To evaluate the effects of intravitreal bevacizumab for non-proliferative type 2 idiopathic macular telangiectasia (type 2 IMT) within a mean follow-up period of 18 months.
The authors ...retrospectively studied six eyes of five patients with type 2 IMT who received two doses of intravitreal bevacizumab (1.5 mg) at a 4-week interval, followed by further applications depending on disease activity. Examinations included biomicroscopy, standardised visual acuity (VA) testing, fluorescein angiography, retinal thickness analysis by optical coherence tomography and fundus-controlled microperimetry.
Mean follow-up time was 18 months (range 16-21 months). The mean VA at four selected time points (1 month after second treatment, 1 month and 3-4 months after last treatment, and at last visit) increased significantly (by 8.8, 6.3, 7.7 and 8.7 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, respectively; all p<or=0.05). Parafoveal leakage in fluorescein angiography and mean central retinal thickness decreased in all eyes following treatment. A rebound effect was observed after 3-4 months, and at the last visit, retinal thickness was increased in selected retinal sectors including the fellow eye.
Inhibition of vascular endothelial growth factor (VEGF) by intravitreally injected bevacizumab may lead to functional improvement as well as a transient decrease in leakage and retinal thickness in patients with type 2 IMT. A VEGF-mediated active disease stage in which treatment might be most effective is discussed.
To characterise the ocular phenotype of a family segregating the splice site mutation c.2189+1G>T in the tyrosine kinase receptor gene MERTK.
Five affected children of a consanguineous Moroccan ...family were investigated by ophthalmic examinations, including fundus photography, autofluorescence (FAF) imaging, optical coherence tomography (OCT), psychophysical and electrophysiological methods.
Affected children were between 5 and 19 years of age, allowing an estimation of disease progression. Electroretinography demonstrated loss of scotopic and photopic function in the first decade of life. Younger siblings showed drusen-like deposits with focal relatively increased FAF in the macular area. With increasing age, a yellowish lesion with relatively increased FAF and subsequent macular atrophy developed. Visual acuity deteriorated with age and ranged between 20/50 in the best eye of the youngest affected and 20/400 in the worst eye of the oldest affected sibling. Spectral-domain OCT revealed debris-like material in the subneurosensory space.
The splice site mutation c.2189+1G>T in MERTK causes rod-cone dystrophy with a distinct macular phenotype. The debris in the subneurosensory space resembles that in the Royal College of Surgeons (RCS) rat being the mertk animal model. Patients might therefore benefit from advances in gene therapy that were previously achieved in the RCS rat.
To investigate the efficacy of intravitreal bevacizumab injections for treating choroidal neovascularisation (CNV) secondary to pseudoxanthoma elasticum (PXE).
Patients with active CNV due to PXE ...received intravitreal bevacizumab (1.5 mg) and were reviewed at monthly intervals. Further treatments were administered depending on disease activity (visual loss of 5 letters or one line, persistent leakage, persistent macular oedema). Baseline and 1-3 monthly follow-up examinations included best corrected visual acuity (BCVA), biomicroscopy, optical coherence tomography (OCT), fluorescein and indocyanine green angiography, fundus autofluorescence and digital fundus photography.
15 patients (16 eyes) with CNV and PXE were treated. Mean (SD) age was 53 (12.3) years (range 24-72). Mean BCVA at baseline was 20/100 (mean (SD) LogMAR 0.68 (0.51)), improved to 20/63 after the first injection (LogMAR 0.49 (0.45); p = 0.028), and was 20/63 (LogMAR 0.48 (0.48); p = 0.126) at the last follow-up. The mean follow-up time was 8 months. Central retinal thickness decreased significantly from 252 mum at baseline to 214 mum at the last follow-up (p = 0.004) as measured by OCT. Eyes were injected an average of 2.4 times. Categorising patients into two groups (group 1 with only mild changes and group 2 with evident morphological changes in the central macula) revealed that group 1 improved significantly more (LogMAR range 0.41-0.06) than group 2 (LogMAR range 0.80-0.66) (p = 0.014).
The results indicate that intravitreal bevacizumab is effective both functionally and morphologically in treating CNV due to PXE. Best recovery can be achieved in eyes with disease that has not progressed too far and if treatment is initiated at the earliest point possible.
To describe the occurrence of discrete arcs of increased fundus autofluorescence (FAF) associated with various retinal dystrophies and to assess their functional significance by fundus-controlled ...microperimetry.
Seven patients, three with pigmented paravenous retinochoroidal atrophy (PPRCA), one with sector retinitis pigmentosa (RP), one with typical RP, and two with macular dystrophy were assessed by retinal imaging including FAF imaging. Serial images were obtained within a review period of 6 and 10 years in a patient with PPRCA and macular dystrophy, respectively. Fundus-controlled microperimetry was performed in eight eyes of five patients to determine light increment sensitivity.
A discrete arched line of increased FAF was observed without obvious correlate on fundus biomicroscopy. The orientation of this line differed from ring shape in RP and macular dystrophy, a semi-circle structure in sector RP to crescent shape with tiplike extensions towards branching retinal veins in PPRCA. Longitudinal investigation revealed slight migration of the arc in PPRCA and peripheral extension of the ring diameter in macular dystrophy. Microperimetry revealed that the arc of increased FAF sharply delineated areas of severely impaired retinal sensitivity.
