Evaluating the long-term biological stability of cytokine biomarkers in ocular fluid samples.

PURPOSE: The quality of biological fluid samples is vital for optimal preanalytical procedures and a requirement for effective translational biomarker research. This study aims to determine the effects of storage duration and freeze-thawing on the levels of various cytokines in the human aqueous humour and vitreous samples. METHODS AND ANALYSIS: Human ocular aqueous humour and vitreous samples were obtained from 25 eyes and stored at -80°C for analysis. All samples were assayed for 27 cytokine biomarker concentrations (pg/mL) using a multiplex assay. Four sample storage durations following sample collection were evaluated (1 week, 3 months, 9 months and 15 months). Additionally, samples underwent up to three freeze-thaw cycles within the study period. RESULTS: Among the 27 cytokine biomarkers, concentrations of four cytokines (Interleukin (IL)-2, IL-10, IL-12 and platelet-derived growth factor-BB) were significantly decreased by storage duration at all time points, as early as 3 months following sample collection (range of 9%-37% decline between 1 week and 15 months, p<0.001). Freeze-thawing of up to three cycles did not significantly impact the cytokine biomarker concentrations in aqueous humour or vitreous. Separability of patient-specific cytokine biomarker profiles in the principal component analysis remained relatively the same over the 15 months of storage duration. CONCLUSION: The findings from this study suggest that several intraocular cytokine biomarkers in human aqueous humour and vitreous samples may be susceptible to degradation with long-term storage, as early as 3 months after collection. The overall patient-specific cytokine biomarker profiles are more stable than concentrations of individual cytokines. Future studies should focus on developing guidelines for optimal and standardised sample handling methods to ensure correct research findings about intraocular biomarkers are translated into clinical practice.

Retinal Microvascular Density and Perfusion during an Insulin-Induced Hypoglycemia Episode: A Warning Call.

Aim: To evaluate retinal vascular perfusion and density by optical coherence tomography angiography (OCTA) before, during, and after hypoglycemia in individuals with diabetes mellitus with or without diabetic retinopathy (DR). Methods: A focused clinical history was performed, followed by an ophthalmological examination to document retinopathy status. OCTA was performed at baseline, at hypoglycemia, and at glucose normalization. Eye tracking and eye alignment devices on the platform were used to obtain a macular thickness cube (512 × 128) and vascular perfusion and density protocols of 3 × 3 mm. Retinal vascular reactivity was analyzed with superficial plexus vascular perfusion and density protocols on OCTA. Results: Fifty-two participants encompassing 97 eyes fulfilled the eligibility criteria. Their mean age was 42.9 ± 15.1 years (range, 22 to 65), and 20 (38.2%) were men. We found a statistically significant difference in vascular perfusion and density when comparing all groups at baseline. The controls had higher vascular perfusion and density values than the cases. Vascular perfusion and density were significantly reduced in all groups during the hypoglycemia episode, except for vascular density in DR cases. Conclusion: Acute hypoglycemia significantly alters the retinal vascularity in DM patients with and without DR, suggesting that repeated episodes of acute hypoglycemia could exacerbate retinopathy in the long term.

Prevalence and clinical implications of subretinal fluid in retinal diseases: a real-world cohort study.

BACKGROUND/AIMS: To characterise the baseline prevalence of subretinal fluid (SRF) and its effects on anatomical and visual acuity (VA) outcomes in diabetic macular oedema (DME) and retinal vein occlusion (RVO) following anti-vascular endothelial growth factor (VEGF). METHODS: This is a retrospective cohort study of 122 DME and 54 RVO patients who were initiated on anti-VEGF therapy with real-world variable dosing. The DME and RVO cohorts were subclassified based on the presence of SRF at presentation. Snellen VA was measured and converted to logarithm of the minimum angle of resolution (LogMAR). Changes in VA and central subfield thickness (CST) were assessed up to 24 months. RESULTS: SRF was present in 22% and 41% in DME and RVO patients, respectively. In the DME subcohort, eyes with SRF showed an improvement of 0.166 logMAR (1.7 Snellen chart lines) at 12 months and 0.251 logMAR (2.6 Snellen chart lines) at 24 months, which were significantly greater compared with those of the non-SRF group. A significantly greater reduction in CST was noted in the SRF eyes compared with the non-SRF eyes at 3 months and 1 month in the DME and RVO subcohorts, respectively. CONCLUSION: Baseline SRF is a good marker for a greater reduction in CST in both DME and RVO, but an improvement in VA associated with SRF may be only noted in DME.

COVID-19: Findings in nuclear medicine from head to toe.

