Multimodal Structural and Functional Characterization of Retinal Vasculopathy with Cerebral Leukoencephalopathy.

OBJECTIVE: To describe and quantify the structural and functional consequences of retinal vasculopathy with cerebral leukoencephalopathy (RVCL) on the neurosensory retina. DESIGN: Cross sectional descriptive study from December 2021 to December 2022. PARTICIPANTS: Retinal vasculopathy with cerebral leukoencephalopathy patients (n = 9, 18 eyes) recruited from the RVCL Research Center at Washington University in St. Louis. METHODS: Retinal vasculopathy with cerebral leukoencephalopathy patients underwent comprehensive ophthalmological evaluation including OCT, OCT angiography (OCTA), ultrawidefield fundus imaging, retinal autofluorescence, dark adaptation, electroretinography (ERG), Goldmann kinetic perimetry, and fluorescein angiography (FA). MAIN OUTCOME MEASURES: Comprehensive characterization from various modalities including best-corrected visual acuity, central subfield thickness (µm) from OCT, foveal avascular zone (mm2) from OCTA, dark adaptation rod intercept (seconds), cone response in ERG, and presence or absence of vascular abnormalities, leakage, neovascularization, and nonperfusion on FA. RESULTS: A total of 18 eyes from 9 individuals were included in this study. The best-corrected visual acuity ranged from 20/15 to 20/70. The mean central subfield thickness from OCT was 275.8 µm (range, 217-488 µm). The mean foveal avascular zone (FAZ) from OCTA was 0.65 (range, 0.18-1.76) mm2. On dark adaptometry, the mean time was 5.02 (range, 2.9-6.5) minutes, and 1 individual had impaired dark adaptation. Electroretinography demonstrated mild cone response impairment in 4 eyes. On FA, there was evidence of macular and peripheral capillary nonperfusion in 16 of 18 eyes and notable areas of vascular leakage and retinal edema in 5 of the 18 eyes. CONCLUSIONS: This study illustrates the phenotypic spectrum of disease and may be clinically valuable for aiding diagnosis, monitoring disease progression, and further elucidating the pathophysiology of RVCL to aid in the development of therapies. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Severe Spontaneous Tilt of Scleral-Fixated Intraocular Lenses.

PURPOSE: To report and evaluate a multicenter series of 18 cases of severe, spontaneous IOL tilt involving the flanged intrascleral haptic fixation technique (FISHF). DESIGN: Clinical study with historical controls. METHODS: We report a cross-sectional study of 46 FISHF cases using the CT Lucia 602 IOL at a single academic center over a period of 24 weeks to determine the incidence of severe rotisserie-style rotational tilt. These rates were then compared with the same time-frame the prior year to help determine if this is a new phenomenon. Additional cases of severe tilt were solicited from another 4 academic centers. RESULTS: Among 46 FISHF cases at a single center, 5 developed severe tilt. No clear pattern in surgical technique, ocular history, or ocular anatomy was evident in these cases compared with controls, although the involved IOLs clustered within a narrow diopter range, indicative of a batch effect. In the same 24-week interval the year before, 33 FISHF cases were performed, none of which exhibited severe rotational tilt. In our multicenter dataset, 18 cases of tilt were identified. Surgeons included fellow and early-career physicians as well as surgeons with multiple years of experience with the Yamane technique. A variety of surgical approaches for FISHF were represented. In at least 8 of the cases, haptic rotation and/or dehiscence at the optic-haptic junction were documented. CONCLUSIONS: The identification of haptic rotation and dehiscence intraoperatively in several cases may reflect a new stability issue involving the optic-haptic junction.

Assessing the Clinical Requirement of 2.5% Phenylephrine for Diagnostic Pupil Examination.

