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Objective: To discuss clinical features and treatments of fungal keratitis, and to provide statistical data for clinical therapy and increase the therapeutic effects. Methods: This is a retrospective case series study. An analysis was performed by collecting patients' demography features, risk factors, onset time, lab results, clinical features and treatment from 1 414 cases of fungal keratitis from January 2006 to October 2016 in Qingdao Eye Hospital, Shandong Eye Institute. Results: In the 1 414 cases (1 414 patients), 1 174 patients (83.0%) came from different areas in Shandong Province, and the rest mainly from provinces on the north of Yangtze River. The age was 40 to 60 years in 874 cases (61.4%). The onset time was often in autumn and winter. The average duration between the onset and treatment was 1 to 74 days; 942 patients (67.1%) visited our hospital in 8-30 days after the appearance of the symptoms. Corneal trauma was the most common risk factor, especially injury by plants (367 cases, 26.4%). The positive rate of direct microscopic examination of potassium hydroxide wet mounts was 96.4%. The positive rate of confocal microscopy was 89.8%. Fungi were detected in corneal ulcer scrapings and (or) diseased corneal tissues obtained during surgery from 973 patients (68.8%). Most of the fungi were Fusarium (595 cases, 61.1%), followed by Alternaria (184 cases, 18.9%) and Aspergillus (119 cases, 12.2%). There were 603 cases (42.7%) of superficial and middle stromal infiltration, 614 cases (43.4%) of deep stromal infiltration and 197 cases (13.9%) of full-thickness corneal infiltration. Diameters of the corneal ulcer lesion were mostly between 4 and 6 mm (725 cases, 51.6%), followed by<3 mm (372 cases, 26.4%) and>6 mm (302 cases, 22.0%). Hypopyon was combined in 498 cases (35.2%), corneal perforation in 34 cases (2.4%), and endophthalmitis in 58 cases (4.1%). Surgery was performed in 1 198 cases (84.8%), including penetrating keratoplasty in 416 cases (29.4%), lamellar keratoplasty in 199 cases (14.1%), and corneal ulcer debridement in 532 cases (37.6%), with an effective rate of 98.1% (408 cases), 97.0% (193 cases) and 92.8% (494 cases), respectively. Two hundred and fifteen cases (15.2%) were treated with medical therapy alone, of which 147 cases (68.4%) were cured. Fifty-six patients (3.9%) finally lost their eye balls, including 54 cases of evisceration and 2 cases of ophthalmectomy. Conclusions: Fusarium is the main causative agent of fungal keratitis in Shandong Province. Direct microscopic examination of potassium hydroxide wet mounts is a simple, rapid and effective test method. Early diagnosis can be made if the result of corneal ulcer scraping examination is positive. Antifungal drug treatments can be done in early onset time. If the drug efficacy is poor or the patient's condition gets worse, immediate surgery is the key to controlling fungal keratitis. (Chin J Ophthalmol, 2020, 56:286-293) .

