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Introduction/Background: OCT-Leakage (OCT-L) is a new method of analysis and mapping sites of lower optical reflectivity (LOR). Purpose: to test OCT-L in eyes with neovascular AMD (nAMD), to identify and locate abnormal fluid and its change after treatment. Methods: Prospective OCT-L analysis of a cohort of nAMD cases, before (V1) and 1-week (V2) after anti-VEGF therapy. Raw scan data from OCT Cirrus AngioPlex (ZEISS,California,USA) was used to calculate LOR maps. These were collected for the whole retina and for each layer, after semi-automated segmentation procedure developed in-house. The LOR area ratio, representing LOR distribution in a given area, was obtained for all layers and the whole retina. LOR ratios were compared between visits. Retinal and layer-by-layer thickness obtained by semi-automated segmentation was compared between visits, and its change correlated to LOR ratio change. Results: Twenty eyes with nAMD on anti-VEGF treatment were included. OCT-L maps delineated well the extension and location of abnormal fluid. The LOR ratio of the whole retina decreased from V1 to V2 (0.43 to 0.32, central subfield). Layer analysis showed that this decrease took place in the external retinal layers and RPE-Bruch layer, where the neovascular process is located, implying a reduction in disease-related abnormal fluid after treatment. Retinal thickness (RT) obtained from segmentation decreased between visits (p = 0.02), and this was also localized to the external retinal layers. LOR ratio change correlated strongly to RT change in the external retinal layers and for the whole retina (p < 0.05). LOR mapping and ratio were more sensitive to identify fluid and its change than RT analysis. Conclusions: OCT-L mapping of LOR sites in nAMD eyes demonstrated the extent and location of abnormal fluid in the external retinal layers and its decrease after treatment. The possibility of complementarity between OCT-L mapping and OCTA could be of potential interest in patient management in nAMD. [ABSTRACT FROM AUTHOR]

In order to investigate Insulin-like growth factor-1 (IGF-1) blood levels in male and female age-matched patients affected by early, intermediate, neovascular age related macular degeneration (AMD) and healthy subjects (no AMD) were enrolled in a prospective, observational study. All patients enrolled were classified according to 4 stages classification of AMD from Age-related eye disease study (AREDS). Each subject underwent a complete ophthalmic examination including best corrected visual acuity (BCVA), applanation tonometry, slit-lamp biomicroscopic examination, color fundus photography, optical coherence tomography (OCT) and, if needed, fluorescein angiography. Overall, 224 anti-VEGF naïve subjects including 56 patients in early AMD group, 56 patients in intermediate AMD group, 56 patients in neovascular AMD group and 56 patients in no AMD group were recruited. For each group 28 male patients and 28 female patients were enrolled. IGF-1 hematic levels were significantly higher (p<0.005) in the neovascular AMD group and in the intermediate AMD group in comparison to no AMD group; no significant difference between early AMD group and no AMD group was found. Our analysis has shown an increment of IGF-1 levels in both neovascular and intermediate stage of AMD supporting the hypothesis that IGF-1 may play a role in the pathogenesis of AMD.

Purpose: Automated segmentation of retinal layers by spectral-domain optical coherence tomography (SD-OCT) is usually erroneous in the presence of retinal diseases. The purpose of this study is to report the changes in ganglion cell complex (GCC) comprising retina nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) in neovascular age-related macular degeneration (AMD) patients by manually correcting the automated segmentation errors., Methods: Thirty eyes of 30 patients with new-onset choroidal neovascularization secondary to neovascular AMD and 30 eyes of 30 healthy subjects were included. The inner retinal thicknesses were measured using early treatment diabetic retinopathy circle in the central 1 mm (fovea) and surrounding 3 mm diameter (parafovea) after checking the accuracy of automated segmentation lines. Manual segmentation was done to ensure the accurate segmentation, when needed., Results: Neovascular AMD patients had thicker mean RNFL, GCL, IPL, and GCC thicknesses within the fovea compared to healthy eyes (p = 0.04, p = 0.001, p = 0.032, and p = 0.005, respectively). In the parafoveal area, among the thickness-related measurements, the only significant difference was a thicker mean RNFL (p = 0.002)., Conclusion: Diffuse thickening of inner retinal layers in neovascular AMD may overestimate actual GCC thickness within fovea. This pseudo-increase in GCC thickness and inner retinal layers in general likely does not reflect more cells or tissue, but rather diffuse edema which leads to a falsely increased reading of layer thickness. Such false readings may also make the assessment of other conditions that lead to reduced inner retinal layer thickness such as glaucoma, optic nerve disease, or retinovascular occlusions more difficult.

