Refractive Corneal Lenticule Extraction on Previous Photorefractive Keratectomy, with Optical Coherence Tomography Study

We report the first case of refractive corneal lenticule extraction with the femtosecond laser application CLEAR as retreatment technique after previous laser vision correction. A 42-year-old woman, operated by bilateral photorefractive keratectomy (PRK) 19 years previously, with moderate dry eye, came for post-PRK regression and underwent correction of a residual myopia of −3 −0.5 × 159° D in the left eye by CLEAR. Surgery was uneventful, with a regular laser pattern and a normal dissection of the lenticule. At day 1, uncorrected visual acuity was 20/25; at 3 months, it was 20/20, with a refraction of +0.25 × 115° D. The cornea and interface were regular and transparent; no dry eye symptoms occurred. At 3 months, on optical coherence tomography, the treatment was well centered, the surgical interface was centrally regular, whereas the anterior profile of the stromal surface was slightly corrugated, compensated by a smooth epithelial surface. The present case demonstrates that myopia after PRK can be achieved by CLEAR; an irregular stromal surface may occur, not affecting the visual result in virtue of epithelial remodeling

Keratoconus and keratoectasia:advancements in diagnosis and treatment

Full text: Keratoconus (KC) and iatrogenic keratoectasia are receiving increasing attention, due to the improvements in diagnostic modalities and the availability of therapeutic options, which now include collagen cross-linking, intrastromal implants, intraocular lenses, microwave remodeling, and anterior lamellar keratoplasty. Limitations of surgical treatments of keratoconus are well known. Intrastromal implants, built in various shapes and now implanted more safely through femtosecond-laser-obtained stromal channels, still retain reduced predictability as for the refractive results and do not modify the structure of the diseased cornea. Anterior lamellar keratoplasty, even in its more advanced and technically difficult variant of deep anterior lamellar keratoplasty (DALK), cures the disease by the (almost) complete replacement of the ectatic stroma but, even when a regular and transparent interface is achieved, final refractive errors and higher-order aberrations may severely affect visual rehabilitation. The use of femtosecond laser in DALK to shape the donor and recipient margins has not significantly improved the picture yet. Parasurgical treatments of KC are therefore regarded as a temporary or definitive alternative to surgical interventions. Among the newest ideas, the promising use of microwave to heat and reshape the corneal apex shares the principle with previous modalities of thermal keratoplasty, which were characterized by regression and induction of irregular astigmatism. The long-term validity of microwave reshaping is, therefore, still being investigated. The use of collagen corneal cross-linking (CXL) with riboflavin and ultraviolet (UV) has rapidly expanded in the world and is currently regarded as the only recognized treatment to slow or arrest KC progression, obtaining in some cases a significant improvement of corneal curvature and regularity. However, as most new treatments, CXL is still far from being ideal. Riboflavin for CXL is unreasonably expensive; the treatment is long and tedious and is followed by postoperative pain and slow visual rehabilitation. Complications are not uncommon, including infections and scarring. The indications to the treatment are still debated as for age, KC stage, and corneal thickness. Alternative attempts to reduce the CXL operating time by increasing the irradiation energy or by avoiding epithelial removal have been made, but all deviations from the defined original protocol may reduce the efficacy of treatment, and therefore new treatment protocols are currently further investigated. In this special issue, various and new aspects of CXL are examined, rehabilitation with contact lenses of KC is reviewed, and the features of posterior KC at ultrasound biomicroscopy are evaluated. Patient selection for CXL is not completely codified, and age limits are conventionally established. For example, the Italian National Health Service limits CXL reimbursement for patients between 12 and 40 years, the lower limit being dictated by common sense and the upper limit by the presumption of spontaneous KC stabilization after 40. A. Caporossi and Mazzotta et al., leading experts of CXL, in their original study in this issue, compare KC stabilization, improvement of corneal curvature, visual acuity, and aberrations 48 months after CXL in different age groups, concluding that the highest benefits were obtained in younger eyes. CXL procedure was originally developed to stiffen the keratoconic cornea, but its indications have been recently extended to postrefractive surgery ectasia, to infectious keratitis (due to a powerful antimicrobial action), and to corneal edema, where CXL temporarily reduces the space for fluid accumulation. These new indications of CXL, as well as its physical and chemical background, biomechanical effects, and clinical results, are thoroughly reviewed in the paper by M. Hovakimyan et al., where the real possibilities of transepithelial CXL and of the new approach combining photorefractive keratectomy (PRK) and CXL are discussed. Several reports of infectious keratitis after CXL have recently raised the issue of CXL safety: it would appear that the risk of infection is considerably higher than after PRK. The length of the procedure or the slow epithelialization time could be the reasons for such increased infectious risk. In addition, the peculiar “demarcation” haze, regarded as a demonstration of the cross-linking effect, can sometimes turn into a significant, long-term scar. These complications and others are well reviewed in the paper by S. Dhawan et al. Fortunately, most patients with KC will never need to undergo any surgical or parasurgical procedure. Visual rehabilitation is sometimes possible with the sole help of spectacles, but the reduction of higher-order aberrations is only possible with contact lenses. The extended wear of contact lenses and the difficult adaptation in keratoconic eyes imply a thorough knowledge of various contact lens models available: this is the subject of the article by Ozkurt et al. The paper by B. Rejdak et al. is a case report of a rare, nonprogressive variant of KC, circumscribed posterior keratoconus. The correct diagnosis of this form of ectasia is only possible by modern three-dimensional imaging technique, and in this case ultrasound biomicroscopy and slit scanning topography were used to reveal the protrusion of the posterior corneal surface. In this historical period we are directly witnessing the rise (and fall) of many therapeutic modalities for KC, but we can nevertheless look with optimism at the future of a complex and multiform disease, characterized by individualised treatment and prognosis. We hope that this special issue will contribute to stimulating discussion

