Bial, Eisai, GlaxoSmithKline, Janssen-Cilag, Novartis, Pfizer, Sanofi-Aventis, UCB, the Netherlands Epilepsy Foundation, and Stockholm County Council.

Objective: To identify morphological and/or functional early markers of choroidal neovascularization (CNV) development in fellow eyes of patients with exudative age-related macular degeneration (AMD). Design: This is a single-center, prospective, observational, longitudinal 2-year study. Patients: Patients were enrolled with the diagnosis of neovascular AMD in 1 eye and early age-related maculopathy (ARM) in the fellow eye. Intervention or Methods: All patients completed the baseline assessment and were followed up for up to 24 months with repeated ophthalmic and imaging assessments performed at 6-month intervals. Main OutcomeMeasures: Each patient underwent a detailed ocular and medical history, a complete ophthalmologic examination with color fundus photography, fluorescein angiography, indocyanine green angiography (ICG), optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging and retinal leakage analysis (RLA). Results: Sixty-two patients were enrolled in the study. Large or intermediate drusen were present in 100% of the study eyes and hyperpigmentation in 46% (24 eyes). Fifty-two patients completed the 2-year study follow-up. Large soft drusen (>125 µm) were observed in 15 out of 17 eyes (88%) that converted and developed CNV during the study and in 25 out of 35 eyes (71.4%) that did not develop CNV. Among the 17 eyes that developed CNV, 9 (53%) showed abnormal findings before conversion, on ICG. No particular FAF pattern was found to be correlated with conversion to wet AMD. OCT was able to document the presence of intra- or subretinal fluid at the time of conversion in all 17 eyes that developed CNV during the study. Alterations of the blood-retinal barrier were identified by RLA before conversion in 76% of the eyes that converted and 23% of the eyes that did not convert during the study. Conclusions: Characterization of early ARM phenotypes is challenging. By combining different imaging modalities of the macula and correlating this information, we were able to determine the presence of functional macular alterations in the fellow eye of patients with this disease before development of CNV.

Purpose: To examine the relationship between microaneurysm turnover (formation rate), using a new semi-automatic method (MA-Tracker) based on color fundus photographs, and diabetic retinopathy (DR) progression to clinically significant macular edema (CSME). Methods: In total, 113 patients/eyes with nonproliferative DR (NPDR) were followed up every 6 months for 2 years as controls of the DR clinical trials, and by conventional general and ophthalmological care for the next 8 years (over a total of 10 years’ follow-up). Microaneurysm turnover for the 2 first years was computed using the MA-Tracker. Results: The 17 patients that developed CSME over the 10 years of follow-up presented a microaneurysm formation rate of 9.2 ± 18.2 microaneurysms/year (mean ± SD) during the first 2 years, which was statistically higher than the eyes that did not develop CSME (0.5 ± 1.2 microaneurysms/year, p < 0.001). These 17 patients also presented higher HbA_1C levels at baseline (8.5 ± 1.2%) compared to the patients who did not develop CSME (7.3 ± 1.2%, p = 0.001). Conclusions: A high microaneurysm formation rate on color fundus photographs appears to be a good biomarker for DR progression to CSME in type 2 diabetic patients with NPDR.

Purpose To analyse and compare the classification of eyes with diabetic retinopathy using fluorescein angiography (FA) and optical coherence tomography angiography (OCTA) performed either with AngioPlex or AngioVue. Methods This was an observational cross-sectional study of 50 eyes from 26 diabetic subjects. Two independent graders classified the FA angiograms, to assess the presence and severity of several characteristics according to the ETDRS Report 11, and a similar evaluation was performed for each 3×3 mm OCTA image from the superficial retinal layer and for the full retina slab. Results Percentages of non-gradable images for the outline of foveal avascular zone (FAZ) in the central subfield (CSF) were 29.0% for FA, 12.0% for AngioVue and 3.0% for AngioPlex. For capillary loss, percentages of non-gradable images in the CSF were 25.0% for FA, 11% for AngioVue and 0.0% for AngioPlex. For the inner ring (IR), percentages of non-gradable images were 12.5% for FA, 11.5% for AngioVue and 0.5% for AngioPlex. Agreement between graders was substantial for outline of FAZ. For capillary loss, the agreement was fair for the CSF, and moderate for the IR. Conclusions The OCTA allows better discrimination of the CSF and parafoveal macular microvasculature than FA, especially for FAZ disruption and capillary dropout, without the need of an intravenous injection of fluorescein. In addition, FA had also a higher number of non-gradable images. The OCTA can replace with advantage the FA, as a non-invasive and more sensitive procedure for detailed morphological evaluation of central macular vascular changes. Trial registration number NCT02391558, Pre-results.

