The Current State in the Diagnosis of Eyelid Margin Disease: A Clinical Review.

The eyelid margin is vital to ocular surface integrity. Much peer-reviewed literature has been established in eyelid margin inflammation, better known as blepharitis. The purpose is to review and understand the impact of eyelid margin disease. Anterior blepharitis causes inflammation at the eyelash base, ciliary follicles, and the palpebral skin. Posterior blepharitis occurs when there is inflammation with the posterior eyelid margin disease. In common usage, the term "blepharitis" used alone almost always refers to anterior blepharitis. Classification of eyelid margin disease should be based on etiopathogenesis, location, primary vs. secondary, and chronicity. Blepharitis has several etiopathologies (infectious, inflammatory, squamous). MGD can refer to the functional and/or structural problems with the MG. Meibomitis (or meibomianitis) occurs when there is inflammation associated with the MGD. The presence of blepharitis and/or MGD (with or without inflammation) can impact the ocular surface and thereby affect anterior segment and cataract surgeries. This review article evaluates the differential diagnoses of eyelid margin disease, including various forms of blepharitis, MGD, and meibomitis.

EYELID MARGIN DISEASE (BLEPHARITIS AND MEIBOMIAN GLAND DYSFUNCTION): CLINICAL REVIEW OF EVIDENCE-BASED AND EMERGING TREATMENTS.

ABSTRACT: Blepharitis is a common ophthalmic condition with multiple etiologies and no definitive, universal treatment. The treatment modalities for managing lid margin diseases vary depending on the disease's cause, location, and severity. For anterior blepharitis, management options include eyelid hygiene with warm compresses, eyelid scrubs, baby shampoo, and over-the-counter eyelid cleansers. Topical antibiotics and antibiotic-steroid combination drops/ointments for the eye and eyelid may accompany these. For posterior blepharitis/meibomian gland dysfunction (MGD), at-home warm compress or in-office administration of heat therapy/thermal pulsation treatment that aims to clear obstruction in the meibomian glands and restore meibum secretions to maintain a healthy tear film, are recommended. In addition to the above treatment strategies, various other compounds to manage lid margin diseases are in the late stages of development. This review summarizes the available treatment modalities or those in the pipeline for treating blepharitis and MGD.

Unusual Male Breast Involvement in Burkitt Lymphoma Detected on Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

Burkitt lymphoma (BL) is a poorly differentiated, aggressive form of B-cell non-Hodgkin's lymphoma. The clinical presentation of this disease is varied and may be nodal, extranodal, or both. BL of the breast, either primary or secondary, with bilateral breast involvement, is extremely rare. Herein, we present a case of BL in a 27-year-old male with unusual bilateral breast involvement.

Primary Dural Acute Lymphoblastic Leukaemia/Lymphoma Masquerading Meningioma: Report of a Case and Review of Literature.

Acute lymphoblastic leukaemia/lymphoma (ALL) is a systemic disease which primarily involves bone marrow or lymphoid organs. Extranodal presentation of ALL is uncommon, and ALL presenting as a dural mass is exceedingly rare. Here we present a case of primary dural B-cell ALL which was preoperatively diagnosed as meningioma on clinico-radiological grounds. A 27-year-old female patient presented with left hemicranial headache for one month's duration along with progressive vision loss of in both eye and altered behaviour. Contrast enhanced magnetic resonance imaging (CE-MRI) suggest dural based mass with dural tail sign. Histopathological examination of the resected specimen revealed B-cell ALL. Further systemic investigations didn't suggest any peripheral blood, bone marrow or lymph node involvement. To the best of our knowledge, only two cases of primary dural ALL have been reported in the literature so far. This report highlights the diagnostic difficulty in extramedullary precursor lymphoid neoplasm.

Fluorescence-tagged salivary small extracellular vesicles as a nanotool in early diagnosis of Parkinson's disease.