Purpose: To evaluate whether the standard dilating drop regimen consisting of phenylephrine, tropicamide, and proparacaine produces clinically significant improvement in pupil size compared to tropicamide and proparacaine during diagnostic eye examination. Methods: Sixty-three adult patients at Washington University School of Medicine Eye Clinic were enrolled in this prospective, randomized trial. Each patient received one of two dilating drop regimens: phenylephrine + tropicamide + proparacaine (PE+T+PP), which is considered the standard therapy, or tropicamide + proparacaine (T+PP). Main outcome measures were the proportion of pupils able to achieve successful clinical examination without need for additional dilating drops and change in predilation to postdilation pupil size. Comparisons were made using McNemar's test, repeated measures analysis of variance, and Fisher's test to determine whether PE is a necessary component of the standard eye examination. Results: There were no statistically significant differences between the PE+T+PP and T+PE treatment groups in predilation to postdilation changes in average resting pupil size (1.58 ± 0.66 and 2.61 ± 0.79; P = 0.57) or constricted pupil size (2.52 ± 0.93 and 3.56 ± 0.96; P = 0.15). There was no statistically significant difference between patients who obtained a successful dilated pupil examination between those receiving PE+T+PP and those receiving T+PP as determined by the examining physicians (Fisher's, P = 0.67). Conclusion: The addition of phenylephrine to tropicamide and proparacaine did not improve pupillary dilation size or ability to conduct a clinical examination. A single dilating agent using tropicamide should be considered in clinical practice.

Plasmapheresis for Management of Antiphospholipid Syndrome in the Neurosurgical Patient.

BACKGROUND AND IMPORTANCE: Antiphospholipid syndrome (APS) is an autoimmune disorder associated with a hypercoagulable state and increased risk of intraoperative and postoperative thrombosis. Few neurosurgical studies have examined the management of these patients, though the standard of care in most other disciplines involves the use of anticoagulation therapy. However, this is associated with risks such as hemorrhage, thrombosis due to warfarin withdrawal, and is not compatible with operative intervention. CLINICAL PRESENTATION: We report the cases of 2 antiphospholipid positive patients who were on anticoagulant therapy and underwent surgical bypasses and received perioperative management with plasmapheresis. The first was a 44-yr-old woman who presented with worsening vision, recurring headaches, and a known left internal carotid artery aneurysm that was unsuccessfully treated twice via extracranial to intracranial (ECIC) bypass at another institution. Preoperative tests at our institution revealed elevated beta 2 glycoprotein 1 IgA autoantibodies. The second case was a 24-yr-old woman with previously diagnosed APS, who presented for surgical evaluation of moyamoya disease after sustaining recurrent left hemispheric strokes. Both cases were managed with perioperative plasmapheresis to avoid the need for anticoagulation during the perioperative period, and both underwent successful ECIC bypass procedures without perioperative ischemic or hemorrhagic complications. CONCLUSION: Management of neurosurgical patients with APS can be a precarious proposition. We describe the successful use of plasmapheresis and antiplatelet therapy to better manage patients undergoing neurosurgical procedures, specifically ECIC bypass, and feel this approach can be considered in future cases.

The relationship of cortical folding and brain arteriovenous malformations.

BACKGROUND: The pathogenesis of human intracranial arteriovenous malformations (AVMs) is not well understood; this study aims to quantitatively assess cortical folding in patients with these lesions. METHODS: Seven adult participants, 4 male and 3 female, with unruptured, surgically unresectable intracranial AVMs were prospectively enrolled in the study, with a mean age of 42.1 years and Spetzler-Martin grade range of II-IV. High-resolution brain MRI T1 and T2 sequences were obtained. After standard preprocessing, segmentation and registration techniques, three measures of cortical folding, the depth difference index (DDI), coordinate distance index (CDI) and gyrification index (GI)), were calculated for the affected and unaffected hemispheres of each subject as well as a healthy control subject set. RESULTS: Of the three metrics, CDI, DDI and GI, used for cortical folding assessment, none demonstrated significant differences between the participants and previously studied healthy adults. There was a significant negative correlation between the DDI ratio between affected and unaffected hemispheres and AVM volume (correlation coefficient r = -0.74, p = 0.04). CONCLUSION: This study is the first to quantitatively assess human brain cortical folding in the presence of intracranial AVMs and no significant differences between AVM-affected versus unaffected hemispheres were found in a small dataset. We suggest longitudinal, larger human MRI-based cortical folding studies to assess whether AVMs are congenital lesions of vascular development or de novo, dynamic lesions.

