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Numerous drivers push specialist diagnostic approaches down to primary care (‘diagnostic downshift’), intuitively welcomed by clinicians and patients. However, primary care’s different population and processes result in under-recognised, unintended consequences. Testing performs poorer in primary care, with indication creep due to earlier, more undifferentiated presentation and reduced accuracy due to spectrum bias and the ‘false-positive paradox’. In low-prevalence settings, tests without near-100% specificity have their useful yield eclipsed by greater incidental or false-positive findings. Ensuing cascades and multiplier effects can generate clinician workload, patient anxiety, further low-value tests, referrals, treatments and a potentially nocebic population ‘disease’ burden of unclear benefit. Increased diagnostics earlier in pathways can burden patients and stretch general practice (GP) workloads, inducing downstream service utilisation and unintended ‘market failure’ effects. Evidence is tenuous for reducing secondary care referrals, providing patient reassurance or meaningfully improving clinical outcomes. Subsequently, inflated investment in per capita testing, at a lower level in a healthcare system, may deliver diminishing or even negative economic returns. Test cost poorly represents ‘value’, neglecting under-recognised downstream consequences, which must be balanced against therapeutic yield. With lower positive predictive values, more tests are required per true diagnosis and cost-effectiveness is rarely robust. With fixed secondary care capacity, novel primary care testing is an added cost pressure, rarely reducing hospital activity. GP testing strategies require real-world evaluation, in primary care populations, of all downstream consequences. Test formularies should be scrutinised in view of the setting of care, with interventions to focus rational testing towards those with higher pretest probabilities, while improving interpretation and communication of results.

Erectile dysfunction is a common problem in primary care. Martin Steggall and colleagues discuss what needs to be assessed and the treatment options available Erectile dysfunction (ED) is defined as the inability of a man to get and maintain an erection that is sufficient for sexual intercourse, and is a common problem. ED commonly has a profound negative impact on quality of life in the patient and his partner, which can result in changes to sexual self-confidence. This article outlines strategies for identifying and managing ED in primary care, outlining what needs to be assessed and the various treatment options available to manage the condition.

The coronavirus pandemic has had significant effects on individuals, healthcare systems and governments. In the UK, whilst routine dentistry was suspended, an urgent dental care system was required to support urgent patient need. Using an adapted model of Donabedians’ framework, a critical evaluation of the services developed and implemented is provided and the various innovative approaches involved in this work are discussed. The three domains of the framework are structure, process and outcome. Structure: We present the principles for selecting and initiating hubs, the integration with secondary care services and the supply of personal protective equipment. Process: The main elements are communication, the development of referral processes to manage complex cases and data collection. Outcome: Through work with local dental stakeholders, 23 clusters and 36 hubs were set up covering a large geographical area. The integrated network of hubs and clusters has strengthened collaboration between providers and policy makers. Various leadership approaches facilitated the readiness for the transition to recovery. The new local collaborative structures could be used to support local programmes such as flexible commissioning, peer-led learning and integration with primary care networks.

BackgroundFungal keratitis (FK) is the leading cause of unilateral blindness in the developing world. Antimicrobial peptides (AMPs) have been shown to play an important role on human ocular surface (OS) during bacterial, viral and protozoan infections. In this study, our aim was to profile a spectrum of AMPs in corneal tissue from patients with FK during the active pase of infection and after healing.MethodsOS samples were collected from patients at presentation by impression cytology and scraping. Corneal button specimens were collected from patients undergoing therapeutic penetrating keratoplasty for management of severe FK or healed keratitis. Gene expression of human beta-defensin (HBD)-1, -2, -3 and -9, S100A7, and LL-37 was determined by quantitative real-time PCR.ResultsMessenger RNA expression (mRNA) for all AMPs was shown to be significantly upregulated in FK samples. The levels of HBD-1 and -2 mRNA were found to be elevated in 18/20 FK samples. Whereas mRNA for HBD-3 and S100A7 was upregulated in 11/20 and HBD9 was increased in 15/20 FK samples. LL-37 mRNA showed moderate upregulation in 7/20 FK samples compared with controls. In healed scar samples, mRNA of all AMPs was found to be low and matching the levels in controls.ConclusionAMP expression is a consistent feature of FK, but not all AMPs are equally expressed. HBD-1 and -2 are most consistently expressed and LL-37 the least, suggesting some specificity of AMP expression related to FK. These results will help to identify HBD sequence templates for designing FK-specific peptides to test for therapeutic potential.

