Search

Importance To determine visual and surgical results in children with Marfan syndrome. Background Marfan syndrome involves ocular complications which can lead to visual disturbance and amblyopia. Data about the visual and surgical results in children with Marfan syndrome is vital for the clinical management of these patients. Design Retrospective data analysis. Participants Eighty‐two eyes of 41 patients with a genetically proved diagnosis of Marfan syndrome. Methods Medical records of patients with Marfan syndrome were reviewed between 2007 and 2017. Ocular complications, visual acuity (VA) of patients with/without lensectomy and surgical method were evaluated. Main Outcome Measures VA outcomes of patients with Marfan syndrome with/without surgical repair of ectopia lentis. Results In 27 (66%) of the 41 patients a bilateral subluxation of the lens was visible and 14 (52%) patients received lensectomy. The mean age at initial presentation was 12.3 ± 9 years and mean follow‐up was 3 years (range 1‐7). VA varied from 1.2 to −0.1 logMAR at first examination. At initial presentation, mean VA was 0.1 ± 0.7 logMAR in patients with a normal lens status (n = 14) and 0.3 ± 0.5 logMAR in patients with subluxation of the lens (n = 27) (P

Graves’ orbitopathy (GO) is the main extrathyroidal manifestation of Graves’ disease (GD). Choice of treatment should be based on the assessment of clinical activity and severity of GO. Early referral to specialized centers is fundamental for most patients with GO. Risk factors include smoking, thyroid dysfunction, high serum level of thyrotropin receptor antibodies, radioactive iodine (RAI) treatment, and hypercholesterolemia. In mild and active GO, control of risk factors, local treatments, and selenium (selenium-deficient areas) are usually sufficient; if RAI treatment is selected to manage GD, low-dose oral prednisone prophylaxis is needed, especially if risk factors coexist. For both active moderate-to-severe and sight-threatening GO, antithyroid drugs are preferred when managing Graves’ hyperthyroidism. In moderate-to-severe and active GO i.v. glucocorticoids are more effective and better tolerated than oral glucocorticoids. Based on current evidence and efficacy/safety profile, costs and reimbursement, drug availability, long-term effectiveness, and patient choice after extensive counseling, a combination of i.v. methylprednisolone and mycophenolate sodium is recommended as first-line treatment. A cumulative dose of 4.5 g of i.v. methylprednisolone in 12 weekly infusions is the optimal regimen. Alternatively, higher cumulative doses not exceeding 8 g can be used as monotherapy in most severe cases and constant/inconstant diplopia. Second-line treatments for moderate-to-severe and active GO include (a) the second course of i.v. methylprednisolone (7.5 g) subsequent to careful ophthalmic and biochemical evaluation, (b) oral prednisone/prednisolone combined with either cyclosporine or azathioprine; (c) orbital radiotherapy combined with oral or i.v. glucocorticoids, (d) teprotumumab; (e) rituximab and (f) tocilizumab. Sight-threatening GO is treated with several high single doses of i.v. methylprednisolone per week and, if unresponsive, with urgent orbital decompression. Rehabilitative surgery (orbital decompression, squint, and eyelid surgery) is indicated for inactive residual GO manifestations.

This article reports on two cases of severe pediatric Graves orbitopathy (GO) in two adolescents of African origin. Two black male adolescents presented with highly active GO and signs of beginning compressive optic neuropathy. Neither of them were smokers nor had a family history of GO. Besides urgent referral to pediatric endocrinologists, intravenous methylprednisolon pulse therapy was initiated. In spite of the fluctuating thyroid hormone levels in the initial phase of antithyroid therapy, intravenous steroid administration stopped the progression of malignant GO rapidly in both of our patients without any considerable side effects. Although the course of GO during childhood is considered to be mild, severe, sight threatening GO—requiring immunosuppression—may occur at young age, as in the reported adolescent patients of African descent.

