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.

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.

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.

Phenotypic and Functional Signatures of Herpes Simplex Virus-Specific Effector Memory CD73+CD45RAhighCCR7lowCD8+ TEMRA and CD73+CD45RAlowCCR7lowCD8+ TEM Cells Are Associated with Asymptomatic Ocular Herpes.

HSV type 1 (HSV-1)-specific CD8+ T cells protect from herpes infection and disease. However, the nature of protective CD8+ T cells in HSV-1 seropositive healthy asymptomatic (ASYMP) individuals (with no history of clinical herpes disease) remains to be determined. In this study, we compared the phenotype and function of HSV-specific CD8+ T cells from HLA-A*02:01-positive ASYMP and symptomatic (SYMP) individuals (with a documented history of numerous episodes of recurrent ocular herpetic disease). We report that although SYMP and ASYMP individuals have similar frequencies of HSV-specific CD8+ T cells, the "naturally" protected ASYMP individuals have a significantly higher proportion of multifunctional HSV-specific effector memory CD8+ T cells (CD73+CD45RAhighCCR7lowCD8+ effector memory RA (TEMRA) and CD73+CD45RAlowCCR7lowCD8+ effector memory (TEM) as compared with SYMP individuals. Similar to humans, HSV-1-infected ASYMP B6 mice had frequent multifunctional HSV-specific CD73+CD8+ T cells in the cornea, as compared with SYMP mice. Moreover, in contrast to wild type B6, CD73-/- deficient mice infected ocularly with HSV-1 developed more recurrent corneal herpetic infection and disease. This was associated with less functional CD8+ T cells in the cornea and trigeminal ganglia, the sites of acute and latent infection. The phenotypic and functional characteristics of HSV-specific circulating and in situ CD73+CD8+ T cells, demonstrated in both ASYMP humans and mice, suggest a positive role for effector memory CD8+ T cells expressing the CD73 costimulatory molecule in the protection against ocular herpes infection and disease. These findings are important for the development of safe and effective T cell-based herpes immunotherapy.

Intraocular lens calculations in patients with keratoectatic disorders.

PURPOSE OF REVIEW: Intraocular lens (IOL) calculations in patients with keratoconus and other keratoectatic disorders continues to be a challenge for today's cataract surgeon. In this article, we review data published over the past 18 months (June 2018 to January 2020). RECENT FINDINGS: Cataract surgery in keratoconus patients has the potential to greatly improve patients' vision. However, keratoconic eyes are notorious for unpredictable outcomes because of difficulty in obtaining proper preoperative biometry and lack of data and consensus on IOL calculation formulas that can reliable in providing the desired outcome. Recent studies suggest the Barrett II Universal calculation is the most accurate in mild-to-moderate keratoconic eyes. All studies note the level of predictability decreases with the steepness of keratometric readings. Historically, the SRK/T has been shown to provide the most reliable calculations. SUMMARY: There is still no consensus on which formula is best for IOL calculation in keratoconic eyes. On the basis of the most recent literature, we recommend using the Barrett II Universal in conjunction with the SRK/T formula for mild-to-moderate eyes. Preoperative counseling of expectations with the patient is the key to achieving a satisfied patient and avoiding an unpleasant situation in the result of refractive surprise.

Bolstering the Number and Function of HSV-1-Specific CD8+ Effector Memory T Cells and Tissue-Resident Memory T Cells in Latently Infected Trigeminal Ganglia Reduces Recurrent Ocular Herpes Infection and Disease.

