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16 pages, 4017 KB  
Article
Evaluation of Antimicrobial Peptide–Antibiotic Combination Treatment for Tackling Ocular and Systemic Staphylococcus aureus Infections
by Eman Khalid Barahim, Ella P. Smith, Sheau Ting Yong, Thet Tun Aung, Rajamani Lakshminarayanan, Imran Mohammed, Harminder S. Dua, Graham R. Wallace, Jose R. Hombrebueno, Saaeha Rauz and Darren S. J. Ting
Int. J. Mol. Sci. 2026, 27(12), 5573; https://doi.org/10.3390/ijms27125573 - 20 Jun 2026
Viewed by 341
Abstract
Staphylococcus aureus is a leading cause of bacterial keratitis and antimicrobial resistance-associated death globally. This study aimed to evaluate the efficacy of CaD23, a human-derived hybrid antimicrobial peptide (AMP), in combination with antibiotics in treating S. aureus infections. The efficacy of CaD23 and [...] Read more.
Staphylococcus aureus is a leading cause of bacterial keratitis and antimicrobial resistance-associated death globally. This study aimed to evaluate the efficacy of CaD23, a human-derived hybrid antimicrobial peptide (AMP), in combination with antibiotics in treating S. aureus infections. The efficacy of CaD23 and six medically important antibiotics (amikacin, cefuroxime, chloramphenicol, fosfomycin, vancomycin and levofloxacin) was examined against six strains of methicillin-sensitive and methicillin-resistant S. aureus using a minimum inhibitory concentration (MIC) assay. CaD23–antibiotic interactions were evaluated using checkerboard and time–kill kinetics assays. 3,3′-dipropylthiadicarbocyanine iodide (DiSC3,5) cytoplasmic membrane depolarisation assay was performed to examine the mechanism of action. Overall, CaD23 exhibited good efficacy against all MSSA and MRSA (MIC = 16–32 μg/mL [6.7–13.3 μM]). Of 20 peptide–antibiotic–organism combinations, 19 (95%) combinations demonstrated positive interactions, with six (31.6%) and 13 (68.4%) exhibiting synergistic (FICI = 0.293–0.412) and additive effects (FICI = 0.521–0.890), respectively. CaD23 was able to achieve complete bacterial eradication significantly faster than cefuroxime and levofloxacin (15 min vs. 8–24 h). When used at a sub-MIC concentration, CaD23 could accelerate the killing of S. aureus of cefuroxime from 8–24 h to within 1 h and enhance the activity of levofloxacin by 90%. CaD23 was shown to rapidly depolarise the inner membrane of S. aureus within seconds of the treatment. In conclusion, CaD23–antibiotic combination therapy serves as a useful strategy for tackling drug-resistant ocular and systemic S. aureus infections. Full article
(This article belongs to the Special Issue Antimicrobial and Antiviral Peptides: 2nd Edition)
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11 pages, 1157 KB  
Article
Analysis of Infectious Keratitis Isolates and Antimicrobial Resistance: An 8-Year Retrospective Study in Southern China
by Jiayi Zheng, Jingyu Liao, Xinlei Zhao, Huijing Huang, Kaili Wu and Fang Duan
Antibiotics 2026, 15(6), 615; https://doi.org/10.3390/antibiotics15060615 - 17 Jun 2026
Viewed by 282
Abstract
Objectives: To characterise the bacterial and fungal spectrum of infectious keratitis (IK) in southern China and to evaluate changes in the bacterial profiles and antimicrobial resistance (AMR) over an 8-year period (2017–2024). Methods: This retrospective study included patients with culture-positive IK treated between [...] Read more.
