Imaging of 3 bright terrestrial gamma-ray flashes by the atmosphere-space interactions monitor and their parent thunderstorms.

The Atmosphere-Space Interactions Monitor (ASIM) on the International Space Station (ISS) includes an instrument designed to geolocate Terrestrial Gamma-ray Flashes (TGF) produced by thunderstorms. It does so with a coded aperture system shadowing the pixelated Low Energy Detector of the Modular X- and Gamma-ray Sensor (MXGS). Additionally, it locates associated lightning flashes with the Modular Multispectral Imaging Array (MMIA). Here we present 3 bright TGFs with very similar duration, fluency and observation distance. The innovative imaging capabilities allow us to determine the TGF position and correlate the TGF-lightning parent event in time and position simultaneously. The accurate position determination and distance to the observer allow us to perform a comparative study of TGF characteristics. These TGFs were produced in association with lightning flashes below the highest cloud tops of developing to mature convective cells. In one event, GLM (Geostationary Lightning Mapper) cloud flash rates were slowing down after the TGF while negative cloud-to-ground flashes suddenly ceased from 10 to 5 min before the TGF. An 8-stroke (strongest: -93 kA) cloud-to-ground flash occurred 31 s before the TGF. Vertical profiles from the ERA5 reanalysis data suggest TGFs may be produced in variety of tropical environments.

Alpelisib for treatment of patients with PIK3CA-related overgrowth spectrum (PROS).

PURPOSE: PIK3CA-related overgrowth spectrum (PROS) encompasses several rare conditions resulting from activating variants in PIK3CA. Alpelisib, a PI3Kα-selective inhibitor, targets the underlying etiology of PROS, offering a novel therapeutic approach to current management strategies. This study evaluated the safety and efficacy of alpelisib in pediatric and adult patients with PROS. METHODS: EPIK-P1 (NCT04285723) was a non-interventional, retrospective chart review of 57 patients with PROS (≥2 years) treated with alpelisib through compassionate use. Patients had severe/life-threatening PROS-related conditions and confirmed PIK3CA pathogenic variant. The primary end point assessed patient response to treatment at Week 24 (6 months). RESULTS: Twenty-four weeks (6 months) after treatment initiation, 12 of 32 (37.5%) patients with complete case records included in the analysis of the primary end point experienced a ≥20% reduction in target lesion(s) volume. Additional clinical benefit independent from lesion volume reduction was observed across the full study population. Adverse events (AEs) and treatment-related AEs were experienced by 82.5% (47/57) and 38.6% (22/57) of patients, respectively; the most common treatment-related AEs were hyperglycemia (12.3%) and aphthous ulcer (10.5%). No deaths occurred. CONCLUSION: EPIK-P1 provides real-world evidence of alpelisib effectiveness and safety in patients with PROS and confirms PI3Kα as a valid therapeutic target for PROS symptom management.

Adherence of patients with age-related macular degeneration to AREDS 2-recommended nutritional supplements.

BACKGROUND: The Age-Related Eye Disease Study 2 (AREDS 2) proved the benefit of vitamin and mineral supplementation in preventing advanced age-related macular degeneration (AMD). AREDS 2 supplements are indicated for patients with either bilateral intermediate AMD (AREDS category 3) or unilateral neovascular AMD (AREDS category 4). AIMS: The aims of this telephone survey were to identify the rate of adherence of patients to AREDS 2 supplements and the factors associated with non-compliance in these patient groups. METHODS: A patient telephone survey was conducted in an Irish tertiary care hospital. Patients were identified by chart review, and their AREDS categorization was reconfirmed. A telephone consultation was conducted with each patient to assess their compliance with the micronutrient supplements. RESULTS: We identified 120 patients who met the AREDS criteria for supplementation. Of these, 103 patients were graded as category 4, and 17 patients were graded as category 3. Almost a fifth (18%) were current smokers. Under two-thirds (60%) of the patients were taking AREDS 2 supplements. Of the remainder, 83% of patients did not recall being advised of their benefit. The cost was cited by 10% of patients as a reason for non-compliance. CONCLUSION: The ophthalmologist not only has a duty of care to treat the neovascular complications of AMD, but they must also strive to improve patient compliance with AREDS supplements. The cessation of smoking needs to be actively promoted in order to stop preventable vision loss in patients with AMD.

