Keratitis Research Articles

A Case of Bacterial Keratitis and Endophthalmitis Caused by Two Types of Antibiotic-resistant Bacteria

Purpose: To report a case of infectious keratitis and endophthalmitis caused by two types of antibiotic-resistant bacteria.Case summary: A 62-year-old female patient presented to our clinic with left ocular pain for 2 weeks and was diagnosed with herpetic keratitis and anterior uveitis. At the initial presentation, slit lamp biomicroscopy revealed round stromal infiltration and edema in the paracentral part of the cornea, a 2 × 2-mm epithelial defect, and hypopyon. Ocular ultrasonography showed vitreous opacities. She was empirically treated with topical 0.5% moxifloxacin, 2% tobramycin, and 5% ceftazidime administered hourly. Intravitreal vancomycin/ceftazidime administration was performed on days 2 and 7 following treatment. Corneal culture revealed extended-spectrum β-lactamase-producing <i>Klebsiella pneumoniae</i> and methicillin-resistant <i>Staphylococcus aureus</i> on day 4 after treatment. Consequently, 2% tobramycin was replaced with 1% vancomycin. The corneal lesion gradually improved and healed completely with a residual corneal opacity at 4 weeks after treatment.Conclusions: Polymicrobial bacterial keratitis caused by antibiotic-resistant bacteria represents a treatment challenge. Therefore, culture is essential to obtain microbiological evidence and guide appropriate antibiotic selection.

Effects of Dexpanthenol on Corneal Neovascularization and Inflammation on Rat Model.

To evaluate the effect of subconjunctival injection of dexpanthenol on corneal neovascularization and inflammation in rats with induced chemical burns. This experimental study included 40 female albino Wistar rats. Chemical burns were induced in the right eye of all rats on the first day, and the left eye was used as a control. Rats were randomly divided into 5 groups. The no-treatment group (group 1) received no injections. Balanced salt solution injection in the sham group (group 2), dexpanthenol injection in the dexpanthenol group (group 3), bevacizumab injection in the bevacizumab group (group 4), and combined dexpanthenol and bevacizumab injection in the combined group (group 5) were administered subconjunctivally on day 7. The right corneas of all rats were photographed on days 7 and 14 to evaluate corneal neovascularization. The 2 corneal images were compared, and the differences were analyzed. All rats were euthanized, and the corneas were isolated. The levels of tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor-A, malondialdehyde (MDA), apoptosis, reduced glutathione (GSH), and total oxidant status were measured in rat corneas. Dexpanthenol reduced corneal neovascularization, and the difference was significant compared with the no-treatment and sham groups (P < 0.05). No significant difference in corneal neovascularization was observed between the dexpanthenol and bevacizumab groups. Dexpanthenol had a significant positive effect on vascular endothelial growth factor-A, TNF-α, total oxidant status, MDA, and GSH levels compared with the sham group (P < 0.05). Dexpanthenol may help control corneal neovascularization and inflammation after chemical burns.

Dexamethasone-Antibiotic Interactions in Canine Ocular Bacteria: InVitro Susceptibility Changes in Common Corneal Infection Pathogens.

To investigate the impact of dexamethasone on the antibiotic susceptibility of common ocular pathogens in dogs and identify safe antibiotic-steroid combinations for veterinary ophthalmology. This study utilized 30 bacterial isolates of Staphylococcus pseudintermedius, Streptococcus canis, and Pseudomonas aeruginosa, collected from canine patients with suspected bacterial keratitis. The isolates were tested against 17 antibiotics in the presence of dexamethasone concentrations ranging from 0 to 2 mg/mL. Minimum inhibitory concentrations (MICs) were determined using standardized broth microdilution techniques, and changes in susceptibility were analyzed statistically. Dexamethasone administration resulted in a significant increase in resistance for ciprofloxacin, ticarcillin, tobramycin, and ceftiofur in S. pseudintermedius; ticarcillin in S. canis; and ciprofloxacin and moxifloxacin in P. aeruginosa. Despite these increases, amikacin and cefazolin showed minimal impact on resistance when combined with dexamethasone, indicating their potential for safe use in combination therapies. The findings highlight the potential for dexamethasone to alter antibiotic susceptibility in canine ocular pathogens. While dexamethasone can increase resistance in certain antibiotics, amikacin and cefazolin appear to be safer options for combination therapy.

