Method to Quickly Map Multifocal Pupillary Response Fields (mPRF) Using Frequency Tagging.

We present a method for mapping multifocal Pupillary Response Fields in a short amount of time using a visual stimulus covering 40° of the visual angle divided into nine contiguous sectors simultaneously modulated in luminance at specific, incommensurate, temporal frequencies. We test this multifocal Pupillary Frequency Tagging (mPFT) approach with young healthy participants (N = 36) and show that the spectral power of the sustained pupillary response elicited by 45 s of fixation of this multipartite stimulus reflects the relative contribution of each sector/frequency to the overall pupillary response. We further analyze the phase lag for each temporal frequency as well as several global features related to pupil state. Test/retest performed on a subset of participants indicates good repeatability. We also investigate the existence of structural (RNFL)/functional (mPFT) relationships. We then summarize the results of clinical studies conducted with mPFT on patients with neuropathies and retinopathies and show that the features derived from pupillary signal analyses, the distribution of spectral power in particular, are homologous to disease characteristics and allow for sorting patients from healthy participants with excellent sensitivity and specificity. This method thus appears as a convenient, objective, and fast tool for assessing the integrity of retino-pupillary circuits as well as idiosyncrasies and permits to objectively assess and follow-up retinopathies or neuropathies in a short amount of time.

PTVR - A software in Python to make virtual reality experiments easier to build and more reproducible.

Researchers increasingly use virtual reality (VR) to perform behavioral experiments, especially in vision science. These experiments are usually programmed directly in so-called game engines that are extremely powerful. However, this process is tricky and time-consuming as it requires solid knowledge of game engines. Consequently, the anticipated prohibitive effort discourages many researchers who want to engage in VR. This paper introduces the Perception Toolbox for Virtual Reality (PTVR) library, allowing visual perception studies in VR to be created using high-level Python script programming. A crucial consequence of using a script is that an experiment can be described by a single, easy-to-read piece of code, thus improving VR studies' transparency, reproducibility, and reusability. We built our library upon a seminal open-source library released in 2018 that we have considerably developed since then. This paper aims to provide a comprehensive overview of the PTVR software for the first time. We introduce the main objects and features of PTVR and some general concepts related to the three-dimensional (3D) world. This new library should dramatically reduce the difficulty of programming experiments in VR and elicit a whole new set of visual perception studies with high ecological validity.

Untargeted Multiomics Approach Coupling Lipidomics and Metabolomics Profiling Reveals New Insights in Diabetic Retinopathy.

Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus (DM) which is the main cause of vision loss in the working-age population. Currently known risk factors such as age, disease duration, and hemoglobin A1c lack sufficient efficiency to distinguish patients with early stages of DR. A total of 194 plasma samples were collected from patients with type 2 DM and DR (moderate to proliferative (PDR) or control (no or mild DR) matched for age, gender, diabetes duration, HbA1c, and hypertension. Untargeted lipidomic and metabolomic approaches were performed. Partial-least square methods were used to analyze the datasets. Levels of 69 metabolites and 85 lipid species were found to be significantly different in the plasma of DR patients versus controls. Metabolite set enrichment analysis indicated that pathways such as metabolism of branched-chain amino acids (methylglutaryl carnitine p = 0.004), the kynurenine pathway (tryptophan p < 0.001), and microbiota metabolism (p-Cresol sulfate p = 0.004) were among the most enriched deregulated pathways in the DR group. Moreover, Glucose-6-phosphate (p = 0.001) and N-methyl-glutamate (p < 0.001) were upregulated in DR. Subgroup analyses identified a specific signature associated with PDR, macular oedema, and DR associated with chronic kidney disease. Phosphatidylcholines (PCs) were dysregulated, with an increase of alkyl-PCs (PC O-42:5 p < 0.001) in DR, while non-ether PCs (PC 14:0-16:1, p < 0.001; PC 18:2-14:0, p < 0.001) were decreased in the DR group. Through an unbiased multiomics approach, we identified metabolites and lipid species that interestingly discriminate patients with or without DR. These features could be a research basis to identify new potential plasma biomarkers to promote 3P medicine.

A New Vessel-Based Method to Estimate Automatically the Position of the Nonfunctional Fovea on Altered Retinography From Maculopathies.

