Background: A multicentre study was carried out in Ghana and southern India to determine the aetiology of suppurative keratitis in two regions located at similar tropical latitudes. Studies of fungal keratitis from the literature were reviewed. Methods: Patients presenting at rural and urban eye units with suspected microbial keratitis were recruited to the study. Corneal ulceration was defined as loss of corneal epithelium with clinical evidence of infection with or without hypopyon. Microscopy and culture were performed on all corneal specimens obtained. Results: 1090 patients were recruited with suspected microbial keratitis between June 1999 and May 2001. Overall the principal causative micro-organisms in both regions were filamentous fungi (42%): Fusarium species and Aspergillus species were the commonest fungal isolates. Pseudomonas species were most frequently isolated from cases of bacterial keratitis in Ghana but in India the commonest bacterial isolates were streptococci. Conclusion: Infections of the cornea due to filamentous fungi are a frequent cause of corneal damage in developing countries in the tropics and are difficult to treat. Microscopy is an essential tool in the diagnosis of these infections. A knowledge of the "local" aetiology within a region is of value in the management of suppurative keratitis in the event that microscopy cannot be performed.

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Aim: To assess whether the presence of characteristic clinical features can be used as a diagnostic aid for suppurative keratitis caused by filamentous fungi. Methods: Patients presenting with suppurative keratitis in India underwent detailed clinical examination followed by microbiological investigation of corneal scrapes. A partial diagnostic score based upon the strength of the association, as estimated by the odds ratio, between reported clinical features and laboratory confirmed diagnoses was devised and subsequently tested using a case series from Ghana. Results: Serrated margins, raised slough, dry texture, satellite lesions and coloration other than yellow occurred more frequently in cases of filamentous fungal keratitis than bacterial keratitis (p,0.05). Hypopyon and fibrinous exudate were observed more frequently in bacterial keratitis (p,0.05). When incorporated into a backwards stepwise logisitic regression model only serrated margins, raised slough, and colour were independently associated with fungal keratitis; these features were used in the scoring system. The probability of fungal infection if one clinical feature was present was 63%, increasing to 83% if all three features were present. Conclusions: Microbiological investigations should be performed whenever possible; however, where facilities are not available, a rapid presumptive diagnosis of suppurative keratitis may be possible by scoring clinical features.

Mycotic or fungal keratitis (FK) is a sight-threatening disease, caused by infection of the cornea by filamentous fungi or yeasts. In tropical, low and middle-income countries, it accounts for the majority of cases of microbial keratitis (MK). Filamentous fungi, in particular Fusarium spp., the aspergilli and dematiaceous fungi, are responsible for the greatest burden of disease. The predominant risk factor for filamentous fungal keratitis is trauma, typically with organic, plant-based material. In developed countries, contact lens wear and related products are frequently implicated as risk factors, and have been linked to global outbreaks of Fusarium keratitis in the recent past. In 2020, the incidence of FK was estimated to be over 1 million cases per year, and there is significant geographical variation; accounting for less than 1% of cases of MK in some European countries to over 80% in parts of south and south-east Asia. The proportion of MK cases is inversely correlated to distance from the equator and there is emerging evidence that the incidence of FK may be increasing. Diagnosing FK is challenging; accurate diagnosis relies on reliable microscopy and culture, aided by adjunctive tools such as in vivo confocal microscopy or PCR. Unfortunately, these facilities are infrequently available in areas most in need. Current topical antifungals are not very effective; infections can progress despite prompt treatment. Antifungal drops are often unavailable. When available, natamycin is usually first-line treatment. However, infections may progress to perforation in ~25% of cases. Future work needs to be directed at addressing these challenges and unmet needs. This review discusses the epidemiology, clinical features, diagnosis, management and aetiology of FK.

Purpose: To describe the epidemiology of Microbial Keratitis (MK) in Uganda. Methods: We prospectively recruited patients presenting with MK at two main eye units in Southern Uganda between December 2016 and March 2018. We collected information on clinical history and presentation, microbiology and 3-month outcomes. Poor vision was defined as vision < 6/60). Results: 313 individuals were enrolled. Median age was 47 years (range 18-96) and 174 (56%) were male. Median presentation time was 17 days from onset (IQR 8-32). Trauma was reported by 29% and use of Traditional Eye Medicine by 60%. Majority presented with severe infections (median infiltrate size 5.2 mm); 47% were blind in the affected eye (vision < 3/60). Microbiology was available from 270 cases: 62% were fungal, 7% mixed (bacterial and fungal), 7% bacterial and 24% no organism detected. At 3 months, 30% of the participants were blind in the affected eye, while 9% had lost their eye from the infection. Delayed presentation (overall p = .007) and prior use of Traditional Eye Medicine (aOR 1.58 [95% CI 1.04-2.42], p = .033) were responsible for poor presentation. Predictors of poor vision at 3 months were: baseline vision (aOR 2.98 [95%CI 2.12-4.19], p < .0001), infiltrate size (aOR 1.19 [95%CI 1.03-1.36], p < .020) and perforation at presentation (aOR 9.93 [95% CI 3.70-26.6], p < .0001). Conclusion: The most important outcome predictor was the state of the eye at presentation, facilitated by prior use of Traditional Eye Medicine and delayed presentation. In order to improve outcomes, we need effective early interventions.

