Improvement in Both Primary and Eccentric Ocular Alignment After Thyroid Eye Disease-Strabismus Surgery With Tenon's Recession.

PURPOSE: To evaluate the improvement in primary and eccentric gaze ocular alignment in thyroid eye disease (TED) patients undergoing horizontal strabismus surgery with Tenon's recession. METHODS: This is an Institutional Review Board-approved retrospective analysis of TED patients undergoing horizontal strabismus surgery for esotropia. The study included all patients from 2007 to 2016 operated on by a single surgeon at Columbia University Medical Center. Surgical success was defined as the ability to fuse at both near and distance either without prismatic correction or with less than 10 prism diopters (PD) of correction. Measurements of ocular alignment were also made in eccentric fields of gaze. This study was Health Insurance Portability and Accountability Act compliant with protection of individually identifiable information. RESULTS: Thirty-eight patients with TED and restrictive horizontal strabismus underwent unilateral or bilateral medial rectus recession to relieve diplopia. All patients underwent Tenon's recession with dissection of Tenon's from the overlying conjunctiva permitting it to retract into the orbit. Overall the success rate was 87% with a reoperation rate of 7.9%. The improvement in horizontal deviation in both primary and eccentric gaze was statistically significant (p < 0.001). The change in vertical deviation in the 5 cardinal positions of gaze was not statistically significant. The postoperative change in vertical deviation was not proportional to the preoperative horizontal deviation or the amount of horizontal recession. CONCLUSIONS: Due to the preoperative incomitance of ocular deviations in TED patients, persistent postoperative eccentric misalignment is expected. The addition of Tenon's recession to TED-horizontal strabismus surgery led to statistically significant improvement in ocular alignment in both primary and eccentric gaze. This is the first study of TED-strabismus surgery to analyze the postoperative results in positions outside of primary and reading gaze. The authors postulate that the release of scar tissue by the addition of Tenon's recession contributes to these improvements.

High-energy, kHz, picosecond hybrid Yb-doped chirped-pulse amplifier.

We report on a diode-pumped, hybrid Yb-doped chirped-pulse amplification (CPA) laser system with a compact pulse stretcher and compressor, consisting of Yb-doped fiber preamplifiers, a room-temperature Yb:KYW regenerative amplifier (RGA), and cryogenic Yb:YAG multi-pass amplifiers. The RGA provides a relatively broad amplification bandwidth and thereby a long pulse duration to mitigate B-integral in the CPA chain. The ~1030-nm laser pulses are amplified up to 70 mJ at 1-kHz repetition rate, currently limited by available optics apertures, and then compressed to ~6 ps with high efficiency. The near-diffraction-limited beam focusing quality is demonstrated with M(x)(2) = 1.1 and M(y)(2) = 1.2. The shot-to-shot energy fluctuation is as low as ~1% (rms), and the long-term energy drift and beam pointing stability for over 8 hours measurement are ~3.5% and <6 µrad (rms), respectively. To the best of our knowledge, this hybrid laser system produces the most energetic picosecond pulses at kHz repetition rates among rod-type laser amplifiers. With an optically synchronized Ti:sapphire seed laser, it provides a versatile platform optimized for pumping optical parametric chirped-pulse amplification systems as well as driving inverse Compton scattered X-rays.

Three-octave-spanning supercontinuum generation and sub-two-cycle self-compression of mid-infrared filaments in dielectrics.

We experimentally and numerically investigate the spectral and temporal structure of mid-infrared (mid-IR) filaments in bulk dielectrics with normal and anomalous group velocity dispersion (GVD) pumped by a 2.1 µm optical parametric chirped-pulse amplifier (OPCPA). The formation of stable and robust filaments with several microjoules of pulse energy is observed. We demonstrate a supercontinuum that spans more than three octaves from ZnS in the normal GVD regime and self-compression of the mid-IR pulse to sub-two-cycle duration in CaF2 in the anomalous GVD regime. The experimental observations quantitatively agree well with the numerical simulations based on a three-dimensional nonlinear wave equation that reveals the detailed spatio-temporal dynamics of mid-IR filaments in dielectrics.

Multi-mJ, kHz, ps deep-ultraviolet source.

