Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Effects of Aging on Intrinsic Protein Disorder in Human Lenses and Zonules

This study aims to compare the levels of intrinsic protein disorder within the human lens and zonule proteomes and investigate the role of aging as a potential influencing factor on disorder levels. A cross-sectional proteomic analysis was employed, utilizing a dataset of 1466 proteins derived from the lens and zonule proteomes previously published by Wang et al. and De Maria et al. Bioinformatics tools, including a composition profiler and a rapid intrinsic disorder analysis online tool, were used to conduct a comparative analysis of protein disorder. Statistical tests such as ANOVA, Tukey's HSD, and chi-squared tests were applied to evaluate differences between groups. The study revealed distinct amino acid compositions for each proteome, showing a direct correlation between aging and increased protein disorder in the zonular proteomes, whereas the lens proteomes exhibited the opposite trend. Findings suggest that age-related changes in intrinsic protein disorder within the lens and zonule proteomes may be linked to structural transformations in these tissues. Understanding how protein disorder evolves with age could enhance knowledge of the molecular basis for age-related conditions such as cataracts and pseudoexfoliation, potentially leading to better therapeutic strategies.This study aims to compare the levels of intrinsic protein disorder within the human lens and zonule proteomes and investigate the role of aging as a potential influencing factor on disorder levels. A cross-sectional proteomic analysis was employed, utilizing a dataset of 1466 proteins derived from the lens and zonule proteomes previously published by Wang et al. and De Maria et al. Bioinformatics tools, including a composition profiler and a rapid intrinsic disorder analysis online tool, were used to conduct a comparative analysis of protein disorder. Statistical tests such as ANOVA, Tukey's HSD, and chi-squared tests were applied to evaluate differences between groups. The study revealed distinct amino acid compositions for each proteome, showing a direct correlation between aging and increased protein disorder in the zonular proteomes, whereas the lens proteomes exhibited the opposite trend. Findings suggest that age-related changes in intrinsic protein disorder within the lens and zonule proteomes may be linked to structural transformations in these tissues. Understanding how protein disorder evolves with age could enhance knowledge of the molecular basis for age-related conditions such as cataracts and pseudoexfoliation, potentially leading to better therapeutic strategies

Post-Radiation Cataract Management: Outcomes in Individuals with Uveal Melanoma

Purpose of review To report the visual, clinical, and surgical outcomes of cataractsurgery following radiation therapy for uveal melanoma (UM) while reviewing theavailable literature discussing these outcomes. Recent Findings Patients were managed with cataractsurgery after radiation for UM at the Bascom Palmer Eye Institute, betweenJanuary 2014 and February 2021, with a minimum follow-up of 6 months. Only theradiated eye was included. Measured outcomes included BCVA (1ogMAR), and OCTmeasurement of macular thickness at 1, 3, 6, and 12 months postoperatively.Paired t-tests were used to compare pre- and postoperative variables.Forty-seven eyes from 47 patients were included. Their mean age was 67.0 +/- 11.0years old; 24 (51%) were male. Preoperatively, 21 (44.6%) had radiationinducedmaculopathy, 8 (17%) exudative retinal detachment, and 4 (8.5%) iris synechiae.Cataract types included nuclear sclerosis (80.8%), posterior subcapsular(55.3%), cortical sclerosis (19.1%), and mixed-type (55.3%). Intraoperativeevents reported were synechialysis (4.2%), floppy iris syndrome (IFIS) (2.1%),sub-tenon's corticosteroid injections (31.9%), and bevacizumab (21.2%). Therewere no complications. There was a significant improvement in best correctedvisual acuity (BCVA) at the 1st month postoperatively (0.68), and up until thel2th month postoperatively (0.71) compared to baseline (1.14, p < 0.01). OCTmeasurements of the macular thickness showed a significant increase (363 um)during the 6th postoperative month compared to baseline (327 um; p < 0.01). Summary Cataract surgery is safe and effectivein improving visual acuity in individuals with post-radiation cataracts. Routine macular thickness monitoring should be considered in order to optimizetheir visual outcome. In the treatment of these patients, a multidisciplinaryapproach and proper surgical planning are essential, with a focus on early,aggressive antiinflammatory and anti-VEGF therapy. Setting Bascom Palmer Eye Institute, USA. Design Retrospective chart review. Methods Patients were managed with cataract surgery after radiation for UM at the Bascom Palmer Eye Institute, between January 2014 and February 2021, with a minimum follow-up of 6 months. Only the radiated eye was included. Measured outcomes included BCVA (logMAR) and OCT measurement of macular thickness at 1, 3, 6, and 12 months postoperatively. Paired t-tests were used to compare pre and postoperative variables. Results Forty-seven eyes from 47 patients were included. Their mean age was 67.0 +/- 11.0 years old; 24 (51%) were male. Preoperatively, 21 (44.6%) had radiation-induced maculopathy, 8 (17%) exudative retinal detachment, and 4 (8.5%) iris synechiae. Cataract types included nuclear sclerosis (80.8%), posterior subcapsular (55.3%), cortical sclerosis (19.1%), and mixed-type (55.3%). Intraoperative events reported were synechialysis (4.2%), floppy iris syndrome (IFIS) (2.1%), subtenon's corticosteroid injections (31.9%), and bevacizumab (21.2%). There were no complications. There was a significant improvement in best corrected visual acuity (BCVA) at the 1st month postoperatively (0.68) and up until the 12th month postoperatively (0.71) compared to baseline (1.14, p < 0.01). OCT measurements of the macular thickness showed a significant increase (363 mu m) during the 6th postoperative month compared to baseline (327 mu m; p < 0.01). Conclusion Cataract surgery is safe and effective in improving visual acuity in individuals with post-radiation cataracts. A multi-disciplinary approach, proper surgical planning, and postoperative anti-inflammatory care are paramount in the management of these individuals

