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Review Article

Corneal Ulcer: Diagnosis and Management Prashant Garg MS In this article we focus on the diagnosis Gullapalli N Rao MD and management of suppurative corneal Sight Savers’ Corneal Training Centre ulcer. L V Prasad Institute Diagnosis L V Prasad Marg Fig.1. Ring infiltrate in Acanthamoeba Banjara Hills A detailed history and thorough clinical Hyderabad 500 034, India examination using the slit-lamp biomicro- Photo: P Garg & G N Rao scope are important steps in the diagnosis Introduction of . Although clinical signs , is rarely experi- may be insufficient to confirm infection, a enced in non-contact related Acanth- orneal scar is a significant cause of break in the continuity of the epithelium amoeba keratitis. The clinical picture is Cvisual impairment and blindness in associated with underlying stromal infil- often confused if the lesions are peripheral, the developing world. Corneal infections trate should be considered infectious or advanced involving the entire are responsible for a large proportion of unless proved otherwise. Similarly, there (Fig. 4). Laboratory investigations are this scarring. A review of the data on indi- are no distinctive or exclusive signs to therefore required if the causative organ- cations for in the identify the responsible organisms, but ism is to be identified. developing world revealed that corneal clinical experience and careful slit-lamp scar was the most common indication examination can point toward a probable Laboratory Investigations (28.1%), of which keratitis accounted for aetiological diagnosis in some cases. 50.5%. Besides this, about 12.2% of all Gram-positive cocci typically cause The laboratory procedures used in the diag- grafts were done for active infectious ker- localised round or oval ulceration with nosis of infectious keratitis are based on: atitis.1 Thus suppurative keratitis and its greyish white stromal infiltrates having (a) direct visualisation of organisms in the complications constitute important causes distinct borders and minimal surrounding material. of ocular morbidity, particularly in the stromal haze. Keratitis due to gram-nega- (b) inoculation of material under appropri- developing world. tive bacteria typically follows a rapid ate conditions to allow multiplication Almost any organism can invade the inflammatory destructive course charac- of organisms. corneal stroma if the normal corneal terised by dense stromal suppuration and defence mechanisms, i.e., lids, tear film hazy surrounding cornea with a ground Whenever a patient with infectious ker- and corneal epithelium are compromised. glass appearance. is usual- atitis presents, after detailed clinical exam- While viral infections are the leading cause ly characterised by a dry raised slough, ination, corneal scrapings are taken under of corneal ulcer in the developed nations stromal infiltrate with feathery edges, topical anaesthesia using a sterile No. 15 (with Acanthamoeba infection in contact satellite lesions, and a thick endothelial Bard Parker blade. Scrapings are taken lens wearers), bacteria, fungi and Acantha- exudate. Acanthamoeba keratitis is charac- from the edges and base of the ulcer (see moebae are important aetiological agents terised by epithelial irregularities with Appendix). The material obtained is exam- in the developing world. The spectrum of single or multiple stromal infiltrates in a ined microscopically using Gram’s (see corneal pathogens shows a wide geograph- classical ring-shaped configuration. Severe Appendix) and Giemsa staining methods ical variation. At L V Prasad Eye Institute, pain and radial keratoneuritis (i.e., inflam- and potassium hydroxide 10% or calcoflu- Hyderabad, 71.9% of all cases of ulcerative mation of the corneal nerves, seen as a or white preparation. Calcofluor white is a keratitis were culture positive. Of the cul- whitish outline of the corneal nerves) are fluorescent dye and requires a fluorescent ture positive cases 63.9% were bacterial, also characteristics of Acanthamoeba microscope. Lactophenol cotton blue stain 33% were fungal, 2.1% were parasitic, and infection. may also be used which does not require 6.2% were due to mixed infection. Various Since the clinical appearance of suppu- a fluorescent microscope (see Appendix). organisms isolated from cases of infectious rative keratitis depends on many variables, The material is also inoculated on various keratitis are shown in Table 1. it is often difficult to arrive at an aetiologi- solid and liquid media that facilitate the cal diagnosis based entirely on slit-lamp examination. For example, apart from Acanthamoeba keratitis (Fig.1), the ring- shaped infiltrate can be seen in fungal ker- atitis (Fig.2), HSV () kerati- tis, and even in Pseudomonas keratitis. Similarly, Nocardia keratitis presents clas- sically with multiple small white infiltrates arranged in a wreath pattern (Fig. 3), and it can have fine filaments extending into the surrounding cornea, similar to fungal kera- titis. Pain out of proportion to the size of Fig.2. Ring infiltrate in fungal keratitis Fig.3. Nocardia keratitis with multiple pin- Photo: P Garg & G N Rao infiltrate and radial keratoneuritis, classi- head infiltrates and cally described for -related Photo: P Garg & G N Rao

