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Apolipoprotein E (APOE) and Galectin-3 (Gal-3) are markers of activated microglia in neurodegenerative diseases of the central nervous system, whose targeting is protective in mouse models of glaucoma. In this study, we examined levels of APOE and Gal-3 in human aqueous humor (AH) and serum samples. Single-center, cross-sectional study. A total of 100 glaucoma and 110 control patients at Massachusetts Eye and Ear. We enrolled patients with various types and stages of glaucoma undergoing planned ophthalmic surgery as part of their routine care and compared them with patients without glaucoma undergoing phacoemulsification for age-related cataract. At the start of ophthalmic surgery, we collected AH and serum from 100 glaucoma and 110 control patients. APOE and Gal-3 levels were quantified by enzyme-linked immunosorbent assays. APOE and Gal-3 levels in AH and serum. APOE and Gal-3 levels were significantly elevated in the AH of glaucoma patients compared to controls (2.72 vs. 0.85 µg/ml, P  < 0.0001 for APOE, and 2.89 vs. 1.45 ng/ml, P  < 0.001 for Gal-3). A positive correlation was observed between AH APOE and Gal-3 levels in the glaucoma cohort ( R  = 0.44, P  < 0.0001). While serum Gal-3 levels were similar between groups (25.5 vs. 25.7 ng/ml, P  = 0.92), APOE levels were significantly elevated in the serum of glaucoma patients compared to controls (58.7 vs. 30.2 µg/ml, P  < 0.0001). Serum APOE levels were not correlated with AH APOE levels in either the glaucoma or the control groups (both R  ~ 0, P  > 0.05) or dependent on APOE genotype. Our findings demonstrate that AH Gal-3 and APOE are elevated in patients with glaucoma. In contrast, only serum APOE was elevated in our glaucoma cohort, possibly reflecting the known dysregulation of lipid metabolism that occurs in this disease.

The purpose of this study was to determine an arcuate incision (AI) nomogram to treat astigmatism during femtosecond laser-assisted cataract surgery. This is a retrospective, cohort study. Femtosecond laser (FSL)-assisted transepithelial AIs were created at a 9.0 mm optical zone, 80% depth, centered on the limbus. We modified the manual Donnenfeld limbal relaxing incision nomogram to 70% for with-the-rule (WTR), 80% for oblique (OBL), and 100% for against-the-rule (ATR) astigmatism. The correction index (CI) equaled AI-induced astigmatism/target-induced astigmatism. Measures included preoperative keratometric corneal cylinder (Pre Kcyl), postoperative Kcyl (Post Kcyl), and postoperative residual refractive astigmatism (Post RRA). Mean Pre Kcyl and 1-2 months Post RRA in 161 eyes of 116 patients were 0.626±0.417 diopters (D) (range 0.5-2 D), and 0.495±0.400 D (range 0-1.5 D), respectively. Mean absolute astigmatic changes (Pre Kcyl-Post Kcyl) without accounting for axis change in the WTR, ATR, and OBL groups were 0.165±0.383 D ( <0.001), 0.374±0.536 D ( <0.001), and 0.253±0.416 D ( =0.02), respectively. Mean absolute astigmatic changes using RRA as the postoperative measurement (Pre Kcyl-Post RRA) without accounting for axis change were 0.440±0.461 D ( <0.001), 0.238±0.571 D ( <0.05), 0.154±0.450 ( =0.111) in WTR, ATR, and OBL groups, respectively. CIs for WTR, ATR, and OBL were 0.53, 1.01, and 0.95, respectively. There were no intraoperative or postoperative complications related to the AIs. Transepithelial FSL-AIs using the modified Donnenfeld nomogram show potential for management of mild to moderate corneal astigmatism. An increase in the magnitude or reduction of the optical zone size for the treatment of WTR and ATR astigmatism for this nomogram may further improve refractive accuracy.

