Incidence and Mitigation of Corneal Pseudomicrocysts Induced by Antibody-Drug Conjugates (ADCs).

Purpose of Review: This study is to highlight the incidence of corneal pseudomicrocysts in FDA-approved antibody-drug conjugates (ADCs), and success of preventive therapies for pseudomicrocysts and related ocular surface adverse events (AEs). Recent Findings: ADCs are an emerging class of selective cancer therapies that consist of a potent cytotoxin connected to a monoclonal antibody (mAb) that targets antigens expressed on malignant cells. Currently, there are 11 FDA-approved ADCs with over 164 in clinical trials. Various AEs have been attributed to ADCs, including ocular surface AEs (keratitis/keratopathy, dry eye, conjunctivitis, blurred vision, corneal pseudomicrocysts). While the severity and prevalence of ADC-induced ocular surface AEs are well reported, the reporting of corneal pseudomicrocysts is limited, complicating the development of therapies to prevent or treat ADC-related ocular surface toxicity. Summary: Three of 11 FDA-approved ADCs have been implicated with corneal pseudomicrocysts, with incidence ranging from 41 to 100% of patients. Of the six ADCs that reported ocular surface AEs, only three had ocular substudies to investigate the benefit of preventive therapies including topical steroids, vasoconstrictors, and preservative-free lubricants. Current preventive therapies demonstrate limited efficacy at mitigating pseudomicrocysts and other ocular surface AEs.

Community Outreach and Engagement in Cancer Research Through a Biobank Clinic at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Pakistan.

INTRODUCTION: Cancer's increasing prevalence across the globe emphasizes the urgency for continued research, prevention, and accessible healthcare to mitigate its impact on individuals and communities. While there have been significant advances made towards controlling cancer morbidity and mortality in recent decades, Pakistan continues to experience a markedly elevated burden of the disease. With this study, we aim to raise awareness about biobank research within the cancer patient community, fostering participation and collaboration to advance the fight against cancer through vital research contributions. METHODS: In October 2022, we initiated the biobank clinic at Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC). Here, patients underwent screening and received invitations to voluntarily participate in biobank research. During these interactions, we engaged patients in discussions about the significance of biobank research, addressed their concerns, and encouraged their participation in advancing our research endeavors. Two-sample independent t-tests were performed to compare the mean number of participants in pre-clinic and post-clinic cohorts. RESULTS: This research involved a total of 958 participants, with 312 participants enrolled before the clinic and 646 participants enrolled after the clinic. We have observed a noticeable increase in the participation of cancer patients in our research endeavors since the inception of the biobank clinic (p-value<0.001). Over an 11-month time frame, we scheduled appointments for 759 patients, and out of those, 656 patients availed themselves to visit the clinic. Impressively, we achieved the enrollment of 646 patients into the clinic, reflecting an exceptional consent rate of 98.47% for their active involvement in our research initiatives. This underscores our commitment to conducting comprehensive discussions and providing thorough explanations regarding the ethical and procedural aspects of our research. CONCLUSION: Biobank clinic plays a pivotal role in raising cancer awareness and fostering research participation, especially in regions with limited healthcare infrastructure and lower literacy rates. It emerges as a community-engagement model that aligns research with local needs, ensuring its relevance and benefit to the population.

Noninfectious Outcomes of Intravitreal Antibiotic Steroid Injection and Topical Nonsteroidal Antiinflammatory Drugs Versus Triple Drop Therapy After Cataract Surgery.

