Fungal keratitis (FK) was a type of keratitis caused by pathogenic fungal, which was an important cause of blindness in corneal diseases in China, especially in areas with low medical care and underdeveloped economies, it often leads to visual loss and was the primary cause of eye removal [1] [2] [3] . The incidence of FK was increasing every year due to corneal injury, especially plant injury, abuse of glucocorticoids, broad-spectrum antibiotics and immunosuppressants, unregulated contact lens wear [4] [5] . According to a study [6] , it was estimated that over 1 million eyes were affected by FK worldwide every year, with approximately 10% of patients suffering corneal perforation or requiring eyeball removal. The condition is most prevalent in tropical and subtropical locations and has been estimated to account for 20% - 60% of all culture-positive corneal infections in these climates. The epidemiology of FK varies with regional and climate differences, with Candida albicans predominantly found in developed countries and colder regions, while fusarium and aspergillus were the main pathogens in developing and warm regions. The Jing Zhou region was located in the Jiang Han Plain and grows a variety of crops such as rice, wheat, rape and cotton, FK was easily caused by plant injury during the harvesting season. This study retrospectively analyzed the case data of 137 FK patients in our hospital, providing a basis for clinical diagnosis and treatment of FK in this area.

FK was increasingly becoming the main cause of corneal blindness in developing countries due to its poor response to drugs [4] . Our region was located in the Jiang Han Plain, with high precipitation, humid climate, rich vegetation, and dense distribution of water resource, which was a favourable environment for fungal growth. Corneal plant injury was more common due to the predominantly agricultural population, but the economic conditions were relatively low, resulting in relatively backward timeliness and accuracy of diagnosis and treatment [7] .

Early diagnosis and treatment of FK was crucial for the prognosis of the disease. Traditional diagnostic methods, including microscopic examination of corneal scraping and culture of isolated fungal hyphae, had always been the gold standard for laboratory diagnosis of FK. As the culture of fungi was very time-consuming, it tends to delayed treatment and lead to false-negative results [8] [9] . Although corneal scraping examination can quickly obtain results, in cases of deep corneal infection, the superficial cornea sample may not contain fungal components. In addition, it was an invasive procedure with a poor patient experience, which was inappropriate for patients with near-perforation of the cornea. The recently developed cornea confocal microscopy was a supplementary diagnostic method for detecting fungi, which allows for non-invasive and direct visualization of potential fungal pathogens, enabling rapid and real-time diagnosis [10] . A study [11] has shown that the positive rate of FK detection was 88.8% using confocal microscopy, which was significantly higher than corneal scraping examination. The sensitivity and accuracy of confocal microscopy in the diagnosis of infectious keratitis had also been confirmed in many publications [12] [13] . However, the instrument was expensive and its application was limited in primary hospitals. Therefore, in order to improve the detection rate of FK, clinical doctors in our hospital directly inoculate corneal scrapings onto Sabouraud dextrose agar and applied to slides at the bedside, and send them directly to the laboratory within 2 hours, ensuring the timeliness of microscopy and culture.

This study shows that the age of FK in Jing Zhou was mainly concentrated between 50 and 69 years old, and the majority patients were male, with farmers as their main occupation, confirming once again that farmers were still the main occupation among FK patients. On the other hand, it indicated that young people were working in the cities, and those engaged in agriculture in the countryside were mainly middle-aged and old people. These people were prone to plant injury during agricultural work, and the symptoms were relatively mild at the early stage of infection. Due to their own cultural level and economic ability, they often failed to consult the doctor in time after infection, missing the critical period of early diagnosis and treatment, which may lead to severe fungal corneal infections, resulting in a poor prognosis or even enucleation of the eyeballs. The onset season was mainly concentrated in May to June and September to December, which may be related to the busy agricultural season during these two time periods. The risk factors for FK infection also include wearing corneal contact lenses, eye surface diseases, ophthalmic surgery, and misuse of eye medications. These patients were prone to corneal damage and infection. Diabetes patients should pay attention to FK. Some studies have shown that diabetes can aggravate FK infection and affect prognosis [14] .

The top three pathogens were Fusarium, Aspergillus, Alternaria, which were consistent with other literature reports [2] [15] [16] , but also inconsistent with other studies showing that Aspergillus ranks the first [11] [17] , indicating that there were geographical differences in the pathogens of FK in China. The clinical characteristics, treatment methods, and outcomes of keratitis caused by different fungal genera were different, which were related to the different growth modes of mycelium in the cornea and the immune status of the organism. The growth mode of Fusarium in the cornea was parallel growth, which can easily cause the area of ulcer to expand. The formation of mycelial tundra was thicker and easy to prevent the infiltration of drugs [18] , and the mycelium that invaded the corneal tissue will appear mycelium wall thickening. This structure enhanced the pathogenicity and drug resistance of Fusarium genus, making treatment more challenging. Aspergillus grow vertically or diagonally in the infected cornea and secretes enzymes that degrade collagen fibers, making it more prone to corneal fusion, corneal perforation, fungal endophthalmitis, leading to a poor clinical prognosis and low drug cure rate. This was also the main reason for enucleation of the eyeball in FK patients. Alternaria has no membrane and low pathogenicity, the area and depth of corneal ulcers caused by Alternaria were smaller than Fusarium and Aspergillus, and were sensitive to various antifungal drugs. Its treatment was mainly drug therapy, with a high clinical cure rate [19] .

The susceptibility of different fungal genus to commonly used antifungal drugs also varies, and the minimum inhibitory concentration (MIC) of fusarium to various drugs was higher than that of other genera [18] . Thet Tun Aung [20] found that voriconazole showed better effects than natamycin and amphotericin B in reducing wound size and viable fungal count in FK. Therefore, it was considered that natamycin and voriconazole could be the preferred drugs for empirical treatment [21] . Temporarily formulated 1% voriconazole eye drops can be stored for 30d at room temperature (25˚C ± 2˚C) or refrigerated (4˚C ± 2˚C) protected in the dark. It was worthy of clinical promotion and use. Now there were many new drug in research, such as novel water soluble sterile natamycin formulation, hybrid natural hydrogels, natamycin solid lipid nanoparticle, which also achieved good results. In addition, as a form of drug treatment, intracorneal stromal injection can achieve good therapeutic effects, with a success rate of 95% [22] . In this study nine eyes were injected into the cornea and all of them were all cured. When the effect of drug treatment was poor or even worsens, surgery should be combined as soon as possible, including conjunctival covering, amniotic membrane transplantation, corneal transplantation.

There were some limitations. The positive rate of fungal culture in FK was low, which needs to be further strengthened. Meanwhile, the sample size of this study is relatively small.

In summary, FK patients in our hospital were more common in the middle-aged and elderly population, and mostly of them were caused by plant injury in the process of farming, with Fusarium and Aspergillus as the main causes. Treatment was based on drug therapy, with natamycin or voriconazole as the first choice of drug therapy, combined with surgical treatment can also achieve good effects. It was necessary to strengthen the health education of patients and the diagnosis and treatment abilities of primary ophthalmologists on FK, early diagnosis and treatment should be made as far as possible, so as to avoid patients’ vision loss or even eyeball enucleation.

The authors declare no conflicts of interest regarding the publication of this paper.

Tian T., Zhang, S., Zhu, Y.N. and Cheng, J.K. (2023) Clinical Analysis of 137 Cases of Fungal Keratitis. Yangtze Medicine, 7, 197-205. https://doi.org/10.4236/ym.2023.74021