Objectives: To characterise the bacterial and fungal spectrum of infectious keratitis (IK) in southern China and to evaluate changes in the bacterial profiles and antimicrobial resistance (AMR) over an 8-year period (2017–2024). Methods: This retrospective study included patients with culture-positive IK treated between 2017 and 2024. Corneal scrapings were obtained for microbiological culture and pathogen identification. Antimicrobial susceptibility testing was performed for all bacterial isolates. Microbial distribution and in vitro antibiotic susceptibility were analysed. Results: A total of 2785 microbial isolates were recovered from 2741 patients. Overall, fungal isolates predominated (59.6%), exhibiting a distinct seasonal distribution, with Fusarium (40.2%) and Aspergillus (14.3%) being the most common genera. Among bacterial isolates, Gram-positive organisms were predominant (63.6%). The most frequently identified Gram-positive organisms were coagulase-negative staphylococci (CNS; 34.9%), while Pseudomonas (18.9%) was the most common Gram-negative pathogen. Over the study period, an increase in the proportions of CNS (p < 0.001) and Serratia was observed (p = 0.017), alongside a decline in Pseudomonas (p = 0.009) and Kocuria (p < 0.001). Resistance among Gram-positive isolates increased for penicillin (from 62.3% to 74.4%; p = 0.002) and levofloxacin (from 26.4% to 46.9%; p < 0.001), whereas Gram-negative resistance generally declined. Conclusions: IK in southern China is characterised by persistent fungal predominance and evolving bacterial composition. AMR patterns differ between Gram-positive and Gram-negative organisms, reflecting both shifts in pathogen distribution and species-specific resistance changes, highlighting the importance of continued regional surveillance to guide empirical therapy. Full article
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16 pages, 1420 KB  
Article
Infectious Keratitis: A Retrospective Analysis of a Tertiary Care Center
by Jana Schaetzel, Taos Batal, Marcus Walckling and Thomas A. Fuchsluger
J. Clin. Med. 2026, 15(11), 4249; https://doi.org/10.3390/jcm15114249 - 30 May 2026
Viewed by 393
Abstract
Background/Objectives: Infectious keratitis is a vision-threatening disease. Its prevalence and specific pathogens vary by geographic location. This study characterizes risk profiles, clinical manifestations, and treatment outcomes for various pathogens in the Rostock area. Results: The study included 65 patients (38 viral, 14 bacterial, [...] Read more.
Background/Objectives: Infectious keratitis is a vision-threatening disease. Its prevalence and specific pathogens vary by geographic location. This study characterizes risk profiles, clinical manifestations, and treatment outcomes for various pathogens in the Rostock area. Results: The study included 65 patients (38 viral, 14 bacterial, seven fungal, six parasitic) with a minimum follow-up of three months. The cohort had a mean age of 59 ± 19 years, with 49% female and 51% male participants. All groups showed significant improvement in visual acuity (viral −0.3 logMAR, p = 0.011; parasitic −0.8 logMAR, p = 0.043; fungal −0.9 logMAR, p = 0.018; Wilcoxon). Only the bacterial group did not reach statistical significance (−0.3 logMAR, p = 0.169; Wilcoxon). Final visual acuity did not differ significantly between medical and surgical treatments. Conclusions: No treatment modality (medical vs. surgical) showed superiority regarding visual outcome across pathogen groups. Early diagnosis and prompt therapy initiation are essential to improve visual prognosis and reduce complications. Full article
(This article belongs to the Special Issue Current Concepts and Updates in Eye Diseases)
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12 pages, 9134 KB  
Article
Investigating the Effects of UVC Exposure at the Limbus
by Bethany P. Torr, Jennifer P. Craig, Simon J. Dean, Trevor Sherwin and Sanjay Marasini
Cells 2026, 15(11), 967; https://doi.org/10.3390/cells15110967 - 23 May 2026
Viewed by 293
Abstract
Purpose: Preclinical studies report low-intensity ultraviolet C (UVC) light to be safe and effective in treating murine bacterial keratitis, however, limbal impacts of UVC have yet to be investigated directly. This study evaluated the depth and density of UVC-induced DNA damage in the [...] Read more.
