Edited by: Giulio Ferrari, San Raffaele Hospital (IRCCS), Italy
Reviewed by: Riccardo Vinciguerra, Humanitas San Pio X Hospital, Italy; Betul Bayraktutar, Tufts Medical Center, United States
This article was submitted to Ophthalmology, a section of the journal Frontiers in Medicine
†These authors have contributed equally to this work
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Infectious keratitis is a major cause of corneal blindness in both developed and developing countries (
Bacterial keratitis (BK) has been consistently shown to be the main causative organisms in the UK and other developed countries. Based on the recent literature, BK represents 90–93% and 72–86% of all culture-proven infectious keratitis cases in the UK and in North America, respectively (
In view of the prevalence of BK in the UK and other parts of the world, it is important to understand the underlying risk factors (for preventative measures) and the clinical outcomes of BK. To date, the majority of UK studies had largely focussed on the epidemiology, causative microorganisms, and antimicrobial resistance of bacteria (
This was a retrospective study of all cases of BK that presented to the Queen's Medical Centre, Nottingham, UK, between January 2015 and December 2019 (a 5-year period). The study was approved by the Clinical Governance team in the Nottingham University Hospitals NHS Trust as a clinical audit (Ref: 19-265C).
Potential cases of BK were first identified via the local microbiological database as described in previous studies (
Relevant data, including demographic factors, risk factors, clinical characteristics, types of bacteria, corrected-distance-visual-acuity (CDVA), management, outcome and complications, were collected using a standardised excel proforma. Risk factors were divided into: (1) contact lens wear; (2) trauma; (3) ocular surface diseases (e.g., dry eye, meibomian gland dysfunction, neurotrophic keratopathy, exposure keratopathy, previous corneal infection, recurrent corneal erosion syndrome, limbal stem cell deficiency, cicatricial conjunctivitis, band keratopathy, and bullous keratopathy); (4) use of topical corticosteroids; (5) previous/recent history of corneal surgery (e.g., corneal graft, pterygium surgery, corneal collagen cross-linking, and corneal debridement/delamination); and (6) systemic immunosuppression (e.g., diabetes, systemic immunosuppressive treatment, malnutrition, and immunodeficiency). The size of epithelial defect and infiltrate were categorised as small (≤3 mm), moderate (3.1–6 mm), or large (>6 mm), based on the maximum linear dimension (
Based on the departmental guideline for infectious keratitis, all patients presented with corneal ulcer(s) of >1 mm diameter, central location, associated with significant anterior chamber reaction/hypopyon, or atypical presentation were subjected to microbiological investigation with corneal scraping for microscopy (with Gram staining) and microbiological culture and sensitivity testing (
All patients with BK were started on hourly topical treatment using either levofloxacin 0.5% monotherapy or combined therapy of fortified cephalosporin (cefuroxime 5%) and aminoglycoside (either amikacin 2.5% or gentamicin 1.5%), based on the severity of cases and the clinician's preference. Hospitalisation was warranted if the ulcer was severe (i.e., central, infiltrate >2 mm, or presence of hypopyon) or was unresponsive to the initial antibiotic treatment, or the patient was unable or unlikely to comply with the intensive treatment regimen. All patients that were admitted for treatment were started on the combined therapy. Further changes to the antibiotic treatment were made, if necessary, based on the clinical course and the microbiological results.
Statistical analysis was performed using SPSS version 26.0 (IBM SPSS Statistics for Windows, Armonk, NY, USA). For descriptive and analytic purposes, the cases were divided into culture-positive and culture-negative BK cases. Comparison between groups was conducted using Pearson's Chi square or Fisher's Exact test where appropriate for categorical variables, and
The main outcome measures were corrected-distance-visual-acuity (CDVA) and time to complete corneal healing, defined as complete resolution of infection with corneal re-epithelialisation. Snellen vision was converted to logMAR vision for analytic purpose. Vision of counting fingers (CF), hand movement (HM), perception of light (PL) and no perception of light (NPL) were quantified as 1.9, 2.3, 2.8, and 3.0 logMAR, respectively (
During the 5-year study period, a total of 283 patients (
Summary of the demographic factors, risk factors, and baseline clinical characteristics of bacterial keratitis presented to Queen's Medical Centre, Nottingham, UK.