We demonstrate a 0.56-GW, 1-kHz, 4.2-ps, 2.74-mJ deep-ultraviolet (DUV) laser at ∼257.7 nm with a beam propagation factor (M2) of ∼2.54 from a frequency-quadrupled cryogenic multi-stage Yb-doped chirped-pulse amplifier. The frequency quadrupling is achieved using LiB3O5 and ß-BaB2O4 crystals for near-infrared (NIR)-to-green and green-to-DUV conversion, respectively. An overall NIR-to-DUV efficiency of ∼10% has been achieved, which is currently limited by the thermal-induced phase mismatching and the DUV-induced degradation of transmittance. To the best of our knowledge, this is the highest peak-power picosecond DUV source from a diode-pumped solid-state laser operating at kHz repetition rates.

Generation of Bright, Spatially Coherent Soft X-Ray High Harmonics in a Hollow Waveguide Using Two-Color Synthesized Laser Pulses.

We investigate the efficient generation of low-divergence high-order harmonics driven by waveform-optimized laser pulses in a gas-filled hollow waveguide. The drive waveform is obtained by synthesizing two-color laser pulses, optimized such that highest harmonic yields are emitted from each atom. Optimization of the gas pressure and waveguide configuration has enabled us to produce bright and spatially coherent harmonics extending from the extreme ultraviolet to soft x rays. Our study on the interplay among waveguide mode, atomic dispersion, and plasma effect uncovers how dynamic phase matching is accomplished and how an optimized waveform is maintained when optimal waveguide parameters (radius and length) and gas pressure are identified. Our analysis should help laboratory development in the generation of high-flux bright coherent soft x rays as tabletop light sources for applications.

Multi-mJ, kHz, 2.1 µm optical parametric chirped-pulse amplifier and high-flux soft x-ray high-harmonic generation.

We report on a multi-mJ 2.1 µm optical parametric chirped-pulse amplification (OPCPA) system operating at 1 kHz repetition rate, pumped by a picosecond cryogenic Yb:YAG laser, and the demonstration of soft x-ray high-harmonic generation (HHG) with a flux of ∼2×10(8) photon/s/1% bandwidth at 160 eV in Ar. The 1 kHz cryogenic Yb:YAG pump laser amplifies pulses up to 56 mJ and delivers compressed 42 mJ, 17 ps pulses to the 2.1 µm OPCPA system. In the three-stage OPCPA chain, we have obtained up to 2.6 mJ of output energies at 2.1 µm and pulses compressed to 40 fs with good beam quality. Finally, we show cut-off extension of HHG driven by this 2.1 µm source in Ar and N2 gas cells to 190 eV with high photon flux. Our 3D propagation simulation confirms the generation of soft x-ray attosecond pulses from the experiment with Ar.

Preventing recurrence in Sonic Hedgehog Subgroup Medulloblastoma using the OLIG2 inhibitor CT-179.

Recurrence is the primary life-threatening complication for medulloblastoma (MB). In Sonic Hedgehog (SHH)-subgroup MB, OLIG2-expressing tumor stem cells drive recurrence. We investigated the anti-tumor potential of the small-molecule OLIG2 inhibitor CT-179, using SHH-MB patient-derived organoids, patient-derived xenograft (PDX) tumors and mice genetically-engineered to develop SHH-MB. CT-179 disrupted OLIG2 dimerization, DNA binding and phosphorylation and altered tumor cell cycle kinetics in vitro and in vivo, increasing differentiation and apoptosis. CT-179 increased survival time in GEMM and PDX models of SHH-MB, and potentiated radiotherapy in both organoid and mouse models, delaying post-radiation recurrence. Single cell transcriptomic studies (scRNA-seq) confirmed that CT-179 increased differentiation and showed that tumors up-regulated Cdk4 post-treatment. Consistent with increased CDK4 mediating CT-179 resistance, CT-179 combined with CDK4/6 inhibitor palbociclib delayed recurrence compared to either single-agent. These data show that targeting treatment-resistant MB stem cell populations by adding the OLIG2 inhibitor CT-179 to initial MB treatment can reduce recurrence.

Ophthalmology Patient Perceptions of Open Payments Information.