Purpose: Preclinical studies report low-intensity ultraviolet C (UVC) light to be safe and effective in treating murine bacterial keratitis, however, limbal impacts of UVC have yet to be investigated directly. This study evaluated the depth and density of UVC-induced DNA damage in the porcine and human limbus following UVC exposures of varying supratherapeutic dose. Methods: The corneoscleral junction (limbus) of full-thickness porcine corneas was exposed to supratherapeutic doses of UVC light (265 nm, 1.93 mW/cm2) for 5, 10, 15, 30, or 60 min (exposure groups) or remained unexposed for the same durations (control groups), with a sample size of 6 per group. In parallel, human corneal tissue was exposed to UVC for 1 or 5 min and processed identically. Following exposure, all tissues were frozen, dissected, and analysed using immunohistochemistry to detect cyclobutane pyrimidine dimers (CPDs) as markers of DNA damage. CPD distribution, depth, and density were subsequently evaluated. Results: CPDs were localised predominantly in the superficial corneal epithelial layers, irrespective of the UVC dose. The mean ± SD thickness of the corneal epithelium in the UVC-exposed groups was 38.9 ± 18.9 µm, and the average depth of CPD formation was 13.3 ± 8.43 µm. The proportions of cells affected by CPDs within the corneal epithelium (mean ± SD) were 47.8 ± 25.6%, 58.5 ± 16.2%, 39.9 ± 26.4%, 41.3 ± 27.3%, and 38.9 ± 28.3% for exposure durations of 5, 10, 15, 30, and 60 min, respectively (p > 0.05). Human cornea showed similarly limited penetration, with no difference in CPD proportions between the 1 and 5 min UVC exposures (p = 0.70). Conclusions: UVC-induced DNA damage in both species was confined to the superficial cellular layers of the cornea, with no detectable damage observed in deeper tissues, including those where limbal stem cells reside, even after supratherapeutic doses of up to one hour of exposure. Full article
(This article belongs to the Special Issue The Role of Light in Ocular Health and Disease)
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14 pages, 238 KB  
Article
Acanthamoeba Keratitis: 34-Year Epidemiological Profile
by Saad H. AlEnezi, Shaimaa Mohammed Alrefaie, Adi Mohammed Al Owaifeer, Hani Basher AlBalawi, Naif Mamdouh Alali, Mohammad Alabduljabbar, Shaker O. Alreshidi, Moustafa S. Magliyah, Entesar A. Altalhi, Shaima Sulaiman Alharbi, Abdulaziz S. Alharthi, Yousef A. Alotaibi and Saad S. Alharbi
Antibiotics 2026, 15(5), 488; https://doi.org/10.3390/antibiotics15050488 - 12 May 2026
Viewed by 516
Abstract
Background/Objectives: Acanthamoeba keratitis (AK) is a rare but sight-threatening corneal infection. This study reviews the clinical profile, diagnostic pathways, treatment strategies, and outcomes of AK cases managed over a 34-year period. Methods: We conducted a retrospective analysis of 52 [...] Read more.
Background/Objectives: Acanthamoeba keratitis (AK) is a rare but sight-threatening corneal infection. This study reviews the clinical profile, diagnostic pathways, treatment strategies, and outcomes of AK cases managed over a 34-year period. Methods: We conducted a retrospective analysis of 52 microbiologically AK cases from 1983 to 2017. Results: The mean age at presentation was 27.7 ± 9.4 years, with a female predominance (63.5%). The majority (82.7%) were contact lens users, almost exclusively soft lens wearers, with documented risk behaviors such as poor hygiene and sleeping with lenses. 44.2% were initially misdiagnosed as nonspecific microbial keratitis. Common clinical findings included epithelial defects (30.8%), ring infiltrates (44.2%), superficial infiltrates (53.8%), hypopyon (30.8%), and corneal thinning (13.5%). Diagnosis was confirmed by culture/stain in 61.5% of cases, while others required confocal microscopy or corneal biopsy. Co-infections with bacteria were noted in ~20%. Prior to referral, 82.7% of patients had received empirical topical therapy. At KKESH, all received dual anti-Acanthamoeba therapy, and 69.2% underwent surgical intervention, including tectonic PKP (46.2%) and optical PKP (19.2%). Visual acuity improved from a mean logMAR of 1.51 at presentation to 0.87 at last follow-up. Anti-Acanthamoeba therapy was discontinued in 95.9% of patients by the end of follow-up, with steroid use tapering from 61.5% at 3 months to 16.3% at final visit. Conclusions: Acanthamoeba keratitis in Saudi Arabia predominantly affects young female contact lens users and often presents with diagnostic delays and misclassification as herpetic or bacterial keratitis. Despite aggressive medical and surgical therapy, visual outcomes remain suboptimal in many cases. Full article
(This article belongs to the Special Issue Antimicrobial Treatment and Antibiotic Use in Ophthalmology)
7 pages, 2549 KB  
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Anterior Segment OCT in Fulminant Pseudomonas aeruginosa Corneal Ulcer with Stromal Melting Requiring Emergency Penetrating Keratoplasty
by Wojciech Luboń, Monika Sarnat-Kucharczyk and Mariola Dorecka
Diagnostics 2026, 16(8), 1189; https://doi.org/10.3390/diagnostics16081189 - 16 Apr 2026
Viewed by 381
Abstract
Rapidly progressive infectious keratitis may involve the anterior uveal tract and lead to anterior segment inflammation, resulting in severe structural damage of the cornea and potentially causing corneal perforation or endophthalmitis if not promptly treated. We report the case of a 63-year-old male [...] Read more.
