Changing from preserved, to preservative-free cyclosporine 0.1% enhanced triple glaucoma therapy: impact on ocular surface disease-a randomized controlled trial.

OBJECTIVE: Halting and reversing glaucoma therapy-related ocular surface disease (GTR-OSD) will improve the success of long-term medical therapy, impacting millions of patients worldwide. METHODS: A single-centre, masked, prospective, placebo-controlled, crossover trial of 41 well-controlled open-angle glaucoma subjects with moderate to severe GTR-OSD on preserved latanoprost and dorzolamide/timolol fixed combination (DTFC) therapy was conducted. Subjects were randomized to preservative-free (PF) tafluprost and DTFC with either placebo or cyclosporine 0.1% drops for 6 months and were then crossed over to the opposite therapy. Oxford score of ocular staining was the primary outcome; osmolarity, matrix-metalloproteinase-9 (MMP-9) testing, tear film break-up time (TFBUT), meibomian gland dysfunction (MGD), punctum evaluation, adverse events and diurnal intraocular pressure (IOP) comprised secondary outcomes. RESULTS: GTR-OSD findings improved with PF therapy. At 6 months the triple PF with placebo group showed improvement compared to baseline in mean Oxford score (mean difference [MD]:-3.76; 95% confidence interval [CI]:-4.74 to -2.77; p < 0.001), osmolarity (MD:-21.93; 95%CI:-27.61 to -16.24 mOsm/l; p < 0.001), punctum stenosis (p = 0.008) and conjunctival hyperaemia (p < 0.001). Similar improvements occurred in the cyclosporine enhanced period, which also provided greater improvement in MMP-9 positivity (24 vs 66%; p < 0.001) and TFBUT (p = 0.022). The cyclosporine group was superior vs placebo in mean Oxford score (MD:-0.78; 95%CI:-1.40 to -0.15); p < 0.001), itchiness and objective adverse events (p = 0.034). Cyclosporine elicited more stinging vs placebo (63 vs 24%; p < 0.001). Both PF regimens reduced mean diurnal IOP more than preserved therapy (14.7 vs 15.9 mmHg; p < 0.001). CONCLUSIONS: Changing from preserved to PF glaucoma medications improves ocular surface health and IOP control. Topical cyclosporine 0.1% further reverses GTR-OSD.

Design and Validation of a New Smartphone-Based Reading Speed App (GDRS-Test) for the Greek Speaking Population.

Purpose: To present a novel smartphone-based application (GDRS-test, Greek Digital Reading Speed - test) for the assessment of reading speed, to evaluate, whether this test could be easily and reliably used by patients with visual impairment and normal individuals serving as an adjunctive tool for their visual examination. Patients and Methods: One hundred and five visually impaired and 32 normal eyes were examined. Depending on existing active ocular pathology, patients were divided into a non-macular and a macular group, We examined the reading performance for continuous text (MNREAD chart) and random unrelated words of the new smartphone-based reading speed app, monocularly. The patients' best-corrected visual acuity ranged from 1.3 to 0.2 logMAR. Examinees were asked to read aloud (at a 40 cm distance) a series of 30 random two-syllable and then 30 three-syllable Greek words, without semantic connection. Reading speed was measured as correct words per minute for critical print size. The individuals were examined twice within 2 weeks for test-retest reliability. Correlations and comparisons concerning each group adjusted for age and visual acuity were performed. Results: There was moderate correlation between MNREAD and 2SYL SPEED (Reading speed for 2-syllable) (Pearson's rho = 0.589, p < 0.001) and 3SYL SPEED (Reading speed for 3-syllable) (Pearson's rho = 0.617, p < 0.001) for healthy individuals. The mean 2SYL SPEED and 3SYL SPEED for Individuals of the maculopathies group or non-maculopathies group were significantly lower compared to normal individuals adjusted for age and visual acuity [B (95% CI): -93.077 (-104.165, -81.98), p < 0.001] and [B (95% CI): -92.254 (-104.196, -80.312), p < 0.001], respectively. The test-retest analysis showed a good agreement for patients and healthy individuals. Conclusion: The novel-reading speed application for the Greek-speaking population was found to accurately detect differences between patients with visual impairment and healthy individuals. It was designed and constructed with the intention to ease and improve the ophthalmic examination allowing individuals to self-evaluate reading speed by transmitting the result to their physician.

