Association between in vitro susceptibility and clinical outcomes in fungal keratitis.

PURPOSE: The purpose of this study was to assess the association between antifungal susceptibility as measured by minimum inhibitory concentration (MIC) and clinical outcomes in fungal keratitis. METHODS: This pre-specified secondary analysis of the Mycotic Ulcer Treatment Trial II (MUTT II) involved patients with filamentous fungal keratitis presenting to Aravind Eye Hospitals in South India. Antifungal susceptibility testing for natamycin and voriconazole was performed on all samples with positive fungal culture results according to Clinical and Laboratory Standards Institute Guidelines. The relationship between MIC and clinical outcomes of best-corrected visual acuity, infiltrate or scar size, corneal perforation, need for therapeutic penetrating keratoplasty, and time to re-epithelialization were assessed. RESULTS: We obtained MIC values from 141 patients with fungal keratitis. The most commonly cultured organisms were Aspergillus (46.81%, n = 66) and Fusarium (44.68%, n = 63) species. Overall, there was no association between antifungal MICs and clinical outcomes. Subgroup analysis revealed that among Fusarium-positive cases, higher voriconazole MIC was correlated with worse three-month best-corrected visual acuity (p = 0.03), increased need for therapeutic penetrating keratoplasty (p = 0.04), and time to re-epithelialization (p = 0.03). No significant correlations were found among Aspergillus-positive cases. There were no significant correlations found between natamycin MIC and clinical outcomes among organism subgroups. CONCLUSIONS: Decreased susceptibility to voriconazole was associated with increased odds of requiring a therapeutic penetrating keratoplasty in Fusarium-positive cases. Susceptibility to natamycin was not associated with any of the measured outcomes.

Association of weather variables with pathogens contributing to conjunctivitis worldwide.

PURPOSE: To identify weather variables associated with pathogens contributing to infectious conjunctivitis globally. METHODS: Sample collection and pathogen identification from patients with acute infectious conjunctivitis was performed from 2017 to 2023. We linked pathogens identified from 13 sites across 8 countries with publicly available weather data by geographic coordinates. Mixed effects logistic regression analysis was performed to estimate the associations between temperature, precipitation, and relative humidity exposures, and the prevalence of infection types (RNA virus, DNA virus, bacteria, and fungus). RESULTS: 498 cases from the United States, India, Nepal, Thailand, Burkina Faso, Niger, Vietnam, and Israel were included in the analysis. 8-day average precipitation (mm) was associated with increased odds of RNA virus infection (odds ratio (OR)=1.47, 95% confidence interval (CI): 1.12 to 1.93, P=0.01) and decreased odds of DNA infection (OR=0.62, 95% CI: 0.46 to 0.82, P<0.001). Relative humidity (%) was associated with increased odds of RNA virus infections (OR=2.64, 95% CI: 1.51 to 4.61, P<0.001), and fungal infections (OR=2.35, 95% CI: 1.19 to 4.66, P=0.01), but decreased odds of DNA virus (OR=0.58, 95%CI: 0.37 to 0.90, P=0.02) and bacterial infections (OR=0.42, 95% CI: 0.25 to 0.71, P<0.001). Temperature (°C) was not associated with ocular infections for any pathogen type. CONCLUSIONS: This study suggests that weather factors affect pathogens differently. Particularly, humidity and precipitation were predictors for pathogens contributing to conjunctivitis worldwide. Additional work is needed to clarify the effects of shifts in weather and environmental factors on ocular infectious diseases.

Biomarker Detection and Validation for Corneal Involvement in Patients With Acute Infectious Conjunctivitis.

