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PubMed2026

Diagnostic Accuracy of a CRISPR-Based Assay in Smear- and Culture-Negative Fungal Keratitis.

IMPORTANCE: Diagnosing fungal keratitis (FK) in patients with negative smear and culture results remains clinically challenging, highlighting the need for alternative diagnostic approaches. OBJECTIVE: To determine the diagnostic accuracy of the clustered regularly interspaced short palindromic repeats (CRISPR)-based Rapid Identification of Mycoses using CRISPR (RID-MyC) assay for detecting FK in patients with negative smear and culture results using in vivo confocal microscopy (IVCM) as the reference standard. DESIGN, SETTING, AND PARTICIPANTS: This prospective diagnostic accuracy study was conducted from December 2024 to March 2025 at Aravind Eye Hospital, a tertiary ophthalmology referral hospital in Coimbatore, India. Consecutive patients clinically suspected to have microbial keratitis with negative smear and culture results were eligible for inclusion. Data were analyzed from March 2025 to June 2025. INTERVENTIONS: All included participants underwent corneal scraping for RID-MyC assay and imaging by IVCM. MAIN OUTCOMES AND MEASURES: The primary outcomes were sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic concordance of the RID-MyC assay compared with IVCM results. RESULTS: Of 245 consecutive patients clinically suspected to have microbial keratitis, 82 were smear negative. After exclusions due to contraindications or positive subsequent cultures, 41 patients with smear- and culture-negative results were ultimately included in the final analysis. Of these 41 patients (mean [SD] age, 51.0 [14.6] years; 21 [51.2%] women), RID-MyC demonstrated sensitivity of 82.1% (95% CI, 63%-94%) and specificity of 76.9% (95% CI, 46%-95%). Positive predictive value was 88.5% (95% CI, 74%-95%) and negative predictive value was 66.7% (95% CI, 46%-82%). Concordance between RID-MyC and IVCM was observed in 33 cases (80.5%). Notably, prior antifungal treatment was most frequent (4 of 5 [80%]) among patients with positive IVCM but negative RID-MyC results. Conversely, all patients (3 of 3 [100%]) with negative IVCM but positive RID-MyC findings had smaller, peripheral, or paracentral lesions. CONCLUSIONS AND RELEVANCE: In this diagnostic study, in patients with smear- and culture-negative FK, the RID-MyC assay showed good diagnostic accuracy comparable with IVCM and was feasible in all cases, including those in whom imaging was not possible. With its rapid turnaround and minimal equipment needs, RID-MyC may serve as a practical adjunct to conventional diagnostics, particularly in high-burden, resource-limited settings where IVCM is unavailable or contraindicated.

Humans↗
PubMed1979

Vitrectomy in experimental endophthalmitis: Part I-Fungal infection.

In studying the dose-related ocular toxicity of amphotericin B in vitrectomized eyes, up to 5 micrograms/0.1 ml concentration of amphotericin C was nontoxic to the ocular structure when injected in the anterior part of the vitreous cavity. Intravitreal injection of 2.5 micrograms of amphotericin B halted fungal endophthalmitis, which was experimentally induced in rabbit eyes, even after 16 days of infection. Combined treatment of vitrectomy and intravitreal injection of amphotericin B not only cured the fungal endophthalmitis but it also cleared the ocular media from opacities.

Amphotericin B↗
PubMed2026

Impact of Contact Lens Use on Clinical Profile and Outcomes of Fungal Keratitis: An 8-Year Retrospective Study.

PURPOSE: To compare clinical characteristics, microbiological profiles, treatment strategies, and outcomes between contact lens-associated (CL) and noncontact lens-associated (non-CL) fungal keratitis. DESIGN: Retrospective, comparative clinical cohort study. METHODS: A review of culture-proven fungal keratitis treated at a tertiary referral center between 2018 and 2025 was conducted. Cases were categorized as CL or non-CL-associated. Demographic, clinical, microbiological, treatment, and outcome data were analyzed and compared between groups. RESULTS: Thirty-seven eyes were included, comprising 16 CL and 21 non-CL cases. CL users presented earlier than non-CL patients (median 7 vs 14 days, P = .007) and had fewer associated ocular risk factors (31% vs 81%, P = .001). Baseline visual acuity and infiltrate size did not differ significantly between groups. Candida species were isolated in 21% cases, Fusarium in 16% and Aspergillus in 8%. Fusarium (19% vs 13%) and Candida (24% vs 19%) infections were slightly more frequent in non-CL cases. Overall, filamentous fungi were the predominant organism group. Topical voriconazole was the most frequently used antifungal agent (78%). All CL-associated cases resolved with medical therapy alone, with a median time to resolution of 38 days (IQR 22-58). In contrast, 76% of non-CL cases resolved medically (median 42 days, IQR 32-76), while 23% required therapeutic keratoplasty (P = .04). Final visual acuity was comparable between groups (logMAR 0.2 vs 0.5, P = .56). CONCLUSION: Contact lens-associated fungal keratitis is characterized by earlier presentation and fewer underlying ocular comorbidities, with favorable outcomes achieved through medical therapy alone. Despite similar microbiological profiles and treatment approaches, noncontact lens-associated fungal keratitis more frequently follows a complicated course requiring surgical intervention.