Drug in Drug: Quorum Sensing Inhibitor in Star-Shaped Antibacterial Polypeptides for Inhibiting and Eradicating Corneal Bacterial Biofilms.

Biofilm-related bacterial keratitis is a severe ocular infection that can result in drastic vision impairment and even blindness. However, the therapeutic efficiency of clinical antibiotic eyedrops is often compromised because the bacteria in the biofilms resist bactericide via the community genetic regulation, namely, bacterial quorum sensing. Herein, quercetin (QCT)-loaded star-shaped antibacterial peptide polymer (SAPP), QCT@SAPP, is developed based on a "drug" in a "drug" strategy for inhibiting and eradicating Pseudomonas aeruginosa biofilms on the cornea. The natural antibacterial peptide-mimic SAPP with the positively charged amphipathic structure not only enables QCT@SAPP to penetrate the biofilms readily but also selectively adheres to the highly negatively charged P. aeruginosa, releasing the loaded QCT into the bacteria to regulate quorum sensing by inhibiting lasI, lasR, rhlR, and rhlI. Thanks to its robust bactericidal ability from SAPP, QCT@SAPP can eliminate more than 99.99% of biofilms. Additionally, QCT@SAPP displayed outstanding performance in relieving ocular inflammation by significantly downregulating pro-inflammatory cytokines and profiting from scavenging reactive oxygen species by releasing QCT, which finally helps to restore visual function. In conclusion, QCT@SAPP, with good compatibility, exerts excellent therapeutic effects in a bacterial keratitis mice model, making it a promising candidate for controlling bacterial biofilm-induced infections, including bacterial keratitis.

A Convolutional Neural Network Using Anterior Segment Photos for Infectious Keratitis Identification.

To develop a comprehensively deep learning algorithm to differentiate between bacterial keratitis, fungal keratitis, non-infectious corneal lesions, and normal corneas. This retrospective study collected slit-lamp photos of patients with bacterial keratitis, fungal keratitis, non-infectious corneal lesions, and normal cornea. Causative organisms of infectious keratitis were identified by either positive culture or clinical response to single treatment. Convolutional neural networks (ResNet50, DenseNet121, VGG19) and Ensemble with probability weighting were used to develop a deep learning algorithm. The performance including accuracy, precision, recall, F1 score, specificity and AUC has been reported. Total of 6478 photos from 2171 eyes, composed of 2400 bacterial keratitis, 1616 fungal keratitis, 1545 non-infectious corneal lesions, and 917 normal corneas were collected from hospital database. DenseNet121 demonstrated the best performance among three convolutional neural networks with the accuracy of 0.8 (95% CI 0.74-0.86). The ensemble technique showed higher performance than single algorithm with the accuracy of 0.83 (95% 0.78-0.88). Convolutional neural networks with ensemble techniques provided the best performance in discriminating bacterial keratitis, fungal keratitis, non-infectious corneal lesions, and normal corneas. Our models can be used as a screening tool for non-ophthalmic health care providers and ophthalmologists for rapid provisional diagnosis of infectious keratitis.

The role of PPAR in fungal keratitis

The treatment of fungal keratitis(FK) remains challenging due to delayed fungal detection and the limited effectiveness of antifungal drugs. Fungal infection can activate both innate and adaptive immune responses in the cornea. Fungi stimulate the production of oxidative stress-related biomarkers and mediate the infiltration of neutrophils, macrophages, and T cells. These cells can induce infiltration of cytokines, chemokines, and matrix metalloproteinases (MMPs), leading to corneal tissue damage and even corneal perforation. The signaling pathway regulates the expression of inflammatory cytokines in fungal keratitis. Immune inflammatory damage is the main mechanism of FK, and oxidative stress damage is also involved in this infection process. Peroxisome proliferator-activated receptor (PPAR) is a member of the nuclear hormone receptor superfamily, with different subtypes of PPAR a, PPAR β/δ, and PPARγ. PPARs play important roles in the antioxidant response, anti-inflammatory, lipid metabolism, neuroprotection, and immune regulation processes. PPAR γ can promote macrophage polarization and reduce oxidative stress damage by regulating ROS production. PPAR has made some progress in the treatment of eye diseases: PPARa agonists can inhibit diabetes keratopathy and corneal neuropathy. PPARa agonists inhibit early immature angiogenesis in corneal alkali burns and have potential therapeutic effects on inflammatory corneal angiogenesis. PPARs can control the progression of dry eye disease and improve the condition of meibomian gland dysfunction. Based on this, we explored the potential roles of PPARs in the treatment of FK.

