An uncommon cause of sub-acute intestinal obstruction in young adult: Wilkie's syndrome.

Abstract: Superior mesenteric artery (SMA) syndrome, also known as Wilkie's syndrome, is a rare disease presenting as an acute abdomen. It has a clinical presentation similar to intestinal obstruction and is often missed during diagnosis. Reduced weight leading to loss of fat pad between SMA and aorta is the main pathophysiology. Diagnosis is made through barium meal and CT scan. Conservative management remains the treatment of choice; however, surgery is opted for in refractory cases. Key Clinical Message: Superior mesenteric artery (SMA) syndrome, also known as Wilkie's syndrome, is a rare disease presenting as an acute abdomen with clinical features similar to intestinal obstruction. This is a case of SMA syndrome in an adult male with a decrease in aortomesenteric angle, with no predisposing condition.

Krupple-like factor 4 (KLF4) methylation signature in host cell in active viral keratitis with epithelial manifestation.

HSV1 presents as epithelial or stromal keratitis or keratouveitis and can lead to sight-threatening complications. KLF4, a critical transcription factor, and regulator of cell growth and differentiation, is essential in corneal epithelium stratification and homeostasis. Here, we want to understand the epigenetic modification specifically the methylation status of KLF4 in epithelium samples of HSV1 keratitis patients. After obtaining consent, epithelial scrapes were collected from 7 patients with clinically diagnosed HSV1 keratitis and 7 control samples (patients undergoing photorefractive keratectomy). Genomic DNA was isolated from the collected samples using the Qiagen DNeasy Kit. Subsequently, bisulfite modification was performed. The bisulphite-modified DNA was then subjected to PCR amplification using specific primers designed to target the KLF4, ACTB gene region, allowing for the amplification of methylated and unmethylated DNA sequences. The amplified DNA products were separated and visualized on a 3% agarose gel. KLF4 hypermethylation was found in 6 out of 7 (85.71%) eyes with viral keratitis, while 1 eye showed hypomethylation compared to PRK samples. Out of these 6, there were 2 each of epithelial dendritic keratitis, epithelial geographical keratitis, and neurotrophic keratitis. The patient with hypomethylated KLF4 had a recurrent case of HSV1 keratitis with multiple dendrites and associated vesicular lesions of the lip along with a history of fever. KLF4 hypermethylation in most viral keratitis cases indicated the under functioning of KLF4 and could indicate a potential association between KLF4 hypermethylation and the development or progression of HSV1 keratitis.

In vitro Assay to Examine the Function of Tears on Corneal Epithelial Cells.

Tears contain numerous secreted factors, enzymes, and proteins that help in maintaining the homeostatic condition of the eye and also protect it from the external environment. However, alterations to these enzymes and/or proteins during pathologies such as mechanical injury and viral or fungal infections can disrupt the normal ocular homeostasis, further contributing to disease development. Several tear film components have a significant role in curbing disease progression and promoting corneal regeneration. Additionally, several factors related to disease progression are secreted into the tear film, thereby serving as a valuable reservoir of biomarkers. Tears are readily available and can be collected via non-invasive techniques or simply from contact lenses. Tears can thus serve as a valuable and easy source for studying disease-specific biomarkers. Significant advancements have been made in recent years in the field of tear film proteomics, lipidomics, and transcriptomics to allow a better understanding of how tears can be utilized to gain insight into the etiology of diseases. These advancements have enabled us to study the pathophysiology of various disease states using tear samples. However, the mechanisms by which tears help to maintain corneal homeostasis and how they are able to form the first line of defense against pathogens remain poorly understood and warrant detailed in vitro studies. Herein, we have developed an in vitro assay to characterize the functional importance of patient isolated tears and their components on corneal epithelial cells. This novel approach closely mimics real physiological conditions and could help the researchers gain insight into the underlying mechanisms of ocular pathologies and develop new treatments. Key features • This method provides a new technique for analyzing the effect of tear components on human corneal epithelial cells. • The components of the tears that are altered in response to diseases can be used as a biomarker for detecting ocular complications. • This procedure can be further employed as an in vitro model for assessing the efficacy of drugs and discover potential therapeutic interventions.

Trends in keratoplasty from central and Northern India. Part I: Indications for keratoplasty.

