The influence of polyacrylamide gel substrate elasticity on primary cultures of rat retinal ganglion cells.

In vitro primary cell culture models of retinal ganglion cells (RGC) are widely used to study pathomechanisms of diseases such as glaucoma. The biomechanic interaction with the culture substrate is known to influence core cellular functions. RGC cultures, however, are usually grown on rigid plastic or glass substrates. We hypothesized that soft polyacrylamide gel substrates may alter survival and neurite outgrowth of primary cultured RGC. Primary retinal cultures from postnatal (day 1-6) Wistar rats were grown on glass coverslips or polyacrylamide (PA) gel substrate with different Young's elastic moduli (0.75, 10 or 30 kPa). Substrates were coated with Poly-l-lysine and / or laminin. RGC were immunostained with anti-beta-III-tubulin. Total neurite length, growth cone morphology, RGC density, mitochondrial morphology and transport as well as pro-survival pathways (Erk1/2, Akt, CREB) were assessed. PA gel substrates of E = 10 kPa significantly increased the total neurite length by factor 1.5 compared to glass (p = 0.02). The growth cone area was significantly larger by factor 5.3 on 30 kPa gels (p = 0.01). The presence of a substrate coating was more important for neurite outgrowth and RGC survival on PA gels (poly-l-lysine > laminin) than on glass. Neither mitochondrial morphology and motility nor the activation of pro-survival pathways significantly differed between the four substrates. PA gel substrates significantly enhanced RGC neurite outgrowth. The signaling cascades mediating this effect remain to be determined.

Benefit of intravitreal injections in patients with sub-threshold baseline visual acuity: a retrospective single-centre study.

PURPOSE: To investigate the lower visual acuity threshold for recommending intravitreal injection therapy (IVI). The lower limit of 1.3 logMAR best-corrected visual acuity (BCVA) was adopted in 2006 and has been maintained since then. METHODS: In this retrospective study, data from patients with a logMAR BCVA ≤ 1.3 and 24 months follow-up were analysed. We included patients with neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DME), or retinal vein occlusion (RVO). RESULTS: The data from 164 patients (nAMD: 107; DME: 15; RVO: 42) were analysed. We observed a significant improvement at all time intervals (0 to 6, 6 to 12, 12 to 18, and 18 to 24 months after initiating IVI) compared to baseline. Across all indications, median BCVA improved from 1.4 to 1.0 within the first 6 months and remained stable within 24 months. Patients received a median of 5 and 10 injections within 6 and 24 months, respectively. Median foveal retinal thickness was 594.5 µm at baseline and dropped to 244.5 µm, 235.5 µm, 183 µm, and 180 µm during the four consecutive time intervals. CONCLUSION: Patients with nAMD, DME, and RVO with poor baseline BCVA may also benefit from intravitreal therapy with VEGF-inhibitors. In the present study, we observed functional and morphological improvement over 2 years irrespective of the underlying macular disease. Those patients should not be excluded from therapy.

Main Principles of Vitrectomy Using Intraocular Tamponades - A Basic Course in Surgery. / Grundlagen der Vitrektomie unter Verwendung intraokularer Tamponaden ­ ein chirurgischer Basiskurs.

This article is intended to clearly present the basic principles for the use of intraocular tamponades in vitreous/retinal surgery in the event of retinal detachment and other pathologies using additional video footage. It examines the various gases, silicone oils and perfluorocarbon liquids with their indications, administration and in particular intraoperative handling including pitfalls and complications. Characteristic animations show the principles of use in surgery in a comprehensible way. The two lead authors dedicate this article to their teacher Prof. Dr. V.-P. Gabel, who in the early 1990s successfully established the first vitrectomy courses for ophthalmologists at Regensburg University Eye Clinic each year. Many colleagues who still work in retinal surgery today first started learning about this segment on these courses. The other coauthors participated under his supervision in annual vitrectomy wet labs run by the German Academy of Ophthalmology.

OCRIPLASMIN FOR VITREOMACULAR TRACTION IN CLINICAL PRACTICE: The INJECT Study.