Retinal diseases are the leading causes of irreversible blindness worldwide. The role of toll-like receptor (TLR) signalling mechanisms (MyD88 and TRIF) in the production of pro-angiogenic growth factors from human microvascular endothelial cells (HMEC-1) under hypoxic stress remains unexplored. HMEC-1 was incubated under normoxic (5% CO2 at 37 °C) and hypoxic (1% O2, 5% CO2, and 94% N2, at 37 °C) conditions for 2, 6, 24, and 48 h, respectively. For TLR pathway analysis, HMEC-1 was pre-treated with pharmacological inhibitors (Pepinh-MyD88 and Pepinh-TRIF) and subjected to normoxia and hypoxia conditions. Gene and protein expressions of vascular endothelial growth factor-A (VEGF-A), fibroblast growth factor (FGF-2), hypoxia inducible factor 1-alpha (HIF1-α) were performed using quantitative polymerase chain reaction (qPCR), ELISA, and Western blot methodologies. Levels of TLR3 and TLR4 were analysed by flow cytometry. Under hypoxia, levels of VEGF-A and FGF-2 were elevated in a time-dependent fashion. Inhibition of MyD88 and TRIF signalling pathways decreased FGF-2 levels but failed to modulate the secretion of VEGF-A from HMEC-1. Blocking a known regulator, endothelin receptor (ETR), also had no effect on VEGF-A secretion from HMEC-1. Overall, this study provides the proof-of-concept to target TLR signalling pathways for the management of blinding retinal diseases.

Purpose To verify the concept of adult acquired flat foot following ACL rupture by Podogram method comparing injured and non injured sides. Material and method From January 2017 to July 2017, Patients who had unilateral and chronic ACL rupture, confirmed clinically and on MRI, formed the material of present study. In all the patients who could stand a Podogram was obtained of foot on a Graph paper including both injured and uninjured sides. On the podograms the area occupied by weight bearing portion of foot was measured. Results Total number of patients studied were 23. Total number of podograms were 46. The mean value of area occupied on podogram on injured and non injured side were 115.26 and 102.36 respectively. The range of difference between the podograms of both limbs (ACL ruptured and normal) was 0.00 cm2–43.75 cm2 calculated p value was 0.0109 which was statistically significant. Conclusion The Podogram data of ACL ruptured limb and uninjured contralateral limb are in support of our hypothesis of Adult Acquired Flat foot in ACL ruptured patients.

Aims: The aim is to study the various factors associated with depressed skull fractures (DSFs) and their relationship with outcomes in patients who underwent surgery. Settings and Design: This was a cross-sectional study in a hospital setting. Patients and Methods: One hundred and fifty patients who underwent surgeries over a period of 6 years at our institute for DSFs were followed up and outcomes were analyzed. Patients having other medical- or trauma-related surgical morbidities were excluded. All age groups were studied. Statistical Analysis Used: The statistical analysis was performed using Chi-square test. Results: There was a significant relationship between the mode of injury, Glasgow coma scale (GCS) score at admission and discharge, and underlying brain injuries with the outcomes. The variables such as pneumocephalus, dural tears, type of fracture and site of the fracture, and age and sex distribution of the patient were not statistically influencing the outcomes. Conclusions: Patients who underwent surgery for DSFs, with good GCS at admission and discharge, with no underlying brain injury, and who did not sustain injuries in a road traffic accident had better outcomes.

