Delay in Treatment Leads to Poor Outcomes in Fungal Keratitis

Computer illustration of conidia (asexual spores) from a Fusarium sp. fungus. Some Fusarium fungi are pathogens of plants and humans.
Ocular trauma with vegetative matter is a major risk factor of fungal keratitis, the study shows.

Older age, delayed treatment onset, and large lesion size are all associated with poor outcomes in patients with fungal keratitis, according to research results published in the Journal of Infection. 

Because there is less predictable susceptibility of fungi to antifungal agents, fungal keratitis is typically more complicated and changeling to treat than bacterial keratitis; this challenge is made worse due to the existence of fewer alternative antimicrobial drugs. 

Researchers in Thailand conducted a retrospective, observational study to evaluate the etiology, treatment outcomes, and risk factors associated with poor visual outcomes in fungal keratitis, as well as to compare both the clinical characteristics and treatment outcomes of nonpigmented and pigmented fungal keratitis. 

The investigators conducted an electronic medical record review of new patients who were diagnosed with culture-positive fungal keratitis at the Chiang Mai University Hospital between 2012 and 2017. All patients with suspected infectious keratitis underwent a thorough slit-lamp examination and a routine workup for multiple microorganisms. Fungal identification was based on macro- and microscopic appearances. 

Patient demographic data, ocular findings, and complications and systemic conditions were reviewed. Lesions were categorized into 2 groups: 5 mm or smaller and larger than 5 mm. Central lesions were defined as the 2 mm diameter zone in the center of the cornea; paracentral was defined as the ring zone 3 mm to 8 mm from the center of the cornea, peripheral was defined as the outermost zone adjacent to the paracentral zone, and nearly total was defined as any area ≥80% of the cornea. 

Patients’ antifungal treatment regimens were chosen based on fungal etiology. 

The study cohort included 113 patients with 113 eyes diagnosed with fungal keratitis across 114 episodes. The majority of patients were men between 51 and 60 years of age; 88.5% were referred from primary or secondary hospitals. Overall, 79 patients had nondematiaceous fungi and 34 had dematiaceous fungi. Among those infected with dematiaceous fungi, 29.4% presented with macroscopic pigmentation on slit-lamp examination. Incidence of fungal keratitis peaked in December (14.2%) and September (12.4%), with no specific distribution pattern trending with monthly precipitation, humidity, or temperature. 

KOH wet mount and CWS from corneal scrapes were positive for fungal elements in 43.4% and 45.1% of patients, respectively. Most eyes had filamentous fungi — 93.9% — while only 6.1% had yeast. 

The most commonly identified fungal pathogen was Fusarium spp in 45.2% of patients. Two patients had a coinfection during the same admission; 1 of these patients had no risk factors, but had a simultaneous fungal/bacterial infection. Another patient, who experienced trauma with an organic foreign body and had no systemic disease, had a coinfection with 2 fungal species. 

The preferred medications for filamentous fungi were topical ketoconazole 2% and natamycin 5%. For yeast, the preferred medication was topical amphotericin B 0.15%. Oral itraconazole was prescribed in 79.8% of patients, and subconjunctival fluconazole and intracameral amphotericin B were used as adjunctive treatments in severe cases. 

Across 114 episodes, 64.1% of eyes received topical antifungal therapy on the first day of hospital admission. In cases where patients had a delay before the beginning of antifungal treatment, medial time to antifungal agent administration was 3 (interquartile range [IQR], 1-5) days. Median follow-up time was 17 (IQR, 14-36) months. 

In terms of outcomes, only 24.8% of eyes were successfully treated with medication followed by slow healing (29.2% of eyes); 42.5% of eyes experienced medication failure. Therapeutic penetrating keratoplasty (TPK) was performed in 22.1% of eyes due to refractoriness to medical treatment or impending corneal perforation, or both. 

At 1 year, graft survival rate was 76%, and nearly half of the TPK cases — 48% — had a failed graft with a median time to failure of 5 months (IQR, 2.5-29 months). 

Median initial LogMAR visual acuity was 2.3 (IQR, 0.6-2.3); Median final visual acuity was 1.0 (0.6-2.3). At the time of presentation, 69% of eyes had a visual acuity <20/200 compared with a <20/200 visual acuity in 45.1% of eyes at the final visit. When comparing pigmented vs nonpigmented fungi, they noted a nonsignificant proportion of medication failure between the 2 groups. 

Ocular complications included ocular hypertension/glaucoma (24.8%), perforated cornea (13.3%), and endophthalmitis (3.5%) during treatment. Thirteen patients required removal of the eye due to endophthalmitis, panophthalmitis, or failed patching procedures following a large perforation. 

Results of a multivariable regression analysis demonstrated that advanced age, delayed antifungal treatment, and more than 5 mm of infiltrate were all significant risk factors for medication failure. 

Study limitations include those inherent to retrospective research, a large number of unidentified dematiaceous fungi and a lack of species identification for most fungal isolates, a lack of sensitivity of culture fungi to antifungal agents in this particular care settings, and a more severe clinical presentation compared with the community due to the tertiary care setting. 

“Our results emphasize that [fungal keratitis] is a significant public health problem in [northern Thailand],” according to the researchers. “Health promotion, particularly eye protection during outdoor activities, should be encouraged to reduce the incidence of this preventable blindness. The impacts of this morbidity on other aspects such as treatment cost, psychosocial problems, and quality of life require further study.” 


Tananuvat N, Upaphong P, Tangmonkongvoragul C, Niparugs M, Chaidaroon W, Pongpom M. Fungal keratitis at a tertiary eye care in Northern Thailand: Etiology and prognostic factors for treatment outcomes. J Infect. Published online May 23, 2021. doi:10.1016/j.jinf.2021.05.016.