PURPOSE: To report the indications for keratoplasty and analyze trends in two decades in India. METHODS: This was a retrospective review of eye bank registries of six tertiary eye care centers located in central and northern India from 2005 to 2021. The patterns of corneal pathology and changes in trends were analyzed. RESULTS: Between 2005 and 2021, 13223 corneal grafts were performed in the six collaborating tertiary eye care centers. The most common indication for keratoplasty in both decades was corneal ulcer (41.1%), followed by corneal scar (25.5%), failed graft (12.0%), post-cataract surgery corneal edema (11.7%), corneal dystrophies (3.1%), corneal ectasia (1.8%), corneal trauma (0.3%), congenital corneal opacity (0.3%), and others (4.1%). An increasing trend was seen in corneal ulcers, failed grafts, and keratoconus. A reducing trend was seen in corneal scar and aphakic bullous keratopathy. There was no change in pseudophakic bullous keratopathy and Fuchs endothelial corneal dystrophy. CONCLUSION: Corneal ulcers, corneal scars, failed grafts, and post-cataract surgery corneal edema remained the foremost indications for keratoplasty in two decades in India. An increasing trend was seen in corneal ulcers and failed grafts which are of concern as these indications carry a poorer outcome. Capacity building in lamellar keratoplasty techniques is the need of the hour as pseudophakic bullous keratopathy was an important indication, and an increasing trend was noticed in keratoconus.

Eye Donation Counsellor Skill Evaluation Tool (EDC-SET): A step toward improved eye donation counseling.

PURPOSE: The expansion of the Hospital Corneal Retrieval Programme (HCRP) and the role of Eye Donation Counsellors (EDCs) have shown promising results in increasing donor cornea availability. To further enhance EDC competency and improve cornea availability for transplantation, the study proposes the Eye Donation Counsellor Skill Evaluation Tool (EDC-SET). Key words: Competency assessment, corneal blindness, Eye Donation Counsellors (EDCs), eye health, Hospital Corneal Retrieval Programme (HCRP), skill evaluation. METHODS: A competency framework for EDCs and a tool for evaluation of the competency level (EDC-SET) was designed, along with scripts for emulating realistic counselling scenarios. Independent assessors were trained on using EDC-SET and evaluated EDCs participating in role-plays based on the pre-designed scripts. EDCs were briefed a priori on the EDC-SET but not on the role play scripts which were used during evaluation. RESULTS: We piloted the tool at a tertiary eye hospital, and it was found to capture EDC competency reliably. The study evaluated seven EDCs each assessed by two independent assessors. Conformity, kappa, and intraclass correlation coefficient (ICC) values were calculated to estimate the parameter-wise reliability of the EDC-SET. The results suggest that the scores from both assessors closely matched for most of the parameters, and overall, their ratings showed moderate agreement. The difficulty level of each parameter as assessed by the two assessors was also calculated. It was observed that most participants found "Initiation of the Case" and "Empathy and Emotional Support" challenging. However, "Body Language," "Cultural Awareness," and "Attentiveness to Family Dynamics" were perceived as relatively easy or not difficult by participants. CONCLUSION: Evaluation of EDCs using EDC-SET revealed the varying competency levels of EDCs and showed agreement on the evaluation between the assessors. Implementing the EDC-SET could help standardise the mapping and measurement of the skill set of EDCs, thereby enhancing their performance and reducing corneal blindness in India.

Trends in keratoplasty from central and northern India. Part II: Types of keratoplasty.

PURPOSE: To report the types of keratoplasty and analyze trends over a period of two decades in central and northern India. METHODS: This was a retrospective review of eye bank registries of six tertiary eye care centers located in central and north India from 2005 to 2021. The indications and various keratoplasty procedures were compared between 2005-2012 and 2013-2021 to analyze the trend. RESULTS: A total of 13,223 corneal grafts were performed, of which therapeutic penetrating keratoplasty (TPK) (5719, 43.3%) was the most common procedure, followed by optical penetrating keratoplasty (OPK) (5528, 41.8%), Descemet stripping endothelial keratoplasty (DSEK) (1279, 9.7%), deep anterior lamellar keratoplasty (DALK) (376, 2.8%), Descemet membrane endothelial keratoplasty (DMEK) (215, 1.6%), patch grafts (75, 0.6%), and keratoprostheses (31, 0.2%). Overall, OPK procedures decreased (-14.1%, P < 0.001), but TPK (+3.1%, P < 0.019), DSEK (+7.1%, P < 0.001), and DMEK (+1.9%, P < 0.001) procedures increased. Although there was an increasing trend in the use of DALK (+0.8%, P < 0.083) and keratoprostheses (+0.3%, P = 0.074) procedures, the trends were not statistically significant. CONCLUSION: In keeping with worldwide trends, an increasing trend in lamellar keratoplasties was observed in central and northern India during the past decade. The trend was significant for DSEK. However, as corneal ulcers and scars were the major indications for keratoplasty, TPK and OPK remained the most common procedures.