Purpose: To assess the value of a monthly injection of Lucentis ® until stable visual acuity (VA) is obtained for three consecutive months without exudation in patients with neovascular age macular degeneration (AMD)., Methods: Prospective, single-center, non-controlled trial including naïve AMD patients with neovascularization. An assessment of VA and a spectral domain optical coherence tomography (SD-OCT) were performed at baseline and every month. Monthly injections of Lucentis ® were performed over three months. The monthly injections were then continued until three consecutive stable VA results were obtained with no signs of exudation., Results: Fifteen out of the 21 patients included were anatomically good responders. A mean gain of +14Le (9) was obtained up to the point at which there was no exudation. There was no additional gain from this point until 3 consecutive stable VA results were obtained. During the PRN phase, an additional mean gain of +3.2Le (7.7) was obtained., Conclusion: This initial VA-guided regimen with ranibizumab might prevent the slight decrease in VA observed during the first year of PRN studies., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objectives: To assess the time from symptom onset to treatment for neovascular age-related macular degeneration (nvAMD) and to measure the awareness of AMD in Southeast Scotland., Design: Retrospective cross-sectional study., Setting: Secondary care, Southeast of Scotland., Methods: Patients treated with intravitreal therapy (IVT) for nvAMD in Southeast Scotland between 2013 and 2015 were identified using a treatment register. Notes were retrospectively reviewed. We measured time from: (A) symptom onset to first presentation at primary care, (B) referral to ophthalmic clinic appointment and (C) ophthalmic clinic appointment to first IVT treatment. To investigate AMD awareness, we performed a cluster random sample survey of patients visiting non-AMD ophthalmic clinics using a previously validated 12-item questionnaire., Results: 195 patients (mean age 78 years) were included in the study. The mean delays between the different stages-A, B and C-were 54.2 (95% CI ±13), 28.2 (95% CI ±4.0) and 31.5 (95% CI ±3.6) days, respectively. There was an additional mean delay of 7.5 (95% CI ±1.6) days when patients were indirectly referred by optometrists via general practitioners (P<0.05). 140 patients (mean age 78) participated in the awareness survey; 62.1% reported being 'aware' of AMD but only 37.3% described AMD symptoms correctly., Conclusions: There was a significant delay at every step of the nvAMD care pathway. The causes for this were multifactorial and included delays in first presentation to a healthcare provider, referral from primary care and initiation of secondary care treatment. Our data are likely to underestimate prehospital delays as a large number of cases are likely to have undefined symptoms and onset. We also identified suboptimal awareness of AMD which could account for a substantial delay in presentation from symptom onset. These findings highlight the need to address AMD awareness and the need for urgent treatment to prevent avoidable vision loss resulting from nvAMD., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To analyse the functional recovery using a pro re nata (PRN) dosing strategy with intravitreal injections of ranibizumab for patients with neovascular age-related macular degeneration (AMD)., Material and Methods: An