BACKGROUND: Parkinson's disease is generally asymptomatic at earlier stages. At an early stage, there is an extensive progression in the neuropathological hallmarks, although, at this stage, diagnosis is not possible with currently available diagnostic methods. Therefore, the pressing need is for susceptibility risk biomarkers that can aid in better diagnosis and therapeutics as well can objectively serve to measure the endpoint of disease progression. The role of small extracellular vesicles (sEV) in the progression of neurodegenerative diseases could be potent in playing a revolutionary role in biomarker discovery. METHODS: In our study, the salivary sEV were efficiently isolated by chemical precipitation combined with ultrafiltration from subjects (PD = 70, healthy controls = 26, and prodromal PD = 08), followed by antibody-based validation with CD63, CD9, GAPDH, Flotillin-1, and L1CAM. Morphological characterization of the isolated sEV through transmission electron microscopy. The quantification of sEV was achieved by fluorescence (lipid-binding dye-labeled) nanoparticle tracking analysis and antibody-based (CD63 Alexa fluor 488 tagged sEV) nanoparticle tracking analysis. The total alpha-synuclein (α-synTotal) in salivary sEVs cargo was quantified by ELISA. The disease severity staging confirmation for n = 18 clinically diagnosed Parkinson's disease patients was done by 99mTc-TRODAT-single-photon emission computed tomography. RESULTS: We observed a significant increase in total sEVs concentration in PD patients than in the healthy control (HC), where fluorescence lipid-binding dye-tagged sEV were observed to be higher in PD (p = 0.0001) than in the HC using NTA with a sensitivity of 94.34%. In the prodromal PD cases, the fluorescence lipid-binding dye-tagged sEV concentration was found to be higher (p = 0.008) than in HC. This result was validated through anti-CD63 tagged sEV (p = 0.0006) with similar sensitivity of 94.12%. We further validated our findings with the ELISA based on α-synTotal concentration in sEV, where it was observed to be higher in PD (p = 0.004) with a sensitivity of 88.24%. The caudate binding ratios in 99mTc-TRODAT-SPECT represent a positive correlation with sEV concentration (r = 0.8117 with p = 0.0112). CONCLUSIONS: In this study, for the first time, we have found that the fluorescence-tagged sEV has the potential to screen the progression of disease with clinically acceptable sensitivity and can be a potent early detection method for PD.

How Can We Best Diagnose Severity Levels of Dry Eye Disease: Current Perspectives.

Dry eye disease (DED) is a common ocular condition, but the diagnosis relative to other ocular conditions and the evaluation of severity of the condition has often been difficult. This challenge can be due to clinical signs and symptoms not always correlating with each other. An understanding of the various components which create the condition, as well as the diagnostic measures used to evaluate these components, is useful to the clinician working with DED patients. This review paper will discuss traditional diagnostic options, diagnostic imaging, and Advanced Point of Care testing capabilities to determine the severity level of dry eye disease more adequately.

Coxsackievirus and Adenovirus Receptor (CAR) Expression in Autopsy Tissues: Organ-Specific Patterns and Clinical Significance.

Coxsackievirus and adenovirus receptor (CAR) homologs have been identified in many species, and their proteins appeared to be highly conserved in evolution. While most of the human studies are about pathological conditions, the animal studies were more about the physiological and developmental functions of receptors. The expression of CAR is developmentally regulated, and its tissue localization is complex. Hence, we planned to study CAR expression in five different human organs at autopsy in different age groups. CAR expression was analyzed in the pituitary, heart, liver, pancreas, and kidney by immunohistochemistry, and CAR mRNA expression in the heart and pituitary by real-time PCR.  In the current study, CAR expression was strong in cells of the anterior pituitary, hepatocytes, and bile ducts in the liver, acini, and pancreas and distal convoluted tubule/collecting duct in the kidney, with uniform expression in all age groups. We have noted high CAR expression in fetuses and infantile hearts, which get reduced drastically in adults due to its presumed developmental role in intrauterine life studied in animal models. In addition, the receptor was expressed in glomerular podocytes around the period of fetus viability (37 weeks) but not in early fetuses and adults. We have hypothesized that this intermittent expression could be responsible for the intercellular contact normally formed between the podocytes during the developmental phase. Pancreatic islets also showed increased expression after the emergence of the viability period but not in early fetuses and adults, which might be related to an increase in fetal insulin secretion at that particular age group.

