Risk Factors for Treatment Outcome in Fungal Keratitis

doi:10.1016/j.ophtha.2005.10.063

Ophthalmology

Volume 113, Issue 4, April 2006, Pages 526-530

https://doi.org/10.1016/j.ophtha.2005.10.063 Get rights and content

Purpose

To identify risk factors at diagnosis that can serve as prognostic indicators of primary treatment failure in cases of fungal keratitis.

Design

Prospective, nonrandomized, interventional, comparative study.

Participants

A total of 115 consecutive patients with fungal keratitis treated at one center during a 6-month period.

Methods

Patients with a microscopic corneal ulcer smear that was positive for fungus were enrolled and treated with 5% natamycin monotherapy according to the protocol of the hospital. Treatment responses were assessed at the end of 4 weeks. The prognostic indicators were used in a Poisson model for multiple regression analysis to estimate the relative risk of the main prognostic variables.

Main Outcome Measures

Response of the ulcer to treatment.

Results

Of the 115 patients analyzed in the study, 52 (45.2%) were treatment successes, 27 (23.5%) had slow-healing ulcers, and 36 (31.3%) were refractory to primary treatment. Multivariate analysis showed that the predictors of treatment failure were ulcers that exceeded 14 mm² (P = 0.009), the presence of hypopyon (P = 0.003), and identification of Aspergillus (P = 0.003).

Conclusion

In patients with fungal keratitis treated with 5% natamycin monotherapy, larger ulcer size and infection with Aspergillus were predictors of a poor outcome.

Section snippets

Materials and Methods

This prospective, nonrandomized, interventional, comparative study was performed at the Cornea Department of Aravind Eye Hospital, Madurai, India, after approval by the institutional review board of the Aravind Medical Research Foundation. Each patient with keratitis underwent a detailed clinical examination using a slit-lamp biomicroscope to measure the size and depth of the ulceration, after the recording of a detailed clinical and demographic history that included duration of the symptoms,

Results

We recruited 140 eyes of 140 patients with fungal keratitis who presented to the cornea clinic from April to September 2004. Because 25 patients (18%) were lost to follow-up, the results presented are from 115 (82%) patients. No patients were debilitated or immunocompromised or had diabetes or human immunodeficiency virus. No patients had a history of contact lens use.

The mean age of the patients was 41.8 years (range, 5–75), and 64 (55.6%) were males. Mean time from the onset of pain to

Discussion

Despite the known potential for visual impairment and blindness associated with fungal keratitis, few research studies have evaluated the risk factors and treatment outcomes.

In the current study, the rate of primary treatment failure was 31%. This number is significantly higher than those reported with bacterial keratitis.8, 9 This factor also has been corroborated by Wong et al,¹⁰ who concluded that fungal ulcers were more likely to perforate, thus requiring keratoplasty more often.

Fusarium

References (15)

S.D. McLeod et al.
The importance of initial management in the treatment of severe infectious corneal ulcers
Ophthalmology
(1995)
B.R. Jones
Principles in the management of oculomycosis
Am J Ophthalmol
(1975)
P.A. Rapoza et al.
Prevalence and causes of vision loss in central Tanzania
Int Ophthalmol
(1991)
L.B. Brilliant et al.
Epidemiology of blindness in Nepal
Bull World Health Organ
(1985)
M.U. Khan et al.
Prevalence and causes of blindness in rural Bangladesh
Indian J Med Res
(1985)
C.A. Gonzales et al.
Incidence of corneal ulceration in Madurai district, south India
Ophthalmic Epidemiol
(1996)
M. Hagan et al.
Causes of suppurative keratitis in Ghana
Br J Ophthalmol
(1995)

There are more references available in the full text version of this article.

Cited by (110)