Examination of the Corneal Endothelium in Patients With Congenital Aniridia With a PAX6 Mutation Using In Vivo Confocal Laser Scanning Microscopy.

In PAX6 syndrome, it is still not clear, whether prenatally, parallel to the iris tissue developmental anomaly, there is neural ectodermal, neural crest, or mesodermal cell deposition at the corneal endothelium, affecting endothelial structure and function. In addition, because of the postnatal corneal inflammation and commonly appearing secondary glaucoma, progressive endothelial changes are expected. Our purpose was to study the corneal endothelium in subjects with PAX6 aniridia, using in vivo confocal laser scanning microscopy. Twenty-seven eyes of 16 subjects with congenital aniridia (age 28.25 ± 16.32 [11-59] years, 8 [50%] female) and 40 eyes of 26 healthy subjects (age 33.8 ± 15.2 [14-67] years, 17 [58.6%] females) were examined. Aniridia-associated keratopathy and iris malformation were graded, and means of endothelial cell density, cell area, cell diameter, spatial pattern of cell centroids (Clark-Evans index), polygonality, neighbor count, percentage of hexagonal cells, and endothelial deposit number were determined by in vivo confocal laser scanning microscopy. Mean cell diameter and mean Clark-Evans index were significantly lower (P = 0.049; P = 0.008) in congenital aniridia eyes than in controls. There were hyperreflective endothelial deposits in congenital aniridia eyes but not in controls (P < 0.001). Only aniridia-associated keratopathy grade correlated positively with mean endothelial deposit number (P = 0.017). In congenital aniridia, the corneal endothelium might possess a slightly better quality and greater reserves than in healthy subjects. Corneal endothelial deposition seems to be independent from developmental abnormalities but may be related to up to date undescribed endothelial inflammatory or metabolic changes.

Targeted Bacterial Keratitis Treatment with Polyethylene Glycol-Dithiothreitol- Boric Acid Hydrogel and Gatifloxacin.

To prolong the ocular residence time of gatifloxacin and enhance its efficacy against bacterial keratitis, this study developed a velocity-controlled polyethylene glycol-dithiothreitol- boric acid (PDB) hydrogel loaded with gatifloxacin. First, the basic properties of the synthesized PDB hydrogel and the gatifloxacin- loaded PDB hydrogel were assessed. Secondly, the in vitro degradation rate of the drugloaded PDB was measured in a simulated body fluid environment with pH 7.4/5.5. The release behavior of the drug-loaded PDB was studied using a dialysis method with PBS solution of pH 7.4/5.5 as the release medium. Finally, a mouse model of bacterial keratitis was established, and tissue morphology was observed using hematoxylin-eosin staining. Additionally, mouse tear fluid was extracted to observe the antibacterial effect of the gatifloxacin-loaded PDB hydrogel. The results showed that the PDB hydrogel had a particle size of 124.9 nm and a zeta potential of -23.3 mV, with good porosity, thermosensitivity, viscosity distribution, rheological properties, and high cell compatibility. The encapsulation of gatifloxacin did not alter the physical properties of the PDB hydrogel and maintained appropriate swelling and stability, with a high drug release rate in acidic conditions. Furthermore, animal experiments demonstrated that the gatifloxacin- loaded PDB hydrogel exhibited superior therapeutic effects compared to gatifloxacin eye drops and displayed strong antibacterial capabilities against bacterial keratitis. This study successfully synthesized PDB hydrogel and developed a gatifloxacin drug release system. The hydrogel exhibited good thermosensitivity, pH responsiveness, stability, and excellent biocompatibility, which can enhance drug retention, utilization, and therapeutic effects on the ocular surface.