Community Eye Health Vol 12 No. 30 1999 21 Corneal Ulcer

scopy using Gram’s staining method and ophthalmologists. A large proportion of potassium hydroxide (KOH) preparation is suppurative keratitis is caused by bacteria simple and quick to perform and often (64%), most of which are sensitive to gives useful information for initial medical broad spectrum antibiotics. It is reason- management. Culture and sensitivity, on able, therefore, to assume that in small the other hand, require more sophisticated lesions that are away from the visual axis facilities. and not associated with risk factors for Although the ophthalmic literature uni- unusual organisms, initial treatment may formly recommends that microbiological be started with a broad spectrum antibiotic investigations must be performed in all at frequent intervals. These patients, how- Fig.4. Corneal destruction due to cases of infectious keratitis, these proce- ever, need close daily follow up to make Pseudomonas infection dures require investment of a certain sure the lesion is improving. At the earliest Photo: P Garg & G N Rao amount of time and expense by the oph- evidence of deterioration the ulcer should thalmologist, the patient and ultimately the be subjected to a detailed microbiology growth of bacteria, fungi, and Acantha- medical system in general. A survey of work-up or referred to a centre where such moeba. These include fresh blood agar, community ophthalmologists in southern facilities exist. chocolate agar, Saburaud’s dextrose agar California showed that less than 20% of Treatment with a commercially avail- (SDA), non-nutrient agar with an overlay corneal ulcers were treated in accordance able antibiotic that has a broad spectrum of of Escherichia coli, thioglycolate broth and with textbook recommendations.2 Another activity against gram-negative and gram- brain heart infusion broth (Fig. 5). These study found that less than 4% cases re- positive organisms, such as ciprofloxacin media are incubated under appropriate quired a change in initial antibiotic therapy or ofloxacin, seems to be the least expen- atmospheric conditions and are examined based on an inadequate clinical response.3 sive first approach. However, there is a risk daily for growth for at least seven days It has also been documented that there may of development of resistance particularly before a negative report is given. The be poor correlation between in vitro with ciprofloxacin. growth on media is then identified antimicrobial sensitivity and in vivo clini- Microbiological investigations should and where appropriate is subjected to cal response. Consequently, there is some always be done for the following cases. an antimicrobial susceptibility test. Micro- controversy over the routine use of micro- biological investigations (including anti- ● Severe ulcers (a rapidly progressing infiltrate which is more than 6mm in Table 1: Various Isolates from Cases microbial sensitivity testing) in the man- agement of suppurative keratitis. Based on diameter or involves deeper stroma or of Infectious Keratitis. L V Prasad the experience gained at the L V Prasad associated with imminent or actual per- Eye Institute: January 1991 – Eye Institute and a relatively higher inci- foration). December 1998 (n=2655) dence of fungal keratitis (33%) in the tropi- ● Cases where history and clinical exami- Bacteria: n=1689 cal climate, we are of the opinion that nation suggest unusual non-bacterial Gram positive cocci microscopic examination of corneal scrap- pathogens. ings using Gram’s staining techniques and Staphylococcus epidermidis 32.4% Initial treatment in these cases should be KOH (10%) preparation can provide useful 7.6% based on the microscopic examination. guidance for initial therapy in a case of Other staphylococci 4.0% Initial treatment in fungal keratitis is suppurative keratitis. Streptococcus pneumoniae 13.1% usually started with natamycin (5%) sus- a -haemolytic streptococci 5.3% pension administered half hourly. Various Other streptococci & micrococci 1.6% Treatment antifungal agents used in the treatment of Gram positive bacilli When treating a patient with suppurative keratitis are shown in Table 2. Corynebacterium 13.9% keratitis the clinician has 3 management For Acanthamoeba keratitis, treatment is Bacillus 1.2% options: usually started with polyhexamethylene Nocardia 1.7% biguanide (PHMB) 0.02% or chlorhexidine Mycobacterium 0.4% 1. Complete microbiological work-up of 0.02% (Table 3). Antifungal and anti- all ulcers, followed by initial therapy Propionibacterium 1.2% Acanthamoeba therapy is started only based on the smear results; when microbiological evidences exists. Gram negative bacilli 2. Empirical therapy (based on previous Pseudomonas 11.1% clinical experience) with one or more Enterobacteriaceae 1.7% commercially available broad spectrum Moraxella 1.4% antimicrobial agents; or Aeromonas 0.4% 3. Microbiology work-up of severe ulcers Acinetobacter 0.7% where the history or clinical findings Haemophilus 0.8% suggest an atypical non-bacterial Fungi: n=893 pathogen. Aspergillus 33.0% It is clear that option 1 is the best Fusarium 35.1% approach for the tertiary referral practice, Dematiaceous fungi 14.4% because most of the ulcers are severe or Other hyaline fungi 16.4% caused by unusual or resistant organisms Candida 1.0% that have failed to respond to initial thera- Fig.5. Various culture media used in Parasites: n=73 py. However, there is a lot of confusion laboratory diagnosis of microbial keratitis Acanthamoeba 100% regarding the best option for community Photo: P Garg & G N Rao

