Misdiagnosed as Fungal Keratitis: Herpes Simplex Virus-1 Keratitis Confirmed by Next-Generation Sequencing.

Objective: The purpose of this study was to report a case of herpes simplex virus-1 (HSV-1) keratitis misdiagnosed as fungal keratitis due to its clinical presentation being similar to that of fungal keratitis, ultimately diagnosed by NGS. Patients and Methods: A 59-year-old male presented with reduced vision in the right eye, combined with a history of trauma with vegetative matter. The corneal ulcer was accompanied with feathery infiltration, satellite lesion, and endothelial plaques. In vivo confocal microscopy (IVCM) showed hyper-reflective linear, thin, and branching interlocking structures. Fungal keratitis was diagnosed. Voriconazole 100 mg orally daily, topical tobramycin and 1% voriconazole were initiated empirically right away. The condition was aggravated and penetrating keratoplasty was performed. Anterior segment optical coherence tomography (AS-OCT) demonstrated the presence of plaques with a clear boundary between plaques and endothelium, resembling the AS-OCT images observed in cases of viral keratitis. Next-generation sequencing (NGS) further detected HSV-1 deoxyribonucleic acid, and no fungal component was found. Antifungal agents were discontinued and antiviral treatments were added. Results: We successfully treated a patient with HSV-1 keratitis who was misdiagnosed due to clinical features and IVCM findings similar to fungal keratitis. The patient's infection was controlled. At 2 years after surgery, the cornea recovered well. Conclusions: HSV-1 keratitis with atypical clinical presentation can be easily misdiagnosed. This case report emphasizes the importance of NGS in diagnosing the pathogens of keratitis.

A Comprehensive Review of Microbial Biofilms on Contact Lenses: Challenges and Solutions.

Contact lenses (CL) have become an immensely popular means of vision correction, offering comfort to millions worldwide. However, the persistent issue of biofilm formation on lenses raises significant problems, leading to various ocular complications and discomfort. The aim of this review is to develop safer and more effective strategies for preventing and managing microbial biofilms on CL, improving the eye health and comfort of wearers. Taking these into consideration, the present study investigates the intricate mechanisms of biofilm formation, by exploring the interplay between microbial adhesion, the production of extracellular polymeric substances, and the properties of the lens material itself. Moreover, it emphasizes the diverse range of microorganisms involved, encompassing bacteria, fungi, and other opportunistic pathogens, elucidating their implications within lenses and other medical device-related infections and inflammatory responses. Going beyond the challenges posed by biofilms on CL, this work explores the advancements in biofilm detection techniques and their clinical relevance. It discusses diagnostic tools like confocal microscopy, genetic assays, and emerging technologies, assessing their capacity to identify and quantify biofilm-related infections. Finally, the paper delves into contemporary strategies and innovative approaches for managing and preventing biofilms development on CL. In Conclusion, this review provides insights for eye care practitioners, lens manufacturers, and microbiology researchers. It highlights the intricate interactions between biofilms and CL, serving as a foundation for the development of effective preventive measures and innovative solutions to enhance CL safety, comfort, and overall ocular health. Research into microbial biofilms on CL is continuously evolving, with several future directions being explored to address challenges and improve eye health outcomes as far as CL wearers are concerned.

[Study of the growth temperature of ocular surface microorganisms in norm and in infectious keratitis]. / Izuchenie temperaturnykh uslovii rosta mikroorganizmov glaznoi poverkhnosti v norme i pri infektsionnykh keratitakh.

