Measurement of light absorption by chromophoric dissolved organic matter using a type-II liquid capillary waveguide: assessment of an achievable accuracy.

Light absorption by chromophoric dissolved organic matter (CDOM) in the ocean is often measured using liquid waveguide capillary cells coupled to spectral array detectors. This type of optical setup is affected by several sources of uncertainties related to the waveguide and the detector. Uncertainties from the waveguide arise from errors in the effective path length and the effects of water salinity, while errors related to the detector are due to the non-linearity in the response, internal stray light, and wavelength accuracy. Here, uncertainties in the measurements of the spectral absorption coefficient of CDOM due to the optical setup itself were investigated in detail. The related systematic errors were very often significant (2-15%) and larger than expected from simple measurement uncertainty (±1%). However, they can be corrected by characterizing the detector's response for non-linearity and stray light, regularly performing calibrations for the detector's wavelength response, and routinely measuring the waveguide's effective path length. Including such corrections and timely calibrations reduces the uncertainties related to the spectrophotometric measurements to about ±2%. Uncertainties related to the necessary handling of samples are not included here.

Artificial intelligence-based computer-aided system for knee osteoarthritis assessment increases experienced orthopaedic surgeons' agreement rate and accuracy.

PURPOSE: The aims of this study were to (1) analyze the impact of an artificial intelligence (AI)-based computer system on the accuracy and agreement rate of board-certified orthopaedic surgeons (= senior readers) to detect X-ray features indicative of knee OA in comparison to unaided assessment and (2) compare the results to those of senior residents (= junior readers). METHODS: One hundred and twenty-four unilateral knee X-rays from the OAI study were analyzed regarding Kellgren-Lawrence grade, joint space narrowing (JSN), sclerosis and osteophyte OARSI grade by computerized methods. Images were rated for these parameters by three senior readers using two modalities: plain X-ray (unaided) and X-ray presented alongside reports from a computer-assisted detection system (aided). After exclusion of nine images with incomplete annotation, intraclass correlations between readers were calculated for both modalities among 115 images, and reader performance was compared to ground truth (OAI consensus). Accuracy, sensitivity and specificity were also calculated and the results were compared to those from a previous study on junior readers. RESULTS: With the aided modality, senior reader agreement rates for KL grade (2.0-fold), sclerosis (1.42-fold), JSN (1.37-fold) and osteophyte OARSI grades (3.33-fold) improved significantly. Reader specificity and accuracy increased significantly for all features when using the aided modality compared to the gold standard. On the other hand, sensitivity only increased for OA diagnosis, whereas it decreased (without statistical significance) for all other features. With aided analysis, senior readers reached similar agreement and accuracy rates as junior readers, with both surpassing AI performance. CONCLUSION: The introduction of AI-based computer-aided assessment systems can increase the agreement rate and overall accuracy for knee OA diagnosis among board-certified orthopaedic surgeons. Thus, use of this software may improve the standard of care for knee OA detection and diagnosis in the future. LEVEL OF EVIDENCE: Level II.

Gingival tissue autophagy pathway gene expression profiles in periodontitis and aging.

OBJECTIVE: We hypothesized that autophagy-related genes will be differentially expressed in periodontitis, suggesting an impaired gingival autophagic response associated with disease. BACKGROUND: Autophagy is a cellular physiologic mechanism to maintain tissue homeostasis, while deficient autophagic responses increase inflammation and susceptibility to infection. METHODS: Rhesus monkeys [<3 years to 23 years of age (n = 34)] were examined for periodontal health and naturally occurring periodontitis. Gingival tissues samples were obtained from healthy or diseased sites, total RNA was isolated, and the Rhesus Gene Chip 1.0 ST (Affymetrix) was used for gene expression analysis of 150 autophagy-related genes. RESULTS: Comparison of expression levels with adult healthy tissues demonstrated a rather limited number of individual genes that were significantly different across the age-groups. In contrast, with periodontitis in the adults and aged animals, about 15% of the genes were significantly increased or decreased. The differences were reflected in the mTOR complex (5/12), ULK1/ATG1 complex (5/9), PI3K complex (5/21), ATG9 complex (2/7), ATG12 conjugation/LC3 lipidation (7/22), and lysosome fusion/vesicle degradation [LF/VD (5/10)] activities within the broader autophagic pathway. The genes most greatly altered in gingival tissues of naturally occurring periodontitis were identified in the ATG12 and LF/VD pathways that approximated 50% of the genes in each of those categories. While healthy gingival aging did not appear to reflect altered autophagy gene expression, substantial differences were noted with periodontitis irrespective of the age of the animals. Future studies into the role of autophagy in periodontitis and could offer potential new therapeutic strategies to prevent and/or treat periodontal disease.

