Quantifying cardiac dysfunction and valvular heart disease associated with subretinal drusenoid deposits in age-related macular degeneration.

BACKGROUND/AIMS: Demonstrate through objective multidisciplinary imaging that subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are linked to both coexistent valvular heart disease (VHD) and reduced systemic perfusion via cardiac index (CI). METHODS: Post-hoc analysis of cross-sectional study. 200 intermediate AMD (iAMD) subjects were assigned by masked readers to two groups: SDD (with or without drusen) and drusen (only) based on multimodal ophthalmic imaging. 65 transthoracic echocardiograms (TTEs) reports were available for cardiologist evaluation of VHD severity of the four cardiac valves and the presences of precursor lesions of aortic sclerosis (ASc) and mitral annular calcification (MAC). Necessary parameters to calculate CI were also obtained. Univariate testing was performed using Fisher's Exact test and t-test. RESULTS: 82.6% (19/23) of the iAMD subjects with at least one moderate/severe VHD had concurrent SDDs (p = 0.0040). All cases of aortic regurgitation (6/6, p = 0.0370) and mitral regurgitation (13/13, p = 0.0004) were found with coexisting SDDs. Stenotic VHD was not significantly associated with SDDs, however 70.7% of subjects with ASc (29/41, p = 0.0108) and 76.0% of subjects with MAC (19/25, 0.0377) had coexisting SDDs. CI was available in 48 subjects and was significantly below normal levels in the SDD cohort (mean CI SDD 1.95 ± 0.60 L/min/m2, non-SDD 2.71 ± 0.73 L/min/m2, p = 0.0004). CONCLUSIONS: Several specific VHDs have been found associated with the SDD form of AMD. Decreased systemic perfusion as measured by CI was also associated with SDDs, which supports a perfusion hypothesis of SDD pathogenesis. Further research is warranted to understand the relationship between cardiovascular disease and SDDs.

Correlation between ellipsoid zone thickness and the presence of subretinal drusenoid deposits in age-related macular degeneration.

PURPOSE: Subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are associated with systemic vascular diseases that compromise ocular perfusion. We demonstrate that SDDs are associated with decreased ellipsoid zone (EZ) thickness, further evidence of hypoxic damage. METHODS: Post hoc analysis of a cross-sectional study. 165 AMD subjects (aged 51-100; 61% women). Spectral-domain optical coherence tomography was obtained in both eyes. Masked readers assigned subjects to three groups: drusen only, SDD+drusen (SDD+D) and SDD only. EZ thickness was measured subfoveally and 2000 µm nasally, temporally, superiorly and inferiorly from the fovea. Univariate testing was performed using two-tailed t-tests with Bonferroni correction. RESULTS: The mean EZ thickness differences between the SDD+D and drusen-only groups were (in µm) 1.10, 0.67, 1.21, 1.10 and 0.50 at the foveal, nasal, temporal, superior and inferior locations, respectively (p=0.08 inferiorly, otherwise p≤0.01); between the SDD-only and drusen-only groups, the differences were 3.48, 2.48, 2.42, 2.08 and 1.42 (p≤0.0002). Differences in EZ thicknesses across all subjects and between groups were not significantly different based on gender, race or age. CONCLUSION: Subjects with SDDs (±drusen) had thinner EZs than those with drusen only, and the inferior EZ was least affected. EZs were thinnest in SDD-only subjects. This thinning gradation is consistent with progressive destruction of highly oxygen-sensitive mitochondria in the EZ from hypoxia. These findings support the reduced ophthalmic perfusion hypothesis for the formation of SDDs secondary to high-risk systemic vasculopathy.

Left ventricular to left arial volume ratio in the assessment of filling pressure in patients with dyspnoea and preserved ejection fraction.