PURPOSE: Randomized clinical trials have demonstrated the safety and efficacy of ocriplasmin in patients with vitreomacular traction (VMT), including those with macular hole (MH). The INJECT study prospectively evaluated ocriplasmin in the setting of clinical practice. METHODS: INJECT was a Phase 4, multicenter, prospective observational study. Patients were followed up for 12 months. Assessments included nonsurgical VMT resolution, nonsurgical MH closure, best-corrected visual acuity, occurrence of vitrectomy, and adverse events. RESULTS: The efficacy population (N = 395) received an ocriplasmin injection and had optical coherence tomography-confirmed VMT at baseline. At Day 28, the rate of nonsurgical VMT resolution was 40.7% in the overall group, and the rate of nonsurgical MH closure was 36.0% in the VMT with MH group. At Month 12, the rate of ≥2-line best-corrected visual acuity gain (irrespective of vitrectomy) was 36.8% in the overall group and 59.6% in the VMT with MH group. The percentage of patients who underwent vitrectomy in the study eye was 29.1% in the overall group and 55.6% in the VMT with MH group. Photopsia (9.8%) and vitreous floaters (6.8%) were the most frequent adverse events. CONCLUSION: The INJECT study showed that ocriplasmin is effective in a clinical setting in patients with VMT, with or without MH. No new safety signals were identified from this large and surgeon-selected patient group, although the significant limitations of the study design without an image reading center and scheduled study visit timings should be noted.

Prevalence of Back Pain among German Ophthalmologists.

INTRODUCTION: The aim of this study was to evaluate the prevalence of back pain among German ophthalmologists, to investigate the relationship towards age, gender, various profession-related factors, to correlate localization of pain to subspecialties, and to explore individual therapeutic and coping strategies. METHODS: In this prospective, cross-sectional survey, a 9-item questionnaire was sent via mail to all members of the German professional association of ophthalmologists "Berufsverband der Augenärzte Deutschlands e.V. (BVA)." Responses were analyzed according to a pre-specified analysis plan. RESULTS: From a total of 5,954 members contacted, 1,861 copies (31%) were received back, of which 1,807 (30%) were suitable for analysis. 913 (51%) participants were female and 876 (48%) were male, with a median age of 50 years (interquartile range: 44; 57). 1,464 ophthalmologists (81%) reported current back problems, considerably more than had been reported in the general population or in other medical specialties. Older age, female gender, and higher number of professional years appeared to be risk factors for developing back pain. Overall, neck pain was the leading symptom in 951 attendees (65%) but differed between ophthalmologists who primarily performed conservative treatment (cervical spine) and those who performed surgery (mainly lumbar spine). 1,037 participants (71%) link their complaints to their occupational activity. Exercising and back training were reported as common strategies for prevention and coping with the problem. Recommendations for improvement were mainly ergonomic optimization of the working place. CONCLUSIONS: The prevalence of back pain complaints in German ophthalmologists is high. Neck pain (65%) was the leading localization, followed by low back pain (53%) and shoulder (38%) problems, which might emphasize a special back pain complaint profile in ophthalmologists. Low back pain seems to be more common in ophthalmologists with surgical specialization than in those with mainly medical tasks. The high prevalence of back pain in ophthalmologists should be communicated with employers, the industry, and professional societies to develop and implement a strategy to prevent occupational-related musculoskeletal disorders and preserve the ability to work and the quality of life.

[Clinical Decision Making for Treatment of Diabetic Macular Oedema with DEX Implant: a Consensus Paper]. / Klinische Entscheidungsfindung bei der Behandlung des diabetischen Makulaödems mit DEX-Implantat: ein Konsenspapier.