Purpose: The purpose of this study was to validate a new automated method to locate the fovea on normal and pathological fundus images. Compared to the normative anatomic measures (NAMs), our vessel-based fovea localization (VBFL) approach relies on the retina's vessel structure to make predictions. Methods: The spatial relationship between the fovea location and vessel characteristics is learnt from healthy fundus images and then used to predict fovea location in new images. We evaluate the VBFL method on three categories of fundus images: healthy images acquired with different head orientations and fixation locations, healthy images with simulated macular lesions, and pathological images from age-related macular degeneration (AMD). Results: For healthy images taken with the head tilted to the side, the NAM estimation error is significantly multiplied by 4, whereas VBFL yields no significant increase, representing a 73% reduction in prediction error. With simulated lesions, VBFL performance decreases significantly as lesion size increases and remains better than NAM until lesion size reaches 200 degrees2. For pathological images, average prediction error was 2.8 degrees, with 64% of the images yielding an error of 2.5 degrees or less. VBFL was not robust for images showing darker regions and/or incomplete representation of the optic disk. Conclusions: The vascular structure provides enough information to precisely locate the fovea in fundus images in a way that is robust to head tilt, eccentric fixation location, missing vessels, and actual macular lesions. Translational Relevance: The VBFL method should allow researchers and clinicians to assess automatically the eccentricity of a newly developed area of fixation in fundus images with macular lesions.

Relevance of Visual Acuity Measurement for Therapeutic Decisions in Diabetic Macular Edema.

This study aimed to determine the validity of basing retreatment decisions on anatomical criteria alone (captured using optical coherence tomography (OCT)-OCT-guided strategy) rather than the gold standard (combined visual acuity (VA) and OCT) in patients with diabetic macular edema (DME). This cross-sectional study included 81 eyes undergoing treatment for DME from September 2021 to December 2021. An initial therapeutic treatment decision based on OCT results was made on inclusion. Subsequently, in light of the patient's VA score, this initial decision was upheld or adjusted, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. In 67 out of the 81 eyes included in the study (82.7%), the OCT-guided strategy produced equivalent results to the gold standard. In this study, the OCT-guided retreatment decision strategy yielded sensitivity and specificity of 92.3% and 73.8%, respectively, and PPV and NPV of 76.6% and 91.2%, respectively. These findings differed according to the patient's treatment regimen: the sensitivity and specificity for eyes under a treat and extend regimen was higher, 100% and 88.9%, respectively, than eyes under a Pro Re Nata regimen, 90% and 69.7%, respectively. These findings show that VA testing could be omitted from the follow-up of certain patients with DME treated with intravitreal injections without impacting the quality of care.

Intra-Ocular Pressure Response to Dexamethasone Implant Injections in Patients with a History of Filtering Surgery: The TRABEX Study.

Patients with both macular edemas, of various etiologies such as diabetes and glaucoma, may suffer serious loss of vision if either disease goes untreated. Where no effective alternative therapies are available, dexamethasone implant (DEX-I) injections may be the only choice of treatment, despite the risk of a possible increase in intraocular pressure (IOP) when using steroids. Although many studies have reported on IOP evolution in eyes treated with DEX-I, little is known specifically about eyes with a history of filtering surgery. The aim of this observational series was to evaluate the IOP response following DEX-I injection in eyes presenting conventional filtering surgeries or microinvasive glaucoma surgeries (MIGS). Twenty-five eyes were included in this study. A total of 64% of the eyes did not experience OHT during follow-up. Additional IOP-lowering therapy was needed for 32% of eyes, and 20% of eyes (all showing bleb fibrosis) required further filtering surgery: 50% of eyes in the MIGS group and 10.5% of eyes in the conventional filtering surgery group. A significant positive correlation was found between IOP at baseline and the maximum IOP throughout follow-ups after DEX-I (r = 0.45, p = 0.02). In conclusion, if DEX-I is used when there are no alternative therapies for treating macular edema, IOP in eyes with a history of filtering surgery is generally manageable. Those eyes which previously underwent conventional therapy with effective blebs obtained better IOP control after DEX-I injections and mostly did not require any additional IOP-lowering therapy or surgery.

A retrospective, multicenter study on the management of macular holes without residual internal limiting membrane: the refractory macular hole (ReMaHo) study.

