The antibiotic resistance profiles of Pseudomonas aeruginosa in the Asia Cornea Society Infectious Keratitis Study.

PURPOSE: To describe the prevalence and antibiotic resistance profiles of Pseudomonas aeruginosa isolated from the Asia Cornea Society Infectious Keratitis Study (ACSIKS). METHODS: All bacterial isolates from ACSIKS underwent repeat microbiological identification in a central repository in Singapore. Minimum inhibitory concentration (MIC) determination was conducted for isolates of P. aeruginosa against thirteen antibiotics from 6 different classes, and categorized based on Clinical Laboratory Standard Institutes' reference ranges. The percentage rates of resistance (non-susceptibility) to each antibiotic included isolates of both intermediate and complete resistance. Multi-drug resistance (MDR) was defined as non-susceptibility to at least one agent in three or more antimicrobial classes. RESULTS: Of the 1493 unique bacterial specimens obtained from ACSIKS, 319 isolates were of P. aeruginosa. The majority of isolates were from centers in India (n = 118, 37%), Singapore (n = 90, 28.2%), Hong Kong (n = 31, 9.7%) and Thailand (n = 30, 9.4%). The cumulative antibiotic resistance rate was the greatest for polymyxin B (100%), ciprofloxacin (17.6%) and moxifloxacin (16.9%), and lowest for cefepime (11.6%) and amikacin (13.5%). Isolates from India demonstrated the highest antibiotic resistance rates of all the centers, and included moxifloxacin (47.5%) and ciprofloxacin (39.8%). Forty-eight of the 59 MDR isolates also originated from India. Antibiotic resistance rates were significantly lower in the other ACSIKS centers, and were typically less than 10%. CONCLUSIONS: The antibiotic resistance profiles of P. aeruginosa varied between different countries. While it was low for most countries, substantial antibiotic resistance and a significant number of multi-drug resistant isolates were noted in the centers from India.

Peripheral ulcerative keratitis secondary to tuberculosis: A case report and literature review.

RATIONALE: Compared with intraocular tuberculosis, ocular tuberculosis with ocular surface involvement is rare. Corneal involvement in ocular tuberculosis may include interstitial keratitis or peripheral ulcerative keratitis. We report a case of peripheral ulcerative keratitis directly caused by tuberculosis. PATIENT CONCERNS: A 20-year-old man complained of vision loss and pain in the left eye that had lasted for 1 week. A slit lamp examination of the left eye showed a corneal epithelial defect, interstitial corneal edema, and a white irregular infiltrative lesion and ulcer (with the dimension of 2 × 2.5 mm) in the inferior temporal region. DIAGNOSES: The corneal ulcer was scraped, and the Mycobacterium tuberculosis deoxyribonucleic acid polymerase chain reaction was positive. INTERVENTIONS AND OUTCOMES: After a month of oral antituberculosis treatment, the corneal ulcer resolved, and the intraocular inflammation improved. LESSONS: Peripheral ulcerative keratitis secondary to tuberculosis can be directly caused by M tuberculosis.

Etiologies of Infectious Keratitis in Malawi.

Infectious keratitis is a leading cause of corneal blindness worldwide with little information known about causative etiologies in Malawi, Africa. This area is resource-limited with ophthalmologist and microbiology services. The Department of Ophthalmology at the Kamuzu College of Health Sciences in Blantyre, Malawi, is a participating site of an international corneal ulcer consortium, capriCORN (Comprehensive Analysis of Pathogens, Resistomes, and Inflammatory-markers in the CORNea). In this study, 50 patients with corneal ulcers were swabbed for pathogen identification using RNA-sequencing. Corneal trauma was reported in 41% and 19% of the patients worked in agriculture. A pathogen was identified in 58% of the cases. Fungal pathogens predominated, followed by viruses and bacteria. Aspergillus, Fusarium, HSV-1, and Gardnerella were the most common pathogens detected. 50% of patients reported treatment with an antibiotic before presentation. Pathogens unusual for infectious keratitis, such as Subramaniula asteroids, Aureobasidium pullulans, and Gardnerella vaginalis, were also detected.