Rapidly progressive infectious keratitis may involve the anterior uveal tract and lead to anterior segment inflammation, resulting in severe structural damage of the cornea and potentially causing corneal perforation or endophthalmitis if not promptly treated. We report the case of a 63-year-old male admitted to the Emergency Ophthalmology Department of the University Clinical Center in Katowice, Poland, with a rapidly progressive corneal ulcer of the left eye that had not responded to two weeks of outpatient topical antibiotic therapy. The condition developed after ocular trauma sustained while chopping wood. At presentation, visual acuity was limited to light perception with preserved projection. Multimodal imaging, including slit-lamp examination, anterior segment optical coherence tomography (AS-OCT), and in vivo confocal microscopy, revealed extensive corneal ulceration with severe stromal destruction, progressive corneal melting, and marked anterior segment inflammation, with an imminent risk of perforation. Microbiological cultures identified Pseudomonas aeruginosa. Despite intensive empiric topical antimicrobial therapy targeting both bacterial infection and a possible fungal component related to trauma with organic material, rapid clinical deterioration necessitated emergency therapeutic penetrating keratoplasty (PK). The procedure resulted in rapid resolution of inflammation and improvement in visual acuity, with best-corrected visual acuity (BCVA) reaching 0.3 logMAR during follow-up. At the three-month follow-up, the corneal graft remained clear with stable visual acuity and no recurrence of infection. The patient remains under regular long-term follow-up, with ongoing monitoring of graft clarity, intraocular pressure (IOP), and visual function. This case differs from routine presentations of infectious keratitis by demonstrating exceptionally rapid stromal melting despite promptly initiated empiric topical therapy. Multimodal imaging, particularly AS-OCT provided clinically meaningful information by revealing structural instability and an imminent risk of perforation not fully appreciable on slit-lamp examination, thereby supporting timely urgent keratoplasty. These findings highlight the practical diagnostic value of imaging-based assessment in advanced infectious keratitis and underscore its role in guiding surgical decision-making in eyes at high risk of corneal perforation. Full article
(This article belongs to the Special Issue Diagnostic Imaging in Ocular Surface)
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10 pages, 217 KB  
Article
Cefiderocol Is Effective In Vitro Against Numerous Gram-Negative Species Isolated from Keratitis Patients
by Jonathan B. Mandell, Robert M. Q. Shanks and Eric G. Romanowski
Antibiotics 2026, 15(4), 348; https://doi.org/10.3390/antibiotics15040348 - 29 Mar 2026
Viewed by 559
Abstract
Background: To evaluate the potential of cefiderocol as a topical ophthalmic antibiotic by determining the susceptibility of keratitis isolates from an extensive panel of Gram-negative bacterial species to this siderophore-cephalosporin class antibiotic. Methods: Minimum Inhibitory Concentrations (MICs) of cefiderocol were determined by the [...] Read more.
Background: To evaluate the potential of cefiderocol as a topical ophthalmic antibiotic by determining the susceptibility of keratitis isolates from an extensive panel of Gram-negative bacterial species to this siderophore-cephalosporin class antibiotic. Methods: Minimum Inhibitory Concentrations (MICs) of cefiderocol were determined by the broth dilution method using iron-depleted, cation-adjusted Mueller–Hinton broth. The following Gram-negative bacteria were included: Acinetobacter baumannii (n = 13), Achromobacter xylosoxidans (n = 14), Escherichia coli (n = 15), Klebsiella aerogenes (n = 14), Klebsiella pneumoniae (n = 13), Klebsiella oxytoca (n = 14), Moraxella spp. (n = 15), Proteus mirabilis (n = 13), Pseudomonas aeruginosa (n = 17), Serratia marcescens (n = 14) and Stenotrophomonas maltophilia (n = 12). MIC90 values were calculated for each of the species. Results: MIC90 values (µg/mL): A. baumannii (0.5), A. xylosoxidans (0.25), E. coli (0.5), K. aerogenes (1.0), K. oxytoca (0.5), K. pneumoniae (0.5), Moraxella spp. (0.5), P. mirabilis (0.25), P. aeruginosa (0.5), S. marcescens (0.5), and S. maltophilia (0.25). In total, 100% of the isolates were determined to be susceptible to cefiderocol in vitro except for A. xylosoxidans and Moraxella spp., for which there are no established breakpoints for cefiderocol. Conclusions: Cefiderocol demonstrated in vitro activity against the tested panel of Gram-negative keratitis isolates. The results of this study suggest cefiderocol may be useful for the treatment of keratitis caused by numerous Gram-negative pathogens. Further development of cefiderocol for the topical treatment of Gram-negative keratitis is indicated. Full article
(This article belongs to the Special Issue Antimicrobial Treatment and Antibiotic Use in Ophthalmology)
11 pages, 244 KB  
Review
The Ocular Surface Bacterial Microbiome and the Impact of Contact Lens Use: A Literature Review
by Laura De Luca, Feliciana Menna, Stefano Lupo, Enzo Maria Vingolo, Matteo Mario Carlà, Maura Mancini, Giovanni William Oliverio, Letteria Minutoli, Antonio Baldascino, Cosimo Mazzotta, Pasquale Aragona and Alessandro Meduri
Microorganisms 2026, 14(3), 518; https://doi.org/10.3390/microorganisms14030518 - 24 Feb 2026
Viewed by 860
Abstract
The ocular surface microbiome plays a critical role in maintaining ocular health, preventing infections, and regulating immune responses. Contact lens (CL) wear has been linked to alterations in microbial composition, potentially leading to dysbiosis and increased susceptibility to ocular infections. This review aims [...] Read more.