Standard bacteriological examinations, which involve culturing microorganisms at 37 °C, are commonly used in clinical practice for diagnosing infectious diseases. However, the growth temperature of microorganisms on the ocular surface (OS) during infectious keratitis (IK) may not coincide with the laboratory standard, which is due to the characteristic features of heat exchange in the eye. PURPOSE: This exploratory study examines the distribution and properties of OS microorganisms isolated under different temperature cultivation conditions in patients with IK and healthy volunteers without ophthalmic pathology. MATERIAL AND METHODS: Fifteen participants were divided into two groups. Group 1 (n=10) consisted of patients with signs of unilateral infectious keratitis, while group 2 (n=5) served as the control group. A novel microbiological method was employed to isolate pure cultures of microorganisms. This method involved cultivating microorganisms at two temperature regimes (37 °C and 24 °C) and subsequently identifying them using biochemical, immunological, and physicochemical techniques, including mass spectrometry. Scanning electron microscopy (SEM) with lanthanide staining used as the reference method. The temperature status of the ocular surface was assessed using non-contact infrared thermography. RESULTS: The study demonstrated the presence of psychrotolerant microorganisms on the ocular surface, which exhibited growth at a relatively low temperature of 24 °C. These psychrotolerant microorganisms were found to be isolated from the ocular surface displaying signs of temperature dysregulation. Among such microorganisms are Acinetobacter lwoffii, Achromobacter xylosoxidans, Bacillus licheniformis, Enterococcus faecalis, Klebsiella oxytoca, Klebsiella pneumoniae, Micrococcus luteus, Pseudomonas luteola, Streptococcus spp. CONCLUSION: When identifying the causative agent of infectious keratitis, it is crucial to consider the divergence of growth temperature of ocular surface microorganisms. The presence of psychrotolerant microorganisms on the ocular surface, which can effectively grow at room temperature, should be taken into account, especially in cases of temperature dysregulation.

An injectable hydrogel based on sodium alginate and gelatin treats bacterial keratitis through multimodal antibacterial strategy.

Bacterial keratitis is among the most prevalent causes of blindness. Currently, the abuse of antibiotics in clinical settings not only lacks bactericidal effects but also readily induces bacterial resistance, making the clinical treatment of bacterial keratitis a significant challenge. In this study, we present an injectable hydrogel (GS-PNH-FF@CuS/MnS) containing self-assembled diphenylalanine dipeptide (FF) and CuS/MnS nanocomposites (CuS/MnS NCs) that destroy bacterial cell walls through a synergistic combination of mild photothermal therapy (PTT), chemodynamic therapy (CDT), ion release chemotherapy, and self-assembled dipeptide contact, thereby eliminating Pseudomonas aeruginosa. Under 808 nm laser irradiation, the bactericidal efficiency of GS-PNH-FF@CuS/MnS hydrogel against P. aeruginosa in vitro reach up to 96.97 %. Furthermore, GS-PNH-FF@CuS/MnS hydrogel is applied topically to kill bacteria, reduce inflammation, and promote wound healing. Hematoxylin-eosin (H&E) staining, Masson staining, immunohistochemistry and immunofluorescence staining are used to evaluate the therapeutic effect on infected rabbit cornea models in vivo. The GS-PNH-FF@CuS/MnS demonstrate good biocompatibility with human corneal epithelial cells and exhibit no obvious eyes side effects. In conclusion, the GS-PNH-FF@CuS/MnS hydrogel in this study provides an effective and safe treatment strategy for bacterial keratitis through a multimodal approach.

Treatment Strategies for Filamentous Fungi Keratitis.

INTRODUCTION: This research aims to describe clinical findings, epidemiology and treatment outcomes in patients with filamentous fungi keratitis of a tertiary centre in Germany over a 7-year period and to compare the efficacy of different antifungal treatments and the effect of additive topical steroids. METHODS: This retrospective study included 25 eyes of 23 patients from October 2013 to December 2020 with cultural isolates of filamentous fungi and corresponding keratitis. Best-corrected visual acuity (BCVA), clinical signs, symptoms, risk factors and outcome were extracted from medical records. RESULTS: Improvement of BVCA was noted in 68% of eyes. Mean BCVA of the study population increased from 0.75 logMAR [median 0.40, standard deviation (SD) 0.82, range 0-2.3] to 0.48 logMAR (median 0.10, SD 0.88, range - 0.1 to 3). The most commonly used antifungal topical treatment was a combination of natamycin 5% and voriconazole 2% (44% of eyes), followed by voriconazole 2% in 36% of cases. An antiinflammatory topical steroid was applied in 52%. In 16% of the eyes, penetrating keratoplasty (pKP) was performed. CONCLUSION: Diagnosis of filamentous fungi keratitis is often difficult or delayed. Outcomes can be poor even with intensive treatment because of high resistance to common antifungals. Access to natamycin 5% seems to lead to favourable outcomes in filamentous fungi keratitis.

Combating the causative agent of amoebic keratitis, Acanthamoeba castellanii, using Padina pavonica alcoholic extract: toxicokinetic and molecular docking approaches.