Introduction: Assessing filling pressure (FP) remains a clinical challenge despite advancements in non-invasive imaging techniques. This study investigates the utility of echocardiographic left ventricular (LV) to left atrial (LA) volume ratio in estimating the resting FP in patients with dyspnoea and preserved ejection fraction (EF). Methods: This study is a prospective, single-centre analysis of 53 consecutive patients with dyspnoea (New York Heart Association grade 2 or 3) and LVEF of ≥50% (mean age 71 ± 10 years) who underwent cardiac catheterisation, including direct measurement of LA pressure at rest using retrograde technique. Echocardiographic data were obtained 1.5 ± 1.0 h after cardiac catheterisation. The patients were divided into two groups: Group 1 consisted of individuals with elevated FP, indicated by a mean LA pressure or mean pulmonary capillary wedge pressure of >12 mmHg, and Group 2 comprised of patients with normal FP. The LV and LA volumes were measured at three specific points: the minimum volume (LVES, LAmin), the volume during diastasis (LVdias, LAdias), and the maximum volume (LVED, LAmax). The corresponding LV/LA volume ratios were analysed: end-systole (LVES/LAmax), diastasis (LVdias/LAdias), and end-diastole (LVED/LAmin). Results: The patients in Group 1 exhibited lower LV/LA volume ratios compared with those in Group 2 (LVES/LAmax 0.44 ± 0.12 vs. 0.60 ± 0.23, P = 0.0032; LVdias/LAdias 1.13 ± 0.30 vs. 1.56 ± 0.49, P = 0.0007; LVED/LAmin 2.71 ± 1.57 vs. 4.44 ± 1.70, P = 0.0004). The LV/LA volume ratios correlated inversely with an increased FP (LVES/LAmax, r = -0.40, P = 0.0033; LVdias/LAdias, r = -0.45, P = 0.0007; LVED/LAmin, r = -0.55, P < 0.0001). Among all the measurements, the LVdias/LAdias ratio demonstrated the highest discriminatory power to distinguish patients with elevated FP from normal FP, with a cut-off value of ≤1.24 [area under the curve (AUC) = 0.822] for the entire group, encompassing both sinus rhythm and atrial fibrillation. For patients in sinus rhythm specifically, the cut-off value was ≤1.28 (AUC = 0.799), with P < 0.0001 for both. The LVdias/LAdias index demonstrated non-inferiority to the E/e' ratio [ΔAUC = 0.159, confidence interval (CI) = -0.020-0.338; P = 0.0809], while surpassing the indices of LA reservoir function (ΔAUC = 0.249, CI = 0.044-0.454; P = 0.0176), LA reservoir strain (ΔAUC = 0.333, CI = 0.149-0.517; P = 0.0004), and LAmax index (ΔAUC = 0.224, CI = 0.043-0.406; P = 0.0152) in diagnosing patients with elevated FP. Conclusion: The study presents a straightforward and reproducible method for non-invasive estimation of FP using routine TTE in patients with dyspnoea and preserved EF. The LVdias/LAdias index emerges as a promising indicator for identifying elevated FP, demonstrating comparable or even superior performance to established parameters.

Spectral and lifetime resolution of fundus autofluorescence in advanced age-related macular degeneration revealing different signal sources.