PURPOSE: To compare noninfectious outcomes of intravitreal antibiotic steroid (IVAS) injection (moxifloxacin-triamcinolone) and postoperative topical nonsteroidal antiinflammatory drugs (NSAID) with a standard 3-drop therapy (TDT) regimen (topical antibiotic, steroid, and NSAID) in patients after cataract surgery. DESIGN: Retrospective comparative clinical cohort study. METHODS: In 3 study centers in the United States, a total of 2143 eyes (N = 2143 patients) underwent cataract surgery with IVAS-NSAID or TDT between 2017 and 2022. Preoperative data were included, including patients' age, iris color, medical history, and ocular history. Postoperative data, including best-corrected visual acuity, intraocular pressure (IOP), and the need for IOP-lowering medications, were recorded at 1-week, 1-month, and 6-month time points. The primary outcome measures were postoperative complications, defined as persistent anterior chamber inflammation, persistent corneal edema (PCE), rebound inflammation, and cystoid macular edema, were compared between the 2 groups. RESULTS: There were 1079 eyes in the IVAS-NSAID group and 1064 eyes in the TDT group. Best-corrected visual acuity and IOP were similar between IVAS-NSAID and TDT eyes at all time points. A portion (11.6%) of TDT eyes experienced postoperative complications compared with 6.5% in IVAS-NSAID eyes (P < .001). Femtosecond laser-assisted cataract surgery was associated with increased rates of PCE in IVAS-NSAID eyes, and eyes with dark irides had a higher incidence of cystoid macular edema, PCE, and rebound inflammation in the IVAS-NSAID group. CONCLUSION: The IVAS-NSAID regimen overall had similar postoperative outcomes and fewer complications compared with the TDT regimen. IVAS-NSAID may be considered a safe alternative to topical regimens in non-femtosecond laser-assisted cataract surgery and patients with light irides.

PD-L1 is Fascinating but IDO Needs Attention in Non-HCV and Non-HBV-Associated Hepatocellular Carcinoma Patients.

Background/Aim: Hepatocellular carcinoma (HCC) is one of the most common forms of liver cancer that is modulated by the immune system. Programmed cell death ligand-1 (PD-L1) has emerged as a novel therapeutic target in various cancers. Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme that is associated with poor prognoses in various cancer types. The aim of this study was to investigate the PD-L1 expression, and clinicopathological features of non-HCV and non-HBV-associated HCC patients, including IDO expression. Patients and Methods: In this study, immunohistochemical analysis was performed to analyze the expression of PD-L1 and IDO. Formalin-fixed paraffin-embedded HCC tumor tissues (n=50) were obtained from the pathology department, at Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC) in Lahore, Pakistan between 2005 and 2022. All the patients were HBV and HCV negative. Furthermore, it was a rare group of patients with no previous history of any viral hepatitis. In addition, for categorical and continuous variables chi-square or Fisher exact test and Mann-Whitney U-test was performed. Results: Of 50 tissue specimens, PD-L1+ was observed in 21 [high: 12 (24%), low: 9 (18%)] and PD-L1- was observed in 29 HCC patients. IDO+ was observed in all 50 specimens [high: 42 (84%), low: 8 (16%)]. Additionally, both PD-L1 and IDO had high expression in 11 (22%) patients. While both PD-L1 and IDO had low expression in 2 (4%) patients. Furthermore, in IDO+/PD-L1- group, 20 (69%) out of 29 patients died while in the IDO+/PD-L1+ group, 9 (43%) out of 21 patients died. Conclusion: Evaluation of IDO and PD-L1 expression may add therapeutic advantage in non-HCV and non-HBV-associated HCC patients that overexpress IDO. Further validation in a larger cohort is warranted.

GIS-based calculation method of surge height generated by three-dimensional landslide.

Combined with the spatial data processing capability of the Geographic Information Systems (GIS), the Pan Jiazheng method is extended from two-dimensional (2D) to three-dimensional (3D), and a 3D landslide surge height calculation method is proposed based on grid column units. First, the data related to the landslide are rasterized to form grid columns, and a force analysis model of 3D landslides is established. Combining the vertical strip method with Newton's laws of motion, dynamic equilibrium equations are established to solve the surge height. Moreover, a 3D landslide surge height calculation expansion module is developed in the GIS environment, and the results are compared with those of the 2D Pan Jiazheng method. Comparisons showed that the maximum surge height obtained by the proposed method is 24.6% larger than that based on the Pan Jiazheng method. Compared with the traditional 2D method, the 3D method proposed in this paper better represent the actual spatial state of the landslide and is more suitable for risk assessment.

Biomarkers of Pediatric Cataracts: A Proteomics Analysis of Aqueous Fluid.