HSV type 1 (HSV-1) is a prevalent human pathogen that infects >3.72 billion individuals worldwide and can cause potentially blinding recurrent corneal herpetic disease. HSV-1 establishes latency within sensory neurons of trigeminal ganglia (TG), and TG-resident CD8+ T cells play a critical role in preventing its reactivation. The repertoire, phenotype, and function of protective CD8+ T cells are unknown. Bolstering the apparent feeble numbers of CD8+ T cells in TG remains a challenge for immunotherapeutic strategies. In this study, a comprehensive panel of 467 HLA-A*0201-restricted CD8+ T cell epitopes was predicted from the entire HSV-1 genome. CD8+ T cell responses to these genome-wide epitopes were compared in HSV-1-seropositive symptomatic individuals (with a history of numerous episodes of recurrent herpetic disease) and asymptomatic (ASYMP) individuals (who are infected but never experienced any recurrent herpetic disease). Frequent polyfunctional HSV-specific IFN-γ+CD107a/b+CD44highCD62LlowCD8+ effector memory T cells were detected in ASYMP individuals and were primarily directed against three "ASYMP" epitopes. In contrast, symptomatic individuals have more monofunctional CD44highCD62LhighCD8+ central memory T cells. Furthermore, therapeutic immunization with an innovative prime/pull vaccine, based on priming with multiple ASYMP epitopes (prime) and neurotropic TG delivery of the T cell-attracting chemokine CXCL10 (pull), boosted the number and function of CD44highCD62LlowCD8+ effector memory T cells and CD103highCD8+ tissue-resident T cells in TG of latently infected HLA-A*0201-transgenic mice and reduced recurrent ocular herpes following UV-B-induced reactivation. These findings have profound implications in the development of T cell-based immunotherapeutic strategies to treat blinding recurrent herpes infection and disease.

Human Asymptomatic Epitopes Identified from the Herpes Simplex Virus Tegument Protein VP13/14 (UL47) Preferentially Recall Polyfunctional Effector Memory CD44high CD62Llow CD8+ TEM Cells and Protect Humanized HLA-A*02:01 Transgenic Mice against Ocular Herpesvirus Infection.

Herpes simplex virus 1 (HSV-1) infection is widespread among humans. The HSV-1 virion protein 13/14 (VP13/14), also known as UL47, is a tegument antigen targeted by CD8+ T cells from HSV-seropositive individuals. However, whether VP13/14-specific CD8+ T cells play a role in the natural protection seen in asymptomatic (ASYMP) individuals (individuals who have never had a clinical herpetic disease) has not been elucidated. Using predictive computer-assisted algorithms, we identified 10 potential HLA-A*02:01-restricted CD8+ T-cell epitopes from the 693-amino-acid sequence of the VP13/14 protein. Three out of 10 epitopes exhibited a high to moderate affinity of binding to soluble HLA-A*02:01 molecules. The phenotype and function of CD8+ T cells specific for each epitope were compared in HLA-A*02:01-positive ASYMP individuals and symptomatic (SYMP) individuals (individuals who have frequent clinical herpetic diseases) using determination of a combination of tetramer frequency and the levels of granzyme B, granzyme K, perforin, gamma interferon, tumor necrosis factor alpha, and interleukin-2 production and CD107a/b cytotoxic degranulation. High frequencies of multifunctional CD8+ T cells directed against three epitopes, VP13/14 from amino acids 286 to 294 (VP13/14286-294), VP13/14 from amino acids 504 to 512 (VP13/14504-512), and VP13/14 from amino acids 544 to 552 (VP13/14544-552), were detected in ASYMP individuals, while only low frequencies were detected in SYMP individuals. The three epitopes also predominantly recalled more CD45RAlow CD44high CCR7low CD62Llow CD8+ effector memory T cells (TEM cells) in ASYMP individuals than SYMP individuals. Moreover, immunization of HLA-A*02:01 transgenic mice with the three CD8+ TEM-cell epitopes from ASYMP individuals induced robust and polyfunctional HSV-specific CD8+ TEM cells associated with strong protective immunity against ocular herpesvirus infection and disease. Our findings outline the phenotypic and functional features of protective HSV-specific CD8+ T cells that should guide the development of a safe and effective T-cell-based herpes simplex vaccine. IMPORTANCE: Although most herpes simplex virus 1 (HSV-1)-infected individuals shed the virus in their body fluids following reactivation from latently infected sensory ganglia, the majority never develop a recurrent herpetic disease and remain asymptomatic (ASYMP). In contrast, small proportions of individuals are symptomatic (SYMP) and develop frequent bouts of recurrent disease. The present study demonstrates that naturally protected ASYMP individuals have a higher frequency of effector memory CD8+ T cells (CD8+ TEM cells) specific to three epitopes derived from the HSV-1 tegument protein VP13/14 (VP13/14286-294,VP13/14504-512, and VP13/14544-552) than SYMP patients. Moreover, immunization of humanized HLA-A*02:01 transgenic mice with the three CD8+ TEM-cell epitopes from ASYMP individuals induced robust and polyfunctional HSV-specific CD8+ T cells associated with strong protective immunity against ocular herpesvirus infection and disease. The findings support the emerging concept of the development of a safe and effective asymptomatic herpes simplex vaccine that is selectively based on CD8+ T-cell epitopes from ASYMP individuals.