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Table 2: Antifungal Agents The role of topical in the Table 3: Anti-Acanthamoeba Agents used in Keratitis management of suppurative keratitis is used in Keratitis controversial and hence they are best Polyenes avoided. Antiseptic biocides Nystatin Simple debridement of necrotic debris in Chlorhexidine Amphotericin B conjunction with intensive topical therapy PHMB Natamycin may help facilitate drug penetration espe- Aminoglycosides cially of anti-fungal agents. Neomycin Pyrimidines Tissue adhesive using N-butyl cyano- Paromomycin Flucytosine acrylate with a bandage contact lens is Diamidines Imidazoles useful in cases with marked thinning or Dibromopropamidine Clotrimazole perforation less than 2mm. Hexamidine Miconazole Penetrating keratoplasty is performed in Ketoconazole cases with advanced disease at presenta- Suppurative keratitis is a sight-threaten- Fluconazole tion where there is no response to medical ing disorder. Early clinical suspicion, ratio- Itraconazole therapy or when a large perforation is pre- nal use of laboratory diagnostic procedures sent. and appropriate therapy can go a long way Modification of therapy is primarily based towards reducing ocular damage from this on clinical response to initial therapy and is Prevention disorder. guided by the results of culture and sensi- tivity tests. Although not always a preventable disease, certain steps may help reduce the potential- References ly severe consequences of suppurative ker- Supplementary Treatment 1. Dandona L, Krishnan R, Janarathanan M et al. atitis. Indications for penetrating keratoplasty in India. Indian J Ophthalmol 1997; 45: 163–8. Cycloplegic agents such as sul- ● Community awareness of risk factors for 2. McDonnell PJ, Nobe J, Gauderman WJ et al. phate 1%, 1% or cyclopento- suppurative keratitis such as minor trau- Community care of corneal ulcers. Am J late 1% instilled three times a day reduce ma and the use of contaminated tradi- Ophthalmol 1992; 114: 531–8. ciliary spasm and produce , tional eye solutions in the eye 3. McLeod SD, Kolahdouz-Isfahani A, Rosamian K et al. The role of smears, cultures and anti- thereby relieving pain and preventing ● Early recognition and institution of biotic sensitivity testing in the management of synechiae formation.Anti-glaucomaagents appropriate therapy by community suspected infectious keratitis. are used when intraocular pressure is high. health workers or ophthalmologists 1996; 103: 23–8. If required, oral analgesics for pain may ● Prompt referral of advanced cases to ter- be used. tiary eye care centres ✩ ✩ ✩

Herpes Simplex Virus Keratitis Herpes simplex virus infection is an effects (see photos), although Drs Garg important cause of corneal scarring and and Rao rightly indicate that in develop- . The clinical features ing countries other causes of corneal and treatment of herpetic corneal ulcera- ulceration arerelativelymore common. tion were the subject of an early edition The subject of herpes simplex virus of the Journal (J Comm Eye Health keratitis is not addressed in this particu- 1990; 3: 1–4). lar issue of the Journal. Herpes simplex virus keratitis Herpes simplex virus is found world- Editor. wide, sometimes with devastating (and stomatitis) in an African child Photos: John Sandford-Smith

Eye Health The Journal of Community Eye Health is published four times a year. Free to Developing Country Applicants 1999/2000 Subscription Rates for Applicants Elsewhere 1 Year: UK£25 / US$40 2 Years: UK £ 4 5 /US $ 7 0 (4 Issues) (8 Issues) To place your subscription, please send an international cheque/banker’s order made payable to UNIVERSITY COLLEGE LONDON or credit card details with a note of your name, full address and occupation (in block capitals please) to the address below. Dr Masresha Abuhay, Dean of Gonder Journal of Community Eye Health, International Centre for Eye Health, Medical College, Ethiopia received a copy Institute of Ophthalmology, 11 – 43 Bath Street, LONDON, EC1V 9EL, UK of Community Eye Health from the Editor’s son, David McGavin Tel: 00 44 (0)171 608 6910. Fax: 00 44 (0)171 250 3207. E-mail: [email protected] Photo: James Moult

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