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Early poor outcomes of intraocular inflammation (IOI) after intravitreal brolucizumab (IVB) have negatively affected the use of brolucizumab in clinical routine. We wished to identify factors related to the treatment details of IOI involving the posterior segment resulting from IVB for neovascular AMD (nAMD), if these were reported in detail. Articles were retrieved from PubMed, Scopus, ClinicalTrials, and CENTRAL using the following search terms: AND AND . The risk of bias was rated using the JBI Critical Appraisal Tool. We included 31 reports (41 patients and 46 eyes). Patients were 75.9 ± 8.5 years, and 58.5% were female. IOI occurred 41.7 ± 37.5 (median 37.0) days after treatment initiation with 2.0 ± 1.3 (1-6) IVB injections. A mean change in visual acuity of -14.6 ± 21.0 (median -6.5) letters was reported. The mean time from first IOI signs to the initiation of any anti-inflammatory treatment was 3.3 ± 6.2 days, with 63% of the patients receiving systemic corticosteroids as standard treatment. Finally, a period effect was observed, with a change in visual acuity of -25.3 ± 27.1 and -2.6 ± 7.3 letters in the chronologically first and last third, respectively, of treated eyes (effect size: r = 0.71; p = 0.006). Functional outcomes markedly improved with increasing experience in managing IOI.

Anti-vascular endothelial growth factor (anti-VEGF) therapies have become the standard of care in the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME), resulting in a remarkable decrease in disease-related vision loss. However, the need for regular injections places a significant burden on patients, caregivers, and the healthcare system and improvements in vision may not be maintained long term. As a result of its drying potency and duration of action, brolucizumab, an intravitreal anti-VEGF therapy approved for the treatment of nAMD and DME, could decrease injection frequency for patients and provide an efficacious treatment; however, balancing its benefits and risks can be challenging. There have been reports of intraocular inflammation (IOI) in patients treated with brolucizumab, which, if left untreated, may result in severe vision loss. Recent evidence, however, indicates that early recognition of IOI and prompt and aggressive systemic corticosteroid treatment in response to posterior segment involvement can lead to favorable outcomes in these relatively rare but severe cases. A series of consensus meetings were conducted in 2022 between Swiss medical retina experts and diabetologists, discussing the current data for brolucizumab and exploring various challenges to its use, including the associated risk of IOI. The outcome is a collation of practical insights and guidance for ophthalmologists on the use of brolucizumab in patients with nAMD and DME, including patient selection and assessment, treatment regimen and monitoring, and the recognition and management of adverse events., (© 2023. The Author(s).)

Even in the absence of manifestations at birth, children with congenital toxoplasmosis (CT) may develop serious long-term sequelae later in life. This systematic review aims to present the current state of knowledge to base an informed decision on how to optimally manage these pregnancies and children. For this, a systematic literature search was performed on 28 July 2022 in PubMed, CENTRAL, ClinicalTrials.gov, Google Scholar and Scopus to identify all prospective and retrospective studies on congenital toxoplasmosis and its long-term outcomes that were evaluated by the authors. We included 31 research papers from several countries. Virulent parasite strains, low socioeconomic status and any delay of treatment seem to contribute to a worse outcome, whereas an early diagnosis of CT as a consequence of prenatal screening may be beneficial. The rate of ocular lesions in treated children increases over time to 30% in European and over 70% in South American children and can be considerably reduced by early treatment in the first year of life. After treatment, new neurological manifestations are not reported, while ocular recurrences are observed in more than 50% of patients, with a mild to moderate impact on quality of life in European cohorts when compared to a significantly reduced quality of life in the more severely affected South American children. Though CT is rare and less severe in Europe when compared with South America, antenatal screening is the only effective way to diagnose and treat affected individuals at the earliest possible time in order to reduce the burden of disease and achieve satisfying outcomes.