Post-LASIK Exophiala jeanselmei Keratitis.

OBJECTIVE: To describe a patient diagnosed with Exophiala jeanselmei keratitis. METHODS: We report a case of a patient who developed infectious keratitis following laser in situ keratomileusis and chronic topical steroid use for approximately six months in both eyes. An atypical infiltrate containing dark pigmentation was noted in the left eye on the initial presentation. During treatment, the infiltrates of the right eye began to exhibit a similar pigmentation. RESULTS: Early treatment with topical antifungals was initiated in the left eye and later in the right eye once culture results returned. Both eyes recovered with good vision after approximately one month. CONCLUSIONS: Patients treated with postoperative topical corticosteroids should be cautioned of potential adverse effects of chronic use and have close follow-up. If infectious keratitis develops, particularly after two weeks, then atypical organisms, such as fungi, should be considered. In addition, our case highlights the significance of recognizing and associating dark-pigmentation with fungal etiologies.

Establishment of a corneal ulcer prognostic model based on machine learning.

Corneal infection is a major public health concern worldwide and the most common cause of unilateral corneal blindness. Toxic effects of different microorganisms, such as bacteria and fungi, worsen keratitis leading to corneal perforation even with optimal drug treatment. The cornea forms the main refractive surface of the eye. Diseases affecting the cornea can cause severe visual impairment. Therefore, it is crucial to analyze the risk of corneal perforation and visual impairment in corneal ulcer patients for making early treatment strategies. The modeling of a fully automated prognostic model system was performed in two parts. In the first part, the dataset contained 4973 slit lamp images of corneal ulcer patients in three centers. A deep learning model was developed and tested for segmenting and classifying five lesions (corneal ulcer, corneal scar, hypopyon, corneal descementocele, and corneal neovascularization) in the eyes of corneal ulcer patients. Further, hierarchical quantification was carried out based on policy rules. In the second part, the dataset included clinical data (name, gender, age, best corrected visual acuity, and type of corneal ulcer) of 240 patients with corneal ulcers and respective 1010 slit lamp images under two light sources (natural light and cobalt blue light). The slit lamp images were then quantified hierarchically according to the policy rules developed in the first part of the modeling. Combining the above clinical data, the features were used to build the final prognostic model system for corneal ulcer perforation outcome and visual impairment using machine learning algorithms such as XGBoost, LightGBM. The ROC curve area (AUC value) evaluated the model's performance. For segmentation of the five lesions, the accuracy rates of hypopyon, descemetocele, corneal ulcer under blue light, and corneal neovascularization were 96.86, 91.64, 90.51, and 93.97, respectively. For the corneal scar lesion classification, the accuracy rate of the final model was 69.76. The XGBoost model performed the best in predicting the 1-month prognosis of patients, with an AUC of 0.81 (95% CI 0.63-1.00) for ulcer perforation and an AUC of 0.77 (95% CI 0.63-0.91) for visual impairment. In predicting the 3-month prognosis of patients, the XGBoost model received the best AUC of 0.97 (95% CI 0.92-1.00) for ulcer perforation, while the LightGBM model achieved the best performance with an AUC of 0.98 (95% CI 0.94-1.00) for visual impairment.

Ochrobactrum anthropi infection following corneal transplantation -a case report and review of literature.

BACKGROUND: Ochrobactrum anthropi is widely distributed and primarily infects patients with compromised immune functions . Historically, O. anthropi has been considered to possess low toxicity and pathogenicity; however, recent studies suggest that it may in fact cause severe purulent infections. In this case study, we examine a case of O. anthropi infection following corneal transplantation, exploring the occurrence and outcomes of such post-operative infections. CASE PRESENTATION: A retrospective analysis of cases involved examinations, genetic testing for diagnosis, and subsequent treatment. In patients undergoing partial penetrating keratoplasty with a fungal corneal ulcer perforation, anterior chamber exudation and purulence were observed post-surgery. Despite antifungal treatment, genetic testing of the anterior chamber fluid and purulent material confirmed O. anthropi infection. The use of antimicrobial treatment specifically targeting O. anthropi was found to be effective in treating the infection. CONCLUSION: Inflammatory reactions following corneal transplantation should be should be monitored for the presence of other infections. Genetic testing has significant implications for clinical diagnosis and treatment.