Outcomes of COVID-19 in people with rheumatic and musculoskeletal disease in Ireland over the first 2 years of the pandemic.

BACKGROUND: Poor COVID-19 outcomes occur with higher frequency in people with rheumatic and musculoskeletal diseases (RMD). Better understanding of the factors involved is crucial to informing patients and clinicians regarding risk mitigation. AIM: To describe COVID-19 outcomes for people with RMD in Ireland over the first 2 years of the pandemic. METHODS: Data entered into the C19-GRA provider registry from Ireland between 24th March 2020 and 31st March 2022 were analysed. Differences in the likelihood of hospitalisation and mortality according to demographic and clinical variables were investigated. RESULTS: Of 237 cases included, 59.9% were female, 95 (41.3%) were hospitalised, and 22 (9.3%) died. Hospitalisation was more common with increasing age, gout, smoking, long-term glucocorticoid use, comorbidities, and specific comorbidities of cardiovascular and pulmonary disease, and cancer. Hospitalisation was less frequent in people with inflammatory arthritis and conventional synthetic or biologic disease-modifying antirheumatic drug use. Hospitalisation had a U-shaped relationship with disease activity, being more common in both high disease activity and remission. Mortality was more common with increasing age, gout, smoking, long-term glucocorticoid use, comorbidities, and specific comorbidities of cardiovascular disease, pulmonary disease, and obesity. Inflammatory arthritis was less frequent in those who died. CONCLUSION: Hospitalisation or death were more frequently experienced by RMD patients with increasing age, certain comorbidities including potentially modifiable ones, and certain medications and diagnoses amongst other factors. These are important 'indicators' that can help risk-stratify and inform the management of RMD patients.

Case study using RWD in the context of a pivotal trial for regulatory approval in a rare disease.

Rare disorders impact millions of children worldwide, and developing new medicines in this setting is associated with multiple challenges. In this paper, we share a successful story of how real-world data (RWD) were leveraged to accelerate evidence generation and patient access to a life-changing therapy in patients with severe manifestations of PIK3CA-related overgrowth spectrum who require systemic therapy. Despite all the existing regulatory guidelines considering real-world evidence (RWE), there is limited regulatory precedent of the use of this framework in support of a new indication. Thus, our case study illustrates design innovations based on the use of a compassionate use program, primarily in children, as a RWD source for approval of a new therapy in a rare disorder. We highlight the systematic considerations and mitigation of potential sources of bias in order to transform the data into actionable evidence. Our experience shows that RWE can be successfully used with appropriate study planning and mitigation in the context of a rare disorder with a high unmet medical need. Some lessons learned from this case study can benefit therapeutic development in rare disorders.

Long-term efficacy and safety of osilodrostat in Cushing's disease: final results from a Phase II study with an optional extension phase (LINC 2).

BACKGROUND: Many patients with Cushing's disease (CD) require long-term medical therapy to control their hypercortisolism. In the core phase of a Phase II study (LINC 2; NCT01331239), osilodrostat normalized mean urinary free cortisol (mUFC) in 78.9% of patients with CD. Here, we report long-term efficacy and safety data for osilodrostat following completion of an optional extension to LINC 2. METHODS: Adult patients with CD were enrolled in a 22-week prospective Phase II study. Patients with mUFC ≤ upper limit of normal (ULN) or receiving clinical benefit at week 22 could enter the optional extension. The proportion of complete (mUFC ≤ ULN) or partial (mUFC > ULN but ≥ 50% decrease from baseline) mUFC responders was assessed over time. RESULTS: Sixteen of 19 enrolled patients entered the extension. Median (range) osilodrostat exposure from baseline to study end was 5.4 years (0.04-6.7); median (range) average dose was 10.6 mg/day (1.1-47.9). Overall response rate (complete and partial mUFC responders) was consistently ≥ 50%. Sustained control of most cardiovascular-related parameters was observed during the extension. The long-term safety profile was consistent with that reported during the core phase. Testosterone levels (females) decreased towards baseline levels during long-term follow-up, with no new or worsening cases of hirsutism during the extension. CONCLUSIONS: In the longest prospective study of a steroidogenesis inhibitor to date, osilodrostat provided sustained reductions in mUFC for up to 6.7 years of treatment, with no new safety signals emerging during the extension. These findings support osilodrostat as an effective long-term treatment for patients with CD.