PURPOSE: To evaluate the surgical management, outcomes and prognostic factors of full thickness macular holes without residual internal limiting membrane (NO-ILM FTMHs). METHODS: We performed a multicenter, retrospective study of 116 NO-ILM FTMHs. Human amniotic membrane (hAM) plug, autologous ILM free flap transplantation (AILMT), and autologous retinal graft transplantation (ART) were performed in 58, 48, and 10 patients, respectively. Data were collected before and up to 12 months after surgery. The primary outcomes were hole closure and final best-corrected visual acuity (BCVA). RESULTS: The final BCVA (0.78 ± 0.51 logMAR) was significantly better than and correlated with the initial BCVA (p < 0.0001 and p = 0.004, respectively). Hole closure was achieved in 92% of eyes. The minimum FTMH diameter was wider and final BCVA was lower in the ART group than in the other groups (p < 0.003 and p < 0.001, respectively). FTMHs with diameter > 680 µm had a higher closure rate with hAM than with AILMT (p = 0.02). CONCLUSIONS: AILMT and hAM were the most frequently performed surgeries with both high closure rate and significant functional improvement. Preoperative BCVA was correlated with final BCVA. The minimum FTMH diameter may guide the treatment choice.

Efficacy and Safety of Intravitreal Fluocinolone Acetonide Implant for Chronic Diabetic Macular Edema Previously Treated in Real-Life Practice: The REALFAc Study.

Diabetic macular edema (DME) is the main cause of visual impairment in diabetic patients and a chronic disease requiring long-term treatments. The fluocinolone acetonide (FAc) implant has recently been approved to treat DME in patients considered insufficiently responsive to available therapies. This study evaluates the functional and anatomical efficacy of the FAc implant in real-life practice. A total of 62 eyes with chronic DME were included and followed for a mean of 13.9 (+7.5) months. Previous treatment included at least anti-vascular endothelial growth factor (VEGF) in 83.9% of eyes, dexamethasone implant (DEX-I) in 100% of eyes, vitrectomy in 29.0% of eyes, and laser photocoagulation (either panretinal or focal photocoagulation) in 75.8% of eyes. The mean baseline best corrected visual acuity (BCVA) was 64.0 (+/−17.2) letters (median: 67.5 letters) with a mean DME duration of 60.3 (+/−30.6) months. The maximum BCVA gain occurred at 21 months with a mean gain of 5.0 (+/−12.7) letters. A total of 50.0% of eyes gained ≥5 letters during follow-up. Patients with lower BCVA at baseline had the lowest final BCVA (p < 0.001) but the highest BCVA gain (p = 0.02). The best overall improvement in mean central macular thickness (CMT) occurred at 18 months (p < 0.0001). The improvement in BCVA was inversely associated with the decrease in CMT and showed a decrease when CMT increased (DME recurrence). According to the history of vitrectomy, we did not find any significant difference in mean final BCVA (p = 0.1) and mean BCVA gain (p = 0.2) between eyes previously vitrectomized or not. A total of 23 eyes (37.1%) required additional treatment for DME, and 17.7% required an IOP-lowering procedure during follow-up. In conclusion, this real-life observational study demonstrated the efficacy and safety of the FAc implant in patients with chronic DME already treated with other available therapies.

Comparative Effectiveness of Intravitreal Anti-Vascular Endothelial Growth Factor Therapies for Managing Neovascular Age-Related Macular Degeneration: A Meta-Analysis.

Intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) have become the standard of care for age-related macular degeneration (AMD). Although most pivotal trials have used monthly injections, alternative strategies that enable the injections to be administered on a more flexible schedule, including pro re nata (PRN) and treat-and-extend (T&E) regimens, are being applied more frequently. This review sought to provide further scientific evidence about the visual outcomes and treatment burden among the currently available anti-VEGF agents and regimens, including aflibercept, ranibizumab, abicipar and brolucizumab. To this end, a systematic review of published randomized studies was conducted from the MEDLINE and EMBASE databases and the Cochrane library, and a meta-analysis was applied to the obtained data using single-means modeling to compare the efficacy and maintenance among the different available treatments and regimens at Years 1 and 2. Quality analysis identified the best-informed data for modeling purposes. Overall, 47 relevant publications were retrieved for the analysis. Superior efficacy, meaning that there were observed improvements in visual acuity (VA) and central retinal thickness (CRT), occurred with monthly versus PRN regimens, yet a higher IVI number was also observed. Conversely, the T&E regimens displayed similar efficacy to the monthly regimens, but with a reduced IVI number. Aflibercept T&E exhibited similar efficacy to ranibizumab T&E, but with significantly lower IVI numbers at both Year 1 (p < 0.0001) and Year 2 (p = 0.0011). Though all of the regimens resulted in maintained efficacy between Years 1 and 2, the required IVI number varied. The retrieved data did not enable other regimens or newer anti-VEGF agents such as brolucizumab to be compared. In conclusion, the T&E regimens were shown to be the most efficient, optimizing durable effectiveness whilst minimizing the IVI number in newly diagnosed exudative AMD, with aflibercept requiring the lowest IVI number.

