Definition of indicators of appropriateness in the management of neovascular age-related macular degeneration: An expert opinion

Wet age-related macular degeneration is a chronic condition culminating, in most cases, in blindness. The introduction of anti-angiogenic agents in 2006 has represented a major breakthrough in the treatment of the disease, but timely and effective treatment with regular follow-up and monitoring is mandatory to stabilize and preserve visual acuity. In clinical practice, however, appropriate therapy provision is frequently challenged by economic and organizational issues that result in suboptimal visual outcomes and increased incidence of legal blindness. International Guidelines have defined a diagnostic and therapeutic pathway to ensure the best practice in wet age-related macular degeneration management, but reference parameters to evaluate and compare the performance of Retina Centers are lacking. To address the appropriateness of wet age-related macular degeneration management in Italy, a multidisciplinary panel of ten experts gathered in three meetings. They defined three sets of indicators and relative benchmark values that each Center should comply with to ensure patients optimal care already from the first access: (a) clinical intervention indicators, to determine the possible Center\u2019s deviation from the diagnostic and therapeutic pathway; (b) outcome indicator, to evaluate the socioeconomic impact of the healthcare systems\u2019 performance; (c) management indicators, to test the size of the gap between the Center\u2019s supply and demand. Once the indicators have been analyzed, healthcare systems can plan actions to improve appropriateness and monitor their effects. However, to put this in practice, a concerted effort by all parts involved in healthcare provision is required, together with adequate systems to analyze clinical and administrative documentation

A high affinity switch for cAMP in the HCN pacemaker channels

Binding of cAMP to Hyperpolarization activated cyclic nucleotide gated (HCN) channels facilitates pore opening. It is unclear why the isolated cyclic nucleotide binding domain (CNBD) displays in vitro lower affinity for cAMP than the full-length channel in patch experiments. Here we show that HCN are endowed with an affinity switch for cAMP. Alpha helices D and E, downstream of the cyclic nucleotide binding domain (CNBD), bind to and stabilize the holo CNBD in a high affinity state. These helices increase by 30-fold cAMP efficacy and affinity measured in patch clamp and ITC, respectively. We further show that helices D and E regulate affinity by interacting with helix C of the CNBD, similarly to the regulatory protein TRIP8b. Our results uncover an intramole- cular mechanism whereby changes in binding affinity, rather than changes in cAMP concentration, can modulate HCN channels, adding another layer to the complex regulation of their activity

Non-nociceptive roles of opioids in the CNS: opioids' effects on neurogenesis, learning, memory and affect.

Mortality due to opioid use has grown to the point where, for the first time in history, opioid-related deaths exceed those caused by car accidents in many states in the United States. Changes in the prescribing of opioids for pain and the illicit use of fentanyl (and derivatives) have contributed to the current epidemic. Less known is the impact of opioids on hippocampal neurogenesis, the functional manipulation of which may improve the deleterious effects of opioid use. We provide new insights into how the dysregulation of neurogenesis by opioids can modify learning and affect, mood and emotions, processes that have been well accepted to motivate addictive behaviours

Indocyanine Green Angiography (Icga) in Pathological Myopia

One hundred and fifty patients (300 eyes), mean age 49±15 years, with degenerative myopia underwent fluorescein and indocyanine green angiography (ICGA). Fluorescence of choroidal neovascularization (CNV) on ICGA was less evident than with fluorescein angiography (FA). FA revealed CNV in 98 eyes; ICGA showed CNV with different angiographic patterns in 82 eyes. ICGA permitted CNV diagnosis when retinal hemorrhages were present. ICGA allowed a more precise evaluation of lacquer cracks which appeared more numerous than the ones identified by FA. ICGA visualized the retrobulbar vasculature. This study shows that ICGA has a useful role for diagnosing and managing pathological myopia. </jats:p

Verteporfin photodynamic therapy combined with intravitreal triamcinolone for choroidal neovascularization due to angioid streaks

To report the visual outcome of photodynamic therapy (PDT) combined with intravitreal triamcinolone acetonide (IVTA) for choroidal neovascularization (CNV) secondary to angioid streaks (AS)

Reproducibility of fluorescein and indocyanine green angiographic assessment for RAP diagnosis : a multicenter study

Purpose. To explore the interobserver agreement in the diagnosis of retinal angiomatous proliferation (RAP) using fluorescein (FA) and indocyanine green angiographies (ICGA) and to detect which morphologic features of the neovascular lesion are associated with RAP diagnosis. Methods. In this cross-sectional study, consecutive patients with newly diagnosed neovascular age-related macular degeneration (AMD) evaluated in 8 retina centers were considered. The FA and ICGA were obtained in all centers according to a standard protocol, both performed either as a static or as a dynamic examination. All images were graded by 2 observers from different institutions. Results. A total of 201 eyes with neovascular AMD of 155 consecutive patients (mean age 76\ub18 years) were considered. Overall RAP prevalence was 30% using FA and 26% using ICGA. Patients studied with dynamic angiography were twice as likely to be diagnosed with RAP as those using static angiography. Interobserver agreement for the overall detection of RAP was high using FA (kappa: 0.868; 95% confidence interval [CI]: 0.793-0.944) and very high using ICGA (kappa: 0.905; 95% CI 0.836-0.974). The agreement between the 2 observers tended to be higher for the truncated vessel than for the anastomosis in FA as well as in ICGA, but no comparison yielded statistical significance (p=0.258 and p=0.584, respectively). Conclusions. The interobserver agreement for RAP detection was very good both using FA and ICGA, but the overall detection of RAP was higher for dynamic strategy compared with static one