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Purpose: To evaluate the impact of drusen-like deposits (DLD) on retinal layer integrity and retinal function by optical coherence tomography (OCT) and multifocal electroretinography (mfERG) in patients with systemic lupus erythematosus (SLE). Methods: We identified 66 eyes of 33 SLE patients treated with hydroxychloroquine (HCQ) that were categorized into two groups according to whether DLDs were present (34 eyes, Group One) or absent (32 eyes, Group Two). The groups were matched for age, sex, HCQ treatment duration, daily, and cumulative dosage. OCT (retinal layer thicknesses, central retinal thickness, CRT) and mfERG concentric ring analysis were analyzed and compared. Results: CRT was significantly thicker in Group One compared to Group Two (273.21 ± 3.96 vs. 254.5 ± 7.62) (p = 0.023). Group One also demonstrated an overall thicker retinal pigment epithelium compared to Group Two; however, the other outer retinal layers, outer nuclear layer, and photoreceptor layer were found to be significantly thinner in Group One compared to Group Two. We found no differences in mfERG parameters between the two groups. Conclusions: DLDs in SLE patients lead to abnormal central retinal layer thickness, which has no measurable impact on cone-mediated retinal function assessed by mfERG.

Contains fulltext : 238066.pdf (Publisher’s version ) (Open Access) PURPOSE: To compare treatment outcomes of treatment-naïve eyes with neovascular age-related macular degeneration (nAMD) with bevacizumab as the first-line treatment, according to the guidelines of the Dutch Ophthalmological Society, with those treated first with either ranibizumab or aflibercept, as used in many other countries, all treated using a treat-and-extend strategy. METHODS: Data were obtained from the prospectively designed Fight Retinal Blindness! outcomes registry. The primary outcome was the mean change from baseline in visual acuity of all treated eyes, after 12, 24 and 36 months of treatment. Secondary outcomes were the number of injections, the number of visits and the rate of switching to a second anti-VEGF drug. RESULTS: The study included 703 treatment-naïve eyes with nAMD with 12 months follow-up, 373 eyes with 24 months follow-up, and 171 eyes with 36 months follow-up in the Netherlands, and 1131, 652, and 303 treatment-naïve eyes with respectively 12, 24, and 36 months of follow-up in all other countries. The change in visual acuity from baseline did not differ between the Netherlands and the other countries at any follow-up time. The median number of injections, visits and the proportion of eyes switching treatment was significantly higher in the Netherlands than in the other countries. CONCLUSION: Starting anti-VEGF treatment for nAMD with bevacizumab, as is mandatory in the Netherlands, delivers outcomes similar to those starting treatment with either ranibizumab or aflibercept, but at a cost of more frequent injections, and visits, and more frequent switching treatment to a second drug.

International audience; PURPOSE: To report the 36-month treatment outcomes of eyes with neovascular age-related macular degeneration (nAMD) receiving vascular endothelial growth factor (VEGF) inhibitors in daily practice who did not develop either subretinal fibrosis (SRFi) or macular atrophy (MA). METHODS: This is a retrospective analysis of data from the Fight Retinal Blindness registry. Treatment-naïve eyes starting intravitreal injection of VEGF inhibitors for nAMD from January 1, 2010, to September 1, 2017, and did not have SRFI and MA at baseline were tracked. RESULTS: We identified 2478 eligible eyes, of which 1712 eyes did not develop SRFi or MA, 291 developed extrafoveal SRFI or MA, and 475 developed subfoveal SRFi or MA over 36 months. The estimated visual acuity stabilized from 6 months to 36 months in eyes that did not develop SRFI or MA with a mean (95% confidence interval [CI]) change in VA of -1 (-2, 0) letters, whereas eyes that developed extrafoveal (-3 [-5, -2] letters) or subfoveal (-10 [-11, -8] letters) SRFi or MA declined in vision in the same period. Eyes with no or extrafoveal SRFi or MA over 36 months were more likely to maintain their visual improvement from six months to 36 months (odds ratio [OR; 95% CI] = 2.3 [1.5, 3.3] for absence vs. subfoveal SRFi or MA, P ≤ 0.01 and OR = 2.0 [1.2, 3.4] for extrafoveal vs. subfoveal MA or SRFi, P = 0.01). CONCLUSIONS: Treatment-naïve nAMD eyes receiving VEGF inhibitors maintain their initial six-month visual improvement over three years if they do not develop SRFI or MA. TRANSLATIONAL RELEVANCE: The nAMD is still a major cause of blindness despite antiangiogenic treatments. We found that eyes that did not develop subretinal fibrosis or macular atrophy maintained their initial vision improvement for at least three years, suggesting that identifying treatments for these complications is the final barrier to achieving excellent outcomes in nAMD.

Purpose: To report the 24-month outcomes of vascular endothelial growth factor (VEGF) inhibitors for myopic choroidal neovascularization (mCNV) in predominantly Caucasian eyes in routine clinical practice. Methods: Retrospective analysis of treatment-na¿ıve eyes starting intravitreal injection of VEGF inhibitors of either bevacizumab (1.25 mg) or ranibizumab (0.5 mg) for mCNV from 1 January 2006 to 31 May 2018 that were tracked in the Fight Retinal Blindness! registry. Results: We identified 203 eyes (bevacizumab-85 and ranibizumab-118) of 189 patients. The estimated mean (95% CI) change in VA over 24 months for all eyes using longitudinal models was +8 (5, 11) letters with a median (Q1, Q3) of 3 (2, 5) injections given mostly during the first year. The estimated mean change in VA at 24 months was similar between bevacizumab and ranibizumab [+9 (5, 13) letters for bevacizumab versus +9 (6, 13) letters for ranibizumab; p = 0.37]. Both agents were also similar in the mCNV activity outcomes, treatment frequency and visit frequency. Conclusions: The 24-month treatment outcomes of VEGF inhibitors for mCNV were favourable in this largest series yet reported of predominantly Caucasian eyes in routine clinical practice,with approximately two lines of visual gain and amedian of three injections given mostly during the first year. These outcomes are similar to those reported for predominantly Asian eyes.Bevacizumab appeared to be as safeandeffective as ranibizumab. Key words: anti-VEGF therapy - Caucasian - high myopia - myopia - myopic choroidal neovascularization - optical coherence tomography - pathologic myopia - VEGF inhibitors