PURPOSE: To determine the fundus autofluorescence (FAF) lifetimes and spectral characteristics of individual drusen and hyperpigmentation independent of those with retinal pigment epithelium (RPE) in geographic atrophy (GA) areas in late-stage age-related macular degeneration (AMD). METHODS: Three consecutive patients with complete RPE and outer retinal atrophy (cRORA) exhibiting drusen that were calcified or associated with hyperpigmentation were investigated with multimodal non-invasive ophthalmic imaging including colour fundus photography (CFP), optical coherence tomography (OCT), near-infrared reflectance (NIR), blue FAF and fluorescence lifetime imaging ophthalmoscopy (FLIO). Fluorescence lifetimes were measured in two spectral channels (short-wavelength spectral channel (SSC): 500-560 nm and long-wavelength spectral channel (LSC): 560-720 nm). RESULTS: Drusen lacking RPE coverage, as confirmed by CFP and OCT, had longer FAF lifetimes than surrounding cRORA by 127 ± 66 ps (SSC) and 113 ± 48 ps (LSC, both p = 0.008 in Wilcoxon test, N = 9) and by 209 ± 100 ps (SSC) and 121 ± 56 ps (LSC, p < 0.001, N = 14) in two patients. Hyperpigmentation in CFP in a third patient shows strong FAF with prolonged lifetimes. In the SSC, persistent FAF was found inside cRORA. A crescent-shaped hyperfluorescence in an area of continuous RPE but lacking outer retina was seen in one eye with a history of anti-VEGF treatment. CONCLUSIONS: Short-wavelength fluorescence in cRORA points to fluorophores beyond RPE organelles. Fluorescence properties of drusen within cRORA differ from in vivo drusen covered by RPE. These limited findings from three patients give new insight into the sources of FAF that can be further elucidated in larger cohorts.

Survival relative to pacemaker status after transcatheter aortic valve implantation.

OBJECTIVES: To determine whether a permanent pacemaker (PPM) in situ can enhance survival after transcatheter aortic valve implantation (TAVI), in a predominantly inoperable or high risk cohort. BACKGROUND: New conduction disturbances are the most frequent complication of TAVI, often necessitating PPM implantation before hospital discharge. METHODS: We performed an observational cohort analysis of the UK TAVI registry (2007-2015). Primary and secondary endpoints were 30-day post-discharge all-cause mortality and long-term survival, respectively. RESULTS: Of 8,651 procedures, 6,815 complete datasets were analyzed. A PPM at hospital discharge, irrespective of when implantation occurred (PPM 1.68% [22/1309] vs. no PPM 1.47% [81/5506], odds ratio [OR] 1.14, 95% confidence interval [CI] 0.71-1.84; p = .58), or a PPM implanted peri- or post-TAVI only (PPM 1.44% [11/763] vs. no PPM 1.47% [81/5506], OR 0.98 [0.51-1.85]; p = .95) did not significantly reduce the primary endpoint. Patients with a PPM at discharge were older, male, had right bundle branch block at baseline, were more likely to have received a first-generation self-expandable prosthesis and had experienced more peri- and post-procedural complications including bailout valve-in-valve rescue, bleeding and acute kidney injury. A Cox proportional hazards model demonstrated significantly reduced long-term survival in all those with a PPM, irrespective of implantation timing (hazard ratio [HR] 1.14 [1.02-1.26]; p = .019) and those receiving a PPM only at the time of TAVI (HR 1.15 [1.02-1.31]; p = .032). The reasons underlying this observation warrant further investigation. CONCLUSIONS: A PPM did not confer a survival advantage in the first 30 days after hospital discharge following TAVI.

Deficits and compensation: Attentional control cortical networks in schizophrenia.

Visual processing and attention deficits are responsible for a substantial portion of the disability caused by schizophrenia, but the source of these deficits remains unclear. In 35 schizophrenia patients (SzP) and 34 healthy controls (HC), we used a rapid serial visual presentation (RSVP) visual search task designed to activate/deactivate the cortical components of the attentional control system (i.e. the dorsal and ventral attention networks, lateral prefrontal regions in the frontoparietal network, and cingulo-opercular/salience networks), along with resting state functional connectivity, to examine the integrity of these components. While we find that behavioral performance and activation/deactivation of the RSVP task are largely similar between groups, SzP exhibited decreased functional connectivity within late visual components and between prefrontal and other components. We also find that performance correlates with the deactivation of the ventral attention network in SzP only. This relationship is mediated by the functional connectivity of critical components of the attentional control system. In summary, our results suggest that the attentional control system is potentially used to compensate for visual cortex deficits. Furthermore, prefrontal deficits in SzP may interfere with this compensatory use of the attentional control system. In addition to highlighting focal deficits and potential compensatory mechanisms in visual processing and attention, our findings point to the attentional control system as a potential target for rehabilitation and neuromodulation-based treatments for visual processing deficits in SzP.