Natural products play a significant role in providing the current demand as antiparasitic agents, which offer an attractive approach for the discovery of novel drugs. The present study aimed to evaluate in vitro the potential impact of seaweed Padina pavonica (P. pavonica) extract in combating Acanthamoeba castellanii (A. castellanii). The phytochemical constituents of the extract were characterized by Gas chromatography-mass spectrometry. Six concentrations of the algal extract were used to evaluate its antiprotozoal activity at various incubation periods. Our results showed that the extract has significant inhibition against trophozoites and cysts viability, with complete inhibition at the high concentrations. The IC50 of P. pavonica extract was 4.56 and 4.89 µg/mL for trophozoites and cysts, respectively, at 24 h. Morphological alterations of A. castellanii trophozoites/cysts treated with the extract were assessed using inverted and scanning electron microscopes and showed severe damage features upon treatment with the extract at different concentrations. Molecular Docking of extracted compounds against Acanthamoeba cytochrome P450 monooxygenase (AcCYP51) was performed using Autodock vina1.5.6. A pharmacokinetic study using SwissADME was also conducted to investigate the potentiality of the identified bioactive compounds from Padina extract to be orally active drug candidates. In conclusion, this study highlights the in vitro amoebicidal activity of P. pavonica extract against A. castellanii adults and cysts and suggests potential AcCYP51 inhibition.

The incidence of severe complications in acanthamoeba keratitis: Qualitative and quantitative systematic assessment.

Acanthamoeba keratitis (AK) is a rare, sight-threating corneal infection. The disease is challenging to diagnose and treat, and the amoeba can rapidly encyst, persisting in the tissue and causing recurrences. Medical therapy is conventionally considered the first line treatment, but advanced cases could require more invasive treatments like a "chaud" corneal transplant. We review the incidence of severe complications in patients affected byAK. Of 439 reports screened, 158 met our inclusion criteria. Incidence of severe complications was low, with 2.21% patients developing perforation, 1% requiring evisceration/enucleation and less than 1% developing endophthalmitis. Corneal transplantation was required in 16.68% of the cases. According to our results, and considering the reported incidences of these complications in other infectious keratitis, AK patients have an overall low risk of developing perforation, endophthalmitis, and enucleation/evisceration. Nevertheless, data available in literature remain poor, and further randomized control trials are needed to confirm our findings.

Relapsed Mpox Keratitis, St. Louis, Missouri, USA.

We describe a case of a 46-year-old man in Missouri, USA, with newly diagnosed advanced HIV and PCR-confirmed mpox keratitis. The keratitis initially resolved after intravenous tecovirimat and penicillin for suspected ocular syphilis coinfection. Despite a confirmatory negative PCR, he developed relapsed, ipsilateral PCR-positive keratitis and severe ocular mpox requiring corneal transplant.

Benefits and risks of orthokeratology treatment: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis reviews the evidence for the risks and benefits associated with orthokeratology (OK) treatment compared with other methods of myopia control in children and adults. METHODS: A systematic search of Cochrane Central Register of Controlled Trials, Pubmed, Embase and Ovid was conducted from database inception to 22nd August 2021. Studies that reported on risks, visual and ocular biometric effects of OK in patients > 5 years of age with myopia (- 0.75 to - 6.00D) were included. Main outcomes are change in axial length and any adverse event. RESULTS: Fourty-five papers were included in this systematic review and meta-analysis. The quality of data was variable and of moderate certainty, and selection bias likely skewed the results towards a relative benefit for OK. The rate of axial elongation in children was lower for OK treatment compared to other treatment modalities at one year (MD - 0.16 mm, 95% CI - 0.25 to - 0.07). Rate of change in axial length in children rebounded after OK discontinuation compared to participants who continued treatment (MD 0.10 mm, 95% CI 0.06 to 0.14). Adults and children wearing OK were up to 3.79 times more likely to experience an adverse event when compared with conventional contact lenses (OR 3.79, 95% CI 1.24 to ll.), though this evidence base is underdeveloped and requires additional well-designed studies for substantial conclusions to be drawn. CONCLUSIONS: OK arrests myopia progression while in use, however, there remain unanswered questions about the optimal duration of treatment, discontinuation effects and long-term risk for adverse events.