Assessing the Effect of Middle Ear Effusions on Wideband Acoustic Immittance Using Optical Coherence Tomography.

OBJECTIVES: Wideband acoustic immittance (WAI) noninvasively assesses middle ear function by measuring the sound conduction over a range of audible frequencies. Although several studies have shown the potential of WAI for detecting the presence of middle ear effusions (MEEs), determining the effects of MEE type and amount on WAI in vivo has been challenging due to the anatomical location of middle ear cavity. The purpose of this study is to correlate WAI measurements with physical characteristics of the middle ear and MEEs determined by optical coherence tomography (OCT), a noninvasive optical imaging technique. DESIGN: Sixteen pediatric subjects (average age of 7 ± 4 years) were recruited from the primary care clinic at Carle Foundation Hospital (Urbana, IL). A total of 22 ears (normal: 15 ears, otitis media with effusion: 6 ears, and acute otitis media: 1 ear, based on physician's diagnosis) were examined via standard otoscopy, tympanometry, OCT imaging, and WAI measurements in a busy, community-based clinical setting. Cross-sectional OCT images were analyzed to quantitatively assess the presence, type (relative turbidity based on the amount of scattering), and amount (relative fluid level) of MEEs. These OCT metrics were utilized to categorize subject ears into no MEE (control), biofilm without a MEE, serous-scant, serous-severe, mucoid-scant, and mucoid-severe MEE groups. The absorbance levels in each group were statistically evaluated at α = 0.05. RESULTS: The absorbance of the control group showed a similar trend when compared with a pediatric normative dataset, and the presence of an MEE generally decreased the power absorbance. The mucoid MEE group showed significantly less power absorbance from 2.74 to 4.73 kHz (p < 0.05) when compared with the serous MEE group, possibly due to the greater mass impeding the middle ear system. Similarly, the greater amount of middle ear fluid contributed to the lower power absorbance from 1.92 to 2.37 kHz (p< 0.05), when compared with smaller amounts of fluid. As expected, the MEEs with scant fluid only significantly affected the power absorbance at frequencies greater than 4.85 kHz. A large variance in the power absorbance was observed between 2 and 5 kHz, suggesting the dependence on both the type and amount of MEE. CONCLUSIONS: Physical characteristics of the middle ear and MEEs quantified from noninvasive OCT images can be helpful to understand abnormal WAI measurements. Mucoid MEEs decrease the power absorbance more than serous MEEs, and the greater amounts of MEE decreases the power absorbance, especially at higher (>2 kHz) frequencies. As both the type and amount of MEE can significantly affect WAI measurements, further investigations to correlate acoustic measurements with physical characteristics of middle ear conditions in vivo is needed.

Surgical treatment of posterior cruciate ligament lesions does not cause growth disturbances in pediatric patients.