BACKGROUND: Currently two intravitreally applied corticosteroids (dexamethasone and fluocinolone) are licensed in Germany for treatment of diabetic macular oedema (DME). The use of DEX implant for DME in daily clinical practice has not been defined in detail. Following a Delphi panel survey, a group of retina experts set out to come up with a consensus for use of the DEX implant in DME. MATERIAL AND METHODS: International and national treatment recommendations were identified from the literature. A steering group generated a catalogue of 72 statements on the aetiology and pathogenesis of DME, therapy with DEX implant, use of DEX implant in patients previously treated with VEGF-inhibitors, use of DEX implant in combination therapy, safety of DME therapies as well as patients' burden of treatment. Twenty-two ophthalmologists from private practice and 6 hospital ophthalmologists participated in the Delphi panel via Survey Monkey. Consensus was reached if at least 75% of participants agreed or disagreed with a statement. Statements for which consensus was not reached were discussed once more during the expert consensus meeting and a vote was taken. Based on these results a treatment algorithm for foveal DME was proposed. RESULTS: If a patient does not show sufficient response after 3 - 6 months of anti-VEGF treatment (visual acuity gain of < 5 ETDRS letters or reduction of central retinal thickness ≤ 20%), a switch to DEX implant should take place. DEX implant is also suitable in eyes with longer presentation of DME, showing e.g. massive lipid exudates. DEX implant is suitable as first-line therapy especially in pseudophakic patients, patients unwilling or able to comply with tight anti-VEGF injection intervals or patients with known vascular diseases. With fixed control visits every 4 - 8 weeks, use of DEX implant is flexible and individual. Decision parameters for repeated use should be visual acuity, retinal thickness and intraocular pressure. Treatment of both eyes on the same day should not take place. CONCLUSION: The algorithm presented reflects survey as well as expert discussion results and may differ from recommendations issued by the German professional society. The consensus recommendations for the treatment of DME generated during the survey and meeting of retina experts are intended to guide use of DEX implant in daily practice.

Reorganization of the perifoveal microvasculature after macular hole closure assessed via optical coherence tomography angiography.

PURPOSE: To quantify short-term microvascular changes after pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling in patients with idiopathic macular hole (IMH) using optical coherence tomography angiography (OCTA). DESIGN: Cohort Study. PARTICIPANTS: This study included patients with IMH. Affected eyes were compared with fellow eyes. METHODS: 6 × 6 mm OCTA (Zeiss Angioplex, Zeiss Meditec, Dublin, CA, USA) images of the study eye and fellow eye were acquired one day before surgery, 4 weeks and 12 weeks after surgery. Microvascular alterations in the superficial and deep capillary plexus were assessed by measuring vessel density and the shortest distance to the surrounding vessels of all intercapillary pixels. Only vessels enclosed by an ETDRS Grid centered on the fovea were analyzed. MAIN OUTCOME MEASURES: Change of vessel density and vessel distance to baseline. RESULTS: OCTA images of the 15 study and 15 fellow eyes of 15 included patients (mean ± SD of age: 67.89 ± 5.2 years) were analyzed and revealed a significant increase in vessel density and decrease in vessel distance of the deep capillary plexus in study eyes 4 weeks after surgery compared to baseline. Our superficial capillary plexus findings were the inverse, namely a significant decrease in vessel density and increase in vessel distance. Postoperative microvascular changes proved to be closely associated with the extent of retinal thickness reduction in the perifoveal deep capillary plexus. CONCLUSIONS: IMH closure after PPV and ILM peeling caused a significantly improved microvasculature in the deep capillary plexus, which may represent reorganized perifoveal microvasculature due to the regression of cystoid spaces.

Risk of perioperative bleeding complications in rhegmatogenous retinal detachment surgery: a retrospective single-center study.

