Sequential Morphological Changes in the CNV Net after Intravitreal Anti-VEGF Evaluated with OCT Angiography

PURPOSE: To assess and describe sequential morphological changes in the choroidal neovascularization (CNV) net using optical coherence tomography angiography (OCTA) in patients undergoing treatment with intravitreal antivascular endothelial growth factor (VEGF). METHODS: Prospective cohort study. OCTA was performed sequentially: before (t0), 1 h (t1), 1 week (t2) and 1 month after the injection (t3), using Avanti RTVue XR equipped with the AngioVue® software (Optovue, Calif., USA). All images were classified by two independent graders. RESULTS: Ten eyes of 10 patients, with a mean age of 72.4 ± 10.5 years, were included. CNV morphology was described as tree-like in 5 eyes, glomerular in 1 and fragmented in 4. A fibrovascular capsule surrounding the CNV net was found in 4 eyes and a feeder trunk was noticed in 6. No changes were observed at t1. Loss of peripheral capillaries, vessel fragmentation and decreased vessel density were evident in 8 eyes at t2. The CNV capillary density and the peripheral anastomosis increased in all of these at t3. Two eyes remained unchanged through the whole length of follow-up. CONCLUSIONS: Significant changes in the CNV net can be observable in OCTA at least 1 week after intravitreal anti-VEGF. The safety of frequent examinations may provide a method of gauging treatment effects

Protocol for a randomised, double-masked, sham-controlled phase 4 study on the efficacy, safety and tolerability of intravitreal aflibercept monotherapy compared with aflibercept with adjunctive photodynamic therapy in polypoidal choroidal vasculopathy: the ATLANTIC study

PURPOSE: The purpose of this study is to compare the efficacy and safety of intravitreal aflibercept (IVA) with sham photodynamic therapy (sPDT) versus IVA with verteporfin PDT (vPDT) in a Caucasian population with treatment-naive polypoidal choroidal vasculopathy (PCV), enrolling into a treat and extend (T&E) regimen. METHODS AND ANALYSIS: Randomised, double-masked, sham-controlled, multicentre phase 4 investigator-driven clinical trial. The primary outcomes are (1) change in best-corrected visual acuity (BCVA) from baseline and (2) polyp regression at week 52, assessed by indocyanine green angiography (ICGA). Fifty patients with treatment-naive PCV will be recruited from Portuguese and Spanish clinical sites. Eligible patients will receive monthly IVA for 3 months (week 0, week 4 and week 8). At week 16, all patients will repeat ICGA and undergo central randomisation (1:1 ratio) into one of the following groups: Group 1-IVA T&E + vPDT; Group 2-IVA T&E + sPDT. PDT will be performed at week 16, week 28 and week 40 in the presence of active polyps. After week 16, the presence of macular fluid on optical coherence tomography will determine the schedule of observations. When present, the interval between visits/injections will decrease 2 weeks (minimum 6 weeks). When not, the interval between visits/injections will increase 2 weeks (maximum 12 weeks). Efficacy will be evaluated based on BCVA, central retinal thickness and polyp regression. Safety parameters will include assessment of intraocular pressure, adverse events and serious adverse events. ETHICS AND DISSEMINATION: This study was designed and shall be implemented and reported in accordance with the International Conference on Harmonisation (ICH) Harmonised Tripartite Guidelines for Good Clinical Practice, with applicable local regulations and with the ethical principles laid down in the Declaration of Helsinki. The study received approval from Comissão de Ética para a Investigação Clínica and Comité Ético de investigación Clínica del Hospital Universitari de Bellvitge. TRIAL REGISTRATION NUMBER: This study is registered under the EudraCT number: 2015-001368-20 and the ClinicalTrials.gov Identifier: NCT02495181.info:eu-repo/semantics/publishedVersio

Long-Term Management of RAP Lesions in Clinical Practice: Treatment Efficacy and Predictors of Functional Improvement

PURPOSE: To evaluate the long-term efficacy of ranibizumab in the treatment of retinal angiomatous proliferation (RAP) and to identify predictors of functional outcome. METHODS: Retrospective case series comprised 79 eyes of 68 consecutive patients with RAP followed up ≥36 months. Primary end-points were best-corrected visual acuity (BCVA) and central macular thickness (CMT) variation at 36 months and at the last visit. RESULTS: Mean follow-up time was 59.8 ± 16.0 months. All eyes were treated with pro re nata ranibizumab, with (n = 33) or without (n = 46) photodynamic therapy (PDT). Stabilization or improvement in BCVA was observed in 50.6% of the patients at 36 months, and in 40.5% at the end of the follow-up, where 20.3% preserved reading vision. A significant decrease in CMT was observed at 36 months (p < 0.001), but not at the end of the follow-up. Geographic atrophy (GA) was present in 59.5% of the eyes at the final visit. Baseline subretinal fluid was associated with better visual outcomes (p = 0.001). Results of combination treatment with intravitreal ranibizumab and PDT did not significantly differ from ranibizumab monotherapy. CONCLUSION: Modest functional outcomes can be expected from the long-term treatment of RAP lesions in clinical practice, most likely due to the advent of GA. Baseline subretinal fluid positively correlated with final BCVA.info:eu-repo/semantics/publishedVersio

RETINAL ANGIOMATOUS PROLIFERATION: A Quantitative Analysis of the Fundoscopic Features of the Fellow Eye