Purpose To describe the care seeking journey and causes of delay among patients with Microbial Keratitis in Uganda. Methods A prospective cohort of patients presenting with microbial keratitis at the two main eye units in Southern Uganda (2016–2018). We collected information on demographics, home address, clinical history, and presentation pathway including, order of facilities where patients went to seek care, treatment advice, cost of care, and use of Traditional Eye Medicine. Presentation time was noted. We compared “direct” presenters versus “indirect” presenters and analysed predictors of delay. Results About 313 patients were enrolled. All were self-referred. Only 19% of the patients presented directly to the eye hospital. Majority (52%) visited one facility before presenting, 19% visited two facilities, 9% visited three facilities, and 2% visited four facilities. The cost of care increased with increase in the number of facilities visited. People in a large household, further distance from the eye hospital and those who used Traditional Eye Medicine were less likely to come directly to the eye hospital. Visiting another facility prior to the eye hospital and use of Traditional Eye Medicine aOR 1.58 (95%CI 1.03–2.43), p = .038 were associated with delayed presentation to the eye hospital. Conclusion This study provided information on patient journeys to seek care. Delay was largely attributable to having visited another health facility: a referral mechanism for microbial keratitis was non-existent. There is need to explore how these health system gaps can be strengthened.

Purpose: Microbial keratitis (MK), is a frequent cause of sight loss worldwide, particularly in low and middle-income countries. This study aimed to investigate the risk factors of MK in Uganda. Methods: Using a nested case control, we recruited healthy community controls for patients presenting with MK at the two main eye units in Southern Uganda between December 2016 and March 2018. Controls were individually matched for age, gender and village of the cases on a 1:1 ratio. We collected information on demographics, occupation, HIV and Diabetes Mellitus status. In STATA version 14.1, multivariable conditional logistic regression was used to generate odds ratios for risk factors of MK and a likelihood ratio test used to assess statistical significance of associations. Results: Two hundred and fifteen case-control pairs were enrolled. The HIV positive patients among the cases was 9% versus 1% among the controls, p = .0003. Diabetes 7% among the cases versus 1.4% among the controls, p = .012. Eye trauma was 29% versus 0% among the cases and controls. In the multivariable model adjusted for age, sex and village, HIV (OR 83.5, 95%CI 2.01-3456, p = .020), Diabetes (OR 9.38, 95% CI 1.48-59.3, p = .017) and a farming occupation (OR 2.60, 95%CI 1.21-5.57, p = .014) were associated with MK. Compared to a low socioeconomic status, a middle status was less likely to be associated with MK (OR 0.29, 95%CI 0.09-0.89, p < .0001). Conclusion: MK was associated with HIV, Diabetes, being poor and farming as the main occupation. More studies are needed to explore how these factors predispose to MK.

IntroductionFungal infections of the cornea, fungal keratitis (FK), are challenging to treat. Current topical antifungals are not always effective and are often unavailable, particularly in low-income and middle-income countries where most cases occur. Topical natamycin 5% is usually first-line treatment, however, even when treated intensively, infections may progress to perforation of the eye in around a quarter of cases. Alternative antifungal medications are needed to treat this blinding disease.Chlorhexidine is an antiseptic agent with antibacterial and antifungal properties. Previous pilot studies suggest that topical chlorhexidine 0.2% compares favourably with topical natamycin. Full-scale randomised controlled trials (RCTs) of topical chlorhexidine 0.2% are warranted to answer this question definitively.Methods and analysisWe will test the hypothesis that topical chlorhexidine 0.2% is non-inferior to topical natamycin 5% in a two-arm, single-masked RCT. Participants are adults with FK presenting to a tertiary ophthalmic hospital in Nepal. Baseline assessment includes history, examination, photography, in vivo confocal microscopy and cornea scrapes for microbiology. Participants will be randomised to alternative topical antifungal treatments (topical chlorhexidine 0.2% and topical natamycin 5%; 1:1 ratio, 2–6 random block size). Patients are reviewed at day 2, day 7 (with reculture), day 14, day 21, month 2 and month 3. The primary outcome is the best spectacle corrected visual acuity (BSCVA) at 3 months. Primary analysis (intention to treat) will be by linear regression, with treatment arm and baseline BSCVA prespecified covariates. Secondary outcomes include epithelial healing time, scar/infiltrate size, ulcer depth, hypopyon size, perforation and/or therapeutic penetrating keratoplasty (corneal transplant), positive reculture rate (day 7) and quality of life (EuroQol-5 dimensions, WHO/PBD-VF20, WHOQOL-BREF).Ethics and disseminationThe Nepal Health Research Council, the Nepal Department of Drug Administration and the London School of Hygiene and Tropical Medicine ethics committee have approved the trial. The results will be presented at local and international meetings and submitted to peer-reviewed journals for publication.Trial registration numberISRCTN14332621; pre-results.