Corrective and preventive actions (CAPAs) in eye bank.

This case series highlights the challenges in eye banking and the importance of a quality assurance program. Three cases triggered corrective and preventive actions (CAPAs) to improve the processes. Case 1 emphasized training to prevent retrieval failures. Case 2 stressed the need for blood samples and comprehensive documentation. In Case 3, mishandling led to policy revisions and staff training. CAPA involved identifying concerns, root cause analysis, action plans, implementation, checks, and closure. Errors can occur in man, machinery, process, and policies. Continuous CAPA ensures continuous quality improvement and safe corneal tissue transplantation, benefiting patients in need.

P25-A123†Indo - German GIZ collaboration - impact and way forward in global eye banking.

PURPOSE: Geographical imbalance in cornea supply is a key feature of global eye banking. Most countries of South Asia particularly India suffer from donor cornea shortage which limits the number of keratoplasties, thereby aggravating the already high burden of removable blindness. The purpose of the project is to identify and cross-pollinate best practices from two leading eye banking institutions in India and Germany, and thereby improve service delivery of both systems. The project is supported by the GIZ Hospital Partnerships funding program on behalf of the Federal Ministry for Economic Cooperation and Development (BMZ) with a co-financing by the Else Kröner-Fresenius Foundation (EKFS). It started in 2021 and will last upto 2023. METHODS: A joint expert group from both organisations conducted a series of workshops to identify the areas of intervention and specific practices to be introduced at the Indian partner's region. The overall increase in cornea collections and transplants, documented systemic improvement measures and research output were defined as the key outcomes. RESULTS: Interim results are presented here. Two interventions identified were expansion of catchment area of cornea collection in India, and improved information management system to monitor the progress and efficiency of the collection centres. Under the former intervention, the hub-and-spoke model from the German partner was introduced to the most populous state of India through establishment of two new cornea collection centres (spokes) for Hospital based Cornea collections. In six months these centres have supplied 79 donor corneas leading to 63 transplants at the hub. Under the latter intervention, the specifications of a baseline data capture and operations management system which can be used in low resource settings are being developed. CONCLUSION: The initiative has shown how best practice from one geography can be adapted and successfully implemented in another geography , Furthermore, the public knowledge resources created in the project can be used by other eye banks to advance eye banking in their respective countries.

Three Consecutive Cases of Ocular Polyhexamethylene Biguanide (PHMB) Toxicity Due to Compounding Error.

Acanthamoeba keratitis is treated with long-term biguanide therapy, and the treatment itself can lead to ocular side effects. Knowledge of possible toxic complications can help in the better titration of the treatment regimen. Here, we describe the toxic side effects of polyhexamethylene biguanide (PHMB), which occurred in three consecutive patients treated with in-house compounded PHMB. There was an error in compounding the solution, with the resultant concentration of PHMB being around 0.2%. Patients developed ocular toxicity like conjunctival inflammation, persistent epithelial defect, and large pigment clumps on endothelium within six weeks of initiation of therapy. All of them developed rapidly progressive cataract and mydriatic pupil within three months. PHMB has the potential to cause irreversible damage to ocular structures, and the toxicity is time and concentration-dependent.

Prolonged Inflammation and Infectious Changes in the Corneal Epithelium Are Associated with Persistent Epithelial Defect (PED).