Neurofilament light chain (NfL) is a neuronal cytoskeletal protein that has been identified as a marker of neurodegeneration in diseases of the central nervous system. In this study, we investigated whether NfL in the aqueous humor (AH) can serve as a marker of neurodegeneration in glaucoma in a racially diverse North American population. Single-center, case-control study. We enrolled patients with various types and stages of glaucoma undergoing planned ophthalmic surgery as part of their routine care and compared them with patients without glaucoma undergoing phacoemulsification for age-related cataract. We collected AH from 39 glaucoma patients and 10 patients without glaucoma. AH NfL was quantified using the Single-Molecule Array (Simoa) NF-light assay (Quanterix). Demographic information, such as age, body mass index, sex, and self-reported race, as well as clinical information, such as pre-operative intraocular pressure (IOP), maximum IOP, and number of pre-operative glaucoma medications, was obtained by reviewing the medical record. Levels of AH NfL. In a model controlling for age and body mass index (BMI), NfL was significantly elevated in AH from glaucoma patients (mean: 429 pg/mL; standard deviation [SD]: 1136 pg/mL) compared to AH from patients without glaucoma (mean: 3.1 pg/mL; SD: 1.9 pg/mg): P = 0.002. Higher AH NfL was associated with higher maximum IOP (R = 0.44, P = 0.005), higher pre-operative IOP (R = 0.46, P = 0.003), and more pre-operative glaucoma medications (R = 0.61, P < 0.001). There was no association between AH NfL and Humphrey visual field mean deviation (R = -0.20, P = 0.220), retinal nerve fiber layer thickness as measured with optical coherence tomography (R = 0.07, P = 0.694), or glaucoma stage (R = 0.015, P = 0.935). Our findings suggest that AH NfL may have clinical utility as a marker of glaucomatous neurodegeneration.

To evaluate the collective user experience with an image-guided femtosecond laser (FSL) for cataract surgery in a high-volume, multi-surgeon, ambulatory surgical center. A detailed online survey was distributed to all surgeons in a single ambulatory surgical center who had performed cataract surgery using a FSL since its acquisition in December 2012. Information collected included the number of cases performed, typical surgical techniques and parameters, satisfaction with individual features of the laser (rated on a scale from 1=completely unsatisfied to 10=extremely satisfied) and commentary on ease of use and suggested improvements. Seventeen of 30 surgeons (56.7%) completed the survey, representing a case volume of 1,967 eyes. Fourteen surgeons (82.4%) felt they required ≤10 cases with the FSL to operate with the same safety and control as in standard phacoemulsification surgery. Satisfaction was highest for capsulotomies, lens fragmentation, lens softening, arcuate incisions and the graphic user interface (mean scores 9.4, 8.7, 8.7, 7.2 and 8.9, respectively). Preferred capsulotomy diameter was 4.8-5.2 mm (64.7% of respondents). About half (52.9%) of respondents centered the capsulotomy on the pupil and the other 47.1% centered the capsulotomy using optical coherence tomography. Most respondents (81.3%) preferred transepithelial arcuate incisions compared to intrastromal incisions. Satisfaction was lowest with FSL-created, main, clear corneal incisions and paracenteses (mean scores 4.4 and 4.2, respectively). Laser-assisted cataract surgery has a short learning curve and a high rate of user satisfaction. Further software and hardware development is warranted to improve user satisfaction with peripheral and clear corneal incisions.

Ophthalmology Q&A Board Review features a compilation of board review questions curated by expert subspecialists and edited by Harvard- and Columbia University-trained ophthalmologist Lora Glass.The text mirrors the multiple-choice format of the Written Qualifying Examination (WQE) portion of the American Board of Ophthalmology.

Over the past four decades, two distinct likelihood-based estimation methods for Exponential-family Random Graph Models (ERGMs) have emerged. One method tries, due to the complexity of the model, to approximate the maximum likelihood estimator (MLE) using Markov Chain Monte Carlo (MCMC) techniques, while the other method optimizes a simpler, but misspecified likelihood function that results in the so-called maximum pseudolikelihood estimator (MPLE). Interestingly, both estimators can be seen as opposite ends of a spectrum in multiple senses. In this dissertation, I examine the theory of these two estimation approaches and, in the process, develop an improved method for determining starting values for the MCMC algorithm that is based on the likelihood principle and uses simulated annealing. I also introduce two approaches for correctly approximating standard errors for the MPLE. These two approaches are based on parametric bootstrapping and the Godambe information matrix, respectively. This dissertation also provides empirical evidence that it is possible, by using an offset term that depends on the sample size, to embed some models in a sequence that renders the MPLE consistent and asymptotically normal. I focus the applications of the proposed techniques on networks predominantly explored in the field of political science. In a first project, a citation ERGM is developed to analyze the citation network among US Supreme Court majority opinions. In addition to finding evidence of exogenous covariates, the model provides evidence for reciprocity, transitivity, and popularity in the network. The other project examines the network of bills introduced in the United State Senate, where ties between bills indicate the similarity of the set of legislators who co-sponsor them.