Small cell lung cancer recurring in the retina.

Intraocular metastases are rare, usually isolating to the uveal tract. Retinal metastases are less common still, presenting a unique diagnostic and therapeutic challenge. This case observes a 66-year-old female ex-smoker presenting with unilateral painful vision loss 2 months from completion of definitive chemoradiotherapy for early-stage small cell lung cancer. A retinal lesion was discovered on examination and initially treated as viral retinitis without improvement. Two vitrectomy procedures were unable to confirm the diagnosis. Eventual retinal biopsy under general anaesthesia confirmed small cell lung cancer oligometastasis (7 months from completion of definitive chemoradiotherapy), without evidence of other sites of disease on imaging. She received local radiation to retina with resolution of eye pain. She eventually developed intrathoracic relapse of disease and was treated with palliative chemotherapy (14 months from completion of definitive chemoradiotherapy).

Temporal trends in COVID-19 outcomes in people with rheumatic diseases in Ireland: data from the COVID-19 Global Rheumatology Alliance registry.

OBJECTIVES: Although evidence is accumulating globally, data on outcomes in rheumatic disease and COVID-19 in Ireland are limited. We used data from the COVID-19 Global Rheumatology Alliance (C19-GRA) to describe time-varying COVID-19 outcomes for people with rheumatic disease in Ireland. METHODS: Data entered into the C19-GRA provider registry from Ireland between 24 March 2020 and 9 July 2021 were analysed. Differences in the likelihood of hospitalization and mortality according to demographic and clinical variables were investigated using Chi-squared test or Fisher's exact test, as appropriate. Trends in odds of hospitalization and mortality over time were investigated using logistic regression with the time period as a categorical variable. RESULTS: Of 212 cases included, 59.4% were female and median age was 58.0 years (range 13-96). Of the 212 cases, 92 (43%) were hospitalized and 22 (10.4%) died. Increasing age, a diagnosis of gout, ever smoking, glucocorticoid use, having comorbidities and specific comorbidities of cancer, cardiovascular and pulmonary disease were more common in those hospitalized. A diagnosis of inflammatory arthritis, csDMARD and/or b/tsDMARD use were less frequent in those hospitalized. Increasing age, a diagnosis of gout, ever smoking, having comorbidities and specific comorbidities of obesity, cardiovascular and pulmonary disease were more common in those who died. Odds of hospitalization or mortality did not change over time. CONCLUSION: No temporal trend was observed in either COVID-19-related hospitalization or mortality outcomes for people with rheumatic disease in Ireland.

Predictors of hospitalization in patients with rheumatic disease and COVID-19 in Ireland: data from the COVID-19 global rheumatology alliance registry.