The contribution of wet labs in the education of ophthalmologists.

BACKGROUND: The need for pre-training in experimental eye surgery is considered necessary. It is an essential way to assess trainees in ophthalmology based on their instrument and tissue handling and skills. This article aims to underline this necessity and demonstrate the ocular health professionals' opinion on this issue. METHODS: 74 participants (45 females and 29 males) were included in the study. Ophthalmology residents, ophthalmologists participated in the wet lab session. The evaluation of the contribution of the wet labs were provided by filling a new questionnaire form. In this way, an interactive questionnaire was developed. RESULTS: Regarding trainees' grading of wet labs' significance as a first step for guiding their surgical career, it was positively correlated with their subjective view of labs' utility to both improve their surgical skills (p = 0.001) and maintain pre-existing ones (p < 0.001). We should also note that all of them (100%) stated that wet labs were necessary during residency, especially in repeated sessions, and that they would recommend them to their colleagues. CONCLUSION: The surgical skills improved significantly after participation in a wet lab, according to participants, who rated the experience as highly educational. Wet labs can reduce the learning curve of difficult surgical techniques, accelerate the rate for trainees to achieve surgical competency, and treat patients safely and effectively.

A modern approach to aortic valve insufficiency: Aortic root restoration via HAART 300 internal annuloplasty ring.

BACKGROUND AND AIM OF THE STUDY: HAART 300 is an internal geometric annuloplasty ring. The safety and efficacy of this novel device in aortic valve (AV) repair in a single referral center are reported. METHODS: Twenty patients with trileaflet AV insufficiency with ascending aorta and/or aortic root enlargement were included. Subannular implantation was performed to correct annular dilatation, whereas concomitant leaflet repair was performed whenever required. All but two patients also received ascending aorta replacement, whereas selective sinus replacement was performed in all but five patients. RESULTS: Follow-up was for a maximum of 3.8 years and a mean of 2.2 years. Mean age was 54.2 years old. Moderate to severe preoperative AV insufficiency was noted in 75% of patients, whereas 70% of them had an ascending aorta over 45 mm. One patient was lost from follow-up. Overall mortality as well as major complication rates were zero. Early postoperatively, no more than mild AV regurgitation was detected, whereas only one patient appeared with moderate AV regurgitation during our 2.2-year follow-up. New York Heart Association class was also significantly lower compared to preoperative values and valve gradients remained low at last follow-up. CONCLUSIONS: Geometric ring annuloplasty is a safe and effective valve sparing approach to deal with AV insufficiency contributing to overall root reconstruction. Short-term results are excellent rendering this easily reproducible and versatile method very attractive.

Valsalva retinopathy associated with intranasal cocaine abuse: A case report.

INTRODUCTION: The purpose of this report is to describe a case of Valsalva retinopathy in an intranasal cocaine user. CASE REPORT: A 49-year-old male presented with a history of sudden loss of vision and inferior visual field defect in his left eye. Clinical evaluation of the affected eye showed best corrected visual acuity of 20/25 and fundus examination revealed a preretinal hemorrhage superior to the disk with multiple intraretinal hemorrhages in and around the posterior pole. On further questioning, the patient revealed intranasal cocaine use the day before the onset of his visual symptoms. Blood tests were requested to exclude blood dyscrasias or predisposition to vascular occlusive disorders and no further treatment measures were taken. The patient was reviewed a month later when his hemorrhages had completely resolved and his visual acuity had improved to 20/20. His blood results were within normal limits. CONCLUSION: Although never been reported before, Valsalva retinopathy can be associated with intranasal cocaine abuse and should be considered in the differential diagnosis of visual reduction in such population.

Preservative-free tafluprost/timolol fixed combination: comparative 24-h efficacy administered morning or evening in open-angle glaucoma patients.