Involvement of cGAS/STING Signaling in the Pathogenesis of Candida albicans Keratitis: Insights From Genetic and Pharmacological Approaches.

Purpose: Fungal keratitis (FK) is an invasive corneal infection associated with significant risk to vision. Although the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway has been recognized for its role in defending against viral infections, its involvement in FK still remains largely unclear. This study sought to elucidate the contribution of the cGAS/STING signaling pathway to the pathogenesis of FK. Methods: The expression of cGAS/STING signaling components was assessed in a murine model of Candida albicans keratitis through RNA sequencing, western blot analysis, immunofluorescence staining, and real-time PCR. Both genetic (utilizing Sting1gt/gt mice) and pharmacological (using C176) interventions were employed to inhibit STING activity, allowing for the evaluation of resultant pathogenic alterations in FK using slit-lamp examination, clinical scoring, hematoxylin and eosin (H&E) staining, fungal culture, and RNA sequencing. Subconjunctival administration of the NOD-like receptor protein 3 (NLRP3) inflammasome inhibitor MCC950 was performed to evaluate FK manifestations following STING activity blockade. Furthermore, the impact of the STING agonist diABZI on FK progression was investigated. Results: Compared to uninfected corneas, those infected with C. albicans exhibited increased expression of cGAS/STING signaling components, as well as its elevated activity. Inhibiting cGAS/STING signaling exacerbated the advancement of FK, as evidenced by elevated clinical scores, augmented fungal load, and heightened inflammatory response, including NLRP3 inflammasome activation and pyroptosis. Pharmacological inhibition of the NLRP3 inflammasome effectively mitigated the exacerbated FK by suppressing STING activity. Conversely, pre-activation of STING exacerbated FK progression compared to the PBS control, characterized by increased fungal burden and reinforced inflammatory infiltration. Conclusions: This study demonstrates the essential role of the cGAS/STING signaling pathway in FK pathogenesis and highlights the necessity of its proper activation for the host against FK.

Topical Vancomycin is More Efficient than Povidone-Iodine Treatment in Controlling Bacterial Growth in Methicillin-Resistant Staphylococcus Aureus Keratitis Model in Rabbits.

To evaluate the efficacy of topical vancomycin and povidone iodine (PI) application on methicillin-resistant Staphylococcus aureus (MRSA) keratitis model in rabbits.MRSA keratitis was induced by injecting 0.1 mL MRSA containing 1000 colony-forming units (CFU) into central cornea of right eyes of 24 New Zealand White rabbits. Animals were divided into four groups (n = 6): control (treated with balanced salt solution), 50 mg/mL topical vancomycin, 5% topical PI, and combination; examined before and after treatment, and corneal tissues were harvested for analysis at 9th hour of treatment.Bacterial load was determined as: 7.63 ± 0.82 log10 CFU/g in control group, 6.95 ± 1.66 log10 CFU/g in PI group, 4.67 ± 0.77 log10 CFU/g in combination group, and 4.33 ± 0.71 log10 CFU/g in vancomycin group (p = 0.001). Median of total clinical score increased significantly from 7 [range: 5-8] to 11.5 [range: 11-15] (p = 0.001) in control group, did not change (6 [range: 5-8] to 7 [range: 5-7]; p = 0.695) in vancomycin group, increased significantly from 7 [range: 5-8] to 12.5 [range: 10-14] (p < 0.001) in PI group, increased significantly from 6.5 [range: 5-7] to 8 [range: 7-9] in combination group (p = 0.002). Post-treatment clinical scores for chemosis, conjunctival injection, iritis, hypopyon, epithelial erosion, and corneal infiltrate were significantly lower in vancomycin-treated groups compared to others (p < 0.05). In PI-treated groups, especially scores for chemosis, conjunctival injection, epithelial erosion and corneal infiltrate were significantly higher than vancomycin (p < 0.05).Topical vancomycin significantly inhibited bacterial growth in MRSA keratitis. However, PI was ineffective in controlling this growth; additionally, exerted toxic effect on ocular surface. When vancomycin was combined with PI, no additional increase in efficacy of treatment was detected compared to only vancomycin.