IMPACT OF FLUID COMPARTMENTS ON FUNCTIONAL OUTCOMES FOR PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Systematic Literature Review.

PURPOSE: Understanding the impact of fluid in different retinal compartments is critical to developing treatment paradigms that optimize visual acuity and reduce treatment burden in neovascular age-related macular degeneration. This systematic review aimed to determine the impact of persistent/new subretinal fluid, intraretinal fluid, and subretinal pigment epithelial fluid on visual acuity over 1 year of treatment. METHODS: Publication eligibility and data extraction were conducted according to Cochrane methods: 27 of the 1,797 screened records were eligible. RESULTS: Intraretinal fluid negatively affected visual acuity at baseline and throughout treatment, with foveal intraretinal fluid associated with lower visual acuity than extrafoveal intraretinal fluid. Some studies found that subretinal fluid (particularly subfoveal) was associated with higher visual acuity at Year 1 and longer term, and others suggested subretinal fluid did not affect visual acuity at Years 1 and 2. Data on the effects of subretinal pigment epithelial fluid were scarce, and consensus was not reached. Few studies reported numbers of injections associated with fluid status. CONCLUSION: To optimally manage neovascular age-related macular degeneration, clinicians should understand the impact of fluid compartments on visual acuity. After initial treatment, antivascular endothelial growth factor regimens that tolerate stable subretinal fluid (if visual acuity is stable/improved) but not intraretinal fluid may enable patients to achieve their best possible visual acuity. Confirmatory studies are required to validate these findings.

Costs comparison of treating diabetic macular edema with aflibercept, ranibizumab or dexamethasone at 1 year in France (INVICOST study).

PURPOSE: INVICOST, a medico-economic analysis, compared costs of managing treatment-naive patients with diabetic macular edema (DME) receiving intravitreal injections (IVIs) of aflibercept (AFL), dexamethasone implant (DXI) or ranibizumab (RAN) over 1 year. METHODS: Healthcare resource use and associated costs were estimated using individual patient data from INVICTUS, a prospective, open-label, monocentric study. Healthcare costs comprised direct medical costs such as drug acquisition and administration, consultations and ophthalmological procedures. Costs were assessed from the French National Health Insurance perspective using published national tariffs expressed in 2019 euros. RESULTS: Of the 60 treated eyes, 48 had no treatment switch; 14 received AFL, 19 received DXI and 15 received RAN. AFL-treated eyes received an average of 6.5 IVIs, DXI-treated patients received 2 IVIs and RAN-treated received 6.8 IVIs. All treated eyes received an initial prescription for adjunctive ocular medications and 349 follow-up procedures were performed including an average of 3.9 optical coherence tomography and 3.2 retinography procedures per eye. Average total direct cost of per-eye treatment was €4516 (€1128-€8257). Average cost was €5782 for eyes treated with AFL, €2779 with DXI and €5536 with RAN. Drug therapy was the cost driver: €4394 (76%) for AFL, €1915 for DXI (69%) and €4268 (77%) for RAN. CONCLUSION: The difference in total treatment cost is largely explained by the significantly lower frequency of IVI and annual cost of therapy with DXI, compared with AFL and RAN. INVICOST is the first study comparing treatment costs with AFL, DXI and RAN in France in current clinical practice.

Recommendations for the management of diabetic macular oedema with intravitreal dexamethasone implant: A national Delphi consensus study.

