Early Letters Research Articles

Two-Year Results of the Phase 3 Randomized Controlled Study of Abicipar in Neovascular Age-Related Macular Degeneration

To report the 2-year efficacy and safety of abicipar every 8 weeks and quarterly (after initial doses) compared with monthly ranibizumab in patients with treatment-naïve neovascular age-related macular degeneration (nAMD). Two multicenter, randomized, phase 3 clinical trials with identical protocols (CEDAR and SEQUOIA). Analyses used pooled trial data. The trials enrolled 1888 patients (1 eye/patient) with active choroidal neovascularization secondary to age-related macular degeneration and best-corrected visual acuity (BCVA) of 24 to 73 Early Treatment Diabetic Retinopathy Study letters. At enrollment, patients were assigned to study eye treatment with abicipar 2 mg every 8 weeks after initial doses at baseline and weeks 4 and 8 (abicipar Q8, n= 630), abicipar 2 mg every 12 weeks after initial doses at baseline and weeks 4 and 12 (abicipar Q12, n= 628), or ranibizumab 0.5 mg every 4 weeks (ranibizumab Q4, n= 630). Efficacy measures included stable vision (<15-letter loss in BCVA from baseline) and change from baseline in BCVA and central retinal thickness (CRT). Safety measures included adverse events (AEs). For patients who completed the study, efficacy of abicipar after initial doses was maintained through week 104. At week 104, the proportion of patients with stable vision was 93.0% (396/426), 89.8% (379/422), and 94.4% (470/498); mean change in BCVA from baseline was+7.8 letters,+6.1 letters, and+8.5 letters, and mean change in CRT from baseline was-147 μm,-146 μm, and-142 μm in the abicipar Q8 (14 injections), abicipar Q12 (10 injections), and ranibizumab Q4 (25 injections) groups, respectively. The overall incidence of intraocular inflammation (IOI) AEs was 15.4%, 15.3%, and 0.3% from baseline through week 52 and 16.2%, 17.6%, and 1.3% from baseline through week 104 in the abicipar Q8, abicipar Q12, and ranibizumab Q4 groups, respectively. Two-year results show efficacy of abicipar Q8 and Q12 in nAMD. First onset of IOI events withabicipar was much reduced in the second year and comparable with ranibizumab (0.8% and 2.3% vs. 1.0%). The extended duration of effect of abicipar allows for quarterly dosing and reduced treatment burden.

Looking at shadows of entanglement wedges

Abstract We present a new method of deriving shapes of entanglement wedges directly from conformal field theory (CFT) calculations. We point out that a reduced density matrix in holographic CFTs possesses a sharp wedge structure such that inside the wedge we can distinguish two local excitations, while outside we cannot. We can determine this wedge, which we call a CFT wedge, by computing a distinguishability measure. We find that CFT wedges defined by the fidelity or Bures distance as a distinguishability measure coincide perfectly with shadows of entanglement wedges in anti-de Sitter (AdS)/CFT. We confirm this agreement between CFT wedges and entanglement wedges for two-dimensional holographic CFTs where the subsystem is chosen to be an interval or double intervals, as well as higher-dimensional CFTs with a round ball subsystem. On the other hand, if we consider a free scalar CFT, we find that there are no sharp CFT wedges. This shows that sharp entanglement wedges emerge only for holographic CFTs owing to the large-$N$ factorization. We also generalize our analysis to a time-dependent example and to a holographic boundary conformal field theory (AdS/BCFT). Finally, we study other distinguishability measures to define CFT wedges. We observe that some of the measures lead to CFT wedges which slightly deviate from the entanglement wedges in AdS/CFT, and we give a heuristic explanation for this. This paper is an extended version of our earlier letter (arXiv:1908.09939 [hep-th]) and includes various new observations and examples.