Corneal Toxicity Associated With Aquarium Coral Palytoxin

To report a series of patients who developed corneal toxicity after exposure to aquarium coral palytoxin. Multicenter retrospective case series. Retrospective review. Seven patients presented with corneal findings ranging from superficial punctate epitheliopathy to bilateral corneal melt with subsequent perforation. Among those with mild corneal findings, resolution was achieved with topical steroids and lubrication, whereas some patients who developed progressive corneal melt required therapeutic penetrating keratoplasty. The history in all patients revealed exposure to aquarium zoanthid corals shortly before disease onset. A review of the literature revealed that there are few prior reports of coral-associated corneal toxicity and that some species of coral secrete a substance known as palytoxin, a potent vasoconstrictor that inhibits the membranous sodium-potassium ATPase pump across cell types and can cause rapid death if inhaled or ingested. This is the largest case series to date demonstrating patients with aquarium coral palytoxin-associated corneal toxicity, and is the first to provide details of related histopathologic findings. Similar to other forms of toxic keratoconjunctivitis, a detailed history and careful clinical assessment are required, as well as timely removal of the offending agent from the patients' ocular milieu and environment. Mild ocular surface and corneal disease may be treated effectively with aggressive topical steroid therapy and lubrication. Given the potential severity of ocular as well as systemic adverse effects, there should be increased awareness of this entity among eye care professionals, aquarium enthusiasts, and the general public

ILC Reference Design Report Volume 1 - Executive Summary

The International Linear Collider (ILC) is a 200-500 GeV center-of-mass high-luminosity linear electron-positron collider, based on 1.3 GHz superconducting radio-frequency (SCRF) accelerating cavities. The ILC has a total footprint of about 31 km and is designed for a peak luminosity of 2x10^34 cm^-2s^-1. This report is the Executive Summary (Volume I) of the four volume Reference Design Report. It gives an overview of the physics at the ILC, the accelerator design and value estimate, the detector concepts, and the next steps towards project realization.The International Linear Collider (ILC) is a 200-500 GeV center-of-mass high-luminosity linear electron-positron collider, based on 1.3 GHz superconducting radio-frequency (SCRF) accelerating cavities. The ILC has a total footprint of about 31 km and is designed for a peak luminosity of 2x10^34 cm^-2s^-1. This report is the Executive Summary (Volume I) of the four volume Reference Design Report. It gives an overview of the physics at the ILC, the accelerator design and value estimate, the detector concepts, and the next steps towards project realization

ILC Reference Design Report Volume 4 - Detectors

This report, Volume IV of the International Linear Collider Reference Design Report, describes the detectors which will record and measure the charged and neutral particles produced in the ILC's high energy e+e- collisions. The physics of the ILC, and the environment of the machine-detector interface, pose new challenges for detector design. Several conceptual designs for the detector promise the needed performance, and ongoing detector R&D is addressing the outstanding technological issues. Two such detectors, operating in push-pull mode, perfectly instrument the ILC interaction region, and access the full potential of ILC physics.This report, Volume IV of the International Linear Collider Reference Design Report, describes the detectors which will record and measure the charged and neutral particles produced in the ILC's high energy e+e- collisions. The physics of the ILC, and the environment of the machine-detector interface, pose new challenges for detector design. Several conceptual designs for the detector promise the needed performance, and ongoing detector R&D is addressing the outstanding technological issues. Two such detectors, operating in push-pull mode, perfectly instrument the ILC interaction region, and access the full potential of ILC physics

ILC Reference Design Report Volume 3 - Accelerator

The International Linear Collider (ILC) is a 200-500 GeV center-of-mass high-luminosity linear electron-positron collider, based on 1.3 GHz superconducting radio-frequency (SCRF) accelerating cavities. The ILC has a total footprint of about 31 km and is designed for a peak luminosity of 2x10^34 cm^-2 s^-1. The complex includes a polarized electron source, an undulator-based positron source, two 6.7 km circumference damping rings, two-stage bunch compressors, two 11 km long main linacs and a 4.5 km long beam delivery system. This report is Volume III (Accelerator) of the four volume Reference Design Report, which describes the design and cost of the ILC.The International Linear Collider (ILC) is a 200-500 GeV center-of-mass high-luminosity linear electron-positron collider, based on 1.3 GHz superconducting radio-frequency (SCRF) accelerating cavities. The ILC has a total footprint of about 31 km and is designed for a peak luminosity of 2x10^34 cm^-2 s^-1. The complex includes a polarized electron source, an undulator-based positron source, two 6.7 km circumference damping rings, two-stage bunch compressors, two 11 km long main linacs and a 4.5 km long beam delivery system. This report is Volume III (Accelerator) of the four volume Reference Design Report, which describes the design and cost of the ILC

International Linear Collider Reference Design Report Volume 2: PHYSICS AT THE ILC

This article reviews the physics case for the ILC. Baseline running at 500 GeV as well as possible upgrades and options are discussed. The opportunities on Standard Model physics, Higgs physics, Supersymmetry and alternative theories beyond the Standard Model are described.This article reviews the physics case for the ILC. Baseline running at 500 GeV as well as possible upgrades and options are discussed. The opportunities on Standard Model physics, Higgs physics, Supersymmetry and alternative theories beyond the Standard Model are described