Purpose: Failure of rapid re-epithelialization within 10-14 days after corneal injury, even with standard supportive treatment, is referred to as persistent corneal epithelial (CE) defect (PED). Though an array of genes regulates reepithelization, their mechanisms are poorly understood. We sought to understand the network of genes driving the re-epithelialization in PED. Method: After obtaining informed consent, patients underwent an ophthalmic examination. Epithelial scrapes and tears samples of six PED patients and six individuals (control) undergoing photorefractive keratectomy (PRK) were collected. RNA isolation and quantification were performed using either the epithelial scrape taken from PED patients or from HCLE cells treated with control tears or tears of PED patients. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of a few important genes in CE homeostasis, inflammation, and cell-cell communication, viz., Kruppel-like factor 4 (KLF4), GPX4, IL6, TNFα, STING, IL8, desmoglein, and E-cadherin, among others. Their expressions were normalized with their respective housekeeping genes and fold changes were recorded. KLF4 localization and MMPs activity was carried out via immunofluorescence and zymography, respectively. Results: KLF4, a transcription factor important for CE homeostasis, was upregulated in tears-treated HCLE cells and downregulated in PED patients compared to the healthy PRK group. Cell-cell communication genes were also upregulated in tears-treated cells, whereas they were downregulated in the PED tissue group. Genes involved in proinflammation (IL6, 282-fold; TNFα, 43-fold; IL8, 4.2-fold) were highly upregulated in both conditions. MMP9 activity increased upon tears treatment. Conclusions: This study suggests that tears create an acute proinflammatory milieu driving the PED disease pathology, whereas the PED patients scrapes are an indicator of the chronic stage of the disease. Interferons, pro-inflammatory genes, and their pathways are involved in PED, which can be a potential target for inducing epithelialization of the cornea.

Role of AS-OCT in Managing Corneal Disorders.

Optical coherence tomography (OCT) is analogous to ultrasound biometry in the cross sectional imaging of ocular tissues. Development of current devices with deeper penetration and higher resolution has made it popular tool in clinics for visualization of anterior segment structures. In this review, the authors discussed the application of AS-OCT for diagnosis and management of various corneal and ocular surface disorders. Further, recent developments in the application of the device for pediatric corneal disorders and extending the application of OCT angiography for anterior segment are introduced.

11†Growing together in diversity - Indo-German cooperation enhancing eye donation in North India.

In India, the most densely populated state is Uttar Pradesh in the Northern region. This state has a huge base of corneal blind population due to cornea infections, ocular trauma, and (chemical) burns.Successful cornea transplantation using human post-mortem donated cornea is a treatment modality. In India lack of availability of donated cornea is a public health challenge. Thus, there is great need to reduce the huge demand and supply gap by increasing the donations for supply of cornea to patients.The Eye Bank at the Dr. Shroff's Charity Eye Hospital (SCEH) and the German Society for Tissue Transplantation (DGFG) collaborate in a project to enhance cornea donation and eye bank's infrastructure in Delhi. The project is supported by the Hospital Partnerships funding programme which is a joint initiative of Germany's Federal Ministry for Economic Cooperation and Development (BMZ) and the Else Kröner-Fresenius Foundation (EKFS) and carried out by the German Society for International Collaboration (GIZ GmbH).The project aims to increase the number of cornea donations by the SCEH eye bank through establishing two new eye collection centers where donation is coordinated and that are integrated into the existing and well-established eye bank and donation infrastructure of SCEH. Further, data management of the eye bank will be improved by developing a concept for an electronic database system that allows faster monitoring and evaluation of the processes. All activities are carried out according to a defined project plan. The basis of the project is an open-minded analysis and understanding of processes of both partners in relation to the respective legislations plus the environment and conditions in both countries.Aside from intercultural exchange and personal contacts both partners benefit from mutual on-site visits and exchanging best practices in eye donation and banking as well as sharing expertise in research topics.This project is a great example on how strong and sustainable relationships can be build across the globe improving the infrastructure for cornea donations to help corneal blind patients.

Post penetrating keratoplasty infectious keratitis: Clinico-microbiological profile and predictors of outcome.

PURPOSE: To study the clinico-microbiological profile, outcomes and prognostic factors of post penetrating keratoplasty (PKP) infectious keratitis. METHODS: Retrospective review of medical records of 78 patients with post PKP infectious keratitis presenting between January 2014 and December 2018. Demographic, clinical and microbiological profile was documented and predictors of treatment and graft success were evaluated using univariate and subsequent multivariate logistic regression analysis. RESULTS: Mean age of patients was 52.17 ± 15.51 years and mean infiltrate size was 19.39 ± 19.68 mm2. Mean duration of presentation with infection post PKP was 11.66 ± 10.65 months. Culture positivity was seen in 64 eyes (82.05%). Bacterial growth was observed in 47 eyes (60.25%), fungal growth in 17 (21.79%) and no microbiological growth in 14 eyes (17.94%). At 3 months the visual acuity (VA) improved in 37 eyes (47.44%), did not change in 27 (34.62%) and deteriorated in 14 (17.95%). Graft failure was noted in 53 eyes (73.08%). Surgical intervention was needed in 47 (60.25%) eyes of which most common was therapeutic PKP in 32 eyes (41.02%). Treatment failure was noted with fungal infection (p = 0.05), poorer vision at presentation (p = 0.02), larger infiltrate area (p = 0.002) and graft infection developing before 1 year (p = 0.02). Graft failure was noted with associated endophthalmitis (p = 0.02), poorer VA at presentation (p = 0.01) and larger infiltrate area (p = 0.02). CONCLUSION: Post PKP infectious keratitis is a sight threatening ocular condition. It is associated with high incidence of graft failure and frequently requires surgical intervention. Fungal etiology, larger infiltrate size, poorer vision at presentation and associated endophthalmitis carries a poorer prognosis.

