fungal keratitis
Introduction
Introduction to fungal keratitis Fungalkeratitis (mycotickeratitis) or corneal mycosis (keratomycosis) is clinically difficult to diagnose and is easily misdiagnosed, often resulting in blindness due to improper treatment. The occurrence of fungal keratitis generally has predisposing factors, the most important of which is corneal trauma. In addition, ocular surface diseases, especially the abnormality of tears, the wearing of contact lenses and the long-term application of antibiotics and glucocorticoids are also common. Factors, fungal keratitis are not uncommon. In the incidence, the south is more than the north; in the middle of the year, the incidence of summer and autumn busy season is high. In terms of age and occupation, it is more common in young adults, old people and farmers. basic knowledge The proportion of illness: 0.003% Susceptible people: no special people Mode of infection: non-infectious Complications: bacterial corneal ulcer glaucoma
Cause
Cause of fungal keratitis
Fungal infections (30%):
In general, fungi do not invade the normal cornea, but when eye trauma, surgery or long-term topical use of antibiotics, corticosteroids and body resistance or corneal inflammation and dry eye syndrome, can cause non-pathogenic fungi to become Pathogens, causing secondary fungal infections of the cornea; or when the cornea is contaminated by fungi such as cereals, hay, branches, etc., and corneal foreign bodies are picked up to cause fungal infections, common pathogens are more common with Aspergillus, followed by It is Fusarium, Candida albicans, cephalosporin and streptomyces.
Fungi infect the cornea in three ways:
(1) Exogenous: There are often plants and history of soil trauma.
(2) The infection of the eye appendage spreads.
(3) Endogenous: deep fungal infections in other parts of the body, blood diffusion, most scholars believe that fungi is a conditional pathogen, because the fungal can be cultured in the normal conjunctival sac, the positive rate of detection is as high as 27%, but not onset Only when long-term use of antibiotics, dysregulation of the flora in the conjunctival sac or long-term application of glucocorticoids, local immunodeficiency and trauma of the cornea, can cause fungal keratitis.
Eye trauma (35%):
Normal cornea will not cause FK even if the cultured fungus is dropped into the eye. Only when the corneal epithelium is damaged or the eye immune function is low, the fungal opportunistic infection can occur. The common risk factors are as follows: Several kinds:
(1) vegetative ocular trauma: the most common type of rice injury, followed by plant leaf abrasions and dust, dirt, sand and other foreign matter.
(2) glucocorticoid eye drops: long-term application can not only cause punctate erosion of the corneal surface, promote the abnormal proliferation of fungi in the conjunctival sac, but also lead to low immune function of the eye, causing opportunistic infection of fungi.
(3) Application of broad-spectrum antibacterial drugs: long-term local and systemic application of antibacterial drugs can cause the occurrence of bacterial alternation in the conjunctival sac and promote fungal growth.
(4) Wearing contact lenses (soft contact lenses and 0K lenses) can directly cause fungal infections due to corneal epithelial erosion or epithelial abrasions, or infections caused by fungal contaminated preservation solutions or cleaning solutions.
Other factors (10%):
Systemic use of long-term anticancer drugs and immunosuppressive drugs can cause host immune function to be low, leading to opportunistic infections of fungi.
Pathogenesis
1. At present, there is no systematic and in-depth study on the pathogenesis of fungal infection in cornea. Some studies have shown that the virulence of fungi itself, namely invasiveness and abnormal body defense, are two major factors in the occurrence of fungal infection. Adhesion of the host epithelium is the first step of fungal infection of the cornea. Recent studies have shown that different infectious fungi have different adhesion to the corneal epithelium. Some studies have also found that fungi are secreted by secreting some specific enzymes during the process of infecting the host. The host cell membrane achieves the purpose of invasion and spread. The enzymes secreted by pathogenic fungi are currently studied with phosphatase and metalloproteinases that degrade peptides. Studies on several common pathogenic fungi proteases have revealed that different fungi are The amount of secreted protease is different at different times of infection.
2. Relationship between growth pattern and clinical characteristics of fungi
(1) The surface layer of corneal lesions is hyphae moss, covering the surface layer of the cornea like a carpet, with inflammatory necrotic tissue in the middle, no fungal hyphae growing in, and the inner layer is completely normal corneal tissue. These patients are clinically The lesions appear as corneal surface, the area is large, the course of disease is slow, the corneal stroma is light, generally there is no satellite foci and immune ring, the anterior chamber reaction is light, and the corneal scraper is easy to find hyphae.