Clinical and morphological features of corneal lymphoma in 26 horses (27 eyes).

Little information describing the biologic behaviour and therapies for corneal lymphoma exist. To characterise histologically confirmed equine corneal lymphoma considering breed, age or sex predisposition, histologic and immunologic features, therapies and outcomes. Retrospective case series. A multicentre retrospective medical record review was used to identify horses that presented with corneal disease confirmed morphologically as corneal lymphoma from 2012 to 2022. Mean age at diagnosis was 10.5 years. Males represented 18/26 cases. Warmblood (14) and Thoroughbred (6) breeds were most commonly represented. 25/26 had unilateral ocular involvement. No cases had evidence of multicentric lymphoma. Most eyes (77.7%) had a history of suspected immune-mediated keratitis (IMMK) or eosinophilic keratitis. Morphological diagnosis confirming lymphoma was available for all cases. B-cell lymphoma was diagnosed in 19/24 eyes for which immunohistochemistry was performed, with intermediate to large B-cell lymphoma being most common. Fifteen of 27 eyes received at least one form of adjunctive therapy following keratectomy. Four eyes, which did not receive adjunctive therapy following keratectomy, experienced recurrence. No horses treated with adjunctive therapy following keratectomy experienced recurrence. Malignant transformation of IMMK to lymphoma was morphologically documented in one eye and suspected in three others based on recurrence of clinical signs. All globes were retained and visualised at the last follow-up. Incomplete medical records, owner subjectivity concerning onset of disease and cases being lost to follow-up. Malignant transformation of IMMK to corneal lymphoma likely occurs in horses. Lymphoma should be a differential for nonulcerative keratitis in horses. Keratectomy and histopathology may be considered in progressive or refractory cases of IMMK to rule out neoplastic disease. Recurrence of corneal lymphoma is unlikely following excision and adjunctive therapy. Cases with large corneal surface area or deep stromal involvement may have a likelihood for recurrence.

Establishing a Severe Corneal Inflammation Model in Rats Based on Corneal Epithelium Curettage Combined with Corneal Sutures.

Corneal inflammation, especially severe corneal inflammation, plays a significant role in the development of corneal limbal stem cell dysfunction. Constructing appropriate animal models can help us focus on the effects of severe inflammation on corneal limbal stem cells. A 2 mm rust removerwasused to remove the central corneal epithelium of Sprague Dawley (SD) rats to create an injury. Then, the central stroma of the cornea was sutured with nylon sutures to induce persistent inflammation. In this way, a corneal inflammation model with central corneal epithelium abrasion and central stroma suturing was constructed, which induced severe corneal inflammation. The changes in corneal inflammation and the condition of the limbal stem cells at 1, 3, and 7 days post-modeling were observed. On the 3rd day after modeling, the rats' corneal limbus was severely edematous, with obvious neovascularization and local hyperplasia, which are typical signs of limbal stem cell deficiency. By the 7th day, the corneal edema gradually worsened, and the neovascularization continued to increase. Through quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunofluorescence staining, we found that the corneal epithelial inflammatory factors were significantly upregulated, the corneal epithelial differentiation was abnormal, the corneal epithelial stem cells were significantly reduced, and the cell proliferation and stemness had also decreased. Therefore, this model demonstrates that severe inflammation can induce limbal stem cell damage without directly damaging the limbal stem cells. The model is beneficial for observing the effects of severe inflammation on the biological mechanisms of stem cells and provides an ideal platform for studying the mechanisms of corneal epithelial stem cell dysfunction induced by inflammation.

Treatment of Acanthamoeba keratitis with high dose PHMB (0.08%) monotherapy in clinical practice: A case series.