Importance: Infectious conjunctivitis can lead to corneal involvement and result in ocular morbidity. The identification of biomarkers associated with corneal involvement has the potential to improve patient care. Objective: To identify biomarkers in patients with acute infectious conjunctivitis. Design, Setting, and Participants: This cross-sectional study took place from December 2016 to March 2024. Analyses were performed in 3 phases. First, logistic regression and machine learning algorithms were used to predict the probability of demonstrating corneal involvement in patients with presumed infectious conjunctivitis. Second, quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to confirm the most important biomarker gene identified by the algorithm. Third, the biomarker gene was validated in prospectively collected conjunctival samples of adult patients from 3 outpatient centers in Thailand and 1 in India. Patients with signs and symptoms of infectious conjunctivitis and onset within less than 14 days were eligible. Exclusion criteria were the inability to consent, presumed toxicity, or allergic conjunctivitis. Exposures: Acute infectious conjunctivitis. Main Outcomes and Measures: The identification and validation of ocular surface gene expression associated with corneal findings on slitlamp examination. Results: Thirteen genes exhibited a 1.5-log2 fold change in expression in patients with corneal involvement compared to patients without corneal involvement. Using the 13 genes to train and cross validate, logistic regression produced the highest mean area under the receiver operating characteristic curve (AUROC; 0.85; 95% CI, 0.84-0.86) for corneal involvement. The removal of apolipoprotein E (APOE) from the gene ensemble led to a decline in predictive performance of the logistic regression classifier (from mean AUROC 0.85 [95% CI, 0.84-0.86] to 0.74 [95% CI, 0.73-0.75]; adjusted P = .001 [Tukey test]). Orthogonal testing of APOE expression level with RT-qPCR showed that APOE expression was higher in patients with corneal involvement compared to patients without (median [IQR], 0.23 [0.04-0.47] vs 0.04 [0.02-0.06]; P = .004 [Mann-Whitney U test]). Using a Youden index of 0.23 Δ threshold cycle, APOE had a sensitivity of 56% (95% CI, 33-77) and a specificity of 88% (95% CI, 79-93) in 106 samples with conjunctivitis at Aravind, India (P < .001 [Fisher exact test]). When applied to a different patient population in Thailand, the same criteria could discriminate between disease states (58 samples; sensitivity, 47%; 95% CI, 30-64 and specificity, 93%; 95% CI, 77-99; P = .001 [Fisher exact test]). Conclusions and Relevance: The results from this study suggest that the host conjunctival immune response can be meaningfully interrogated to identify biomarkers for ocular surface diseases.

In vitro and ex vivo models of microbial keratitis: Present and future.

Microbial keratitis (MK) is an infection of the cornea, caused by bacteria, fungi, parasites, or viruses. MK leads to significant morbidity, being the fifth leading cause of blindness worldwide. There is an urgent requirement to better understand pathogenesis in order to develop novel diagnostic and therapeutic approaches to improve patient outcomes. Many in vitro, ex vivo and in vivo MK models have been developed and implemented to meet this aim. Here, we present current in vitro and ex vivo MK model systems, examining their varied design, outputs, reporting standards, and strengths and limitations. Major limitations include their relative simplicity and the perceived inability to study the immune response in these MK models, an aspect widely accepted to play a significant role in MK pathogenesis. Consequently, there remains a dependence on in vivo models to study this aspect of MK. However, looking to the future, we draw from the broader field of corneal disease modelling, which utilises, for example, three-dimensional co-culture models and dynamic environments observed in bioreactors and organ-on-a-chip scenarios. These remain unexplored in MK research, but incorporation of these approaches will offer further advances in the field of MK corneal modelling, in particular with the focus of incorporation of immune components which we anticipate will better recapitulate pathogenesis and yield novel findings, therefore contributing to the enhancement of MK outcomes.

A Hospital-Based Cross-Sectional Study on the Histopathology of Upper Gastrointestinal Tract Endoscopic Biopsy in Dyspeptic Patients.

Background Dyspepsia is one of the most common GI complaints encountered in clinical practice. Histopathological assessment of endoscopic gastric mucosa biopsy is crucial to delineate the exact cause of dyspepsia to guide patients' management. Objectives The aim of this study was to determine the histopathological spectrum of upper gastrointestinal (GI) tract endoscopic biopsies and to study the age and sex distribution of the predominant upper GI lesions. Methods A cross-sectional study was conducted in the Department of Pathology, Rajendra Institute of Medical Sciences, Ranchi, Jharkhand, India, from January 2022 to December 2023. All endoscopic mucosal biopsies of the esophagus, stomach, and duodenum (first and second parts) lesions were examined under a microscope for histopathological findings. Results Out of 250 endoscopic biopsies studied, there were 76 cases of esophageal biopsies, 149 cases of gastric biopsies, and 25 cases of duodenal biopsies. The male-to-female ratio was 1.2:1. Non-neoplastic lesions were more common than neoplastic lesions. The most common lesions encountered were esophagitis in the esophagus, gastritis in the stomach, and duodenitis in the duodenum. Conclusion The main organic cause of dyspepsia in our setting was chronic gastritis. We conclude that endoscopy of the upper GI tract and histopathological examination help in the earlier detection of both benign and malignant lesions. This aids in better timely management of the patients and improves the overall treatment provided resulting in a better prognosis.