HSR: A History of New Beginnings and a Tribute to Founding Editor Nándor F. Dreisziger

<i>HSR</i>: A History of New Beginnings and a Tribute to Founding Editor Nándor F. Dreisziger

Age-related differences in presentation and outcomes of anti-VEGF treatment of retinal vein occlusion

ObjectiveTo assess age-related differences at baseline and treatment outcomes in patients with retinal vein occlusion (RVO) and macular edema treated with anti-vascular endothelial growth factor (VEGF) therapy DesignSingle-centre retrospective chart review. Participants295 treatment-naïve RVO patients. Methods295 RVO patients included were separated into age quartiles: group A (22–61 years), group B (62–70 years), group C (71–79 years), and group D (80–95 years). Outcomes including central subfield thickness (CST), cubic volume, cubic average thickness, and visual acuity (VA) were collected at baseline and at 6 and 12 months after treatment. The primary outcome of the study was the CST at 12 months after anti-VEGF therapy. ResultsMean baseline CST for groups A, B, C, and D was 406.3 ± 161.2 μm, 463.4 ± 165.5 μm, 470.6 ± 187 μm, and 427.3 ± 187.2 μm, respectively. No significant differences in CST were observed between groups at baseline, 6 months, or 12 months (p ≥ 0.08). Mean baseline VA for groups A, B, C, and D was 55.8 ± 19.5, 54.4 ± 19.8, 54.7 ± 19, and 51.4 ± 20.4 Early Treatment Diabetic Retinopathy letters, respectively. VA did not differ significantly between age groups at baseline, 6 months, or 12 months (p ≥ 0.06). ConclusionsThe presentation of RVO and the visual outcomes of anti-VEGF therapy do not vary based on age.

Pre-literacy heterogeneity in Dutch-speaking kindergartners: latent profile analysis.

Research demonstrated that a dyslexia diagnosis is mainly given after the most effective time for intervention has passed, referred to as the dyslexia paradox. Although some pre-reading cognitive measures have been found to be strong predictors of early literacy acquisition, i.e., phonological awareness (PA), letter knowledge (LK), and rapid automatized naming (RAN), more insight in the variability of pre-reading profiles might be of great importance for early identification of children who have an elevated risk for developing dyslexia and to provide tailor-made interventions. To address this issue, this study used a latent profile analysis (LPA) to disentangle different pre-reading profiles in a sample of 1091 Dutch-speaking kindergartners. Four profiles emerged: high performers (16.50%), average performers (40.24%), below-average performers with average IQ (25.57%), and below-average performers with below-average IQ (17.69%). These results suggested two at-risk profiles diverging in IQ, which are presumably more likely to develop dyslexia later on. Although below-average profiles differed significantly in rapid naming and IQ, no clear evidence for the double-deficit theory was found in Dutch-speaking kindergartners. Educational level and reading history of the parents appeared to be predictive for children's classification membership. Our results point towards the heterogeneity that is already present in kindergartners and the possibility to identify at-risk profiles prior to reading instruction, which may be the foundation for earlier targeted interventions. However, more extended research is needed to determine the stability of these profiles across time and across different languages.

Lamb, Coleridge, and the Poetics of Publication

This essay explores the poetics of Lamb's early letters to Coleridge. I argue for a sharp awareness, on Lamb's part, of the potentially negative effect publication can have on literary writing. Lamb resists this at the level of epistolary form, by entwining his sonnets with the letters into which he writes them. Where Lamb's poems, taken in themselves, remain modest performances, the letter-poem hybrid texts in which they participate are of significant critical interest. Among other things they establish a critique of Coleridge and his paying court to the literary marketplace. These insights, I go on to suggest, can also help us to understand both writers’ more mature work, notably the complex lyric-epistolary compound that is Coleridge's ‘This Lime-Tree Bower My Prison’.

The impact of structural optical coherence tomography changes on visual function in retinal vein occlusion.

PurposeWe aimed to determine the correlation between optical coherence tomography (OCT)‐ and demographic features and baseline best corrected visual acuity (BCVA) in treatment‐naïve patients with retinal vein occlusion (RVO).MethodsThis was a cross‐sectional posthoc analysis of OCT images that included RVO patients from two prospective, open‐label, multicentre studies. The morphological grading was done manually, in the standardized setting of a reading centre. Main outcome measure was the estimated difference in Early Treatment Diabetic Retinopathy Study letters associated with each individual biomarker.ResultsIncluded were 381/301 treatment‐naïve patients with BRVO/CRVO. For BRVO, statistically significant correlations with BCVA were seen for a 100 µm increase in central subfield thickness (CST; −3.1 letters), intraretinal cysts at centre point (CP; +4.1), subretinal fluid (SRF) at CP (+3.0) and hyperreflective foci (HRF) at the central B‐scan (−2.2). In CRVO, a 100 µm increase in CST was associated with a loss of −3.4 letters. In the total cohort, 100 µm increase in CST, SRF at CP and HRF at the central B‐scan correlated with a difference of −3.2,+3.2 and −2.0 letters. A 10‐year increase in age and female gender yielded a −2.0 and −2.5 letter decrease in the total cohort. Adjusted multiple R 2 for the respective group was 18.3%/26.3%/23.5%.ConclusionsOf all parameters studied, only CST and age were consistently associated with worse BCVA in treatment‐naïve RVO patients. Morphology on OCT explained only a modest part of functional loss in this patient cohort.