observational, retrospective, single-centre study, was conducted on patients with neovascular AMD managed with a PRN strategy with ranibizumab, and were followed-up for a minimum of 18 months. Sociodemographic and clinical data were collected from medical records. The percentage of visual acuity (VA) recovered after losing 5 or more letters was calculated taking into account the previous visit, as well as considering the best VA recorded prior to the retreament., Results: The analysis included 128 patients. The mean (SD) follow-up period was 18.9 (2.3) months. The mean (SD) elapsed days between onset of symptoms and diagnosis, and between prescription and administration of treatment was 50.2 (57.4) and 10.9 (16.0), respectively. Only 108 patients were prescribed ranibizumab after losing 5 or more letters of VA. The mean (SD) VA recovery compared to the previous VA was 70.3% (114.4). On the other hand, the mean (SD) VA recovery when considering the best VA registered before the retreatment was 43.5% (112.9), with 59.4% of re-treatments having a VA recovery below 75%, and with 11.7% not presenting any VA recovery., Conclusions: A PRN dosing strategy with intravitreal ranibizumab for neovascular AMD may not be efficient in preserving and/or recovering VA in the long-term, due to a cumulative irreversible VA loss., (Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Purpose: To evaluate the efficacy of a dexamethasone intravitreal implant in combination with intravitreal anti-VEGF agents for treatment resistant neovascular age-related macular degeneration (nvAMD)., Methods: This study was designed as a single-center, retrospective interventional case series. Consecutive patients with treatment-resistant nvAMD underwent simultaneous combined injection of anti-VEGF agent and dexamethasone intravitreal implant. Eighteen patients with mean age of 81.5 years were included. Patients received average of 26.3 anti-VEGF injections before dual therapy, with mean follow up of 8.2 months after dual therapy., Results: Dual therapy produced a significant mean decrease in CFT (126.3 μm), compared to a mean increase of 29.9 μm when treated with anti-VEGF monotherapy (p=0.0017). Patients also had mean decrease in MCV of -0.85 mm 3 with dual therapy compared with anti-VEGF monotherapy (p=0.0014). There was a moderate correlation between the number of prior anti-VEGF injections and the magnitude of anatomic response, suggesting that shorter disease duration may positively influence response to combined treatment. Although there was a slight trend towards improved mean visual acuity after dual therapy, these differences did not reach statistical significance. Nevertheless, with combination treatment, 33% of patients gained one or more lines of vision. Dual therapy resulted in a significantly lower number of required anti-VEGF injections (4.25 vs 5.33) and an increase of the anti-VEGF injection-free interval to 1.41 months from 1.12 months during the 6 months following dual therapy compared to the same interval before dual therapy. Dual therapy was well tolerated; two eyes developed mild IOP elevation effectively managed with topical therapy and one patient developed worsening cataract., Conclusions: Combined treatment of anti-VEGF with the dexamethasone intravitreal implant is a viable alternative for treatment-resistant nvAMD, and may reduce treatment burden. Earlier treatment with dual therapy may be beneficial to maximize anatomic and visual outcomes in these patients.