Background Graves’ disease (GD) is characterized by thyrotoxicosis and goiter and arises through circulating autoantibodies that bind to, and stimulate, the thyroid hormone receptor (TSHR). A temporal relation between the onset of hyperthyroidism and the onset of ophthalmopathy, a common extrathyroidal manifestation, has been demonstrated. Graves’ ophthalmopathy (GO) is typically characterized by an inflammation and expansion of the extraocular muscles and an increase in retroorbital fat. There are currently three forms of therapies offered for hyperthyroidism caused by Graves’ disease: antithyroid drugs (ATD) (thionamides), radioiodine ablation (RAI) and thyroidectomy (Tx). To date, there is no clear recommendation on the treatment of Graves’ disease and GO, mainly due to the individuality of the disease in each patient. The aim of the study is to examine the difference in the outcome of GO in patients with moderate-to-severe GO who receive Tx versus further ATD after suffering their first relapse of GO, or in which GO stays the same following the initial decrease in ATD therapy after 6 months. Methods/Design This prospective randomized clinical trial with observer-blinded analysis will analyze 60 patients with moderate-to-severe GO who receive Tx versus ATD without surgery. Main outcome variables include: muscle index measurements via ultrasound and thyroid antibody levels. Additional outcome variables include: Clinical Activity Score (CAScore), NOSPECS score, superonasal index measurements via ultrasound, and quality of life score. Discussion This study should allow for better therapeutic choices in patients with moderate-to-severe GO. In addition, it should demonstrate whether the outcome of GO in patients with moderate-to-severe GO is better in those who receive early Tx versus further ATD. Furthermore, this study will aim to establish a standard glucocorticoid scheme before and after Tx in patients with moderate-to-severe EO. Trial registration Eudra-CT: 2015–003515-38; Medical University of Vienna Protocol Record 1839/2015. Date of Ethics Committee approval: 19 January 2017. Registered on 27 January 2017.

PURPOSE To evaluate the effect of patients' clinical information on experts' diagnoses of retinopathy of prematurity (ROP) and decisions to treat. METHODS Seven experts assessed wide-field fundus photographs of eyes of 52 premature infants of ≤30 weeks' gestational age or ≤1,500 g birthweight (BW) for ROP diagnosis (stage, plus disease, and aggressive posterior ROP) and the necessity for treatment for 2 days. On Day 1, they were masked to all patient data. On Day 2, they were given information on gestational age and BW. RESULTS A significant shift in the experts' ratings toward a less aggressive ROP grading stage (P = 0.006) and less frequent decision for intervention (P = 0.021) was observed after receipt of patients' clinical information. This was truer for heavier/less premature infants (gestational age ≥ 28 0/7 weeks or BW ≥ 900 g) than those with very low BWs/high prematurity (gestational age < 24 0/7 weeks or BW < 600 g) (ROP stage P = 0.009 vs. P = 0.399, treatment decision P = 0.022 vs. P = 0.648). CONCLUSION These results suggest knowledge of patients' clinical information influences the grading of ROP disease and decision for treatment. Retinopathy of prematurity staging seemed to be set at a lower level and the decision for treatment at a higher threshold for heavier/less premature babies. Our findings may have implications for further refinements in ROP assessment.