Importance: Since 2014, medical industry payment data to physicians have been public via the Open Payments database. Patient opinions regarding these data help us to understand concerns and policymakers to improve reporting mechanisms for such payments. Objective: To assess patient perceptions of Open Payments information. Design, Setting, and Participants: This cross-sectional, questionnaire-based study was conducted in 3 ophthalmology clinic sites of an academic institution in Manhattan, New York City, New York. All patients older than 18 years who were waiting for appointments were eligible. Data were collected from January to June 2016 and analyzed from June to September 2016. Exposures: Participants answered 27 questions about the Open Payments database in English or Spanish. Demographic information was also collected. Main Outcomes and Measures: Key questionnaire results included patient awareness of the Open Payments database and perceptions of physicians' financial relationships. Cronbach α validation of the survey was performed, and Poisson multivariable regression analysis was performed to evaluate the association between patient characteristics and responses. Results: A total of 407 individuals participated. The mean (SD) age of study participants was 58.8 (17.9) years, and 220 (54.2%) were women. Of these, 30 (7.3% [95% CI, 5.1%-19.4%]) were aware of the Open Payments database, and 109 (26.8% [95% CI, 24.8%-34.0%]) planned to access it. More than half (n = 212; 53.5% [95% CI, 48.6%-58.5%]) wanted to know if their physician receives industry payments. Regarding payments of any kind valuing $100, 161 (41.9% [95% CI, 37.0%-46.9%]) disapproved. Similarly, 178 (45.8% [95% CI, 40.8%-50.7%]) disapproved of $500 payments, and 221 (57.0% [95% CI, 52.0%-61.9%]) disapproved of $25 000 payments. Poisson multivariable regression analysis demonstrated that participants who took the survey in Spanish were 38% more likely to approve of physicians receiving payments than were those who took the survey in English (incidence rate ratio [IRR], 1.38 [95% CI, 1.19-1.59]; P < .001). For every 1 year of age, the likelihood of approval for a physician receiving payments decreased by 1% (IRR, 0.995 [95% CI, 0.99-1.00]; P = .007). Participants with graduate degrees were 20% less likely to approve of physicians receiving payments, compared with those with less than a high school degree (IRR, 0.80 [95% CI, 0.66-0.97]; P = .02). Conclusions and Relevance: If the survey is validated, and if these results are generalizable outside of the 3 academic centers in ophthalmology surveyed, the findings suggest that many patients disapprove of physicians receiving payments from industry. However, few patients had accessed the Open Payments database or planned to access it. Further investigation is required to determine if these results can be generalized for other settings.

SURGICAL TREATMENT OF A MACULAR HOLE IN X-LINKED RETINOSCHISIS.

PURPOSE: To report a case of full-thickness macular hole in a patient with X-linked retinoschisis and the outcome after surgical repair. METHODS: A 15-year-old boy with a history of X-linked retinoschisis presented to his ophthalmologist for routine follow-up and was found to have a Stage-3 macular hole in his left eye. His vision was 20/200. The patient underwent pars plana vitrectomy and internal limiting membrane peeling, and he received long-acting gas. Color fundus photography and spectral domain optical coherence tomography (Cirrus; Carl Zeiss Meditech Inc, Dublin, CA) recorded images at office visits, before and after surgical repair. RESULTS: The initial spectral domain optical coherence tomography of the left eye showed a full-thickness macular hole of 1,370 µm in diameter as well as schisis cavities in the macula. After pars plana vitrectomy and repeat fluid-gas exchange, the hole was closed at the sixth-week follow-up visit. The patient noted a subjective decrease in the size of a central scotoma. Best-corrected visual acuity returned to the baseline of 20/80. CONCLUSION: A large full-thickness macular hole can develop in X-linked retinoschisis, and pars plana vitrectomy with internal limiting membrane peeling may be helpful for successful surgical closure.

Vitrectomy for macular hole following Nd:YAG laser injury.

The Q-switched Nd:YAG laser can cause significant ocular injury, because it can emit an invisible and powerful load of energy in a short period of time. One of these injuries is macular hole formation. We report the case of a 21-year-old woman who presented with acute floaters in her left eye after exposure to a Q-switched Nd:YAG laser. Her initial best-corrected visual acuity (BCVA) in the left eye was 20/80. Examination demonstrated an acute vitreous hemorrhage, and spectral-domain optical coherence tomography (SD-OCT) confirmed a full-thickness macular hole (FTMH). Four months after her injury, her BCVA deteriorated to 20/400, and she underwent vitrectomy, internal limiting membrane peeling, and gas injection. Three weeks following the procedure, her FTMH was closed, however, her BCVA remained 20/150. At her last office visit, 19 months after the surgery, the examination was unchanged. There are few reports of vitrectomy to close an FTMH after Nd:YAG laser exposure, and the factors that contribute to visual recovery remain unclear. The aim of this case report is to emphasize the importance of early diagnosis and surgical repair, and to review the literature and surgical outcomes of cases of Nd:YAG laser-induced macular holes. Imaging with SD-OCT was essential in evaluating the visual outcome, as it was dependent on the degree of photoreceptor and retinal pigment epithelium injury.