OBJECTIVES: Given the limited data regarding the risk of hospitalization in patients with rheumatic disease and coronavirus disease 2019 (COVID-19) in Ireland, we used the COVID-19 Global Rheumatology Alliance (GRA) registry data to study outcomes and their predictors. The primary objective was to explore potential predictors of hospitalization. METHODS: We examined data on patients and their disease-related characteristics entered in the COVID-19 GRA provider registry from Ireland (from 24 March 2020 to 31 August 2020). Multivariable logistic regression was used to assess the association of demographic and clinical characteristics with hospitalization. RESULTS: Of 105 patients, 47 (45.6%) were hospitalized and 10 (9.5%) died. Multivariable logistic regression analysis showed that age [odds ratio (OR) = 1.06, 95% CI 1.01, 1.10], number of co-morbidities (OR = 1.93, 95% CI 1.11, 3.35) and glucocorticoid use (OR = 15.01, 95% CI 1.77, 127.16) were significantly associated with hospitalization. A diagnosis of inflammatory arthritis was associated with lower odds of hospitalization (OR = 0.09, 95% CI 0.02, 0.32). CONCLUSION: Increasing age, co-morbidity burden and glucocorticoid use were associated with hospitalization, whereas a diagnosis of inflammatory arthritis was associated with lower odds of hospitalization.

Analyzing the Carbon Footprint of an Intravitreal Injection.

PURPOSE: To estimate the carbon footprint of a single intravitreal injection in a hospital-based intravitreal service. METHODS: Greenhouse gas emissions attributable to the delivery of an intravitreal injection were calculated using a hybrid lifecycle analysis technique. Data were collected regarding procurement of materials, patient travel, and building energy use. RESULTS: Carbon emissions associated with a single intravitreal injection, excluding the anti-VEGF agent, were 13.68 kg CO 2 eq. This equates to 82,100 kg CO 2 eq annually for our service. Patient travel accounted for the majority of emissions at 77%, with procurement accounting 19% for and building energy usage for 4% of total emissions. The omission of items considered dispensable from injection packs would reduce carbon emissions by an estimated 0.56 kg per injection - an annual saving of 3,360 kg CO 2 eq for our service. Similar savings, if extrapolated to a country the size of the United Kingdom, could yield annual carbon savings of 450,000 kg CO 2 eq. For context, a single one-way economy transatlantic flight produces 480 kg CO 2 eq per person. CONCLUSION: Wasteful practice in healthcare increases greenhouse gas production and drives climate change. The healthcare sector should be a leader in sustainable practice promotion and changes to high volume procedures have the largest impact on emissions. Long-acting agents offer the greatest future potential for meaningful reductions.

Correlation of magnetic resonance and arthroscopy in the diagnosis of shoulder injury.

BACKGROUND: Advances in shoulder magnetic resonance imaging (MRI) and arthrography (MRA) have revolutionised musculoskeletal diagnosis and surgical planning. Despite this, the overall accuracy of MRI, with or without intra-articular contrast, can be variable. METHODS: In this prospective non-randomised analysis, 200 participants (74.5% males) with suspected shoulder injuries underwent MRI (41.0%) or MRA followed by arthroscopy. A study specific proforma was developed to ensure consistency of reporting by radiologists and surgeons. The reports were compared to assess the predictive power of MRI/MRA. Specific assessment of rotator cuff tendon appearance, long head of biceps (LHB) tendon appearance, position and anchor, subacromial space, glenoid labrum and humeral cartilage grade were included. RESULTS: Shoulder MRA demonstrated a higher agreement with arthroscopy than MRI for supraspinatus, infraspinatus and subscapularis tendon appearance (κ = 0.77 vs. κ = 0.61, κ = 0.55 vs. κ = 0.53 and κ = 0.58 vs. κ = 0.46 respectively). There were also superior agreement rates with MRA compared to MRI for LHB tendon appearance (κ = 0.70 vs. κ =0.54) and position (κ = 0.89 vs. κ = 0.72). As an overall assessor of shoulder pathology we found significantly higher total agreement scores when MRA was used (p = 0.002). DISCUSSION: Whilst magnetic resonance imaging with arthrography is an extremely useful tool to assess underlying pathological shoulder states it does not confer 100% accuracy. In cases whereby this modality is inconclusive, an examination under anaesthesia and diagnostic arthroscopic assessment for the detection of intra-articular shoulder pathology may be considered.

A tool to evaluate proportionality and necessity in the use of restrictive practices in forensic mental health settings: the DRILL tool (Dundrum restriction, intrusion and liberty ladders).