Acanthamoeba keratitis (AK) is a rare sight-threatening infectious disease with no approved pharmacological treatments. Topical polihexanide 0.8 mg/ml (PHMB 0.08%) completed a pivotal clinical trial showing a medical cure rate of 84.9%. The purpose of this study is to evaluate the efficacy and safety of PHMB 0.08%, given as monotherapy, in clinical practice. consecutive cases of AK were included. Diagnosis was confirmed by in vivo confocal microscopy or PCR. Patients were treated with PHMB 0.08% as part of a name-based compassionate use program. Treatment delivery frequency and termination were as advised in the pivotal clinical trial. Medical cure was defined as clinical evidence of healed epithelium and absence of corneal inflammation lasting 3 months after discontinuing all treatments. twelve eyes of 11 contact lens wearers with AK of variable severity were evaluated. Eleven of 12 (91.7%) eyes achieved a medical cure with no surgery. One eye had a corneal perforation and required emergency therapeutic keratoplasty. The median time of treatment with PHMB 0.08% was 100 days (range 35-222). Seven eyes (58.3%) reached a final visual acuity of 20/50 Snellen or better. Two subject reported worsening of conjunctival hyperaemia during the intensive phase of the treatment. No other adverse drug reactions were observed. topical treatment with PHMB 0.08% monotherapy successfully cured AK in 11 of 12 eyes when used in real-world clinical practice, thereby confirming that results observed in the clinical trial could be obtained in this setting.

Virtual Screening and Meta-Analysis Approach Identifies Factors for Inversion Stimulation (Fis) and Other Genes Responsible for Biofilm Production in Pseudomonas aeruginosa: A Corneal Pathogen.

Bacterial keratitis caused by Pseudomonas aeruginosa is indeed a serious concern due to its potential to cause blindness and its resistance to antibiotics, partly attributed to biofilm formation and cytotoxicity to the cornea. The present study uses a meta-analysis of a transcriptomics dataset to identify important genes and pathways in biofilm formation of P. aeruginosa induced keratitis. By combining data from several studies, meta-analysis can enhance statistical power and robustness, enabling the identification of 83 differentially expressed candidate genes, including fis that could serve as therapeutic targets. The approach of combining meta-analysis with virtual screening and in vitro methods provides a comprehensive strategy for identifying potential target genes and pathways crucial for bacterial biofilm formation and development anti-biofilm medications against P. aeruginosa infections. The study identified 83 candidate genes that exhibited differential expression in the biofilm state, with fis proposed as an ideal target for therapy for P. aeruginosa biofilm formation. These techniques, meta-analysis, virtual screening, and invitro methods were used in combination to diagnostically identify these genes, which play a significant role in biofilms. This finding has highlighted a hallmark target list for P. aeruginosa anti-biofilm potential treatments.

Clinical characteristics, risk factor analysis and outcomes in 61 eyes with graft rejection after descemet stripping endothelial keratoplasty, with a review of literature.

To report the demographic profile, clinical characteristics, risk factors and outcomes of graft rejection after DSEK. A total of 3073 eyes had DSEK between 2012 and 2019, of which 1710 eyes that had follow up of more than one year. Sixty-one eyes who had graft rejection during this period were studied. Overall, incidence of graft rejection during the study period was 3.6% (61/1710 eyes) in those with follow up more than one year. The median age of patients was 58 (IQR 37.5-68) years. The indications were prior failed graft (34 eyes: 28 penetrating keratoplasty; 6 DSEK), post cataract surgery edema (12 eyes), Fuchs corneal endothelial dystrophy (6 eyes), corneal edema post inflammation (5 eyes) and iridocorneal endothelial syndrome (4 eyes). Of the 34 eyes with failed grafts, nine were post-rejection graft failures (two after endothelial keratoplasty and seven after penetrating keratoplasty), remaining 25 eyes were non-rejection graft failures. Ocular co-morbidities were noted in 41 eyes, of which secondary glaucoma was the most common (14 eyes). Clinical signs of graft rejection were diffuse edema, keratic precipitates and endothelial rejection line. Rejection episode occurred between 6-12months after surgery in 20 (33%) eyes, 12-24months in 15 (25%) eyes, 2-3years in 12 (20%) eyes, and beyond 3years in 14(23%) eyes. Graft clarity was restored in 55 (90%) eyes, which was complete in 41 (67%) eyes, partial in 14 (23%) eyes, and clarity was not restored in 6 (10%) eyes. The statistically significant risk factors for rejection were non-use of steroids (p value < 0.001), DSEK for failed graft (p value < 0.02) and DSEK for corneal edema post-inflammation (p value < 0.0014). DSEK for failed graft was a significant risk factor for graft failure after the rejection episode (p value < 0.05). Graft rejection may occur as late as 5years post-DSEK, emphasizing the need for long-term steroids instillation. Non-use of topical steroids, DSEK for failed graft and corneal edema post inflammation are risk factors for graft rejection. DSEK for failed graft was also seen as a risk factor for failure after the rejection episode The graft survival rate after the rejection episode was 90% at 6months, 50% at 2years and 10% at 5years.