COVID-19 is a multisystemic disease, and hence its potential manifestations on nuclear medicine imaging can extend beyond the lung. Therefore, it is important for the nuclear medicine physician to recognize these manifestations in the clinic. While FDG-PET/CT is not indicated routinely in COVID-19 evaluation, its unique capability to provide a functional and anatomical assessment of the entire body means that it can be a powerful tool to monitor acute, subacute, and long-term effects of COVID-19. Single-photon scintigraphy is routinely used to assess conditions such as pulmonary embolism, cardiac ischemia, and thyroiditis, and COVID-19 may present in these studies. The most common nuclear imaging finding of COVID-19 vaccination to date is hypermetabolic axillary lymphadenopathy. This may pose important diagnostic and management dilemmas in oncologic patients, particularly those with malignancies where the axilla constitutes a lymphatic drainage area. This article aims to summarize the relevant literature published since the beginning of the pandemic on the intersection between COVID-19 and nuclear medicine.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY MORPHOLOGY AFTER RHEGMATOGENOUS RETINAL DETACHMENT REPAIR: ALIGN Post Hoc Analysis.

PURPOSE: To compare foveal avascular zone (FAZ) geometric indices using optical coherence tomography angiography (OCTA) in pneumatic retinopexy (PnR) versus pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD). FAZ morphology was assessed as a possible imaging feature of retinal displacement. METHODS: This ALIGN post hoc analysis included primary fovea-off RRDs that underwent successful PnR or PPV, and performed OCTA, and fundus autofluorescence at (FAF) 3 months postoperatively at St. Michael's Hospital, Toronto, Canada. FAZ area (mm 2 ), axial ratio, circularity, and roundness were measured, and FAF images were assessed for retinal displacement. RESULTS: Seventy-two patients were included, 78% (56/72) were male mean age was 60 ± 9 years, and 60% (43/72) were phakic. Sixty-five percent (47/72) and 35% (25/72) underwent PnR and PPV, respectively. The mean baseline logarithm of the minimum angle of resolution visual acuity was 1.49 ± 0.76. FAZ circularity was lower after PPV (0.629 ± 0.120) versus PnR (0.703 ± 0.122); P = 0.016. Sixty-six patients had gradable FAF images. Retinal displacement was present in 29% (19/66), 84.2% (16/19) of which had displacement in the macula. FAZ circularity was lower in eyes with displacement in the macula (0.613 ± 0.110) versus those without displacement (0.700 ± 0.124); P = 0.015. There was a moderate negative correlation between 12-month aniseikonia and FAZ circularity(r = -0.262; P = 0.041). CONCLUSION: FAZ circularity was lower after PPV and in eyes with retinal displacement in the macula. Circularity was negatively correlated with 12-month aniseikonia scores. FAZ circularity may be another imaging feature to consider postoperatively after RRD repair.

Shovel and Cut Technique: Beveled Vitrectomy Probes to Address Diabetic Tractional Retinal Detachments.

PURPOSE: To describe a surgical technique using the structural advantages of beveled tip cutters. METHODS: The introduction of beveled tips has been one of the few modifications that have been performed to vitrectomy probes since first described by Machemer in 1972. Shovel and cut technique uses this incredible modification to access tighter planes and remove broad diabetic membranes. DESCRIPTION OF TECHNIQUE: The shovel and cut technique can be used with any gauge probe to which the bevel tip is applied. The beveled tip of the cutter is used in a shovel manner to create a tissue plane between the diabetic plaque and the retina. As the beveled tip of the cutter moves parallel to the underlying retina, scar tissue naturally feeds into the cutting port where it is cut and aspirated with low flow rates. CONCLUSION: Shovel and cut technique takes advantage of beveled tip technological innovation to allow easy access and tissue dissection of the most difficult plaques in diabetic membranes. This technique allows us to remove these plaques in a safer, more controlled manner than previous described techniques.

Standard Adult Gastric Emptying Scintigraphy Criteria Is Applicable for Partial Meal Ingestion.