CoQ10 selective miscibility and penetration into lipid monolayers with lower lateral packing density.

CoQ10 is ubiquitously present in eukaryotic cells. It acts as electron carrier in the electron transport chain of the inner membrane of the mitochondria to facilitate aerobic cellular respiration. A highly stable lipid nanodispersion formulation containing CoQ10 (BPM31510) is currently in clinical investigation for treatment of cancer. This study was designed to determine whether biophysical interactions between CoQ10 and lipid, in part, explain the observed stability and cellular accumulation of CoQ10 in cells and tissues. A lipid monolayer at the air-water interface was used as an experimental membrane model to measure CoQ10 penetration and solubility. Lipid monolayers with varying proportions of CoQ10 were laterally compressed to measure CoQ10 miscibility and lateral organization. Additionally, lipid monolayers with varying lateral packing densities were spread at the air-water interface and CoQ10 was injected in proximity to measure its rate of penetration. Our results demonstrate that CoQ10 selectively penetrates into lipid monolayers with a lower lateral packing density, and is excluded by monolayers of higher packing densities. Data also indicates that CoQ10-lipid mixing is non-ideal. CoQ10 presence in lipid monolayers is biphasic, with one phase occupying the interstitial space between the DMPC lipids, and the other phase is present as pure CoQ10 domains. This work provides further insight into mechanism of action of CoQ10 based formulations that can significantly increase intracellular CoQ10 concentration to show pleotropic effects on cellular functions.

Reconciling Differences between Lipid Transfer in Free-Standing and Solid Supported Membranes: A Time-Resolved Small-Angle Neutron Scattering Study.

Maintaining compositional lipid gradients across membranes in animal cells is essential to biological function, but what is the energetic cost to maintain these differences? It has long been recognized that studying the passive movement of lipids in membranes can provide insight into this toll. Confusingly the reported values of inter- and, particularly, intra-lipid transport rates of lipids in membranes show significant differences. To overcome this difficulty, biases introduced by experimental approaches have to be identified. The present study addresses the difference in the reported intramembrane transport rates of dimyristoylphosphatidylcholine (DMPC) on flat solid supports (fast flipping) and in curved free-standing membranes (slow flipping). Two possible scenarios are potentially at play: one is the difference in curvature of the membranes studied and the other the presence (or not) of the support. Using DMPC vesicles and DMPC supported membranes on silica nanoparticles of different radii, we found that an increase in curvature (from a diameter of 30 nm to a diameter of 100 nm) does not change the rates significantly, differing only by factors of order ∼1. Additionally, we found that the exchange rates of DMPC in supported membranes are similar to the ones in vesicles. And as previously reported, we found that the activation energies for exchange on free-standing and supported membranes are similar (84 and 78 kJ/mol, respectively). However, DMPC's flip-flop rates increase significantly when in a supported membrane, surpassing the exchange rates and no longer limiting the exchange process. Although the presence of holes or cracks in supported membranes explains the occurrence of fast lipid flip-flop in many studies, in defect-free supported membranes we find that fast flip-flop is driven by the surface's induced disorder of the bilayer's acyl chain packing as evidenced from their broad melting temperature behavior.

Phenotypic and functional characterization of herpes simplex virus glycoprotein B epitope-specific effector and memory CD8+ T cells from symptomatic and asymptomatic individuals with ocular herpes.