Purpose: To evaluate the long-term safety and efficacy of intravitreal ranibizumab in the treatment of myopic choroidal neovascularization (CNV). Methods: Three-year retrospective, nonrandomized, interventional case series. Forty eyes of 39 patients with myopic CNV were included; 15 with previous photodynamic therapy, and 25 naïve eyes. Best-corrected visual acuity (BCVA) changes, central foveal thickness (CFT), and number of treatments were assessed, from baseline to month 36. Results: Mean visual acuity improved from 55.4 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline to 59.7 letters at 12 months (p = 0.07), 61.8 letters at 24 months (p = 0.008) and 63.4 letters at 36 months (p = 0.039). Twenty-five percent of the patients gained ≧15 letters (3 lines) at 12 months, 30% at 24 months and 35% at 36 months. There was a mean reduction of 80 µm in CFT (p < 0.001). A mean of 4.1 injections were performed in the first year, 2.4 in the second year and 1.1 in the third year. Fifty-three percent of the eyes had no need for treatment during the third year of follow-up. Conclusions: Intravitreal ranibizumab seems to be an effective and safe therapeutic procedure to treat CNV in highly myopic eyes, with a high proportion of patients gaining or stabilizing BCVA at a 3-year follow-up.

Standard photodynamic therapy with verteporfin was effective and safe in chronic central serous chorioretinopathy treatment with a significant improvement in the long term, both anatomic and visual, without inducing additional retinal atrophy or systemic adverse effects.

Purpose To evaluate morphological and functional chorioretinal changes 5 years after standard photodynamic therapy (PDT) for chronic central serous chorioretinopathy (CSC). Methods A retrospective, nonrandomized study, including patients with chronic CSC treated with standard PDT and followed for at least 60 months. All patients underwent a complete ophthalmological examination, and the location and number of treatments were registered. Five or more years after treatment, subfoveal and non-subfoveal treated areas were evaluated with Spectralis optical coherence tomography and microperimetry. Results Seventeen eyes of 15 patients were included, with mean age of 48.3±8.4 years and a mean follow-up of 80.6± 12.4 months (range from 62 to 104 months). All eyes had neurosensory detachment (NSD) at baseline. Treatment was performed under the fovea in 58.8 % and in a non-foveal area in 41.2 % of the eyes. At the final visit all eyes had resolution of the NSD, with a statistical significant reduction in central macular thickness (p=0.005) and preserved neuroretinal thickness (p=0.839). There was a statistical difference between initial and final BCVA (p<0.001) and a mean gain of 8.4±7.8 letters. Subfoveal morphological changes in external limiting membrane (ELM) and in photoreceptor inner and outer segment junction (IS/OS) were correlated with final BCVA (p=0.015 and p=0.014 respectively), but not with the variation of BCVA. There was a statistical correlation between morphological changes in IS/OS line and retinal sensitivity in the central 12°and 2°(p=0.003 and p=0.002 respectively). The morphological changes in the subfoveal layers were not dependent on treatment location (p=0.154, p=0.644, and p=1.0 for ELM, IS/OS line, and retinal pigment epithelium respectively). Subfoveal final mean choroidal thickness was 295.1±68.7 μm, and showed no statistical difference from the normal population (p=0.633). Conclusions Morphological and functional chorioretinal changes, observed 5 or more years after standard PDT for chronic CSC, were not correlated with the location of treatment, neither with the progression of visual acuity or with the location of treatment, and are more likely to be related to the disease itself than with the treatment provided.

Background: To identify alterations of retinal capillary blood flow in the papillomacular area in preclinical diabetic retinopathy using the Heidelberg scanning laser Doppler flowmeter. Methods: Ten eyes from ten patients with type 2 diabetes and no lesions visible on fundus photography (level 10 of Wisconsin grading) and ten eyes from ten healthy subjects of similar age range were examined with the HRF. Intravisit reproducibility of retinal capillary blood flow measurements was assessed in normal subjects and in type 2 diabetic patients, comparing different measurement areas and different analysis procedures: (a) 10×10 pixel box with original software, (b) 10×10 pixel box with SLDF software, and (c) whole-scan analysis with SLDF software (automatic full-field perfusion image analysis