Introduction: The purpose was to compare two flexible regimens of intravitreal aflibercept (IVT-AFL) with fixed dosing every 8 weeks, beyond the first year of treatment, in patients with diabetic macular edema (DME). VIOLET was a 100-week, randomized, Phase IIIb, non-inferiority study in patients with center-involving DME previously treated with IVT-AFL for ≥ 1 year according to the European label., Methods: Patients received an initial dose of IVT-AFL at study baseline and were randomly assigned (1:1:1) to treat-and-extend (T&E), pro re nata (PRN), or fixed regimens. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline (randomization) to Week 52., Results: Full analysis set comprised 458 patients (baseline mean BCVA: 72.5, 71.0, and 72.7 letters in the T&E, PRN, and fixed-dose groups, respectively). Patients received a mean (min-max) of 10.0 (2-14; T&E), 11.5 (1-25; PRN), and 12.3 (3-13; fixed) injections over 100 weeks, with 13.3 (4-23), 25.0 (3-29), and 16.1 (5-25) clinic visits, respectively. At Week 52, mean (± standard deviation) BCVA changes from baseline were + 0.5 ± 6.7 (T&E), + 1.7 ± 6.8 (PRN), and + 0.4 ± 6.7 (fixed-dosing) letters (least squares mean difference [95% confidence interval]: T&E 0.01 [- 1.46, 1.47] and PRN 0.95 (- 0.52, 2.42) letters versus fixed dosing; p < 0.0001 for both non-inferiority tests [4-letter margin]). The IVT-AFL safety profile was consistent with previous studies., Conclusion: The treatment burden associated with intravitreal injections for DME is lowest with T&E regimens, but there are a range of flexible IVT-AFL dosing regimens, allowing physicians to adopt an individualized treatment plan., Trial Registration: ClinicalTrials.gov identifier: NCT02818998., (© 2022. The Author(s).)

Purpose: To compare the efficacy and safety of brolucizumab with aflibercept in patients with diabetic macular edema (DME)., Design: Double-masked, 100-week, multicenter, active-controlled, randomized trials., Methods: Subjects were randomized 1:1:1 to brolucizumab 3 mg/6 mg or aflibercept 2 mg in KESTREL (n = 566) or 1:1 to brolucizumab 6 mg or aflibercept 2 mg in KITE (n = 360). Brolucizumab groups received 5 loading doses every 6 weeks (q6w) followed by 12-week (q12w) dosing, with optional adjustment to every 8 weeks (q8w) if disease activity was identified at predefined assessment visits; aflibercept groups received 5 doses every 4 weeks (q4w) followed by fixed q8w dosing. The primary endpoint was best-corrected visual acuity (BCVA) change from baseline at Week 52; secondary endpoints included the proportion of subjects maintained on q12w dosing, change in Diabetic Retinopathy Severity Scale score, and anatomical and safety outcomes., Results: At Week 52, brolucizumab 6 mg was noninferior (NI margin 4 letters) to aflibercept in mean change in BCVA from baseline (KESTREL: +9.2 letters vs +10.5 letters; KITE: +10.6 letters vs +9.4 letters; P < .001), more subjects achieved central subfield thickness (CSFT) <280 µm, and fewer had persisting subretinal and/or intraretinal fluid vs aflibercept, with more than half of brolucizumab 6 mg subjects maintained on q12w dosing after loading. In KITE, brolucizumab 6 mg showed superior improvements in change of CSFT from baseline over Week 40 to Week 52 vs aflibercept (P = .001). The incidence of ocular serious adverse events was 3.7% (brolucizumab 3 mg), 1.1% (brolucizumab 6 mg), and 2.1% (aflibercept) in KESTREL; and 2.2% (brolucizumab 6 mg) and 1.7% (aflibercept) in KITE., Conclusion: Brolucizumab 6 mg showed robust visual gains and anatomical improvements with an overall favorable benefit/risk profile in patients with DME., (Copyright © 2022. Published by Elsevier Inc.)

Background: The recently introduced tumor therapies including immune checkpoint and BRAF/MEK inhibitors (ICI) have substantially contributed to survival and quality of life of the affected patients, but are associated with class-specific, non-toxic immune-related side effects including uveitis. This narrative review focusses to summarize the immune-related adverse event profile associated with the use of ICI., Methods: A literature search in PubMed, the publication database of the National Institute of Health in the USA (https://www.ncbi.nlm.nih.gov/pubmed) used the search terms "uveitis" AND "drug-induced" AND/OR "immune checkpoint inhibitor". All articles published in the last five years and the for the purpose of this review relevant cross references were evaluated., Results: A class-specific phenomenon of ICI and BRAF/MEK inhibitors is their capability to induce systemic and ocular autoimmunity. Ocular side effects are observed in up to 3% of patients and should be differentiated from toxic side effects, since this is not dose-dependent. Melanoma as underlying disease and Pembrolizumab as ICI significantly increase the risk. If timely recognized, systemic treatment with corticosteroids allows to preserve vision without cessation of the tumor treatment in more than 90% of these potentially life-threatening instances., Conclusion: Given their impact onto the survival of cancer and namely melanoma patients, ICI and BRAF/MEK inhibitors are increasingly used alone and in combination, which enhances their inherent risk of developing drug-induced ocular autoimmunity. Favorable functional outcomes are closely linked to early recognition and aggressive treatment of these complications considering the fact that these immune-related adverse events affect multiple organ systems and have an untreated lethality of up to 3%., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: The continuation of anti-vascular endothelial growth factor (anti-VEGF) treatment after achieving stability in patients with neovascular age-related macular degeneration has generally been advocated. In our own patients, we thought to assess whether continued anti-VEGF treatment is capable of preventing recurrences., Methods: In this retrospective observational case series, patients with stable disease either opted to continue treatment every 12-14 weeks (Group 1) or stopped treatment with subsequent follow-up visits every 8-12 weeks (Group 2)., Results: Of the 103 eyes of 103 patients achieving stability, 49 eyes continued treatment (Group 1), whereas treatment was stopped in 54 eyes undergoing regular follow-up (Group 2). Recurrent disease was observed in 21 (42.9%) and 33 (61.1%) cases in Group 1 and Group 2, respectively (p = 0.08). Time between achieving stable disease and recurrence was comparable between Group 1 and Group 2 (11.1 ± 8.2 months vs. 9.2 ± 6.7 months; p = 0.43). The number of visits between achieving stability and disease recurrence was similar, but not the number of injections (3.5 ± 2.0 vs. 0.2 ± 0.4; p < 0.001)., Conclusions: Continuing anti-VEGF therapy after achieving functional and morphological stability every 12-14 weeks does not prevent recurrences. Patients deserve to be informed of a potential lifetime risk of recurrences, even under continued therapy., (© 2021. The Author(s).)