Creation of a Corneal Flap for Laser In Situ Keratomileusis Using a Three-Dimensional Femtosecond Laser Cut: Clinical and Optical Coherence Tomography Features

Laser in situ keratomileusis (LASIK) is the most frequently used technique for the surgical correction of refractive errors on the cornea. It entails the creation of a superficial hinged corneal flap using a femtosecond laser, ablation of the underlying stromal bed using an excimer laser, and repositioning of the flap. A corneal flap with an angled side cut reduces the risk of flap dislocation and infiltration of epithelial cells and confers unique biomechanical properties to the cornea. A new laser software creating three-dimensional (3D) flaps using a custom angle side cut was retrospectively evaluated, comparing optical coherence tomography 3D (with intended 90° side cut) and 2D flaps (with tapered side cuts) as well as respective intra- and early postoperative complications. Four hundred consecutive eyes were included, two hundred for each group. In the 3D group, the mean edge angle was 92°, and the procedure was on average 5.2 s slower (p = 0). Non-visually significant flap folds were found in thirteen eyes of the 2D group and in seven eyes of the 3D group (p = 0.17). In conclusion, the creation of a LASIK flap using a 3D femtosecond laser cut, although slightly slower, was safe and effective. The side cut angle was predictable and accurate

il contributo della pet tc con 18f fdg nelle vasculiti dei grossi vasi applicazioni e limiti della metodica nella pratica clinica

Summary Introduction 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) plays a key role in oncology, and it is now being used increasingly to diagnose, characterize, and monitor disease activity in inflammatory disorders, including vasculitis. Unfortunately, its role in the management of vasculitis is still not well-defined, and clinicians are often unsure how this metabolic imaging technique should be used in these diseases, although its usefulness in diagnosing large-vessel vasculitis has been clearly demonstrated. Materials and methods We reviewed the literature about the use of PET/CT in the management of vasculitis in an attempt to identify the applications and the limitations of this technique in clinical practice. Results and discussion Our literature review revealed that 18 F-FDG PET/CT is a useful tool for diagnosing vasculitis (especially when the symptoms of the disease are non-specific); guiding biopsy procedures (areas with high glucose consumption); evaluating disease extension; and monitoring treatment responses. The main limitations of this method are the relatively low spatial resolution of the tomograph, which can lead to false-negative results in the presence of small-vessel vasculitis, and risk of false positive results, especially those related to the presence of atherosclerosis and to post-treatment vascular remodeling