The ocular surface microbiome plays a critical role in maintaining ocular health, preventing infections, and regulating immune responses. Contact lens (CL) wear has been linked to alterations in microbial composition, potentially leading to dysbiosis and increased susceptibility to ocular infections. This review aims to summarize current evidence on the effects of CL use on the ocular microbiome and to discuss strategies to preserve microbial homeostasis. A literature search was conducted in PubMed, Scopus, Web of Science, and Google Scholar for English-language human studies published between January 2005 and January 2025. We included original studies and systematic reviews evaluating the ocular surface bacterial community in contact lens (CL) wearers using either sequencing-based approaches (microbiome; e.g., 16S rRNA gene sequencing/metagenomics) or culture-based methods (microbiota). Two authors screened titles/abstracts and full texts. Overall, 12 studies met the inclusion criteria and were qualitatively synthesized. Across included studies, CL wear was associated with reproducible changes in the ocular surface bacterial community, most commonly a shift toward a skin-like profile and increased detection/relative abundance of opportunistic taxa (e.g., Pseudomonas, Acinetobacter, and Staphylococcus aureus) together with reduced representation of typical ocular commensals in several sequencing-based datasets. Culture-based studies reported increased recovery of opportunistic bacteria from lenses and storage cases, supporting contamination/biofilm-related mechanisms. Lens care solutions and preservatives were reported to modulate bacterial profiles and may contribute to dysbiosis, although evidence remains heterogeneous across study designs and analytic pipelines. CL use is associated with significant alterations in the ocular microbiome, increasing the risk of microbial keratitis and corneal inflammatory events. Strategies to maintain microbial balance, including careful selection of lens care products and development of antimicrobial lenses, may improve ocular surface health in CL wearers. Future longitudinal studies with standardized sampling and analytic workflows are needed to clarify causal links between CL-associated microbial changes and clinical outcomes. Full article
(This article belongs to the Section Medical Microbiology)
19 pages, 805 KB  
Article
Trends of Microorganisms and Antibiotic Resistance Isolated from Patients with Bacterial Keratitis from a Tertiary Hospital in Southeastern Korea: A 26-Year Retrospective Medical Record Review
by Chan-Ho Cho, Jong Ho Lee and Sang-Bumm Lee
Antibiotics 2026, 15(2), 207; https://doi.org/10.3390/antibiotics15020207 - 13 Feb 2026
Cited by 2 | Viewed by 1014
Abstract
Background. The aim of this study is to analyze changing trends in isolated organisms and antibiotic resistance of bacterial keratitis (BK) over 26 years. Methods. A retrospective medical record review included 542 strains isolated from 462 BK patients between 1998 and 2023. We [...] Read more.
