Results

Table 1 summarises the baseline clinical characteristics of the patients who failed primary treatment (14 patients, 12%), had slow healing (17 patients, 14%) or indolent ulcers (15 patients, 13%). Further details of the clinical characteristics of the patients who failed primary treatment are described in Table 2. The age, demographic, and culture results are shown in Figure1.

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Figure 1

Age distribution and culture results of patients with suspected microbial keratitis.

Multivariate analysis identified large culture positive ulcers in patients 60 years or older as the most significant risks for primary treatment failure (Tables 3 and 4). Surgery was required by 10/14 patients who failed primary therapy, all of whom were 60 years or older (p<0.0001) and the significant prognostic indicators identified for this subgroup were culture positive ulcers and previous corneal disease (Table 5).

Significant prognostic indicators of slow healing were previous ocular disease and a positive culture (Table 6). However, if previous ocular disease was divided into the various diagnoses, ulcer size larger than 5 mm² predominated as the sole predictive factor (RR 4.35, 95% CI 1.65–11.76, p = 0.004). The significant prognostic indicators of indolent ulceration were any previous ocular disease or topical steroid use at diagnosis (Table 7). The main predictor for a culture positive ulcer was large ulcer size (Table8).

Discussion

A positive culture had prognostic value in the management of microbial keratitis in the elderly, regardless of the organism cultured or sensitivity data. However, the results also suggest that microbial investigation of small ulcers was rarely useful for the purpose of predicting prognosis, especially for young patients.

The value of culturing ulcers as part of the initial management of microbial keratitis was questioned by McDonnell et al following their survey of 64 general ophthalmologists practising in California.12 Only 14 (23%) considered a corneal scrape was always necessary, the majority (35, 57%) considered a scrape only necessary for large ulcers. McDonnell took the debate further in his editorial which outlined three approaches to the issue: (i) scrape all ulcers (as is the current expert opinion), (ii) scrape none initially and scrape those that fail primary empirical therapy, (iii) scrape only those patients who have severe ulcers or a history and appearance suspicious for an unusual pathogen.11Although our results would support McDonnell’s latter approach, the 70% reduction in our number of microbiological investigations, would also have resulted in the loss of 23/49 (47%) of our culture positive specimens. This would seriously dilute the usefulness of the culture data for epidemiological purposes. For an appropriate empirical therapy, it is necessary to collect local contemporaneous data about the presenting causative organisms of microbial keratitis. All our primary treatment failures were culture positive, but there is no guarantee that a culture subsequent to primary treatment would have provided the same results.

Our results confirm the original observation by Coster and Badenoch9 that ulcer size was an important risk factor.10 In their retrospective study Blantonet al also reported that increasing ulcer size was significantly correlated with failure of therapy (although the statistical analysis in their report was incomplete and underestimated the effect).10

A bimodal age distribution of patients presenting with microbial keratitis was reported in three previous papers, with the 60+ year old group predominating.7-9 The present study had a larger preponderance of younger patients (Fig 1) who were more likely to be contact lens users (43/76, 57% v 3/42, 7% in the 60+ group, p<0.0001). The diagnosis of suspected microbial keratitis in this group probably reflects the clinicians’ concern about the well documented risk of microbial keratitis in contact lens users. However, most of the lesions scraped in this group were not culture positive and may have been sterile infiltrated ulcers as previously described in contact lens users.14 The finding by Blanton et al that contact lens use was a predictor of a good outcome may have been confounded by the age of the contact lens users in their study.10

Primary treatment failure varies between reports but recently McLeodet al 15 highlighted the importance of prescribing the appropriate antibiotics as primary therapy. Although many of the numbers in their paper did not add up, they reported that 8/26 (31%) of the patients referred for further management were definitely prescribed inappropriate therapy and that 8/11 (73%) with poor initial therapy failed treatment compared with 8/41 (20%) given appropriate initial therapy. They also found that 26/34 (77%) of ulcers that failed previous antibiotic treatment were subsequently culture positive but many of these patients were on an inappropriate antibiotic.15 In 1987 Coster and Badenoch9 reported 22/78 (28%) treatment failures giving poor outcome from a series that had a large number of primary care patients and Gudmundsson et al  8 reported 31/175 (18%) of their series of culture positive cases (selected from about 673 corneal cultures between 1977–81) had a major complication with 27 requiring surgery. In another more recent report concerning mainly primary care patients, McLeod et al reported 3/81, 4% (3/56, 5% of the culture positive cases) failed primary treatment, all of whom occurred in the severe ulceration group (41 patients).13We found a primary treatment failure of 14/118, 12% (13/39, 33% of the culture positive cases) in our prospective study of predominately primary care patients. It is difficult to compare the efficacy of the treatments used in these studies because of the differences in the age demographics and differences in the rate of fungal isolation.

Poor healing not surprisingly was associated with previous ocular disease, prior steroid treatment, and large ulcers. However, a positive culture result alone was predictive of poor healing regardless of the organism obtained, suggesting that such information is useful when patients present with large ulcers (>5.0 mm²). Stern and Buttross presented a comprehensive discussion of the role of topical corticosteroids in microbial keratitis.16 Although steroids may potentially worsen the outcome of microbial keratitis if used too early, we did not find steroid use was a significant risk factor for primary treatment failure in our group of patients after adjustment for confounding effects of age, ulcer size, and culture result. Prior steroid use was a risk for indolent ulceration possibly as a result of inhibition of wound healing, or of the nature of the underlying ocular problem which was also an associated risk. These findings have management implications for patients with surface disease and/or who have been using topical steroids. Such patients may benefit from modified therapeutic measures to ensure prompt ulcer epithelialisation; these may include avoidance of toxic antibiotic therapy (that is, the aminoglycosides) where possible, treatment of surface disease such as dry eye, and early use of protective ptosis with botulinum toxin, eyelid splints, or other temporary tarsorrhaphy.

As Coster and Badenoch pointed out, a poor outcome still occurs even when the patient presents early, appropriate empirical therapy is initiated, the causative organism is identified, and drug susceptibility is confirmed.9 A rationalisation of the use of corneal scrape and microbiological culture may be justified, but at the cost of diluting local contemporaneous data upon which empirical primary treatment is based, and with the loss of prognostic information about the risk of primary treatment failure and poor healing.