Spelling ability influences early letter encoding during reading: Evidence from return-sweep eye movements.

In recent years, there has been an increase in research concerning individual differences in readers’ eye movements. However, this body of work is almost exclusively concerned with the reading of single-line texts. While spelling and reading ability have been reported to influence saccade targeting and fixation times during intra-line reading, where upcoming words are available for parafoveal processing, it is unclear how these variables affect fixations adjacent to return-sweeps. We, therefore, examined the influence of spelling and reading ability on return-sweep and corrective saccade parameters for 120 participants engaged in multiline text reading. Less-skilled readers and spellers tended to launch their return-sweeps closer to the end of the line, prefer a viewing location closer to the start of the next, and made more return-sweep undershoot errors. We additionally report several skill-related differences in readers’ fixation durations across multiline texts. Reading ability influenced all fixations except those resulting from return-sweep error. In contrast, spelling ability influenced only those fixations following accurate return-sweeps—where parafoveal processing was not possible prior to fixation. This stands in contrasts to an established body of work where fixation durations are related to reading but not spelling ability. These results indicate that lexical quality shapes the rate at which readers access meaning from the text by enhancing early letter encoding, and influences saccade targeting even in the absence of parafoveal target information.

Associations of Variation in Retinal Thickness With Visual Acuity and Anatomic Outcomes in Eyes With Neovascular Age-Related Macular Degeneration Lesions Treated With Anti–Vascular Endothelial Growth Factor Agents

When initiating anti-vascular endothelial growth factor (VEGF) treatment for patients with neovascular age-related macular degeneration (nAMD), knowledge of prognostic factors is important for advising patients and guiding treatment. We hypothesized that eyes with greater fluctuation in retinal thickness over time have worse outcomes than eyes with less variation. To investigate whether visual and anatomic outcomes in eyes with nAMD initiating anti-VEGF treatment are associated with fluctuations in retinal thickness. In this study using data from the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) and the Inhibition of VEGF in Age-Related Choroidal Neovascularization (IVAN) randomized clinical trial, people with previously untreated nAMD were included. Data were collected from February 2008 to November 2012, and data were analyzed from April 2017 to April 2020. Foveal center point thicknesses (FCPTs) were extracted from 1165 study eyes from CATT and 566 study eyes from the IVAN trial, excluding those with 3 measurements or less. For each eye, the SD of FCPT was calculated. Eyes were grouped by FCPT SD quartile. Associations of FCPT SD quartile with outcomes were quantified at month 24 or the last available visit by linear or logistic regression, adjusting for baseline best-corrected visual acuity (BCVA) and randomized allocations to drug and treatment regimen, for BCVA, development of fibrosis, and development of macular atrophy. Of the 1731 included patients, 1058 (61.1%) were female, and the mean (SD) age was 78.6 (7.4) years. The median (interquartile range) FCPT SD was 40.2 (27.1-61.2) in the IVAN cohort and 59.0 (38.3-89.4) in the CATT cohort. After adjustment for baseline BCVA and trial allocations, BCVA worsened significantly across the quartiles of FCPT SD; the difference between the first and fourth quartiles was -6.27 Early Treatment Diabetic Retinopathy Study letters (95% CI, -8.45 to -4.09). The risk of developing fibrosis and macular atrophy also increased across FCPT SD quartiles. Odds ratios ranged from 1.40 (95% CI, 1.03 to 1.91) for quartile 2 to 1.95 (95% CI, 1.42 to 2.68) for quartile 4 for fibrosis and from 1.32 (95% CI, 0.90 to 1.92) for quartile 2 to 2.10 (95% CI, 1.45 to 3.05) for quartile 4 for macular atrophy. Greater variation in retinal thickness in eyes with nAMD during treatment with anti-VEGF was associated with worse BCVA and development of fibrosis and macular atrophy in these post hoc analyses, despite protocol-directed treatment frequency. Practitioners may want to consider variation in retinal thickness when advising patients about their prognosis.