Cataracts are among the most common causes of childhood vision loss worldwide. This study seeks to identify differentially expressed proteins in the aqueous humor of pediatric cataract patients. Samples of aqueous humor were collected from pediatric and adult cataract patients and subjected to mass spectrometry-based proteomic analysis. Samples of pediatric cataracts were grouped by subtype and compared to adult samples. Differentially expressed proteins in each subtype were identified. Gene ontology analysis was performed using WikiPaths for each cataract subtype. Seven pediatric patients and ten adult patients were included in the study. Of the pediatric samples, all seven (100%) were male, three (43%) had traumatic cataracts, two (29%) had congenital cataracts, and two (29%) had posterior polar cataracts. Of the adult patients, seven (70%) were female and seven (70%) had predominantly nuclear sclerotic cataracts. A total of 128 proteins were upregulated in the pediatric samples, and 127 proteins were upregulated in the adult samples, with 75 proteins shared by both groups. Gene ontology analysis identified inflammatory and oxidative stress pathways as upregulated in pediatric cataracts. Inflammatory and oxidative stress mechanisms may be involved in pediatric cataract formation and warrant further investigation.

High Indoleamine 2,3-Dioxygenase Expression along with Low Bridging Integrator-1 Expression in Hepatocellular Carcinoma Patients.

BACKGROUND: Hepatocellular carcinoma (HCC) adopts several tumor immune escape mechanisms; therefore, it has the potential to be targeted by immunotherapy. Indoleamine 2, 3-dioxygenase (IDO) is an immunosuppressive enzyme that has been observed to be overexpressed in HCC patients with poor prognoses. Bridging integrator 1 (Bin1) loss promotes immune escape in cancer by deregulating IDO. Our aim is to investigate IDO expression along with Bin1 expression to find evidence of immunosuppression in HCC patients. MATERIALS AND METHODS: In this study, we investigated IDO and Bin1 expression in HCC tissue specimens and the correlation of IDO and Bin1 expression with clinicopathological characteristics and prognosis of HCC patients (n=45). Immunohistochemical analysis was performed to analyze the expression of IDO and Bin1. RESULTS: IDO was overexpressed in 38 (84.4%) out of 45 HCC tissue specimens. In addition, tumor size was significantly increased with an increase in the IDO expression (P=0.03). Low Bin1 expression was observed in 27(60%) HCC tissue specimens, whereas the remaining 18(40%) showed high Bin1 expression. CONCLUSION: Our data showed that expression of IDO along with Bin1 expression could be investigated for clinical evaluation in HCC. IDO might be used as an immunotherapeutic target for HCC. Therefore, further studies in larger patient cohorts are warranted.

Indoleamine 2,3-Dioxygenase: A Novel Immunotherapeutic Target for Osteosarcoma.

Introduction: Tumour-emitted molecules induce immunosuppression in the tumour microenvironment. An immunosuppressive enzyme, indoleamine 2,3-dioxygenase (IDO/IDO1), facilitates immune escape in several malignant tumours, including osteosarcoma. Upregulation of IDO establishes a tolerogenic environment in the tumour and the tumour-draining lymph nodes. IDO-induced downregulation of effector T-cells and upregulation of local regulatory T-cells creates immunosuppression and promotes metastasis. Observations: Osteosarcoma is the most common bone tumour characterised by immature bone formation by the tumour cells. Almost 20% of osteosarcoma patients present with pulmonary metastasis at the time of diagnosis. The improvement in therapeutic modalities for osteosarcoma has been in a stagnant phase for two decades. Therefore, the development of novel immunotherapeutic targets for osteosarcoma is emergent. High IDO expression is associated with metastasis and poor prognosis in osteosarcoma patients. Conclusion and Relevance: At present, only a few studies are available describing IDO's role in osteosarcoma. This review describes the prospects of IDO not only as a prognostic marker but also as an immunotherapeutic target for osteosarcoma.

Pediatric herpes zoster ophthalmicus: a systematic review.

