Evaluating the Effectiveness of Lacrimal Gland Botulinum Toxin Using the TEARS Score.

PURPOSE: Botulinum toxin (BoNTA) lacrimal gland injections are one treatment option for managing epiphora. Outcomes for epiphora in existing studies are subjective and lack grading. This study utilized validated grading instruments to evaluate the efficacy of BoNTA lacrimal gland injections. METHODS: Prospective study evaluating the TEARS score and quality of life in patients receiving incobotulinum toxin (Xeomin) lacrimal gland injections for epiphora. Epiphora was graded using the TEARS score. Quality of life was evaluated using the watery eye quality of life score. Etiology, benefit duration, complications and additional injections were recorded. RESULTS: Of the 28 patients, (median age 67.5 years), 19 (68%) had facial palsy gustatory epiphora (GE). Median effect duration was 13 weeks. Improvements in tearing frequency (T), clinical effects (E), and activity limitation (A) were seen in 57%, 57%, and 71% of patients, respectively. Median watery eye quality of life score improved from 42.4/100 ± 10.1 to 10.6 ± 15.5 (p < 0.001). Alongside crocodile tears, reflex tearing R-scores improved in 68% of patients with GE vs. 11% with non-GE causes (p = 0.004618). In total 89% of patients with GE and 56% with non-GE requested repeat injections. Self-reported percentage improvement ranged from 0% to 100% (median 60%, interquartile range 10%-76.25%). CONCLUSIONS: This is the first study reporting the outcomes of BoNTA lacrimal gland injections using validated TEARS and watery eye quality of life scores. Clinical and quality of life improvements are seen in most patients. Patients with GE achieve an additional improvement in dry eye-related reflex tearing alongside crocodile tears which both improve with BoNTA. TEARS data supports using BoNTA in these patients and is a useful validated grading instrument for epiphora.

Novel use of an autologous scleral button graft to close the anterior defect in evisceration surgery.

PURPOSE: To present an alternative evisceration technique with long-term follow-up data. This technique involves the insertion of an acrylic implant into a modified scleral shell which is closed using an autologous scleral graft. METHODS: This was a retrospective analysis of eviscerations performed in a district-general hospital in the UK. All patients underwent conventional ocular evisceration after total keratectomy. A full thickness scleral graft is harvested from the posterior sclera, using an internal approach, with an 8 mm dermatological punch. An 18-20 mm acrylic implant is placed into the shell, and the scleral graft is used to close the anterior defect. Demographic characteristics, implant size and type, and cosmetic results from pictures of all patients were recorded. All patients were invited for a review to measure motility, eyelid height, patient recorded satisfaction and complications. RESULTS: Of the five patients identified, one had since died. The remaining four attended a review in person. The mean time between surgery and review was 48 months. The mean implant size was 19 mm. There were no cases of implant extrusion or infection. All four had a <1 mm asymmetry in measured eyelid height and ≥5 mm horizontal gaze motility. All patients self-reported "good" cosmesis. An independent assessment identified "mild asymmetry" in two cases and "moderate" in the other two. CONCLUSION: Evisceration with this novel autologous scleral graft technique restores volume in the anterior orbit with good cosmetic results, and with no cases of implant exposure reported in this small case series. This technique should be compared prospectively to established techniques.

A Systematic Review of Patient-Reported Outcomes for Surgically Amenable Epiphora.

PURPOSE: In evaluating epiphora and its management, the bottom line for all stakeholders is whether an intervention confers any real benefit on quality of life. A review was conducted to identify and appraise patient-reported outcome measures (PROMs) in surgically amenable epiphora. METHODS: A systematic search was conducted of studies relating to surgical intervention for epiphora. Patient-reported outcome measures were identified and assessed against standard criteria. RESULTS: Of 30,544 identified articles, 227 were eligible for data extraction. Of these, 69% reported a PROM as the primary outcome. PROMs identified included single-item symptom scores (48% of primary outcome PROMs), single-item reports of improvement (30%), the Glasgow Benefit Inventory (3%), Lacrimal Symptom Questionnaire (0.5%), Nasolacrimal Duct Obstruction Symptom Score (0.5%), Ocular Surface Disease Index (0.5%), Visual Function Questionnaire-25, the Short Form-36 Health Survey, and 3 other symptom scores. None were developed through consultation with the target population, and there was inadequate testing of content validity. The strengths and limitations of each PROM are presented, with regard to interpretation, responsiveness, reliability, and validity. DISCUSSION: The importance of robust and psychometrically sound PROMs is essential if the under-reporting of quality of life improvement in patients treated for epiphora is to change. Recommendations for the use of each identified PROM are discussed. CONCLUSIONS: Several PROMs have been used in the recent literature to evaluate patients undergoing surgery to treat epiphora. Assessed against standard criteria, no PROM has proven to be both psychometrically robust and clinically meaningful for use in this population. Future PROM development should be guided by this standard framework.

The Electrochemical Synthesis of Polycationic Clusters.