UNLABELLED: Herpes simplex virus 1 (HSV-1) glycoprotein B (gB)-specific CD8(+) T cells protect mice from herpes infection and disease. However, whether and which HSV-1 gB-specific CD8(+) T cells play a key role in the "natural" protection seen in HSV-1-seropositive healthy asymptomatic (ASYMP) individuals (who have never had clinical herpes disease) remain to be determined. In this study, we have dissected the phenotypes and the functions of HSV-1 gB-specific CD8(+) T cells from HLA-A*02:01 positive, HSV-1 seropositive ASYMP and symptomatic (SYMP) individuals (with a history of numerous episodes of recurrent ocular herpes disease). We found the following. (i) Healthy ASYMP individuals maintained a significantly higher proportion of differentiated HSV-1 gB-specific effector memory CD8(+) T cells (TEM cells) (CD45RA(low) CCR7(low) CD44(high) CD62L(low)). In contrast, SYMP patients had frequent less-differentiated central memory CD8(+) T cells (TCM cells) (CD45RA(low) CCR7(high) CD44(low) CD62L(high)). (ii) ASYMP individuals had significantly higher proportions of multifunctional effector CD8(+) T cells which responded mainly to gB342-350 and gB561-569 "ASYMP" epitopes, and simultaneously produced IFN-γ, CD107(a/b), granzyme B, and perforin. In contrast, effector CD8(+) T cells from SYMP individuals were mostly monofunctional and were directed mainly against nonoverlapping gB17-25 and gB183-191 "SYMP" epitopes. (iii) Immunization of an HLA-A*02:01 transgenic mouse model of ocular herpes with "ASYMP" CD8(+) TEM cell epitopes, but not with "SYMP" CD8(+) TCM cell epitopes, induced a strong CD8(+) T cell-dependent protective immunity against ocular herpes infection and disease. Our findings provide insights into the role of HSV-specific CD8(+) TEM cells in protection against herpes and should be considered in the development of an effective vaccine. IMPORTANCE: A significantly higher proportion of differentiated and multifunctional HSV-1 gB-specific effector memory CD8(+) T cells (TEM cells) (CD45RA(low) CCR7(low) CD44(high) CD62L(low)) were found in healthy ASYMP individuals who are seropositive for HSV-1 but never had any recurrent herpetic disease, while there were frequent less-differentiated and monofunctional central memory CD8(+) T cells (TCM cells) (CD45RA(low) CCR7(high) CD44(low) CD62L(high)) in SYMP patients. Immunization with "ASYMP" CD8(+) TEM cell epitopes, but not with "SYMP" CD8(+) TCM cell epitopes, induced a strong protective HSV-specific CD8(+) T cell response in HLA-A*02:01 transgenic mice. These findings are important for the development of a safe and effective T cell-based herpes vaccine.

Results of toric intraocular lenses for post-penetrating keratoplasty astigmatism.

PURPOSE: Evaluate the usefulness of toric intraocular lens (IOL) implantation during cataract surgery in patients after penetrating keratoplasty (PKP). DESIGN: Retrospective case review. PARTICIPANTS: A total of 21 eyes of 16 patients with prior PKP and moderate to high regular astigmatism after full suture removal underwent phacoemulsification and implantation of a single-piece acrylic toric IOL (SN6AT series; Alcon, Fort Worth, TX). METHODS: Patients underwent comprehensive examinations at standard intervals, including visual acuity, manifest refraction, and corneal topography. MAIN OUTCOME MEASURES: Uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA) expressed as the logarithm of the minimum angle of resolution (logMAR) and manifest refraction astigmatism. RESULTS: From preoperatively to the last visit (mean, 14.7 ± standard deviation 12.8 months), the 21 eyes had significant improvement in UDVA (logMAR, 0.90 ± 0.48 to 0.23 ± 0.25; P = 0.0001) and CDVA (logMAR, 0.31 ± 0.14 to 0.08 ± 0.13; P = 0.0001). A total of 14 of 21 eyes (67%) and 17 of 21 eyes (81%) had UDVA and CDVA of ≥ 20/30, respectively. Preoperative topographic astigmatism was 4.57 ± 2.05 diopters (D). Postoperative manifest refraction astigmatism was 1.58 ± 1.25 D overall, but lower (0.75 ± 0.54 D) in the T7-T9 subgroup (excluding 1 outlier whose corneal astigmatism doubled after surgery) than in the T4-T6 subgroup (1.88 ± 1.28 D; P = 0.013). A total of 16 of all 21 eyes (76.2%) and 8 of 9 eyes (89%) in the T7-T9 subgroup were within 1 D of postoperative manifest astigmatism as predicted or better. CONCLUSIONS: Toric IOLs placed during cataract surgery after PKP and full suture removal can reduce manifest refraction cylinder to predictably low levels with corresponding improvement in UDVA and CDVA in patients with moderate to high regular preoperative topographic astigmatism.