Sodium Metabisulfite Inhibits Acanthamoeba Trophozoite Growth through Thiamine Depletion.

Acanthamoeba keratitis (AK) is a severe infection of the cornea. Prevention and treatment are difficult due to the inefficacy of currently available compounds. The impact of many commonly used compounds for routine examinations of Acanthamoeba is unexplored but might offer insight useful in combatting AK. In this study, we demonstrate that sodium metabisulfite, a common preservation constituent of eye care solutions, was found to be active against Acanthamoeba trophozoites at concentrations lower than that commonly found in eye drops (IC50 0.03 mg/mL). We demonstrate that sodium metabisulfite depletes thiamine from growth medium and that Acanthamoeba is a thiamine auxotroph, requiring thiamine salvage for growth. The inhibitory effects of sodium metabisulfite can be overcome by thiamine supplementation. These results are consistent with the lack of key enzymes for thiamine biosynthesis in the genome of Acanthamoeba, an area which might prove exploitable using new or existing compounds. Indeed, this study highlights sodium metabisulfite as a useful inhibitor of Acanthamoeba castellanii trophozoites in vitro and that it acts, at least in part, by limiting available thiamine.

Retinoic Acid Neutralizes the Effects of Herpes Simplex Virus Type 1-Infected Cell Protein 0 (ICP0) in Retinal Pigment Epithelial Cells.

BACKGROUND: Herpes simplex virus (HSV) infection of the cornea, uvea, and retina is the leading infectious cause of blindness worldwide. This study examined the effects of retinoic acid (RA) on the protein levels of interleukin (IL)-17A and IL-23 cytokines with known proinflammatory effects and toll-like receptor 3 (TLR3) messenger RNA (mRNA) expression in retinal pigment epithelial (ARPE-19) cells treated with HSV-1-infected cell protein 0 (ICP0). METHODOLOGY: We used 3-[4.5-dimethylthiazol-2-yl]-2.5-diphenyl tetrazolium bromide assay to calculate the half maximal inhibitory concentration (IC50) doses of RA and ICP0 in ARPE-19 cells. At the end of 24 hours, protein levels of IL-17A and IL-23 were analyzed using enzyme-linked immunosorbent assay. TLR3 mRNA expression levels were also calculated using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: RA administration decreased IL-17A levels, which were elevated by ICP0. The IL-23 levels were similar between the ICP0-treated and control groups, but the difference was significant between the ICP0-treated group and RA+ICP0 combination. These results showed that RA can significantly increase IL-23 levels in the presence of ICP0. Although ICP0 dramatically increased TLR3 mRNA expression compared with that in the control group, the RA+ICP0 combination returned TLR3 mRNA expression to a level similar to that in the control group (P = 0.419). CONCLUSIONS: RA may potentially neutralize HSV-1 ICP0 negative effects in ARPE-19 cells.

Bilateral Multiple Herpetic Epithelial Keratitis: A Case Report and Review of the Literature.

Herpetic epithelial keratitis is a viral infection of the cornea caused by the herpes simplex virus (HSV). It typically presents as a unilateral disease. Bilateral involvement is a rare manifestation of herpetic epithelial keratitis, accounting for only a small percentage of cases. By sharing this case, we aim to contribute to the understanding of bilateral herpetic epithelial keratitis and stimulate further research in this area to optimize patient care and outcomes A 13-year-old child, a known case of atopy, presented to the ophthalmology clinic with a complaint of pain, photophobia, and redness in the right eye (OD) for three days. The patient was diagnosed as a case of bilateral herpetic epithelial keratitis; he was started on moxifloxacin eye drops four times a day, Artelac (sodium hyaluronate) every two hours, carbomer HS, ganciclovir ointment five times per day. Bilateral herpetic epithelial keratitis is a rare manifestation of HSV infection, and its management poses unique challenges compared to unilateral disease. The diagnosis of bilateral herpetic epithelial keratitis is primarily based on clinical findings, including bilateral dendritic or geographic ulcers on the cornea. Fluorescein staining is a valuable tool for visualizing corneal ulcers. In our case, the presence of bilateral dendritic ulcers in the absence of significant anterior chamber inflammation supported the diagnosis of bilateral herpetic epithelial keratitis Despite the limited literature on bilateral herpetic epithelial keratitis, the principles of management remain consistent with those of unilateral disease. Early recognition, prompt initiation of antiviral therapy, and close follow-up are crucial for successful outcomes.

