PSS21 The Cost-Effectiveness of Intravitreal Aflibercept (IVT-AFL) in Treating Neovascular Age-Related Macular Degeneration in an Italian Setting

n/

Optic pathway glioma in type 1 neurofibromatosis: Review of its pathogenesis, diagnostic assessment, and treatment recommendations

Type 1 neurofibromatosis (NF1) is a dominantly inherited condition predisposing to tumor development. Optic pathway glioma (OPG) is the most frequent central nervous system tumor in children with NF1, affecting approximately 15-20% of patients. The lack of well-established prognostic markers and the wide clinical variability with respect to tumor progression and visual outcome make the clinical management of these tumors challenging, with significant differences among distinct centers. We reviewed published articles on OPG diagnostic protocol, follow-up and treatment in NF1. Cohorts of NF1 children with OPG reported in the literature and patients prospectively collected in our center were analyzed with regard to clinical data, tumor anatomical site, diagnostic workflow, treatment and outcome. In addition, we discussed the recent findings on the pathophysiology of OPG development in NF1. This review provides a comprehensive overview about the clinical management of NF1-associated OPG, focusing on the most recent advances from preclinical studies with genetically engineered models and the ongoing clinical trials

A short-duration dark adaptation protocol for assessment of age-related maculopathy

Dark adaptometry may be a useful diagnostic test and clinical trial endpoint for age-related maculopathy (ARM) because impaired night vision is a hallmark of early ARM. A novel dark adaptometer, the AdaptDx, was evaluated for the detection of ARM. The AdaptDx incorporates a 20-minute protocol optimized for the detection of ARM. ARM patients (N = 17) exhibited substantial dark adaptation impairment compared with normal adults (N = 17). The diagnostic sensitivity was 88% and the specificity was 100%. The diagnostic test characteristics of the AdaptDx are similar to previously reported studies using 60- to 120-minute protocols

Quantification of Visual Field Loss in Age-Related Macular Degeneration

Background An evaluation of standard automated perimetry (SAP) and short wavelength automated perimetry (SWAP) for the central 10–2 visual field test procedure in patients with age-related macular degeneration (AMD) is presented in order to determine methods of quantifying the central sensitivity loss in patients at various stages of AMD. Methods 10–2 SAP and SWAP Humphrey visual fields and stereoscopic fundus photographs were collected in 27 eyes of 27 patients with AMD and 22 eyes of 22 normal subjects. Results Mean Deviation and Pattern Standard Deviation (PSD) varied significantly with stage of disease in SAP (both p<0.001) and SWAP (both p<0.001), but post hoc analysis revealed overlap of functional values among stages. In SWAP, indices of focal loss were more sensitive to detecting differences in AMD from normal. SWAP defects were greater in depth and area than those in SAP. Central sensitivity (within 1°) changed by −3.9 and −4.9 dB per stage in SAP and SWAP, respectively. Based on defect maps, an AMD Severity Index was derived. Conclusions Global indices of focal loss were more sensitive to detecting early stage AMD from normal. The SWAP sensitivity decline with advancing stage of AMD was greater than in SAP. A new AMD Severity Index quantifies visual field defects on a continuous scale. Although not all patients are suitable for SWAP examinations, it is of value as a tool in research studies of visual loss in AMD

Functional and structural findings of neurodegeneration in early stages of diabetic retinopathy:cross-sectional analyses of baseline data of the EUROCONDOR project

Cross-sectional study evaluating the relationship between: a) functional and structural measurements of neurodegeneration in initial stages of diabetic retinopathy (DR); and b) presence of neurodegeneration and early microvascular impairment. We analyzed baseline data of patients with type 2 diabetes (n=449) enrolled in the EUROCONDOR study (NCT01726075). Functional studies by multifocal ERG (mfERG) evaluated neurodysfunction and structural measurements using spectral domain optical-coherence tomography (SD-OCT) evaluated neurodegeneration. The mfERG P1 amplitude was more sensitive than the P1 implicit time (IT), and was lower in patients with ETDRS 20-35 than in patients with ETDRS <20 (p=0.005). In 58% of cases, mfERG abnormalities were present in the absence of visible retinopathy. Correspondence between SD-OCT thinning and mfERG abnormalities was shown in 67% of the eyes with ETDRS <20 and in 83% of the eyes with ETDRS 20-35. Notably, 32% of patients with ETDRS 20-35 presented no abnormalities in mfERG or SD-OCT. We conclude that there is a link between mfERG and SD-OCT measurements which increases with the presence of microvascular impairment. However, in our particular study population (ETDRS ≤ 35) a significant proportion of patients had normal GC-IPL thickness and normal mfERG findings. We raise the hypothesis that neurodegeneration may play a role in the pathogenesis of DR in many, but not in all type 2 diabetic patients

Effects of Topically Administered Neuroprotective Drugs in Early Stages of Diabetic Retinopathy:Results of the EUROCONDOR Clinical Trial