PURPOSE: The aim of the present study was to describe epidemiology, management and outcome of pediatric and adolescent patients with posterior cruciate ligament (PCL) injuries. METHODS: Sixteen patients of less than 18 years of age with 7 PCL avulsion fractures and 9 PCL tears were included over a 10-year period. Trauma mechanism, additional injuries and treatment methods were analyzed. Follow-up examination included range of motion and ability to perform squats. Pedi-IKDC and Lysholm score were obtained and posterior shift was measured in kneeling view radiographs and compared to the contralateral side. Patients were grouped into pediatric patients with open physes at the time surgery and adolescent patients with closing or closed physes. In case of open physes, growth disturbances were assessed. RESULTS: Six of the treated patients (median age 12.5 years, range 10-13) had open physes at time of surgery. Five of those sustained avulsion fractures and treatment consisted of open reduction and screw fixation in four cases and graft reconstruction in one case. One patient sustained a PCL tear and underwent graft reconstruction. Follow-up at a median of 71.5 months (range 62-100) did not reveal any growth disturbances. Median Pedi-IKDC was 71.9 (range 51.7-92.1), median Lysholm score was 81.5 (range 66-88) and median posterior shift difference was 2.5 mm (range 0-11). The remaining 10 patients (median age 16 years, range 14-17) had closing/closed physis at the time of operation. Two patients presented with avulsion fractures treated with open reduction and screw fixation and 8 patients sustained PCL tears treated with graft reconstruction. At a median follow-up of 69.5 months (range 11-112), median Pedi-IKDC was 86.8 (range 36.8-97.7), median Lysholm score was 84.0 (range 45-95) and median posterior shift difference was 4 mm (range 0-15). CONCLUSIONS: In our small number of pediatric patients with PCL injuries, open reduction and epiphyseal screw fixation of displaced avulsed fractures and steep tunnel drilling in case of PCL reconstruction did not cause growth disturbances. Nevertheless, long-term functional impairment should be expected and close follow-up has to be recommended. LEVEL OF EVIDENCE: Therapeutic, Level IV.

Outcome following excision of the radial head in children with open physes for impaired elbow motion.

BACKGROUND: Only few reports have described the outcome of pediatric patients following radial head resection. Therefore, the aim of the present study was to assess clinical and radiologic outcome of patients with open physes following resection of the radial head. MATERIALS AND METHODS: Skeletally immature patients treated with resection of the radial head were included. Range of motion (ROM) of the elbow joint was compared with preoperative values. Grip strength, pronation and supination strength, and carrier angle were compared with the unaffected side. Radiographs were assessed for signs of arthrosis, radial migration, and perifocal ossification. Disabilities of the Arm, Shoulder and Hand and Mayo Elbow Performance scores were obtained. RESULTS: The study included 7 patients (mean age, 11 years), 5 with post-traumatic and 2 with congenitally impaired elbow joint motion. Mean follow-up was 47 months. Pronation/supination ROM improved significantly (P = .018). Extension/flexion ROM did not improve significantly (P = .122). Although grip strength (P = .027) and pronation strength (P = .028) of the affected side were significantly lower compared with the contralateral side, supination strength did not differ significantly (P = .176). The carrying angle was increased in 3 patients. Significant radial migration occurred (mean, 3 mm; standard deviation [SD], 3 mm; P = .018). Arthrosis was found in 3 patients. The mean Disabilities of the Arm, Shoulder and Hand score was 16.1 (range 8.8-30.8; SD, 10.1) and mean Mayo Elbow Performance Score was 88 (range, 70-100; SD, 12). CONCLUSIONS: Radial head excision may be considered for selected patients with open physes in cases of severe impairment of pronation/supination. However, sequelae such as radial migration, arthrosis, and elevation of the carrying angle should be expected.

Hypoxia-inducible transcription factors, HIF1A and HIF2A, increase in aging mucosal tissues.