Aim To assess and compare the clinical, radiological, and functional outcomes of anterolateral and posterolateral decompression and spinal stabilization in the thoracolumbar tuberculous spine. Material and methods 30 patients with thoracolumbar spinal tuberculosis were treated surgically between September 2014 and 2018. Fifteen patients underwent anterolateral decompression and spinal stabilization from September 2014 to September 2016. These patients were studied retrospectively (group A). Fifteen patients underwent posterolateral decompression by costotransversectomy and spinal stabilization from September 2016 to September 2017 were studied prospectively. Neurological recovery, correction of kyphotic deformity, pain (visual analog score) and ESR, and duration of stay were assessed. Neurological outcome was assessed using Frankel grading, and pain was assessed using visual analog scale. Results The average follow-up period in both the groups is 12 months. There was a statistically significant difference in the kyphotic angle correction between anterolateral and posterolateral groups at the end of 12 months (follow up). No statistically significant difference was found between the two groups for ESR, visual analog scale for pain, and neurological recovery (Frankel's grading) at the end of 12 months. Conclusion Both anterolateral and posterolateral approaches are sufficient thoracic and thoracolumbar tuberculous spine but, the posterolateral approach allows a significant correction of kyphotic angle, better improvement of pain and lesser duration of stay.

PurposeTo report the real-world experience of using topical ciclosporin, Ikervis, in the management of ocular surface inflammatory diseases (OSIDs).MethodsThis was a retrospective study of patients treated with Ikervis for OSIDs at the Queen’s Medical Centre, Nottingham, between 2016 and 2019. Relevant data, including demographics, indications, clinical parameters, outcomes and adverse events, were collected and analysed for patients who had completed at least 6 months follow-up. For analytic purpose, clinical outcome was categorised as ‘successful’ (resolved or stable disease), ‘active disease’ and ‘drug intolerance’.Results463 patients were included; mean age was 51.1±21.6 years, with a 59.0% female predominance. Mean follow-up was 14.6±9.2 months. The most common diagnosis was dry eye disease (DED; 322, 69.5%), followed by allergic eye disease (AED; 53, 11.4%) and ocular mucous membrane pemphigoid/Steven-Johnson syndrome (OMMP/SJS; 38, 8.2%). Successful treatment was achieved in 343 (74.1%) patients, with 44 (9.5%) requiring additional treatment and 76 (16.4%) reporting drug intolerance. The efficacy of Ikervis was highest in DED (264, 82.0%), followed by OMMP/SJS (25, 65.8%) and post-keratoplasty (7, 50.0%; pConclusionsIkervis is a useful steroid-sparing topical treatment for managing OSIDs in the real-world setting. Preparations with improved tolerability are needed to benefit a larger number of patients.

The golden era of antibiotics, heralded by the discovery of penicillin, has long been challenged by the emergence of antimicrobial resistance (AMR). Host defense peptides (HDPs), previously known as antimicrobial peptides, are emerging as a group of promising antimicrobial candidates for combatting AMR due to their rapid and unique antimicrobial action. Decades of research have advanced our understanding of the relationship between the physicochemical properties of HDPs and their underlying antimicrobial and non-antimicrobial functions, including immunomodulatory, anti-biofilm, and wound healing properties. However, the mission of translating novel HDP-derived molecules from bench to bedside has yet to be fully accomplished, primarily attributed to their intricate structure-activity relationship, toxicity, instability in host and microbial environment, lack of correlation between in vitro and in vivo efficacies, and dwindling interest from large pharmaceutical companies. Based on our previous experience and the expanding knowledge gleaned from the literature, this review aims to summarize the novel strategies that have been employed to enhance the antimicrobial efficacy, proteolytic stability, and cell selectivity, which are all crucial factors for bench-to-bedside translation of HDP-based treatment. Strategies such as residues substitution with natural and/or unnatural amino acids, hybridization, L-to-D heterochiral isomerization, C- and N-terminal modification, cyclization, incorporation with nanoparticles, and “smart design” using artificial intelligence technology, will be discussed. We also provide an overview of HDP-based treatment that are currently in the development pipeline.