Objective: To detect the change process of substance P (SP)expression and the difference between fungus and bacterial keratitis and explore effects of SP on the damage and repair process of keratitis model of Wistar rats., Methods: Wistar rats were divided randomly as blank controlled group, fungal keratitis group and bacterial keratitis group. Inoculate fusarium and staphylococcus into cornea of Wistar rats to make animal keratitis model. Choose the right eye as experimental eye and the left eye as control. After the model was created successfully, 25 rats were executed randomly at 1, 5, 8, 10 and 14 days after the surgery. Detailed record and hematoxylin-eosin dye were done to each group to examine the process of ulcer. Expression of SP were detected through immunohistochemistry and reverse transcription polymerase chain reaction. Use variance analysis, T test and Q test to evaluate the results., Results: One day after infection, the cornea of experimental group showed ulcer with disordered shallow matrix layer collagenous fibre arrangement and neutral granular cell infiltration; after 5 days, ulcer worsened and granular cells infiltrated through the whole layer; after 8 days, ulcer shrinked and fibroblast began to increase with new vessels formed; after 10 days, new vessels began to decrease; after 14 days, the matrix level textile fiber assumes scar type restructuring. The expression of SP increased in endothelium cells, inflammatory cells, fibroblast cells and endothelium of new vessels 1 d after surgery (absorbance for fusarium and staphylococcus group were 0.3313 ± 0.0133 and 0.3995 ± 0.0191 respectively; mRNA were 0.4525 ± 0.0170 and 0.5532 ± 0.0258), peaked at 8 d (for fusarium and staphylococcus group were 0.5525 ± 0.0171 and 0.7050 ± 0.0119 respectively; mRNA were 0.5975 ± 0.0221 and 0.7150 ± 0.0238), began to decrease at 10 d (for fusarium and staphylococcus group were 0.1533 ± 0.0176 and 0.3125 ± 0.0170 respectively; mRNA were 0.2416 ± 0.0082 and 0.4835 ± 0.0082) and dropped to lower than normal at 14 d (for fusarium and staphylococcus group were 0.1150 ± 0.0128 and 0.1675 ± 0.0126 respectively; mRNA were 0.1275 ± 0.0126 and 0.2325 ± 0.0171), which had significant difference (the absorbance of SP: for fusarium group, F = 832.24, q = 35.3675, 12.9044, 27.3621, 34.6506, 22.4632, 62.7296, 70.0182, 40.2664, 47.5550, 7.2886, P < 0.01;for staphylococcus group F = 636.17, q = 38.7494, 11.4245, 10.8298, 28.6082, 27.3249, 49.5791, 67.3575, 22.2543, 40.0327, 17.7784, P < 0.01. mRNA expression: for fusarium group F = 658.60, q = 18.9941, 9.5132, 27.4719, 42.0007, 9.4809, 46.4661, 60.9948, 36.9852, 51.5139, 14.5287, P < 0.01; for staphylococcus group F = 335.13, q = 16.9266, 4.1677, 7.1081, 32.4724, 12.7589, 24.0347, 49.3990, 11.2759, 36.6402, 25.3643, P < 0.01). Two experimental groups showed similar changes as time changes, the bacterial group showed more SP expression than fungal group, which had significant difference (absorbance of SP t = 6.5493, 7.3867, 16.0505, 14.5479, 6.5360, P < 0.05; mRNA expression t = 7.2878, 9.5232, 8.8149, 43.6256, 11.1269, P < 0.05). Controlled eyes showed increased SP expression at 1 d (absorbance was 0.2840 ± 0.0212; mRNA was 0.3950 ± 0.0129) and dropped to normal at 5 d (absorbance was 0.2125 ± 0.0174; mRNA was 0.3321 ± 0.0041). There was significant difference between bacterial group, fungal group and controlled eyes (absorbance of SP: compared with fusarium group t = 4.2261, 18.3314, 35.5163, 5.3609, 13.4826; compared with staphylococcus group t = 9.0508, 25.6639, 63.4924, 7.4828, 7.1301, P < 0.05. mRNA expression: compared with fusarium group t = 6.0249, 31.9158, 26.0413, 9.1550, 19.1741; compared with staphylococcus group t = 12.2636, 53.4404, 36.8727, 15.8687, 8.2939, P < 0.05)., Conclusion: SP possibly participated in the early time damage and the later period repair process in fungus keratitis and its lower expression level possibly participated in the mechanism of lighter ache in fungus keratitis.