A New and Improved Method for Automated Screening of Age-Related Macular Degeneration Using Ensemble Deep Neural Networks.

In this paper, we provide a new framework on deep learning based automated screening method for finding individuals at risk of developing Age-related Macular Degeneration (AMD). We studied the appropriateness of using the transfer learning to screen AMD by using color fundus images. We make use of the Age-Related Eye Disease Study (AREDS) dataset with nearly 150,000 images, which also provided qualitative grading information by expert graders and ophthalmologists. We use ensemble learning technique with two deep neural networks, namely, Inception-ResNet-V2 and Xception with a custom fine-tuning approach. For our study, we have identified two experiments that are most useful in the screening of AMD. First, we have categorized the images into two classes based on the clinical significance: None or early AMD and Intermediate or Advanced AMD. Second, we have categorized the images into four classes: No AMD, early AMD, Intermediate AMD and Advanced AMD. On AREDS dataset, we have achieved an accuracy of over 95.3% for two-class experiment with our ensemble method. With accuracies ranging from 86% (for four-class) to 95.3% (for two-class), we have demonstrated that the training of a deep neural network with the transfer of learned features with a sufficient number of images fares very well and is comparable to human grading.

Spectral characterization of a supercontinuum source based on nonlinear broadening in an aqueous K2ZnCl4 salt solution.

We report on investigations concerning the shot-to-shot spectral stability properties of a supercontinuum source based on nonlinear processes such as self-phase modulation and optical wave-breaking in a highly concentrated K2ZnCl4 double salt solution. The use of a liquid medium offers both damage resistance and high third-order optical nonlinearity. Approximately 40 µJ pulses spanning a spectral range between 390 and 960 nm were produced with 3.8% RMS energy stability, using infrared input pulses of 500±50 fs FWHM durations and 2.42±0.04 mJ energies with an RMS stability of 2%. The spectral stability was quantified via acquiring single-shot spectra and studying shot-to-shot variation across a spectral range of 200-1100 nm, as well as by considering spectral correlations. The regional spectral correlation variations were indicative of nonlinear processes leading to sideband generation. Spectral stability and efficiency of energy transfer into the supercontinuum were found to weakly improve with increasing driver pulse energy, suggesting that the nonlinear broadening processes are more stable when driven more strongly, or that self-guiding effects in a filament help to stabilize the supercontinuum generation.

Micrometer-thickness liquid sheet jets flowing in vacuum.

Thin liquid sheet jet flows in vacuum provide a new platform for performing experiments in the liquid phase, for example X-ray spectroscopy. Micrometer thickness, high stability, and optical flatness are the key characteristics required for successful exploitation of these targets. A novel strategy for generating sheet jets in vacuum is presented in this article. Precision nozzles were designed and fabricated using high resolution (0.2 µm) 2-photon 3D printing and generated 1.49 ± 0.04 µm thickness, stable, and <λ/20-flat jets in isopropanol under normal atmosphere and under vacuum at 5 × 10-1 mbar. The thin sheet technology also holds great promise for advancing the fields of high harmonic generation in liquids, laser acceleration of ions as well as other fields requiring precision and high repetition rate targets.

Occlutech percutaneous patent foramen ovale closure: Safety and efficacy registry (OPPOSE).