BACKGROUND/AIMS: Gastric emptying scintigraphy is commonly performed to assess for dysmotility. A standardized meal with associated threshold criteria was established in 2000 to enable robust interpretation. However, no guidance is available to interpret results when patients do not ingest the entire meal. The purpose of this study is to determine the continued appropriateness of the threshold criteria in contemporary clinical practice and its relevance for partially ingested meals. METHODS: This retrospective study analyzed patients (n = 1365 total) who underwent solid-phase gastric emptying scintigraphy at an academic medical center. Patients were stratified based on their completion of the standard meal. Patients were further stratified into normal and delayed gastric emptying cohorts based on the current criteria. Percent gastric retention values at 1, 2, 3, and 4 h were compared. RESULTS: Median (95% upper reference) normal gastric retention values for the complete standard meal were 64% (87%) at 1 h, 25% (60%) at 2 h, 13% (54%) at 3 h and 4% (9%) at 4 h. Consumption of at least 50% of the standard meal yielded similar retention; 53% (86%) at 1 h, 19% (58%) at 2 h, 6% (29%) at 3 h and 3% (10%) at 4 h. There was no significant age- or gender-specific differences using the current criteria, and no differences were observed based on diabetic status. Retention values matched well with the current criteria and validated with data-driven clustering. CONCLUSION: Adult normative standards for gastric emptying scintigraphy are appropriate for differentiating normal and delayed populations and can be applied to partial meals with at least 50% completion.

Key Factors to Attract More U.S. Diagnostic Radiology Residents into the Field of Nuclear Medicine and Molecular Imaging: A National Survey.

RATIONALE AND OBJECTIVES: To understand the current state of radiology residents' exposure to nuclear medicine and molecular imaging (NM/MI), determine key factors that may attract more trainees into the field, and identify differentiating aspects between those specializing in NM/MI and those who are not. MATERIALS AND METHODS: An anonymous web-based survey was sent to contacts at all diagnostic radiology residency programs in the United States for dissemination to their residents, collecting information about trainees' NM/MI exposure during residency and factors that may attract them to NM/MI. RESULTS: A total of 198 trainees responded to the survey, 34 of whom plan on pursuing a career in NM/MI. Most trainees reported early exposure to NM/MI during residency; most (97.4%) reported ample exposure to general NM/MI and oncologic studies. Less than 3% of trainees reported adequate exposure to therapies, neurological applications, molecular imaging/research advances, and physics. Respondents reported a need for better quality education (38.9%) and exposure to mentors (28.8%) as ways to attract trainees to NM/MI. Routinely encountered clinical pathology was the most interesting for those specializing in NM/MI (29.4%), whereas lifestyle was the most attractive aspect of NM/MI for those not pursuing a career in the field (27.4%). NM/MI-associated research was the least attractive for those specializing in NM/MI (35.3%), while job market concerns was the least attractive aspect for those not specializing in NM/MI (37.2%). Trainees planning to specialize in NM/MI reported higher satisfaction with their orientation to NM/MI during their first clinical rotation compared to those who do not plan to specialize in the field (3.03/5.00 and 2.67/5.00, respectively, p = 0.04). CONCLUSION: This survey highlights several factors that training programs and national societies can target to improve interest in NM/MI among radiology residents. We found that optimized education initiatives, including improved orientation to the field, increased mentoring, and career opportunities are essential levers for recruiting radiology trainees into the NM/MI workforce.

Effects of Sleep Deprivation, Non-Dominant Hand Employment, Caffeine and Alcohol Intake During Surgical Performance: Lessons Learned From the Retina Eyesi Virtual Reality Surgical Simulator.

Purpose: Determine whether real-life surgical experience correlates with scores on a retina virtual simulator and the effects of various challenges on surgical performance. Methods: The study was performed using the Eyesi Surgical Simulator, a virtual reality retina surgical simulator. Residents, fellows, and retina staff were assessed on surgical simulations to determine surgical skills. Participants were assigned baseline scores on speed, efficiency of movement, and ability to avoid retinal damage. After receiving their baseline scores, participants were challenged to use their non-dominant hand or to use the simulator after sleep deprivation or the intake of caffeine or alcohol. Results: At baseline, junior residents had an average score of 943; senior residents, 1045; retina fellows, 1153; and surgical retina staff, 1161. A 12.5% overall improvement in scores was achieved when comparing baseline 1 to baseline 2; a major improvement was recorded in residents (14.5%) compared with fellows and retina staff (9.97%). A statistically significant difference was observed between residents and fellows (P = 0.027), as well as between residents and retina staff (P = 0.04). A significant decrease in performance (15.7%) was observed when the non-dominant hand was used (P = 0.043). Performance after sleep deprivation and alcohol intake decreased, but not with a statistically significant difference (P = 0.6 and P = 0.5, respectively). A trend toward increasing performance was observed after caffeine intake (6.1%; P = 0.06). Conclusions: The retina virtual simulator is a novel teaching tool for retinal surgery. A significant association was observed between real surgical experience and the retina surgery virtual simulator results based on surgical experience. Translational Relevance: An association between real surgical experience and retina surgery virtual simulator results was demonstrated. A complete training program with a cut-off threshold score should be validated for retina training programs.