Pioglitazone Improves Myocardial Blood Flow and Glucose Utilization in Nondiabetic Patients With Combined Hyperlipidemia A Randomized, Double-Blind, Placebo-Controlled Study

ObjectivesThis study’s aim was to examine whether treatment with pioglitazone, added to conventional lipid-lowering therapy, would improve myocardial glucose utilization (MGU) and blood flow (MBF) in nondiabetic patients with familial combined hyperlipidemia (FCHL).BackgroundThiazolidinediones were found to improve insulin sensitivity and MGU in type 2 diabetes and MBF in Mexican Americans with insulin resistance. Familial combined hyperlipidemia is a complex genetic disorder conferring a high risk of premature coronary artery disease, characterized by high serum cholesterol and/or triglyceride, low high-density lipoprotein (HDL) cholesterol, and insulin resistance.MethodsWe undertook a randomized, double-blind, placebo-controlled study in 26 patients with FCHL, treated with pioglitazone or matching placebo 30 mg daily for 4 weeks, followed by 45 mg daily for 12 weeks. Positron emission tomography was used to measure MBF at rest and during adenosine-induced hyperemia and MGU during euglycemic hyperinsulinemic clamp at baseline and after treatment.ResultsWhereas no change was observed in the placebo group after treatment, patients receiving pioglitazone showed a significant increase in whole body glucose disposal (3.93 ± 1.59 mg/kg/min to 5.24 ± 1.65 mg/kg/min; p = 0.004) and MGU (0.62 ± 0.26 μmol/g/min to 0.81 ± 0.14 μmol/g/min; p = 0.0007), accompanied by a significant improvement in resting MBF (1.11 ± 0.20 ml/min/g to 1.25 ± 0.21 ml/min/g; p = 0.008). Furthermore, in the pioglitazone group HDL cholesterol (+28%; p = 0.003) and adiponectin (+156.2%; p = 0.0001) were increased and plasma insulin (−35%; p = 0.017) was reduced.ConclusionsIn patients with FCHL treated with conventional lipid-lowering therapy, the addition of pioglitazone led to significant improvements in MGU and MBF, with a favorable effect on blood lipid and metabolic parameters. (A study to investigate the effect of pioglitazone on whole body and myocardial glucose uptake and myocardial blood flow/coronary vasodilator reserve in patients with familial combined hyperlipidaemia; http://www.controlled-trials.com/mrct/trial/230761/ISRCTN78563659; ISRCTN78563659

Nomogram predicting response after chemoradiotherapy in rectal cancer using sequential PETCT imaging: a multicentric prospective study with external validation.

Abstract Purpose To develop and externally validate a predictive model for pathologic complete response (pCR) for locally advanced rectal cancer (LARC) based on clinical features and early sequential 18 F-FDG PETCT imaging. Materials and methods Prospective data (i.a. THUNDER trial) were used to train ( N =112, MAASTRO Clinic) and validate ( N =78, Universita Cattolica del S. Cuore) the model for pCR (ypT0N0). All patients received long-course chemoradiotherapy (CRT) and surgery. Clinical parameters were age, gender, clinical tumour (cT) stage and clinical nodal (cN) stage. PET parameters were SUV max , SUV mean , metabolic tumour volume (MTV) and maximal tumour diameter, for which response indices between pre-treatment and intermediate scan were calculated. Using multivariate logistic regression, three probability groups for pCR were defined. Results The pCR rates were 21.4% (training) and 23.1% (validation). The selected predictive features for pCR were cT-stage, cN-stage, response index of SUV mean and maximal tumour diameter during treatment. The models' performances (AUC) were 0.78 (training) and 0.70 (validation). The high probability group for pCR resulted in 100% correct predictions for training and 67% for validation. The model is available on the website www.predictcancer.org. Conclusions The developed predictive model for pCR is accurate and externally validated. This model may assist in treatment decisions during CRT to select complete responders for a wait-and-see policy, good responders for extra RT boost and bad responders for additional chemotherapy

Effect of Dapagliflozin on Myocardial Insulin Sensitivity and Perfusion: Rationale and Design of The DAPAHEART Trial