PURPOSE: The goal of this study was to analyze the incidence of perioperative bleeding complications in rhegmatogenous retinal detachment. The handling of perioperative anticoagulation during vitreoretinal surgery remains controversial, since the risk of bleeding complications by its continuation has to be balanced against the risk of progression of retinal detachment and the risk of thromboembolic events when anticoagulation is interrupted. Nevertheless, only few studies have investigated the risk of perioperative bleeding complications in an emergency such as retinal detachment surgery. METHODS: We therefore examined the rate of all perioperative hemorrhages and separately the rate of only severe bleedings during vitrectomy, scleral buckling with or without drainage of subretinal fluid (SRD), or combined procedures due to retinal detachment in patients undergoing different types of perioperative anticoagulation including acetylsalicylic acetate (ASA), clopidogrel, heparin, low molecular weight heparin, and phenprocoumon. RESULTS: This retrospective single-center study included 893 patients with primary rhegmatogenous retinal detachment, n = 192 on anticoagulation and n = 701 serving as control without anticoagulation. Our analysis revealed no significantly increased rate of perioperative hemorrhages under anticoagulation with ASA 100 mg (all, 11.4%; severe, 5.0%) or phenprocoumon (all, 11.6%; severe, 2.3%) compared with controls (all, 13.0%; severe, 5.4%). However, frequencies of bleeding complications varied markedly regarding the type of surgical procedure: Scleral buckling plus SRD showed the highest rates of hemorrhages (all, 18.9%; severe, 9.1%) with significant difference (P < 0.001) compared with scleral buckling without SRD (all, 3.8%; severe, 0.6%) and vitrectomy (all, 9.2%; severe, 1.5%), respectively. Furthermore, subretinal bleeding was the most common type of perioperative hemorrhage. CONCLUSIONS: The data suggest not to stop ASA therapy prior to vitreoretinal surgery. Furthermore, we found no evidence of an increased risk for perioperative bleedings in patients under anticoagulation with vitamin-k antagonists with an INR within the sub-therapeutic range. SRD during scleral buckling procedure should be avoided as possible and regardless of any type of anticoagulation.

Bevacizumab versus bevacizumab and macular grid photocoagulation for macular edema in eyes with non-ischemic branch retinal vein occlusion: results from a prospective randomized study.

BACKGROUND: The objective of the study was the investigation of the effects of intravitreal bevacizumab (BEV) with or without additional macular grid laser photocoagulation (GRID) for macular edema (ME) secondary to branch retinal vein occlusion (BRVO). METHODS: Prospective, randomized, monocentric study. Thirty-two patients were included. Initially, all eyes in both groups received three monthly injections of BEV, followed by additional injections if re-treatment criteria were met. In the BEV + GRID group, photocoagulation was performed 2 weeks after the first BEV injection and laser re-treatment was allowed. The follow-up was 38 weeks. Main outcome measures were best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Changes of foveal avascular zone (FAZ) and of retinal ischemia, as well as the number of injections were also evaluated. RESULTS: Sixteen eyes were randomized into each group. At baseline, BCVA was similar in both groups (BEV + GRID: 20/71; BEV: 20/60; P = 0.51). At 38 weeks, BCVA significantly improved in the two groups (BEV + GRID gain of 9 ± 11.2 letters and 16.25 ± 10.08 letters in the BEV) with no difference between them (P < 0.06). With regard to anatomical findings, initial CRT in BEV + GRID was 496.2 µm ± 138.4 µm and 538.9 µm ± 156.9 µm in BEV (P < 0.1697). At 38 weeks, CRT decreased in both groups significantly, 98.2 µm in the BEV + GRID (P = 0.02) and 141.7 µm in the BEV group (P = 0.01), with no significant difference between groups (P < 0.17). The area of FAZ a significantly increased in both groups (41% (P = 0.04) in BEV + GRID; 35% (P = 0.03) in BEV) during the study and the grade of peripheral ischemia remained unchanged. The mean number of injections was 3.8 (range 3-6) with no significant difference between groups. CONCLUSIONS: Our data demonstrate a beneficial effect of bevacizumab in ME in eyes with BRVO. A loading phase of three injections led to a significant improvement in vision in both groups, which persisted at week 38. Additional grid laser photocoagulation exhibited no beneficial functional or anatomical effect during the study, nor did it reduce the number of injections. The FAZ area increased significantly in both groups, but overall retinal ischemia did not. Further studies investigating more numerous eyes and longer follow-up are needed to confirm these data.