Purpose To investigate the influence of the vitreomacular interface (VMI) on the functional and anatomic efficacy of ranibizumab therapy in patients with neovascular age-related macular degeneration (AMD). Design Subanalysis of a prospective, 12-month, multicenter, phase IIIb trial. Participants A total of 353 treatment-naive patients with subfoveal choroidal neovascularization (CNV) receiving quarterly or monthly ranibizumab therapy. Methods On monthly optical coherence tomography (OCT) scan sets, the VMI configuration was graded by a certified reading center into one of the following conditions: continuous posterior vitreoretinal attachment (PVA), vitreomacular adhesion (VMA), partial vitreous detachment without vitreomacular contact, or complete posterior vitreous detachment (PVD). Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) measurements were performed at monthly intervals. Analysis included patients with a minimum of 10 OCT examinations, including baseline and month 12 (n = 251). After integration of the VMI configuration over 12 months, patients were divided into one of the following categories: PVD (n = 162), release of vitreomacular contact (RELEASE; n = 48), VMA (n = 37), or PVA (n = 4). General estimation equation analyses were applied to test for noninferiority of quarterly versus monthly treatment. Main Outcome Measures The BCVA and CRT changes at month 12. Results Mean BCVA changes in letters were +4.7 (PVD), +3.2 (RELEASE), and −0.2 (VMA) in the quarterly regimen and +4.9 (PVD), +12.7 (RELEASE), and +7.5 (VMA) in the monthly regimen. No difference in therapeutic efficiency between monthly and quarterly intervention was found in eyes with PVD, and quarterly treatment was noninferior to monthly treatment ( P = 0.001). However, monthly treatment was superior to quarterly treatment in the RELEASE ( P = 0.008) and VMA ( P = 0.043) groups. Mean CRT changes were −98 and −96 μm (PVD), −117 and −136 μm (RELEASE), and −93 and −87 μm (VMA) in the monthly and quarterly regimens, respectively, without statistically significant differences. Conclusions The configuration of the VMI seems to have an important effect on visual outcomes and need for retreatment. In patients with PVD, a lower treatment frequency may be feasible, whereas patients with RELEASE or VMA may benefit from intensive retreatment. These findings may serve as a basis for individualized treatment decisions in anti-angiogenic therapy of neovascular AMD and perhaps other indications. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Purpose To evaluate inter-expert and intra-expert agreement on the diagnosis and treatment of retinopathy of prematurity (ROP). Design Prospective intra- and inter-rater reliability analysis. Methods In this multicenter study, 260 wide-field digital photographs of 52 patients were presented to 7 recognized ROP experts on 2 consecutive assessment days 8 weeks apart. Experts were asked to assess the patients for ROP stage, presence of plus disease, presence of aggressive posterior ROP, necessity for treatment, and suggested treatment. Agreement levels were measured with Fleiss' kappa and Cohen's kappa. Results Inter-expert agreement was fair for the ROP stage (κ = 0.24), plus disease (κ = 0.32), and aggressive posterior ROP (κ = 0.35); moderate for the necessity for treatment (κ = 0.41); and fair for the kind of treatment (κ = 0.38). Perfect inter-expert agreement was found in 9.6% of all patients for ROP stage 0–5, 45.1% for ≥ stage 2 ROP, 17.3% for plus disease, 57.7% for aggressive posterior ROP, and 25% for the necessity for treatment. Intra-expert agreement was higher than inter-expert agreement and was moderate for the ROP stage (κ = 0.56) and plus disease (κ = 0.51), moderate to substantial for aggressive posterior ROP (κ = 0.60), moderate for the necessity for treatment (κ = 0.47), and substantial for the kind of treatment (κ = 0.63). Conclusions ROP diagnosis and treatment decisions differ between experts and by 1 expert made on different days, indicating that the grading process is subjective and there is an observer bias when diagnosing ROP. These results could influence current practice in ROP assessment and training, and prompt further refinement of international ROP guidelines.

Uridine, like adenosine, is released under sustained depolarization and it can inhibit hippocampal neuronal activity, suggesting that uridine may be released during seizures and can be involved in epileptic mechanisms. In an in vivo microdialysis study, we measured the extracellular changes of nucleoside and amino acid levels and recorded cortical EEG during 3-aminopyridine-induced epilepsy. Applying silver impregnation and immunohistochemistry, we examined the degree of hippocampal cell loss. We found that extracellular concentration of uridine, adenosine, inosine, and glutamate increased significantly, while glutamine level decreased during seizures. The release of uridine correlated with seizure activity. Systemic and local uridine application was ineffective. The number of parvalbumin- and calretinin-containing interneurons of dorsal hippocampi decreased. We conclude that uridine is released during epileptic activity, and suggest that as a neuromodulator, uridine may contribute to epilepsy-related neuronal activity changes, but uridine analogues having slower turnover would be needed for further investigation of physiological role of uridine.

In the present study, we compared in vivo changes of extracellular amino acid levels and nucleotide derivatives to a single ip dose of lindane (10-60 mg/kg) and picrotoxin (5 mg/kg) in the hippocampus of halothane anaesthetized rat by microdialysis-coupled HPLC analysis. Brain activity was monitored by EEG. The effects of lindane and picrotoxin on EEG pattern of rats as well as on hippocampal amino acid and nucleotide status were studied in 0-50 min, 50-100 min and 100-150 min periods post-dosing. Significant decreases in Glu and Asp were found after picrotoxin treatment. After 50-100 min post-dosing, hippocampal hypoxanthine and inosine levels increased to both lindane (10 mg/kg) and picrotoxin whereas xanthine and uridine levels increased to picrotoxin, only. Lindane elicited a dose-dependent occurrence of negative spikes accompanied with rhythmic activity at 4-5 Hz. The picrotoxin-induced 4-5 Hz activity did not display negative sharp waves and was accompanied by 10 Hz oscillations.