Introduction Fluorescein sodium is one of the fluorophores that is used in the resection of intracranial lesions. It is commonly used along with a customized microscope, which is expensive and not available universally. In this study, we describe a simple, inexpensive method for better visualization of intracranial and spinal cord lesions with fluorescein. Materials and Methods After a test dose, 20 mg/kg of fluorescein sodium was administered intravenously at the time of intubation. A blue light source was used before resection for precise localization of the intracranial lesions after durotomy. Most of the resection was done under the white light, while the blue light was used intermittently to delineate the pathologic tissue from the normal tissue and to ensure safe maximal resection. The intensity of fluorescein staining under white light and blue light was noted. Results The study comprised 40 cases of gliomas, meningiomas, abscesses, spinal cord tumors, and cerebellopontine angle lesions. Thirty-five lesions showed good fluorescence under the blue light, which helped us achieve better resection of the pathologic lesions. Conclusions Fluorescein sodium is a safe dye; it can be used to aid in precise localization and safe maximal resection of the pathologic tissue with the help of a blue light source at any center with challenged resources. The blue light enhances the fluorescence and visualization of the pathologic tissue, and this technique can be adopted by any surgeon without much difficulty even with a basic neurosurgical setup.

AimsTo demonstrate and characterise distinct subepithelial compact nerve endings (CNE) at the human corneoscleral limbus.MethodsTen fresh human donor corneoscleral discs (mean age, 67 years) and 26 organ-cultured corneoscleral rims (mean age, 59 years) were studied. All samples were subjected to enzyme histochemical staining related to endogenous acetylcholinesterase present in nerve tissue and H&E staining. Whole-mount en face imaging with NanoZoomer digital pathology microscope and serial cross-section imaging with light microscope were undertaken.ResultsNerves entering the corneoscleral limbus and peripheral cornea terminate under the epithelium as enlarged multiloculated and multinucleated ovoid structures within a 2 mm zone. They are closely associated with the rete pegs of the limbal palisades and the limbal epithelial crypts, often located within characteristic stromal invaginations of these structures. Their numbers ranged from 70 to 300 per corneoscleral rim. The size ranged from 20 to 100 µm. They had one or more nerve connections and were interconnected to other similar endings and to the limbal nerve plexus.ConclusionHuman corneoscleral limbus demonstrates a population of nerve terminals resembling CNE with distinct morphological features. They are closely associated with the limbal stem cell niches, suggesting a potential contribution to the niche environment.

ObjectivesThe largest proportion of general practitioner (GP) magnetic resonance imaging (MRI) is musculoskeletal (MSK), with consistent annual growth. With limited supporting evidence and potential harms from early imaging overuse, we evaluated practice to improve pathways and patient safety.MethodsCohort evaluation of routinely collected diagnostic and general practice data across a UK metropolitan primary care population. We reviewed patient characteristics, results and healthcare utilisation.ResultsOf 306 MSK-MRIs requested by 107 clinicians across 29 practices, only 4.9% (95% CI ±2.4%) appeared clearly indicated and only 16.0% (95% CI ±4.1%) received appropriate prior therapy. 37.0% (95% CI ±5.5%) documented patient imaging request. Most had chronic symptoms and half had psychosocial flags. Mental health was addressed in only 11.8% (95% CI ±6.3%) of chronic sufferers with psychiatric illness, suggesting a solely pathoanatomical approach to MSK care. Only 7.8% (95% CI ±3.0%) of all patients were appropriately managed without additional referral. 1.3% (95% CI ±1.3%) of scans revealed diagnoses leading to change in treatment (therapeutic yield). Most imaged patients received pathoanatomical explanations to their symptoms, often based on expected age or activity-related changes. Only 16.7% (95% CI ±4.2%) of results appeared correctly interpreted by GPs, with spurious overperception of surgical targets in 65.4% (95% CI ±5.3%) who suffered ‘low-value’ (ineffective, harmful or wasteful) post-MRI referral cascades due to misdiagnosis and overdiagnosis. Typically, 20%–30% of GP specialist referrals convert to a procedure, whereas MRI-triggered referrals showed near-zero conversion rate. Imaged patients experienced considerable delay to appropriate care. Cascade costs exceeded direct-MRI costs and GP-MSK-MRI potentially more than doubles expenditure compared with physiotherapist-led assessment services, for little-to-no added therapeutic yield, unjustifiable by cost–consequence or cost–utility analysis.ConclusionUnfettered GP-MSK-MRI use has reached unaccceptable indication creep and disutility. Considerable avoidable harm occurs through ubiquitous misinterpretation and salient low-value referral cascades for two-thirds of imaged patients, for almost no change in treatment. Any marginally earlier procedural intervention for a tiny fraction of patients is eclipsed by negative consequences for the vast majority. Only 1–2 patients need to be scanned for one to suffer mismanagement. Direct-access imaging is neither clinically, nor cost-effective and deimplementation could be considered in this setting. GP-MSK-MRI fuels unnecessary healthcare utilisation, generating nocebic patient beliefs and expectations, whilst appropriate care is delayed and a high burden of psychosocial barriers to recovery appear neglected.