PURPOSE: To quantitatively analyze and compare the fundoscopic features between fellow eyes of retinal angiomatous proliferation and typical exudative age-related macular degeneration and to identify possible predictors of neovascularization. METHODS: Retrospective case-control study. Seventy-nine fellow eyes of unilateral retinal angiomatous proliferation (n = 40) and typical exudative age-related macular degeneration (n = 39) were included. Fundoscopic features of the fellow eyes were assessed using digital color fundus photographs taken at the time of diagnosis of neovascularization in the first affected eye. Grading was performed by two independent graders using RetmarkerAMD, a computer-assisted grading software based on the International Classification and Grading System for age-related macular degeneration. RESULTS: Baseline total number and area (square micrometers) of drusen in the central 1,000, 3,000, and 6,000 μm were considerably inferior in the fellow eyes of retinal angiomatous proliferation, with statistically significant differences (P 510,196 μm2 in the central 6,000 μm was associated with an increased risk of neovascularization (hazard ratio, 4.35; 95% confidence interval [1.56-12.15]; P = 0.005). CONCLUSION: Baseline fundoscopic features of the fellow eye differ significantly between retinal angiomatous proliferation and typical exudative age-related macular degeneration. A large area (>510,196 μm2) of soft drusen in the central 6,000 μm confers a significantly higher risk of neovascularization and should be considered as a phenotypic risk factor

Quantitative evaluation of visual function 12 months after bilateral implantation of a diffractive trifocal IOL

PURPOSE: To quantitatively evaluate visual function 12 months after bilateral implantation of the Physiol FineVision® trifocal intraocular lens (IOL) and to compare these results with those obtained in the first postoperative month. METHODS: In this prospective case series, 20 eyes of 10 consecutive patients were included. Monocular and binocular, uncorrected and corrected visual acuities (distance, near, and intermediate) were measured. Metrovision® was used to test contrast sensitivity under static and dynamic conditions, both in photopic and low-mesopic settings. The same software was used for pupillometry and glare evaluation. Motion, achromatic, and chromatic contrast discrimination were tested using 2 innovative psychophysical tests. A complete ophthalmologic examination was performed preoperatively and at 1, 3, 6, and 12 months postoperatively. Psychophysical tests were performed 1 month after surgery and repeated 12 months postoperatively. RESULTS: Final distance uncorrected visual acuity (VA) was 0.00 ± 0.08 and distance corrected VA was 0.00 ± 0.05 logMAR. Distance corrected near VA was 0.00 ± 0.09 and distance corrected intermediate VA was 0.00 ± 0.06 logMAR. Glare testing, pupillometry, contrast sensitivity, motion, and chromatic and achromatic contrast discrimination did not differ significantly between the first and last visit (p&gt;0.05) or when compared to an age-matched control group (p&gt;0.05). CONCLUSIONS: The Physiol FineVision® trifocal IOL provided satisfactory full range of vision and quality of vision parameters 12 months after surgery. Visual acuity and psychophysical tests did not vary significantly between the first and last visit

Treatment of Retinal Vein Occlusion with Ranibizumab in Clinical Practice: Longer-Term Results and Predictive Factors of Functional Outcome

To evaluate long-term results and predictors of efficacy in patients with macular edema due to retinal vein occlusion (RVO) treated with intravitreal ranibizumab in a clinical practice setting.info:eu-repo/semantics/publishedVersio

Guidelines for the Management of Center-Involving Diabetic Macular Edema: Treatment Options and Patient Monitorization

Diabetic macular edema (DME) is the main cause of visual impairment associated with diabetic retinopathy (DR) and macular laser, during approximately three decades, and was the single treatment option. More recently, intravitreous injections of anti-angiogenics and corticosteroids modified the treatment paradigm associated with significant vision improvements. Nevertheless, not all patients respond satisfactorily to anti-VEGF or corticosteroid injections, so an adequate treatment choice and a prompt switch in therapeutic class is recommended. Several algorithms and guidelines have been proposed for treating center involving DME to improve patients' vision and quality of life. However, in Portugal, such guidelines are lacking. The present review aimed to provide guidelines for the treatment options and patient monitorization in the management of center-involving DME. We recommend anti-vascular endothelial growth factor (VEGF) as first-line therapy after a clinical evaluation accompanied by a rigorous metabolic control. Depending on the response obtained after 3-6 monthly intravitreal injections we suggest switching outside the class in case of a non-responder, maintaining the anti-VEGF-therapy in responders to anti-angiogenics. The treatment regimen for Dexamethasone intravitreal implant (DEXii) should be pro-re-nata with bi-monthly or quarterly monitoring visits (with a scheduled visit at 6-8 weeks after DEXii for intraocular pressure control). If a patient does not respond to DEXii, switch again to anti-VEGF therapy, combine therapies, or re-evaluate patients diagnose. There is a resilient need to understand the disease, its treatments, regimens available, and convenience for all involved to propose an adequate algorithm for the treatment of diabetic retinopathy (DR) and DME in an individualized regimen. Further understanding of the contributing factors to the development and progression of DR should bring new drug discoveries for more effective and better-tolerated treatments.info:eu-repo/semantics/publishedVersio

A CDCL-style calculus for solving non-linear constraints

In this paper we propose a novel approach for checking satisfiability of non-linear constraints over the reals, called ksmt. The procedure is based on conflict resolution in CDCL style calculus, using a composition of symbolical and numerical methods. To deal with the non-linear components in case of conflicts we use numerically constructed restricted linearisations. This approach covers a large number of computable non-linear real functions such as polynomials, rational or trigonometrical functions and beyond. A prototypical implementation has been evaluated on several non-linear SMT-LIB examples and the results have been compared with state-of-the-art SMT solvers.Comment: 17 pages, 3 figures; accepted at FroCoS 2019; software available at <http://informatik.uni-trier.de/~brausse/ksmt/