Utilizing confocal microscopy and topical natamycin in metarhizium keratitis of Caribbean origin.

A 32-year-old contact lens-wearing man with recent travel history to the Caribbean was referred for a corneal infiltrate in the left eye that worsened following 1-week of steroid-antibiotic therapy. Corneal cultures were obtained and sent to our facility's clinical microbiology laboratory for analysis. Same-day in vivo confocal microscopy revealed fungal elements. Nucleic acid sequencing performed on the isolated determined it to be a member of the entomopathogenic genus Metarhizium. Over the course of 3 months, the patient's corneal infiltrate ultimately resolved following topical natamycin 5 % therapy. This is the first reported case to have originated in the Caribbean and to utilize in vivo confocal microscopy to aid diagnosis. Our case also supports previous reports of success with natamycin therapy in treatment of Metarhizium sp. keratitis.

Post-refractive Surgery Dry Eye: A Systematic Review Exploring Pathophysiology, Risk Factors, and Novel Management Strategies.

Dry eye disease frequently manifests following corneal refractive procedures, significantly impacting patients' quality of life. This review systematically synthesizes current evidence on the pathophysiological mechanisms, risk factors, and therapeutic interventions for post-refractive surgery dry eye. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a systematic review of literature published until August 2023 was conducted, focusing on post-refractive surgery dry eye. Eighteen relevant studies were identified through screening and eligibility assessment. A qualitative synthesis of outcomes was performed using narrative and thematic analysis methods. Surgically induced neurotrophic deficiency, stemming from nerve transection, triggers a cascade of events including apoptosis, inflammation, and lacrimal dysfunction, ultimately leading to tear film instability. Risk factors such as female gender, thyroid eye disease, meibomian gland dysfunction, higher ablation depths, and the use of LASIK over surface ablation exacerbate the condition. While conventional treatments like artificial tears provide temporary relief, emerging interventions such as nerve growth factors, matrix metalloproteinase inhibitors, serum eye drops, and specialized contact lenses show promise in promoting nerve regeneration and epithelial healing. Strategies such as customized ablation profiles, smaller optical zones, and nerve-sparing techniques like small incision lenticule extraction demonstrate potential advantages. A multifaceted therapeutic approach targeting neuroprotection, anti-inflammatory mechanisms, and tear film stabilization is imperative for effectively managing post-refractive surgery dry eye. Future research should focus on evaluating prognostic biomarkers, exploring precision medicine approaches, and investigating neuroprotective adjuvants to further enhance treatment outcomes.

Ocular Leptospirosis: Report of a Challenging Diagnosis.

PURPOSE: To report a challenging case of serologically confirmed posterior uveitis due to leptospirosis. METHODS: Review of medical records. RESULTS: Thirteen-year-old boy presented focal necrotizing retinochoroiditis after flood exposure. Laboratory work-up confirmed leptospirosis infection and proper antibiotic treatment was done. The patient evolved well. but during late follow-up he developed nummular keratitis. CONCLUSION: Leptospirosis is a possible etiology of necrotizing posterior uveitis. The use of antimicrobial therapy is controversial but was used in this case, in association with corticosteroids, leading to resolution of retinal inflammation. Despite treatment, the patient developed late corneal opacities, which did not lead to visual impairment.

Fungal Keratitis, Epidemiology and Outcomes in a Tropical Australian Setting.

BACKGROUND: Fungal keratitis is an ophthalmic emergency that can cause visual impairment and blindness. We reviewed the epidemiology and clinical features of fungal keratitis in a tropical Australian setting. OBJECTIVES: To document the clinical and microbiological characteristics of fungal keratitis in an Australian tropical setting. METHODS: A retrospective cohort study of patients with fungal keratitis from October 2014 to December 2022 was conducted at Royal Darwin Hospital, Northern Territory, Australia. We reviewed all patients with culture-proven fungal keratitis and their outcomes. RESULTS: There were 31 patients identified. Aboriginal and Torres Strait Islander (ATSI) patients were of a significantly younger median age (28 years) compared to non-ATSI patients (42 years), and they also presented later to health care. Contact lens use and ocular trauma were the most common predisposing factors. Most patients presented with a corneal infiltrate and corneal epithelial defect, and the central visual axis was affected in 54% of patients. Curvularia spp. and Fusarium spp. were the commonest causative fungi (39% and 30% respectively). CONCLUSIONS: Our series is different and reveals a wider range of fungal species identified over the 7 years of the study, in particular, a range of Curvularia spp. were detected. Access to eye health services in rural and remote settings is important, particularly for ATSI patients, as morbidity remains high.