As a new method for the synthesis of chalcogen polycationic clusters, the electrochemical dissolution of elemental tellurium in ionic liquids (IL) or in liquid SO2 is presented. ILs used are ethylmethylimidazolium triflate [OTf](-) and tetraalkylammonium triflylimide [NTf2](-). Tristriflylmethanide [CTf3](-) was used as [BuMeIm][CTf3] as the electrolyte in SO2. This allowed for the isolation of [Te4][CTf3]2, [Te6][OTf]4, and [Te8][NTf2]2 containing the square [Te4](2+), the prismatic [Te6](4+), and the novel barrelane-shaped [Te8](2+). The compounds are novel compositions as they do not contain the usual halometalate anions, but rather common weakly coordinating anions. The (125)Te NMR spectrum of an IL solution containing [Te8](2+) features only one broad signal at 2700 ppm. DFT calculations show that slight concerted displacements within the [Te8](2+) cluster lead to a fluxional molecular structure and a fast valence isomerism with a very low activation barrier of about 8 kJ mol(-1).

Spectroscopic Observation of Calcium-Induced Reorientation of Cellobiose Dehydrogenase Immobilized on Electrodes and its Effect on Electrocatalytic Activity.

Cellobiose dehydrogenase catalyzes the oxidation of various carbohydrates and is considered as a possible anode catalyst in biofuel cells. It has been shown that the catalytic performance of this enzyme immobilized on electrodes can be increased by presence of calcium ions. To get insight into the Ca(2+) -induced changes in the immobilized enzyme we employ surface-enhanced vibrational (SERR and SEIRA) spectroscopy together with electrochemistry. Upon addition of Ca(2+) ions electrochemical measurements show a shift of the catalytic turnover signal to more negative potentials while SERR measurements reveal an offset between the potential of heme reduction and catalytic current. Comparing SERR and SEIRA data we propose that binding of Ca(2+) to the heme induces protein reorientation in a way that the electron transfer pathway of the catalytic FAD center to the electrode can bypass the heme cofactor, resulting in catalytic activity at more negative potentials.

Polyethyleneimine as a promoter layer for the immobilization of cellobiose dehydrogenase from Myriococcum thermophilum on graphite electrodes.

Cellobiose dehydrogenase (CDH) is a promising enzyme for the construction of biofuel cell anodes and biosensors capable of oxidizing aldoses as cellobiose as well as lactose and glucose and with the ability to connect to an electrode through a direct electron transfer mechanism. In the present study, we point out the beneficial effect of a premodification of spectrographic graphite electrodes with the polycation polyethyleneimine (PEI) prior to adsorption of CDH from Myriococcum thermophilum (MtCDH). The application of PEI shifts the pH optimum of the response of the MtCDH modified electrode from pH 5.5 to 8. The catalytic currents to lactose were increased up to 140 times, and the K(M)(app) values were increased up to 9 times. The previously investigated, beneficial effect of divalent cations on the activity of CDH was also present for graphite/PEI/MtCDH electrodes but was less pronounced. Polarization curves revealed a second unexpected catalytic wave for graphite/PEI/MtCDH electrodes especially pronounced at pH 8. Square wave voltammetric studies revealed the presence of an unknown redox functionality present at 192 mV vs Ag|AgCl (0.1 M KCl) at pH 8, probably originating from an oxidized adenosine derivative. Adenosine is a structural part of the flavin adenine dinucleotide (FAD) cofactor of the dehydrogenase domain of CDH. It is suggested that for some enzyme molecules FAD leaks out from the active site, adsorbs onto graphite, and is oxidized on the electrode surface into a product able to mediate the electron transfer between CDH and the electrode. PEI is suggested and discussed to act in several manners by (a) increasing the surface loading of the enzyme, (b) possibly increasing the electron transfer rate between CDH and the electrode, and (c) facilitating the creation or immobilization of redox active adenosine derivatives able to additionally mediate the electron transfer between CDH and the electrode.

Determination of Lactose in Lactose-Free and Low-Lactose Milk, Milk Products, and Products Containing Dairy Ingredients by the LactoSens®R Amperometry Method: Final Action 2020.01.

BACKGROUND: The LactoSens®R method was previously shown to have acceptable accuracy and repeatability precision as required by AOAC Standard Method Performance Requirements (SMPR®) 2018.009 for determination of lactose in low-lactose or lactose-free milk, milk products, and products containing dairy ingredients and was awarded Official Method of AnalysisSM (OMA) First Action status in 2020. OBJECTIVE: The method was subjected to a multilaboratory validation (MLV) study to evaluate the reproducibility precision of the method. METHODS: Fourteen validation materials were provided to 15 laboratories in seven countries as blind duplicates. The materials ranged from 0 to 173 mg/100 g lactose. Each laboratory analyzed the blind duplicates according to OMA 2020.01. The data were analyzed for repeatability and reproducibility precision. RESULTS: RSDr values varied from 2.81 to 8.76%, and RSDR values varied from 4.25 to 12.5%. When sorted by category and concentration range, these results met the repeatability and reproducibility criteria required by SMPR 2018.009. CONCLUSIONS: The data generated in the MLV support the adoption of OMA 2020.01 as Final Action status. HIGHLIGHTS: The LactoSensR method, as described by OMA 2020.01, provides an accurate and precise determination of lactose in a variety of low-lactose and lactose-free milk, milk products, and products containing dairy ingredients in minutes.

