surface among the currently available drugs. One of the drawbacks with this drug is its greater potential for developing resistant strains. Oral acyclovir though effective even in epithelial keratitis has a more use­ful role in necrotizing stromal disease, endothelitis and keratouveitis. [68] There is some evidence to suggest that it reduces the risk of recurrence .[68]

V. D.1.a. Specific Treatment

V. D.1.a.i. Recurrent Epithelial Keratitis Without Stromal Disease

Debridement may be equal to or superior to antiviral treatment for epithelial herpes. [69] A combi-nation of debridement and antiviral treatment is more effective than antiviral treatment alone.

V. D.1.a.ii. Limbitis

This is usually recalcitrant to treatment. Artificial tears are probably as effective as any other therapy. Corticosteroids should be used only if visual axis is involved.

V. D.1.a.iii. Disciform Keratitis

Some prefer to adopt conservative management with topical cycloplegics. The usage of corticosteroids is deferred since these may prolong the disease course without having any effect on the final outcome. The other school of thought believes that use of steroids offer both short- and long-term visual benefits. We recommend the use of steroids when vision is sig­nificantly reduced or pain is a significant concern. It must be remembered however, that once steroids are used, control of recurrence may not be possible without further recourse to steroids, thus very dilute doses may be sufficient. Treatment may be initiated at two to four times daily and tapered to as low a 1:200 dilution daily or 1:125 dilution to be used once a week. [70] Concurrent antiviral shedding or reinfection may occur.

V. D.1.a.iv. Persistent Epithelial Defects With or Without Stromal Ulceration

One should first determine the exact cause of persistent epithelial defect. These may be due to:

(1) Recurrence, viral resistance or poor compliance with therapy

(2) Antiviral agent toxicity

(3) Persistent anterior stromal inflammation

(4) Impaired epithelial healing due to recurrent attacks (5) Associated bacterial/fungal infections

The dose of antiviral drugs should be reduced if no active disease exists. In the absence of bacterial infection one should discontinue the antibiotics. An attempt should be made to look for any associated adnexal problems like lagophthalmos and trichiasis. Use of topical corticosteroids under careful supervi­sion may help reduce stromal inflammation. One should be cognizant of the potential for stromal degradation and perforation. Lubricating agents, patching or a bandage contact lens facilitates reep­ithelialization. A temporary tarsorraphy or conjunc­tival flap may be needed.

Necrotising Stromal Keratitis (Stromal Ulcer With Infiltration): One should always look for and rule out secondary infection. After several days of antiviral therapy, topical steroids can be cautiously added initially in low doses. Oral prednisolone (0.5 - 1 mg/ kg) is preferable to topical steroids till the epithelium has healed.

V. D.1.a.v. Endothelitis

Active infection is a possibility in these cases. Topical acyclovir is able to achieve an adequate drug level in the aqueous. Topical steroids can be used in addition, if the epithelium is intact. Both, acyclovir and steroids should be tapered very slowly.

No treatment can prevent latency or eliminate latent infection. However, early treatment of recur­rence seem to have beneficial effect on the severity and duration of attack.

V. D.2. Herpes Zoster Ophthalmicus

The treatment for the various forms of this dis­ease are summarised in [Table - 10]. The management of pain in herpes zoster can be a serious problem. The administration of levodopa (100 mg tds) [71] and cimetidine (300 to 400 mg daily x 14 days) [72]sub have been shown to be effective in relieving pain. Other agents have not been very successful. Intractable pain may need stellate ganglion block. [73]


The decision to surgically intervene in a case of active infectious keratitis should be made after proper appraisal of the clinical progress. The role of surgery may be diverse and as follows:

1. Aid in medical management

(a) by increasing drug penetration

(b) by bringing in blood vessels in the form of conjunctival flaps

2. Stabilise the corneal epithelial surface by conjunc­tival flaps

3. Excise the infected corneal tissue and eliminate or reduce the microbial load

4. Tectonically support the globe where the integrity is threatened as in cases of thinning or perfora­tion of the cornea.