Hypoxia (i.e. oxygen deprivation) activates the hypoxia-signalling pathway, primarily via hypoxia-inducible transcription factors (HIF) for numerous target genes, which mediate angiogenesis, metabolism and coagulation, among other processes to try to replenish tissues with blood and oxygen. Hypoxia signalling dysregulation also commonly occurs during chronic inflammation. We sampled gingival tissues from rhesus monkeys (Macaca mulatta; 3-25 years old) and total RNA was isolated for microarray analysis. HIF1A, HIF1B and HIF2A were significantly different in healthy aged tissues, and both HIF1A and HIF3A were positively correlated with aging. Beyond these transcription factor alterations, analysis of patterns of gene expression involved in hypoxic changes in tissues showed specific increases in metabolic pathway hypoxia-inducible genes, whereas angiogenesis pathway gene changes were more variable in healthy aging tissues across the animals. With periodontitis, aging tissues showed decreases in metabolic gene expression related to carbohydrate/lipid utilization (GBE1, PGAP1, TPI1), energy metabolism and cell cycle regulation (IER3, CCNG2, PER1), with up-regulation of transcription genes and cellular proliferation genes (FOS, EGR1, MET, JMJD6) that are hypoxia-inducible. The potential clinical implications of these results are related to the epidemiological findings of increased susceptibility and expression of periodontitis with aging. More specifically the findings describe that hypoxic stress may exist in aging gingival tissues before documentation of clinical changes of periodontitis and, so, may provide an explanatory molecular risk factor for an elevated capacity of the tissues to express destructive processes in response to changes in the microbial biofilms characteristic of a more pathogenic microbial challenge.

The adsorption of dissolved organic carbon onto glass fiber filters and its effect on the measurement of particulate organic carbon: A laboratory and modeling exercise.

Particulate organic carbon (POC) represents a small portion of total carbon in the ocean. However, it plays a large role in the turnover of organic matter through the biological pump and other processes. Early on since the development of the POC measurement technique in the 1960s, it was known that dissolved organic carbon (DOC) adsorbs and is retained both on and in the filter. That retained DOC is measured as if it was part of the particulate fraction, an artifact that can cause significant overestimates of POC concentration. We set out to address the long-standing question of whether the magnitude of the DOC adsorption is affected by the quantity and quality of the dissolved organic matter in the sample. However, our results precluded an unequivocal answer to that question; nevertheless, the experimental data generated did allow us to develop and test predictive models that relate the mass of carbon adsorbed to the volume of sample filtered. The results indicate that the uptake of DOC can be predicted using an exponential model and that a saturation point is approached when approximately a half-liter of water is filtered. This model can be a valuable tool for correcting existing POC data sets that did not account for DOC adsorption. Nonetheless, this approach should not be regarded as a substitute for collecting in situ filter blanks in parallel with POC samples to prop-erly correct for this artifact.

Bone biology-related gingival transcriptome in ageing and periodontitis in non-human primates.

AIM: Cellular and molecular immunoinflammatory changes in gingival tissues drive alveolar bone loss in periodontitis. Since ageing is a risk factor for periodontitis, we sought to identify age-related gingival transcriptome changes associated with bone metabolism in both healthy and in naturally occurring periodontitis. MATERIALS AND METHODS: Adult (12-16 years) and aged (18-23 years) non-human primates (M. mulatta) (n = 24) were grouped into healthy and periodontitis. Gingival tissue samples were obtained and subjected to microarray analysis using the Gene Chip Macaque Genome Array. Gene expression profiles involved in osteoclast/osteoblast proliferation, adhesion and function were evaluated and compared across and between the age groups. QPCR was also performed on selected genes to validate microarray data. RESULTS: Healthy aged tissues showed a gene profile expression that suggest enhancement of osteoclastic adhesion, proliferation/survival and function (SPP1, TLR4, MMP8 and TFEC) and impaired osteoblastic activity (SMEK3P and SMAD5). The gingival transcriptome in both adult and aged animals with naturally occurring periodontitis (FOS, IL6, TLR4, MMP9, MMP10 and SPP1 genes) was consistent with a local inflammatory response driving towards bone/connective tissue destruction. CONCLUSION: A pro-osteoclastogenic gingival transcriptome is associated with periodontitis irrespective of age; however; a greater bone-destructive molecular environment is associated with ageing in healthy tissues.

Read My Lips: Brain Dynamics Associated with Audiovisual Integration and Deviance Detection.