Exploring the therapeutic potential: sinomenine and melatonin in alkali-induced corneal burns.

This study aimed to investigate the effects of sinomenine and melatonin on corneal alkali burns. Twenty-seven female Wistar albino rats, aged 3-6months and weighing 200-300g, were used in this study. After the induction of general anesthesia, 2mol/L sodium hydroxide (NaOH) solution was used to create corneal alkali burns in all experimental animals. The rats were divided into three groups: Group C, control group with no additional treatment; Group M, topical melatonin drop group; and Group S, topical sinomenine group. The rats were sacrificed under general anesthesia on the 7th day. Various parameters, including corneal inflammation, neovascularization, epithelialization, epithelial proliferating cell nuclear antigen (PCNA), epithelial inducible nitric oxide synthase (INOS), stromal INOS, and thickness, were evaluated. The experiment was completed with 27 rats distributed into three groups of nine rats each. Significant differences were observed between the groups in terms of stromal thickness, inflammation, epithelial iNOS, stromal iNOS, and epithelialization (p = 0.008, p = 0.005, p = 0.020, p = 0.037, and p = 0.000, respectively). The best stromal thickness was observed in Group M. Vascularization, inflammation, epithelial INOS, stromal iNOS, and epithelialization were most effectively reduced in Group S, followed by Group M. Group S outperformed Group C significantly in all these aspects (p = 0.049, p = 0.004, p = 0.015, p = 0.036, p = 0.000, respectively). There was no significant difference between the groups in terms of the epithelial PCNA levels (p = 0.259). The results suggest that topical sinomenine and melatonin have anti-inflammatory, anti-angiogenic, and reepithelialization effects when applied after alkali burns in rat corneas.

Subclinical corneal inflammation and subbasal nerve alterations in keratoconus detected by in vivo confocal microscopy: a cross-sectional study.

To investigate the intracorneal inflammation and subbasal nerve alterations in keratoconus. This prospective cross-sectional study recruited patients with keratoconus, who were diagnosed and graded the severity based on clinical examination and Schiempflug tomography. Laser in vivo confocal microscopy (IVCM) was performed on the corneal subbasal layer centrally to explore the inflammatory cells (ICs), subbasal nerve density (SND), and nerve tortuosity. Keratoconus severity and related factors including ocular allergy, systemic atopy, eye rubbing, floppy eyelids, and contact lens use were recorded. Association between the factors, IC density, SND and keratoconus severity were analyzed. Thirty-four keratoconus eyes were enrolled, and their IVCM findings were compared with those of 20 age-matched normal eyes. Keratoconus showed a significant increase in ICs (44.25 ± 7.01 vs. 13.06 ± 7.51 cells/mm2, p < 0.001) and a significant decrease in SND (16.54 ± 0.79 vs. 20.62 ± 0.72mm/mm2, p < 0.001) when compared to controls. The alterations were pronounced in severe keratoconus as the IC density was significantly higher (p < 0.001), whereas SND was lower (p = 0.001) in high-graded keratoconus than in low-graded keratoconus. However, there was no significant correlation between the number of IC and SND in keratoconus eyes (p = 0.835). Corneal sensitivity and nerve tortuosity were not different between keratoconus and the controls. No keratoconus-related factors were associated with IC density except the severity of keratoconus (p < 0.001, 95% CI [0.70, 0.95]). Keratoconus, a clinically noninflammatory corneal disease, demonstrates subclinical corneal inflammation and subbasal nerve decline as shown by IVCM. These alterations correlate considerably with the severity of keratoconus. What is known Traditionally, Keratoconus is a clinically noninflammatory corneal disease. What is new Our study suspected keratoconus may be subclinical corneal inflammatory disease. In our research, A Keratoconus patient was discovered to have corneal inflammation and a reduction in sub-basal nerve density through the use of In Vivo Confocal Microscopy. Increase in corneal inflammation is considerably correlated with the severity of keratoconus.