Humans↗
PubMed1979

Fusarium oxysporum endophthalmitis.

A 27-year-old man sustained a thorn injury to his left eye and a culture-proven Fusarium oxysporum endophthalmitis developed. This was successfully treated with a vitrectomy, intravitreal and intravenous amphotericin B, and oral flucytosine. The patient maintains 20/20 vision at this time in his left eye. We recommend combined therapy for this filamentous fungal infection.

Adult↗
PubMed1978

Aspergillus flavus keratitis.

Corneal infection due to the species Aspergillus flavus is rare and often destructive. This report describes a case of Aspergillus flavus corneal ulcer that failed to respond to amphotericin B, pimaricin, and clotrimazole. The eye subsequently became phthisical. The rational approach to the management of fungal corneal infection is to culture or perform sensitivity tests on the isolated organism. Early surgical intervention should be done if the infection fails to respond to medical treatment, and if the disease process extends deep into the stromal tissue and anterior chamber. Fungal malignant glaucoma requires excisional keratoplasty, lens extraction, and anterior vitrectomy.

Aspergillosis↗
PubMed1979

Orbitofacial mucormycosis with unusual pathological features.

A 52-year-old man with mild diabetes and acute stem cell leukaemia developed an orbitofacial mucormycosis. Cultures showed the fungus to be Rhizopus oryzae. Vigorous treatment with amphotericin B and other bactericidal and bacteriostatic antibiotics for a concurrent sepsis failed to suppress the infections, and the patient died. On post-mortem examination characteristic haematoxylin-staining, broad, aseptate fungal hyphae were found in the right eye, orbit, and lung. A striking and unusual feature of this case is the presence of brightly birefringent crystals within the severely degenerated eye. These were found by histochemical staining and x-ray diffraction studies to be calcium salts of fatty acids, apparently liberated from necrotic adipose tissue of the orbit.

Calcinosis↗
PubMed1979

[Orbital aspergillosis--a contribution to its diagnosis and treatment (author's transl)].

In connection with a case report, the mycological diagnosis and treatment of orbital aspergillosis are reviewed. In a 59-year-old male patient an exophthalmus on the right side could be diagnosed as aspergillosis spreading from the corresponding sinus maxillaris into retro- and peri-orbicular regions, after other causes had been excluded by differential diagnosis. In a biopsy specimen from the retrobulbar tumor, a fungal granuloma was found which, histologically and by isolation of the fungus, could be identified as an infection by A. fumigatus. Because of the good visus of the right eye, no exenteratio orbitae but an enoral revision of the sinus maxillaris, ethmoidal bone, and bottom of orbita was performed.--By infusions of amphotericin B and local washings with pimaricin (natamycin) in the sinus maxillaris and the region of the operation, a complete healing of the mycotic process was achieved.--Since 1 1/2 years, the patient has not had a relaps. This success of therapy was possible by exemplary cooperation of otorhinolaryngologists, ophthalmologists, pathologists and microbiologists.--In view of the prophylaxis of such infections, recent contributions to the epidemiology of aspergillosis are discussed.

Amphotericin B↗
PubMed1979

Amphotericin B methyl ester: evaluation for intravitreous use in experimental fungal endophthalmitis.

Amphotericin B methyl ester, a water-soluble derivative of amphotericin B, is an experimental antifungal agent. Intravitreous injection of 5 and 10 micrograms of amphotericin B methyl ester in the normal rabbit eye does not cause toxic changes that can be detected clinically, microscopically, or by electroretinography. A single intravitreous injection of 5 micrograms was effective in reversing the course of exogenous Candida fungal endophthalmitis when administered within five days after inoculation of the infecting organism.

Amphotericin B↗
PubMed1978

Prevention of surface bacterial contamination of donor corneas.

A simple method has been developed to reduce contamination in postmortem donor human eyes in anticipation of corneal transplantation. In vivo investigation of albino rabbits demonstrates that vigorous saline solution irrigation is extremely effective in decreasing the surface bacterial counts of the postmortem eye. In vitro and in vivo studies show that Neosporin kills bacteria at room temperature and further show that a tenfold increase in the thimerosal concentration of the Neosporin will kill fungus. Postmortem eyes contaminated by pathogenic organisms can be effectively cleaned by a combination of saline solution irrigation and the new Neosporin-thimerosal solution. No substantial damage of the donor tissue was noted by scanning electron microscopy. Human eyes cultured before this procedure were all contaminated, but after cleansing and immersion, no bacterial or fungal growth occurred.