Information from different modalities is initially processed in different brain areas, yet real-world perception often requires the integration of multisensory signals into a single percept. An example is the McGurk effect, in which people viewing a speaker whose lip movements do not match the utterance perceive the spoken sounds incorrectly, hearing them as more similar to those signaled by the visual rather than the auditory input. This indicates that audiovisual integration is important for generating the phoneme percept. Here we asked when and where the audiovisual integration process occurs, providing spatial and temporal boundaries for the processes generating phoneme perception. Specifically, we wanted to separate audiovisual integration from other processes, such as simple deviance detection. Building on previous work employing ERPs, we used an oddball paradigm in which task-irrelevant audiovisually deviant stimuli were embedded in strings of non-deviant stimuli. We also recorded the event-related optical signal, an imaging method combining spatial and temporal resolution, to investigate the time course and neuroanatomical substrate of audiovisual integration. We found that audiovisual deviants elicit a short duration response in the middle/superior temporal gyrus, whereas audiovisual integration elicits a more extended response involving also inferior frontal and occipital regions. Interactions between audiovisual integration and deviance detection processes were observed in the posterior/superior temporal gyrus. These data suggest that dynamic interactions between inferior frontal cortex and sensory regions play a significant role in multimodal integration.

Noninvasive in vivo optical detection of biofilm in the human middle ear.

Otitis media (OM), a middle-ear infection, is the most common childhood illness treated by pediatricians. If inadequately treated, OM can result in long-term chronic problems persisting into adulthood. Children with chronic OM or recurrent OM often have conductive hearing loss and communication difficulties and require surgical treatment. Tympanostomy tube insertion, the placement of a small drainage tube in the tympanic membrane (TM), is the most common surgical procedure performed in children under general anesthesia. Recent clinical studies have shown evidence of a direct correspondence between chronic OM and the presence of a bacterial biofilm within the middle ear. Biofilms are typically very thin and cannot be recognized using a regular otoscope. Here we report the use of optical coherent ranging techniques to noninvasively assess the middle ear to detect and quantify biofilm microstructure. This study involves adults with chronic OM, which is generally accepted as a biofilm-related disease. Based on more than 18,537 optical ranging scans and 742 images from 13 clinically infected patients and 7 normal controls using clinical findings as the gold standard, all middle ears with chronic OM showed evidence of biofilms, and all normal ears did not. Information on the presence of a biofilm, along with its structure and response to antibiotic treatment, will not only provide a better fundamental understanding of biofilm formation, growth, and eradication in the middle ear, but also may provide much-needed quantifiable data to enable early detection and quantitative longitudinal treatment monitoring of middle-ear biofilms responsible for chronic OM.

Visualizing individual carbon nanotubes with optical microscopy.

This paper reports a high-throughput, label-free technique to visualize individual carbon nanotubes (CNTs) on a silicon wafer using a conventional optical microscope. We show that individual CNTs can locally enhance the rate of vapor-phase HF etching of SiO2 to produce a SiO2 trench that is several to several tens of nanometers in depth. The trench is visible under an optical microscope due to a change in the optical interference in the SiO2 layer, allowing the location of an individual CNT to be determined. With this technique, we demonstrate high-throughput Raman characterization and reactivity studies on individual CNTs.

Comparative analysis of gingival tissue antigen presentation pathways in ageing and periodontitis.