Background: Ideal dosing for the preservative-free (PF) tafluprost/timolol fixed combination (TTFC) remains to be elucidated. Research design and methods: This study was a prospective, observer-masked, placebo-controlled, crossover, comparison in 42 consecutive open-angle glaucoma patients whose intraocular pressure (IOP) was insufficiently controlled with preserved latanoprost monotherapy (mean 24-h IOP >20 mmHg). Patients were randomized to either morning (08:00) or evening (20:00) PF TTFC for 3 months and then crossed over. After each treatment period, patients underwent habitual 24-h IOP monitoring with Goldmann tonometry in the sitting position (at 10:00, 14:00, 18:00, and 22:00) and Perkins tonometry in the supine position (at 02:00 and 06:00). Results: Mean 24-h IOP on latanoprost was 22.2±3.9 mmHg. Both PF TTFC dosing regimens obtained greater reduction in mean 24-h, daytime, nighttime, and peak 24-h IOP (P < 0.001). Evening dosing provided tighter 24-h IOP fluctuation versus latanoprost (P < 0.001). Evening dosing was superior to morning dosing at four time points (P < 0.01), for the mean daytime IOP (P < 0.001) and mean 24-h IOP fluctuation (P < 0.001). Hyperemia was more common with preserved latanoprost (21.4 vs. 7.1%; P = 0.031). Patients (n = 19; 45%) preferred evening dosing. Conclusions: PF TTFC provided greater 24-h IOP control and less hyperemia compared with preserved latanoprost. Evening administration of this novel medication offered superior 24-h efficacy. Trial registration: Clinicaltrials.gov (NCT03612817).

Assessing the role of ranibizumab in improving the outcome of glaucoma filtering surgery and neovascular glaucoma.

INTRODUCTION: Ranibizumab was the first anti-vascular endothelial growth factor (VEGF) agent approved for the treatment of neovascular age-related macular degeneration. The use of ranibizumab and other anti-VEGF medications in recent years has revolutionized the treatment of several sight-threatening retinal disorders. Emerging evidence has demonstrated that anti-VEGF treatment can offer advantages in the management of other ocular conditions where VEGFs play a key role: ocular scarring following glaucoma filtering surgery and neovascular glaucoma (NVG). Areas covered: We critically review available evidence on the use of ranibizumab as a wound healing modulator in glaucoma filtering surgery and as an adjunct in the management of NVG. Expert opinion: Based on the available evidence and the authors' clinical experience, ranibizumab is a valuable adjunct in the management of NVG. In glaucoma filtering surgery, however, the role of ranibizumab is less clear and does not provide a significant advantage over mitomycin C. Drawbacks for its use in glaucoma include cost, its off-label use, uncertainty and limited evidence on the various routes of administration, the optimal dosing schemes and its toxicity profile. Future advances in ranibizumab delivery systems allowing less frequent dosing may change this treatment paradigm.

A Review of the Clinical Usefulness of Selective Laser Trabeculoplasty in Exfoliative Glaucoma.

In the last decade, selective laser trabeculoplasty (SLT) has been commonly used in the management of several different types of glaucoma, as either primary or adjunct therapy. The technique has an excellent safety profile and is at least as effective as argon laser trabeculoplasty. Although the actual mechanism of action of SLT remains unclear, evidence has shown that it does not induce morphologically evident trabecular meshwork alterations. SLT's non-disruptive mode of action offers the advantage of repeatability. Exfoliation glaucoma (XFG) is a secondary open-angle glaucoma with unfavorable intraocular pressure (IOP) characteristics, which typically carries a poorer long-term prognosis than primary open-angle glaucoma. Consequently, patients with XFG often need multiple medications to achieve IOP levels that prevent disease progression. Because complicated pharmacotherapy regimens undermine the long-term tolerability and compliance of patients with XFG, options such as SLT may decrease the burden of multiple therapies and ultimately improve prognosis. In fact, SLT may be a particularly attractive option in XFG because the pigment-laden trabecular tissue of these patients enhances the absorption of laser energy and thus augments the biologic effects induced by this treatment. The current article reviews the postulated mechanisms of action of SLT, discusses practical aspects of SLT therapy, and examines selected peer-reviewed literature pertaining to the clinical usefulness of this modality in XFG patients.