Purpose: To assess disease stability (absence of intra- and/or subretinal fluid) and the portion of eyes being capable to extend their treatment interval to ≥ 12 weeks in exudative age-related macular degeneration (AMD)., Methods: A systematic literature search was performed in NCBI, PubMed, CENTRAL, and ClinicalTrials.gov to identify clinical studies reporting treatment outcomes for ranibizumab, aflibercept, and brolucizumab in exudative AMD under a treat-and-extend protocol and a follow-up of ≥ 12 months. Weighted mean differences and subgroup comparisons were used to integrate the different studies., Results: This meta-analysis refers to 29 published series, including 27 independent samples and 5629 patients. In the pooled group, disease stability was reported in 62.9% and 56.0%, respectively, after 12 and 24 months of treatment, whereas treatment intervals were extended to ≥ 12 weeks in 37.7% and 42.6%, respectively. Ranibizumab, aflibercept, and brolucizumab differed regarding their potential to achieve disease stability (56.3%, 64.5%, and 71.5% after 12, and 50.0%, 52.7% and 75.7% after 24 months; p = < 0.001) and to allow an interval extension to ≥ 12 weeks (28.6%, 34.2%, and 53.3% after 12, and 34.2%, 47.7%, and 41.7% after 24 months; p = < 0.001)., Conclusion: The portion of eyes achieving disease stability regressed in the second year, whereas the portion of eyes under a ≥ 12-week interval increased. This discrepancy may reflect the challenges in balancing between under-treatment and a reduced treatment burden., (© 2021. The Author(s).)

Purpose : To standardize a nomenclature system for defining clinical phenotypes, and outcome measures for reporting clinical and research data in patients with ocular tuberculosis (OTB). Methods : Uveitis experts initially administered and further deliberated the survey in an open meeting to determine and propose the preferred nomenclature for terms related to the OTB, terms describing the clinical phenotypes and treatment and reporting outcomes. Results : The group of experts reached a consensus on terming uveitis attributable to tuberculosis (TB) as tubercular uveitis. The working group introduced a SUN-compatible nomenclature that also defines disease "remission" and "cure", both of which are relevant for reporting treatment outcomes. Conclusion : A consensus nomenclature system has been adopted by a large group of international uveitis experts for OTB. The working group recommends the use of standardized nomenclature to prevent ambiguity in communication and to achieve the goal of spreading awareness of this blinding uveitis entity.