PURPOSE: The intravitreal dexamethasone implant (DEX-I) is an alternative to anti-VEGF for the first-line treatment of diabetic macular oedema (DME). However, several questions remain regarding its routine use and its place in certain situations not always specified in current recommendations. A national consensus approach was, therefore, initiated by French retinal experts. METHODS: An iterative Delphi consensus approach was used. A steering committee (SC) of seven experts analysed data from the literature to formulate statements divided into five key areas of treatment. These statements were submitted to the independent and anonymous electronic vote of 87 French retina experts among whom 39 expressed their opinion and therefore constituted the voting panel. RESULTS: After two rounds of voting, 22 and 7 of 38 statements received a strong consensus and a good consensus, respectively. The consensus level was higher for statements regarding first-line indications and safety of DEX-I compared to those regarding efficacy assessment, reprocessing time or pathophysiological biomarkers. The panellists recommended the preferential use of DEX-I for patients with limited availability for multiple injections, those who needed to undergo cataract surgery or who had a recent cardiovascular history, and as a therapeutic alternative to anti-VEGF in patients with a history of vitrectomy, retinal serous detachment, hyper-reflective points or dry exudates in optical coherence tomography (OCT). However, some statements proposed by SC experts were not validated. CONCLUSION: This study provides some key recommendations to clinicians treating diabetic macular oedema, which may be useful when using intravitreal dexamethasone implants in daily practice.

The AflibeRcept use in rEal life study for the treatment of diabetiC macular oedema In the French overseas territories: A 12 months follow-up Study - The RECIF Study.

PURPOSE: The incidence and severity of diabetes is particularly high in the French overseas territories (FOT). The RECIF study evaluated real life management of diabetic macular oedema (DME) treated by aflibercept in FOT. METHODS: A prospective, noncomparative, multicentric, non-interventional, study that evaluated functional and anatomical results of patients treated by aflibercept. Twelve retina specialists working in French Polynesia, La Reunion, Guadeloupe and Martinique participated in the study. RESULTS: 67 eyes of 57 patients were followed for 12 months. Average VA gain was 7.8 ETDRS letters. 29.9% of eyes gained at least 15 letters, 6% lost 15 letters or more. 67.2% of eyes achieved visual acuity of 70 letters or better. Average central retinal thickness decrease was 115.3 µm. The mean number of injections during the 1st year of treatment was 4.9. 69% of eyes had a loading dose of at least three-monthly injections. 3 eyes were switched to steroid injections during the follow-up for lack of efficacy. CONCLUSION: This study confirmed the efficacy of intravitreal treatment of DME by aflibercept, in the French overseas territories. This evaluation of real-life management of DME underlines the importance of improvement of patient education and collaboration with referring physicians.

Use of the heads-up NGENUITY 3D Visualization System for vitreoretinal surgery: a retrospective evaluation of outcomes in a French tertiary center.

Heads-up three-dimensional (3D) surgical visualization systems allow ophthalmic surgeons to replace surgical microscope eyepieces with high-resolution stereoscopic cameras transmitting an image to a screen. We investigated the effectiveness and safety of the heads-up NGENUITY 3D Visualization System in a retrospective evaluation of 241 consecutive vitreoretinal surgeries performed by the same surgeon using conventional microscopy (CM group) over a 1-year period versus the NGENUITY System (3D group) over a consecutive 1-year period. We included for study vitreoretinal surgeries for treatment of retinal detachment (RD) (98 surgeries), macular hole (MH) (48 surgeries), or epiretinal membrane (ERM) (95 surgeries). A total of 138 and 103 eyes were divided into 3D and CM groups, respectively. We found no differences in 3-month postoperative rates of recurrence of RD (10% versus 18%, p = 0.42), MH closure (82% versus 88%, p = 0.69), or decrease in central macular thickness of ERMs (134 ± 188 µm versus 115 ± 105 µm, p = 0.57) between the 3D and CM groups, respectively. Surgery durations and visual prognosis were also similar between both groups. We consolidate that the NGENUITY System is comparable in terms of visual and anatomical outcomes, giving it perspectives for integration into future robotized intervention.

Visual Acuity Gain Profiles and Anatomical Prognosis Factors in Patients with Drug-Naive Diabetic Macular Edema Treated with Dexamethasone Implant: The NAVEDEX Study.