Survey of pharmacy involvement in hospital medication reconciliation programs across the United States.

OBJECTIVE: The objective of this study is to conduct a review of pertinent literature, assess pharmacy involvement in medication reconciliation, and offer insight into best practices for hospitals to implement and enhance their medication reconciliation programs. METHOD: Pharmacists in hospitals nationwide were asked to complete an anonymous survey via the American College of Clinical Pharmacy online database. The multiple choice survey analyzed the roles that healthcare professionals play in medication reconciliation programs at hospitals. RESULTS: Of the survey responses received, 32/91 (35%) came from pharmacists at hospitals with a pharmacy-led medication reconciliation program. Of these pharmacy-led programs, 17/32 (53%) have a dedicated pharmacist or pharmacy staff to perform medication reconciliation. CONCLUSION: A comprehensive review of literature suggests that pharmacy involvement has the potential to reduce medication reconciliation errors and may improve patient satisfaction. Focused, full-time medication reconciliation pharmacists can help hospitals save time and money, improve outcomes, and meet higher standards issued by the Joint Commission. Data obtained in this study show the extent to which pharmacists contribute to achieving these goals in healthcare systems nationwide. This baseline study provides a strong case for hospitals to implement a pharmacy-led medication reconciliation program.

Quantitative Fundus Autofluorescence and Optical Coherence Tomography in ABCA4 Carriers.

PURPOSE: To assess whether carriers of ABCA4 mutations have increased RPE lipofuscin levels based on quantitative fundus autofluorescence (qAF) and whether spectral-domain optical coherence tomography (SD-OCT) reveals structural abnormalities in this cohort. METHODS: Seventy-five individuals who are heterozygous for ABCA4 mutations (mean age, 47.3 years; range, 9-82 years) were recruited as family members of affected patients from 46 unrelated families. For comparison, 57 affected family members with biallelic ABCA4 mutations (mean age, 23.4 years; range, 6-67 years) and two noncarrier siblings were also enrolled. Autofluorescence images (30°, 488-nm excitation) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference. The gray levels (GLs) of each image were calibrated to the reference, zero GL, magnification, and normative optical media density to yield qAF. Horizontal SD-OCT scans through the fovea were obtained and the thicknesses of the outer retinal layers were measured. RESULTS: In 60 of 65 carriers of ABCA4 mutations (age range, 9-60), qAF levels were within normal limits (95% confidence level) observed for healthy noncarrier subjects, while qAF levels of affected family members were significantly increased. Perifoveal fleck-like abnormalities were observed in fundus AF images in four carriers, and corresponding changes were detected in the outer retinal layers in SD-OCT scans. Thicknesses of the outer retinal layers were within the normal range. CONCLUSIONS: With few exceptions, individuals heterozygous for ABCA4 mutations and between the ages of 9 and 60 years do not present with elevated qAF. In a small number of carriers, perifoveal fleck-like changes were visible.

Muscle and nerve biopsies: techniques for the neurologist and neurosurgeon.

OBJECTIVE: Muscle and nerve biopsies are commonly performed procedures for the diagnosis of neuromuscular disorders. Neurologists and neurosurgeons are often consulted to perform these procedures in clinical practice. We provide guidelines in the performance of muscle and nerve biopsies. METHODS: We describe the technique for performance of muscle and nerve biopsy, and review the relevant literature. RESULTS: The quadriceps muscle is the most typical biopsy site for most myopathies, whereas the sural nerve is the most common nerve biopsy site for most peripheral neuropathies. Other sites may be utilized depending upon the pattern of symptoms or the differential diagnosis. Motor nerves may be sampled in the setting of motor neuron disease, for example. We advocate the use of conduit repair to allow for sensory or motor recovery to occur following nerve biopsy. CONCLUSION: The muscle biopsy and nerve biopsy may be performed with high yield, low morbidity, and rare complications.