BACKGROUND: To assess the efficacy of combined 5FU and Avastin injections in the treatment of primary pterygium METHODS: Sixteen eyes with primary pterygium received intralesional 5 fluorouracil and Avastin (2.5–5 mg) injections every 2 weeks for a maximum of five injections. Fourteen eyes of 14 patients received five injections, one eye received three injections and one eye received two injections. All eyes were followed at monthly intervals for 3 months after last injection. Tissue was obtained by surgical excision of primary pterygium from four eyes who received injections and three eyes with primary pterygium who did not receive injections (control) and subjected to immunohistological examination for beta fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), von-Willebrand factor (vWF), lymphatic vessel endothelial hyaluronan receptor (LYVE-1) and collagen-I. RESULTS: Pterygium progression was arrested in all patients. Sixty-two percent of patients had improvement of redness while 89% had reduced thickness of the lesion. VEGF, bFGF, EGF, vWF, LYVE-1 and collagen-I were all reduced in the injected samples. CONCLUSIONS: The injection of 5 fluorouracil and Avastin act synergistically to arrest progression and induce atrophy in primary pterygium. This is related to the effect of agents on fibroblasts, collagen, and vascular tissues. Such medical intervention is a safe and viable option in the management of primary pterygium though excision of residual tissue is still required in some cases. Longer follow up is needed to ascertain whether this will reduce the recurrence rate following excision.

Purpose\ud \ud Descemet membrane endothelial keratoplasty (DMEK) and pre-Descemet endothelial keratoplasty (PDEK) tissues always scroll with the endothelial cells (EC) outside. We designed a study to understand the reason for this behavior.\ud \ud Design\ud \ud Experimental study.\ud \ud Methods\ud \ud Elastin content in Descemet membrane (DM), pre-Descemet layer (PDL), central and peripheral stroma, sclera, and trabecular meshwork were measured by the Fastin elastin assay kit. Distribution of elastin in DM, PDL, and anterior lens capsule (ALC) were examined by immunohistology. The effect of recombinant elastase enzyme and the effect of complete removal of EC and epithelial cells on the scrolling of DM and ALC, respectively, were studied.\ud \ud Results\ud \ud PDL showed the highest elastin content among the different tissues studied. Elastin localized as a distinct anterior band in the DM and was uniformly distributed in the PDL demarcating the latter from corneal stroma. Enzymatic treatment of DM with elastase reversed scrolling and corresponded with degradation or disappearance of elastin. Removal of EC did not affect the direction of scrolling. ALC behaved in the same manner with regard to distribution of elastin, scrolling, and removal of epithelial cells.\ud \ud Conclusions\ud \ud This pattern of elastin distribution in DM explains why DMEK and PDEK tissues always scroll with the EC outside. This behavior is not influenced by the EC. High elastin content and uniform distribution in the PDL suggest a structural difference from the posterior stroma.