Automated Measurement and Three-Dimensional Fitting of Corneal Ulcerations and Erosions via AI-Based Image Analysis.

PURPOSE: Artificial intelligence (AI)-tools hold great potential to compensate for missing resources in health-care systems but often fail to be implemented in clinical routine. Intriguingly, no-code and low-code technologies allow clinicians to develop Artificial intelligence (AI)-tools without requiring in-depth programming knowledge. Clinician-driven projects allow to adequately identify and address real clinical needs and, therefore, hold superior potential for clinical implementation. In this light, this study aimed for the clinician-driven development of a tool capable of measuring corneal lesions relative to total corneal surface area and eliminating inaccuracies in two-dimensional measurements by three-dimensional fitting of the corneal surface. METHODS: Standard slit-lamp photographs using a blue-light filter after fluorescein instillation taken during clinical routine were used to train a fully convolutional network to automatically detect the corneal white-to-white distance, the total fluorescent area and the total erosive area. Based on these values, the algorithm calculates the affected area relative to total corneal surface area and fits the area on a three-dimensional representation of the corneal surface. RESULTS: The developed algorithm reached dice scores >0.9 for an automated measurement of the relative lesion size. Furthermore, only 25% of conventional manual measurements were within a ± 10% range of the ground truth. CONCLUSIONS: The developed algorithm is capable of reliably providing exact values for corneal lesion sizes. Additionally, three-dimensional modeling of the corneal surface is essential for an accurate measurement of lesion sizes. Besides telemedicine applications, this approach harbors great potential for clinical trials where exact quantitative and observer-independent measurements are essential.

Peripheral Ulcerative Keratitis: Clinical Characteristics, Differential Diagnoses and Therapeutic Concepts. / Periphere ulzerative Keratitis: Klinik, Differenzialdiagnosen und Therapiekonzepte.

Peripheral ulcerative keratitis (PUK) is an inflammatory disease of the peripheral cornea, which may frequently be associated with several rare, but potentially life-threatening systemic diseases. The inflammatory pathogenesis of PUK results from humoral and cell-mediated inflammation. The diagnosis is usually based on the typical clinical findings and always requires detailed diagnostic testing to identify a potential systemic underlying disease. Treatment includes topical and systemic immunosuppressive and immunomodulatory therapeutic strategies and, in the event of impending or existing perforation, also various surgical interventions. PUK is a potentially blinding disease that initially affects the periphery, but, if left untreated, can lead to destruction of the entire cornea. Interdisciplinary diagnostic testing and therapy are crucial to preserve vision in the affected patients and reduce morbidity and mortality. The following article provides an overview of the pathophysiology, clinical findings, possible underlying systemic diseases, relevant differential diagnoses and therapeutic strategies.

Real-life experience on the effectiveness of conjunctival flap and amniotic membrane graft in the treatment of refractory fungal corneal ulcer.

PURPOSE: To evaluate and compare the results of the conjunctival flap (CF) and cryopreserved amniotic membrane graft (AMG) in the management of fungal corneal ulcers either with complications or non-responsive to medical treatment. STUDY DESIGN: A retrospective observational study. METHODS: Medical records of 30 patients with culture-positive fungal corneal ulcer treated with either CF or AMG (15 eyes in each group) in real world settings were retrieved for analysis. After the surgical procedure, patients were followed up on days 1, 7, 14, 21, 30, 60, 90, 120, and 180 to explore the outcomes of the operations along with complications. RESULTS: Infecting fungi were of genus Fusarium (n = 11), Aspergillus (n = 10), Mucor (n = 4) and Penicillium (n = 10). The most common indication was resistant ulcer with perforation. After the procedure, epithelization was completed in 11(73.33%) patients in the CF, and 13 patients in the (86.67%) AMG group. Visual acuity improvement was significantly better in the latter group (CF: 1 [6.67%] vs. AMG: 7 [46.67%], p = 0.023). Flap failure occurred in 4 patients (26.67%) from the CF and 2 (13.33%) from the AMG group. No significant differences were found between the two groups regarding success rate (p = 0.651), epithelialization time (p = 0.691), healing of corneal ulcer (p = 0.651), and postoperative stability (p = 0.651) of the flaps. CONCLUSIONS: CF and AMG are both effective for the management of refractory fungal corneal ulcers. However, AMG appears to improve visual acuity better than CF.