To assess the rate of unplanned vitrectomies with femtosecond laser-assisted cataract surgery (FLACS) compared to conventional phacoemulsification at a single, high-volume, multi-surgeon ambulatory surgical center. Retrospective, comparative study of phacoemulsification cases performed in a community-based ambulatory surgical center. A chart review of 2,480 consecutive FLACS procedures performed by 30 surgeons and 36,865 consecutive conventional phacoemulsification surgeries performed by 47 surgeons was conducted. The rate of unplanned vitrectomies was evaluated. In eyes with unplanned vitrectomy, the rates of posterior capsule tear, anterior capsule tear, and zonular dehiscence were analyzed. The unplanned vitrectomy rates between early and late FLACS cases were compared using thresholds of greater than 10, 20, and 50 cases. There were 230 (0.62%) and 16 (0.65%) unplanned vitrectomies in the conventional phacoemulsification and FLACS groups, respectively (P = .89). Of the cases requiring unplanned vitrectomy, posterior capsule tear, anterior capsule tear, and zonular dehiscence rates (conventional phacoemulsification vs FLACS) were 70.9% versus 56.3%, 8.3% versus 12.5%, and 20.9% versus 31.3%, respectively (P = .35). The difference in unplanned vitrectomy rates between early and late cases did not reach statistical significance in any threshold group. FLACS had a rate of unplanned vitrectomy comparable to conventional phacoemulsification. There was no statistically significant difference in unplanned vitrectomy rates between early and late FLACS cases suggesting a short learning curve. [J Refract Surg. 2018;34(9):610-614.].

Realizing neurotechnologies that enable long-term neural recordings across multiple spatial-temporal scales during naturalistic behaviors requires new modeling and inference methods that can simultaneously address two challenges. First, the methods should aggregate information across all activity scales from multiple recording sources such as spiking and field potentials. Second, the methods should detect changes in the regimes of behavior and/or neural dynamics during naturalistic scenarios and long-term recordings. Prior regime detection methods are developed for a single scale of activity rather than multiscale activity, and prior multiscale methods have not considered regime switching and are for stationary cases. Here, we address both challenges by developing a Switching Multiscale Dynamical System model and the associated filtering and smoothing methods. This model describes the encoding of an unobserved brain state in multiscale spike-field activity. It also allows for regime-switching dynamics using an unobserved regime state that dictates the dynamical and encoding parameters at every time-step. We also design the associated switching multiscale inference methods that estimate both the unobserved regime and brain states from simultaneous spike-field activity. We validate the methods in both extensive numerical simulations and prefrontal spike-field data recorded in a monkey performing saccades for fluid rewards. We show that these methods can successfully combine the spiking and field potential observations to simultaneously track the regime and brain states accurately. Doing so, these methods lead to better state estimation compared with single-scale switching methods or stationary multiscale methods. These modeling and inference methods effectively incorporate both regime-detection and multiscale observations. As such, they could facilitate investigation of latent switching neural population dynamics and improve future brain-machine interfaces by enabling inference in naturalistic scenarios where regime-dependent multiscale activity and behavior arise. Competing Interest Statement The authors have declared no competing interest.

China has been affected by some of the world’s most serious geological disasters and experiences high economic damage every year. Geohazards occur not only in remote areas but also in highly populated cities. In the framework of the Dragon-4 32365 Project, this paper presents the main results and the major conclusions derived from an extensive exploitation of Sentinel-1, ALOS-2 (Advanced Land Observing Satellite 2), GF-3 (GaoFen Satellite 3), and latest launched SAR (Synthetic Aperture Radar), together with methods that allow the evaluation of their importance for various geohazards. Therefore, in the scope of this project, the great benefits of recent remote sensing data (wide spatial and temporal coverage) that allow a detailed reconstruction of past displacement events and to monitor currently occurring phenomena are exploited to study different areas and geohazards problems, including: surface deformation of mountain slopes; identification and monitoring of ground movements and subsidence; landslides; ground fissure; and building inclination studies. Suspicious movements detected in the different study areas were cross validated with different SAR sensors and truth data.