Multi-time point imaging in 99m Tc-pertechnetate scintigraphy of ectopic gastric mucosa in duplication cysts: value-added services.

OBJECTIVES: The aim of our study was to describe the scintigraphic patterns of 99m Tc-pertechnetate uptake in patients who were referred to the department of nuclear medicine for evaluating and diagnosing ectopic gastric mucosa in foregut and midgut duplication cysts. MATERIALS AND METHODS: This hospital-based, retrospective cum prospective research spans a period of 8 years from April 2014 to January 2022. Previous hospital medical records were analyzed and subsequently, a database was prepared which included the age, sex, clinical indication of a 99m Tc-pertechnetate scan, and the planar and SPECT-computed tomography (CT) imaging findings. Postoperative histopathological reports were available for 21 patients. Dynamic and planar static imaging was performed. We included SPECT-CT in suspected duplication cysts to increase the sensitivity and specificity which is a tradeoff for a small amount of additional radiation exposure. A total of 69 patients were subjected to a 99m Tc-pertechnetate scan for suspected foregut or midgut duplication cysts. All were subjected to dynamic planar and delayed static images up to 24 h or until focal uptake of radiotracer was noted which corroborated the anatomical findings, whichever was earlier. SPECT-CT was performed along with the planar study in 31 patients which confirmed the findings. Previously performed CT scans were used for anatomical correlation in the remaining ones. RESULTS: Duplication cysts were localized in a total of 28 patients (19 foregut duplication cysts and 12 small bowel duplications - 3 patients had dual duplication cysts, both foregut, and midgut). Forty-one patients had no scintigraphic evidence of ectopic gastric mucosa. Of these 69 patients, histopathological diagnosis was available for 21 patients (22 lesions). The report was concordant with the scan findings in 15 patients (16 lesions) and 6 patients showed discordance in histopathological diagnosis and scan findings. CONCLUSION: In conclusion, multi-time point imaging is the key to diagnosing ectopic gastric mucosa of various sizes and in various locations. An abnormal radiotracer uptake in dynamic sequences, even before the appearance of the stomach in the region of the small bowel is indicative of intestinal duplication, and delayed radiotracer visualization in the region of the thorax is characteristic of intrathoracic foregut duplication cyst.

Renal Dynamic Scintigraphy as a Sensitive Tool for Detecting Small Volume Urinoma Following Live-Related Renal Transplant.

Renal transplant (RT) is the preferred treatment modality in patients with end-stage renal disease (ESRD). However, it is associated with a significant rate of complications. Early diagnosis and management of these complications are essential to prevent graft loss. Herein, we describe a case of a 48-year-old male who developed ESRD due to underlying autosomal-dominant polycystic kidney disease and underwent an RT. A routine renal dynamic scintigraphy (RDS) performed on day 4 posttransplant showed a focal minute area of radiotracer accumulation on the delayed static images raising suspicion for urinoma. However, it was deemed normal considering the normal renogram curve and stable clinical condition of the patient. However, on day 9 posttransplant, in view of clinical deterioration marked by decreasing urine output and rising serum creatinine levels, ultrasonography - kidney, ureter, and bladder (USG-KUB) and a repeat RDS were performed. Although the USG-KUB described a peri-nephric fluid collection, the nature of the collection could not be determined. RDS confirmed that the collection was urinoma. On retrospective analysis, the focal area of increased radiotracer uptake corresponded to the site of initial suspicion, although there was an increase in the size of the same. In experienced hands, RDS thus proves to be a highly sensitive tool for the diagnosis of urinoma, much before the clinical complications set in.

Interim Analysis of STREAMLINE® Surgical System Clinical Outcomes in Eyes with Glaucoma.