The purpose of this study is to evaluate the visual acuity (VA) gain profiles between patients with drug-naive diabetic macular edema (DME) treated by dexamethasone implant (DEX-implant) and assess the baseline anatomical and functional factors that could influence the response to the treatment in real-life conditions. A retrospective, multi-center observational study included 129 eyes with drug-naive DME treated by DEX-implant. The Median follow-up was 13 months. Two groups of VA gain trajectories were identified-Group A, with 71% (n = 96) of patients whose average VA gain was less than five letters and Group B, with 29% (n = 33) of patients with an average gain of 20 letters. The probability of belonging to Group B was significantly higher in patients with baseline VA < 37 letters (p = 0.001). Ellipsoid zone alterations (EZAs) or disorganization of retinal inner layers (DRILs) were associated with a lower final VA (53.0 letters versus 66.4, p = 0.002) but without a significant difference in VA gain (4.9 letters versus 6.8, p = 0.582). Despite a low baseline VA, this subgroup of patients tends to have greater visual gain, encouraging treatment with DEX-implant in such advanced-stage disease. However, some baseline anatomic parameters, such as the presence of EZAs or DRILs, negatively influenced final vision.

Real-World Efficacy and Safety of Fluocinolone Acetonide Implant for Diabetic Macular Edema: A Systematic Review.

To assess real-world outcomes of fluocinolone acetonide (FAc) implant in treating diabetic macular edema (DME), a systematic literature review was conducted on PubMed in order to identify publications assessing the efficacy and safety of the FAc implant in DME in daily practice. Case reports and randomized controlled trials were excluded. Twenty-two observational real-world studies analyzing a total of 1880 eyes were included. Mean peak visual gain was +8.7 letters (11.3 months post-FAc injection) and was greater for lower baseline best corrected visual acuity (BCVA) and for more recent DME. Mean central retinal thickness (CRT) decreased 34.3% from baseline. 77.0% of the analyzed studies reported both BCVA improvement of at least five letters and a CRT decrease by 20% or more. Rescue therapy was needed more frequently when FAc was administered for chronic DME. FAc-induced ocular hypertension was reported in 20.1% of patients but only 0.6% needed surgery. Cataract extraction was performed in 43.2% of phakic patients. Adequate patient selection is essential for optimal FAc response and better safety profile. Currently positioned as second- or third-line treatment in the management algorithm, FAc implant decreases treatment burden and provides better letter gain when administered for more recent DME.

Safety and efficacy of high-intensity focused ultrasound in severe or refractory glaucoma.

PURPOSE: The aim of this study was to evaluate the efficacy and safety of ultrasonic cyclocoagulation in severe or refractory glaucoma, and to analyze the procedure-related inflammation. PATIENTS AND METHODS: In this retrospective study, 15 eyes of 13 patients suffering from severe or refractory glaucoma with uncontrolled intraocular pressure of ⩾21 mmHg underwent 8-s ultrasonic cyclocoagulation. A complete ophthalmic evaluation, quality of life assessment using Glau-Qol-17, endothelial cell count, and flare measurement were performed. Primary outcome was qualified surgical success (defined as intraocular pressure reduction from baseline ⩾20% and intraocular pressure >5 mmHg without hypotensive medication adjunction). Secondary outcomes were flare, endothelial cell loss, and quality of life. RESULTS: Qualified success was achieved in 67% of eyes at 6 months (mean intraocular pressure reduction = 42% in these eyes). During the first month after the procedure, the mean flare reached its maximum value when the intraocular pressure was minimal; the flare slowly decreased until normalization at month 3 when the maximal intraocular pressure was noted. At month 3, there was moderate but significant endothelial cell loss (11%), and no significant alteration in quality of life was demonstrated. CONCLUSION: The efficacy of ultrasonic cyclocoagulation in the present study is comparable to that reported in the literature. The kinetics of intraocular pressure and flare suggest that postoperative inflammation could be partly responsible for the early intraocular pressure decrease. The moderate endothelial cell loss, which could be caused by localized heating, and the preservation of quality of life confirm the safety of ultrasonic cyclocoagulation.

INVICTUS: Intravitreal anti-VEGF and dexamethasone implant comparison for the treatment of diabetic macular edema: A 12 months follow-up study.