AimsTo describe the in vivo confocal microscopy (IVCM) features of human limbal nerve corpuscles (LNCs) and correlate these with the histological features.MethodsWe examined 40 eyes of 29 healthy living subjects (17 female, 12 male; mean age=47.6) by IVCM. Four limbal quadrants were scanned through all epithelial layers and stroma to identify the LNCs and associated nerves. Ten fresh normal human corneoscleral discs from five deceased patients with a mean age of 67 years and 17 eye-bank corneoscleral rims with a mean age of 57.6 years were stained as whole mounts by the acetylcholinesterase (AChE) method to demonstrate LNCs and corneal nerves. Stained tissue was scanned in multiple layers with the NanoZoomer digital pathology microscope. The in vivo results were correlated to the histological findings.ResultsOn IVCM, LNCs were identified in 65% of the eyes studied and were mainly (84%) located in the inferior or superior limbal regions. They appeared either as bright (hyper-reflective) round or oval single structures within the hyporeflective, relatively acellular fibrous core of the palisades or were clustered in groups, often located anterior to the palisades of Vogt. They measured 36 µm in largest diameter (range 20–56 µm). The in vivo features were consistent with the histology, which showed LNCs as strongly AChE positive round or oval structures.ConclusionThe strong correlation with histology will enable use of IVCM to study LNCs in normal and disease conditions.

Purpose Dense deposit disease (DDD) is caused by dysregulation of the alternative pathway of the complement cascade and characterized by electron-dense deposits in the kidney glomerular basement membrane (GBM) and drusen in Bruch's membrane (BrM). Complement factor H (fH) and factor properdin (fP) regulate complement activation; fH inhibits alternative pathway (AP) activation, whereas fP promotes it. We report pathologic changes in eyes of an fH and fP double-mutant mouse, which we previously showed have dense deposits in the GBM and early mortality from nephropathy. Methods fHm/m, fP-/-, and fHm/m/fP-/- mice were generated on a C57BL/6-129J background. Fundus imaging at 8 weeks of age was followed by analysis via light and electron microscopy. Retinal function was assessed by electroretinography (ERG). Complement levels and localization were tested by immunohistochemistry and ELISA. Retinas of fHm/m/fP-/- mice treated with intraperitoneal injections of an anti-C5 antibody were compared to those of age- and genotype-matched mice injected with an isotype control antibody. Results fHm/m/fP-/- mice suffered early-onset retinal hypopigmented spots detected using in vivo retinal photography, and histologic examination showed basal laminar deposits (BLamD), degeneration of the photoreceptors, and RPE vacuolization. ERG showed diminished retinal function. The anti-C5 antibody was retina-protective. Conclusions This unique mouse represents a new model of complement-mediated rapid-onset DDD, and could be useful in exploring the pathologic changes associated with BLamD in age-related macular degeneration.

Purpose: To measure the pressure and volume of air required to create a big bubble (BB) in simulated deep anterior lamellar keratoplasty (DALK) in donor eyes and ascertain the bursting pressure of the BB.Patients and methods: Twenty-two human sclera-corneal discs were used. Air was injected into the corneal stroma to create a BB and the pressure measured by means of a pressure converter attached to the system via a side port. A special clamp was designed to prevent air leak from the periphery of the discs. The pressure at which air emerged in the corneal tissue; the bursting pressure measured after advancing the needle into the bubble cavity and injecting more air; the volume of air required to create a BB and the volume of the BB were ascertained.Results: Type-1 BB were achieved in 19 and type-2 BB in 3 eyes. The maximum pressure reached to create a BB was 96.25+/- 21.61?kpa; the mean type-1 intrabubble pressure was 10.16 +/- 3.65?kpa. The mean bursting pressure of a type-1 BB was 66.65 +/- 18.65?kpa, while that of a type-2 BB was 14.77 +/- 2.44?kpa. The volume of air required to create a type-1 BB was 0.54?ml and the volume of a type-1 BB was consistently 0.1?ml.Conclusions: Dua's layer baring DALK can withstand high intraoperative pressures compared to Descemet's membrane baring DALK. The study suggests that it could be safe to undertake procedures such as DALK-triple with a type-1 BB but not with a type-2 BB.