Age, years | 54.4 ± 21.0 | 58.5 ± 21.3 | 51.1 ± 20.1 | |
0.66 | ||||
Female | 139 (49.1) | 61 (47.7) | 78 (50.3) | |
Male | 144 (50.9) | 67 (52.3) | 77 (49.7) | |
0.13 | ||||
Left | 145 (51.2) | 72 (56.3) | 73 (47.1) | |
Right | 138 (48.8) | 56 (43.7) | 82 (52.9) | |
OSD |
134 (47.3) | 59 (46.1) | 75 (48.4) | 0.70 |
Contact lens wear | 100 (35.3) | 41 (32.0) | 59 (38.1) | 0.29 |
Immunosuppression |
52 (18.4) | 27 (21.1) | 25 (16.1) | 0.28 |
Prior corneal surgery | 39 (13.8) | 25 (19.5) | 14 (9.0) | |
Topical corticosteroids | 31 (11.0) | 21 (16.4) | 10 (6.5) | |
Trauma | 25 (8.8) | 10 (7.8) | 15 (9.7) | 0.58 |
None identified | 10 (3.5) | 3 (2.3) | 7 (4.5) | 0.32 |
Mean duration of symptoms, day | 5.3 ± 7.2 | 5.8 ± 7.2 | 5.0 ± 7.3 | 0.41 |
0.0–0.3 | 89 (31.4) | 20 (15.6) | 69 (44.5) | |
<0.3–0.6 | 41 (14.5) | 20 (15.6) | 21 (13.5) | |
<0.6–1.0 | 29 (10.2) | 15 (11.7) | 14 (9.0) | |
<1.0 | 124 (43.8) | 73 (57.0) | 51 (32.9) | |
Small (≤ 3 mm) | 172 (60.8) | 58 (45.3) | 114 (73.5) | |
Moderate (3.1–6 mm) | 63 (22.3) | 43 (33.6) | 20 (12.9) | |
Large (>6 mm) | 48 (17.0) | 27 (21.1) | 21 (13.5) | |
Small (≤ 3 mm) | 183 (64.7) | 65 (50.8) | 118 (76.1) | |
Moderate (3.1–6 mm) | 62 (21.9) | 40 (31.2) | 22 (14.2) | |
Large (>6 mm) | 38 (13.4) | 23 (18.0) | 15 (9.7) | |
Central | 110 (38.9) | 57 (44.5) | 53 (34.2) | |
Paracentral | 106 (37.5) | 53 (41.4) | 53 (34.2) | |
Peripheral | 67 (23.7) | 18 (14.1) | 49 (31.6) | |
Yes | 82 (29.0) | 60 (46.9) | 22 (14.2) | |
No | 201 (71.0) | 68 (53.1) | 133 (85.8) | |
Yes | 162 (57.2) | 95 (74.2) | 67 (43.2) | |
No | 121 (42.8) | 33 (25.8) | 88 (56.8) | |
Duration of hospitalisation, days | 8.0 ± 8.3 | 8.8 ± 9.2 | 6.0 ± 4.9 | 0.06 |
Yes | 46 (16.3) | 21 (16.4) | 25 (16.1) | 0.95 |
No | 237 (83.7) | 107 (83.6) | 130 (83.9) |
Nearly all (273, 96.5%) patients were found to have at least one risk factor, with 66 (23.3%) patients having two risk factors, and 18 (6.4%) patients having three or more risk factors for BK. Ocular surface diseases (134, 47.3%) were the most common risk factor, followed by contact lens wear (100, 35.3%), systemic immunosuppression (52, 18.4%), prior corneal surgery (39, 13.8%), use of topical corticosteroids at presentation (31, 11.0%), and trauma (25, 8.8%;
Summary of risk factors based on different age groups.
0.66 | |||
None | 4 (3.4) | 6 (3.6) | |
One | 78 (66.1) | 111 (67.3) | |
Two | 26 (22.0) | 40 (24.2) | |
Three or more | 10 (8.5) | 8 (4.8) | |
OSD |
54 (45.8) | 80 (50.6) | 0.65 |
Contact lens wear | 68 (57.6) | 32 (19.4) | |
Immunosuppression |
9 (7.6) | 43 (26.1) | |
Prior corneal surgery | 15 (12.7) | 24 (14.5) | 0.19 |
Topical corticosteroids | 8 (6.8) | 23 (14.6) | 0.06 |
Trauma | 10 (8.5) | 15 (9.1) | 0.86 |
Of the 128 culture-positive cases, 10 (7.8%) cases grew more than one species, with a total of 138 bacteria being identified (
Summary of causative organisms of bacterial keratitis in Nottingham, UK, and their association with different risk factors.