The objective of this study was to evaluate the correlation between twin-twin transfusion syndrome (TTTS) and the development of retinopathy of prematurity (ROP) in premature infants.Fifty-one infants who were less than 32 postmenstrual gestational weeks at birth or with a birth weight less than 1,501grams were included in this longitudinal observational study. The infants were matched by gestational age and birth weight, and divided into three groups: multiples with TTTS, multiples without TTTS, and singletons. The primary outcome variable was the incidence of ROP in infants affected by TTTS versus infants not affected by TTTS. Secondary outcome variables were multiple pregnancy, gestational age, and birth weight.Infants affected by TTTS showed a significantly higher incidence of ROP than infants not affected by TTTS (p 0.01). TTTS donors and TTTS recipients were both at greater risk of developing ROP. ROP occurred in infants with TTTS whose gestational age at birth was significantly higher than that of infants with ROP who were not affected by TTTS (p = 0.01). Multiple pregnancy itself was not a risk factor for ROP disease.Infants affected by TTTS during pregnancy are at high risk of developing ROP, even if they were born at an older gestational age. Special awareness in ROP screening is necessary for these infants.

This study examines the glutathione status of red blood cells in patients with retinopathy of prematurity (ROP) both in vivo and after an in vitro oxidative challenge. Fifty ROP patients of different ages (between 6 weeks and 6 years), born prematurely (gestational age: 28.7 +/- 1.3 weeks; birth weight: 1210 +/- 313 g; mean +/- SD) suffering either from active ROP (

Purpose To report the visual, refractive, and functional outcomes of photorefractive keratectomy (PRK) and of laser-assisted subepithelial keratectomy in a group of children with significant refractive error and underlying medical conditions or ocular pathology who were noncompliant with traditional management. Setting Nonhospital surgical facility and a hospital clinic. Methods This case series comprised 5 individual cases of anisometropic amblyopia and/or high myopia. Underlying medical and ocular conditions were as follows: upper eyelid hemangioma with oblique myopic astigmatism, Pelizaeus-Merzbacher leukodystrophy with nystagmus, Klippel-Trenaunay-Weber syndrome with glaucoma, incontinentia pigmenti with unilateral optic nerve atrophy, and Goldenhar syndrome with unilateral optic nerve hypoplasia. Photorefractive keratectomy or LASEK was performed in 6 eyes of 5 patients. Age range at the time of surgery was 1.0 to 7.0 years. All procedures were performed under general anesthesia. Results Best corrected visual acuity improved by 2 lines in 2 patients and 1 line in 2 patients by 6 months after surgery. Stereopsis and/or fusional status improved in 3 patients. Amblyopia treatment compliance improved in 1 patient. Alignment improved without strabismus surgery in 2 cases. A functional vision survey demonstrated a positive effect on the ability of all 5 children to function in their environment. Conclusion During the period of visual cortical plasticity, refractive surgery, by eliminating the refractive component of amblyopia and by promoting fusional ability, provides considerable improvement in children, even those with underlying medical conditions associated with ocular pathology.

We hypothesized that activation of the xanthine oxidase (XO) enzyme system is a potential source of free radicals in pregnancy-induced hypertension (PIH).A prospective observational study was carried out on 16 pregnant women who met the criteria of gestational hypertension [rise in blood pressure (BP) of 30 mm Hg systolic or 15 mm Hg diastolic after 20 weeks gestation or BP140/90 mm Hg if earlier pressure is unknown] without proteinuria or any signs of renal impairment. Fourteen women with a clinically normal pregnancy matched for maternal age, parity, and gestational age acted as pregnant controls. Nonpregnant control women were members of the laboratory staff ( n=15).Concentrations of free sulfhydryl (SH) groups, purine catabolites, lipid peroxidation products in plasma, and blood carboxyhemoglobin levels were used to follow oxidative stress and potential hemolysis. A noninvasive measurement of functional XO activity was carried out (i.e., the urinary ratio of the two metabolites of caffeine was estimated).A pronounced oxidative stress was demonstrated in plasma samples of patients with hypertension by the elevated concentrations of uric acid and lipid peroxidation products. A reduced level of free sulfhydryl groups and an increased concentration of hypoxanthine (HX) were shown in normotensive pregnant individuals. The XO activity index was substantially higher in overweight pregnant subjects with mild hypertension [0.849+/-0.096 ( p0.01)] than in normotensive pregnant women or in age-matched nonpregnant subjects [0.596+/-0.105, 0.542+/-0.049 (means+/-SD), respectively].Our study of mildly hypertensive pregnant subjects provides additional evidence of the putative role of XO activation as a source of free radicals in the early stage of endothelial dysfunction.