Cholesterol solubility limit in lipid membranes probed by small angle neutron scattering and MD simulations.

The solubility limits of cholesterol in small unilamellar vesicles made of POPS and POPC were probed using Small Angle Neutron Scattering (SANS) and coarse grained (CG) molecular dynamics (MD) simulations. SANS, being non-invasive, allowed the direct and quantitative measurement of cholesterol in intact vesicles. Our experimental measurements reveal a 61% mole fraction solubility limit of cholesterol in POPC, consistent with previous studies. However, in POPS the solubility limit of cholesterol is found to be 73% mole fraction. Previous work reports solubility limits of cholesterol in POPS varying significantly, ranging from 36% up to 66%. The CG MD simulations are in remarkable quantitative agreement with our experimental results showing similar solubility limits. Further, neither experiments nor simulations show evidence of stable nanodomains of cholesterol in POPS membranes as suggested in some previous reports.

Iris defect management in the context of presbyopia-correcting intraocular lenses.

A 65-year-old man had uneventful cataract surgery in the right eye with a toric diffractive intraocular lens (IOL) placed fully within the capsule bag. On postoperative day 1 and week 1, the IOL was well positioned and his eye was healing normally. The plan was to proceed with cataract surgery in the left eye in the near future. One month postoperatively, he presented with blurred vision, glare, and halos and was noted to have iris prolapse out of the temporal clear corneal main incision. Of interest, the patient reported some itching and eye rubbing in the early postoperative period. He was taken back to surgery by the referring doctor, and despite 2 heroic attempts to reposit and save the iris tissue, there was significant iris loss causing transillumination defects and debilitating glare and halos. Ocular examination revealed an uncorrected distance visual acuity (UDVA) of 20/40 - 2 J3 and binocular corrected distance visual acuity (CDVA) 20/30 J1 in the right eye and UDVA of 20/60 J3 and binocular CDVA of 20/25 J1 in the left eye. Manifest refraction was -0.25 -1.25 × 155 in the right eye and plano -2.25 × 090 in the left eye. Fortunately, there was no relative afferent pupillary defect, and intraocular pressures were normal off all drops. On slitlamp examination of the right eye, pertinent findings revealed a protective ptosis, trace conjunctival injection with 1 large subconjunctival polypropylene flange at 8:30 o'clock 1.5 mm from the limbus and 1 exposed irregular polypropylene flange eroded through the conjunctiva at 10 o'clock 0.5 mm from the limbus (Figures 1 and 2JOURNAL/jcrs/04.03/02158034-202408000-00019/figure1/v/2024-07-30T221851Z/r/image-tiffJOURNAL/jcrs/04.03/02158034-202408000-00019/figure2/v/2024-07-30T221851Z/r/image-tiff). There was a localized area of erythema and scleral thinning surrounding the exposed flange. The cornea was edematous over the main incision. The iris was disinserted with atrophic changes and a residual iridodialysis extending from 8:30 to 10 o'clock. The trifocal IOL was fully in the capsule bag with trace fibrosis of the capsule and rotated approximately 7 degrees off the capsulotomy tab, designating the intended axis of 1 degree. The anterior chamber was deep and quiet, and the posterior segment was unremarkable with a 0.45 cup-to-disc ratio. Pertinent examination findings in the left eye included a 2 + NS cataract and a 0.45 cup-to-disc ratio. The remainder of the examination was otherwise unremarkable. What testing and surgical plan would you offer this patient? How would you counsel regarding postoperative expectations?

Current state and future perspectives in the diagnosis of eyelid margin disease: 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 was 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, and squamous). Meibomian gland dysfunction (MGD) can refer to the functional and/or structural problems with the meibomian gland. Meibomitis (or meibomianitis) occurs when there is inflammation associated with the MGD. The presence of blepharitis and/or MGD (with or without inflammation) can affect 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.

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 is 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.

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.

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.