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Keywords = recalcitrant keratitis

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21 pages, 835 KB  
Review
Emerging Ocular Pathogen Resistance and Clinically Used Solutions: A Problem That Is More than Meets the Eye
by Marusha Ather and Christopher D. Conrady
Pharmaceuticals 2026, 19(1), 31; https://doi.org/10.3390/ph19010031 - 23 Dec 2025
Viewed by 344
Abstract
Background/Objectives: Antimicrobial resistance (AMR) in ocular infections has become a serious concern with major implications for vision preservation. Bacterial AMR contributed to 4.71 million deaths worldwide in 2021, and ophthalmology mirrors these trends with multidrug resistance rates as high as 66% documented in [...] Read more.
Background/Objectives: Antimicrobial resistance (AMR) in ocular infections has become a serious concern with major implications for vision preservation. Bacterial AMR contributed to 4.71 million deaths worldwide in 2021, and ophthalmology mirrors these trends with multidrug resistance rates as high as 66% documented in some regions and persistently high methicillin resistance among common ocular pathogens. Across regions and care settings, traditional empiric therapies are losing effectiveness against an expanding range of pathogens, resulting in slower recovery, more complications, and, in many cases, permanent vision loss. This review aims to synthesize recent clinical, microbiologic, and pharmacologic evidence on ocular AMR, focusing on recent studies to capture current resistance patterns, therapeutic challenges, and evolving management strategies. Methods: Most included papers were published between 2020 and 2025, with additional foundational studies referenced where appropriate. Reports and systematic reviews addressing bacterial, viral, fungal, and parasitic ocular pathogens were evaluated to characterize current resistance mechanisms and management strategies across ocular pathogens. Results: The eye’s anatomic and physiologic barriers limit drug penetration, often promoting resistance and reducing therapeutic efficacy. Resistance mechanisms vary by pathogens; Pseudomonas keratitis is driven mainly by efflux pumps and biofilm formation, while CMV retinitis’ mutations in UL97 and UL54 are linked with clinical failure, and in MRSA associated Staphylococcus keratitis, the presence of mecA necessitates vancomycin-based therapy across bacterial, viral, fungal, and parasitic infections, with mechanisms such as β-lactamase production, efflux pump overexpression, target-site mutation, and biofilm formation contributing to poor response to standard therapy. MDR Pseudomonas keratitis remains the leading cause of rapidly progressive corneal infection with high risk of perforation and vision loss, while resistant CMV retinitis continues to threaten sight in immunocompromised patients despite antiviral advances. MDR organisms are recalcitrant to treatment and may lead to longer treatment courses and potentially worse outcomes and are discussed in detail within the manuscript. Conclusions: Ocular AMR represents an urgent and expanding clinical challenge. This review centers on the two most encountered multidrug-resistant organisms and their corresponding ocular sites, Pseudomonas aeruginosa (anterior segment) and CMV (posterior segment), while contextualizing them within the broader spectrum of resistant bacterial, viral, fungal, and parasitic pathogens. Despite growing awareness of AMR in ophthalmology, comprehensive surveillance data and longitudinal epidemiologic studies remain limited, making it difficult to track evolving resistance trends or guide region-specific therapy. Preserving vision in the AMR era will require faster diagnostics, improved ocular drug-delivery systems, and pathogen-specific therapies. Full article
(This article belongs to the Section Medicinal Chemistry)
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8 pages, 958 KB  
Case Report
Efficacy of the Combined Intrastromal Injection of Voriconazole and Amphotericin B in Recalcitrant Fungal Keratitis
by Antonio Moramarco, Arianna Grendele, Danilo Iannetta, Simone Ottoboni, Giulia Gregori, Natalie di Geronimo, Margherita Ortalli, Tiziana Lazzarotto and Luigi Fontana
Microorganisms 2024, 12(5), 922; https://doi.org/10.3390/microorganisms12050922 - 30 Apr 2024
Cited by 6 | Viewed by 3048
Abstract
This study aims to report the efficacy of a combined intrastromal injection in optimizing the outcome of severe mycotic keratitis. Herein, we report a case series of 20 consecutive patients with positive fungal cultures not responding to topical antifungal treatment. Patients received cycles [...] Read more.