DEEP PHENOTYPING AND FURTHER INSIGHTS INTO ITM2B-RELATED RETINAL DYSTROPHY.

To reappraise the presentation and the course of ITM2B-related retinal dystrophy and give further insights into ITM2B expression in the retina. The clinical data of nine subjects with ITM2B-related retinal dystrophy were retrospectively reviewed. The genetic mutation was assessed for its influence on splicing in cultured fibroblasts. The cellular expression of ITM2B within the inner retina was investigated in wild-type mice through mRNA in situ hybridization. All patients complained of decreased vision and mild photophobia around their twenties-thirties. The peculiar feature was the hyperreflective material on optical coherence tomography within the inner retina and the central outer nuclear layer with thinning of the retinal nerve fiber layer. Although retinal imaging revealed very mild or no changes over the years, the visual acuity slowly decreased with about one Early Treatment Diabetic Retinopathy Study letter per year. Finally, full-field electroretinography showed a mildly progressive inner retinal and cone dysfunction. ITM2B mRNA is expressed in all cellular types of the inner retina. Disease mechanism most likely involves mutant protein misfolding and/or modified protein interaction rather than misplicing. ITM2B-related retinal dystrophy is a peculiar, rare, slowly progressive retinal degeneration. Functional examinations (full-field electroretinography and visual acuity) seem more accurate in monitoring the progression in these patients because imaging tends to be stable over the years.

Importance of continuous treatment with intravitreal aflibercept injections in patients with neovascular age-related macular degeneration\u201412-month post hoc analysis of the PERSEUS real-world evidence study

PurposeTo investigate the influence of treatment regularity with intravitreal aflibercept injections (IVT-AFL injections) on visual acuity (VA) outcomes in patients with neovascular age-related macular degeneration (nAMD) enrolled in the PERSEUS trial who received at least 7 IVT-AFL injections during the first year.MethodsThis was a post hoc analysis of the PERSEUS trial, a prospective, non-interventional, multicenter cohort study, and included 370 patients with nAMD who had received ≥ 7 IVT-AFL injections during year 1. In addition to the prespecified subgroups of treatment-naïve and previously treated patients, results were compared between patients with regular (n = 209) and irregular (n = 161) treatment. Regular treatment was defined as initial dosing with monthly IVT-AFL injections for 3 months, then bimonthly IVT-AFL injections until month 12. Irregular treatment was defined as any deviation from regular treatment (provided ≥ 7 injections were received). The outcome of primary interest was the mean change in VA from baseline after 12 months. Further outcomes of interest included VA gain or loss, proportion of patients achieving reading vision, and percentage of patients with fluid.ResultsAt month 12, the mean (± standard deviation, SD) VA improvement from baseline was 6.1 ± 15.6 Early Treatment Diabetic Retinopathy Study letters in the regular cohort and 2.5 ± 16.7 letters in the irregular cohort with ≥ 7 IVT-AFL injections (P = 0.0514). Best results were obtained in the treatment-naïve regular sub-cohort with a mean ± SD VA improvement of 8.0 ± 17.7 letters, whereas treatment-naïve patients with irregular treatment experienced a considerably lower VA gain (2.8 ± 20.0 letters). Irregular treatment consistently correlated with inferior results in treatment-naïve patients. At month 12, the proportion of treatment-naïve patients who had experienced a worsening of ≥ 5 letters was 29.6% in the irregular sub-cohort versus 13.6% in the regular sub-cohort (P = 0.0049). However, among the treatment-naïve patients, the mean number of injections was significantly higher in the irregular than in the regular sub-cohort (8.0 ± 1.2 vs. 7.4 ± 0.6; P = 0.0001). Furthermore, compared with the treatment-naïve, regular sub-cohort, patients in the irregular sub-cohort had more visits (19.1 ± 8.6 vs. 16.1 ± 5.7), VA tests (14.2 ± 6.9 vs. 12.0 ± 4.6), and optical coherence tomography examinations (5.1 ± 3.7 vs. 3.4.0 ± 3.0).ConclusionsAlthough irregularly treated patients received more injections and more monitoring visits during the first year of IVT-AFL treatment, they experienced worse VA outcomes than regularly treated patients.