Background. The aim of this study is to analyze changing trends in isolated organisms and antibiotic resistance of bacterial keratitis (BK) over 26 years. Methods. A retrospective medical record review included 542 strains isolated from 462 BK patients between 1998 and 2023. We analyzed routinely generated in vitro antibiotic susceptibility testing results recorded in the laboratory information system and did not perform additional susceptibility testing for research purposes. The entire period was divided into two (first half: 1998–2010, 297 isolates from 255 patients; second half: 2011–2023, 245 isolates from 207 patients) and compared. Results. During the entire period, Staphylococcus spp. (32.3%) and Pseudomonas spp. (18.1%) were common isolates, and a significant increase in Acinetobacter spp. (1.3% vs. 10.6%, p < 0.001) was observed. Among Gram-positive bacteria, methicillin resistance rates remained stable between the two periods (52.6% vs. 46.7%, p = 0.525), and an increase in vancomycin-resistant Enterococci (VRE, 0% vs. 26.1%, p = 0.074) was found. Among Gram-negative bacteria (GNB), ciprofloxacin (7.5% vs. 14.4%, p = 0.108) and imipenem (2.9% vs. 6.5%, p = 0.255) resistance increased slightly, resistance to ceftazidime (8.3% vs. 8.8%, p > 0.999) was maintained, and resistance to aminoglycosides (17.8% vs. 7.2%, p = 0.010) decreased. Conclusions. Our study suggests that conventional topical fortified antibiotic eye drops (tobramycin, ceftazidime) can still be considered as an empirical treatment option for BK. However, our findings revealed a long-term trend of increasing Acinetobacter spp. and VRE, as well as a slight trend of increasing resistance to ciprofloxacin and imipenem in GNB, which may present future challenges in BK treatment. Full article
(This article belongs to the Collection Antibiotics in Ophthalmology Practice)
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21 pages, 1377 KB  
Systematic Review
Current Challenges and Long-Term Outcomes in Corneal Transplantation in Infectious Keratitis—A Systematic Review
by Ancuța-Georgiana Onofrei, Alina Gabriela Gheorghe, Ana Maria Dascalu, Bogdan Mihai Cristea, Sinziana Istrate, Ana Maria Arghirescu, Dragos Serban, Corneliu Tudor, Paul Lorin Stoica, Marina-Ionela Nedea and Dan Dumitrescu
J. Clin. Med. 2026, 15(2), 871; https://doi.org/10.3390/jcm15020871 - 21 Jan 2026
Viewed by 935
Abstract
Background/Objectives: Infectious keratitis remains a major cause of blindness worldwide, and many cases progress to therapeutic keratoplasty despite advances in antimicrobial therapy. This systematic review aims to evaluate the outcomes of therapeutic keratoplasty in microbial keratitis and examine factors influencing anatomical success, graft [...] Read more.
Background/Objectives: Infectious keratitis remains a major cause of blindness worldwide, and many cases progress to therapeutic keratoplasty despite advances in antimicrobial therapy. This systematic review aims to evaluate the outcomes of therapeutic keratoplasty in microbial keratitis and examine factors influencing anatomical success, graft survival, and visual rehabilitation. Methods: A systematic review was conducted following PRISMA guidelines, including English-language studies, published between 2000 and 2025. Studies with ≥10 eyes and ≥6 months follow-up were included. Data on infection control, graft clarity, anatomical success, visual acuity, and complications were extracted. Results: Fourteen studies encompassing 1527 eyes were analyzed. TPK accounted for 89% of procedures; DALK was used selectively for anterior or mid-stromal infections. Overall infection control ranged from 69 to 100%, with globe preservation in 85–100% of cases. Bacterial keratitis had higher cure rates and graft clarity than fungal or Acanthamoeba keratitis. Larger grafts (>8 mm) and deep stromal involvement were associated with increased graft rejection and postoperative complications. DALK offered higher graft survival and lower immunologic risk when the endothelium was spared. Visual outcomes were generally limited, reflecting preoperative disease severity, timing of surgery, and postoperative immunomodulation constraints. Early surgical intervention improved anatomical outcomes in severe fungal keratitis. Conclusions: Therapeutic keratoplasty is an effective globe-preserving intervention in advanced microbial keratitis, but with limited functional outcomes. Further prospective studies are needed to refine surgical indications, postoperative management, and long-term functional results. Full article
(This article belongs to the Special Issue New Insights in Ophthalmic Surgery)
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17 pages, 3104 KB  
Article
Genotypic Resistance Analysis of Bacterial Species Involved in Infectious Keratitis
by Andrei Theodor Bălășoiu, Ovidiu Mircea Zlatian, Maria Balasoiu, Andrei Osman, Alice Elena Ghenea, Ramona Cioboată, Simona-Daniela Neamtu and Andreea Loredana Golli
Diagnostics 2026, 16(1), 135; https://doi.org/10.3390/diagnostics16010135 - 1 Jan 2026
Viewed by 993
Abstract
Background/Objectives: Infectious keratitis represents a major ophthalmological emergency and a leading cause of corneal blindness worldwide. Rapid progression, frequent antimicrobial resistance, and poor therapeutic outcomes make genotypic surveillance essential. This study aimed to analyze the distribution of bacterial pathogens involved in infectious [...] Read more.