AIM: Gingival tissues of periodontitis lesions contribute to local elevations in mediators, including both specific T cell and antibody immune responses to oral bacterial antigens. Thus, antigen processing and presentation activities must exist in these tissues to link antigen-presenting cells with adaptive immunity. We hypothesized that alterations in the transcriptome of antigen processing and presentation genes occur in ageing gingival tissues and that periodontitis enhances these differences reflecting tissues less capable of immune resistance to oral pathogens. MATERIALS AND METHODS: Rhesus monkeys (n = 34) from 3 to 23 years of age were examined. A buccal gingival sample from healthy or periodontitis sites was obtained, total RNA isolated, and microarray analysis was used to describe the transcriptome. RESULTS: The results demonstrated increased transcription of genes related to the MHC class II and negative regulation of NK cells with ageing in healthy gingival tissues. In contrast, both adult and ageing periodontitis tissues showed decreased transcription of genes for MHC class II antigens, coincident with up-regulation of MHC class I-associated genes. CONCLUSION: These transcriptional changes suggest a response of healthy ageing tissues through the class II pathway (i.e. endocytosed antigens) and altered responses in periodontitis that could reflect host-associated self-antigens or targeting cytosolic intracellular microbial pathogens.

Cytokine gene expression profiles during initiation, progression and resolution of periodontitis.

AIM: Variations in the expression of cytokines during the progression of periodontitis remain ill-defined. We evaluated the expression of 19 cytokine genes related to T-cell phenotype/function during initiation, progression and resolution of periodontitis, and related these to the expression of soft and bone tissue destruction genes (TDGs). MATERIALS AND METHODS: A ligature-induced periodontitis model was used in rhesus monkeys (M. mulatta) (n = 18). Gingival tissues were taken at baseline pre-ligation, 2 weeks and 1 month (Initiation) and 3 months (progression) post ligation. Ligatures were removed and samples taken 2 months later (resolution). Total RNA was isolated and the Rhesus Gene 1.0 ST (Affymetrix) used for gene expression analysis. Significant expression changes were validated by qRT-PCR. RESULTS: Disease initiation/progression was characterized by overexpression of Th17/Treg cytokine genes (IL-1ß, IL-6, TGFß and IL-21) and down-regulation of Th1/Th2 cytokine genes (IL-18 and IL-25). Increased IL-2 and decreased IL-10 levels were seen during disease resolution. Several Th17/Treg cytokine genes positively correlated with TDGs, whereas most Th1/Th2 genes exhibited a negative correlation. CONCLUSION: Initiation, progression and resolution of periodontitis involve over- and underexpression of cytokine genes related to various T-helper subsets. In addition, variations in individual T-helper response subset/genes during disease progression correlated with protective/destructive outcomes.

Phytoplankton optical fingerprint libraries for development of phytoplankton ocean color satellite products.

Phytoplankton respond to physical and hydrographic forcing on time and space scales up to and including those relevant to climate change. Quantifying changes in phytoplankton communities over these scales is essential for predicting ocean food resources, occurrences of harmful algal blooms, and carbon and other elemental cycles, among other predictions. However, one of the best tools for quantifying phytoplankton communities across relevant time and space scales, ocean color sensors, is constrained by its own spectral capabilities and availability of adequately vetted and relevant optical models. To address this later shortcoming, greater than fifty strains of phytoplankton, from a range of taxonomic lineages, geographic locations, and time in culture, alone and in mixtures, were grown to exponential and/or stationary phase for determination of hyperspectral UV-VIS absorption coefficients, multi-angle and multi-spectral backscatter coefficients, volume scattering functions, particle size distributions, pigment content, and fluorescence. The aim of this publication is to share these measurements to expedite their utilization in the development of new optical models for the next generation of ocean color satellites.

Improving the charge transport in self-assembled monolayer field-effect transistors: from theory to devices.

A three-pronged approach has been used to design rational improvements in self-assembled monolayer field-effect transistors: classical molecular dynamics (MD) simulations to investigate atomistic structure, large-scale quantum mechanical (QM) calculations for electronic properties, and device fabrication and characterization as the ultimate goal. The MD simulations reveal the effect of using two-component monolayers to achieve intact dielectric insulating layers and a well-defined semiconductor channel. The QM calculations identify improved conduction paths in the monolayers that consist of an optimum mixing ratio of the components. These results have been used both to confirm the predictions of the calculations and to optimize real devices. Monolayers were characterized with X-ray reflectivity measurements and by electronic characterization of complete devices.