Purpose: To characterize the clinical outcomes of a novel ab interno minimally invasive procedure with the STREAMLINE® Surgical System for creation of incisional goniotomies and canal of Schlemm viscodilation in eyes with mild to severe primary open-angle glaucoma (POAG). Methods: In a prospective, single-arm, first-in-human case series, 20 eyes of 20 subjects with mild to severe POAG underwent creation of incisional goniotomies and canal of Schlemm viscodilation following phacoemulsification cataract extraction after washout of all intraocular pressure (IOP)-lowering medications. The angle surgery portion was performed with a single-use handpiece tipped with a microcannula that creates precise goniotomies through the trabecular meshwork into the canal of Schlemm and delivers a small volume of ophthalmic viscosurgical device directly into the canal via precise catheterization. Outcomes in this interim analysis included mean reduction in IOP and medications through 6 months of follow-up, as well as the proportion of eyes achieving IOP reduction ≥20% from baseline. Results: At month 6, mean IOP reduction of ≥20% from baseline was achieved in 89.5% of eyes (17/19). Mean (standard deviation) medicated IOP at screening was 16.3 (3.6) mmHg and unmedicated baseline IOP (after washout) was 23.5 (2.5) mmHg. Mean IOP was significantly reduced from baseline through 6 months of follow-up to 14.7 (2.4) mmHg (p<0.001), representing an IOP reduction of 8.8 mmHg (36.9%). Overall, 57.9% (11/19) of eyes decreased dependence on IOP-lowering medications by at least one medication, and 42.1% (8/19) were medication free. Mean medication use was reduced from 2.0 (0.8) at screening to 1.1 (1.1) at 6 months (p<0.001). Three eyes had transient IOP spikes treated with topical medications. Conclusion: The creation of incisional goniotomies and canal of Schlemm viscodilation safely and effectively reduced IOP and the need for IOP-lowering medications by both clinically and statistically significant magnitudes in eyes with mild to severe POAG undergoing concomitant phacoemulsification cataract extraction through the first 6 months of follow-up.

Effective Parameters Controlling Sterol Transfer: A Time-Resolved Small-Angle Neutron Scattering Study.

Though cholesterol is the most prevalent and essential sterol in mammalian cellular membranes, its precursors, post-synthesis cholesterol products, as well as its oxidized derivatives play many other important physiological roles. Using a non-invasive in situ technique, time-resolved small angle neutron scattering, we report on the rate of membrane desorption and corresponding activation energy for this process for a series of sterol precursors and post-synthesis cholesterol products that vary from cholesterol by the number and position of double bonds in B ring of cholesterol's steroid core. In addition, we report on sterols that have oxidation modifications in ring A and ring B of the steroid core. We find that sterols that differ in position or the number of double bonds in ring B have similar time and energy characteristics, while oxysterols have faster transfer rates and lower activation energies than cholesterol in a manner generally consistent with known sterol characteristics, like Log P, the n-octanol/water partitioning coefficient. We find, however, that membrane/water partitioning which is dependent on lipid-sterol interactions is a better predictor, shown by the correlation of the sterols' tilt modulus with both the desorption rates and activation energy.

Twelve-month clinical outcomes after implantation of a new, modular, anterior shape-changing fluid optic intraocular lens.

PURPOSE: To report the initial safety and effectiveness profile for an anterior shape-changing, modular IOL, Juvene IOL (JIOL), for the treatment of aphakia and presbyopia after removal of the natural crystalline lens due to cataract. SETTING: 2 private practices in Monterrey and Tijuana, Mexico. DESIGN: Exploratory prospective multicenter open-label noncomparative clinical trial. METHODS: A convenience sample of patients aged 50 to 80 years with planned cataract surgery was recruited to undergo unilateral or bilateral implantation with the JIOL. Patients were required to complete an informed consent and be able to dilate to at least 6.0 mm pharmacologically, be in good overall health, and have no significant eye health history to qualify. Visual acuities, defocus curves, and contrast sensitivity were measured for all patients 12 months postoperatively. RESULTS: 51 of 58 eyes completed the 12-month visit. Intraoperative complication rates were extremely low (n = 1; missed base lens tab). The most frequent adverse events (AEs) were prolonged inflammation (N = 6) and cystoid macular edema (N = 4); all AEs were resolved without sequelae by the 12-month visit. The mean monocular logMAR corrected distance visual acuity, distance-corrected intermediate visual acuity, and distance-corrected near visual acuity were 0.01, 0.08, and 0.24, respectively. Defocus testing showed visual acuity > 20/40 from approximately +1.00 through -2.00 diopters. Binocular implantation (n = 16) provided superior performance over monocular implantation. CONCLUSIONS: The JIOL offers a new solution to treat presbyopia, providing clear functional vision performance across a range of distances with an acceptable initial safety profile.