Corneal Complications Related to Dupilumab Use.

OBJECTIVES: The aim of this report is to describe atypical corneal complications associated with dupilumab use. METHODS: This is a series of four cases of adult patients with infiltrative or ulcerative keratitis secondary to dupilumab use. RESULTS: All four patients in this series were prescribed dupilumab for the treatment of atopic dermatitis and developed infiltrative or ulcerative corneal lesions. In all cases, corneal disease was successfully managed with immediate discontinuation of dupilumab and topical steroid treatment. In two cases, the patient also received antibiotic eye drops for infection precautions. CONCLUSIONS: Although dupilumab is most commonly associated with conjunctivitis, physicians should be aware of potential severe corneal complications for early identification and intervention.

Immediate postoperative keratitis caused by Rhizopus species following standard CXL for keratoconus: A case report and literature review.

PURPOSE: To report the first case of Rhizopus sp keratitis in a 15-year-old male patient who had undergone a conventional Epi-off CXL procedure for progressive keratoconus. METHODS: A 15-year-old male studying at school presented with defective vision in both eyes recently. He was diagnosed with progressive keratoconus in the right eye more than left eye. After the conventional CXL procedure, the patient developed corneal ulcer on third postoperative day. RESULTS: The microbiological diagnosis of both BCL and ulcer revealed Rhizopus sp. The patient responded to topical antifungals, and the ulcer entirely healed with a large central scar. CONCLUSION: Rhizopus keratitis is rare in a healthy individual. Ours is the first case report of Rhizopus keratitis in patient undergone CXL.

Trends and Clinical Outcomes of Fungal Keratitis in Canada: A 20-year Retrospective Multicentre Study.

PURPOSE: An increase in fungal and particularly filamentous keratitis has been observed in many geographic areas, mostly in contact lens wearers. This study seeks to characterize long-term trends in fungal keratitis in a continental climate area to provide guidance for diagnosis and treatment. DESIGN: Retrospective multicentric case series. METHODS: Cases of microbiology-confirmed fungal keratitis from 2003 to 2022 presenting to tertiary care centers across Canada were included. Charts were reviewed for patient demographics, risk factors, visual acuity, and treatments undertaken. RESULTS: A total of 138 patients were identified: 75 had yeast keratitis while 63 had filamentous keratitis. Patients with yeast keratitis had more ocular surface disease (79% vs 28%) while patients with filamentous keratitis wore more refractive contact lenses (78% vs 19%). Candida species accounted for 96% of all yeast identified, while Aspergillus (32%) and Fusarium (26%) were the most common filamentous fungi species. The mean duration of treatment was 81 ± 96 days. Patients with yeast keratitis did not have significantly improved visual acuity with medical treatment (1.8 ± 1 LogMAR to 1.9 ± 1.5 LogMAR, P = .9980), in contrast to patients with filamentous keratitis (1.4 ± 1.2 LogMAR to 1.1 ± 1.3 LogMAR, P = .0093). CONCLUSIONS: Fungal keratitis is increasing in incidence, with contact lenses emerging as one of the leading risk factors. Significant differences in the risk factors and visual outcomes exist between yeast keratitis and filamentous keratitis which may guide diagnosis and treatment.

Limbal reconstruction in uveitic glaucoma patient with exposed Ahmed valve coincident with corneal melting and iris prolapse using multiple corneoscleral allografts.