Importance Neovascular age-related macular degeneration (nAMD), the largest single cause of irreversible severe vision loss in high-income countries, can now be treated with vascular endothelial growth factor (VEGF) inhibitors, but to our knowledge, no data on lifetime outcomes are available. Objective To determine visual acuity (VA) outcomes of anti-VEGF treatment for nAMD in both eyes for patients' remaining lifetime. Design, setting, and participants Multistate modeling using real-world cohort data of 3192 patients with nAMD (>67 000 visits) treated in routine eye clinics in Australia, New Zealand, and Switzerland. Data were analyzed between 2007 and 2015. Exposures Intravitreal anti-VEGF treatment at the treating physician's discretion and prospective data collection in standardized registry. Main outcomes and measures Visual acuity in both eyes over the remaining lifetime. Results For the mean remaining lifetime of 11 years, an estimated 12% (n = 371; 95% CI, 345-400) of the sample retained driving VA and an estimated 15% (n = 463; 95% CI, 434-495) reading VA in at least 1 eye. At that time, an estimated 82% of the sample (n = 2629; 95% CI, 2590-2660) had dropped out. Younger age at baseline and more injections during the first year of treatment were associated with better long-term outcomes. Conclusions and relevance Anti-VEGF treatment was associated with preserved useful visual acuity in almost 20% of patients over their average remaining lifetime. More than 80% of patients will cease treatment over that time, having likely experienced a deterioration of vision beforehand. This is a remarkable outcome compared with outcomes without intervention, which lead to legal blindness within 3 years of disease onset in 80% of those affected. These findings underline the public health necessity of providing anti-VEGF treatment to persons in need.

PURPOSE To assess whether smoking status affects 1-year visual outcomes in eyes treated with vascular endothelial growth factor inhibitors for neovascular age-related macular degeneration. METHODS Retrospective analysis of data from a prospectively designed, multicenter, observational database. Nine hundred and eighty seven treatment-naive eyes of patients with neovascular age-related macular degeneration were tracked by the Fight Retinal Blindness! outcome registry in Australia, New Zealand, Singapore, and Switzerland who had documented smoking status at baseline and commenced vascular endothelial growth factor inhibitor therapy from January 2006 to December 2016. Generalized additive models were used to display visual acuity results. RESULTS There was a significant difference in mean improvement in visual acuity at 12 months between nonsmokers, ex-smokers, and current smokers (7.7 vs. 6.1 vs. 3.5 letters of change; P = 0.046) among patients who completed 12 months of treatment when adjusted for age, baseline visual acuity, and choroidal neovascular membrane lesion type and nested for practice. There was no significant difference in the median number of injections over 12 months of treatment by smoking status. Current smokers were a mean of 6.2 years younger than nonsmokers when they started treatment (P < 0.001). CONCLUSION This study found inferior 12-month visual outcomes in patients who continued to smoke while receiving vascular endothelial growth factor inhibitor therapy for neovascular age-related macular degeneration.

To report and compare 10-year treatment outcomes of vascular endothelial growth factor (VEGF) inhibitors for neovascular age-related macular degeneration (nAMD) from Australia and New Zealand (ANZ) and Switzerland.Retrospective, comparative, interventional case series.We analyzed 712 treatment-naive eyes (ANZ, n = 474; Switzerland, n = 321) starting anti-VEGF for nAMD in routine clinical practice between January 1, 2006, and December 31, 2008, tracked in the prospectively designed observational database, the Fight Retinal Blindness! registry. The primary outcome was mean change in visual acuity (VA [in logMAR letters]) in eyes that completed 10 years of treatment.The mean VA in 132 eyes (28%) from ANZ patients who completed 10 years of treatment dropped by 0.9 letters from baseline (95% confidence interval [CI], -4.9 to 3.1; P = 0.7) with 42% achieving ≥20/40, whereas the 37 eyes (12%) from Swiss subjects lost 14.9 letters (95% CI, -24 to -5.7; P0.001) with 35% achieving ≥20/40. Eyes from ANZ patients received more injections than eyes from Swiss subjects over 10 years (a median of 53 vs 42, respectively) from fewer visits with better disease control (proportion of visits with active disease: 38% vs 69%, respectively), suggesting a treat-and-extend regimen versus a pro re nata regimen (treatment given only when the lesion is active). Macular atrophy and subretinal fibrosis were the main reasons for 10 letter loss in the subset of eyes analyzed retrospectively. The mean VA of eyes from both regions that discontinued treatment within 10 years had fallen below the baseline at their final visit.Eyes with nAMD may achieve satisfactory long-term visual outcomes if they receive adequate treatment. Central macular atrophy does not develop universally in eyes receiving long-term treatment with VEGF inhibitors as previously feared. Visual outcomes were better in eyes from ANZ patients, likely because they received more injections.

Choroidal neovascularization (CNV) is a major cause of severe vision loss in patients with age-related macular degeneration. Despite intensive research, the pathogenesis of choroidal neovascularization is still poorly understood. Many factors were identified to be involved in the development of choroidal neovascularization. Choroidal blood flow and hemodynamic changes with consecutive impairment of the perfusion, especially of the choriocapillaris, as well as reduction of clearance of debris from the retinal pigment epithelium and Bruch’s membrane were proposed to play a role. Imbalance of the angiogenic process including different factors such as vascular endothelial growth factor, angiopoietins, basal fibroblast growth factor and pigment epithelium-derived factor as well as degradation of extracellular matrix are also important factors for the development of CNV. Transgenic and knockout studies have provided important insights into the development of CNV, the main cause of vision impairment and loss in patients with age-related macular degeneration.