[Peri-/Postoperative Anti-Inflammatory Therapy in Vitreoretinal Interventions]. / Peri-/Postoperative antientzündliche Therapie im Rahmen von vitreoretinalen Eingriffen.

The perioperative treatment of retinal surgery with anti-inflammatory drugs is an everyday procedure for ophthalmologists in Germany. Nevertheless, little data are available to investigate the efficacy of vitreoretinal surgery. Treatment is usually analogous to procedures on the anterior segment of the eye, for which much more robust data are available. In this article, the relevant clinical questions will be answered and, when possible, documented with study data.

Efficacy and safety of a fixed bimonthly ranibizumab treatment regimen in eyes with neovascular age-related macular degeneration: results from the RABIMO trial.

PURPOSE: To evaluate prospectively the efficacy and safety of a fixed bimonthly ranibizumab treatment regimen (RABIMO) in eyes with neovascular age-related macular degeneration (nAMD) and to compare these results with a pro re nata (PRN) treatment scheme. METHODS: This was a 12-month, phase IV, single center, randomised, non-inferiority study. Following three initial monthly injections, patients were randomised to receive either ranibizumab bimonthly (RABIMO group) or ranibizumab PRN (PRN group) (n = 20 each). Main outcome measures were best-corrected visual acuity (BCVA), central retinal thickness (CRT), number of injections, and adverse events (AEs). RESULTS: BCVA [median (interquartile range, IQR)] increased significantly in both groups after 12 months [RABIMO group +8.5 (14); PRN group +6.5 (16) ETDRS letters] when compared to baseline (p < 0.0001; p = 0.0085). At month 12, the RABIMO treatment regimen was non-inferior to the PRN scheme (∆BCVA = 3.5 ETDRS letters; p < 0.0001). CRT was significantly reduced in both groups after the 12-month study period (p < 0.0001 each), with no significant difference between groups (p = 0.6772). Number of overall injections [median (IQR)] was 8 (0) in the RABIMO versus 4 (5) in the PRN group (p = 0.0037). Three patients in the RABIMO group received one additional unscheduled injection. We observed no significant differences between groups in the number of patients with reported SAEs/AEs (RABIMO group n = 6/15; PRN group n = 7/13) (p = 0.7357/p = 0.4902). CONCLUSIONS: We found no evidence of significant functional or anatomical differences between the RABIMO and PRN treatment regimens. However, the RABIMO group's number of injections was twice as high as the PRN group's (protocol-driven). In light of potential side effects, the fixed bimonthly treatment regimen might not be advisable for routine clinical care, but it might be a worthwhile treatment option if monthly monitoring is not possible. Eudra-CT number: 2009-017324-11.

Risk of progression in macula-on rhegmatogenous retinal detachment.

PURPOSE: To identify factors that may lead to a rapid progression in macula-on rhegmatogenous retinal detachment (RRD), in particular, those that may lead to macular involvement. METHODS: Observational, prospective, single-center study. Patients referred for surgery due to primary rhegmatogenous retinal detachment with the macula on between 2009 and 2013 were included. Relevant factors analyzed included age, time delay until surgery, lens status, myopia, the detachment's location and configuration as well as number, size and type of retinal breaks. Eyes underwent optical coherence tomography to detect macular detachment. A multivariate analysis was performed to investigate the effect of several factors in the progression of retinal detachment. RESULTS: A total of 116 eyes of 116 patients were included. Mean time delay between admission and surgery was 1.8 ± 1.4 days. Progression was observed in 19.8% of the eyes. Of those, 47.8% presented macular detachment. Ten of the 11 (90.9%) eyes presenting progression involving the macula also exhibited a bullous configuration, which was the only parameter that correlated significantly with detachment progression in patients with (p = 0.0036) and without (p = 0.0014) macular involvement. CONCLUSIONS: For the first time in a prospective trial, a bullous configuration was found to be a highly significant predictor for progression in macula-on detachments. Our data support prompt surgery in patients diagnosed with bullous macula-on RRD.