Age-related macular degeneration (AMD) is a common condition causing progressive visual impairment, leading to irreversible blindness. Existing diagnostic tools for AMD are limited to clinical signs in the macula and the visual assessment of the patient. The presence of circulating microRNAs (miRNAs) in the peripheral circulatory system with potential as diagnostic, prognostic and/or predictive biomarkers has been reported in a number of conditions/diseases. miRNAs are key regulators of several biological processes, and miRNA dysregulation has been linked with numerous diseases, most remarkably cancer. miRNAs have been shown to be involved in AMD pathology and several miRNAs target genes and signaling pathways were identified in relation to AMD pathogenesis. Exosomes are 50-90 nm membrane micro-vesicles (MVs), released by several cell types. Although exosomal functions are not completely understood, there is much evidence to suggest that exosomes play an essential role in cell-cell communication. They may stimulate target cells by transferring different bioactive molecules such as miRNA. Here we discuss methods to isolate exosome using serum specimens from AMD patients and miRNA profiling for the better understanding of the disease.

Age-related macular degeneration (AMD) is a chronic degenerative disease of the central retina and a major cause of vision impairment and blindness with millions of people affected in the elderly population. In recent years, considerable efforts have been made to understand disease pathology with the long-term goal of designing novel and effective treatment options for this devastating disease. Although striking advances in treating the neovascular stage of late AMD have occurred, no therapy is available for almost half of all AMD patients, specifically those who are affected by the atrophic form of the disease. This review highlights current knowledge on the genetic factors associated with early- and late-stage forms of the disease. It also summarizes the findings regarding the extent to which these factors may play a role in the transition from one disease stage to another, and it emphasizes the need to explore further the underlying mechanisms for both development and progression of this disease as a starting point for designing innovative therapies for it.

Purpose: To relate the functional response to distinct morphological features of the retina during aflibercept treatment for neovascular AMD (nAMD)., Methods: A total of 726 retinal locations in 22 consecutive eyes presenting with treatment-naive nAMD underwent a standardized examination with spectral-domain optical coherence tomography (SD-OCT) and topographic microperimetry (MP) at baseline, after 3 and 12 months of continuous intravitreal aflibercept therapy. The retinal sensitivity at each stimulus location was registered to the corresponding location on SD-OCT morphology. Subsequently, the microperimetric responses were evaluated with respect to the following underlying SD-OCT features: neovascular complex (NVC), subretinal fluid (SRF), intraretinal fluid (IRF), intraretinal cystoid space (IRC), serous pigment epithelium detachment (sPED), and fibrovascular pigment epithelium detachment (fPED)., Results: Baseline sensitivity was reduced to mean values of 1.8 dB in NVC, 2.2 dB in IRC, 2.8 dB in IRF, 2.6 dB in sPED, 3.6 dB in SRF, and 4.6 dB in fPED. Improvements in retinal sensitivity were most pronounced during the initial 3-month interval, when significant recovery was documented for SRF and sPED with +4.0/5.5 dB (P < 0.0001) and to a lesser extent for IRF, IRC, fPED, with +1.1, 1.7, 2.3 dB, respectively. From month 3 to 12, the additional benefit ranged from 0.3 to 1.0 dB (P > 0.05 for each category)., Conclusions: Significant functional benefits following intravitreal aflibercept treatment could be detected over all defined morphological pathologies. The level of improvement varied dependent on the associated feature with the best prognosis for visual improvement in SRF and sPED and least with intraretinal fluid and particularly intraretinal cysts., (Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.)

Purpose: To quantitatively analyze morphological features in eyes with neovascular AMD (nAMD) at baseline, after 12 months, and after 24 months of intravitreal ranibizumab treatment and to perform a structure/function correlation., Methods: Eyes with treatment-naïve nAMD were treated with intravitreal ranibizumab according to a standardized dosing regimen over 2 years and followed continuously in a prospective study design. The central foveal area of 1000 μm (horizontal)×960 μm (vertical) of spectral-domain optical coherence tomography (SD-OCT) volume scans was evaluated quantitatively (using proprietary software) for the following pathologies: alteration of the external limiting membrane (ELM), alteration of the ellipsoid zone, subretinal fluid, pigment epithelium detachment, drusen, intraretinal cysts, subretinal mass, and subretinal pigment epithelium mass. The total area of each pathology was calculated in mm2 at baseline and after 1 and 2 years of ranibizumab therapy and correlated with BCVA results., Results: In total, 480 central SD-OCT scans of 20 consecutive patients were evaluated. In the multivariate regression analysis, the area of ELM alteration, the area of intraretinal cysts, and foveal retinal thickness were significant variables influencing visual acuity at baseline (R=-0.827; R2=0.684; P<0.001). The area of ELM alteration was the only significant factor to be directly associated with visual acuity at 12 months (R=-0.846; R2=0.716; P<0.001) and 24 months (R=-0.778; R2=0.606; P<0.001)., Conclusions: The integrity of the ELM appears to be the most important feature correlating with visual acuity in native nAMD as well as nAMD treated with intravitreal ranibizumab at each time interval, but not prospectively. In general, no significant predictors for an individual gain or loss in mid- (12 months) or long-term BCVA results (24 months) were found by OCT., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)