Chemistry of ring-substituted 4-(benzothiazol-2-yl)phenylnitrenium ions from antitumor 2-(4-aminophenyl)benzothiazoles.

Ring-substituted derivatives of 2-(4-aminophenyl)benzothiazole, 1a, 1b-g, are under development as antitumor agents. One derivative, 1f, has reached phase 1 clinical trials as the prodrug 2f, Phortress (NSC 710305). These amines are activated by CYP450 1A1, apparently into hydroxylamines 8a-g that are likely metabolized into esters that ionize into nitrenium ions responsible for cellular damage. Previously we showed that 9a, the acetic acid ester of 8a, generates the long-lived (530 ns) nitrenium ion 11a by hydrolysis or photolysis in water. In this study, azide trapping shows that 9b-g generate 11b-g via rate-limiting N-O heterolysis. Ion lifetimes, estimated from azide/solvent selectivities, range from 250 to 1150 ns with identical lifetimes for 11a and 11f. Differences in biological activity of the amines are likely not due to differences in the chemistry of the cations but to differences in metabolic activation/deactivation of individual amines. Unlike the nitrenium ions, lifetimes of the esters are strongly dependent on the 3'-Me substituent. Esters containing 3'-Me (9b, 9f, 9g) have lifetimes of 5-10 s compared to 400-800 s for esters without 3'-Me (9a, 9c, 9d, 9e). This restricts 3'-Me esters to cells/tissues in which activation occurs, concentrating their effects in tumor cells if metabolism is restricted to those cells.

In Vivo Optical Characterization of Middle Ear Effusions and Biofilms During Otitis Media.

Otitis media (OM), a common ear infection, is characterized by the presence of an accumulated middle ear effusion (MEE) in a normally air-filled middle ear cavity. While assessing the MEE plays a critical role in the overall management of OM, identifying and examining the MEE is challenging with the current diagnostic tools since the MEE is located behind the semi-opaque eardrum. The objective of this cross-sectional, observational study is to non-invasively visualize and characterize MEEs and bacterial biofilms in the middle ear. A portable, handheld, otoscope-integrated optical coherence tomography (OCT) system combined with novel analytical methods has been developed. In vivo middle ear OCT images were acquired from 53 pediatric subjects (average age of 3.9 years; all awake during OCT imaging) diagnosed with OM and undergoing a surgical procedure (ear tube surgery) to aspirate the MEE and aerate the middle ear. In vivo middle ear OCT acquired prior to the surgery was compared with OCT of the freshly extracted MEEs, clinical diagnosis, and post-operative evaluations. Among the subjects who were identified with the presence of MEEs, 89.6% showed the presence of the TM-adherent biofilm in in vivo OCT. This study provides an atlas of middle ear OCT images exhibiting a range of depth-resolved MEE features, which can only be visualized and assessed non-invasively through OCT. Quantitative metrics of OCT images acquired prior to the surgery were statistically correlated with surgical evaluations of MEEs. Measurements of MEE characteristics will provide new readily available information that can lead to improved diagnosis and management strategies for the highly prevalent OM in children.

Switching to brolucizumab: injection intervals and visual, anatomical and safety outcomes at 12 and 18 months in real-world eyes with neovascular age-related macular degeneration.