VITRECTOMY FOR PERSISTENT MACULAR HOLES FOLLOWING OCRIPLASMIN INJECTION: A Comparative Multicenter Study.

PURPOSE: To determine functional and anatomical outcomes of pars plana vitrectomy for persistent full-thickness macular hole (MH) after intravitreal injection of ocriplasmin. METHODS: This is a multicenter retrospective interventional study of 37 eyes of 37 patients who underwent pars plana vitrectomy with internal limiting membrane peeling for persistent MH after ocriplasmin treatment between December 2013 and December 2015 and comparison with 35 eyes of 35 patients who were offered ocriplasmin injection but underwent pars plana vitrectomy alone without pharmacologic vitreolysis before surgery. In addition, 24 matched pairs (MH diameter at baseline ±5 µm) were analyzed. Clinical data such as visual acuity, intraoperative characteristics, and spectral domain optical coherence tomography images were reviewed. Main outcome measures were visual acuity and MH closure rate. RESULTS: After a mean follow-up period of 9 months, postoperative mean visual acuity showed no significant differences between ocriplasmin-treated eyes (logarithm of minimum angle of resolution 0.37 ± 0.26, Snellen 20/47) and eyes without ocriplasmin treatment (logarithm of minimum angle of resolution 0.39 ± 0.25; Snellen 20/49) (P > 0.9). After ocriplasmin injection, mean MH diameter enlarged from 217 ± 102 µm to 384 ± 239 µm (P < 0.001). Matched-pair analysis revealed no difference in gain of visual acuity between the first visit and the last follow-up (P = 0.29). Macular hole closure was observed in similar proportion in ocriplasmin-treated eyes (97%) and vitrectomy-only eyes (94%) (P > 0.5). CONLCUSION: Eyes with persistent MH after ocriplasmin injection showed significant visual improvement after pars plana vitrectomy. Matched-pair analysis revealed no statistical differences in functional and anatomical postoperative results comparing with eyes of similar MH diameter that proceeded directly to surgery without ocriplasmin pretreatment.

Intravitreal Sustained-Release Steroid Implants for the Treatment of Macular Edema following Surgical Removal of Epiretinal Membranes.

PURPOSE: To evaluate the efficacy of intravitreal dexamethasone implant for the treatment of postoperative persistent cystoid macular edema (CME) following macular pucker surgery. METHODS: In this multicenter study, we retrospectively reviewed the data of 37 patients (39 eyes) who had been treated with intravitreal dexamethasone implant (Ozurdex®) for persistent CME following macular pucker surgery. Main outcome measures were change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). RESULTS: All eyes underwent spectral domain optical coherence tomography examination within 130 days after implantation. We observed a significant decrease in mean CRT from 519.9 to 392.9 µm (p < 0.0001). By this time, mean BCVA had improved from 0.60 to 0.43 logMAR (p = 0.003). Seventeen eyes (43.6%) required at least 1 repeat injection of dexamethasone. Of these, 8 (47%) eyes received a total number of 3 or more dexamethasone injections. CONCLUSION: Intravitreal dexamethasone implant injection is an effective treatment option for persistent CME following macular pucker surgery.

TREAT-AND-EXTEND REGIMENS WITH ANTI-VEGF AGENTS IN RETINAL DISEASES: A Literature Review and Consensus Recommendations.

PURPOSE: A review of treat-and-extend regimens (TERs) with intravitreal anti-vascular endothelial growth factor agents in retinal diseases. METHODS: There is a lack of consensus on the definition and optimal application of TER in clinical practice. This article describes the supporting evidence and subsequent development of a generic algorithm for TER dosing with anti-vascular endothelial growth factor agents, considering factors such as criteria for extension. RESULTS: A TER algorithm was developed; TER is defined as an individualized proactive dosing regimen usually initiated by monthly injections until a maximal clinical response is observed (frequently determined by optical coherence tomography), followed by increasing intervals between injections (and evaluations) depending on disease activity. The TER regimen has emerged as an effective approach to tailoring the dosing regimen and for reducing treatment burden (visits and injections) compared with fixed monthly dosing or monthly visits with optical coherence tomography-guided regimens (as-needed or pro re nata). It is also considered a suitable approach in many retinal diseases managed with intravitreal anti-vascular endothelial growth factor therapy, given that all eyes differ in the need for repeat injections. CONCLUSION: It is hoped that this practical review and TER algorithm will be of benefit to health care professionals interested in the management of retinal diseases.