INTRODUCTION: Safety and efficacy data on patent foramen ovale (PFO) closure with the Occlutech Figulla Flex II device are lacking. We undertook a fully monitored prospective Registry on PFO closure using this device. METHODS: 100 patients undergoing PFO closure were enrolled into the OPPOSE Registry at 6 UK centres. The primary endpoint was PFO closure (grade 0 or 1 shunt) at 6-month BCTTE assessed by Corelab. Secondary endpoints included implantation success, complications, and atrial fibrillation during follow-up. RESULTS: 100 patients aged 43.8±11.5years, 53% male, were recruited. Indications for PFO closure included stroke (56%), TIA (29%) systemic embolism (4%) and MI (3%). Closure was undertaken under GA (44%) or LA (56%), with TOE (45%), ICE (31%), no imaging (20%) or TTE (3%). Balloon sizing was used in 98% of cases and showed a tunnel length of 7.3±3.6mm, primum-secundum separation of 7.0±2.9mm and basal inlet width of 8.5±3.5mm. Implantation was successful in all cases using 18mm (9%), 25mm (80%), 30mm (10%) and 35mm (1%) devices. 5 patients were lost to follow-up. 92 patients underwent six-month BCTTE. The primary endpoint of PFO closure (grade 0 or 1 shunt) at six months was 79.3%. One patient developed major bleeding (BARC 3b), one patient required vascular surgery, and in one patient device embolization was noted at six months and a larger device implanted. There was one case of new atrial fibrillation. CONCLUSIONS: This first prospective monitored data for the Occlutech Figulla Flex II device demonstrates good safety and efficacy data at implant and six-month follow-up.

Choroidal thickness in patients with coronary artery disease.

PURPOSE: To evaluate choroidal thickness (CTh) in patients with coronary artery disease (CAD) compared to healthy controls. DESIGN: Cross-sectional. METHODS: Setting: Ambulatory clinic of a large city hospital. Patient population: Thirty-four patients had documented CAD, defined as history of >50% obstruction in at least one coronary artery on cardiac catheterization, positive stress test, ST elevation myocardial infarction, or revascularization procedure. Twenty-eight age-matched controls had no self-reported history of CAD or diabetes. Patients with high myopia, dense cataracts, and retinal disease were excluded. Observation procedures: Enhanced depth imaging optical coherence tomography and questionnaire regarding medical and ocular history. Main outcome measures: Subfoveal CTh and CTh 2000 µm superior, inferior, nasal, and temporal to the fovea in the left eye, measured by 2 readers. RESULTS: CTh was significantly lower in patients with CAD compared to controls at the subfoveal location (252 vs. 303 µm, P = 0.002) and at all 4 cardinal macular locations. The mean difference in CTh between the 2 groups ranged from 46 to 75 µm and was greatest in the inferior location. Within the CAD group, CTh was significantly lower temporally (P = 0.007) and nasally (P<0.001) than subfoveally, consistent with the pattern observed in controls. On multivariate analysis, CAD was negatively associated with subfoveal CTh (P = 0.006) after controlling for diabetes, hypertension, and hypercholesterolemia. CONCLUSIONS AND RELEVANCE: Patients with CAD have a thinner macular choroid than controls, with preservation of the normal spatial CTh pattern. Decreased CTh might predispose patients with CAD to high-risk phenotypes of age-related macular degeneration such as reticular pseudodrusen and could serve as a potential biomarker of disease in CAD.

Conduction Abnormalities and Permanent Pacemaker Implantation After Transcatheter Aortic Valve Replacement Using the Repositionable LOTUS Device: The United Kingdom Experience.