The Efficacy of Clinical Tests to Diagnose Evaporative Dry Eye Disease Related to Meibomian Gland Dysfunction.

OBJECTIVES: To determine the efficacy of widely available subtype clinical tests to characterize evaporative dry eye disease (EDED) related to meibomian gland dysfunction (MGD) compared to normal and to validate those clinical cut points in an independent sample. METHODS: A diagnostic accuracy study (52 subjects), an investigator-masked study, was followed by a larger independent sample (364 subjects) analysis to confirm efficacy in normal and EDED subjects. All subjects were 18 years of age and older and were classified using a battery of clinical tests for dry eye that included symptoms, tear meniscus height, tear stability, ocular staining, evaporative-specific tests, and the Schirmer I test. RESULTS: Normal (nondry eye; n = 26) and EDED (n = 26) subjects completed the efficacy study. The global tests of tear breakup time, staining, and symptoms all produced AUCs ≥ 0.70, representing acceptable discrimination. EDED-specific tests of eyelid marginal signs, gland secretion quality, and gland loss did not demonstrate acceptable test efficacy or differences between normal and EDED subjects. In a larger, independent sample of normal and EDED subjects, gland secretion quality and eyelid marginal score achieved acceptable diagnostic levels: AUCs of 0.789 (CI: 0.734-0.844) and 0.729 (CI: 0.648-0.810), respectively, but not lipid interferometry grade or lower eyelid gland dropout estimated using meiboscopy. CONCLUSIONS: Meibomian gland secretion quality is an efficient and useful functional indicator in EDED and should be incorporated into core outcome sets for this dry eye subtype.

Application of Hans Algorithm for Subcategorization of Diffuse Large B-Cell Lymphoma in Fine-Needle Aspiration Biopsy Cytology.

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with remarkably variable clinical presentation and outcome. Hans algorithm subclassified DLBCL into prognostically distinct molecular subtypes by using immunohistochemistry (IHC). Fine-needle aspiration biopsy cytology (FNABC) is a first-line diagnostic modality in lymphadenopathy. The study aims to perform IHC on FNABC cell blocks (CBs) for subclassifying according to the Hans algorithm and correlate with case-matched histopathology. METHODS: This was a retrospective study carried out between January 2017 and December 2019. All DLBCL FNABC cases with CBs and smears and which had follow-up histopathology were included in the study. Detailed cytomorphological evaluation and CD10, B-cell lymphoma 6 (BCL6), and multiple myeloma oncogene 1 IHCs were performed on CBs. The cases are divided into 3 distinct molecular subtypes based on the Hans algorithm as germinal centre B-cell (GCB), activated B-cell (ABC), and unclassified subtypes. The results were compared with the final histopathology. RESULTS: A total of 44 cases were diagnosed as DLBCL, and 33 cases with sufficient material for further IHC were included in the study. Twelve cases were of the GCB type, 19 were of the ABC type, and 2 remained unclassified. Follow-up histopathology was available in 20 cases. Overall, histopathological concordance was found in 95% of cases (19/20). The single discordant case was classified as GCB on FNABC and was ABC on histopathology. CONCLUSION: FNABC with CBs is an acceptable alternative to biopsy for providing a complete diagnosis of DLBCL as per the current WHO classification.

Lower Gastrointestinal Bleed Playing Hide and Seek.