Isolated ocular Jarisch-Herxheimer reaction after initiating tuberculostatic therapy in a child.

After being exposed to a kindergarten teacher with infectious pulmonary tuberculosis, a7-year-old girl with a positive tuberculin skin test was treated with isoniazid. 3 days after initiation of the tuberculostatic therapy, the girl was referred to our hospital with an acute onset of blurred vision. Visual acuity (VA) was 20/200 in both eyes. Examination revealed mild anterior chamber inflammation, optic disc swelling, cystoid macular edema and periphlebitis in both eyes. However, although active tuberculosis was ruled out, the interferon-gamma release assay was positive. The anti-tuberculosis therapy was intensified with pyrazinamide, isoniazid, rifampicin and methylprednisolone. Within 10 days we saw a resolution of the macular edema and VA was 20/25. The paradoxical worsening of the patient's condition after initiation of tuberculostatic therapy with isoniazid and the prompt response to systemic steroids are typical for Jarisch-Herxheimer reaction (JHR). Our patient presented no symptoms before the isoniazid therapy was started and the reaction was ocular without any generalized symptoms. This is unique among all other reported cases of ocular JHR.

Real-World Management of Macular Edema Secondary to Retinal Vein Occlusion with Intravitreal Aflibercept: 24-month Results from the AURIGA Observational Study.

INTRODUCTION: AURIGA is the largest real-world study to date to evaluate intravitreal aflibercept (IVT-AFL) treatment of diabetic macular edema or macular edema secondary to retinal vein occlusion (RVO) in routine clinical practice. Here, we report the 24-month outcomes in the RVO cohort from France, Germany, Italy, and Taiwan. METHODS: AURIGA (NCT03161912) was a prospective observational study. Eligible patients with RVO were enrolled for whom the decision to treat with IVT-AFL had already been made by the attending physician. Patients were treated with IVT-AFL for up to 24 months at physician discretion according to local practice. The primary endpoint was mean change in visual acuity (VA; Early Treatment Diabetic Retinopathy Study [ETDRS] letters) from baseline to month (M) 12. All statistical analyses were descriptive. RESULTS: In 554 treatment-naïve and 65 previously treated patients with RVO, the respective mean (95% confidence interval) change in VA from baseline was + 12.5 (10.8, 14.3) and + 7.9 (3.3, 12.6) letters by M12 and + 11.4 (9.4, 13.3) and + 4.4 (- 0.6, 9.5) letters by M24 (baseline mean ± standard deviation: 51.0 ± 21.9 and 51.9 ± 20.4 letters); 44.0% of treatment-naïve and 27.9% of previously treated patients reported ≥ 15-letter gains by M24. By M24, the mean change in central retinal thickness from baseline was - 247 (- 267, - 227) µm in treatment-naïve patients and - 147 (- 192, - 102) µm in previously treated patients. From baseline to M6, M12, and M24, treatment-naïve patients received a total of 4.0 ± 1.3, 5.5 ± 2.5, and 6.9 ± 4.2 injections, respectively, and previously treated patients received 3.8 ± 1.5, 5.0 ± 2.2, and 6.3 ± 3.7 injections, respectively. The safety profile of IVT-AFL was consistent with that of previous studies. CONCLUSIONS: In AURIGA, patients with RVO experienced clinically relevant functional and anatomic improvements following IVT-AFL treatment in routine clinical practice. These improvements were largely maintained in treatment-naïve patients over the 24-month study despite the decreasing treatment frequency, suggesting long-term durability of IVT-AFL treatment outcomes. Infographic available for this article. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03161912 (May 19, 2017). INFOGRAPHIC.