The primary objective of this study was to assess whether the topical administration of two neuroprotective drugs (brimonidine and somatostatin) could prevent or arrest retinal neurodysfunction in patients with type 2 diabetes. For this purpose, adults aged between 45 and 75 years with a diabetes duration ≥5 years and an Early Treatment of Diabetic Retinopathy Study (ETDRS) level of ≤35 were randomly assigned to one of three arms: placebo, somatostatin, or brimonidine. The primary outcome was the change in implicit time (IT) assessed by multifocal electroretinography between baseline and at the end of follow-up (96 weeks). There were 449 eligible patients allocated to brimonidine (n = 152), somatostatin (n = 145), or placebo (n = 152). When the primary end point was evaluated in the whole population, we did not find any neuroprotective effect of brimonidine or somatostatin. However, in the subset of patients (34.7%) with preexisting retinal neurodysfunction, IT worsened in the placebo group (P < 0.001) but remained unchanged in the brimonidine and somatostatin groups. In conclusion, the topical administration of the selected neuroprotective agents appears useful in preventing the worsening of preexisting retinal neurodysfunction. This finding points to screening retinal neurodysfunction as a critical issue to identify a subset of patients in whom neuroprotective treatment might be of benefit

The Pediatric Choroidal and Ciliary Body Melanoma Study A Survey by the European Ophthalmic Oncology Group

Purpose: To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18 to 24 years of age, females, and those with CBI. Design: Retrospective, multicenter observational study. Participants: Two hundred ninety-nine patients from 24 ocular oncology centers, of whom 114 were children (median age, 15.1 years; range, 2.7-17.9 years) and 185 were young adults. Methods: Data were entered through a secure website and were reviewed centrally. Survival was analyzed using Kaplan-Meier analysis and Cox proportional hazards regression. Main Outcome Measures: Proportion of females, tumor-node-metastasis (TNM) stage, cell type, and melanoma-related mortality. Results: Cumulative frequency of having CCBM diagnosed increased steadily by 0.8% per year of age between 5 and 10 years of age and, after a 6-year transition period, by 8.8% per year from age 17 years onward. Of children and young adults, 57% and 63% were female, respectively, which exceeded the expected 51% among young adults. Cell type, known for 35% of tumors, and TNM stage (I in 22% and 21%, II in 49% and 52%, III in 30% and 28%, respectively) were comparable for children and young adults. Melanoma-related survival was 97% and 90% at 5 years and 92% and 80% at 10 years for children compared with young adults, respectively (P = 0.013). Males tended to have a more favorable survival than females among children (100% vs. 85% at 10 years; P = 0.058). Increasing TNM stage was associated with poorer survival (stages I, II, and III: 100% vs. 86% vs. 76%, respectively; P = 0.0011). By multivariate analysis, being a young adult (adjusted hazard rate [HR], 2.57), a higher TNM stage (HR, 2.88 and 8.38 for stages II and III, respectively), and female gender (HR, 2.38) independently predicted less favorable survival. Ciliary body involvement and cell type were not associated with survival. Conclusions: This study confirms that children with CCBM have a more favorable survival than young adults 18 to 25 years of age, adjusting for TNM stage and gender. The association between gender and survival varies between age groups. (C) 2016 by the American Academy of Ophthalmology.Peer reviewe

Indicators of "Healthy Aging" in older women (65-69 years of age). A data-mining approach based on prediction of long-term survival

<p>Abstract</p> <p>Background</p> <p>Prediction of long-term survival in healthy adults requires recognition of features that serve as early indicators of successful aging. The aims of this study were to identify predictors of long-term survival in older women and to develop a multivariable model based upon longitudinal data from the Study of Osteoporotic Fractures (SOF).</p> <p>Methods</p> <p>We considered only the youngest subjects (<it>n </it>= 4,097) enrolled in the SOF cohort (65 to 69 years of age) and excluded older SOF subjects more likely to exhibit a "frail" phenotype. A total of 377 phenotypic measures were screened to determine which were of most value for prediction of long-term (19-year) survival. Prognostic capacity of individual predictors, and combinations of predictors, was evaluated using a cross-validation criterion with prediction accuracy assessed according to time-specific AUC statistics.</p> <p>Results</p> <p>Visual contrast sensitivity score was among the top 5 individual predictors relative to all 377 variables evaluated (mean AUC = 0.570). A 13-variable model with strong predictive performance was generated using a forward search strategy (mean AUC = 0.673). Variables within this model included a measure of physical function, smoking and diabetes status, self-reported health, contrast sensitivity, and functional status indices reflecting cumulative number of daily living impairments (HR ≥ 0.879 or RH ≤ 1.131; P < 0.001). We evaluated this model and show that it predicts long-term survival among subjects assigned differing causes of death (e.g., cancer, cardiovascular disease; P < 0.01). For an average follow-up time of 20 years, output from the model was associated with multiple outcomes among survivors, such as tests of cognitive function, geriatric depression, number of daily living impairments and grip strength (P < 0.03).</p> <p>Conclusions</p> <p>The multivariate model we developed characterizes a "healthy aging" phenotype based upon an integration of measures that together reflect multiple dimensions of an aging adult (65-69 years of age). Age-sensitive components of this model may be of value as biomarkers in human studies that evaluate anti-aging interventions. Our methodology could be applied to data from other longitudinal cohorts to generalize these findings, identify additional predictors of long-term survival, and to further develop the "healthy aging" concept.</p