Efficacy of Every Four Monthly and Quarterly Dosing of Faricimab vs Ranibizumab in Neovascular Age-Related Macular Degeneration

Faricimab neutralizes angiopoietin-2 and vascular endothelial growth factor A via both simultaneous and independent binding. To evaluate extended dosing with faricimab, the first bispecific antibody designed for intraocular use, in patients with neovascular age-related macular degeneration. This phase 2 randomized clinical trial was a 52-week multicenter, active comparator-controlled, parallel-group study. Study participants were enrolled in 25 sites in the US from January and March 2017 with treatment-naive choroidal neovascularization secondary to neovascular age-related macular degeneration and best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study letter score of 73 (approximate Snellen equivalent, 20/40) to 24 (approximate Snellen equivalent, 20/320). Analysis began January 2017 and ended March 2018. Participants were randomized 1:2:2 to receive intravitreal ranibizumab, 0.5 mg, every 4 weeks or faricimab, 6.0 mg, every 12 or 16 weeks. Participants in the faricimab arms initially received 4 monthly injections of faricimab. No rescue injections were allowed. Participants randomized to dosing every 16 weeks were assessed for disease activity at week 24 using prespecified criteria. Those with no active disease continued dosing every 16 weeks through trial end; participants with disease activity continued received dosing every 12 weeks. Mean change in BCVA from baseline at week 40. Of 76 participants enrolled (mean [SD] age, 78.5 [8.5] years; age range, 56-94 years; 41 women [58%]; 69 white [97%]), 16 (21.0%) were randomized to ranibizumab every 4 weeks, 29 (38.2%) to faricimab every 12 weeks, and 31 (40.8%) to faricimab every 16 weeks. At week 24, 12 weeks after their last initiation injection, 65% (36 of 55) of all faricimab-treated participants had no disease activity. At week 40, adjusted mean BCVA gains from baseline (Early Treatment Diabetic Retinopathy Study letters) were +11.4 (80% CI, 7.8-15.0), +9.3 (80% CI, 6.4-12.3), and +12.5 (80% CI, 9.9-15.1) for the ranibizumab every 4 weeks, faricimab every 12 weeks, and faricimab every 16 weeks arms, respectively. Participants received a mean (SD) total of 12.9 (0.25), 6.7 (0.91), and 6.2 (0.93) injections, for the ranibizumab every 4 weeks, faricimab every 12 weeks, and faricimab every 16 weeks arms, respectively, through week 52. The secondary BCVA and anatomical imaging end points supported the primary end point and were comparable with ranibizumab every 4 weeks. No new or unexpected safety signals were identified. At week 52, faricimab dosing every 16 weeks and every 12 weeks resulted in maintenance of initial vision and anatomic improvements comparable with monthly ranibizumab. These results suggest a role for simultaneous neutralization of angiopoietin-2 and vascular endothelial growth factor A in providing sustained efficacy through extended durability, warranting further investigation. ClinicalTrials.gov Identifier: NCT03038880.

Outcomes by Baseline Choroidal Neovascularization Features in Age-Related Macular Degeneration: A Post Hoc Analysis of the VIEW Studies