(2) The lesions in the corneal tissue showed that the fungus was a focal lamellar growth. The hyphae spread only vertically and horizontally at the lesion. The inflammatory cells infiltrated around the lesion. The farther away from the lesion, the closer the corneal tissue was to normal, the clinically a single ulcer. Changda corneal stroma deep, the surface is often covered with lipid-like pus, the surrounding satellite stove is obvious, generally no pseudo-foot, penetrating keratoplasty easy to remove the lesion, the positive rate of corneal scraping is low, the positive rate of corneal biopsy is obvious improve.
(3) The corneal tissue of the lesion is a fungal hyphae in the whole layer. The hyphae are vertically embedded in the tissue, and they are disorderly growing, and some have penetrated into the posterior elastic layer. The severe inflammation is coagulative necrosis, and the inflammatory reaction is light. Inflammatory tissue and normal tissue, the clinical manifestations of patients with obvious inflammatory response, a wide range of lesions, often a full-corneal inflammatory response, there are obvious satellite lesions around the ulcer, pseudo-foot, short and fierce, with anterior chamber empyema.
3. According to the clinical manifestations of fungal keratitis combined with the corresponding pathological changes, fungal keratitis can be roughly divided into two forms:
(1) Horizontal growth type: The fungus is a surface carpet growth, which has a good antifungal effect and a high positive rate of the scraper, and is an indication for lamellar corneal transplantation.
(2) Vertical and oblique growth type: for clinically serious fungal infections, specific fungal infections pseudopods, satellite stoves, etc., antifungal drugs are often ineffective, lamellar transplantation is contraindicated, PKP should be removed as much as possible Above 0.5mm range, you can control inflammation.
Prevention
Fungal keratitis prevention
Corneal trauma and drug abuse are the main factors related to the pathogenesis of fungal keratitis; avoid corneal trauma, prohibit the abuse of antibiotics and corticosteroids and other hormonal drugs, for patients with long-term local need to apply hormones should be monitored, is the prevention of this The key to illness.
Complication
Fungal keratitis complications Complications bacterial corneal ulcer glaucoma
Complications, such as bacterial corneal ulcers, anterior chamber hemorrhage, recurrence of infection, etc., endophthalmitis, glaucoma and even eyeball atrophy occur after surgery.
Symptom
Fungal keratitis symptoms common symptoms corneal ulcer conjunctival edema and corneal ulcer bacterial infection corneal burns scratch fungal infection conjunctival hyperemia exposed...
The onset is slow, subacute, and the symptoms are mild, with visual impairment.
The corneal infiltrating foci is white or gray, dense, and the surface is opaque. It has a toothpaste-like or greasy-like appearance. There is a shallow groove formed by collagen dissolution around the ulcer, or an immune ring formed by antigen-antibody reaction. Sometimes a pseudopod or satellite-like invasive foci can be seen next to the corneal lesion, and there may be plaque fibroids after the lesion. The anterior chamber is empyema, grayish white, viscous or mushy. The fungus is highly penetrating, and it is easy to cause fungal endophthalmitis when entering the anterior chamber or the cornea is worn.
Examine
Examination of fungal keratitis
Diagnosis is difficult, must be differentiated from bacterial corneal ulcer, a history of agricultural ocular trauma, typical clinical manifestations, is the main basis for diagnosis, in addition, suspected fungal infection, should be used as a corneal lesion scraping, will take Place the necrotic tissue on the slide, drop 5% potassium hydroxide, cover the fragment, and immediately check for fungal hyphae. If possible, fungal culture should be carried out.
Scraper inspection
(1) Material: Surface anesthesia (preferably 0.5% propoxycaine, because the drug is lighter than other surface anesthetics), use a round blade to scrape tissue from the deep or edge of the lesion.
(2) Dyeing method: Common methods include Gram staining, Giemsa staining and KOH wet film method, and sometimes special fungal staining (Gomori mefhenamine), the positive rate of dyeing is 55%, 66%, respectively. 33% and 85%, Gram staining is the simplest, the fungus is Gram-positive (dark purple), the other tissues are negative (red), and the KOH wet-film method uses KOH to dissolve non-fungal impurities in the scraper to show hyphae. It has been reported that the addition of bright green, greenish or ink staining (a mixture of 10% potassium hydroxide and ink mixed in a ratio of 9:1) can increase the contrast, and the fungal cell wall can be seen to have ink or green small particles attached under the light microscope. Collagen fibers and inflammatory cells are not stained, and the contrast is strong and easy to identify. The disadvantage is that they are prone to false positive or false negative. Recently, caleofluor-white staining (CFW staining) has been used, and this stain can bind to the shell of fungal cell wall. The polysaccharide and cellulose are tightly bound, and the fungus shows a strong dark green color under a fluorescence microscope.