This study aims to report the efficacy of a combined intrastromal injection in optimizing the outcome of severe mycotic keratitis. Herein, we report a case series of 20 consecutive patients with positive fungal cultures not responding to topical antifungal treatment. Patients received cycles of intrastromal injections of voriconazole (50 µg/0.1 mL) and amphotericin B (2.5 µg/0.1 mL); all patients continued their topical antifungal therapy. The organisms isolated were Fusarium (n = 5), Aspergillus (n = 4), Candida (n = 4), Rhodotorula (n = 2), Penicillium (n = 2), Alternaria (n = 1), Bipolaris (n = 1), and Curvularia (n = 1). The size of the infiltrate varied from 6.5 to 1.5 mm. At presentation, the best corrected visual acuity (BCVA, namely, the best visual acuity achieved with glasses, if needed) was less than 20/400 in all patients, improving to better than 20/400 in eleven patients. Seven patients required surgical intervention; four of them underwent penetrating keratoplasty (PK) à chaud one month after the first intrastromal injection. Patients who underwent surgery achieved a BCVA of 20/40 or better. Combined intrastromal injections before therapeutic penetrating keratoplasty (TPK) effectively reduced ulcer size and graft diameter, preventing infection recurrence. Our results highlight the efficacy of combined intrastromal injections in optimizing outcomes for severe mycotic keratitis undergoing TPK. Full article
(This article belongs to the Special Issue Ocular Infections and Microbiota in Health and Disease 2.0)
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15 pages, 1138 KB  
Review
New Frontiers in Acanthamoeba Keratitis Diagnosis and Management
by Omar Shareef, Sana Shareef and Hajirah N. Saeed
Biology 2023, 12(12), 1489; https://doi.org/10.3390/biology12121489 - 5 Dec 2023
Cited by 10 | Viewed by 5529
Abstract
Acanthamoeba Keratitis (AK) is a severe corneal infection caused by the Acanthamoeba species of protozoa, potentially leading to permanent vision loss. AK requires prompt diagnosis and treatment to mitigate vision impairment. Diagnosing AK is challenging due to overlapping symptoms with other corneal infections, [...] Read more.
Acanthamoeba Keratitis (AK) is a severe corneal infection caused by the Acanthamoeba species of protozoa, potentially leading to permanent vision loss. AK requires prompt diagnosis and treatment to mitigate vision impairment. Diagnosing AK is challenging due to overlapping symptoms with other corneal infections, and treatment is made complicated by the organism’s dual forms and increasing virulence, and delayed diagnosis. In this review, new approaches in AK diagnostics and treatment within the last 5 years are discussed. The English-language literature on PubMed was reviewed using the search terms “Acanthamoeba keratitis” and “diagnosis” or “treatment” and focused on studies published between 2018 and 2023. Two hundred sixty-five publications were initially identified, of which eighty-seven met inclusion and exclusion criteria. This review highlights the findings of these studies. Notably, advances in PCR-based diagnostics may be clinically implemented in the near future, while antibody-based and machine-learning approaches hold promise for the future. Single-drug topical therapy (0.08% PHMB) may improve drug access and efficacy, while oral medication (i.e., miltefosine) may offer a treatment option for patients with recalcitrant disease. Full article
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13 pages, 291 KB  
Review
Intrastromal Injections in the Management of Infectious Keratitis
by Mihail Zemba, Madalina Radu, Sinziana Istrate, Otilia-Maria Dumitrescu, Mihai Alexandru Ionescu, Andrei Vatafu and Ileana Ramona Barac
Pharmaceutics 2023, 15(4), 1091; https://doi.org/10.3390/pharmaceutics15041091 - 29 Mar 2023
Cited by 12 | Viewed by 4304
Abstract
Infectious keratitis is a major global cause of vision loss and blindness. Prompt diagnosis and targeted antibiotic treatment are crucial for managing the condition. Topical antimicrobials are the most effective therapy for bacterial keratitis, but they can lead to unsatisfactory results due to [...] Read more.
Infectious keratitis is a major global cause of vision loss and blindness. Prompt diagnosis and targeted antibiotic treatment are crucial for managing the condition. Topical antimicrobials are the most effective therapy for bacterial keratitis, but they can lead to unsatisfactory results due to ocular perforation, scarring, and melting. Intrastromal injection is a newer technique for delivering antimicrobials directly to the site of infection and has been successful in treating severe, treatment-resistant infectious keratitis, especially when surgery is not recommended. In cases where deep stromal disease is resistant to topical treatment, intrastromal antimicrobial injections may be necessary to achieve higher drug concentration at the infection site. However, the use of intrastromal antibiotics is limited, as topical antibacterial agents have better penetration than antifungal agents. Bacterial and fungal keratitis have been extensively researched for intrastromal medication injections, while there is limited evidence for viral keratitis. This review emphasizes the potential of intrastromal antimicrobial injections as an alternative for managing severe refractory infectious keratitis. The technique offers direct targeting of the infection site and faster resolution in some cases compared to topical therapy. However, further research is needed to determine the safest antimicrobials options, minimal effective doses, and concentrations for various pathogens. Intrastromal injections may serve as a non-surgical treatment option in high-risk cases, with benefits including direct drug delivery and reduced epithelial toxicity. Despite promising findings, more studies are required to confirm the safety and efficacy of this approach. Full article
(This article belongs to the Special Issue Recent Advances in Prevention and Treatment of Infectious Diseases)
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