Objective: To investigate the visual functional therapeutic effects of deep lamellar keratoplasty (DLK) and penetrating keratoplasty (PK) on perforated fungal keratitis., Methods: 64 patients (64 eyes) of fungal corneal ulcer in Ophthalmology Center of Ningbo Yinzhou People Hospital from 2004 to 2009 were retrospected, of which undergo DLK (36 patients, 36 eyes) and PK (28 patients, 28 eyes), and followed up by 12 to 24 months. Check two sets of patients' VA and refraction before operation, and analyze the best-corrected visual acuity (BCVA), corneal refraction changes, corneal endothelium counting and complications, using χ(2) test and t-test., Results: The BCVA after the operation of two sets are both improved, 32 eyes of DLK set were above 0.4, 19 eyes of PK set were above 0.4, of which the DKL set is a bit better than PK set (χ(2) = 4.304, P > 0.05). The astigmatism of DLK set is smaller than the PK set after operation, and there is significant difference (χ(2) = 4.98, P < 0.05). The astigmatism of two sets on the average were all no more than 5.00 D. The reject reaction of keratoplasty of DLK is less than PK, there is obviously significant difference (χ(2) = 34.17, P < 0.05)., Conclusions: There is less complications of DLK than PK for fungal corneal ulcer. DLK can reduce the occurrence of reject reaction of endothelium type, and the BCVA, refraction of DLK after operation is similar to PK, the incidence rate of surgical operation failure is low.

Objective: To analyze causes of serious fungal corneal ulcer resulting in infectious endophthalmitis and explore clinical strategies of avoiding the failure of antifungal therapy., Methods: Etiological factors, pre-hospital treatments, clinical features and laboratory findings of 47 inpatients with fungal corneal ulcer resulting in endophthalmitis from January 1999 to December 2008 in Qingdao eye hospital were retrospectively reviewed., Results: Rural residents (95.7%) dominated in 47 cases with a mean age of (49.8 ± 10.1) years. Ocular trauma was the leading cause of fungal corneal ulcer (66.0%). Three patients were ever treated with hormone drugs after the fungal infection. Primary, secondary and tertiary hospital accounted for 68.1%, 17.0% and 14.9% among first medical consultation sites. Diagnostic accuracies of fungal corneal ulcer in three grade hospitals were 31.3%, 62.5% and 71.4% respectively. The average interval from the onset of disease to the admission into our hospital was (29 ± 23) days. The dominating pathogen was genus Fusarium (91.5%) with F. solani (48.9%), F. oxysporum (31.9%) and F. moniliforme (8.5%). Antifungal drug sensitivity tests were performed in 21 patients. The first three sensitive drugs were natamycin (88.9%), voriconazole (78.6%) and amphotericin B (61.9%). The first three drug-resistant ones were miconazole (90.5%), fluconazole (66.7%) and itraconazole (61.9%)., Conclusion: Main causes of fungal corneal ulcer resulting in infectious endophthalmitis included lower diagnostic accuracies of first medical consultation in primary hospitals, abuses of non-sensitive drug and delayed treatment of patients. Improving clinical capabilities of doctors in primary hospitals, emphasizing antifungal drug susceptibility tests, and consummating the social security system and the referral system could be effective measures to avoid therapeutic failures.

Purpose: To screen proper concentration of clarithromycin ophthalmic gel by observing the efficacy of different concentrations of clarithromycin ophthalmic gel for treating staphylococcal corneal ulcers., Methods: Corneal ulcer was induced in the right eye of 40 rabbits, 3.0 x 10(9) CFU/ml staphylococcus aureus suspension was injected midstromally into the central corneal. These rabbits were divided randomly into 5 groups, each group received respectively topical blank matrix, clarithromycin ophthalmic gel 0.1%, clarithromycin ophthalmic gel 0.25%, levofloxacin ophthalmic gel, clarithromycin ophthalmic gel 0.25% and recombinant bovine basic fibroblast growth factor (Rb-bFGF), 4 times every day, 2 drops each time. The eyes were examined respectively with the slit lamp before treatment (day 0), on day 3, day 5, day 7, day 10, day 14 to observe the progression of corneal ulceration, including the area of the corneal ulcer and mark of keratitis., Results: Under the same way of giving medicine, experimental corneal ulcer studies showed a statistically significant decrease in all treatment groups on measurements of the area of the corneal ulcer and mark of keratitis (P < 0.05), and clarithromycin ophthalmic gel 0.25% had a better action than clarithromycin ophthalmic gel 0.1% against staphylococcus aureus corneal ulcer., Conclusion: Clarithromycin ophthalmic gel 0.25% was proved to be an effective ocular medication for the therapy of gram-positive bacterial corneal ulcer.