OBJECTIVES: The authors report the incidence of pacemaker implantation up to hospital discharge and the factors influencing pacing rate following implantation of the LOTUS bioprosthesis (Boston Scientific, Natick, Massachusetts) in the United Kingdom. BACKGROUND: Transcatheter aortic valve replacement (TAVR) is associated with a significant need for permanent pacemaker implantation. Pacing rates vary according to the device used. The REPRISE II (Repositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus Valve System) trial reported a pacing rate of 29% at 30 days after implantation of the LOTUS device. METHODS: Data were collected retrospectively on 228 patients who had the LOTUS device implanted between March 2013 and February 2015 across 10 centers in the United Kingdom. Twenty-seven patients (12%) had pacemakers implanted pre-procedure and were excluded from the analysis. RESULTS: Patients were aged 81.2 ± 7.7 years; 50.7% were male. The mean pre-procedural QRS duration was 101.7 ± 20.4 ms. More than one-half of the cohort (n = 111, 55%) developed new left bundle branch block (LBBB) following the procedure. Permanent pacemakers were implanted in 64 patients (32%) with a median time to insertion of 3.0 ± 3.4 days. Chief indications for pacing were atrioventricular (AV) block (n = 46, 72%), or LBBB with 1st degree AV block (n = 11, 17%). Amongst those who received a pacemaker following TAVR the pre-procedural electrocardiogram findings included: No conduction disturbance (n = 41, 64%); 1st degree AV block (n = 10, 16%); right bundle branch block (n = 6, 9%) and LBBB (n = 5, 8%). LBBB (but not permanent pacemaker) occurred more frequently in patients who had balloon aortic valvuloplasty before TAVR (odds ratio [OR]: 1.25; p = 0.03). Pre-procedural conduction abnormality (composite of 1st degree AV block, hemiblock, right bundle branch block, LBBB) was independently associated with the need for permanent pacemaker (OR: 2.54; p = 0.048). The absence of aortic valve calcification was also associated with a higher pacing rate (OR: 0.55; p = 0.031). Multivariate regression analysis did not show an independent association between depth of implant, valve oversizing, balloon post-dilatation, and the need for pacing post-procedure. CONCLUSIONS: Following implantation of the repositionable LOTUS valve, 55% of patients developed LBBB and 32% of patients required a pacemaker during their index hospital admission. Patients with pre-procedural conduction disturbance and non-calcified aortic valves were more likely to need pacing. No other anatomic features were identified with increased pacing requirement with the LOTUS device.

Use of the Lotus Transcatheter Valve to Treat Severe Native Aortic Regurgitation.

Transcatheter aortic valve implantation (TAVI) has become the standard treatment for aortic stenosis in high-risk patients. TAVI for native valve aortic regurgitation is technically more demanding because of a lack of anchoring calcification, a lower index incidence, heterogeneous causes, and larger anatomy. We present 3 cases in which the Lotus TAV was used to treat severe native aortic regurgitation (AR) successfully.

Rapid pacing using the 0.035-in. Retrograde left ventricular support wire in 208 cases of transcatheter aortic valve implantation and balloon aortic valvuloplasty.

INTRODUCTION AND METHOD: Transcatheter aortic valve implantation (TAVI) and balloon aortic valvuloplasty (BAV) are now well established percutaneous procedures. These procedures almost always require bursts of rapid ventricular pacing to temporarily reduce cardiac output to facilitate the procedure, usually done via a temporary pacing wire inserted into the right ventricle. We describe a case series of 132 cases of TAVI and 76 BAV done using ventricular pacing via the left ventricular lead by simply connecting one electrode to the patient's skin and one electrode through the left ventricular (LV) wire. RESULTS: All of the 132 TAVI cases (a mixture of Edwards Sapien, Medtronic CoreValve and Boston Scientific Lotus) and 76 BAV were successfully performed using pacing through the LV wire. No BAV patients required temporary pacing wire (TPW) or permanent pacemaker (PPM) insertion. Of the TAVI patients, 6 (4.5%) required TPW during the procedure due to complete heart block to facilitate removal of the LV wire. 1 patient (0.8%) required a PPM urgently due to complete heart block and haemodynamic instability. Twenty eight Patients (21.2%) required PPM following TAVI, 9 of which were within the first 24 hr. Average time to pacemaker implantation was 3.7 days. CONCLUSION: Rapid ventricular pacing via the LV wire is a simple, safe and effective strategy for percutaneous aortic valve intervention and balloon aortic valvuloplasty. It eliminates the need for a temporary pacing wire with its attendant risks in the vast majority of cases. Furthermore, most pacemakers following TAVI are required late, after the first 24 hr period, by which time the TPW has already usually been removed. © 2016 Wiley Periodicals, Inc.