Background/Objectives: Infectious keratitis represents a major ophthalmological emergency and a leading cause of corneal blindness worldwide. Rapid progression, frequent antimicrobial resistance, and poor therapeutic outcomes make genotypic surveillance essential. This study aimed to analyze the distribution of bacterial pathogens involved in infectious keratitis and characterize their resistance mechanisms at the genotypic level, with emphasis on extended-spectrum β-lactamase (ESBL) genes. Methods: Corneal scrapings were collected from patients diagnosed with bacterial keratitis at the County Clinical Emergency Hospital of Craiova. Isolates were identified using standard microbiological techniques, followed by antimicrobial susceptibility testing. Genotypic resistance markers, including tem, shv, and ctx-M gene families, were investigated using PCR-based methods, while phenotypic resistance was investigated using the Vitek2 system. Results: Gram-positive bacteria were the predominant isolates, with coagulase-negative staphylococci and Staphylococcus aureus accounting for most cases. Among Gram-negative pathogens, Pseudomonas aeruginosa and Enterobacteriaceae were frequently detected. Genotypic analysis revealed tem genes in a substantial proportion of ocular isolates, often plasmid-mediated, while shv genes showed low prevalence and ctx-M genes were less frequent. The genetic determinants correlated well with phenotypic resistance expressed by MICs. Conclusions: The study highlights the significant correlation between genotypic markers and resistance phenotypes in bacterial keratitis. Continuous molecular surveillance is essential to guide targeted therapy, prevent therapeutic failure, and improve patient outcomes in infectious keratitis. Full article
(This article belongs to the Special Issue Diagnosis and Management of Ophthalmic Disorders)
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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
Cited by 4 | Viewed by 1685
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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20 pages, 1978 KB  
Article
Antibiofilm and Immunomodulatory Effects of Cinnamaldehyde in Corneal Epithelial Infection Models: Ocular Treatments Approach
by Ashraf Khalifa, Muthukumar Thangavelu, Krishnaraj Thirugnanasambantham and Hairul-Islam M. Ibrahim
Pharmaceutics 2026, 18(1), 5; https://doi.org/10.3390/pharmaceutics18010005 - 19 Dec 2025
Cited by 1 | Viewed by 1293
Abstract
Background: Bacterial keratitis, a major cause of corneal blindness, is frequently associated with biofilm-forming pathogens such as Klebsiella pneumoniae. Cyclic-di-GMP (c-di-GMP) controls biofilm development, which increases antibiotic resistance and makes treatment more difficult, highlighting the need for innovative therapeutic approaches. Methods: [...] Read more.
Background: Bacterial keratitis, a major cause of corneal blindness, is frequently associated with biofilm-forming pathogens such as Klebsiella pneumoniae. Cyclic-di-GMP (c-di-GMP) controls biofilm development, which increases antibiotic resistance and makes treatment more difficult, highlighting the need for innovative therapeutic approaches. Methods: This study investigated cinnamaldehyde as a potential ocular therapeutic using combined computational and experimental approaches. Molecular docking and in vitro assays (XTT, resazurin reduction, crystal violet staining, qRT-PCR, and fluorescence microscopy) were used to evaluate the anti-biofilm and immunomodulatory activities of cinnamaldehyde (CA) against Klebsiella pneumoniae. Results: CA inhibited biofilm formation in a dose-dependent manner (≈89% at 1000 µM; >50% at 250 µM), reduced bacterial attachment to contact lenses, and downregulated key biofilm genes (mrkA, mrkC, ybtS, bolA). Docking analysis revealed strong binding affinity to the mrkH regulator (−5.46 kcal/mol. CA maintained more than 80% corneal cell viability by increasing IL-10, suppressing inflammatory mediators (IL-1β, IL-6, and TNF-α), and improving bacterial clearance. Conclusions: This study combines computational docking, biofilm quantification, immune cell assays, and functional gene expression analyses to reveal the ability of cinnamaldehyde not only to suppress biofilm formation but also to enhance macrophage-mediated clearance and modulate corneal immune responses, a multi-target approach not previously described in the context of bacterial keratitis. Such effects highlight its potential as a novel ocular drug candidate for protecting corneal integrity in infectious keratitis. Full article
(This article belongs to the Special Issue Ophthalmic Drug Delivery, 3rd Edition)
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28 pages, 762 KB  
Review
Mechanisms and Evolution of Antimicrobial Resistance in Ophthalmology: Surveillance, Clinical Implications, and Future Therapies
by Isaiah Osei Duah Junior, Josephine Ampong and Cynthia Amaning Danquah
Antibiotics 2025, 14(11), 1167; https://doi.org/10.3390/antibiotics14111167 - 20 Nov 2025
Cited by 6 | Viewed by 2716
Abstract
Antimicrobial resistance (AMR) is a growing global health concern with profound implications for ophthalmology, where it compromises the management of ocular infections such as bacterial keratitis, conjunctivitis, endophthalmitis, and postoperative complications. Resistance in common ocular pathogens, including Staphylococcus aureus (S. aureus), [...] Read more.