Animals↗
PubMed1978

Ocular sporotrichosis mimicking mucormycosis in a diabetic.

Primary sporotrichosis of the eye is very rare; most infections are limited to the conjunctiva or adnexa. We report a case of Sporothrix endophthalmitis associated with necrotizing ethmoid sinusitis developing in a young diabetic man with ketoacidosis. The infection clinically resembled rhino-ophthalmic mycormycosis. Cure followed evisceration and an abbreviated course (215 mg) of amphotericin B. Sporothrix must now be regarded as another fungal agent capable of causing primary rhino-ophthalmic infection similar to Mucor.

Adult↗
PubMed1979

Fungal invasion of a therapeutic soft contact lens and cornea.

A fungal corneal infection occurred in a 66-year-old man who wore a therapeutic soft contact lens for 12 months during treatment for a metaherpetic corneal epithelial erosion. The infection was documented by finding positive cultures from both the contact lens and the cornea, and histologic evidence of fungal infiltration of the therapeutic soft lens. The fungus was identified as Cephalosporium acremonium. Pathogenic fungal invasion of soft lenses is unusual. Corneal infections associated with such conditions are rare. This case demonstrates histologically, a pathogenic fungal corneal infection arising from therapeutic contact lens wear. Factors that may influence soft lens infiltration by fungi are: (1) enzymatic activity produced by the fungus, and (2) lens material properties which provide a matrix and a nutrient source for fungal growth. Continuous-wear soft contact lens treatment with topical steroid and prophylactic antibiotics used in combination in an already compromised cornea were thought to be responsible in an already compromised cornea were thought to be responsible for this complication. A therapeutic penetrating keratoplasty was performed when the infection and its accompanying inflammation became clinically unresponsive to multifold therapy, and a corneal perforation was imminent. The eye was salvaged with a resulting clear graft and stable intraocular pressures.

Acremonium↗
PubMed1979

Laboratory isolation techniques in human and experimental fungal infections.

In laboratory experience with a heterogenous group of 26 human ocular fungal isolates, brain-heart infusion broth proved to be the most useful medium for isolation. Although Candida and Fusarium species grew out within four days of inoculation, one fourth of the cultures did not become positive until 14 to 19 days had elapsed. In an animal model of endophthalmitis due to F. solani infection, brain-heart infusion broth again was the most useful. The highly nutritious media used for fungal isolation are prone to contamination by organisms that are difficult to distinguish from true pathogens. Sham culture studies demonstrated that this contamination can easily occur during the process of sampling the lesion and inoculating the media.

Animals↗
PubMed1977

Immunosuppression and eye disease. First Vail lecture.

Several viral, fungal, and protozoal diseases of the eye are significantly associated with immunologic deficiencies. Of the viral agents, cytomegaly and herpes simplex and zoster cause a discrete necrotizing retinopathy that has the characteristics of vascular occlusion. Measles may result in a delayed retinopathy that is predominantly macular and associated with subacute progressive encephalopathy. Of the fungal agents, Candida and Aspergillus are apt to involve the eye, beginning as choroidal lesions with extension forward to involve the pigment epithelium and retina secondarily. Mucor and Cryptococcus are less common. Toxoplasmosis is the one ocular protozoal disease whose incidence is increased by immunosuppression, and, like the viral diseases, is characterized by a discrete necrotizing retinopathy and probably results from activation of dormant organisms in the retina. Autoimmunity undoubtedly plays an important role in eye disease but its ocular pathogenesis is obscure.

Adult↗
PubMedDate not supplied

Ocular and orbital phycomycosis.

Cerebro-rhino-orbital phycomycosis (CROP) occurs predominantly in individuals with diabetes mellitus in a state of metabolic acidosis. Other forms of metabolic acidosis, especially in infants, may predispose to phycomycotic infections. CROP has also been reported in patients with leukemia or lymphoma. CROP usually begins in the palate or paranasal sinuses and rapidly spreads to the orbital contents. Proptosis, loss of vision, and ophthalmoplegia occur and death from cerebral involvement commonly ensues. The fungus tends to invade arteries and cause thrombosis and tissue infarction. Rhizopus is the most commonly isolated genus in CROP, accounting for almost all cases. The diagnosis can be strongly suspected by the characteristic clinical manifestations. Therapy includes treatment of the underlying disease, surgical excision of the necrotic tissue containing fungal elements and the systemic administration of amphotericin-B. The effect of treatment has improved since the disease was first described, but the condition still has a high mortality, especially if it is not diagnosed early.

Adolescent↗