Aim: To present a complex case of Ahmed tube exposure 6 months after the implantation associated with corneal melting and iris prolapse, and the surgical reposition that required multiple allografts and limbal reconstruction. Methods: A 60-year-old patient arrived at the emergency room with tube exposure combined with corneal melting and iris prolapse from a previously placed Ahmed valve 6 months prior. Our approach was to use one corneoscleral graft to repair the melted cornea and avoid further iris prolapse and a second scleral graft to cover the repositioned tube. Upon completion of conjunctival dissection, cleaning and deepithelization of the melted cornea and the tube by application of alcohol 100% followed. A new entry point was made for the tube and was covered using an alcohol-preserved scleral allograft and the previous entry point was repaired using a corneoscleral allograft with the corneal aspect restoring the limbus and avoiding further iris protrusion. Results: 6 months follow-up of the patient showed excellent recovery, anatomical restoration, and IOP normalization. Conclusion: Surgical repair of these cases can be very demanding, and requires surgical improvisation and prolonged surgical time. The literature remains very limited on how a surgeon should approach similar cases, which are the crucial tips, and which are the missteps that should be avoided. In this case, we used multiple scleral/corneoscleral allografts in a specific orientation and different sutures to reconstruct the damaged limbal area and restore the anatomy. Abbreviations: VA = Visual Acuity, GDD = Glaucoma Drainage Device, IOP = Intra Ocular Pressure.

Ocular manifestations of liver disease: an important diagnostic aid.

PURPOSE: This review examined existing literature to determine various ocular manifestations of liver pathologies, with a focus on metabolic deficiencies as well as viral and immune liver conditions. METHODS: Recent data were compiled from PubMed from 2000 to 2020 using keywords that were relevant to the assessed pathologies. Ocular presentations of several liver pathologies were researched and then summarized in a comprehensive form. RESULTS: Several ocular manifestations of liver disease were related to vitamin A deficiency, as liver disease is associated with impaired vitamin A homeostasis. Alcoholic liver cirrhosis can result in vitamin A deficiency, presenting with Bitot spots, xerosis, and corneal necrosis. Congenital liver diseases such as mucopolysaccharidoses and peroxisomal disorders are also linked with ocular signs. Viral causes of liver disease have associations with conditions like retinal vasculitis, keratoconjunctivitis sicca, retinopathies, Mooren's ulcer, and Sjogren's syndrome. Autoimmune hepatitis has been linked to peripheral ulcerative keratitis and uveitis. CONCLUSIONS: Building strong associations between ocular and liver pathology will allow for early detection of such conditions, leading to the early implementation of management strategies. While this review outlines several of the existing connections between hepatic and ophthalmic disease, further research is needed in the area in order to strengthen these associations.

Microbial keratitis and its management at a rural centre: achieving success with limited resources.

PURPOSE: Microbial keratitis is a sight-threatening condition with a higher incidence in agrarian populations. In countries with a high indigent population, due to financial and other constraints, patients prefer to seek therapy locally rather than travel to advanced centres. The aim of this study is to describe the epidemiology, clinical characteristics, and outcomes of 60 consecutive patients with microbial keratitis managed at a rural centre. METHODS: Descriptive case series. All patients clinically diagnosed with infectious keratitis were included. Corneal scrapings were obtained and microbiological identification was done by Gram stain. Anti-microbial therapy was commenced based on smear findings and the patients were followed up till disease resolution. RESULTS: Sixty eyes of 60 patients were diagnosed with microbial keratitis in the study period. The mean age was 47.43 ± 18.69 years. Male:female ratio was 47:53. Risk factors included ocular trauma in the majority of patients (46/60; 76.7%). Microorganisms were identified on 75.6% of smears, with fungal filaments (65.4%) being the most common. Ulcers were central in over half (32/60; 53.3%), and > 3 mm in diameter in over three-fourths (81.6%) of patients. Forty-four patients (73.3%) achieved treatment success whereas 16/60 (26.6%) required referral to our tertiary-eye care facility for management. The median time to resolution was 14 days (IQR 10-26 days). CONCLUSION: Our series demonstrates the feasibility of microbiology-guided therapy in microbial keratitis by ophthalmologists at the secondary rural eye-care level. Two-thirds of the patients could be successfully managed at the rural centre and only severe cases needed a referral to tertiary centres.