Objective: To study the clinical and pathogenic characteristics of keratitis caused by Alternaria alternata and to provide evidence for the diagnose and treatment of mycotic keratitis., Methods: The patients with keratitis were examined by lamp microscope; the direct smears of corneal scrapings were stained using 10% potassium hydroxide and Giemsa's staining and the results were observed under microscope. After hypha was found, the samples from corneal were taken for fungal culture and fungal susceptibility test in vitro according to the National Community of Clinical Laboratory Standard (NCCLS) document M38-A at the same time. Ketoconazole, Amphotericin B and Fluconazole eye drops were applied into eyes frequently and alternately. The affectivity of the treatment were also observed. The isolates of Alternaria alternata from patients were used to induce keratitis in rabbits. The rabbits were sacrificed by air after 5 days and 14 days and their corneas were taken for pathology and inoculating for fungi., Results: All the patients have only one eye with Alternaria alternata's keratitis and their average age was 50 years old. The lesions of corneal necrosis in the patients and Alternaria alternata's keratitis in the rabbits were appeared as light grey, shallow and a diffused edge. Alternaria alternata showed as thick transparent hypha and a great of spherical chlamydospores on the top of hypha or cluster one and the other in corneal scraping under microscope. The hypha and spores of Alternaria alternata in the culture medium were all brown and the spores were separated into cells like wall brick and grew on the top of spores linking like chains. Anti-microbial susceptibility testing in vitro showed that Alternaria alternata was susceptible to Voriconazole, Amphotericin B, Ketoconazole, Miconazole, Econazole, Terbinafine and Fluconazole but it was resistant to Clotrimazole, Flucytosine ang Itraconazole. 22 of the patients were cured by dropping Amphotericin B, Ketoconazole and Fluconazole frequently and alternately but surgery was performed in one case. The mean cured time was 34 day. The lesion of rabbits keratitis caused by Alternaria alternata was thin and localized only in the region of lacking epicytes. The isolate from the rabbit's keratitis model was Alternaria alternata., Conclusions: The keratitis caused by Alternaria alternata has its distinct clinical and laboratory characteristics. The virulence of Alternaria alternata is relatively low to cornea and the combination of anti-fungal agents could cure Alternaria alternata keratitis.

Objective: To evaluate the outcome of penetrating keratoplasty (PKP) for the treatment of fungal keratitis with corneal perforation., Methods: 40 patients (40 eyes) with corneal perforation secondary to fungal keratitis underwent PKP at Qingdao Eye Hospital from 1994 to 2003. The follow-up ranged from 6-24 months. The postoperative visual acuity and complications were documented., Results: 39 (97.5%) patients preserved the eyeballs. The visual acuity improved in 38 (95.0%) eyes. Fungal infection recurred in 4 eyes, 3 of which were controlled with antifungal medication and 1 was enucleated because of the uncontrolled endophthalmitis. Graft rejection was observed in 15 (37.5%) eyes, 12 of which were cured with medication and 3 received secondary PKP. 3 (7.5%) eyes had graft ulceration, 2 of which were cured and the other one was regrafted because of severe endothelial cell loss. 5 (12.5%) eyes had secondary glaucoma, and the intraocular pressure was controlled medically and surgically. Complicated cataract occurred in 5 (12.5%) eyes, 3 of which underwent cataract extraction. Most complications were controlled successfully. At last follow-up, 36 (90.0%) grafts were clear., Conclusion: PKP is an effective approach for preservation of eyeballs and restoration of visual function in patients eyes with fungal keratitis and corneal perforation.