The purpose of the study was to analyze imaging findings in spectral domain en face optical coherence tomography (SD OCT) in patients with laser‐induced and solar maculopathies focusing on the possible regeneration of the ellipsoid zone. In a retrospective case series of 3 patients (4 eyes) with solar maculopathy and 2 patients (3 eyes) with laser‐induced maculopathy who underwent a comprehensive ocular examination, ellipsoid zone (EZ) was segmented from SD OCT data. Evaluation of EZ in en face OCT revealed a hyporeflective lesion surrounded by a hyperreflective border. The area of EZ alteration was measured manually in en face OCT. All patients showed partial EZ regeneration. Mean EZ alteration decreased from 0.12 mm2 (range: 0.05–0.32) at baseline to 0.07 mm2 (range: 0.01–0.22) at last follow‐up (p=0.018, mean follow‐up: 372 days; range: 115–592). Mean best visual acuity (BVA) improved from 20/36 at baseline to 20/30 (p=0.018). In conclusion, en face OCT imaging clearly delineated the area of EZ alteration in patients with laser‐induced and solar maculopathies. Follow-up showed significant reformation of the EZ as well as improvement of BVA.

ObjectiveTo compare the outcomes of trainee-led and specialist-led management of neovascular age-related macular degeneration.DesignProspective multicentre registry-based observational study.SettingOphthalmology training centres in Australia and Europe where both trainee-led and specialist-led models of care coexist.ParticipantsTreatment-naïve eyes with neovascular age-related macular degeneration and at least 12 months follow-up. 726 eyes were included in the study from two centres, 534 receiving trainee-led treatment and 192 specialist-led treatment.InterventionsThe management and outcomes of patients receiving trainee-led care were compared with those receiving specialist-led care.Main outcomes measuresThe primary outcome was the mean change in visual acuity at 12 months from first injection. Outcomes were also presented at 36 months where available.ResultsThe mean age of participants was 79 years and 65% were female. The adjusted change in acuity at 12 months in trainee-led vs specialist-led eyes was +3.2 letters vs +4.1 letters (difference −0.9 letters, 95% CI −3.4 to 1.5, p=0.473). The mean adjusted change in acuity at 36 months was −0.9 letters in trainees vs +0.2 letters for specialists (difference −1.1 letters, 95% CI −5.1 to 2.9, p=0.596). Eyes treated by trainees received fewer injections on average to 36 months (15.0 vs 19.0, p=0.004), although this trend was observed at one centre only.ConclusionsNo significant differences in outcome between eyes managed by trainees and eyes managed by specialists were observed. Appropriately structured trainee-led management of neovascular age-related macular degeneration is a reasonable approach where regulatory and practical considerations allow it.

International audience; PURPOSE:To explore various methods for assessing the early response to vascular endothelial growth factor (VEGF) inhibitors for neovascular age-related macular degeneration and investigate their association with 3-year visual acuity (VA) outcomes.DESIGN:Database study, prospectively designed.PARTICIPANTS:Treatment-naïve eyes in the Fight Retinal Blindness! registry that commenced anti-VEGF therapy between January 1, 2007, and March 1, 2014, that received 3 anti-VEGF injections within the first 3 months.METHODS:The early response was defined as occurring up until the fourth injection. Various early response metrics were explored: (1) achieving good VA (≥70 letters; Snellen equivalent, 20/40), (2) absolute change in VA from baseline, (3) time to first grading of the choroidal neovascular lesion as inactive, and (4) maximum rate of VA change between successive injections.MAIN OUTCOME MEASURES:Proportion of eyes achieving ≥70 letters 3 years.RESULTS:This study included 2051 treatment-naïve eyes from 1828 patients. Achieving good vision at 3 years was associated significantly with (1) having good vision by the fourth injection (VA ≥70 vs. VA 5 letters) early VA gains (vs. early VA loss: OR, 1.8; 95% CI, 1.2-2.6; P = 0.002; and OR, 1.8; 95% CI, 1.3-2.5; P < 0.001), (3) fewer injections until first grading of lesion inactivity (≤3 vs. >3 injections: OR, 1.6; 95% CI, 1.2-2.1; P < 0.001), (4) gradual change (between -4 and 4 letters) or rapid gains (≥5 letters) between successive injections (vs. rapid loss: OR, 1.7; 95% CI, 1.1-2.6; P = 0.015; and OR, 1.6; 95% CI, 1.1-2.3; P = 0.018). Eyes that achieved small or large early gains had similar vision at 3 years (65.0 and 64.7 letters, respectively) and had better vision than eyes with early VA loss (57.2 letters).CONCLUSIONS:Attainment of good vision by the fourth injection was associated strongly with 3-year visual outcomes, whereas other early response parameters showed a moderate association. The early response during the initial 3 monthly injections can be a useful guide for subsequent treatment decisions.

Aims To examine 12-month outcomes of eyes switching from intravitreal ranibizumab to aflibercept for neovascular age-related macular degeneration (nAMD). Methods Database observational study of eyes with nAMD tracked by the Fight Retinal Blindness outcome registry that received ranibizumab for at least 12 months before switching to aflibercept and followed for at least 12 months after the switch. Visual acuity (VA) recorded at 12 months after the switch was analysed using locally weighted scatterplot smoothing curves. Lesion activity was graded according to a prospectively identified definition. Main outcomes were change in VA and treatment intervals 12 months after the treatment switch. Secondary outcomes included change in activity grading, effect of duration of treatment before switching and analysis of eyes that switched back. Results A total of 384 eyes switched from ranibizumab to aflibercept after a mean duration of 39.8 months on the original treatment. The mean VA did not change from the time of switching treatment (63.4, SD 15.9 logarithm of the minimum angle of resolution letters) to 12 months later (63.3, SD 16.7). While 10% of eyes gained 10 or more letters 12 months after the switch, 13% lost the same amount. The mean number of injections decreased by around one injection in the 12 months after switching (p