BACKGROUND: Prevention of violence due to severe mental disorders in psychiatric hospitals may require intrusive, restrictive and coercive therapeutic practices. Research concerning appropriate use of such interventions is limited by lack of a system for description and measurement. We set out to devise and validate a tool for clinicians and secure hospitals to assess necessity and proportionality between imminent violence and restrictive practices including de-escalation, seclusion, restraint, forced medication and others. METHODS: In this retrospective observational cohort study, 28 patients on a 12 bed male admissions unit in a secure psychiatric hospital were assessed daily for six months. Data on adverse incidents were collected from case notes, incident registers and legal registers. Using the functional assessment sequence of antecedents, behaviours and consequences (A, B, C) we devised and applied a multivariate framework of structured professional assessment tools, common adverse incidents and preventive clinical interventions to develop a tool to analyse clinical practice. We validated by testing assumptions regarding the use of restrictive and intrusive practices in the prevention of violence in hospital. We aimed to provide a system for measuring contextual and individual factors contributing to adverse events and to assess whether the measured seriousness of threating and violent behaviours is proportionate to the degree of restrictive interventions used. General Estimating Equations tested preliminary models of contexts, decisions and pathways to interventions. RESULTS: A system for measuring adverse behaviours and restrictive, intrusive interventions for prevention had good internal consistency. Interventions were proportionate to seriousness of harmful behaviours. A 'Pareto' group of patients (5/28) were responsible for the majority (80%) of adverse events, outcomes and interventions. The seriousness of the precipitating events correlated with the degree of restrictions utilised to safely manage or treat such behaviours. CONCLUSION: Observational scales can be used for restrictive, intrusive or coercive practices in psychiatry even though these involve interrelated complex sequences of interactions. The DRILL tool has been validated to assess the necessity and demonstrate proportionality of restrictive practices. This tool will be of benefit to services when reviewing practices internally, for mandatory external reviewing bodies and for future clinical research paradigms.

Efficacy and safety of osilodrostat in patients with Cushing's disease (LINC 3): a multicentre phase III study with a double-blind, randomised withdrawal phase.