An Analysis of Antibody Response to COVID-19 Vaccination Among Medicos in a Predominantly Tribal State in India: A Comparative Study.

Introduction Global health is still being impacted by the coronavirus disease 2019 (COVID-19) pandemic. Objectives We evaluated the antibody response in this study in individuals who received two doses of the COVID-19 vaccination, both with and without a history of SARS-CoV-2 infection. Methodology It was a hospital-based cross-sectional study conducted among healthcare personnel at a tertiary institution of a predominantly tribal state in India. Results A total of 187 medical students made up the vaccinee group; the majority (152; 81.3%) were between the ages of 18 and 23; 128 (68.4%) of the students were female; and 104 (55.6%) had received the Covishield (AstraZeneca plc, England, UK) vaccination. Of the subjects, 51 (27.3%) had a history of COVID-19 infection. For those who were infected, the antibody titer peaked after six months, whereas it took twice as long for those who were not. Up to a year later, the antibody titers for Covaxin (Bharat Biotech, Hyderabad, India) and Covishield remained equal; however, Covishield titers drastically decreased while Covaxin stayed constant when an infection history was present. Conclusion The study's findings show that immunization in individuals who have previously contracted COVID-19 induces a higher level of antibody response than immunization in individuals who have not previously contracted the virus.

A Comparative Study of Elective Sublay Versus Onlay Repair for Non-complex, Small, and Medium-Size Incisional Hernia: Post-operative Complications in a Tertiary Hospital in Ranchi, India.

BACKGROUND: The most difficult hernia surgery is the repair of the ventral hernia, which is caused by aberrant organ or tissue protrusions through the abdominal wall. Factors like obesity, smoking, and chronic medical conditions contribute to their formation. Surgical strategies have evolved from anatomical repair to mesh hernioplasty, with mesh placement playing a significant role in outcomes. The ideal anatomical location for mesh placement remains debated due to varying results. So, the objective of the study is to compare early postoperative complications, surgical site infection, and incidence of recurrence between sublay and onlay mesh placement repair of incisional hernias of <10 cm in diameter, at a tertiary hospital in Ranchi. METHODS:  This retrospective comparative study was conducted over a period of January 2022 to January 2024 at the Rajendra Institute of Medical Science, Ranchi, India. During the study period, 96 patients were operated on, and their demographic details, along with their position of mesh placement and postoperative complications (seroma formation, wound infection, postoperative hospital stays, and recurrence), were retrieved from the hospital data. Comparisons between onlay and sublay groups in terms of post-operative complications were made. RESULTS: Within the study period, a total of 96 patients were operated on for incisional hernia. In this study, 36 (37.5%) were male and 60 (62.5%) were female, with a male-to-female ratio of 0.6:1. Out of the total number of patients, 56 (58.4%) had a past history of emergency surgery. It was observed that there was a higher incidence of seroma formation in the onlay group compared to the sublay with a statistical significance p-value of 0.027. The incidence of wound infection was found to be statistically significant (p-value = 0.035) between the onlay and sublay groups. In a period of six-month follow-up, three patients of the total study population had an incidence of recurrent incisional hernia, of which two from the onlay group and one from the sublay group were present, and there was no statistical significance (p-value > 0.5). CONCLUSIONS: Based on our retrospective analysis, we can say that there is a lower incidence of postoperative complications and recurrence in sublay repair, along with a shorter postoperative hospital stay, making it a preferred method of repair over onlay.

A Descriptive Study of the Demographic and Clinicopathological Characteristics of Individuals With Gallstone-Induced Pancreatitis in a Tertiary-Level Hospital in Ranchi, Jharkhand.