Reduced Pneumonia Risk in Advanced Dementia Patients on Careful Hand Feeding Compared With Nasogastric Tube Feeding.

OBJECTIVES: To compare survival and pneumonia risk among hospitalized patients with advanced dementia on nasogastric tube feeding (NGF) vs careful hand feeding (CHF) and to examine outcomes by feeding problem type. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Advanced dementia patients aged ≥60 years with indication for tube feeding admitted to 2 geriatric convalescent hospitals between January 1, 2015, and June 30, 2019. METHODS: Comparison on the effect of NGF and CHF on survival and pneumonia risk using Kaplan Meier survival analysis and Cox proportional hazards models. RESULTS: Of the 764 patients (mean age 89 years, 61% female, 74% residential care home residents), 464 (61%) were initiated on NGF and 300 (39%) on CHF. The primary feeding problem types were dysphagia (50%), behavioral feeding problem (33%), or both (17%). There was no difference in 1-year survival rate between NGF and CHF groups (36% vs 37%, P = .71) and survival did not differ by feeding problem type. Nasogastric tube feeding was not a significant predictor for survival (adjusted hazard ratio 1.15, 95% CI 0.94-1.39). Among 577 (76%) patients who survived to discharge, pneumonia rates were lower in the CHF group (48% vs 60%, P = .004). After adjusting for cofounders, NGF was a significant risk factor for pneumonia (adjusted hazard ratio 1.41, 95% CI 1.08-1.85). In subgroup analyses, NGF was associated with increased pneumonia risk for patients with both dysphagia and behavioral feeding problem (P = .01) but not in patients with behavioral feeding problem alone (P = .24) or dysphagia alone (P = .30). CONCLUSIONS AND IMPLICATIONS: For advanced dementia patients with feeding problems, there is no difference in survival between NGF and CHF. However, NGF is associated with a higher pneumonia risk, particularly for patients with both dysphagia and behavioral feeding problem. Further research on how the feeding problem type impacts pneumonia risk for patients on NGF is needed.

Treatment of Diabetic Macular Edema with Aflibercept and Micropulse Laser (DAM Study).

Purpose: To investigate the safety and efficacy of micropulse (MP) macular laser in combination with intravitreal aflibercept for the treatment of center-involved diabetic macular edema (CI-DME). Methods: A single-blind prospective randomized controlled pilot trial was performed. In total, 30 eyes of 30 patients with CI-DME and best corrected visual acuity (BCVA) between, and including, 20/30 and 20/400 were enrolled. Enrolled eyes were randomized to 2 groups. Group 1 received intravitreal aflibercept injections (IVT-AFL) with sham laser. Group 2 received IVT-AFL with MP laser. Both groups were followed every 4 weeks for 48 weeks and retreatment was performed on pro re nata basis according to preset criteria. The main outcome measure was the average number of intravitreal injections for each group at 48 weeks. Secondary outcome measures included changes in BCVA and central macular thickness (CMT) at 24 and 48 weeks. Results: The average number of intravitreal injections at 48 weeks was similar between the groups (8.5±3.3 in Group 1 vs 7.9±3.6 in Group 2, p=0.61). After 48 weeks, both groups demonstrated an improvement in BCVA and CMT. However, the difference in improvement between the groups was not statistically significant (p=0.18 for BCVA and p=0.57 for CMT). Conclusion: Intravitreal injections of aflibercept led to improvements in BCVA and CMT at 24 and 48 weeks. Addition of MP laser to eyes in group 2 did not offer additional benefit in reducing treatment burden or improving CMT. Eyes that received MP laser showed a numerically greater improvement in BCVA, although this was not statistically significant. Clinicaltrialsgov Identifier: NCT03143192 March 8, 2017.

Thoracic Imaging Manifestations of Treated Lymphomas: Response Evaluation, Posttherapeutic Sequelae, and Complications.

Lymphoma is the most common hematologic malignancy comprising a diverse group of neoplasms arising from multiple blood cell lineages. Any structure of the thorax may be involved at any stage of disease. Imaging has a central role in the initial staging, response assessment, and surveillance of lymphoma, and updated standardized assessment criteria are available to assist with imaging interpretation and reporting. Radiologists should be aware of the modern approaches to lymphoma treatment, the role of imaging in posttherapeutic surveillance, and manifestations of therapy-related complications.

The effect of latency on surgical performance and usability in a three-dimensional heads-up display visualization system for vitreoretinal surgery.