BACKGROUND: Cushing's disease is a rare endocrine disorder characterised by cortisol overproduction with severe complications. Therapies for cortisol reduction are often necessary. Here we report the outcomes from the pivotal phase III study of osilodrostat (a potent oral inhibitor of cytochrome P450 11B1, mitochondrial [11ß-hydroxylase]; Novartis Pharma AG, Basel, Switzerland) in patients with Cushing's disease. METHODS: LINC 3 was a prospective, multicentre, open-label, phase III study with a double-blind randomised withdrawal period, that comprised four periods. Patients aged 18-75 years, with confirmed persistent or recurrent Cushing's disease (defined as mean 24-h urinary free cortisol [UFC] concentration >1·5 times the upper limit of normal [ULN] and morning plasma adrenocorticotropic hormone above the lower limit of normal) who had previously had pituitary surgery or irradiation, or were newly diagnosed and who refused surgery or were not surgical candidates, were recruited from 66 hospital sites and private clinical practices in 19 countries. In period 1, open-label osilodrostat was initiated in all participants and adjusted every 2 weeks (1-30 mg twice daily; film-coated tablets for oral administration) on the basis of mean 24-h UFC concentration and safety until week 12. In period 2, weeks 13-24, osilodrostat was continued at the therapeutic dose determined during period 1. In period 3, beginning at week 26, participants who had a mean 24-h UFC concentration of less than or equal to the ULN at week 24, without up-titration after week 12, were randomly assigned (1:1), via an interactive-response technology, stratified by osilodrostat dose at week 24 and history of pituitary irradiation, to continue osilodrostat or switch to placebo for 8 weeks. Participants and investigators were masked to treatment assignment. Ineligible participants continued open-label osilodrostat. In period 4, weeks 35-48, all participants were given open-label osilodrostat until core-study end. The primary objective was to compare the efficacy of osilodrostat versus placebo at the end of period 3. The primary endpoint was the proportion of participants who had been randomly assigned to treatment or placebo with a complete response (ie, mean 24-h UFC concentration of ≤ULN) at the end of the randomised withdrawal period (week 34), without up-titration during this period. The key secondary endpoint was the proportion of participants with a complete response at the end of the single-arm, open-label period (ie, period 2, week 24) without up-titration during weeks 13-24. Analysis was by intention-to-treat for all patients who received at least one dose of osilodrostat (full analysis set; key secondary endpoint) or randomised treatment (randomised analysis set; primary endpoint) and safety was assessed in all enrolled patients who received at least one dose of osilodrostat and had at least one post-baseline safety assessment. LINC 3 is registered with ClinicalTrials.gov, NCT02180217, and is now complete. FINDINGS: Between Nov 12, 2014, and March 22, 2017, 202 patients were screened and 137 were enrolled. The median age was 40·0 years (31·0-49·0) and 106 (77%) participants were female. 72 (53%) participants were eligible for randomisation during the withdrawal phase, of whom 36 were assigned to continue osilodrostat and 35 were assigned to placebo; one patient was not randomly assigned due to investigator decision and continued open-label osilodrostat. More patients maintained a complete response with osilodrostat versus with placebo at week 34 (31 [86%] vs ten [29%]; odds ratio 13·7 [95% CI 3·7-53·4]; p<0·0001). At week 24, 72 (53%; 95% CI 43·9-61·1) of 137 patients maintained a complete response without up-titration after week 12. Most common adverse events (ie, occurred in >25% of participants) were nausea (57 [42%]), headache (46 [34%]), fatigue (39 [28%]), and adrenal insufficiency (38 [28%]). Hypocortisolism occurred in 70 (51%) patients and adverse events related to adrenal hormone precursors occurred in 58 (42%) patients. One patient died, unrelated to study drug, after the core study phase. INTERPRETATION: Twice-daily osilodrostat rapidly reduced mean 24-h UFC and sustained this reduction alongside improvements in clinical signs of hypercortisolism; it was also generally well tolerated. Osilodrostat is an effective new treatment option that is approved in Europe for the treatment of endogenous Cushing's syndrome and in the USA for Cushing's disease. FUNDING: Novartis Pharma AG.

SURGICAL MANAGEMENT OF TRAUMATIC MACULAR HOLE: Optical Coherence Tomography Features and Outcomes.

PURPOSE: To report the outcomes of eyes receiving surgical management for traumatic macular holes. To describe the preoperative and postoperative optical coherence tomography features of traumatic macular holes and to explore associations between preoperative clinical and optical coherence tomography features, and visual outcome. METHODS: Retrospective study of patients undergoing vitrectomy for traumatic macular hole and entered into the Australian and New Zealand Society of Retinal Specialists surgical registry. Preoperative clinical data, surgical details, and 3-month postoperative outcomes were recorded prospectively. Longer-term outcomes at 12 months were requested retrospectively, as were preoperative and postoperative optical coherence tomography scans. RESULTS: Hole closure was achieved in 91% (21/23) of patients with a single procedure. The average preoperative visual acuity was 20/120. At 3 months postoperatively, the mean visual acuity had improved to 20/70 (P < 0.001), 11/23 (48%) of eyes improved ≥15 letters, and the number of eyes with 20/40 acuity or better increased from 1/23 to 7/23. Eyes with worse visual outcomes (visual acuity < 20/80) had larger holes, worse preoperative acuity, and a greater extent of preoperative ellipsoid band attenuation than those with better postoperative visual acuity. CONCLUSION: Eyes receiving surgical management for traumatic macular hole achieved good anatomical results and approximately half had a substantial improvement in acuity. Ellipsoid band attenuation on preoperative optical coherence tomography and worse preoperative acuity were associated with poorer visual outcomes.

Rhegmatogenous retinal detachments: primary reattachment rates and visual outcomes over a 4-year period.