BACKGROUND: Gallstones are a major cause of acute pancreatitis, which is associated with high recurrence, morbidity, and mortality. Careful consideration of demographic and clinicopathological features is required to understand the association between the cause and severity of pancreatitis in various populations, and such crucial information is lacking for Jharkhand's population. Here, we sought to describe the demographic and clinicopathological features of gallstone-induced acute pancreatitis at a tertiary hospital in Ranchi. METHODS: This hospital-based descriptive study was conducted at Rajendra Institute of Medical Sciences in Ranchi. The hospital records of patients admitted to the surgical unit with acute gallstone-induced pancreatitis from January 2023 to December 2023 were analyzed. The study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. RESULTS: Of the 72 patients admitted with acute gallstone-induced pancreatitis (mean age: 42.5 years), 46 (64%) were males and 26 (36%) were females. All 72 patients had abdominal pain and 44 (61%) were vomiting. The severe vs. non-severe pancreatitis groups differed significantly in age (≥40) and male gender (p = 0.013 and 0.031, respectively). A total of 45 (62.5%) patients had severe gallstone-induced pancreatitis, and the most common complication was acute kidney injury, followed by pleural effusion (18 (25%) and 13 (18.1%) cases, respectively). CONCLUSIONS: Our study revealed that gallstone-induced pancreatitis was more common in males and that age and gender were significantly associated with severity. However, late presentation to the hospital may have influenced our study, resulting in more severe cases being reported, with the most common complication being acute kidney injury. To our knowledge, this is the first study to describe the demographic, clinicopathological, and outcome data of acute gallstone-induced pancreatitis in Ranchi. These results can guide hospital policy development to improve patient outcomes.

Validation of the C-DU(KE) Calculator as a Predictor of Outcomes in Patients Enrolled in Steroids for Corneal Ulcer and Mycotic Ulcer Treatment Trials.

PURPOSE: The aim of this study was to validate the C-DU(KE) calculator as a predictor of treatment outcomes on a data set derived from patients with culture-positive ulcers. METHODS: C-DU(KE) criteria were compiled from a data set consisting of 1063 cases of infectious keratitis from the Steroids for Corneal Ulcer Trial (SCUT) and Mycotic Ulcer Treatment Trial (MUTT) studies. These criteria include corticosteroid use after symptoms, visual acuity, ulcer area, fungal etiology, and elapsed time to organism-sensitive therapy. Univariate analysis was performed followed by multivariable logistic regressions on culture-exclusive and culture-inclusive models to assess for associations between the variables and outcome. The predictive probability of treatment failure, defined as the need for surgical intervention, was calculated for each study participant. Discrimination was assessed using the area under the curve for each model. RESULTS: Overall, 17.9% of SCUT/MUTT participants required surgical intervention. Univariate analysis showed that decreased visual acuity, larger ulcer area, and fungal etiology had a significant association with failed medical management. The other 2 criteria did not. In the culture-exclusive model, 2 of 3 criteria, decreased vision [odds ratio (OR) = 3.13, P < 0.001] and increased ulcer area (OR = 1.03, P < 0.001), affected outcomes. In the culture-inclusive model, 3 of 5 criteria, decreased vision (OR = 4.9, P < 0.001), ulcer area (OR = 1.02, P < 0.001), and fungal etiology (OR = 9.8, P < 0.001), affected results. The area under the curves were 0.784 for the culture-exclusive model and 0.846 for the culture-inclusive model which were comparable to the original study. CONCLUSIONS: The C-DU(KE) calculator is generalizable to a study population from large international studies primarily taking place in India. These results support its use as a risk stratification tool assisting ophthalmologists in patient management.

Automatic Classification of Slit-Lamp Photographs by Imaging Illumination.

PURPOSE: The aim of this study was to facilitate deep learning systems in image annotations for diagnosing keratitis type by developing an automated algorithm to classify slit-lamp photographs (SLPs) based on illumination technique. METHODS: SLPs were collected from patients with corneal ulcer at Kellogg Eye Center, Bascom Palmer Eye Institute, and Aravind Eye Care Systems. Illumination techniques were slit beam, diffuse white light, diffuse blue light with fluorescein, and sclerotic scatter (ScS). Images were manually labeled for illumination and randomly split into training, validation, and testing data sets (70%:15%:15%). Classification algorithms including MobileNetV2, ResNet50, LeNet, AlexNet, multilayer perceptron, and k-nearest neighborhood were trained to distinguish 4 type of illumination techniques. The algorithm performances on the test data set were evaluated with 95% confidence intervals (CIs) for accuracy, F1 score, and area under the receiver operator characteristics curve (AUC-ROC), overall and by class (one-vs-rest). RESULTS: A total of 12,132 images from 409 patients were analyzed, including 41.8% (n = 5069) slit-beam photographs, 21.2% (2571) diffuse white light, 19.5% (2364) diffuse blue light, and 17.5% (2128) ScS. MobileNetV2 achieved the highest overall F1 score of 97.95% (CI, 97.94%-97.97%), AUC-ROC of 99.83% (99.72%-99.9%), and accuracy of 98.98% (98.97%-98.98%). The F1 scores for slit beam, diffuse white light, diffuse blue light, and ScS were 97.82% (97.80%-97.84%), 96.62% (96.58%-96.66%), 99.88% (99.87%-99.89%), and 97.59% (97.55%-97.62%), respectively. Slit beam and ScS were the 2 most frequently misclassified illumination. CONCLUSIONS: MobileNetV2 accurately labeled illumination of SLPs using a large data set of corneal images. Effective, automatic classification of SLPs is key to integrating deep learning systems for clinical decision support into practice workflows.