International audience; INTRODUCTION:To report 12-month pharmacoepidemiologic data on aflibercept and ranibizumab use in treatment-naïve eyes with neovascular age-related macular degeneration (nAMD).METHODS:Participants were treatment-naïve eyes with nAMD tracked by the Fight Retinal Blindness! registry starting therapy with aflibercept or ranibizumab treatment between January 1st, 2013 and 31st December, 2016. Demographic and clinical characteristics were compared between treatment groups.RESULTS:During the study period, 689 eyes initiated treatment with ranibizumab compared to 568 with aflibercept. We found a similar rate of use of both drugs. Ranibizumab-treated patients were older than aflibercept-treated patients (overall mean [SD] 82.0 [8.4] vs. 78.6 [8.1], P

International audience; Clinical trials identified intravitreal vascular endothelial growth factor inhibitors (anti-VEGF agents) have the potential to stabilise or even improve visual acuity outcomes in neovascular age-related macular degeneration (AMD), a sight-threatening disease. Real-world evidence allows us to assess whether results from randomised controlled trials can be applied to the general population. We describe the development of global registries, in particular the Fight Retinal Blindness! registry that originated in Australia, the United Kingdom AMD Electronic Medical Records User Group and the IRIS registry in the USA. Real-world observations relating to efficacy, safety and resource utilisation of intravitreal anti-VEGF therapy for neovascular AMD are then summarised. Novel observations that would have been challenging to identify in a clinical trial setting are then highlighted, including the risk of late disease reactivation, outcomes in second versus first treated eyes, and the increased risk of posterior capsular rupture during cataract surgery in patients who have received intravitreal anti-VEGF therapy. We conclude by exploring future directions in the field. This includes the development of a global consensus on real-world outcome measures to allow greater comparison of results. Real-world neovascular AMD outcome registries can be linked with other databases to determine systemic safety or genetic predictors of treatment efficacy. Machine learning offers opportunities to extract useful insights from "Big Data" often collected in these registries. Real-world registries could be used by drug regulatory authorities and industry as an alternative to more costly and time-consuming phase 4 clinical trials, potentially allowing medication costs to be based on outcomes achieved.

Purpose To study a novel and fast optical coherence tomography (OCT) device for home-based monitoring in age-related macular degeneration (AMD) in a small sample yielding sparse OCT (spOCT) data and to compare the device to a commercially available reference device. Methods In this prospective study, both eyes of 31 participants with AMD were included. The subjects underwent scanning with an OCT prototype and a spectral-domain OCT to compare the accuracy of the central retinal thickness (CRT) measurements. Results Sixty-two eyes in 31 participants (21 females and 10 males) were included. The mean age was 79.6 years (age range, 69-92 years). The mean difference in the CRT measurements between the devices was 4.52 μm (SD ± 20.0 μm; range, -65.6 to 41.5 μm). The inter- and intrarater reliability coefficients of the OCT prototype were both >0.95. The laser power delivered was

International audience; PURPOSE:To determine the characteristics and outcomes of eyes with neovascular age-related macular degeneration (nAMD) in which choroidal neovascular (CNV) lesion activity was graded as uncertain.DESIGN:Prospective, database, observational study.PARTICIPANTS:Treatment-naïve patients with nAMD tracked by the Fight Retinal Blindness! (FRB!) registry initiating treatment between January 1, 2008, and January 1, 2014, with 2 years of follow up.METHODS:Lesion activity was determined by the clinical judgment of the providing physician on the basis of clinical examination with ancillary testing. Eye-based analysis investigated clinical characteristics and outcomes by proportion of visits with uncertain CNV lesion activity. Encounter-based analysis investigated CNV lesion grading over time with corresponding treatment and follow up.MAIN OUTCOME MEASURES:Change in mean visual acuity (number of letters read on a logarithm of the minimum angle of resolution chart) at 2 years. Secondary outcomes included the number of visits and injections.RESULTS:We identified 1631 eyes of 1419 patients with 27 974 visits to 46 retinal specialists. The CNV lesion activity was uncertain at 4601 encounters (16.4%) and experienced by the majority of eyes (52%) and providers (72%). Uncertainty of CNV lesion activity did not significantly decline with increasing number of visits in individual patients (P = 0.97) but did decline from 32% in 2010 to 4% in 2015 (P < 0.001). Eyes having no visits with uncertain CNV lesion grading gained more letters (mean, 7.0) than eyes with moderate or high levels of uncertainty (mean, 3.98 and 3.37; P = 0.03 and 0.02, respectively). The mean probability of receiving an injection was higher in visits with active (0.89) compared with inactive (0.68, P < 0.001) and uncertain (0.69, P < 0.001) CNV lesion activity. Subsequent follow-up length was also decreased in visits with active (mean ± standard deviation [SD], -0.9±39 days) compared with inactive and uncertain CNV lesion activity (mean ± SD, 1.9±39 days, P < 0.001, and 2.4±39 days, P < 0.001, respectively).CONCLUSIONS:Rates of uncertainty regarding CNV lesion activity were high, and eyes with higher rates of uncertain CNV activity had worse outcomes. Further studies are warranted to establish whether eyes should be treated more aggressively when the activity status of the CNV lesion is uncertain.