Retinal vessel morphology in rheumatoid arthritis: Association with systemic inflammation, subclinical atherosclerosis, and cardiovascular risk.

OBJECTIVE: Quantification of retinal vessel morphology has emerged as a marker of cardiovascular health. We examined retinal microvascular diameters in RA, particularly in regard to systemic inflammation, subclinical atherosclerosis, and cardiovascular risk. METHODS: Retinal images from RA patients and controls were processed using computerized software, to obtain CRAE and CRVE and AVR. Subclinical atherosclerosis was assessed with cIMT, and 10-year risk of general cardiovascular disease was calculated. RESULTS: Both CRAE (78.8 ± 8.9 vs 90.2 ± 9.9 µm, P < .001) and AVR (0.69 ± 0.09 vs 0.81 ± 0.09, P < .001) were decreased in RA patients (n = 87) compared to controls (n = 46), whereas CRVE did not differ. Among RA patients, CRAE and AVR were inversely associated with both cIMT and CRP, whereas CRVE positively correlated with CRP (P < .05 for all). CRAE additionally correlated with cardiovascular risk score (r = -.396, P = .001). In the multivariate analysis, cardiovascular risk was associated with CRAE; age with CRVE, while CRP independently predicted AVR. CONCLUSIONS: Our study shows altered retinal microvascular morphology in RA patients. Inflammation appears as the biological link for the observed association between retinal microvascular abnormalities and subclinical atherosclerosis. Retinal arteriolar narrowing might play its own role in cardiovascular risk prediction in RA.

Graphic kinematics, visual virtual work and elastographics.

In this paper, recent progress in graphic statics is combined with Williot displacement diagrams to create a graphical description of both statics and kinematics for two- and three-dimensional pin-jointed trusses. We begin with reciprocal form and force diagrams. The force diagram is dissected into its component cells which are then translated relative to each other. This defines a displacement diagram which is topologically equivalent to the form diagram (the structure). The various contributions to the overall Virtual Work appear as parallelograms (for two-dimensional trusses) or parallelopipeds (for three-dimensional trusses) that separate the force and the displacement pieces. Structural mechanisms can be identified by translating the force cells such that their shared faces slide across each other without separating. Elastic solutions can be obtained by choosing parallelograms or parallelopipeds of the appropriate aspect ratio. Finally, a new type of 'elastographic' diagram-termed a deformed Maxwell-Williot diagram (two-dimensional) or a deformed Rankine-Williot diagram (three-dimensional)-is presented which combines the deflected structure with the forces carried by its members.

Aerial Oxidation of a V(IV)-Iminopyridine Hydroquinonate Complex: A Trap for the V(IV)-Semiquinonate Radical Intermediate.

The reaction of 2,5-bis[N,N'-bis(2-pyridyl-aminomethyl)aminomethyl]-p-hydroquinone (H2bpymah) with VO(2+) salts in acetonitrile or water at a low pH (2.2-3.5) results in the isolation of [{V(IV)(O)(Cl)}2(µ-bpymah)], the p-semiquinonate complex [{V(IV)(O)(Cl)}2(µ-bpymas)](OH), the cyclic mixed-valent hexanuclear compound [{V(V)(O)(µ-O)V(IV)(O)}(µ-bpymah)]3, and [(V(V)O2)2(µ-bpymah)]. [{V(IV)(O)(Cl)}2(µ-bpymas)](OH) is an intermediate of the radical-mediated oxidation of [{V(IV)(O)(Cl)}2(µ-bpymah)] from O2. At lower pH values (2.2), a reversible intramolecular electron transfer from the metal to the ligand of [{V(IV)(O)(Cl)}2(µ-bpymas)](OH) is induced with the concurrent substitution of chlorine atoms by the oxygen-bridging atoms, resulting in the formation of [{V(V)(O)(µ-O)V(IV)(O)}(µ-bpymah)]3. The metal complexes were fully characterized by X-ray crystallography, infrared (IR) spectroscopy, and magnetic measurements in the solid state, as well as by conductivity measurements, UV-vis spectroscopy, and electrochemical measurements in solution. The oxidation states of the metal ions and ligands were determined by the crystallographic data. The [{V(IV)(O)(Cl)}2(µ-bpymah)]-[{V(IV)(O)(Cl)}2(µ-bpymas)](OH) redox process is electrochemically reversible. The V(IV) ion in the semiquinonate compound exhibits a surprisingly low oxophilicity, resulting in the stabilization of OH(-) counterions at acidic pH values. An investigation of the mechanism of this reaction reveals that these complexes induce the reduction of O2 to H2O2, mimicking the activity of enzymes incorporating two redox-active centers (metal-organic) in the active site.