To assess the influence of baseline choroidal neovascularization (CNV) features on visual change and fluid resolution after anti-vascular endothelial growth factor (VEGF) treatment of eyes with neovascular age-related macular degeneration (nAMD). Post hoc analysis of 52-week data from the phase 3 Vascular Endothelial Growth Factor VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration (AMD) Studies (VIEW) 1 and 2 clinical trials. One thousand eight hundred four patients with nAMD. Integrated data from VIEW 1 and 2 of 1804 eyes receiving intravitreal aflibercept injections (IAIs) 2 mg every 4 weeks, IAIs 2 mg every 8 weeks after 3 initial monthly doses, and ranibizumab every 4 weeks with documented baseline CNV type, total area, and leakage area were analyzed. Time to an event and cumulative incidence were evaluated by Kaplan-Meier analysis, and relative risks were estimated using proportional hazards analysis. Cumulative incidence of time to first sustained vision gain of 15 or more Early Treatment Diabetic Retinopathy Study letters, vision loss of more than 5 Early Treatment Diabetic Retinopathy Study letters from baseline, as well as first sustained absence of retinal fluid and intraretinal fluid as evaluated by OCT with respect to CNV type, total CNV, and leakage area. Eyes with predominantly classic CNV (mean best-corrected visual acuity [BCVA], 48.2 letters at baseline) showed a higher incidence rate of first sustained gain of 15 letters or more than eyes with occult CNV (mean BCVA, 57.9 letters at baseline; P < 0.01). Eyes with occult CNV at baseline showed higher incidence rates of first sustained absence of retinal fluid and of intraretinal fluid than eyes with predominantly classic CNV (both P < 0.01). With increasing baseline CNV total area and leakage area, the incidence rate of first sustained gain of 15 letters or more decreased. This post hoc analysis provided additional evidence for the role of baseline CNV features (CNV type, total area, and leakage area) in influencing visual and anatomic outcomes in eyes with nAMD after anti-VEGF treatment.

An open-source data set of anti-VEGF therapy in diabetic macular oedema patients over 4 years and their visual acuity outcomes.

The objective of this paper is to evaluate visual acuity (VA) outcomes of intravitreal anti-vascular endothelial growth factor (VEGF) in diabetic macular oedema (DMO). In this retrospective cohort study, electronic medical records for all patients undergoing intravitreal injections in a tertiary referral centre between March 2013 and October 2018 were analysed. Treatment response in terms of VA outcomes was reported for all eyes over a 4-year observation period. Our cohort includes 2614 DMO eyes of 1964 patients over 48 months. Cox proportional-hazards modelling identified injection number (hazard ratio (HR) = 1.18), male gender (HR = 1.13) and baseline VA (HR = 1.09) as independent predictors to reach a favourable visual outcome of more than 70 Early Treatment Diabetic Retinopathy Study letters. Half of our cohort reached 70 letters 1.9 months after starting anti-VEGF therapy. Of those that reached 70 letters, 50% fell below 70 lettersby 14.7 months. To date, this is the largest single centre cohort study and over the longest observation period reporting on real-life outcomes of anti-VEGF in DMO. We have made an anonymised version of our data set available on an open-source data repository as a resource for clinical researchers globally.

Motor-Enriched Encoding Can Improve Children's Early Letter Recognition.

It is not known how effective specific types of motor-enriched activities are at improving academic learning and early reading skills in children. The aim of this study was to investigate whether fine or gross motor enrichment during a single session of recognizing letters “b”/“d” can improve within-session performance or delayed retention the following day in comparison to letter recognition practice without movement. Furthermore, the aim was to investigate children’s motivation to perform the specific tasks. We used a randomized controlled intervention study-design to investigate the effect of 10-min motor-enriched “b”/“d” letter training on children’s ability to recognize the letters “b” and “d” (n = 127, mean age = 7.61 ± SD = 0.44 years) acutely, and in a delayed retention test. Three groups were included: a fine motor-enriched group (FME), a gross motor-enriched group (GME), that received 10 min of “b” and “d” training with enriched gestures (fine or gross motor movements, respectively), and a control group (CON), which received non motor-enriched “b”/“d” training. The children’s ability to recognize “b” and “d” were tested before (T0), immediately after (T1), and one day after the intervention (T2) using a “b”/“d” Recognition Test. Based on a generalized linear mixed model a significant group-time interaction was found for accuracy in the “b”/“d” Recognition Test. Specifically, FME improved their ability to recognize “b”/“d” at post intervention (T0→T1, p = 0.008) and one-day retention test (T0→T2, p < 0.001) more than CON. There was no significant difference in change between GME and CON. For reaction time there were no significant global interaction effects observed. However, planned post hoc comparisons revealed a significant difference between GME and CON immediately after the intervention (T0→T1, p = 0.03). The children’s motivation-score was higher for FME and GME compared to CON (FME-CON: p = 0.01; GME-CON: p = 0.01). The study demonstrated that fine motor-enriched training improved children’s letter recognition more than non motor activities. Both types of motor training were accompanied by higher intrinsic motivation for the children compared to the non motor training group. The study suggests a new method for motor-enriched letter learning and future research should investigate the underlying mechanisms.