BACKGROUND: The anti-vascular endothelial growth factor (anti-VEGF) injection interval influences treatment burden and compliance in neovascular age-related macular degeneration (nAMD). This real-world study investigates visual acuity (VA), injection-interval extension, central macular thickness (CMT) and safety in nAMD eyes switched to the anti-VEGF agent brolucizumab and followed for up to 18 months. METHODS: This retrospective study included patients with nAMD who were switched from other anti-VEGF agents to brolucizumab only. Patient eyes were grouped into three nested cohorts with the overall cohort receiving ≥ 1 brolucizumab injection, the second receiving ≥ 3 brolucizumab injections with a follow-up period of ≥ 12 months and the third cohort receiving ≥ 3 brolucizumab injections with a follow-up period of ≥ 18 months. Study endpoints included changes from baseline at 12 or 18 months in VA, injection intervals, and CMT. Sub-group analyses were conducted using baseline injection interval length or baseline VA as qualifiers. RESULTS: Overall, 482 eyes received ≥ 1 brolucizumab injection; 174 eyes received ≥ 3 brolucizumab injections with ≥ 12 months of follow-up, and 95 eyes received ≥ 3 brolucizumab injections with ≥ 18 months of follow-up. VA (mean [95% confidence intervals]) remained stable relative to baseline after 12 months (- 1.1 [- 3.7, 1.6] letters; p = 0.42) and 18 months (0.0 [- 3.1, 3.1] letters; p = 0.98) of brolucizumab treatment, respectively, and pre-switch injection intervals or baseline VA had no notable effect. Following the switch to brolucizumab, injection intervals were extended from baseline to month 12 by 26.9 (19.7, 34.0) days (p < 0.0001), and eyes with pre-switch injection intervals < 8 weeks were able to have their injection intervals extended by 23.6 days longer than eyes with pre-switch injection intervals ≥ 8 weeks. At 18 months, injection intervals were extended by 36.3 (25.6, 46.9) days (p < 0.0001) compared to baseline. Following switch to brolucizumab, CMT was reduced at both 12 and 18 months (12 months: - 35.2 (- 51.7, - 18.8) µm, p < 0.0001; 18 months: - 38.9 (- 54.3, - 22.0) µm, p < 0.0001). Intraocular inflammation-related adverse events were reported in 4.6% of brolucizumab-treated eyes. CONCLUSIONS: This real-world study demonstrates that injection intervals may be significantly extended with maintained vision and reduced CMT in nAMD eyes switching to brolucizumab therapy from other anti-VEGFs.

One-Year and 18-Month Outcomes in nAMD Patient Eyes Switched to Brolucizumab Alone versus to Brolucizumab Alternating with Other Anti-VEGF Agents.

Objective: Retrospective, real-world study to evaluate visual acuity (VA), anti-vascular endothelial growth factor (anti-VEGF) injection intervals, and central macular thickness (CMT) in neovascular age-related macular degeneration (nAMD) eyes switched to brolucizumab only or to brolucizumab alternating with another anti-VEGF. Methods: The overall study population comprised eyes that were given ≥1 brolucizumab injection between 1 October 2019 and 30 November 2021. The brolucizumab-only (BRO) cohort consisted of prior anti-VEGF-treated eyes treated exclusively with ≥3 brolucizumab injections over ≥12 or ≥18 months; the alternating brolucizumab (ALT) cohort comprised prior anti-VEGF-treated eyes treated with ≥2 brolucizumab injections and ≥1 other anti-VEGF over ≥12 or ≥18 months. Results: A total of 482 eyes received ≥1 brolucizumab injection during the study period. Mean VA changes from baseline were -1.1±15.1 letters (BRO cohort; n = 174) and 1.3±13.0 letters (ALT cohort; n = 47) at Month 12, and 0.0±13.5 letters (BRO cohort; n = 95) and -7.3±17.2 letters (ALT cohort; n = 29) at Month 18. Mean changes in injection intervals were +26.9±48.1 days (BRO cohort) and +11.1±17.3 days (ALT cohort) at Month 12 and +36.3±52.3 days (BRO cohort) and +14.0±19.9 days (ALT cohort) at Month 18. Mean changes in CMT were -35.2±108.1 µm (BRO cohort) and -31.5±91.2 µm (ALT cohort) at Month 12 and -38.9±75.0 µm (BRO cohort) and -9.0±59.9 µm (ALT cohort) at Month 18. Intraocular inflammation-related adverse events were recorded in 22/482 (4.6%) eyes. Conclusion: Treatment with either brolucizumab alone or brolucizumab alternating with another anti-VEGF can preserve vision, reduce CMT, and extend anti-VEGF injection intervals in patients with nAMD.