Introduction: Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have been shown to have beneficial effects on various cardiovascular (CV) outcomes in patients with type 2 diabetes (T2D) in primary prevention and in those with a high CV risk profile. However, the mechanism(s) responsible for these CV benefits remain elusive and unexplained. The aim of the DAPAHEART study will be to demonstrate that treatment with SGLT-2 inhibitors is associated with greater myocardial insulin sensitivity in patients with T2D, and to determine whether this improvement can be attributed to a decrease in whole-body (and tissue-specific) insulin resistance and to increased myocardial perfusion and/or glucose uptake. We will also determine whether there is an appreciable degree of improvement in myocardial-wall conditions subtended by affected and non-affected coronary vessels, and if this relates to changes in left ventricular function. Methods: The DAPAHEART trial will be a phase III, single-center, randomized, two-arm, parallel-group, double-blind, placebo-controlled study. A cohort of 52 T2D patients with stable coronary artery disease (without any previous history of myocardial infarction, with or without previous percutaneous coronary intervention), with suboptimal glycemic control (glycated hemoglobin [HbA1c] 7\u20138.5%) on their current standard of care anti-hyperglycemic regimen, will be randomized in a 1:1 ratio to dapagliflozin or placebo. The primary outcome is to detect changes in myocardial glucose uptake from baseline to 4 weeks after treatment initiation. The main secondary outcome will be changes in myocardial blood flow, as measured by 13N-ammonia positron emission tomography/computed tomography (PET/CT). Other outcomes include cardiac function, glucose uptake in skeletal muscle, adipose tissue, liver, brain and kidney, as assessed by fluorodeoxyglucose (FDG) PET-CT imaging during hyperinsulinemic-euglycemic clamp; pericardial, subcutaneous and visceral fat, and browning as observed on CT images during FDG PET-CT studies; systemic insulin sensitivity, as assessed by hyperinsulinemic-euglycemic clamp, glycemic control, urinary glucose output; and microbiota modification. Discussion: SGLT-2 inhibitors, in addition to their insulin-independent plasma glucose-lowering effect, are able to directly (substrate availability, fuel utilization, insulin sensitivity) as well as indirectly (cardiac after-load reduction, decreased risk factors for heart failure) affect myocardial functions. Our study will provide novel insights into how these drugs exert CV protection in a diabetic population. Trial registration: EudraCT No. 2016-003614-27; ClinicalTrials.gov Identifier: NCT03313752

Dapagliflozin treatment is associated with a reduction of epicardial adipose tissue thickness and epicardial glucose uptake in human type 2 diabetes

Objective: We recently demonstrated that treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) leads to an increase in myocardial flow reserve in patients with type 2 diabetes (T2D) with stable coronary artery disease (CAD). The mechanism by which this occurs is, however, unclear. One of the risk factors for cardiovascular disease is inflammation of epicardial adipose tissue (EAT). Since the latter is often increased in type 2 diabetes patients, it could play a role in coronary microvascular dysfunction. It is also well known that SGLT-2i modify adipose tissue metabolism. We aimed to investigate the effects of the SGLT-2i dapagliflozin on metabolism and visceral and subcutaneous adipose tissue thickness in T2D patients with stable coronary artery disease and to verify whether these changes could explain observed changes in myocardial flow. Methods: We performed a single-center, prospective, randomized, double-blind, controlled clinical trial with 14 T2D patients randomized 1:1 to SGLT-2i dapagliflozin (10 mg daily) or placebo. The thickness of visceral (epicardial, mediastinal, perirenal) and subcutaneous adipose tissue and glucose uptake were assessed at baseline and 4 weeks after treatment initiation by 2-deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography/Computed Tomography during hyperinsulinemic euglycemic clamp. Results: The two groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, BMI, renal and heart function). Dapagliflozin treatment significantly reduced EAT thickness by 19% (p = 0.03). There was a significant 21.6% reduction in EAT glucose uptake during euglycemic hyperinsulinemic clamp in the dapagliflozin group compared with the placebo group (p = 0.014). There were no significant effects on adipose tissue thickness/metabolism in the other depots explored. Conclusions: SGLT-2 inhibition selectively reduces EAT thickness and EAT glucose uptake in T2D patients, suggesting a reduction of EAT inflammation. This could explain the observed increase in myocardial flow reserve, providing new insights into SGLT-2i cardiovascular benefits