PURPOSE: While typically affecting older adults and immunocompromised individuals, herpes zoster ophthalmicus (HZO) has been reported with varying manifestations and complications in children. In this review, we evaluate reported cases of pediatric HZO in the literature and discuss the epidemiology, risk factors, clinical presentation, treatment and outcomes. METHODS: A literature search on PubMed, Scopus, and Web of Science databases was performed using the terms "pediatric herpes zoster ophthalmicus" and "herpes zoster ophthalmicus children." Publications that were not specific to HZO or pediatric populations were excluded, as were publications that were not available to review or not published in the English language. RESULTS: Fifty-seven reports describing 130 cases of HZO or HZO-related complications were reviewed. Major risk factors for pediatric HZO included intrauterine exposure to varicella or primary varicella infection at a young age; HZO also occurred in patients who had received varicella vaccination. Both healthy and immunocompromised children were affected, with the majority of affected children being immunocompetent. The diagnosis of HZO is primarily clinical. Children appear to have good vision recovery and resolution of symptoms if they are treated promptly and if they adhere to treatment regimens, except for irreversible vision loss related to uncommon complications such as optic neuritis. CONCLUSION: HZO occurs in both healthy and immunocompromised children. Recognizing this treatable condition is essential for reducing ocular and systemic morbidity. Long-term follow-up and assessments of the impact on health in adulthood are lacking. More systematic study is needed to determine the incidence of HZO in children and appropriate diagnostic and treatment protocols for the care of pediatric patients with HZO.

Immunotherapy and targeted therapy for lung cancer: Current status and future perspectives.

Lung cancer has the highest incidence of morbidity and mortality throughout the globe. A large number of patients are diagnosed with lung cancer at the later stages of the disease. This eliminates surgery as an option and places complete dependence on radiotherapy or chemotherapy, and/or a combination of both, to halt disease progression by targeting the tumor cells. Unfortunately, these therapies have rarely proved to be effective, and this necessitates the search for alternative preventive approaches to reduce the mortality rate of lung cancer. One of the effective therapies against lung cancer comprises targeting the tumor microenvironment. Like any other cancer cells, lung cancer cells tend to use multiple pathways to maintain their survival and suppress different immune responses from the host's body. This review comprehensively covers the role and the mechanisms that involve the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in lung adenocarcinoma and methods of treating it by altering the tumor microenvironment. It focuses on the insight and understanding of the lung cancer tumor microenvironment and chemokines, cytokines, and activating molecules that take part in angiogenesis and metastasis. The review paper accounts for the novel and current immunotherapy and targeted therapy available for lung cancer in clinical trials and in the research phases in depth. Special attention is being paid to mark out single or multiple genes that are required for malignancy and survival while developing targeted therapies for lung cancer treatment.

COVID-19 in cancer patients with diabetes in Pakistan: Clinical features and management.

Background: Diabetes and cancer are the leading causes of mortality all over the world. Infectious diseases are more common and/or life-threatening in patients with diabetes. Cancer patients with diabetes are individuals that are more susceptible to the current COVID-19 pandemic. We investigated the clinical features of survivor and non-survivor COVID-19-infected cancer patients with diabetes. Patients and Methods: We did a retrospective study of 43 diabetic cancer patients with PCR-confirmed COVID-19 infection from Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan between March 03, 2020, and May 18, 2021. These patients either were discharged from the hospital or had died by Jun 16, 2021. Clinicopathological and radiological features were compared between survivors and non-survivors by fisher's exact test and chi-square test. Results: Forty-three diabetic cancer patients with SARS-CoV-2 infection were enrolled and the majority were males 26 (60.5%). The overall mean age was 61.67 ± 11.80. 39 (90.7%) had solid tumors and 3 (7.0%) had hematological malignancies. Fever (74.4%) and dyspnea (58.1%) were the most common symptoms. Complications were reported in 36 (83.7%) patients; during the course of the disease. Additionally, all the deceased patients (n=15) had acquired the complications. 11 (25.6%) patients were admitted to an intensive care unit (ICU). Furthermore, 29 (67.4%) out of 43 patients showed abnormal features in the radiological findings. We found significantly elevated levels of C-reactive protein (P=0.005), serum lactate (P=0.01), albumin (P=0.02), alkaline phosphate (P=0.03), and neutrophil count (P=0.04) in the non-survivors as compared to the survivors. Conclusion: Cancer patients with diabetes are a vulnerable population in the current pandemic. Identifying how diabetes in cancer patients affects the severity of SARS-CoV-2 infection is crucial for the clinical management of these patients. Rigorous scrutiny of clinicopathological features of COVID-19 infected cancer patients with diabetes especially values of C-reactive protein, lactate, albumin, alkaline phosphate, neutrophils, and regular monitoring of blood glucose levels may play a critical role in the outcome of the disease.