PURPOSE: Although latency has been cited as a disadvantage of the three-dimensional heads-up display (3D HUD) visualization system for vitreoretinal surgery, there have been no publications evaluating the effect of latency on surgical performance. METHODS: Thirty participants conducted two tasks (external suturing and inner limiting membrane peeling) on a 3D HUD at 4 levels of latency: 50 ms (ms), 68 ms, 92 ms, and 122 ms. The task completion time was measured and patients answered a subjective questionnaire on usability. RESULTS: No difference in completion times was found between different levels of latencies in either task. Regarding usability, significant decreases were found at 122 ms for both the suturing and peeling task overall, but for experienced HUD users, there was less of a decrease. CONCLUSION: This study is the first to evaluate the effect of latency on 3D HUD for vitreoretinal surgery. The levels of latency in the current models of 3D HUD are unlikely to contribute to a decrease in surgical performance and usability with current technologies which have a latency of 70 ms.

Identification and Mitigation of Defensins in the Immunopurification of Peptide MHC-I Antigens from Lung Tissue.

The class I major histocompatibility (MHC-I) complex is a set of diverse cell surface receptors encoded by the human leukocyte antigen gene complex. These receptors present intracellular antigens to cytotoxic T cells providing information on the state and health of cells. Changes in the immunopeptidome during cancer may provide novel targets for therapeutic intervention. To understand how the tumor immunopeptidome is altered, we developed a mass spectrometry (MS) based platform for isolating and identifying MHC-I peptide antigens in lung tumors. In the course of our work, we encountered several large unknown peptide contaminants which had not been previously reported. To understand the source of these major contaminants, we isolated them using offline fractionation and identified them by liquid chromatography-tandem mass spectrometry (LC-MS/MS) as members of the host defense protein family known as the defensins. To mitigate their detrimental effects, we modified our "Original" data-dependent acquisition (DDA) MS method to narrowly target the MHC-I peptides based on their physical properties including charge state and molecular weight ("z state" DDA), evaluated field asymmetric ion mobility spectrometry to attempt gas-phase separation prior to MS analysis, and developed an immunodepletion approach using defensin specific antibodies. This modified approach improves peptide identification and reduces the impact of defensin contamination in lung tissue samples.

Two-Year Results of the Phase 3 Randomized Controlled Study of Abicipar in Neovascular Age-Related Macular Degeneration.

PURPOSE: To report the 2-year efficacy and safety of abicipar every 8 weeks and quarterly (after initial doses) compared with monthly ranibizumab in patients with treatment-naïve neovascular age-related macular degeneration (nAMD). DESIGN: Two multicenter, randomized, phase 3 clinical trials with identical protocols (CEDAR and SEQUOIA). Analyses used pooled trial data. PARTICIPANTS: The trials enrolled 1888 patients (1 eye/patient) with active choroidal neovascularization secondary to age-related macular degeneration and best-corrected visual acuity (BCVA) of 24 to 73 Early Treatment Diabetic Retinopathy Study letters. METHODS: At enrollment, patients were assigned to study eye treatment with abicipar 2 mg every 8 weeks after initial doses at baseline and weeks 4 and 8 (abicipar Q8, n = 630), abicipar 2 mg every 12 weeks after initial doses at baseline and weeks 4 and 12 (abicipar Q12, n = 628), or ranibizumab 0.5 mg every 4 weeks (ranibizumab Q4, n = 630). MAIN OUTCOME MEASURES: Efficacy measures included stable vision (<15-letter loss in BCVA from baseline) and change from baseline in BCVA and central retinal thickness (CRT). Safety measures included adverse events (AEs). RESULTS: For patients who completed the study, efficacy of abicipar after initial doses was maintained through week 104. At week 104, the proportion of patients with stable vision was 93.0% (396/426), 89.8% (379/422), and 94.4% (470/498); mean change in BCVA from baseline was +7.8 letters, +6.1 letters, and +8.5 letters, and mean change in CRT from baseline was -147 µm, -146 µm, and -142 µm in the abicipar Q8 (14 injections), abicipar Q12 (10 injections), and ranibizumab Q4 (25 injections) groups, respectively. The overall incidence of intraocular inflammation (IOI) AEs was 15.4%, 15.3%, and 0.3% from baseline through week 52 and 16.2%, 17.6%, and 1.3% from baseline through week 104 in the abicipar Q8, abicipar Q12, and ranibizumab Q4 groups, respectively. CONCLUSIONS: Two-year results show efficacy of abicipar Q8 and Q12 in nAMD. First onset of IOI events with abicipar was much reduced in the second year and comparable with ranibizumab (0.8% and 2.3% vs. 1.0%). The extended duration of effect of abicipar allows for quarterly dosing and reduced treatment burden.