The various modalities of treatment available in such cases are:

A. Removal of epithelium and anterior lamellar keratectomy

B. Conjunctival flaps

C. Tissue adhesives

D. Penetrating keratoplasty

VI. A. Epithelial Removal and Anterior Lamellar Keratectomy

This modality of treatment is useful particularly in cases of fungal keratitis. Regular debridement of the base of the ulcer helps in elimination of organ­isms and necrotic material. This procedure facilitates penetration of antifungal drugs. [74] This can be done under topical anaesthesia leaving a margin of 1 to 2 mm at the limbus with a no.15 Bard-Parker blade.

Anterior lamellar keratectomy helps in removal of the thick mat of fungal filaments on the cornea and facilitates increased drug penetration in cases of de­matiaceous fungal filaments. Anterior stromal corneal infiltrates can also be ablated with excimer laser for therapeutic purposes . [75]

VI. B. Conjunctival Flaps

Conjunctival flaps help in achieving a stable epithelial surface in cases of persistent or recurrent epithelial defects and progressive ulceration especially in viral keratitis.

These are particularly helpful in chronic periph­eral disease where the flap does not encroach onto the visual axis . [76] In peripheral fungal corneal ulcers, the blood vessels brought in by conjunctival flaps help in healing of the ulcer. A superficial lamellar kerat­ectomy with removal of necrotic stroma is to be done with anchoring of a thin conjunctival flap over the ulcerated site [Figure - 17].

VI. C. Tissue Adhesives

Tissue adhesive (cyanoacrylates) helps in support­ing corneal thinning and sealing corneal perforation upto 2mm. [77],[78] Cyanoacrylate adhesive is bacteriostatic for gram-positive bacteria . [79] sub Necrotic stroma or epi­thelium and other debris must be removed from the base of the ulcer before the adhesive is applied. Usually a bandage contact lens must be fitted after the application. The adhesive is left in place until it loosens spontaneously, or the bed becomes vascular­ized [Figure - 18], [Figure - 19] or keratoplasty is performed. This modality of treatment has a valuable role in the management of infectious keratitis.

VI. D. Penetrating Keratoplasty

The indications for penetrating keratoplasty are (a) perforation, (b) descemetocele or impending perfora­tion [Figure - 20][Figure - 21], (c) continued progression despite maximal medical treatment, (d) post-infectious cor­neal scar. The results of keratoplasty in acutely infected or inflamed eyes are relatively poor, the risk of rejection and glaucoma greater especially in larger grafts. [77]

In all these cases at least 0.5 mm of clear tissue all around the infected area is to be excised to decrease the incidence of recurrence. Postoperative antimicrobial treatment is to be continued. In fungal keratitis, postoperative topical steroids are to be used with caution. Surgery when performed with 8 mm or smaller diameter donor grafts had better results than larger grafts. [80] Hence, penetrating keratoplasty is to be considered early when fungal ulcers do not respond to antifungal medication. The results of penetrating keratoplasty for Acanthamoeba keratitis are poor and surgery is to be considered only in patients with gross corneal thinning or perforation.


While infectious keratitis continues to have the potential for high rate of ocular morbidity, advances in diagnosis and treatment have changed the outlook for the management of this problem. Rapid methods of isolation of causative organisms, newer drugs with greater potency and specificity of action delivered to ensure appropriate dosage constantly make the prognosis better for these cases. One could be optimistic that the role of surgery will be relegated to only visual rehabilitation of central corneal scars[81].

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  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6], [Figure - 7], [Figure - 8], [Figure - 9], [Figure - 10], [Figure - 11], [Figure - 12], [Figure - 13], [Figure - 14], [Figure - 15], [Figure - 16], [Figure - 17], [Figure - 18], [Figure - 19], [Figure - 20], [Figure - 21]

  [Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5], [Table - 6], [Table - 7], [Table - 8], [Table - 9], [Table - 10]

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