Assessing the Impact of Image Quality on Deep Learning Classification of Infectious Keratitis.

Objective: To investigate the impact of corneal photograph quality on convolutional neural network (CNN) predictions. Design: A CNN trained to classify bacterial and fungal keratitis was evaluated using photographs of ulcers labeled according to 5 corneal image quality parameters: eccentric gaze direction, abnormal eyelid position, over/under-exposure, inadequate focus, and malpositioned light reflection. Participants: All eligible subjects with culture and stain-proven bacterial and/or fungal ulcers presenting to Aravind Eye Hospital in Madurai, India, between January 1, 2021 and December 31, 2021. Methods: Convolutional neural network classification performance was compared for each quality parameter, and gradient class activation heatmaps were generated to visualize regions of highest influence on CNN predictions. Main Outcome Measures: Area under the receiver operating characteristic and precision recall curves were calculated to quantify model performance. Bootstrapped confidence intervals were used for statistical comparisons. Logistic loss was calculated to measure individual prediction accuracy. Results: Individual presence of either light reflection or eyelids obscuring the corneal surface was associated with significantly higher CNN performance. No other quality parameter significantly influenced CNN performance. Qualitative review of gradient class activation heatmaps generally revealed the infiltrate as having the highest diagnostic relevance. Conclusions: The CNN demonstrated expert-level performance regardless of image quality. Future studies may investigate use of smartphone cameras and image sets with greater variance in image quality to further explore the influence of these parameters on model performance. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Rapid Point-of-Care Identification of Aspergillus Species in Microbial Keratitis.

Importance: Microbial keratitis (MK) is a common cause of unilateral visual impairment, blindness, and eye loss in low-income and middle-income countries. There is an urgent need to develop and implement rapid and simple point-of-care diagnostics for MK to increase the likelihood of good outcomes. Objective: To evaluate the diagnostic performance of the Aspergillus-specific lateral-flow device (AspLFD) to identify Aspergillus species causing MK in corneal scrape and corneal swab samples of patients presenting with microbial keratitis. Design, Setting, and Participants: This diagnostic study was conducted between May 2022 and January 2023 at the corneal clinic of Aravind Eye Hospital in Madurai, Tamil Nadu, India. All study participants were recruited during their first presentation to the clinic. Patients aged 15 years or older met the eligibility criteria if they were attending their first appointment, had a corneal ulcer that was suggestive of a bacterial or fungal infection, and were about to undergo diagnostic scrape and culture. Main Outcomes and Measures: Sensitivity and specificity of the AspLFD with corneal samples collected from patients with MK. During routine diagnostic scraping, a minimally invasive corneal swab and an additional corneal scrape were collected and transferred to aliquots of sample buffer and analyzed by lateral-flow device (LFD) if the patient met the inclusion criteria. Photographs of devices were taken with a smartphone and analyzed using a ratiometric approach, which was developed for this study. The AspLFD results were compared with culture reports. Results: The 198 participants who met the inclusion criteria had a mean (range) age of 51 (15-85) years and included 126 males (63.6%). Overall, 35 of 198 participants with corneal scrape (17.7%) and 17 of 40 participants with swab samples (42.5%) had positive culture results for Aspergillus species. Ratiometric analysis results for the scrape samples found that the AspLFD achieved high sensitivity (0.89; 95% CI, 0.74-0.95), high negative predictive value (0.97; 95% CI, 0.94-0.99), low negative likelihood ratio (0.12; 95% CI, 0.05-0.30), and an accuracy of 0.94 (95% CI, 0.90-0.97). Ratiometric analysis results for the swab samples showed that the AspLFD had high sensitivity (0.94; 95% CI, 0.73-1.00), high negative predictive value (0.95; 95% CI, 0.76-1.00), low negative likelihood ratio (0.07; 95% CI, 0.01-0.48), and an accuracy of 0.88 (95% CI, 0.73-0.96). Conclusions and Relevance: Results of this diagnostic study suggest that AspLFD along with the ratiometric analysis of LFDs developed for this study has high diagnostic accuracy in identifying Aspergillus species from corneal scrapes and swabs. This technology is an important step toward the provision of point-of-care diagnostics for MK and could inform the clinical management strategy.