Objective: To identify the variance of pathogens of purulent keratitis and their resistance patterns to antibiotics., Methods: From January 1995 to October 2000, all patients with suspected infectious corneal ulcer were examined by bacterial, fungal and Acanthameoba culture. The results of microorganism-culture were compared with those in literature., Results: Of the specimens in 1 430 cases, there were 790 cases (55.2%) with positive culture including bacterial isolates in 258 cases (18.0%), fungal isolates in 498 cases (34.8%) and parasites in 34 cases (2.4%). The Staphylococcus aureous and Pseudomonas aeruginosa that had markedly declined since 1980s represented 6.2% and 21.7% of bacterial isolates respectively. However, the opportunity organism such as Staphylococcus epidermidis represented 27.5%, a tendency of gradual increase. The most common fungal pathogen was fusarium spp that represented 64.5% of all positive fungal cultures, and Aspergillus spp (13.6%) occupied the second place. The resistance of the ocular bacteria to fluoroquinolones gradually increased. Although the Pseudomonas aeruginosa was resistant to gentamycin in 36.2%, it was almost no resistance to tobramycin (3.4%). The fusarium spp was shown to be resistant to a number of the anti-fungal agents, but it is sensitive to natamycin., Conclusion: The survey of pathogens in purulent ulcerative keratitis and their resistance patterns to antibiotics helps in clinical treatment.

Objective: To investigate the clinical course, treatment and outcome of infective corneal ulcer induced by orthokeratology., Methods: Sixteen cases of infective corneal ulcer caused by orthokeratology were reported, including 7 cases of pseudomonas corneal ulcers, 8 cases of acanthamoeba keratitis and 1 case of mycotic keratitis. Smears and cultures from corneal scrapings for bacteria, fungi and amoeba were performed for all of the patients. According to the results of pathogenic microorganisms, different therapeutic approaches were given. Lamellar keratoplasty or penetrating keratoplasty was performed for 9 patients whose corneal lesions were serious and unresponsive to medical therapy., Results: After medical treatment or keratoplasty, corneal infections of all the patients were controlled. The visual acuity of most cases was improved., Conclusions: The infective corneal ulcer is the most serious complication of orthokeratology. The treatment of infective corneal ulcer should be directed toward the elimination of the pathogenic microorganisms from the cornea. Keratoplasty continues to have a central role in the management of some advanced cases. Although the infections can be controlled, the vision of these patients is seriously damaged.

Objective: The study was designed to explore the pathological mechanisms and effective methods of treatment for pseudomonas corneal ulcer., Method: The nearly perforating pseudomonas corneal ulcer was treated by lamellar keratoplasty and the corneal bottoms were studied histopathologically., Results: 21 cases 21 eyes with pseudomonas corneal ulcers were treated by lamellar keratoplasty, the corneal contour was recovered successfully and a good optical outcome was attained. The study revealed that in the disease not only there was the corneal violent inflammatory reaction, but also there was a large amount of immune cells in the limbal bulbar conjunctiva, sclera, surroundings and base of corneal ulcer. The corneal collagen was degenerative and neovascular vessels invaded the lesion., Conclusions: Possibly, both the inflammatory and immune reactions exist in the pathological mechanisms of the pseudomonas corneal ulcer. The pathological processes can be stopped by lamellar keratoplasty and a better clinical outcome can be attained.

Among 385 specimens of presumed microbial keratitis cultured at Beijing Institute of Ophthalmology from April 1988 to December 1990, 21(6%) were associated with extended-wear contact lenses. Of the latter, 10(48%) were cultured bacterio-positive, including 8(80%) of gram-negative and 2(20%) of gram-positive bacteria. Pseudomonas aeruginosa was found in 6 specimens, accounting for 60% of the bacterio-positive cultures. In the meantime, among the 364 specimens not associated with contact lens wear, 87(24%) were cultured positive, including 27(31%) of gram-negative bacteria, 32(37%) of gram-positive bacteria and 20(23%) of fungi, while mixed cultures and nocardia each accounted for 4(5%). 9 contact lens containers and all cleaning solutions of 11 cases of pseudomonas corneal ulcers were cultured to find them 100% positive of P. aeruginosa.

Keratitis associated with contact lens wear in 50 eyes (37 patients) was analyzed. The results revealed that lenses of extended-wear induced more cases of keratitis than did lenses of daily-wear. The pathogenetic mechanism was discussed.