2. Fungal culture
The blade inspection is simple and rapid, but it can only be determined as a fungus, and the fungal species cannot be identified and the drug sensitivity test is performed. Therefore, fungal culture must also be carried out. The commonly used culture methods and culture temperatures are as follows.
(1) Blood agar, cultured at 25 ° C and 37 ° C.
(2) Sabouraud dextrose agar, cultured at 25 ° C and 37 ° C.
(3) Potato dextrose agar, cultured at 25 ° C and 37 ° C.
Most yeasts are easy to grow in blood agar. Filamentous bacteria are easy to grow on sabouraud agar and potato dextrose agar (note that Fusarium can grow in 2 to 3 days at 37 ° C, while other fungi need 1 in 37 ° C It takes more than a week to grow).
3. Polymerase chain reaction (PCR)
The fungi isolated from clinical isolates have been cultured in vitro, and PCR technology has been used for typing diagnosis. It is considered that PCR technology has a good application prospect for the rapid diagnosis of corneal fungi, but it needs to solve the problem of false positive results.
4. Application of chitin to identify fungi
Lamps (1995) pointed out that chitin is a polysaccharide structure contained in fungi and arthropods, but lacks in mammals. The chitin component of fungal cell wall varies with strains and therefore has high specificity. Different fluorescently labeled lectins can specifically bind to different chitins and emit specific fluorescence to rapidly diagnose and identify the bacterial species. This technique is currently considered as a rapid and specific fungal diagnostic method in foreign countries, and has not been reported in China.
5. Corneal biopsy
When the scraping and culture are negative, the clinical still suspected fungal infection should be repeated after repeated examinations, corneal biopsy should be performed, the lesion tissue should be cut with a sharp blade, or the lesion can be drilled with penetrating keratoplasty. Tissue, paraffin-embedded and fixed for pathological section, and then stained microscopic examination, light microscopy staining methods: PAS staining, HE (hematoxylin-eosin) staining and acid-fast staining; fluorescence microscopy with acridine orange (acridine orange) staining and CFW staining, histologically seen:
(1) "Mycelium moss" is composed of a large number of neutrophil infiltration, coagulative necrosis of the corneal stroma layer and swelling of collagen fibers, and complete fungi are rarely seen.
(2) There are a large number of hyphae around the lesion, and the mycelium spreads along the corneal plate layer in parallel. It can also vertically penetrate the corneal plate to grow forward and backward, and pass through the elastic membrane to reach the anterior or posterior chamber to cause inflammation. .
(3) "Feather-like edge" is a round cell and plasma cell infiltration, not a mycelium of fungi.
6. Confocal microscope
Confocal microscopy is a new, non-invasive method for examining corneal diseases in the mid-1990s. It can be used to observe different layers of the cornea at the cellular level. It has been applied to the diagnosis of HSK and Acanthamoeba keratitis, Winchester ( 1997) Conservative microscope was used to observe Aspergillus keratitis. High-resolution hyphae diameter 6m and length 60~40m were observed in the cornea. The confocal microscope was superior to any previous one in terms of time, sensitivity and safety. a diagnostic method.
Diagnosis
Diagnosis and differentiation of fungal keratitis
diagnosis
History
The cornea is often accompanied by a history of traumaticity such as plant and soil, and long-term use of glucocorticoids and broad-spectrum antibiotics in the eyes and throughout the body.
2. Typical clinical manifestations, mainly typical signs of the eye.
3. According to the laboratory examination and histopathological examination results can help the diagnosis.
Differential diagnosis
Severe FK, especially Fusarium keratitis, due to rapid onset, often combined with anterior chamber empyema and corneal perforation, often misdiagnosed as Pseudomonas aeruginosa corneal ulcer, the main identification is the former with typical mycelium By the lesion, the latter ulcer is pale green, the surface is moist and shiny (consisting of viscous necrotic tissue and secretions), the edge is smooth, there is an infiltration edema between the normal cornea, in addition, the disease is caused by herpes simplex virus The clinical manifestations of necrotic keratitis and advanced discoid stromal abscess in Acanthamoeba keratitis are very similar and can be identified by medical history and laboratory diagnosis.
It is also often necessary to identify with bacterial keratitis, viral keratitis.