Purpose To evaluate variability of central corneal thickness measurement (CCT) devices using a hitherto unprecedented number of CCT devices. Methods CCT was measured consecutively in 122 normal corneas of 61 subjects with seven different devices using three distinct measurement technologies: Scheimpflug, Ultrasound, and Optical Coherence Tomography (OCT). Per device deviation from the mean CCT value per eye was used to determine which of the devices performed best, compared to the mean value. Results Cirrus OCT yielded the lowest deviation. Deviations of the individual devices from the mean CCT of each eye were (OS/OD) 12.8±5.0/14.9±9.4 μm for Topcon noncontact specular microscopy (NCSM), 11.3±5.9/10.6±7.3 μm for Pentacam, 10.7±5.2/10.4±4.8 μm for Spectralis OCT, 6.0±3.9/6.2±4.9 μm for Topcon DRI OCT, 5.1±3.4/5.9±10.3 μm for AngioVue OCT, 4.8±4.1/5.7±4.6 μm for US pachymetry, and 4.2±3.2/5.7±4.6 μm for Cirrus OCT. The maximum differences between US pachymetry and the other devices were very high (up to 120 μm). Conclusion Central corneal thickness may be under- or overestimated due to high interdevice variations. Measuring CCT with one device only may lead to inappropriate clinical and surgical recommendations. OCT showed superior results.

PURPOSE: To analyze submacular perforating scleral vessels (PSVs) using enhanced depth imaging spectral domain optical coherence tomography (EDI-SDOCT). METHODS: Twenty-two eyes of 11 healthy women were included in this retrospective study. Central EDI-SDOCT scans (3 × 4.5 × 1.9 mm, 13.5 mm scan area) were acquired and postprocessed by denoising, manual sclera segmentation, and PSV investigated by five graders. RESULTS: Mean age was 22.4 ± 6.2 years. Mean refractive error was -0.44 ± 0.8 diopters. Mean axial length was 23.08 ± 0.63 mm. The coefficient of agreement for grading was good. Mean number of submacular PSVs was 0.33 ± 0.2 per mm (range from 0 to 9 per eye). Subfield analysis showed 0.2 ± 0.5 (range 0-2) and 2.1 ± 1.8 (range 0-7) vessels, respectively, for central 1-mm diameter and 3-mm diameter. Quadrant analysis showed 0.7 ± 0.9, 0.5 ± 0.9, 0.3 ± 0.6, and 0.4 ± 0.6 vessels, respectively for superior, inferior, nasal, and temporal quadrants. Total number of PSV showed no significant side difference (median difference 0.5, confidence interval -3.0 to 3.0, P = 0.94) or an influence of axial length (P = 0.16). CONCLUSION: This is the first description of three-dimensional EDI-SDOCT visualization of submacular PSV in healthy eyes. This method allows for in vivo imaging of a critical component of outer retinal perfusion at the posterior pole.

Endothelial progenitor cells (EPCs) are a group of rare cells that play an important role in the repair of injured vascular endothelial cells and assist in reperfusion of ischemic tissue. Decreased production and/or loss of function of EPCs are associated with diabetic vasculopathy. The molecular mechanisms by which diabetes impairs EPCs remain unclear. We conducted microarray experiments followed by integrative regulatory analysis on cells isolated from Akita diabetic mice (18-weeks after onset of diabetes) and age-matched non-diabetic controls. Two types of cells were isolated from mice bone marrow; Lin+ cells and Lin-/VEGF-R2+ EPCs. RNA was hybridized to mouse WG-6 V2 beadchips followed by comprehensive gene network analysis and computational validation of the obtained results. In total, 80 genes were exclusively DE between non-diabetic Lin-/VEGF-R2+ EPCs and diabetic Lin-/VEGF-R2+ EPCs, of which the 3 genes Clcnka, Pik3c2a, and Ptf1a are known to be associated with diabetic complications. Further analysis led to the establishment of a TF-miRNA mediated regulatory network specific to diabetic Lin-/VEGF-R2+ EPCs and to identify 11 central-hub TFs (Tbp, Ahr, Trp53, Gata1, Foxo1, Foxo4, Yy1, Max, Pparg, Myc, Cebpa), and 2 miRNAs (mir-139-5p, mir-709) that might act as putative genomic drivers of diabetic pathogenesis in Lin-/VEGF-R2+ EPCs. Moreover, we identified multiple TF-miRNA co-regulatory network motifs for which we validated their contribution to diabetic Lin-/VEGF-R2+ EPCs in terms of statistical significance and relevance to biological evidence. Our findings suggest that diabetic Lin-/VEGF-R2+ EPCs have specifically altered signature genes and miRNAs that render their capacity to proliferate and differentiate.

Purpose To assess the incidence, cumulative rate, and long-term outcomes of infectious and noninfectious endophthalmitis after intravitreal injections (IVTs) of anti-vascular endothelial growth factor (VEGF) agents. Design Database study, prospectively designed. Participants Treatment-naive eyes with neovascular age-related macular degeneration (nAMD) tracked by the Fight Retinal Blindness! (FRB!) registry that commenced anti-VEGF therapy between January 1, 2006, and November 30, 2016. Methods Cumulative rate of endophthalmitis and survival curves were measured using Cox-proportional hazards models. Locally weighted scatterplot smoothing curves were used to display visual acuity (VA). Main Outcome Measures Incidence and cumulative rate of endophthalmitis, and change in VA 12 months after endophthalmitis. Results Infectious endophthalmitis developed in 18 of 88 150 injections (1/4897 injections [0.020%]; 95% confidence interval [CI], 0.012–0.032) with no difference found between types of anti-VEGF medications ( P = 0.896). The cumulative rate of infectious endophthalmitis per patient was 0.055%, 0.183%, 0.360%, 0.360%, 0.555%, and 0.843% after 10, 20, 30, 40, 50, and 60 IVTs, respectively. However, the "risk" of infectious endophthalmitis did not increase with each successive injection ( P = 0.202). Noninfectious endophthalmitis developed in 11 of 88 150 injections (1/8013 injections [0.012%]; 95% CI, 0.006–0.022). The cumulative rate of noninfectious endophthalmitis per patient was 0.087% and 0.228% after 10 and 20 IVTs, respectively, and then remained stable up to 60 IVTs. The incidence of noninfectious endophthalmitis was higher for bevacizumab (8/9931, 0.081%) compared with ranibizumab (3/54 776, 0.005%; P = 0.005) and aflibercept (0/23 425; P = 0.016), and no differences were observed between ranibizumab and aflibercept ( P = 1.0). The 12-month VA in infectious and noninfectious endophthalmitis was within ±2 lines of before endophthalmitis in 53% and 75% of eyes, respectively; a loss >2 lines was observed in 31% and 25% of eyes, respectively. Conclusions The incidences of infectious and noninfectious endophthalmitis after IVT were low, and the risk did not increase with each successive injection. We found higher rates of noninfectious endophthalmitis with bevacizumab compared with ranibizumab or aflibercept. Three quarters of cases with infectious and two thirds of cases with noninfectious endophthalmitis retained vision within 10 letters of the pre-endophthalmitis level.