Sight depends on the passage of light through the transparent cornea and being focused on the fovea. Its exposed position renders it vulnerable to microbial infection. The cornea has developed a wide array of defense mechanisms against infection, of which endogenous antimicrobial peptides (AMPs) are key. AMPs are essentially small molecular weight cationic peptides with a wide range of activity against virus, bacteria, fungi and parasites. Some proteins such as RNases and S100As are also included in this group. Several AMPs act synergistically allowing low expression of multiple AMPs to act efficiently. AMPs also have a range of non-microbicidal functions and serve as signaling molecules, immunomodulators; show anti-tumour activity, and influence vascularization and wound healing. Different toll-like receptors (TLR) have been implicated in the preferential induction of specific AMPs. A range of bacteria, including mycobacteria tuberculosis, viruses including herpes virus, fungi and parasites including acanthamoeba, that cause ocular infections have been shown to induce specific AMPs via TLR activation. Non-TLR mediated induction of AMP expression can occur and several molecules such as L-isoleucine, sodium butyrate, vitamin D3, phenylbutyrate, vasoactive intestinal peptide, and etinostat have been identified in this regard. Given the rising microbe resistance to antibiotics, the slow rate of development of new antibiotics and the limited access to effective antibiotics by patients living in the developing world, an ideal solution would be to find AMPs that are effective singly or in combination with each other or other antimicrobial proteins to reduce, if possible eliminate reliance on antibiotics alone.

Orbital lymphangioma is an infrequent benign cystic lesion manifesting in childhood and presenting with slowly progressive proptosis, and restriction of eye movements. Here we report a rare case of 8 year old male patient presenting with unilateral painful proptosis and subconjunctival hemorrhage with decrease of vision and restriction of eye movements. CT scan and MRI were done which revealed an intraorbital and intraconal cystic space occupying lesion. Fronto-orbito zygomatic craniotomy was done for orbital decompression and subtotal excision of tumor and blood evacuation. Histopathological findings were suggestive of lymphangioma.

Craniofacial epidermoid cysts are rare tumors representing 0.2%–1% of all the intracranial tumors. Intradiploic variants account for 25% of these cysts. These cysts are benign, slow-growing, congenital tumors derived from ectodermal remnants misplaced during embryogenesis. Mean age at presentation of these lesions is 40 years; epidermoid cysts are typically asymptomatic (Toglia JU, Netsky MG, Alexander E Jr. Epithelial (epidermoid) tumors of the cranium. Their common nature and pathogenesis. J Neurosurg 1965;23:384-93). Giant extradural epidermoid cysts with profound deformation of the brain and extensive lytic skull lesions may allow a normal life without any significant neurological deficits. Computed tomography scan and magnetic resonance imaging play an important role in the diagnosis of the lesion and management protocol. Histologically, epidermoid cysts are lined by stratified squamous epithelium and are filled with anucleatic keratin (Hao S, Tang J, Wu Z, Zhang L, Zhang J, Wang Z. Natural malignant transformation of an intracranial epidermoid cyst. J Formos Med Assoc 2010;109:390-6). Complete removal of the cyst along with its capsule is the treatment of choice. Recurrences of intradiploic epidermoid cyst have been reported. Here, we report a case of 14-year-old girl presenting with a giant frontal intradiploic epidermoid cyst with an intracranial and extracranial extension without any neurological deficits. Bifrontal craniotomy was performed and cyst was excised in toto.

Increased expression of cathepsins has diagnostic as well as prognostic value in several types of cancer. Here, we demonstrate a novel magnetic resonance imaging (MRI) method, which uses poly-L-glutamate (PLG) as an MRI probe to map cathepsin expression in vivo, in a rat brain tumor model. This noninvasive, high-resolution and non-radioactive method exploits the differences in the CEST signals of PLG in the native form and cathepsin mediated cleaved form. The method was validated in phantoms with known physiological concentrations, in tumor cells and in an animal model of brain tumor along with immunohistochemical analysis. Potential applications in tumor diagnosis and evaluation of therapeutic response are outlined.