Bandage Contact Lens Associated Infection after Amnion Membrane Transplantation in Peripheral Ulcerative Keratitis Case with Spondyloarthritis

Introduction: Bacterial keratitis causes around 90% of all cases of microbial keratitis. The global rise in contact lens usage has contributed to an increased risk of microbial keratitis. Peripheral ulcerative keratitis (PUK) is essential to diagnose as it can be the first presenting feature of a sight-threatening and associated with rheumatic autoimmune disease. Case Presentation: The case presents a 35-year-old woman with redness, discharge, and tenderness in her right eye (RE) since the day before, along with light sensitivity and tearing. Three months prior, she underwent multilayer amniotic membrane transplantation (AMT) surgery for corneal thinning due to peripheral ulcerative keratitis (PUK) and wore a contact lens postoperatively as a bandage. She had a history of conjunctival resection related to the PUK a year ago. She received oral cyclosporin and methylprednisolone for spondyloarthritis. Initially, her visual acuity of the RE was limited to hand movement. Diagnosis included RE keratoconjunctivitis related to contact lens and PUK post-AMT surgery; treatment comprised intravenous and topical antibiotics, artificial tears, cycloplegics, analgesics, and oral ascorbic acid. After four days of treatment, clinical signs were improved, with visual acuity progressing from hand movement to counting fingers at one meter. Conclusions: Careful management is essential for PUK patients after AMT surgery, especially those using contact lenses as bandages due to the potential risk of infection. Early PUK identification is crucial, as it may indicate sight-threatening issues and underlying systemic diseases. Meticulous examination and multidisciplinary management are required to ensure patient safety.

Bacterial isolates and antibiotic sensitivity in canine bacterial keratitis in Korea.

To analyze bacterial isolates associated with canine bacterial keratitis and their antibiotic susceptibility patterns in Korea, focusing on multidrug resistance (MDR) and identifying effective antibiotic combinations for clinical treatment. A total of 146 dogs diagnosed with suspected bacterial keratitis between October 2022 and October 2023 in Korea, with 157 eye samples collected for analysis. Eye samples were cultured to isolate bacteria, and antibiotic susceptibility testing was performed using the minimum inhibitory concentration (MIC) method. Bacterial identification was conducted using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF). The study assessed the efficacy of individual antibiotics and combination therapies. Bacteria were isolated in 55.4% of the samples. The most common genera were Staphylococcus species (48.5%, 48/99), Streptococcus species (13.1%, 13/99), Pseudomonas species (9.1%, 9/99), and Escherichia coli (9.1%, 9/99). Amikacin (84.8%) showed the highest antibiotic susceptibility, while doxycycline exhibited the lowest (17.2%). The most effective antibiotic combinations were amikacin-moxifloxacin (93%). MDR isolates accounted for 52.5% (52/99) of the total bacterial samples. Staphylococcus species were the most common isolates, with 52.5% showing MDR, underscoring the need to curb antibiotic misuse. While antibiotics like amikacin demonstrated high susceptibility rates, their use should be reserved for resistant infections to prevent further resistance development. Rather than focusing solely on finding effective combinations of antibiotics, it is crucial to consider alternative treatment strategies that offer more sustainable solutions. Rather than relying on antibiotic combinations, attention should shift to sustainable alternatives to treat bacterial keratitis and reduce antibiotic dependence in clinical practice.