COMPARISON OF INTRAVITREAL DEXAMETHASONE IMPLANT AND AFLIBERCEPT IN PATIENTS WITH TREATMENT-NAIVE DIABETIC MACULAR EDEMA WITH SEROUS RETINAL DETACHMENT.

To compare the efficacy and safety of intravitreal dexamethasone (DEX) implant versus aflibercept in patients with treatment-naive diabetic macular edema with inflammatory biomarkers. Ninety-eight eyes of 62 treatment-naive patients with diabetic macular edema with serous retinal detachment and hyperreflective foci were enrolled. Each patient was randomized to receive either aflibercept or DEX implant treatment. The treatment protocol included 3 monthly injections of 2 mg of aflibercept as a loading phase in the anti-vascular endothelial growth factor group and 0.7 mg of DEX implant in the DEX group and then pro re nata treatment. Primary outcome measures were mean changes in visual acuity and central retinal thickness at the end of the 12-month follow-up. Forty-eight eyes of 29 patients were received DEX implant, and 50 eyes of 33 patients received the aflibercept injection. Mean central retinal thickness decreased from 615.2 µm at baseline to 297.7 µm at 12 months in the DEX group (P < 0.001) and from 576.5 µm to 367.4 µm in the aflibercept group (P < 0.001). Except for the first month, mean central retinal thickness reduction was significantly higher in the DEX group (P < 0.05, Mann-Whitney U Test). Visual acuity improved significantly at the end of the follow-ups (46.3-52.7 Early Treatment Diabetic Retinopathy Study letters in the DEX group and 47.5-56.8 Early Treatment Diabetic Retinopathy Study letters in the aflibercept group at 12 months, P < 0.001, paired-sample t-test). Adjusting by baseline values, the increase in mean visual acuity during the 12-month follow-ups favored the aflibercept group (P < 0.01), 25% of the DEX-treated eyes and 42% of the aflibercept treated eyes experienced 10 or more Early Treatment Diabetic Retinopathy Study letters visual gain (P: 0.058). The DEX group received significantly fewer (2.6 vs. 7.2) injections (P: 0.001). It was observed that the both of DEX implant and aflibercept were effective and safe in treatment-naive diabetic macular edema patients with inflammatory phenotype. Anatomical results were found to be better in the DEX group, and functional results were found to be better in the aflibercept group. In pseudophakic eyes, the functional superiority of aflibercept ceased to exist, and the low number of injections in the DEX implant group was seen as an advantage.

One-year real-life results on effect of intravitreal aflibercept in patients with diabetic macular oedema switched from ranibizumab.

To assess visual and optical coherence tomography-derived anatomical outcomes of treatment with intravitreal aflibercept (Eylea®) for diabetic macular oedema in patients switched from intravitreal ranibizumab (Lucentis®). Retrospective, cohort study. Ninety eyes (of 67 patients) receiving intravitreal anti-vascular endothelial growth factor therapy were included. This is a retrospective, real-life, cohort study. Each patient had visual acuity measurements and optical coherence tomography scans performed at baseline and 12 months after the first injection of aflibercept was given. We measured visual acuities in Early Treatment Diabetic Retinopathy Study letters, central foveal thickness and macular volume at baseline and at 12 months after the first aflibercept injection was given. Ninety switched eyes were included in this study. The mean (standard deviation) visual acuity was 63 (15.78) Early Treatment Diabetic Retinopathy Study letters. At baseline, the mean (standard deviation) central foveal thickness was 417.7 (158.4) μm and the mean macular volume was 9.96 (2.44) mm3. Mean change in visual acuity was +4 Early Treatment Diabetic Retinopathy Study letters (p = 0.0053). The mean change in macular volume was -1.53 mm3 in SW group (p = 0.21), while the change in central foveal thickness was -136.8 μm (p = 0.69). There was a significant improvement in visual acuity and in anatomical outcomes in the switched group at 12 months after commencing treatment with aflibercept for diabetic macular oedema.