Background: Minimally invasive transconjunctival sutureless vitrectomy (MIVS) has evolved into the standard of care, smaller incisions thought to result in lower ocular surface trauma and shorter times to recovery. The currently most relevant limitations in macular surgery may be light intensity and 27G instrument stability. Therefore, we thought to compare standard 23 and 27G vitrectomy with a hybrid technique using one 23G and two 27G ports regarding surgical times and short-term outcomes., Methods: This retrospective comparison included 90 single-center consecutive cases of eyes undergoing elective micro-invasive vitrectomy for epiretinal membranes or idiopathic macular holes between October 2017 and June 2018. The main criteria for the comparison were total surgical time as primary outcome parameter and treatment-demanding intra- and postoperative complications along with recovery of best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from prior to surgery to 1 month thereafter as secondary parameters as independent parameters for the recovery from the pre-existing pathology and the surgical trauma., Results: Surgical times were shorter with 23G and 23/27G compared to 27G (23G: 38.4±13.1; 27G: 48.1±15.3; 23/27G: 34.9±9 mins; p =0.0005) with no differences in BCVA and CRT outcomes. Switching from 27G to a larger port size was not necessary in any instance. Cryotherapy was applied in 15%, 30%, and 22.5% to suspected retinal pathologies, beyond these, in 5%, 0%, and 7.5% for retinal tears. Four postoperative retinal detachments occurred (4.4%), one in the 23G and three in the 23/27G group requiring re-vitrectomy., Conclusion: In this exploratory case series, 23/27G hybrid vitrectomy, combining the advantages of 23G and 27G techniques, resulted in shorter surgical times without evident disadvantages. The combination with cataract surgery was unproblematic., Competing Interests: JGG is an adviser for several pharmaceutical companies (Alcon, Allergan, Bayer, Novartis) and participates in a number of international multicenter clinical studies in the fields of AMD and diabetic retinopathy that have received sponsors by industry partners (Novartis, Bayer). These activities had no bearing on the study that gave rise to the submitted article, for which JGG received neither direct nor indirect financial support; nor has he conflicts of interest with any of the presented data. The remaining authors report no potential conflicts of interest., (© 2020 Garweg et al.)

Background: To evaluate the efficacy and safety of two individualized ranibizumab retreatment schemes in neovascular age-related macular degeneration., Methods: Patients (N = 671) were randomized (1:1) to receive three initial monthly ranibizumab 0.5 mg injections, then retreatment guided by either best-corrected visual acuity (BCVA) loss (Group I) or BCVA loss and/or signs of disease activity on optical coherence tomography (OCT; Group II). The study was terminated prematurely and the decision to discontinue the study was made by the sponsor. Efficacy analyses were performed on patients who completed 12 months of the originally planned 24-month study. Safety analyses are presented for all safety analyzable patients., Results: Of 671 randomized patients, 305 completed 12 months of the study. For the 12-month completers, baseline mean (standard deviation) BCVA and reading-center evaluated central subfield thickness (CSFT) were comparable [Group I: 60.9 (13.10) letters and 517.7(201.79) μm; Group II: 60.2 (12.21) letters and 515.3 (198.37) μm]. The change from baseline at Month 12 in BCVA was 6.7 (13.48) letters in Group I and 8.3 (13.53) letters in Group II and the change in CSFT was - 161.3 (163.48) μm and - 175.3 (170.45) μm, respectively. The mean number of ranibizumab injections was 8.2 in Group I and 8.4 in Group II., Conclusion: Ranibizumab treatment resulted in visual and anatomic gains at 12 months for both retreatment strategies, with a trend in favor of OCT-guided vs BCVA loss guided retreatment. No new safety signals were seen., Trial Registration: www.ClinicalTrials.gov (NCT01780935). Registered 31 January 2013.

Background: Modern treatment of uveitis aims at a complete control of inflammatory activity, preservation of visual function and the prevention of secondary organ damage as a consequence of the underlying inflammatory disease and its treatment., Objective: This article gives an update about the strategies of pharmacological and surgical options for uveitis., Material and Methods: The outcomes reported here are based on a PubMed search using the terms <"uveitis" AND "therapy"> and <"uveitis" AND "surgery" OR "surgical treatment">. All prospective studies and case series with more than 20 cases as well as review articles from the last 5 years along with cited cross-references were evaluated., Results: Local and systemic corticosteroids form the foundation of treatment after exclusion of an infectious etiology. If uveitis activity is not controlled within 6 weeks or if the daily corticosteroid dosage is unacceptably high, a treatment escalation using immunomodulatory drugs is required. If a complete control of inflammatory activity is not achieved, in a third phase treatment is supplemented by antibody-based treatment or cytokines, so-called biologics, with the aim of complete long-term freedom from disease without local or systemic steroid treatment. This target is achieved in 65-80% and guarantees long-term functional stability and anatomical integrity. Early treatment escalation in cases of persisting or recurrent activity as a rule prevents new secondary organ damage. Surgical options are utilized for diagnostic purposes, the administration of intravitreal drugs and for treatment of secondary complications., Conclusion: Just like the majority of immunological diseases, uveitis is a chronic disease requiring long-term and possibly lifelong treatment and remission (absence of inflammation without treatment) is achieved in only <20%. Surgical interventions can be performed with a good prognosis, if the optic nerve head and macula are not involved. They have a substantially lower complication rate when freedom from symptoms exists preoperatively for at least 3 months.