Characterization of complications associated with open and endoscopic craniosynostosis surgery at a single institution.

OBJECT The authors present a retrospective cohort study examining complications in patients undergoing surgery for craniosynostosis using both minimally invasive endoscopic and open approaches. METHODS Over the past 10 years, 295 nonsyndromic patients (140 undergoing endoscopic procedures and 155 undergoing open procedures) and 33 syndromic patients (endoscopic procedures in 10 and open procedures in 23) met the authors' criteria. Variables analyzed included age at surgery, presence of a preexisting CSF shunt, skin incision method, estimated blood loss, transfusions of packed red blood cells, use of intravenous steroids or tranexamic acid, intraoperative durotomies, procedure length, and length of hospital stay. Complications were classified as either surgically or medically related. RESULTS In the nonsyndromic endoscopic group, the authors experienced 3 (2.1%) surgical and 5 (3.6%) medical complications. In the nonsyndromic open group, there were 2 (1.3%) surgical and 7 (4.5%) medical complications. Intraoperative durotomies occurred in 5 (3.6%) endoscopic and 12 (7.8%) open cases, were repaired primarily, and did not result in reoperations for CSF leakage. Similar complication rates were seen in syndromic cases. There was no death or permanent morbidity. Additionally, endoscopic procedures were associated with significantly decreased estimated blood loss, transfusions, procedure length, and length of hospital stay compared with open procedures. CONCLUSIONS Rates of intraoperative durotomies and surgical and medical complications were comparable between endoscopic and open techniques. This is the largest direct comparison to date between endoscopic and open interventions for synostosis, and the results are in agreement with previous series that endoscopic surgery confers distinct advantages over open surgery in appropriate patient populations.

Spermine detection via metal-mediated ethynylarene 'turn-on' fluorescence signaling.

A dicarboxylated ethynylarene was shown to behave as a fluorescent chemosensor for millimolar concentrations of polyamines when mixed with Cd(II), Pb(II) or Zn(II) ions at micromolar concentrations. A bathochromic shift and intensification of fluorescence emission was observed with increasing amounts of metal ion in the presence of aqueous polyamines buffered at pH = 7.6. Such perturbations manifested as 'turn-on' signals from a ratiometric comparison of emission intensities at 390 nm versus 340 nm. Using Pb(II) as the metal mediator, spermine was selectively detected as a 40-fold signal enhancement relative to spermidine, putrescine, cadaverine and several other non-biogenic diamines. Evaluation of additional triamine and tetraamine analytes showed the influence that amine group quantity and spacing had on signal generation. By increasing the ratio of Pb(II) relative to ethynylarene, the detection limit for spermine was successfully lowered to a 25 micromolar level. Noncovalent association between ethynylarene, metal ion and polyamine are believed to promote the observed spectroscopic changes. This study exploits the subtle impact that polyamine structural identity has on transition metal chelation to define a new approach towards polyamine chemosensor development.

Dicarboxylated ethynylarenes as buffer-dependent chemosensors for Cd(II), Pb(II) and Zn(II).

Two dicarboxylated ethynylarenes were prepared efficiently from condensation of 1,3-bis(3-aminoph enylethynyl)benzene with two equivalents of either succinic anhydride or glutaric anhydride. These compounds behave as fluorescent chemosensors selective for Cd(II), Pb(II) and Zn(II) cations under buffered aqueous conditions, with analyte binding observed as bathochromically shifted, intensified fluorescence. It was noteworthy that the fluorescence responses varied significantly with buffer identity. A conformational restriction mechanism involving reversible interactions between the fluorophore, metal cation and buffer itself is proposed.