Retour aux années 1960 : le rôle de 1968 dans la vie et l’œuvre de Paul Auster

This essay explores the impact of 1968 on Paul Auster’s life and work. Its main analytical focus is on Auster’s critique of the anti-authoritative ethos of his generation in the early fictional autobiography Moon Palace (1989), but it draws comparisons to his later work as well, including 4 3 2 1 (2017) and the autobiographies Hand to Mouth (1997) and Report from the Interior (2013). Auster’s participation in the 1968 student uprising and his subsequent witnessing of the radicalization of the student movement have resulted in an authorial stance on ’68 that is marked by ambivalence and hindsight bias. Auster’s early letters show that Auster subscribed to a Marxist worldview before ’68, that his experiences in April changed him, and that he has since assumed center-left position in his prose work. Originally founded on Merleau-Ponty’s post-Cartesian philosophy, this position enables Auster to remain sympathetic to the egalitarian and antiwar causes of the Left, but critical of the general rejection of authorities that so characterized the late 1960s. The essay concludes that Moon Palace can be read as an appeal for the depolarization of the American political past.

Intravitreal aflibercept for diabetic macular oedema in real-world: 36-month visual acuity and anatomical outcomes.

To assess structural and functional outcomes of treatment with intravitreal aflibercept (®Eylea) for diabetic macular oedema in treatment-naïve patients. Sixty-four eyes receiving intravitreal anti-vascular endothelial growth factor therapy were included in the data analysis of this retrospective, real-life study which follow-up was 3 years. Each patient had corrected visual acuity in Early Treatment Diabetic Retinopathy Study letters and optical coherence tomography central foveal thickness and macular volume performed at baseline, 12, 24 and 36 months. Patients were initiated on a loading phase of five 1-monthly intravitreal aflibercept injections, followed by injections if needed as per clinicians' discretion. The mean number of aflibercept injections received over 3 years was 12.59. At baseline, the mean visual acuity (standard deviation) (Snellen) was 61.45 (16.30) (20/63) Early Treatment Diabetic Retinopathy Study letters, the mean central foveal thickness (standard deviation) was 422 (138) µm, while the mean macular volume (standard deviation) was 9.51 (2.01) mm3. At 36 months, the mean visual acuity (standard deviation) (Snellen) was 68.34 (13.66) (20/50) Early Treatment Diabetic Retinopathy Study letters (p = .0003). Mean central foveal thickness (standard deviation) was 303 (106) µm (p < .0001) and mean macular volume (standard deviation) was 8.35 (1.62) mm3 (p = .0022) at 36 months. Sixteen (25%) eyes gained ≥15 ETDRS letters at month 36, and 33 (52%) eyes had a decrease in central foveal thickness of ≥ 100 µm at the same time. There was a significant improvement in visual acuity and in anatomical outcomes in aflibercept-treated eyes at 36 months after commencing treatment for diabetic macular oedema in real-life settings. The good vision and anatomical outcomes were maintained over second and third year of treatment with mean 2.93 and 2.57 intravitreal injections, respectively.

PERFLUOROCARBON LIQUID-ASSISTED INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE VERSUS INTERNAL LIMITING MEMBRANE PEELING FOR HIGHLY MYOPIC MACULAR HOLE RETINAL DETACHMENT.

To compare the efficacy of a modified perfluorocarbon liquid-assisted inverted internal limiting membrane (ILM) flap technique with the standard ILM peeling for the treatment of macular hole retinal detachment in highly myopic eyes. This was a retrospective, consecutive, nonrandomized comparative study. Forty-two macular hole retinal detachment eyes of 42 patients were included into either a perfluorocarbon liquid-assisted inverted ILM flap technique group (n = 22, inverted group) or standard ILM removal group (n = 20, peeling group). Outcomes measured were macular hole closure, retinal reattachment, and best-corrected visual acuity at least 6 months after surgery. Macular hole closure was achieved in 20 eyes (90.9%) in the inverted group and in eight eyes (40%) in the peeling group (P < 0.01). Reattachment rates were 100% in the inverted group and 95% in the peeling group (P = 0.476). The mean best-corrected visual acuity improvement from baseline was 27.4 ± 19.9 Early Treatment Diabetic Retinopathy Study letters in the inverted group while the best-corrected visual acuity improvement was 13.6 ± 22.5 Early Treatment Diabetic Retinopathy Study letters in the peeling group (P = 0.044). The perfluorocarbon liquid-assisted inverted ILM flap technique was effective in sealing the macular hole, reattaching retina, and improving visual function postoperatively in highly myopic macular hole retinal detachment.