The History of Nerve Growth Factor: From Molecule to Drug.

Nerve growth factor (NGF), the first neurotrophin to be discovered, has a long and eventful research journey with a series of turning points, setbacks, and achievements. Since the groundbreaking investigations led by Nobel Prize winner Rita Levi-Montalcini, advancements in the comprehension of NGF's functions have revolutionized the field of neuroscience, offering new insights and opportunities for therapeutic innovation. However, the clinical application of NGF has historically been hindered by challenges in determining appropriate dosing, administration strategies, and complications related to the production process. Recent advances in the production and scientific knowledge of recombinant NGF have enabled its clinical development, and in 2018, the United States Food and Drug Administration approved cenegermin-bkbj, a recombinant human NGF, for the treatment of all stages of neurotrophic keratitis. This review traces the evolutionary path that transformed NGF from a biological molecule into a novel therapy with potential research applications beyond the eye. Special emphasis is put on the studies that advanced NGF from discovery to the first medicinal product approved to treat a human disease.

The Topical Novel Formulations of Interferon α-2в Effectively Inhibit HSV-1 Keratitis in the Rabbit Eye Model and HSV-2 Genital Herpes in Mice.

Herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) are widespread human pathogens that establish chronic latent infections leading to recurrent episodes. Current treatments are limited, necessitating the development of novel antiviral strategies. This study aimed to assess the antiviral efficacy of novel topical formulations containing interferon alpha-2b (IFN α-2b) against HSV-1 and HSV-2. The formulations, Oftalmoferon® forte (eye drops) and Interferon Vaginal Tablets, demonstrated potent antiviral effects against HSV-1 and HSV-2 in Vero cells, respectively, with concentration-dependent inhibition of viral replication. Subsequently, their efficacy was tested in animal models: HSV-1 keratitis in the rabbit eye model and HSV-2 genital herpes in mice. Oftalmoferon® forte effectively treated HSV-1 keratitis, reducing clinical symptoms and ulcerations compared to virus control. Interferon Vaginal Tablets showed promising results in controlling HSV-2 genital herpes in mice, improving survival rates, reducing clinical signs, weight loss and viral replication. The novel IFN α-2b formulations exhibited significant antiviral activity against HSV infections in cell culture and animal models. These findings suggest the potential of these formulations as alternative treatments for HSV infections, particularly in cases resistant to current therapies. Further studies are warranted to optimize treatment regimens and assess clinical efficacy in humans.

Clinical efficacy of cyclosporin and natamycin for fungal keratitis.

Objectives: To investigate the clinical efficacy of cyclosporin (CYSP) and natamycin (NAT) as a combination therapy in patients with fungal keratitis. Methods: This is a retrospective study. A total of 64 patients (64 eyes) with fungal keratitis treated by Baoding No.1 Central Hospital between December 2018 and May 2022 according to their treatment methods were divided into a monotherapy (MT) group receiving NAT eye drops solely and a combination therapy (CT) group given CYSP eye drops in addition to the exact treatment provided for the MT group. The clinical responses, visual acuity changes, severity of eye symptoms, and adverse reactions were compared between the two groups. Results: At two and four weeks post-treatment, the CT group had an overall response rate (ORR) significantly higher than that of the MT group (P< 0.05, respectively); both groups showed improved visual acuity and eye symptoms compared with the pre-treatment condition, and these improvements were more pronounced in the CT group (P < 0.05, respectively). Compared with the MT group, the CT group experienced a significantly shorter duration of eye symptoms (P < 0.05). The adverse reaction rate(ARR) was 9.38% in the CT group and 6.25% in the MT group, and the difference was not significant (P > 0.05). Conclusion: Using CYSP and NAT as a combination therapy for fungal keratitis can substantially heighten the therapeutic effects, promote visual acuity recovery, and induce rapid remission of eye symptoms without increasing the risk of adverse reactions.