Antimicrobial resistance (AMR) is a growing global health concern with profound implications for ophthalmology, where it compromises the management of ocular infections such as bacterial keratitis, conjunctivitis, endophthalmitis, and postoperative complications. Resistance in common ocular pathogens, including Staphylococcus aureus (S. aureus), Streptococcus pneumoniae (S. pneumoniae), Pseudomonas aeruginosa (P. aeruginosa), and coagulase-negative staphylococci (CoNS) emerge through genetic mutations, horizontal gene transfer, and biochemical mechanisms such as enzymatic degradation, target modification, efflux pumps, and reduced membrane permeability. Biofilm formation further complicates eradication on the ocular surface and interior. The key drivers of resistance include inappropriate or prolonged topical antibiotic use, routine prophylaxis in ocular surgery, subtherapeutic dosing, and cross-resistance with systemic antimicrobials. The rise in multidrug-resistant strains, particularly methicillin-resistant S. aureus, fluoroquinolone-resistant P. aeruginosa, and drug-resistant S. pneumoniae has been linked to delayed treatment response, increased healthcare costs, and sight-threatening outcomes. Recent advances in rapid diagnostics, molecular assays, and point-of-care testing support earlier and more precise detection of resistance, enabling timely therapeutic decisions. Promising strategies to address AMR in ophthalmology include antimicrobial stewardship, novel drug delivery platforms, and alternative approaches such as bacteriophage therapy and antimicrobial peptides. Emerging tools, including genomic surveillance, artificial intelligence (AI)-driven resistance prediction, and personalized antimicrobial regimens, further expand opportunities for innovation. Collectively, this review synthesizes current evidence on AMR in ocular disease, summarizing patterns of resistance, underlying mechanisms, and clinical consequences, while highlighting strategies for mitigation and underscoring the need for global awareness and collaboration among clinicians, researchers, and policymakers to safeguard vision. Full article
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15 pages, 824 KB  
Article
Infectious Keratitis: A Tertiary Center’s Approach to Diagnosis, Management, and Enhanced Outcomes Through Microbiological Analysis
by Antonio Moramarco, Federico Cassini, Natalie di Geronimo, Giovanni Zanini, Michele Potenza, Matteo Farnè, Viviana Schisa, Erica De Carolis, Margherita Ortalli, Piera Versura, Tiziana Lazzarotto and Luigi Fontana
Microorganisms 2025, 13(10), 2308; https://doi.org/10.3390/microorganisms13102308 - 5 Oct 2025
Cited by 2 | Viewed by 2105
Abstract
Background: The study aimed to assess the diagnostic and therapeutic management of infectious keratitis at a tertiary referral center, focusing on how microbiological analysis influences clinical outcomes. Methods: A retrospective review was conducted on 220 patients (221 eyes) with infectious keratitis treated between [...] Read more.
Background: The study aimed to assess the diagnostic and therapeutic management of infectious keratitis at a tertiary referral center, focusing on how microbiological analysis influences clinical outcomes. Methods: A retrospective review was conducted on 220 patients (221 eyes) with infectious keratitis treated between November 2021 and January 2025. Data collected included clinical presentation, microbiological findings, treatment approaches, and outcomes. Statistical analyses examined the relationships between microbiological results, improvements in visual acuity, and the need for rescue surgery. Results: Bacterial keratitis accounted for 64% of cases, followed by viral (20%), fungal (13%), and Acanthamoeba (3%). Microbiological testing was performed in 107 cases, with a culture positivity rate of 75.7%. Positive microbiological findings were significantly associated with better visual acuity (p = 0.019) and a reduced, though not statistically significant, need for rescue surgery. Use of contact lenses and ocular trauma were independent risk factors for culture positivity. Delayed referral (more than 15 days) was linked to longer treatment durations and a higher likelihood of surgical intervention (p < 0.001). Microbiological diagnosis correlates with improved visual outcomes and a decreased need for surgical procedures. Conclusion: Early referral and targeted therapy are essential for optimizing prognosis. The use of contact lenses and cases of ocular trauma should prompt early diagnostic sampling. Full article
(This article belongs to the Special Issue Mycosis and Antifungal Agents)
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