PURPOSE: To compare the efficacy of intravitreal injections (IVI) of ranibizumab (Lucentis®, Novartis, Basel, Switzerland; RAN), aflibercept (Eylea®, Bayer, Leverkusen, Germany; AFL) and dexamethasone implant (Ozurdex®, Allergan, Irvine, California; DXI) in the treatment of naive diabetic macular oedema (DME) during a 12-month follow-up, in real life. METHODS: Nineteen eyes treated with RAN, 20 with AFL and 21 with DXI were analysed from inclusion up to 12 months (M12) with intermediate analysis at M6. Best corrected visual acuity (BCVA), fundus and central retinal thickness (CRT) using spectral-domain optical coherence tomography (SD-OCT; Spectralis/HRA, Heidelberg Engineering, Germany) were performed at inclusion, M3, M6 and M12. RESULTS: BCVA improved until 67.9 letters ±13.3 SD (+5.5 letters) at M6 and 69.6 letters ±12 SD (+7.2 letters) at 12 months for RAN group (p = 0.036). For the AFL group it improved until 63.6 letters ±15.2 SD (+6.6 letters) at M6 and 67.5 letters ±12.2 SD (+8.5 letters) at 12 months (p = 0.014). Lastly DXI group improved by 66.9 letters ±15.1 SD (+7.9 letters) at M6 and 68.4 letters ±11.2 SD (+9.4 letters) at 12 months (p = 0.0023). CRT decreased by 124.4 µm at M6 and 99.3 µm at M12 in RAN group, 144.3 µm and 101.5 µm in AFL group and finally 95.6 µm and 162.7 µm in DXI group. CONCLUSION: In summary, these three drugs provide an efficient treatment option with an acceptable benefit-risk ratio for the treatment of naive patients with DME, whether on BCVA or CRT on the first year of treatment.

The inhibitory effect of word neighborhood size when reading with central field loss is modulated by word predictability and reading proficiency.

For normally sighted readers, word neighborhood size (i.e., the total number of words that can be formed from a single word by changing only one letter) has a facilitator effect on word recognition. When reading with central field loss (CFL) however, individual letters may not be correctly identified, leading to possible misidentifications and a reverse neighborhood size effect. Here we investigate this inhibitory effect of word neighborhood size on reading performance and whether it is modulated by word predictability and reading proficiency. Nineteen patients with binocular CFL from 32 to 89 years old (mean ± SD = 75 ± 15) read short sentences presented with the self-paced reading paradigm. Accuracy and reading time were measured for each target word read, along with its predictability, i.e., its probability of occurrence following the two preceding words in the sentence using a trigram analysis. Linear mixed effects models were then fit to estimate the individual contributions of word neighborhood size, predictability, frequency and length on accuracy and reading time, while taking patients' reading proficiency into account. For the less proficient readers, who have given up daily reading as a consequence of their visual impairment, we found that the effect of neighborhood size was reversed compared to normally sighted readers and of higher amplitude than the effect of frequency. Furthermore, this inhibitory effect is of greater amplitude (up to 50% decrease in reading speed) when a word is not easily predictable because its chances to occur after the two preceding words in a specific sentence are rather low. Severely impaired patients with CFL often quit reading on a daily basis because this task becomes simply too exhausting. Based on our results, we envision lexical text simplification as a new alternative to promote effective rehabilitation in these patients. By increasing reading accessibility for those who struggle the most, text simplification might be used as an efficient rehabilitation tool and daily reading assistive technology, fostering overall reading ability and fluency through increased practice.

VEGF is an autocrine/paracrine neuroprotective factor for injured retinal ganglion neurons.

Vascular endothelial growth factor-A (VEGF) is the angiogenic factor promoting the pathological neovascularization in age-related macular degeneration (AMD) or diabetic macular edema (DME). Evidences have suggested a neurotrophic and neuroprotective role of VEGF, albeit in retina, cellular mechanisms underlying the VEGF neuroprotection remain elusive. Using purified adult retinal ganglion cells (RGCs) in culture, we demonstrated here that VEGF is released by RGCs themselves to promote their own survival, while VEGF neutralization by specific antibodies or traps drastically reduced the RGC survival. These results indicate an autocrine VEGF neuroprotection on RGCs. In parallel, VEGF produced by mixed retinal cells or by mesenchymal stem cells exerted a paracrine neuroprotection on RGCs. Such neuroprotective effect was obtained using the recombinant VEGF-B, suggesting the involvement of VEGF-R1 pathway in VEGF-elicited RGC survival. Finally, glaucomatous patients injected with VEGF traps (ranibizumab or aflibercept) due to either AMD or DME comorbidity, showed a significant reduction of RGC axon fiber layer thickness, consistent with the plausible reduction of the VEGF autocrine stimulation of RGCs. Our results provide evidence of the autocrine neuroprotective function of VEGF on RGCs is crucially involved to preserve injured RGCs such as in glaucomatous patients.