A high spatio-temporal resolution optical pyrometer at the ORION laser facility.

A streaked pyrometer has been designed to measure the temperature of ≈100 µm diameter heated targets in the warm dense matter region. The diagnostic has picosecond time resolution. Spatial resolution is limited by the streak camera to 4 µm in one dimension; the imaging system has superior resolution of 1 µm. High light collection efficiency means that the diagnostic can transmit a measurable quantity of thermal emission at temperatures as low as 1 eV to the detector. This is achieved through the use of an f/1.4 objective, and a minimum number of reflecting and refracting surfaces to relay the image over 8 m with no vignetting over a 0.4 mm field of view with 12.5× magnification. All the system optics are highly corrected, to allow imaging with minimal aberrations over a broad spectral range. The detector is a highly sensitive Axis Photonique streak camera with a P820PSU streak tube. For the first time, two of these cameras have been absolutely calibrated at 1 ns and 2 ns sweep speeds under full operational conditions and over 8 spectral bands between 425 nm and 650 nm using a high-stability picosecond white light source. Over this range the cameras had a response which varied between 47 ± 8 and 14 ± 4 photons/count. The calibration of the optical imaging system makes absolute temperature measurements possible. Color temperature measurements are also possible due to the wide spectral range over which the system is calibrated; two different spectral bands can be imaged onto different parts of the photocathode of the same streak camera.

Comparative study on the temporal contrast of femtosecond mode-locked laser oscillators.

We have investigated the temporal intensity contrast characteristics from a broad range of mode-locked short-pulse oscillators used for seeding high-power terawatt and petawatt-class laser systems. Saturable absorber (SESAM), Kerr lens (KLM), nonlinear polarization evolution (NPE) in optical fibers and synchronously pumped optical parametric oscillator (OPO) mode-locked sources have been measured using a third-order autocorrelator with up to 1010 dynamic range. We restricted the temporal characterization to features <30 ps about the laser pulse that reflect fundamental mode-locking processes. We find additional nonlinear terms and residual higher-order dispersion limits the performance of KLM and NPE sources up to the 105 contrast level, while >108 contrast was observed from the SESAM and OPO laser pulse trains.

Flat-top picosecond pulses generated by chirped spectral modulation from a Nd:YLF regenerative amplifier for pumping few-cycle optical parametric amplifiers.

In this paper we present an optically synchronized Nd:YLF regenerative amplifier optimized for use as a preamplifier in a few-cycle optical parametric chirped pulse amplification pump laser. In the pump amplification process we employ a combination of spectral modulation and chirping in order to control and optimize the temporal shape of the pulses. We report on a comparative study of two methods for generating near-flat-top or custom real-time variable-shaped pump pulses using either controlled chirp and shaping of the spectrum of the pulses seeding a regenerative amplifier or intracavity spectral filtering to broaden the gain bandwidth of the system. We show that in addition to minimizing gain narrowing and B-integral, the efficiency of the cascaded nonlinear processes of the parametric amplifiers can be increased.

Reticular macular lesions: a review of the phenotypic hallmarks and their clinical significance.

Reticular macular lesions, also known as 'reticular macular disease', 'reticular drusen', 'reticular pseudodrusen', or 'subretinal drusenoid deposits', are a pattern of lesions commonly found in age-related macular degeneration and best visualized using at least two imaging techniques in combination. Reticular lesions have four stages of progression observable on spectral domain optical coherence tomography, but they do not show the usual signs of regression of soft drusen (calcification and pigment changes). Furthermore, reticular lesions correlate histologically with subretinal drusenoid deposits localized between the retinal pigment epithelium and the inner segment ellipsoid band. Reticular lesions are most commonly seen in older age groups of female patients with age-related macular degeneration and are usually bilateral. They are not clearly associated with known age-related macular degeneration genes and are highly associated with late-stage age-related macular degeneration and an increased mortality rate. They are also associated with alterations in the neural retina and choroid.