In the neonatal period, there is a high iron load, while both the level and molar oxidase activity of ceruloplasmin are low. On the other hand, the neonatal xanthine oxidase (XO) activity is higher than later in life and XO has a significant iron-oxidizing capacity. We therefore studied the physiological contribution of XO to the ferroxidase activity of the plasma in 20 full-term newborn infants. Ferroxidase activity was measured spectrophotometrically, with Fe++ as substrate. The uric acid formed by XO was assayed by means of HPLC, with electrochemical detection. The total ferroxidase activity in the plasma was about one-fourth of the adult level and rapidly increased doubling within 3 days after birth. About 90% of the plasma ferroxidase activity was due to ceruloplasmin, the remainder being accounted for by ferroxidase II. The XO activity underwent a 30% (statistically non-significant) elevation at 24 h, though ferroxidase activity attributable to XO was not detected at any time. Accordingly, XO does not seem to add substantially to the total iron-oxidizing capacity of the plasma in the neonatal period. The high molar ferroxidase activity is probably of importance at the endothelial cell surface.

Joint ESC/EASD guidelines recommend testing for diabetes (DM) using oral glucose tolerance test (OGTT) in patients with CAD. SWEETHEART enrolled 2,767 consecutive patients (pts) with STEMI or NSTEMI to identify newly diagnosed DM (new DM) and to document outcome. In pts without DM, OGTT was

A method for the preparation of an in vivo eyecup and a complex stimulating-sampling device are described; these are suitable for long-term parallel neurochemical and electrophysiological experiments on the rat retina without any additives into the eyecup. In this in vivo eyecup the extracellular microenvironment is under the normal homeostatic control of the vascular system; no continuous exchange of the eyecup fluid and no addition of glutamate is necessary to maintain stable retinal electric responses and amino acid concentrations. The eyecup viability was tested by monitoring the electroretinogram (ERG) and the amino acid contents of the eyecup fluid sampled from the preretinal space by means of microdialysis. After the initial increase the b-wave of the ERG changed by less than 10% in maximal amplitude during experiments lasting 5 h. The glutamate, glutamine, and glycine levels proved comparatively, whereas the taurine level rose continuously throughout the experimental protocol. Recovery of ERG was achieved following exposure to bright background illumination. Total exchange of the eyecup volume requires 20 min at a flow rate of 1 microl/min. The effect of L-AP4 on the ERG was successfully reproduced, which suggests the applicability of this in vivo eyecup for pharmacological experiments on the rat retina.

Background:Four premature babies (eight eyes) undergoing simultaneous bilateral cataract surgery are presented and discussed.Methods:All four babies underwent simultaneous bilateral cataract surgery. Three babies (six eyes) had primary implantation of posterior chamber intraocular lenses (IOLs) and one baby (two eyes) had primary lensectomies with secondary visual correction with contact lenses. Results: In all eight eyes, there was no endophthalmitis and no spontaneous choroidal hemorrhages. All eyes experienced large myopic shifts, as high as –15.00 D. All six eyes with IOLs required secondary membranectomies, which did not reoccur. Case 4 had Lowe’s syndrome, was bilaterally aphakic post-op, and subsequently developed glaucoma requiring bilateral glaucoma surgery. Conclusions: Simultaneous bilateral cataract surgery in severely premature babies can be successful in restoring vision over the long term. Strategies to successfully deal with the timing of surgery, IOLs, secondary membranes, secondary glaucoma, appropriate IOL powers, and IOL formulas is discussed. Successful long-term successful visual outcomes are now possible in this complex group of premature babies.

There is a considerable prevalence of glucose abnormalities in patients presenting with an acute myocardial infarction. The present analysis reports the prevalence of dysglycemia and the impact of newly diagnosed diabetes on mortality at the 3-year follow-up. A total of 2,767 consecutive patients