Gram-positive | 70 (50.7) | 38 (60.3) | 15 (33.3) | 16 (64.0) | 13 (61.9) | |
Staphylococci | 36 (26.1) | 20 (31.7) | 9 (20.0) | 10 (40.0) | 7 (33.3) | |
Streptococci | 16 (11.6) | 9 (14.3) | 2 (4.4) | 4 (16.0) | 5 (23.8) | |
Other GP | 18 (13.0) | 9 (14.3) | 4 (8.9) | 2 (8.0) | 2 (9.5) | |
Gram-negative | 68 (49.3) | 25 (39.7) | 30 (66.7) | 9 (36.0) | 8 (38.1) | |
Pseudomonas | 44 (31.9) | 13 (20.6) | 23 (51.1) | 6 (24.0) | 4 (19.0) | |
Moraxella | 14 (10.1) | 8 (12.7) | 3 (6.7) | 3 (12.0) | 3 (14.3) | |
Other GN | 10 (7.2) | 4 (6.3) | 4 (8.9) | 0 (0.0) | 1 (4.8) |
The baseline clinical characteristics are summarised in
A total of 237 (83.7%) patients were successfully treated with medical treatment alone, while 46 (16.3%) patients required additional surgical interventions for controlling the infection and/or its sequelae. Various surgical interventions were performed, including corneal gluing (22, 7.8%), temporary/permanent tarsorrhaphy (13, 4.6%), single or multi-layer amniotic membrane transplant (11, 3.9%), conjunctival hooding (3, 1.1%), and emergency therapeutic/tectonic keratoplasty (2, 0.7%), evisceration (2, 0.7%), and enucleation (2, 0.7%). Five (1.8%) patients required elective optical penetrating keratoplasty after the resolution of infection.
The mean CDVA (in logMAR) improved from 1.17 ± 1.03 at presentation to 0.80 ± 1.00 at final follow-up (
Summary of corrected-distance-visual-acuity (CDVA) of patients with bacterial keratitis at initial presentation and at final follow-up.
Prognostic factors for poor visual outcome [defined as corrected-distance-visual-acuity (CDVA) of <0.60 logMAR] and poor corneal healing (defined as >30 days to achieve complete healing or occurrence of corneal perforation or uncontrolled infection) in bacterial keratitis.
Age > 50 years | 2.61 (1.24–5.47) | 1.86 (1.06–3.24) | ||
Female gender | 0.81 (0.41–1.62) | 0.56 | 1.27 (0.73–2.19) | 0.40 |
Right eye | 0.81 (0.41–1.60) | 0.54 | 1.82 (1.05–3.16) | |
Epithelial defect size >3 mm | 0.69 (0.19–2.50) | 0.57 | 1.23 (0.44–3.44) | 0.69 |
Infiltrate size > 3 mm | 4.07 (1.21–13.73) | 3.46 (1.24–9.70) | ||
Central ulcer | 2.13 (1.01–4.51) | 1.30 (0.67–2.54) | 0.43 | |
Presence of hypopyon | 0.47 (0.21–1.08) | 0.08 | 1.02 (0.50–2.07) | 0.96 |
Positive culture results | 1.17 (0.56–2.46) | 0.67 | 1.15 (0.63–2.10) | 0.65 |
Presenting CDVA <0.6 | 29.70 (10.47–84.18) | 2.22 (1.19–4.15) |
Although our analysis showed that patients with duration of ocular symptoms of ≥7 days had a worse visual outcome (<0.6 logMAR CDVA), the association was not significant in the multivariable regression analysis (not presented herein). We had not included the duration of ocular symptoms as one of the independent variables in our current regression model in view of the high amount (~15%) of missing data in this parameter, which could negatively affect the multivariable regression analysis.
In terms of complete corneal healing, 278 (98.2%) patients achieved complete corneal healing at final follow-up, with four patients requiring evisceration/enucleation and one patient was still undergoing active treatment. The mean corneal healing time was 1.6 ± 1.5 months, with 157 (55.5%) patients having a corneal healing time of >30 days. Multivariable logistic regression analysis demonstrated that poor corneal healing (>30 days to achieve complete healing) was significantly affected by age >50 years (OR 1.86; 95% CI, 1.06–3.24;
A number of complications were observed in this study, including raised intraocular pressure (>21 mmHg)/glaucoma (32, 11.3%), recurrence of infection (28, 9.9%), threatened/actual corneal perforation (25, 8.8%), complete loss of vision/NLP (11, 3.9%), loss of eye (4, 1.4%), and phthisis bulbi (1, 0.4%). The rate of recurrence of infection was similar between culture-positive (13, 10.2%) and culture-negative cases (15, 9.7%;
BK is the most common cause of infectious keratitis in the UK and in many developed countries. To the best of our knowledge, this study represents one of the largest and most up-to-date studies in the UK specifically examining the risk factors, clinical characteristics, outcomes and prognostic factors of BK.
