Intrasession and Between-Visit Variability of Sector Peripapillary Angioflow Vessel Density Values Measured with the Angiovue Optical Coherence Tomograph in Different Retinal Layers in Ocular Hypertension and Glaucoma

PURPOSE: To evaluate intrasession and between-visit reproducibility of sector peripapillary angioflow vessel-density (PAFD, %) values in the optic nerve head (ONH) and radial peripapillary capillaries (RPC) layers, respectively, and to analyze the influence of the corresponding sector retinal nerve fiber layer thickness (RNFLT) on the results. METHODS: High quality images acquired with the Angiovue/RTVue-XR Avanti optical coherence tomograph (Optovue Inc., Fremont, USA) on 1 eye of 18 stable glaucoma and ocular hypertension patients were analyzed using the Optovue 2015.100.0.33 software version. Three images were acquired in one visit and 1 image 3 months later. RESULTS: PAFD image quality for all images necessary to calculate reproducibility was sufficient to analysis only in 18 of the 83 participants (21.7%) who were successfully imaged for RNFLT. Intrasession coefficient of variation (CV) ranged between 2.30 and 3.89%, and 3.51 and 5.12% for the peripapillary sectors in the ONH and RPC layers, respectively. The corresponding between-visit CV values ranged between 3.05 and 4.26%, and 4.99 and 6.90%, respectively. Intrasession SD did not correlate with the corresponding RNFLT in any sector in either layer (P>/=0.170). In the ONH layer sector PAFD values did not correlate with the corresponding RNFLT values (P>/=0.100). In contrast, in the RPC layer a significant positive correlation between the corresponding sector PAFD and RNFLT values was found for all but one peripapillary sectors (Pearson-r range: 0.652 to 0.771, P</=0.0046). CONCLUSION: Though in several patients routine use of PAFD measurement may be limited by suboptimal image quality, in the successfully imaged cases (21.7% of the study eyes in the current investigation) reproducibility of sector PAFD values seems to be sufficient for clinical research. In stable patients intrasession variability explains most of the between-visit variability. Sector PAFD variability is independent from sector RNFLT, a marker of glaucoma severity. In the RPC layer sector PAFD and RNFLT show strong to very strong positive correlation

Development and validation of novel clinical endpoints in intermediate age-related macular degeneration in MACUSTAR

Background Currently, no validated clinical endpoints for treatment studies exist for intermediate age-related macular degeneration (iAMD). Objective The European MACUSTAR study aims to develop and clinically validate adequate clinical endpoints for future treatment studies in iAMD and to identify early determinants of disease progression to late stage AMD. Material and methods The MACUSTAR study protocol was developed by an international consortium of researchers from academia, the pharmaceutical industry and medical device companies. The MACUSTAR project is funded by the Innovative Medicines Initiative 2 (IMI2) of the European Union. Results The MACUSTAR study consists of a cross-sectional and a longitudinal investigation. A total of 750 subjects with early, intermediate and late AMD as well as control subjects with no signs of AMD will be included with a follow-up period of 3 years. Overall, 20 European study centers are involved. Conclusion The MACUSTAR project will generate large high-quality datasets, which will allow clinical validation of novel endpoints for future interventional trials in iAMD. The aim is that these endpoints will be accepted as suitable for medication approval studies by the regulatory authorities and that understanding of the disease process will be improved

Unraveling the genetic complexities of combined retinal dystrophy and hearing impairment.

Usher syndrome, the most prevalent cause of combined hereditary vision and hearing impairment, is clinically and genetically heterogeneous. Moreover, several conditions with phenotypes overlapping Usher syndrome have been described. This makes the molecular diagnosis of hereditary deaf-blindness challenging. Here, we performed exome sequencing and analysis on 7 Mexican and 52 Iranian probands with combined retinal degeneration and hearing impairment (without intellectual disability). Clinical assessment involved ophthalmological examination and hearing loss questionnaire. Usher syndrome, most frequently due to biallelic variants in MYO7A (USH1B in 16 probands), USH2A (17 probands), and ADGRV1 (USH2C in 7 probands), was diagnosed in 44 of 59 (75%) unrelated probands. Almost half of the identified variants were novel. Nine of 59 (15%) probands displayed other genetic entities with dual sensory impairment, including Alström syndrome (3 patients), cone-rod dystrophy and hearing loss 1 (2 probands), and Heimler syndrome (1 patient). Unexpected findings included one proband each with Scheie syndrome, coenzyme Q10 deficiency, and pseudoxanthoma elasticum. In four probands, including three Usher cases, dual sensory impairment was either modified/aggravated or caused by variants in distinct genes associated with retinal degeneration and/or hearing loss. The overall diagnostic yield of whole exome analysis in our deaf-blind cohort was 92%. Two (3%) probands were partially solved and only 3 (5%) remained without any molecular diagnosis. In many cases, the molecular diagnosis is important to guide genetic counseling, to support prognostic outcomes and decisions with currently available and evolving treatment modalities

OCT Angiography: an Upcoming Non-invasive Tool for Diagnosis of Age-Related Macular Degeneration

To review the most recent findings, characteristics, faults and future perspectives of optical coherence tomography angiography (OCTA) in age-related macular degeneration (AMD). In dry AMD, OCTA is useful on the evaluation of choriocapillaris perfusion and detection of naïve quiescent non-exudative choroidal neovascularization (CNV). In wet AMD, OCTA can provide detailed anatomic and morphologic information of CNVs, which may help to understand why and how they develop and become active. In other hand, the many artifacts present in OCTA images may lead to misinterpretation and misdiagnosis. OCTA is a still developing technology that is able to provide a large amount of anatomic, functional and morphologic information in macular diseases and, particularly, AMD. As the technology evolves, the need of dye-based modalities tends to decrease

Clinical phenotype of PDE6B-associated retinitis pigmentosa

Contains fulltext : 231653.pdf (publisher's version ) (Open Access)In this retrospective, longitudinal, observational cohort study, we investigated the phenotypic and genotypic features of retinitis pigmentosa associated with variants in the PDE6B gene. Patients underwent clinical examination and genetic testing at a single tertiary referral center, including best-corrected visual acuity (BCVA), kinetic visual field (VF), full-field electroretinography, full-field stimulus threshold, spectral domain optical coherence tomography, and fundus autofluorescence imaging. The genetic testing comprised candidate gene sequencing, inherited retinal disease gene panel sequencing, whole-genome sequencing, and testing for familial variants by Sanger sequencing. Twenty-four patients with mutations in PDE6B from 21 families were included in the study (mean age at the first visit: 32.1 ± 13.5 years). The majority of variants were putative splicing defects (8/23) and missense (7/23) mutations. Seventy-nine percent (38/48) of eyes had no visual acuity impairment at the first visit. Visual acuity impairment was mild in 4% (2/48), moderate in 13% (6/48), and severe in 4% (2/48). BCVA was symmetrical in the right and left eyes. The kinetic VF measurements were highly symmetrical in the right and left eyes, as was the horizontal ellipsoid zone (EZ) width. Regarding the genetic findings, 43% of the PDE6B variants found in our patients were novel. Thus, this study contributed substantially to the PDE6B mutation spectrum. The visual acuity impairment was mild in 83% of eyes, providing a window of opportunity for investigational new drugs. The EZ width was reduced in all patients and was highly symmetric between the eyes, making it a promising outcome measure. We expect these findings to have implications on the design of future PDE6B-related retinitis pigmentosa (RP) clinical trials