Apollo Rising: Acute Conjunctivitis Outbreak in India, 2022.

Purpose: To identify pathogens associated with the 2022 conjunctivitis outbreak in Tamil Nadu, India. Methods: This prospective study was conducted in November of 2022. Patients with presumed acute infectious conjunctivitis presenting to the Aravind Eye Clinic in Madurai, India were eligible. Anterior nares and conjunctival samples from participants were obtained and processed for metagenomic RNA deep sequencing (RNA-seq). Results: Samples from 29 patients were sequenced. A pathogen was identified in 28/29 (97%) patients. Coxsackievirus A24v, a highly infectious RNA virus, was the predominant pathogen and detected in 23/29 patients. Human adenovirus D (HAdV-D), a DNA virus commonly associated with conjunctivitis outbreaks, was detected in the remaining patients (5/29). Hemorrhagic conjunctiva was documented in both HAdV-D and coxsackievirus A24v affected patients but was not the predominant clinical presentation. Phylogenetic analysis of coxsackievirus A24v revealed a recent divergence from the 2015 outbreak. Conclusions: Coxsackievirus A24v and HAdV-D were co-circulating during the 2022 conjunctivitis outbreak in Tamil Nadu, India. Clinical findings were similar between patients with HAD-V and coxsackievirus A24v associated conjunctivitis. As high-throughput technologies become more readily accessible and cost-effective, unbiased pathogen surveillance may prove useful for outbreak surveillance and control.

FluoroPi Device With SmartProbes: A Frugal Point-of-Care System for Fluorescent Detection of Bacteria From a Pre-Clinical Model of Microbial Keratitis.

Purpose: Rapid and accurate diagnosis of microbial keratitis (MK) could greatly improve patient outcomes. Here, we present the development of a rapid, accessible multicolour fluorescence imaging device (FluoroPi) and evaluate its performance in combination with fluorescent optical reporters (SmartProbes) to distinguish bacterial Gram status. Furthermore, we show feasibility by imaging samples obtained by corneal scrape and minimally invasive corneal impression membrane (CIM) from ex vivo porcine corneal MK models. Methods: FluoroPi was built using a Raspberry Pi single-board computer and camera, light-emitting-diodes (LEDs), and filters for white-light and fluorescent imaging, with excitation and detection of bacterial optical SmartProbes: Gram-negative, NBD-PMX (exmax 488 nm); Gram positive, Merocy-Van (exmax 590 nm). We evaluated FluoroPi with bacteria (Pseudomonas aeruginosa and Staphylococcus aureus) isolated from ex vivo porcine corneal models of MK by scrape (needle) and CIM with the SmartProbes. Results: FluoroPi provides <1 µm resolution and was able to readily distinguish bacteria isolated from ex vivo models of MK from tissue debris when combined with SmartProbes, retrieved by both scrape and CIM. Single bacteria could be resolved within the field of view, with limits of detection demonstrated as 103 to 104 CFU/mL. Sample preparation prior to imaging was minimal (wash-free), and imaging and postprocessing with FluoroPi were straightforward, confirming ease of use. Conclusions: FluoroPi coupled with SmartProbes provides effective, low-cost bacterial imaging, delineating Gram-negative and Gram-positive bacteria directly sampled from a preclinical model of MK. Translational Relevance: This study provides a crucial stepping stone toward clinical translation of a rapid, minimally invasive diagnostic approach for MK.

The effect of social determinants of health on severity of microbial keratitis presentation at a tertiary eye care hospital in Southern India.