Inhaled nitric oxide plus iloprost in the setting of post-left assist device right heart dysfunction.

BACKGROUND: Pulmonary hypertension and right ventricular (RV) dysfunction may complicate the implantation of a left ventricular assist device (LVAD). We examined whether inhaled vasodilators can sufficiently reduce RV afterload, avoiding the need for temporary RV mechanical support. METHODS: The study includes 7 patients with RV dysfunction after LVAD insertion. Treatment consisted of inotropes, inhaled nitric oxide (10 ppm), and iloprost (10 µg) in repeated doses. Full hemodynamic profile was obtained before inhalation, during administration of inhaled NO alone (before and after iloprost), as well as after the first two doses of inhaled iloprost. Tricuspid annular velocity was estimated at baseline and before and after adding iloprost. RESULTS: There was a statistically significant reduction in pulmonary vascular resistance (PVR), mean pulmonary artery pressure (MPAP), RV systolic pressure, and pulmonary capillary wedge pressure, and a considerable increase in LVAD flow, LV flow rate index, and tricuspid annular velocity at all points of evaluation versus baseline. By the end of the protocol, MPAP/mean systemic arterial pressure, and PVR/systemic vascular resistance ratios were reduced by 0.17±0.03 (95% confidence interval, 0.10 to 0.25, p=0.001) and 0.12±0.025 (95% confidence interval, 0.06 to 0.18; p=0.003), respectively. The tricuspid annular velocity increased by 2.3±0.18 cm/s (95% confidence interval, 1.83 to 2.73 cm/s; p<0.001). Pairwise comparisons before and after iloprost showed an important decrease in PVR (p=0.022), MPAP (p=0.001), pulmonary capillary wedge pressure (p=0.002), and RV systolic pressure (p<0.001), and a rise in tricuspid annular velocity (p=0.008). CONCLUSIONS: Inhaled vasodilators mainly affected the pulmonary vasculature. Combination treatment with inhaled NO and iloprost sufficiently decreased PVR and MPAP on the basis of an additive effect, improved RV function, and avoided the need for RV assist device.

Circuit design and simulation of a transmit beamforming ASIC for high-frequency ultrasonic imaging systems.

This paper describes the design of a programmable transmit beamformer application-specific integrated circuit (ASIC) with 8 channels for ultrasound imaging systems. The system uses a 20-MHz reference clock. A digital delay-locked loop (DLL) was designed with 50 variable delay elements, each of which provides a clock with different phase from a single reference. Two phase detectors compare the phase difference of the reference clock with the feedback clock, adjusting the delay of the delay elements to bring the feedback clock signal in phase with the reference clock signal. Two independent control voltages for the delay elements ensure that the mark space ratio of the pulses remain at 50%. By combining a 10- bit asynchronous counter with the delays from the DLL, each channel can be programmed to give a maximum time delay of 51 µs with 1 ns resolution. It can also give bursts of up to 64 pulses. Finally, for a single pulse, it can adjust the pulse width between 9 ns and 100 ns by controlling the current flowing through a capacitor in a one-shot circuit, for use with 40-MHz and 5-MHz transducers, respectively.