Development and multi-center validation of machine learning model for early detection of fungal keratitis
2023, eBioMedicine
Fungal keratitis (FK) is a leading cause of corneal blindness in developing countries due to poor clinical recognition and laboratory identification. Here, we aimed to identify the distinct clinical signature of FK and develop a diagnostic model to differentiate FK from other types of infectious keratitis.
We reviewed the electronic health records (EHRs) of all patients with suspected infectious keratitis in Beijing Tongren Hospital from January 2011 to December 2021. Twelve clinical signs of slit-lamp images were assessed by Lasso regression analysis and collinear variables were excluded. Three models based on binary logistic regression, random forest classification, and decision tree classification were trained for FK diagnosis and employed for internal validation. Independent external validation of the models was performed in a cohort of 420 patients from seven different ophthalmic centers to evaluate the accuracy, specificity, and sensitivity in real world.
Three diagnostic models of FK based on binary logistic regression, random forest classification, and decision tree classification were established and internal validation were achieved with the mean AUC of 0.916, 0.920, and 0.859, respectively. The models were well-calibrated by external validation using a prospective cohort including 210 FK and 210 non-FK patients from seven eye centers across China. The diagnostic model with the binary logistic regression algorithm classified the external validation dataset with a sensitivity of 0.907 (0.774, 1.000), specificity 0.899 (0.750, 1.000), accuracy 0.905 (0.805, 1.000), and AUC 0.903 (0.808, 0.998).
Our model enables rapid identification of FK, which will help ophthalmologists to establish a preliminary diagnosis and to improve the diagnostic accuracy in clinic.
The Open Research Fund from the National Key Research and Development Program of China (2021YFC2301000) and the Open Research Fund from Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beijing Tongren Hospital, Beihang University & Capital Medical University (BHTR-KFJJ-202001) supported this study.
Laccase-mediated functionalization of natamycin by gallic acids for the therapeutic effect on Aspergillus fumigatus keratitis
2022, European Journal of Pharmacology
Citation Excerpt :
Fungal keratitis (FK) is a serious type of keratitis that easily causes blindness (Mahmoudi et al., 2018). Due to the popularity of corneal contact lenses, the abuse of glucocorticoids or antibiotics, corneal transplantation, and the decrease of ocular immunity, the incidence of FK is increasing year by year (Lalitha et al., 2006; Yang et al., 2019). However, current treatments for A. fumigatus keratitis have many limitations, causing repeated infections and prolonged course with serious corneal symptoms and even vision loss (Brown et al., 2021).
To improve the therapeutic effect of natamycin on fungal keratitis (FK), the grafted derivatives of natamycin and gallic acid were obtained, and the effects of the grafted derivatives on Aspergillus fumigatus (A. fumigatus) keratitis were investigated. The structure of natamycin grafted with gallic acid was identified by FT-IR and UV–Vis, and the successful synthesis of Gallic-Natamycin (GA-NAT) was proved. CCK-8 and the Draize eye test showed that GA-NAT had less cytotoxicity. Then, through in vitro antibacterial experiments such as minimum inhibitory concentration (MIC), adhesion, biofilm formation, and calcium fluorescence staining and in vivo experiments such as clinical score and plate counting, the results showed that GA-NAT had similar antifungal activity to natamycin, but had a better therapeutic effect than natamycin. Myeloperoxidase assay and immunofluorescence staining also showed that GA-NAT significantly inhibited neutrophil recruitment and activity. Moreover, It was further found that GA-NAT could inhibit the mRNA and protein expressions of LOX-1, TNF-α, and IL-1β. These results indicated that GA-NAT inhibited the fungal growth, reduced the neutrophil infiltration into cornea, and down-regulated the expression of inflammatory factors in lesions, which provides a new choice for FK treatment.
Fungal keratitis: A review of clinical presentations, treatment strategies and outcomes
2022, Ocular Surface
Infectious keratitis is a significant cause of corneal blindness worldwide. Although less prevalent in the developed world, cases of fungal keratitis account for almost half of all keratitis cases, occurring in the developing countries. These cases are one of the most refractory types of infectious keratitis and present various challenges to the treating physician such as delayed presentation, long waiting time for culture positivity, limited availability effective antifungal drugs, prolonged duration for response to therapy, a highly variable spectrum of anti-fungal drug sensitivity and a high recurrence rate following keratoplasty. The advent of rapid diagnostic tools, molecular methods, in vitro anti-fungal drug sensitivity testing, alternatives to natamycin, targeted drug delivery and most importantly the results of large randomized controlled trials have significantly improved our understanding and approach towards the diagnosis and management of cases with fungal keratitis.