BACKGROUND AND AIMS: To describe rhegmatogenous retinal detachment surgery in a Dublin tertiary referral centre over a 4-year period and to examine factors predictive of surgical and anatomical success. METHODS: A retrospective study was performed by reviewing the surgical log and the charts of patients who underwent a primary retinal detachment repair in a specialist centre over a 4-year period between 2012 and 2015. We excluded exudative and tractional cases. Multiple parameters were recorded including macular status, visual acuity, type of procedure, complications and visual and anatomical outcomes at 6 months post operation. Primary reattachment rate was calculated alongside change in visual acuity. Chi-square testing and analysis of variance were utilized to determine the effect which lens status, macular status, extent of breaks and type of procedure had on outcome and visual success. RESULTS: A total of 613 primary rhegmatogenous retinal detachment repairs were performed over the 4-year period. Our primary reattachment rate was calculated to be 88.58% (annual range 85.25-91.30%) with a perioperative complication rate of 2.94%. We noted a statistical significant improvement in VA with a median logMAR VA of 1.0 at presentation to 0.5 at 6 months post procedure. Macular status (chi-square test p = 0.15, X2 = 2.072) and lens status (chi-square test p = 0.2974, X2 = 1.086) had no statistical effect on the final anatomical outcome. However, eyes with giant retinal tears were more likely to redetach than those without (chi-square test p = 0.0069, X2 = 7.3). There was no statistical significant difference in the proportion of eyes achieving visual success by surgery category (one-way ANOVA analysis p = 0.501). CONCLUSIONS: This is the first study of its kind in Ireland and will help surgeons benchmark their results against international standards in the future. Accurate recording of logMAR acuity and intraoperative complications is imperative to assist with prospective studies.

MANAGEMENT OF GIANT RETINAL TEARS USING TRANSSCLERAL DIODE LASER RETINOPEXY AND SHORT-TERM POSTOPERATIVE TAMPONADE WITH PERFLUORO-N-OCTANE.

PURPOSE: To determine the results of pars plana vitrectomy for giant retinal tear detachments using transscleral diode laser retinopexy and short-term postoperative tamponade with perfluoro-n-octane (PFnO). METHODS: Twenty consecutive patients with fresh giant retinal tears were enrolled in a single-arm prospective study. One case was withdrawn for technical reasons. The remainder all underwent pars plana vitrectomy, PFnO injection, transscleral diode laser retinopexy to the edge of the giant retinal tear, and short-term postoperative heavy liquid tamponade. None of the cases had scleral buckling or lensectomy. RESULTS: Nineteen cases (18 male and 1 female) with a mean age of 41 years (range 10-69 years) were followed up for a period of 6 months. Postoperative tamponade with PFnO was maintained for a mean of 7.6 days (range 4-21 days), after which it was exchanged for sulfur hexafluoride (SF6), perfluoropropane (C3F8) gas, or balanced salt solution. Final reattachment rate was 100%, with 3 (15.7%) patients requiring additional surgery. Best-corrected visual acuity at final follow-up was 20/40 or better in 11 eyes (58%), between 20/60 and 20/200 in 7 (37%), and 20/400 in 1 (5%). CONCLUSION: In this series of acute giant retinal tears, transscleral diode laser retinopexy together with the use of PFnO for short-term postoperative tamponade achieved excellent anatomical and visual results.

A terrestrial gamma-ray flash and ionospheric ultraviolet emissions powered by lightning.

Terrestrial gamma-ray flashes (TGFs) are transient gamma-ray emissions from thunderstorms, generated by electrons accelerated to relativistic energies in electric fields. Elves are ultraviolet and optical emissions excited in the lower ionosphere by electromagnetic waves radiated from lightning current pulses. We observed a TGF and an associated elve using the Atmosphere-Space Interactions Monitor on the International Space Station. The TGF occurred at the onset of a lightning current pulse that generated an elve, in the early stage of a lightning flash. Our measurements suggest that the current onset is fast and has a high amplitude-a prerequisite for elves-and that the TGF is generated in the electric fields associated with the lightning leader.