The findings indicate that arcs of increased FAF in PPRCA and other retinal dystrophies demarcate areas of impaired retinal function and may migrate over time. FAF imaging may therefore reveal the exact extent of neurosensory dysfunction that may exceed the dimensions anticipated by conventional examinations.
To describe patients with full-thickness macular holes (FTMHs) and lamellar macular holes (LMHs) in association with type 2 idiopathic macular telangiectasia (type 2 IMT).
Six patients with either ...FTMH or LMH and type 2 IMT were evaluated by means of optical coherence tomography (OCT) imaging, funduscopy, and fluorescein angiography.
The age of the examined patients ranged from 57 to 70 years (mean 62.5+/-5.2), and best-corrected visual acuity of the affected eyes ranged from 20/50 to 20/200 (mean 20/100). All eyes showed macular abnormalities typical for nonproliferative type 2 IMT except for one eye with a proliferative disease stage. Three patients had an FTMH, one presenting with bilateral FTMH, and three had an LMH on OCT. In all cases of FTMH, the macular holes did not have elevated margins. Surgery was performed in two patients with a FTHM without subsequent functional improvement.
The altered foveal anatomy with progressive atrophic changes within the neurosensory retina in type 2 IMT may predispose to the development of FTMH and LMH. Type 2 IMT should be considered in the differential diagnosis in patients presenting with macular holes. The association between the two may reflect alternative pathogenetic mechanisms in the development of macular holes.
We analyzed the polysomnographic records of 15 children and 20 infants with obstructive sleep apnea (OSA) to examine the interaction between central and obstructive breathing abnormalities and ...arousal from sleep. Each patient was matched for age with an infant or child who had no OSA. We found that the majority of respiratory events in infants and children was not terminated with arousal. In children, arousals terminated 39.3 +/- 7.2% of respiratory events during quiet sleep and 37.8 +/- 7.2% of events during active (rapid-eye-movement) sleep. In infants, arousals terminated 7.9 +/- 1.0% of events during quiet sleep and 7.9 +/- 1.2% of events during active sleep. In both infants and children, however, respiratory-related arousals occurred more frequently after obstructive apneas and hypopneas than after central events. Spontaneous arousals occurred in all patients with OSA during quiet and active sleep. The frequency of spontaneous arousals was not different between children with OSA and their matched controls. During active sleep, however, infants with OSA had significantly fewer spontaneous arousals than did control infants. We conclude that arousals is not an important mechanism in the termination of respiratory events in infants and children and that electroencephalographic criteria are not essential to determine the clinical severity of OSA in the pediatric population.
The aim of this study was to evaluate the short- and long-term seizure outcome and to find predictors of outcome after epilepsy surgery in lesional posterior cortical epilepsies (PCEs).
The operative ...outcome in 80 consecutive adult patients with lesional PCEs who underwent resective surgery for intractable partial epilepsy between 1991 and 2006 was retrospectively studied.
The probability of remaining in Engel Class I was 66.3% (95% CI 60 to 72) at 6 months, 52.5% (95% CI 47 to 57) at 2 years, 52.9% (CI 45 to 59) at 5 years and 47.1% (CI 42 to 52) at 10 years. Factors predicting poor outcome were the presence of a somatosensory aura, extraregional spikes, incomplete resection, interictal epileptiform discharge (IED) in EEG 6 months and 2 years postsurgery, history of generalised tonic-clonic seizure (GT-CS) and the presence of focal cortical dysplasia in the resected specimen. Factors predicting good outcome were childhood onset of epilepsy, short epilepsy duration, ipsilateral spikes, visual aura, presence of well-circumscribed lesion in preoperative MRI and a pathologically defined tumour. In the multivariate analysis, predictors were different in the long and short term as follows: incomplete resection as proven by postoperative MRI (hazard ratio (HR) 2.059 (CI 1.19 to 3.67)) predicts seizure relapse in short-term follow-up. The presence of IED in the EEG performed 6 months after surgery (HR 2.3 (CI 1.128 to 4.734)) predicts seizure relapse in the long-term fellow-up. However, the absence of a history of GT-CS independently predicts seizure remission in short- and long-term follow-up.
Surgery in PCEs proved to be effective in short- and long-term follow-up. Lesional posterior cortical epilepsy may be a progressive process in a substantial number of cases.
Transplant glomerulopathy (TG) is a histopathologic entity of kidney allografts related to anti-human leukocyte antigen (HLA) antibodies. The goal of this study was to determine the relationships ...among antibody characteristics (level and specificity), risk for TG, and graft survival.
The presence and characteristics of anti-HLA antibody were assessed by single antigen beads assays in stored pretransplant sera from 598 kidney recipients with negative T-cell crossmatch. Transplant glomerulopathy was diagnosed by surveillance and clinical biopsies.