A 13-year-old adolescent male presented with an episode of rectal bleed. He has had five such episodes in the past year where he witnessed black tarry stools mixed with fresh blood, painless, not associated with fever or hematemesis. Clinical examination revealed pallor and a soft, non-tender abdomen. Vitals were stable. Blood investigations revealed haemoglobin of 102g/L, WBC count of 10 X 109/L and platelet count of 165 × 109/L. The clotting screen was normal. Upper GI endoscopy and colonoscopy revealed no abnormality. The patient underwent Tc-99m pertechnetate scintigraphy to look for Meckel's Diverticulum in view of painless lower GI bleed.

Deciphering lipid transfer between and within membranes with time-resolved small-angle neutron scattering.

This review focuses on time-resolved neutron scattering, particularly time-resolved small angle neutron scattering (TR-SANS), as a powerful in situ noninvasive technique to investigate intra- and intermembrane transport and distribution of lipids and sterols in lipid membranes. In contrast to using molecular analogues with potentially large chemical tags that can significantly alter transport properties, small angle neutron scattering relies on the relative amounts of the two most abundant isotope forms of hydrogen: protium and deuterium to detect complex membrane architectures and transport processes unambiguously. This review discusses advances in our understanding of the mechanisms that sustain lipid asymmetry in membranes-a key feature of the plasma membrane of cells-as well as the transport of lipids between membranes, which is an essential metabolic process.

Fine-Needle Aspiration Diagnosis of Lymphoma Based on Cytomorphology Alone: How Accurate is it? - A Cyto-Histopathology Correlative Study.

CONTEXT: Fine-needle aspiration cytology (FNAC) is a rapid and accurate first-line diagnostic modality in lymphadenopathy. AIMS: To determine the utility of FNAC for the diagnosis of lymphoma and highlight the various pitfalls in morphological interpretation. SETTINGS AND DESIGN: This was a retrospective study of 3 years duration in which cytology diagnosis was compared with the follow-up histopathology diagnosis wherever available. RESULTS: A cytodiagnosis of lymphoma was made in a total of 868 cases (2.8%) out of nearly 33,000 FNAC performed during the study period; 556 (64.1%) cases were diagnosed as non-Hodgkin lymphoma (NHL), 198 (22.8%) as Hodgkin lymphoma (HL), and in 114 (13.1%) cases, a cytological diagnosis of lymphoma without further categorization was given. Histopathological reports were available in 348 cases, with an overall concordance rate of 93.1% (324), which was slightly higher in the HL cases (95.8%) as compared to NHL (91.7%). Twenty-four cases (6.9%) showed discordant cytological diagnosis with subsequent histopathology. The main reasons for the erroneous diagnosis were the over-interpretation of the germinal center cells as atypical lymphoid cells, over-interpretation of immunoblasts with prominent nucleoli as Hodgkin cells, and sheets of monomorphic lymphoid cells interpreted as low-grade lymphoma. CONCLUSION: Cytomorphology alone can make a correct basic diagnosis of lymphoma with a high degree of accuracy. The errors in interpretation can be further reduced by careful attention to the diagnostic pitfalls and common differential diagnoses.

The Effects of Glaucoma and Glaucoma Therapies on Corneal Endothelial Cell Density.

A healthy corneal endothelium is required for corneal clarity. Both the glaucoma disease state and its various forms of treatment can have adverse effects on the corneal endothelium. Both the presence of glaucoma and the magnitude of intraocular pressure elevation are related to endothelial cell loss (ECL). Topical medical therapy, laser procedures, and both traditional surgeries-trabeculectomy and tube-shunts-and newer minimally invasive glaucoma surgeries have variable effects on ECL. This review will summarize the reported effects of glaucoma and its treatment on ECL. Concerns for corneal endothelial cell health should be part of the decision-making process when planning glaucoma therapy for lowering intraocular pressure, with added caution in case of planned device implantation in eyes with preexisting ECL and low endothelial cell density at high risk for corneal endothelial decompensation.