Optical frequency domain imaging (OFDI) represents a novel technique for the diagnosis of giant cell arteritis.

BACKGROUND/OBJECTIVES: Giant cell arteritis (GCA) is an inflammatory vascular disease in which prompt and accurate diagnosis is critical. The efficacy of temporal artery biopsy (TAB) is limited by 'skip' lesions and a delay in histological analysis. This first-in-man ex-vivo study aims to assess the accuracy of optical frequency domain imaging (OFDI) in diagnosing GCA. SUBJECTS/METHODS: 29 TAB samples of patients with suspected GCA were submerged in 0.9% sodium chloride and an OFDI catheter was passed through the lumen to create cross-sectional images prior to histological analysis. The specimens were then preserved in formalin for histological examination. Mean intimal thickness (MIT) on OFDI was measured, and the presence of both multinucleate giant cells (MNGCs) and fragmentation of the internal elastic lamina (FIEL) was assessed and compared with histology, used as the diagnostic gold standard. RESULTS: MIT in patients with/without histological evidence of GCA was 0.425 mm (±0.43) and 0.13 mm (±0.06) respectively compared with 0.215 mm (±0.09) and 0.135 mm (±0.07) on OFDI. MIT measured by OFDI was significantly higher in patients with histologically diagnosed arteritis compared to those without (p = 0.0195). For detecting FIEL and MNGCs, OFDI had a sensitivity of 75% and 28.6% and a specificity of 100% and 77.3% respectively. Applying diagnostic criteria of MIT > 0.20 mm, or the presence of MNGCs or FIEL, the sensitivity of detecting histological arteritis using OFDI was 91.4% and the specificity 94.1%. CONCLUSIONS: OFDI provided rapid imaging of TAB specimens achieving a diagnostic accuracy comparable to histological examination. In-vivo imaging may allow imaging of a longer arterial section.

Cellobiose dehydrogenase modified electrodes: advances by materials science and biochemical engineering.

The flavocytochrome cellobiose dehydrogenase (CDH) is a versatile biorecognition element capable of detecting carbohydrates as well as quinones and catecholamines. In addition, it can be used as an anode biocatalyst for enzymatic biofuel cells to power miniaturised sensor-transmitter systems. Various electrode materials and designs have been tested in the past decade to utilize and enhance the direct electron transfer (DET) from the enzyme to the electrode. Additionally, mediated electron transfer (MET) approaches via soluble redox mediators and redox polymers have been pursued. Biosensors for cellobiose, lactose and glucose determination are based on CDH from different fungal producers, which show differences with respect to substrate specificity, pH optima, DET efficiency and surface binding affinity. Biosensors for the detection of quinones and catecholamines can use carbohydrates for analyte regeneration and signal amplification. This review discusses different approaches to enhance the sensitivity and selectivity of CDH-based biosensors, which focus on (1) more efficient DET on chemically modified or nanostructured electrodes, (2) the synthesis of custom-made redox polymers for higher MET currents and (3) the engineering of enzymes and reaction pathways. Combination of these strategies will enable the design of sensitive and selective CDH-based biosensors with reduced electrode size for the detection of analytes in continuous on-site and point-of-care applications.

Automated extraction of clinical measures from videos of oculofacial disorders using machine learning: feasibility, validity and reliability.

OBJECTIVES: To determine the feasibility, validity and reliability of automatically extracting clinically meaningful eyelid measurements from consumer-grade videos of individuals with oculofacial disorders. METHODS: A custom computer program was designed to automatically extract clinical measures from consumer-grade videos. This program was applied to publicly available videos of individuals with oculofacial disorders, and age-matched controls. The primary outcomes were margin reflex distance 1 (MRD1) and 2 (MRD2), blink lagophthalmos, and ocular surface area exposure. Test-retest reliability was evaluated using Bland-Altman analysis to compare the agreement in obtained measures between separate videos of the same individual taken within 48 h of each other. RESULTS: MRD1 was reduced in individuals with ptosis versus controls (2.2 mm versus 3.4 mm, p < 0.001), and increased in individuals with facial nerve palsy (FNP) (3.9 mm, p = 0.049) and thyroid eye disease (TED) (4.1 mm; p = 0.038). Blink lagophthalmos was increased in individuals with FNP (3.7 mm); p < 0.001) and those with TED (0.1 mm, p = 0.003) versus controls (0.0 mm). Ocular surface exposure was reduced in individuals with ptosis compared with controls (12.2 mm2 versus 13.1 mm2; p < 0.001) and increased in TED (13.7 mm2; p 0.002). Bland-Altmann analysis demonstrated 95% limits of agreement for video-derived measures: median MRD1: -1.1 to 1.1 mm; median MRD2: -0.9 to 1.0 mm; blink lagophthalmos: -3.5 to 3.7 mm; and average ocular surface area exposure: -1.6 to 1.6 mm2. CONCLUSIONS: The presented program is capable of taking consumer grade videos of patients with oculofacial disease and providing clinically meaningful and reliable eyelid measurements that show promising validity.