Thirty-nine percent of patients presented with anti-HLA antibodies pretransplant. Transplant glomerulopathy was diagnosed in 73 patients (12%) during 54+/-19 months of follow-up. The risk of TG increased with higher anti-HLA-II antibody levels (HR=1.890, 95% CI 1.42-2.52; P<0.0001), donor specificity of the antibodies (3.524 1.67-7.44; P=0.001), and in patients with history of antibody-mediated rejection (4.985 2.77-8.97; P<0.0001, multivariate Cox). Graft survival during the follow-up period was 95% without TG and 62% with TG (P<0.0001). The presence of C4d in peritubular capillaries was an independent risk factor for graft failure after TG diagnosis. Thus, 25% of TG/C4d and 80% of TG/C4d+ grafts failed (P<0.0001). Of interest, higher anti-HLA-II levels were related to the presence of C4d (3.216 1.376-7.517; P=0.007).
In T-cell negative crossmatch patients, higher anti-HLA-II antibody levels are related to the increase in the risk of developing TG. Higher antibody levels are also related to the presence of C4d in peritubular capillaries in TG biopsies. Furthermore, the presence of C4d in TG is related to the reduced graft survival.
For patients with painful chronic pancreatitis, surgical treatment is postponed until medical and endoscopic treatment have failed. Observational studies have suggested that earlier surgery could ...mitigate disease progression, providing better pain control and preserving pancreatic function.
To determine whether early surgery is more effective than the endoscopy-first approach in terms of clinical outcomes.
The ESCAPE trial was an unblinded, multicenter, randomized clinical superiority trial involving 30 Dutch hospitals participating in the Dutch Pancreatitis Study Group. From April 2011 until September 2016, a total of 88 patients with chronic pancreatitis, a dilated main pancreatic duct, and who only recently started using prescribed opioids for severe pain (strong opioids for ≤2 months or weak opioids for ≤6 months) were included. The 18-month follow-up period ended in March 2018.
There were 44 patients randomized to the early surgery group who underwent pancreatic drainage surgery within 6 weeks after randomization and 44 patients randomized to the endoscopy-first approach group who underwent medical treatment, endoscopy including lithotripsy if needed, and surgery if needed.
The primary outcome was pain, measured on the Izbicki pain score and integrated over 18 months (range, 0-100 increasing score indicates more pain severity). Secondary outcomes were pain relief at the end of follow-up; number of interventions, complications, hospital admissions; pancreatic function; quality of life (measured on the 36-Item Short Form Health Survey SF-36); and mortality.
Among 88 patients who were randomized (mean age, 52 years; 21 (24%) women), 85 (97%) completed the trial. During 18 months of follow-up, patients in the early surgery group had a lower Izbicki pain score than patients in the group randomized to receive the endoscopy-first approach group (37 vs 49; between-group difference, -12 points 95% CI, -22 to -2; P = .02). Complete or partial pain relief at end of follow-up was achieved in 23 of 40 patients (58%) in the early surgery vs 16 of 41 (39%)in the endoscopy-first approach group (P = .10). The total number of interventions was lower in the early surgery group (median, 1 vs 3; P < .001). Treatment complications (27% vs 25%), mortality (0% vs 0%), hospital admissions, pancreatic function, and quality of life were not significantly different between early surgery and the endoscopy-first approach.
Among patients with chronic pancreatitis, early surgery compared with an endoscopy-first approach resulted in lower pain scores when integrated over 18 months. However, further research is needed to assess persistence of differences over time and to replicate the study findings.
ISRCTN Identifier: ISRCTN45877994.
Abstract Background Renal failure is the most important comorbidity in patients with heart transplantation, it is associated with increased mortality. The major cause of renal dysfunction is the ...toxic effects of calcineurin inhibitors (CNI). Sirolimus, a proliferation signal inhibitor, is an imunossupressant recently introduced in cardiac transplantation. Its nonnephrotoxic properties make it an attractive immunosuppressive agent for patients with renal dysfunction. In this study, we evaluated the improvement in renal function after switching the CNI to sirolimus among patients with new-onset kidney dysfunction after heart transplantation. Methods The study included orthotopic cardiac transplant (OHT) patients who required discontinuation of CNI due to worsening renal function (creatinine clearance < 50 mL/min). We excluded subjects who had another indication for initiation of sirolimus, that is, rejection, malignancy, or allograft vasculopathy. The patients were followed for 6 months. The creatinine clearance (CrCl) was estimated according to the Cockcroft-Gault equation using the baseline weight and the serum creatinine at the time of introduction of sirolimus and 6 months there after. Nine patients were included, 7 (78%) were males and the overall mean age was 60.1 ± 12.3 years and time since transplantation 8.7 ± 6.1 years. The allograft was beyond 1 year in all patients. There was a significant improvement in the serum creatinine (2.98 ± 0.9 to 1.69 ± 0.5 mg/dL, P = .01) and CrCl (24.9 ± 6.5 to 45.7 ± 17.2 mL/min, P = .005) at 6 months follow-up. Conclusion The replacement of CNI by sirolimus for imunosuppressive therapy for patients with renal failure after OHT was associated with a significant improvement in renal function after 6 months.
PDF