Purpose: Understanding the association between social determinants of health (SDoHs) and microbial keratitis (MK) can inform underlying risk for patients and identify risk factors associated with worse disease, such as presenting visual acuity (VA) and time to initial presentation. Methods: This was a cross-sectional study was conducted with patients presenting with MK to the cornea clinic at a tertiary care hospital in Madurai, India. Patient demographics, SDoH survey responses, geographic pollution, and clinical features at presentation were collected. Descriptive statistics, univariate analysis, multi-variable linear regression models, and Poisson regression models were utilized. Results: There were 51 patients evaluated. The mean age was 51.2 years (SD = 13.3); 33.3% were female and 55% did not visit a vision center (VC) prior to presenting to the clinic. The median presenting logarithm of the minimum angle of resolution (logMAR) VA was 1.1 [Snellen 20/240, inter-quartile range (IQR) = 20/80 to 20/4000]. The median time to presentation was 7 days (IQR = 4.5 to 10). The average particulate matter 2.5 (PM2.5) concentration, a measure of air pollution, for the districts from which the patients traveled was 24.3 µg/m3 (SD = 1.6). Age- and sex-adjusted linear regression and Poisson regression results showed that higher levels of PM2.5 were associated with 0.28 worse presenting logMAR VA (Snellen 2.8 lines, P = 0.002). Patients who did not visit a VC had a 100% longer time to presentation compared to those who did (incidence rate ratio = 2.0, 95% confidence interval = 1.3-3.0, P = 0.001). Conclusion: Patient SDoH and environmental exposures can impact MK presentation. Understanding SDoH is important for public health and policy implications to mitigate eye health disparities in India.

Association of Serious Adverse Effects With the Contamination of Ocular Medications-A Global Perspective.

This Viewpoint offers examples of the causes of infectious keratitis around the world and emphasizes the need for vigilance among ophthalmologists to reduce the risk of sight-threatening complications.

Deep Convolutional Neural Networks Detect no Morphological Differences Between Culture-Positive and Culture-Negative Infectious Keratitis Images.

Purpose: To determine whether convolutional neural networks can detect morphological differences between images of microbiologically positive and negative corneal ulcers. Methods: A cross-sectional comparison of prospectively collected data consisting of bacterial and fungal cultures and smears from eyes with acute infectious keratitis at Aravind Eye Hospital. Two convolutional neural network architectures (DenseNet and MobileNet) were trained using images obtained from handheld cameras collected from culture-positive and negative images and smear-positive and -negative images. Each architecture was trained on two image sets: (1) one with labels assigned using only culture results and (2) one using culture and smear results. The outcome measure was area under the receiver operating characteristic curve for predicting whether an ulcer would be microbiologically positive or negative. Results: There were 1970 images from 886 patients were included. None of the models were better than random chance at predicting positive microbiologic results (area under the receiver operating characteristic curve ranged from 0.49 to 0.56; all confidence intervals included 0.5). Conclusions: These two state-of-the-art deep convolutional neural network architectures could not reliably predict whether a corneal ulcer would be microbiologically positive or negative based on clinical photographs. This absence of detectable morphological differences informs the future development of computer vision models trained to predict the causative agent in infectious keratitis using corneal photography. Translational Relevance: These deep learning models were not able to identify morphological differences between microbiologically positive and negative corneal ulcers. This finding suggests that similar artificial intelligence models trained to identify the causative pathogen using only microbiologically positive cases may have potential to generalize well, including to cases with falsely negative microbiologic testing.

The Case for Fungal Keratitis to Be Accepted as a Neglected Tropical Disease.

Amongst the treatable cause of blindness among young people, fungal keratitis ranks high. There are an estimated 1,051,787 to 1,480,916 eyes affected annually, with 8-11% of patients having to have the eye removed. Diagnosis requires a corneal scraping, direct microscopy and fungal culture with a large number of airborne fungi implicated. Treatment involves the intensive application of antifungal eye drops, preferably natamycin, often combined with surgery. In low-resource settings, inappropriate corticosteroid eye drops, ineffective antibacterial therapy, diagnostic delay or no diagnosis all contribute to poor ocular outcomes with blindness (unilateral or bilateral) common. Modern detailed guidelines on fungal keratitis diagnosis and management are lacking. Here, we argue that fungal keratitis should be included as a neglected tropical disease, which would facilitate greater awareness of the condition, improved diagnostic capability, and access to affordable antifungal eye medicine.