BK rarely occurs in the absence of any predisposing factor. In this study, relevant risk factors were identified in 96.5% of the patients, with 29.7% of them having two or more risk factors. Identification of risk factors for BK is important as it allows the clinicians to manage the identified risk factors to reduce the risk of recurrence of infection and helps provide some insights into the underlying causative organisms, thereby guiding the choice of antimicrobial treatment, especially in the absence of positive microbiological culture results.
Risk factors for infectious keratitis have been shown to vary considerably across different studies (
In contrast, Khoo et al. (
We observed that contact lens-related BK was most commonly caused by
In our study, we observed that many of the BK cases were of mild severity (i.e., small ulcer size without the presence of hypopyon). This was likely attributed to the fact that the majority of our patient sought medical attention within the first week of their ocular symptoms. This may also explain the lesser (16%) need for additional surgical interventions compared to other studies. An Indian study of infectious keratitis conducted a decade ago showed that only 0.02% of their patients presented within the first week of ocular symptoms, with 12% of the cohort presenting 1 month after the onset of symptoms (
Corneal scraping for culture and sensitivity testing remains the most common microbiological investigations for infectious keratitis. While the culture yield has been shown to be variably low (23.7–77%) (
The majority (84%) of our cases healed with medical treatment alone. While 25 (9%) patients developed threatened/actual perforation, most of them (21, 84%) were amenable to corneal gluing, multi-layer amniotic membrane transplant or conjunctival hooding, with only 2 (0.7%) requiring emergency tectonic keratoplasty. This is in contrast with the findings of the Asia Cornea Society Infectious Keratitis Study (ASCIKS) whereby ~10% of the cohort required emergency therapeutic keratoplasty (
A number of important prognostic factors for visual outcome and corneal healing were identified in our study. We observed that poor visual outcome was significantly influenced by older age, larger infiltrate, central ulcer, and poor presenting CDVA. Khoo et al. (
Additionally, we showed that corneal healing was negatively affected by older age, larger infiltrate size and poorer presenting vision. Gaining a better knowledge of these prognostic factors may enable earlier interventions (e.g., temporary tarsorrhaphy or amniotic membrane transplant) to help promote corneal healing and re-epithelialisation (
This study serves as one of the largest and most up-to-date examination of the risk factors, clinical characteristics and outcomes of BK in the UK. One of the limitations of this study was the inclusion of culture-negative BK cases. However, we had examined the medical case notes to ensure that these cases were true BK cases based on the clinical presentation and the clinical course. In addition, inclusion of the culture-negative cases enabled the examination of potential predictive factors for culture positivity and the outcome of these cases as culture-negative BK cases represents a large proportion of infectious keratitis in clinical practise. The issue with low culture yield in infectious keratitis has been consistently highlighted in many studies (
In conclusion, BK represents a significant ocular morbidity in the UK. It not only significantly affects the patients' vision but also places considerable burden on the healthcare services as hospital admission is often required for intensive medical treatment and/or surgical intervention for BK. Affected patients are usually working adults (18–64 years) and hence the disease can have significant impact on the public and private workforce. As the visual outcome of BK is affected by the initial severity of the infection and the presenting vision, the importance of “prevention is better than cure” cannot be overemphasised. Ocular surface diseases, contact lens wear and systemic immunosuppression are important risk factors for BK and better preventative strategies need to be developed and targeted towards these areas. Future studies evaluating the risk factors and outcomes of other types of infectious keratitis, including fungal and Acanthamoeba keratitis, would be invaluable.
The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.
The study was approved by the Clinical Governance team in the Nottingham University Hospitals NHS Trust as a clinical audit (Ref: 19-265C).
DT, DS, and HD: study conceptualisation and design. DT, JC, BG, CH, LK, AE, and ML: data collection. DT: data analysis. DT, DS, and HD: data interpretation. DT: manuscript drafting. JC, BG, CH, LK, AE, ML, DS, and HD: critical revision of manuscript. All authors contributed to the article and approved the submitted version.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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