International audience; PURPOSE:To report 24-month outcomes of a treat and extend (T&E) regimen using aflibercept in eyes with neovascular age-related macular degeneration.METHODS:This was a database observational study that included treatment-naive eyes with neovascular age-related macular degeneration tracked by the Fight Retinal Blindness! outcome registry completing 24 months of sole monotherapy with aflibercept treatment under a T&E regimen between November 1, 2012 and January 31, 2014. Locally weighted scatterplot smoothing curves were used to display visual acuity outcomes. Main outcome measures were change in visual acuity at 24 months and number of injections and visits during the study period.RESULTS:The study population, identified by reviewing the database, consisted of 136 eyes from 123 patients completing 24 months of follow-up on aflibercept. Mean (SD) age was 77.2 (7.0) years, 59% were female. Mean visual acuity increased from 61.4 (∼20/60; SD 17.4) letters at baseline to 67.4 (∼20/45; SD 17.7) letters at 24 months (+6.0 letters [95% confidence interval: 3.3-8.5]; P < 0.001). From baseline to 24 months, the proportion of eyes with visual acuity ≥70 letters (20/40) increased (40%-58%, P < 0.001) and the proportion of eyes with visual acuity ≤35 letters (20/200) remained the same (10%; P = 0.547). Ninety-eight per cent of eyes starting with visual acuity ≥70 letters (20/40) were able to maintain this up to 24 months. From the first to the second year of treatment, the mean number of injections (7.8 [2.1] vs. 5.7 [2.6]; P < 0.001) and visits (8.7 [1.7] vs. 6.5 [2.4]; P < 0.001) decreased for eyes completing 24 months of treatment. When data from 60 eligible eyes that did not complete 2 years follow-up, along with 14 eyes that switched to ranibizumab, were included using last observation carried forward, the mean change in visual acuity from baseline was +5.6 letters (95% confidence interval: 3.3-7.7).CONCLUSION:These data indicate that eyes treated with aflibercept, as a sole therapy, in routine clinical practice with a T&E regimen can achieve good visual outcomes while decreasing the burden of treatments and clinic visits.

Purpose Various hypoxia-related proteins are differentially expressed in the retina and secreted to the vitreous and/or aqueous humor of patients affected by dry or neovascular age-related macular degeneration (nAMD). To determine whether these conditions alter concentrations of cytokines also in the systemic circulation, we measured plasma levels of six hypoxia-related proteins. Methods Plasma was prepared from EDTA blood that was collected from patients affected by dry AMD (n = 5), nAMD (n = 11), proliferative diabetic retinopathy (PDR; n = 9), and patients with an epiretinal membrane (ERM; n = 11). ERM samples served as negative controls, PDR samples as positive controls. Protein concentrations of vascular endothelial growth factor (VEGF), erythropoietin (EPO), angiopoietin-like 4 (ANGPTL4), placental growth factor (PlGF), tumor necrosis factor alpha (TNF-α), and pigment epithelium-derived factor (PEDF) were determined by enzyme-linked immunosorbent assay (ELISA). Results The concentration of PlGF was significantly increased in plasma of patients affected by nAMD. Although no statistically significant differences were found for EPO, ANGPTL4, PlGF, TNF-α, and PEDF, the mean concentration of VEGF was lowest in the nAMD group. Plasma concentrations of the six factors did not correlate with gender or age of patients. Conclusions nAMD may increase plasma concentrations of PlGF, making it a candidate as a biomarker for the neovascular form of AMD. Other factors, however, were not differentially regulated, suggesting that their systemic concentrations are not generally increased in hypoxia-related retinal diseases.

Purpose: To define the phenotype of C2orf71 associated retinopathy and to present novel mutations in this gene. Methods: A retrospective multicenter study of patients with retinopathy and identified C2orf71 mutations was performed. Ocular function (visual acuity, visual fields, electroretinogram [ERG] responses); retinal morphology (fundus, optical coherence tomography); and underlying mutations were analyzed. Results: Thirteen patients from 11 families, who were aged 7 to 63 years (mean: 32.1 years) at their first examination with presumed compound heterozygous (6/13 patients) or homozygous (7/13 patients) C2orf71 mutations were identified. Eight of the mutations were novel. Truncation mutations were responsible in all cases. Nyctalopia was observed in less than 50% of patients. Visual acuity ranged from 20/20 to light perception. Severe visual loss was associated with atrophic maculopathy. Full-field ERG responses showed severe progressive cone-rod or rod-cone dysfunction. Typical fundus changes were progressive symmetrical retinopathy with an early mild maculopathy and patchy circular midperipheral RPE atrophy. Normal retinal lamination was preserved despite early disruption of the ellipsoid zone and RPE irregularities. Outer retinal tubulations were associated with better-preserved visual acuity. Conclusions: On the basis of our multicenter analysis, C2orf71 might represent a more frequently mutated gene in autosomal recessive retinitis pigmentosa in some populations. The phenotype analysis over a wide age range showed a variable and progressive retinal degeneration with early onset maculopathy and a better visual potential before the age of 30 years., Investigative Ophthalmology & Visual Science, 58 (10), ISSN:0146-0404