Experiences of Shaukat Khanum Memorial Cancer Hospital and Research Centre Biobank during COVID-19 Pandemic.

Pakistan has an approximate population of 228.9 million. In 2020, 178,388 new cancer cases were diagnosed in Pakistan. In 2019, we established the biobanking facility at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. Shaukat Khanum Memorial Cancer Hospital and Research Centre is a tertiary care charitable, not-for-profit cancer hospital in Pakistan. In 2020-21, 22,745 new cancer patients were registered in the Shaukat Khanum Memorial Cancer Hospital and Research Centre for cancer treatment. The hospital treats around 75% of accepted cancer patients free of charge, regardless of race or nationality. In December 2019, a novel coronavirus SARS-Cov-2 (COVID-19) was identified in China. The World Health Organization acknowledged the COVID-19 outbreak as a pandemic. Pakistan was hit by the first wave of COVID-19 in March 2020. We have highlighted the challenges faced during the COVID-19 pandemic. We emphasized the significance of collaborations between low and middle-income countries' biobanks and international biobanks to achieve the global perspective of biobanking.

Conjunctival chronic lymphocytic leukemia presenting as bilateral chronic conjunctivitis.

Purpose: This report describes a case of conjunctival chronic lymphocytic leukemia (CLL) in a 73 year-old female with a prior history of CLL thought to be in remission who presented with bilateral chronic conjunctivitis. Observation: Examination revealed bilateral conjunctival injection, mildly purulent discharge, and the presence of large follicle-like lesions involving the bilateral superior and inferior palpebral conjunctiva. Conjunctival cultures grew Corynebacterium species. The patient was treated with topical antibiotics and steroids which improved the conjunctival injection and discharge, but the follicle-like lesions persisted. A conjunctival biopsy was performed and was consistent with the diagnosis of chronic lymphocytic leukemia. Fundoscopic exam did not demonstrate posterior uveal or retinal involvement. She was referred to her oncologist for further evaluation and management. Marked clinical improvement was noted after starting treatment with ibrutinib. Conclusions and importance: This case demonstrates a rare ocular manifestation of the most common form of leukemia. It happened to present with common, nonspecific symptoms of eye redness, discharge, and follicular reaction consistent with a bilateral chronic conjunctivitis. Clinical appearance and symptoms improved with topical steroids and eventually resolved with systemic bruton kinase inhibitor therapy.

Ocular Injuries From Drive-by Paintball Shootings.

PURPOSE: To characterize ocular injuries from drive-by paintball shootings with a focus on the severity of injuries sustained, clinical management, and visual outcomes. DESIGN: Retrospective, interventional case series. METHODS: Setting: University practice and emergency department. PATIENT POPULATION: Patients evaluated by the ophthalmology service for paintball injuries. OBSERVATION PROCEDURE: Age, sex, eye laterality, mechanism of injury, initial best-corrected visual acuity (BCVA), and initial diagnosis. MAIN OUTCOME MEASURES: Clinical intervention(s), BCVA at last follow-up visit, and severity of injuries with a focus on ruptured globes. RESULTS: Twenty patients suffered unilateral ocular injuries from drive-by paintball shootings between January 2020 and December 2021. The median follow-up interval was 7.1 weeks (range: 3 days to 11.4 months). The average patient age at presentation was 36.6 years (range: 13-64 years). Fourteen patients (70%) had an initial BCVA of counting fingers or worse. Six patients (30%) suffered a ruptured globe injury requiring surgical repair, of whom 3 (15%) underwent subsequent evisceration. Twelve patients (60%) suffered ocular injuries requiring surgical intervention. Fifteen ocular surgeries were performed on 9 patients (45%) at our institution with 3 patients referred to outside providers for definitive surgical management due to insurance. BCVA at last follow-up visit was no light perception in 5 patients. CONCLUSIONS: The severity of injury after paintball-induced ocular trauma is higher in this case series than what has previously been reported in the literature. Paintball guns can cause devastating ocular injury when used as an assault weapon, and their use in unregulated settings bears further scrutiny.