Effects of miR-204-5p modulation on PAX6 regulation and corneal inflammation

Congenital aniridia is a rare eye disease characterized by loss of PAX6 protein leading to aniridia-associated keratopathy that significantly reduces vision. The miR-204-5p is a possible regulator of PAX6 function and here we evaluate its effect in multiple in vitro and in vivo models. In vitro, miR-204-5p overexpression suppressed vascular factor ANGPT1 in human limbal stem cells (T-LSC) and Pax6-knockdown LSC (mut-LSC), and in primary human limbal epithelial cells (LEC) at the gene and protein levels and following LPS stimulation. However, miR-204-5p inhibited VEGFA expression only in mut-LSCs and LPS-stimulated LEC. Also, miR-204-5p increased PAX6 expression in mut-LSC and differentiated corneal epithelial cells, but not in LEC. Topical miR-204-5p after LPS-induced keratitis in mice failed to suppress Vegfa, Angpt1, Il-1β, and Tnf-α or rescue Pax6 levels in contrast to in vitro results, although it significantly reduced the inflammatory infiltrate in the cornea. In Pax6Sey/+ aniridia mice, miR-204-5p did not rescue PAX6 levels or suppress Vegfa, Angpt1, or inhibit the ERK1/2 pathway. While short-term miR-204-5p treatment effectively suppresses VEGFA and ANGPT1 and enhances PAX6 expression in multiple corneal epithelia, effects are variable across primary and immortalized cells. Effects of longer-term in vivo treatment, however, require further study.

Multimodal Deep Learning for Differentiating Bacterial and Fungal Keratitis Using Prospective, Representative Data

ObjectiveThis study develops and evaluates multimodal machine learning models for differentiating bacterial and fungal keratitis using a prospective, representative dataset from South India. DesignMachine learning classifier training and validation study. Participants599 subjects diagnosed with acute infectious keratitis at Aravind Eye Hospital in Madurai, India. MethodsWe developed and compared three prediction models to distinguish bacterial and fungal keratitis using a prospective, consecutively-collected, representative dataset gathered over a full calendar year (the MADURAI dataset). These models included a clinical data model, a computer vision model using the EfficientNet architecture, and a multimodal model combining both imaging and clinical data. We partitioned the MADURAI dataset into 70% train/validation and 30% test sets. Model training was performed with 5-fold cross-validation. We also compared the performance of the MADURAI-trained computer vision model against a model with identical architecture but trained on a pre-existing dataset collated from multiple prior bacterial and fungal keratitis randomized clinical trials (the RCT-trained computer vision model). Main Outcome MeasuresThe primary evaluation metric was the area under the precision-recall curve (AUPRC). Secondary metrics included area under the receiver operating curve (AUROC), accuracy, and F1 score. ResultsThe MADURAI-trained computer vision model outperformed the clinical data model and the RCT-trained computer vision model on the hold-out test set, with an AUPRC 0.94 (95% CI: 0.92-0.96), AUROC 0.81 (0.76-0.85), accuracy 77%, and F1 score 0.85. The multimodal model did not substantially improve performance compared to the computer vision model. ConclusionsThe best-performing machine learning classifier for infectious keratitis was a computer vision model trained using the MADURAI dataset. These findings suggest that image-based deep learning could significantly enhance diagnostic capabilities for infectious keratitis, and emphasize the importance of using prospective, consecutively-collected, representative data for machine learning model training and evaluation.

Developments in Emerging Topical Drug Delivery Systems for Ocular Disorders.

According to the current information, using nano gels in the eyes have therapeutic benefits. Industry growth in the pharmaceutical and healthcare sectors has been filled by nanotechnology. Traditional ocular preparations have a short retention duration and restricted drug bioavailability because of the eye's architectural and physiological barriers, a big issue for physicians, patients, and chemists. In contrast, nano gels can encapsulate drugs within threedimensional cross-linked polymeric networks. Because of their distinctive structural designs and preparation methods, they can deliver loaded medications in a controlled and sustained manner, enhancing patient compliance and therapeutic efficacy. Due to their excellent drugloading capacity and biocompatibility, nano-gels outperform other nano-carriers. This study focuses on using nano gels to treat eye diseases and provides a brief overview of their creation and response to stimuli. Our understanding of topical drug administration will be advanced using nano gel developments to treat common ocular diseases such as glaucoma, cataracts, dry eye syndrome, bacterial keratitis, and linked medication-loaded contact lenses and natural active ingredients.