Background There are different treatment options for ocular toxoplasmosis (OT). “Classic” therapy consists of pyrimethamine, sulfadiazine and folinic acid combined with systemic steroids and is still widely used. However, potentially severe side effects of this therapy have been reported. The aim of this retrospective study was to evaluate the incidence and types of adverse drug reactions in patients treated for OT. Clinical management of each adverse drug reaction was assessed. Patients and Methods In this retrospective analysis, we reviewed data of patients with OT, who were consecutively examined between December 2011 and December 2015 at the Department of Ophthalmology, University Hospital Zurich. Results In total, 49 patients had at least one episode of active OT. In 54 (83.0 %) of 65 treated episodes, the classic regimen was used. Of the 37 patients who received classic treatment, 9 (24.3 %) developed at least one adverse drug reaction which led to drug discontinuation, including elevated creatinine (5.4 %), elevated liver enzymes (5.4 %), vomiting (5.4 %), rash (5.4 %) and facial swelling (2.7 %). In 5 patients, treatment was switched to another drug, while in the other 4 patients, therapy was stopped. In these 9 patients, inflammation was well controlled 8 weeks after onset of therapy. No patient suffered from severe side effects, such as potentially life-threatening allergic reactions or pancytopenia. Conclusions In OT patients who were treated with classic therapy, adverse drug reactions are common. Therefore, clinical and laboratory monitoring is mandatory. Adverse drug reactions may require interdisciplinary management.

Purpose To investigate and characterize clinical and histopathologic ocular findings in patients with disseminated infection with Mycobacterium chimaera , a slow-growing nontuberculous mycobacterium (NTM), subsequent to cardiothoracic surgery. Design Observational case series. Participants Five white patients (10 eyes). Methods Analysis of clinical ocular findings, including visual acuity, slit-lamp biomicroscopy, spectral-domain optical coherence tomography (SD OCT), fundus autofluorescence (FAF), and fluorescein angiography/indocyanine green (ICG) angiography findings, of patients with a disseminated M. chimaera infection. Biomicroscopic and multimodal imaging findings were compared with the histopathology of 1 patient. Main Outcome Measures Clinical and histopathologic ocular findings of M. chimaera . Results The mean age of the 5 male patients, diagnosed with endocarditis or aortic graft infection, was 57.8 years. Clinical ocular findings included anterior and intermediate uveitis, optic disc swelling, and white-yellowish choroidal lesions. Multifocal choroidal lesions were observed bilaterally in all patients and were hyperfluorescent on fluorescein angiography, hypofluorescent on ICG angiography, and correlated with choroidal lesions on SD OCT. The extent of choroidal lesions varied from few in 2 patients to widespread miliary lesions in 3 patients leading to localized choroidal thickening with elevation of the overlying retinal layers. Spectral-domain optical coherence tomography through regressing lesions revealed altered outer retinal layers and choroidal hypertransmission. The ocular findings were correlated with the course of the systemic disease. Patients with few choroidal lesions had a favorable outcome, whereas all patients with widespread chorioretinitis died of systemic complications of M. chimaera infection despite long-term targeted antimicrobial therapy. Ocular tissue was obtained from 1 patient at autopsy. Necropsy of 2 eyes of 1 patient revealed prominent granulomatous lymphohistiocytic choroiditis with giant cells. Conclusions M. chimaera infection subsequent to cardiothoracic surgery is a novel entity that has been recently described. It involves multiple organ systems and can cause life-threatening disseminated disease. The ocular manifestations documented using multimodal imaging allow us to use the eye as a window to the systemic infection.

Aicardi syndrome is a rare X-linked cerebro-retinal disorder characterized by agenesis or dysgenesis of the corpus callosum, seizures, and chorioretinal lacunae; microphthalmia or optic nerve coloboma may also be observed. We report the case of an infant born with severe ocular malformations, including an anterior chamber cyst in one eye, which was surgically removed.

PurposeTo define a minimum set of outcome measures for tracking, comparing, and improving macular degeneration care.DesignRecommendations from a working group of international experts in macular degeneration outcomes registry development and patient advocates, facilitated by the International Consortium for Health Outcomes Measurement (ICHOM).MethodsModified Delphi technique, supported by structured teleconferences, followed by online surveys to drive consensus decisions. Potential outcomes were identified through literature review of outcomes collected in existing registries and reported in major clinical trials. Outcomes were refined by the working group and selected based on impact on patients, relationship to good clinical care, and feasibility of measurement in routine clinical practice.ResultsStandardized measurement of the following outcomes is recommended: visual functioning and quality of life (distance visual acuity, mobility and independence, emotional well-being, reading and accessing information); number of treatments; complications of treatment; and disease control. Proposed data collection sources include administrative data, clinical data during routine clinical visits, and patient-reported sources annually. Recording the following clinical characteristics is recommended to enable risk adjustment: age; sex; ethnicity; smoking status; baseline visual acuity in both eyes; type of macular degeneration; presence of geographic atrophy, subretinal fibrosis, or pigment epithelial detachment; previous macular degeneration treatment; ocular comorbidities.ConclusionsThe recommended minimum outcomes and pragmatic reporting standards should enable standardized, meaningful assessments and comparisons of macular degeneration treatment outcomes. Adoption could accelerate global improvements in standardized data gathering and reporting of patient-centered outcomes. This can facilitate informed decisions by patients and health care providers, plus allow long-term monitoring of aggregate data, ultimately improving understanding of disease progression and treatment responses.