Hybrid feature selection-based machine learning Classification system for the prediction of injury severity in single and multiple-vehicle accidents.

To undertake a reliable analysis of injury severity in road traffic accidents, a complete understanding of important attributes is essential. As a result of the shift from traditional statistical parametric procedures to computer-aided methods, machine learning approaches have become an important aspect in predicting the severity of road traffic injuries. The paper presents a hybrid feature selection-based machine learning classification approach for detecting significant attributes and predicting injury severity in single and multiple-vehicle accidents. To begin, we employed a Random Forests (RF) classifier in conjunction with an intrinsic wrapper-based feature selection approach called the Boruta Algorithm (BA) to find the relevant important attributes that determine injury severity. The influential attributes were then fed into a set of four classifiers to accurately predict injury severity (Naive Bayes (NB), K-Nearest Neighbor (K-NN), Binary Logistic Regression (BLR), and Extreme Gradient Boosting (XGBoost)). According to BA's experimental investigation, the vehicle type was the most influential factor, followed by the month of the year, the driver's age, and the alignment of the road segment. The driver's gender, the presence of a median, and the presence of a shoulder were all found to be unimportant. According to classifier performance measures, XGBoost surpasses the other classifiers in terms of prediction performance. Using the specified attributes, the accuracy, Cohen's Kappa, F1-Measure, and AUC-ROC values of the XGBoost were 82.10%, 0.607, 0.776, and 0.880 for single vehicle accidents and 79.52%, 0.569, 0.752, and 0.86 for multiple-vehicle accidents, respectively.

Corneal perforation in ocular graft-versus-host disease.

PURPOSE: Corneal perforation is a rare, vision-threatening complication of ocular graft-versus-host disease (GVHD) and is not well understood. Our objective was to examine the clinical disease course and histopathologic correlation in patients who progressed to this outcome. METHODS: This study is a retrospective case series from four academic centers in the United States. All patients received a hematopoietic stem cell transplant (HSCT) prior to developing ocular GVHD. Variables of interest included patient demographics, time interval between HSCT and ocular events, visual acuity throughout clinical course, corticosteroid and infection prophylaxis regimens at time of corneal perforation, medical/surgical interventions, and histopathology. RESULTS: Fourteen eyes from 14 patients were analyzed. Most patients were male (86%) and Caucasian (86%), and average age at time of hematopoietic stem cell transplant was 47 years. The mean interval between hematopoietic stem cell transplant and diagnosis of ocular graft-versus-host disease was 9.5 months, and between hematopoietic stem cell transplant and corneal perforation was 37 months. Initial best-corrected visual acuity was 20/40 or better in 9 eyes, and all eyes had moderate or poor visual outcomes despite aggressive management, including corneal gluing in all patients followed by keratoplasty in 8 patients. The mean follow-up after perforation was 34 months (range 2-140 months). Oral prednisone was used prior to perforation in 11 patients (79%). On histopathology, representative specimens in the acute phase demonstrated ulcerative keratitis with perforation but minimal inflammatory cells and no microorganisms, consistent with sterile corneal "melt" in the setting of immunosuppression; and in the healed phase, filling in of the perforation site with fibrous scar. CONCLUSIONS: In these patients, an extended time interval was identified between the diagnosis of ocular graft-versus-host disease and corneal perforation. This represents a critical window to potentially prevent this devastating outcome. Further study is required to identify those patients at greatest risk as well as to optimize prevention strategies.