Overall, Aspergillus and Fusarium species are the most common causes ones of fungal keratitis. History of antecedent trauma is a significant predisposing factor. Corneal scrapings for microscopic evaluation and culture preparation, is the standard of care for establishing the diagnosis of fungal keratitis. Molecular identification of cultures offers accurate identification of fungal pathogens, especially the rare species. Natamycin is an approved first-line drug. Voriconazole is the best alternative, especially for non-fusarium cases. Management involves administration of drugs usually by a combination of various routes, the treatment regimen being individualized depending upon the response to therapy. Photodynamic therapy is a newer treatment modality, being tried for non-responsive cases, before resorting to a therapeutic graft.
Fungal keratitis at a tertiary eye care in Northern Thailand: Etiology and prognostic factors for treatment outcomes
2021, Journal of Infection
Citation Excerpt :
Fungal keratitis is often refractory to medication despite given a specific antifungal drug. A previous study also showed that FK did not respond to initial treatment in 31%, which was worse than the bacterial group. 11 In our series, the great proportion of cases (42.5%) had failed medication treatment and 22.5% of the patients required TPK to eradicate infection while 11.5% underwent destructive eye procedures.
To evaluate etiology and prognostic factors for treatment outcomes of fungal keratitis (FK).
Culture-positive FK patients between 2012 and 2017 were reviewed. Treatment outcomes were categorized into success (resolved within two weeks), slow response and medication failure (no improvement or required surgery). Etiology and risk factors for poor treatment outcomes were analyzed.
A total of 113 eyes of 113 patients (77% males) were recruited. Ocular trauma (69.0%) was the most common predisposing factor. Of this, 80% were exposed to organic foreign bodies. The most common pathogen was Fusarium spp. (45.2%), while dematiaceous fungi were discovered in 29.6%. Medical treatment was successful in 24.8% of eyes, while 29.2% had a slow response and 42.5% failed medication. Therapeutic keratoplasty was performed in 22.1% of eyes and 11.5% eventually required eye removal. Significant risk factors for medication failure were advanced age (P = 0.005), delayed antifungal treatment (P = 0.038) and large-size lesion (P = 0.003).
Ocular trauma was the major predisposing factor of FK in the Northern Thailand. Fusarium was the most common identified pathogen. Many cases were refractory to medications and required surgical intervention. Aging, delayed treatment and a large lesion were predictors for poor outcomes.
The role of fungi in fungal keratitis
2021, Experimental Eye Research
Citation Excerpt :
In spite of appropriate treatment, FK has higher odds for perforation and longer healing time than bacterial keratitis (Prajna et al., 2013a). The poor prognostic factors identified are larger infiltrate size at presentation, larger epithelial defect, ulcers caused by Aspergillus, presence of hypopyon and smear positivity in spite of prior antifungal treatment (Lalitha et al., 2006). The MUTT (Mycotic Ulcer Treatment Trial) II study defined a high risk case with high chances of perforation and TPK requirement as an ulcer with geometric mean infiltrate size more than 6.63 mm, involving the posterior one third of cornea with associated hypopyon (Prajna et al., 2017a).
Fungal keratitis (FK) accounts for approximately half of the microbial keratitis encountered in low middle income countries (LMICs) and predominantly affect the working rural-poor. FK causes significant morbidity with the majority of patients left with moderate or worse visual impairment and approximately 25% requiring expensive and often unsuccessful surgical interventions. The severity of FK and the resultant corneal damage or resolution can be attributed to i) the virulence and bioburden of the fungal pathogen, ii) the host defense mechanism and immune response and iii) sub-optimal diagnostics and anti-fungal treatment strategies. This review provides a comprehensive overview of the multifaceted components that drive FK progression and resolution, highlighting where knowledge gaps exist and areas that warrant further research.
Antifungal susceptibility profiles for fungal isolates from corneas and contact lenses in the United Kingdom
2024, Eye (Basingstoke)

View all citing articles on Scopus

: Manuscript no. 2005-209

: No author has a financial interest or conflicting interest in any materials or methods mentioned in the article

View full text

Original ArticleRisk Factors for Treatment Outcome in Fungal Keratitis

Purpose

Design

Participants

Methods

Main Outcome Measures

Results

Conclusion

Section snippets

Materials and Methods

Results

Discussion

Ophthalmology

Am J Ophthalmol

Prevalence and causes of vision loss in central Tanzania

Int Ophthalmol

Epidemiology of blindness in Nepal

Bull World Health Organ

Prevalence and causes of blindness in rural Bangladesh

Indian J Med Res

Incidence of corneal ulceration in Madurai district, south India

Ophthalmic Epidemiol

Causes of suppurative keratitis in Ghana

Br J Ophthalmol

Original Article
Risk Factors for Treatment Outcome in Fungal Keratitis