Intravitreal triamcinolone acetonide (IVTA) is an effective treatment for recalcitrant diabetic macular oedema (DMO). It has been shown to improve vision with benefits persisting up to five years. The most common initial side effect of IVTA treatment is rise in intraocular pressure, occurring in approximately 50% of patients within the first 6 months of treatment. We evaluated whether there is a correlation between the development of intraocular pressure rise and improvement in vision. Analysis of individual data from 33 eyes of 33 participants treated with IVTA for DMO from a prospective, randomised, double-masked, placebo controlled trial. The degree of intraocular pressure (IOP) rise was correlated with improvement in best-corrected visual acuity (BCVA) at 1 and 6 months. The proportion of eyes gaining 5 or more logMAR letters was higher in eyes with greater IOP rise (p = 0.044). Better absolute improvement in BCVA at 6 months (p = 0.045) was also found in eyes with greater IOP rise. Regression analyses revealed a correlation between IOP rise of 10 or more mmHg and absolute BCVA improvement at 6 months (odds ratio 1.22, 95% confidence interval 1.01-1.48, p = 0.039), but not at 1 month. IOP rise and vision improvement appear to be correlated following IVTA for DMO, suggesting that the mechanisms that cause both may be linked. Clinical trials.gov NCT00167518 , September 5, 2005.

PURPOSE: To describe the development of a web-based high-quality data collection tool to track the outcomes of treatment of macular disease in routine practice. METHODS: Testing of a larger data collection tool established which fields a clinician would reliably fill out. The program, which was developed using freely available software, consists of modules interacting with a core system. The module for neovascular age-related macular degeneration is described here. RESULTS: Data for initial visits can be entered within 30 seconds, 15 seconds for follow-up visits. Fifteen centers from Australia, New Zealand, and Switzerland are currently contributing data. Finalized data from 2,052 eyes of 1,693 participants dating from January 2006 were analyzed. Median (25th and 75th percentiles) visual acuity at the index visit was 55 (41, 68) logarithm of the minimum angle of resolution letters with the following lesion types: minimally classic 17.2%, predominantly classic 24.6%, occult 52.0%, idiopathic polypoidal choroidal vasculopathy 1.2%, and retinal angiomatous proliferation 3.2%. CONCLUSION: This software tool will facilitate the collection of large amounts of data on the routine use of treatments of neovascular age-related macular degeneration. This will allow us to analyze important potentially modifiable variables, such as the effect of different treatment patterns on visual outcomes, and to evaluate new treatments as they are introduced into practice.

Background: The aim of this study was to evaluate the early response of aflibercept as first-line therapy in treatment-naive patients with newly diagnosed choroidal neovascularization (CNV) in age-related macular degeneration (AMD). Patients and Methods: An analysis of 35 eyes (35 patients, 28 female, 7 male) with treatment-naive active CNV was undertaken. Lesion activity was determined based on fluorescein angiography, clinical and optical coherence tomography (OCT) findings, including the presence of sub-, intraretinal fluid, retinal pigment epithelial (RPE) detachment and hemorrhage. Logarithm of the minimum angle of resolution (LogMAR) charts were used for testing best corrected or best available visual acuity (BCVA). Treatment response was evaluated based on changes in BCVA and lesion activity. Results: Classic or predominantly classic CNV was diagnosed in 7 eyes (20.0 %), occult or minimally classic in 21 eyes (60.0 %), retinal angiomatous proliferation in 5 eyes (14.3 %) and polypoidal choroidal vasculopathy in 2 eyes (5.7 %). Lesion activity was evaluated as unchanged in only one eye. In all other eyes, a definite treatment response was observed with complete resolution of fluid in 20 eyes after a single injection. Three eyes did not show improved sub-RPE fluid with smaller pigment epithelial detachments. A rip of the RPE was seen in 3 eyes. All patients maintained vision, 7 patients (7 eyes) gained > 15 letters from baseline to month 2 follow-up, of whom 4 reached this level of visual acuity after one injection. The visual acuity gains in this study were maintained through 6 months. Conclusion: There seems to be a rapid treatment response to aflibercept independent of the underlying CNV. Aflibercept may be beneficial even in eyes with large pigment epithelial detachments due to exudative AMD.

Roderick O'Day,1 Daniel Barthelmes,1 Meidong Zhu,1 Tien Yin Wong,2,3 Ian L McAllister,4 Jennifer J Arnold,5 Mark C Gillies11Clinical Ophthalmology and Eye Health, The University of Sydney, Sydney, NSW, Australia; 2Singapore Eye Research Institute, National University of Singapore, Singapore; 3Center for Eye Research Australia, The University of Melbourne, Melbourne, VIC, Australia; 4Lions Eye Institute, The University of Western Australia, Perth, WA, Australia; 5Marsden Eye Specialists, Sydney, NSW, AustraliaPurpose: To identify baseline characteristics that predict the number of treatments with intravitreal triamcinolone acetonide (IVTA) plus laser photocoagulation needed to treat diabetic macular edema over a 2-year period.Methods: Individual data from 42 eyes of 42 participants treated with IVTA plus laser photocoagulation for diabetic macular edema during a prospective, randomized, double-masked, placebo-controlled trial were used for this post hoc analysis. Baseline characteristics – age, gender, best-corrected visual acuity, glycosylated hemoglobin, phakic status, intraocular pressure, and central macular thickness (CMT) – were correlated with the number of IVTA plus laser treatments received during the 2 years of this study.Results: The median number of treatments received over the 2-year period was 2.5 (interquartile range 1.0–3.0), with 21 (50%) eyes needing three or more treatments. Eyes that received more IVTA plus laser treatments had a higher mean baseline CMT and eyes with a higher baseline CMT were more likely to receive three or more treatments (odds ratio 5.13, 95% confidence interval 1.75–15.04, P=0.003 per 100 µm increase in CMT). No significant relationship was found between other baseline characteristics and the number of IVTA plus laser treatments received.Conclusion: Higher baseline CMT was strongly linked with receiving more IVTA plus laser treatments. These patients may be at higher risk of developing dose-dependent steroid-related adverse events, cataract progression, and intraocular pressure rise.Keywords: diabetic macular edema, intravitreal triamcinolone, central macular thickness