Infectious Keratitis: An Update on Role of Epigenetics.

Epigenetic mechanisms modulate gene expression and function without altering the base sequence of DNA. These reversible, heritable, and environment-influenced mechanisms generate various cell types during development and orchestrate the cellular responses to external stimuli by regulating the expression of genome. Also, the epigenetic modifications influence common pathological and physiological responses including inflammation, ischemia, neoplasia, aging and neurodegeneration etc. In recent past, the field of epigenetics has gained momentum and become an increasingly important area of biomedical research As far as eye is concerned, epigenetic mechanisms may play an important role in many complex diseases such as corneal dystrophy, cataract, glaucoma, diabetic retinopathy, ocular neoplasia, uveitis, and age-related macular degeneration. Focusing on the epigenetic mechanisms in ocular diseases may provide new understanding and insights into the pathogenesis of complex eye diseases and thus can aid in the development of novel treatments for these diseases. In the present review, we summarize the clinical perspective of infectious keratitis, role of epigenetics in infectious keratitis, therapeutic potential of epigenetic modifiers and the future perspective.

Risk of SARS-CoV-2 virus transmission from donor corneal tissue: A review.

Since the outbreak of respiratory coronavirus disease (COVID-19) caused by the coronavirus SARS-CoV-2, there is an ongoing discussion about whether the virus could be transmitted through corneal transplantation from donor to recipient. The purpose of this review was to summarize the current knowledge in the scientific community to provide aid in risk evaluation for potential virus transfer by corneal transplants. Literature was searched in PubMed.gov for relevant articles on coronavirus in conjunction with cornea processing, cornea transplantation and eye banking. Further, guidelines of health authorities and eye banking associations were reviewed. Studies have shown that SARS-CoV-2 RNA can be detected in ocular swabs and/or fluid of patients with COVID-19. However, the risk of SARS-CoV-2 virus transmission through these ocular tissues or fluid of patients is judged differently. To date, per literature and official guidelines, no evidence of viable virus in ocular tissue and no cases of transmission of SARS-CoV-2 via tissue preparations have been reported.

Resuming eye bank services during the COVID-19 pandemic: Experience and inferences.

PURPOSE: The aim of this study was to formulate a methodological approach for resuming eye bank services during COVID-19 pandemic. METHODS: Eye bank operations were temporarily halted in March after the government-mandated "Lockdown" in response to COVID-19 pandemic. Before restarting eye bank operations in May, we studied sources of exposure, performed risk assessment, instituted additional process validations and redefined the Standard Operating Procedures (SOPs) in consultation with the guidelines published by the Eye bank Association of India and All India Ophthalmological Society. The eye bank staff were rigorously trained before and after operations were restarted. We conducted a survey at the end of July to gauge staff attitude and reaction. RESULTS: Eye banks services resumed on 20th May 2020. Since reopening till the end of July total 41 keratoplasties have been done. 91.75% of all keratoplasties done were therapeutic surgeries and 17% of the surgeries were done using glycerine preserved tissues. No staff had COVID-19 symptoms when the operations restarted and none developed symptoms up to the end of July. All eye bank staff were aware of COVID-19 pandemic and 86% said they felt safe working at the eye bank. 86% of the staff said that they received adequate training and 66% of the staff expressed that they always received proper PPE and kits. Overall, 93% of the staff expressed that the measures taken by the eye bank ensured their safety. CONCLUSION: Based on our experience we suggest the following activities for planned resumption of eye bank services during the pandemic: Exposure Risk Analysis, Personal Protective Equipment usage training, SOP Revision and staff training on modified SOPs. Criteria based selection of donor sources, participatory planning involving the staff and double-checking at critical process junctions helped us in managing a smooth transition.