Purpose: To review published evidence for a treatment interval extension to ≥12-weeks in neovascular macular degeneration treated with intravitreal Aflibercept., Methods: A systematic search was performed in the NCBI/PubMed database to identify pro- and retrospective studies retrieved by the key terms or and or AND AND and included all papers that used a treat-and-extend (T&E) protocol including a loading phase of 3 intravitreal anti-VEGF injections and a minimal follow-up of 2 years. Disease stability was defined as the absence of any intraocular and absence or stability of subretinal fluid and pigment-epithelial detachment., Results: Four studies were identified that reported information pertaining to disease stability or treatment extension beyond 12 weeks under intravitreal Aflibercept therapy including 1,102 eyes in total. Following a T&E protocol, a mean of 62.9% achieved disease stability and a 6.9 letter gain based on 11.9 injections over 24 months of Aflibercept treatment. As much as 43.0% of all eyes or 64.1% of the eyes with stable disease were maintained on ≥12-weekly injection intervals., Conclusions: A consequent treatment with a null tolerance for intraretinal fluid is prerequisite to induce stability and maintain visual gain after the loading phase. Using Aflibercept in a T&E protocol, disease stability and interval extension to ≥12 weeks were reported in 43% of the eyes by end of the second year with less injections, but similar results as under fix dosing. A lower treatment burden strongly argues for an individualized proactive treatment regimen., Competing Interests: JGG acts as an advisor for several pharmaceutical companies (AbbVie, Alcon, Allergan, Bayer, Novartis) and contributes to several international industry-sponsored clinical studies. The underlying manuscript is independent of these activities. The author received no direct or indirect support for this study nor has he conflicting interests with the data that are presented herein. The author reports no other conflicts of interest in this work.

Purpose: To compare the cytokine profiles of phakic (p) and pseudophakic (ps) eyes with primary rhegmatogenous retinal detachment (RD) to eyes with macular holes (MH) and to identify differences in the specific cytokine profiles., Methods: Aqueous humour (AH) and vitreous fluid (VF) were obtained from patients with primary RD without proliferative vitreoretinopathy undergoing vitrectomy. AH and VF of patients with macular holes (MH) served as controls. Forty-three different cytokines were quantified using multiplex cytokine analysis. Intergroup and intragroup comparisons were performed. To control for multiple comparisons, Holm's correction was applied., Results: VF and AH samples of 71 eyes with RD (pRD N = 38; psRD N = 33) and 26 eyes with MH were included. Cytokine levels in psRD and pRD were similar (none with >10-fold difference). The levels of 39 of 43 cytokines in the VF were significantly higher in eyes with RD than in those with MH (>10-fold: CXLC5, CCL26, CCL1, IL-6, CXCL11, CCL7, CCL13, MIG/CXCL9, CCL19 and TGF-β1). In the AH, 23 of 43 cytokines were significantly higher compared to MH (>10-fold: CXCL5, IL-4, IL-6, IL-8/CXCL8 and CCL7)., Conclusion: A complex, but nonspecific cytokine environmental response seems to initiate immunological and profibrotic processes following RD. Relevant differences in the cytokine profiles of eyes with pRD and psRD were not identified, whereas cytokine differences between AH and VF in RD could be explained by upregulation in the vitreous, a higher turn around in the anterior chamber, or differences in inflammatory cascades in both compartments., (© 2018 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To report outcomes in patients with neovascular age-related macular degeneration (nAMD) after treatment with aflibercept for up to 4 years using a treat-and-extend (T&E) regimen., Design: Observational study., Participants: Patients with newly diagnosed nAMD treated with aflibercept in a T&E protocol., Methods: Subjects received 3 injections of aflibercept at monthly intervals followed by a T&E protocol for at least 12 months. At each clinical visit after the loading phase, OCT and best-corrected visual acuity (BCVA) testing were performed to monitor disease activity., Main Outcome Measures: Change in BCVA over time, number of injections and visits per year, and percentage of patients reaching a treatment interval of ≥12 weeks., Results: Of 231 consecutive eyes (231 patients) with a mean follow-up time of 2.9 (1-5.5) years, 173 were followed up for ≥2 years, 112 were followed up for ≥3 years, and 62 were followed up for ≥4 years. Mean BCVA increased from 59.8 letters (20/60) at diagnosis to 65.8 letters (20/50) after the loading phase (+6.0 letters; standard deviation [SD], 11.1) and to 65.5 letters at 12 months (+5.7 letters; [SD], 17). After 4 years of treatment, mean BCVA was maintained insignificantly better than baseline (63.4 letters, +3.6 letters gain, SD, 20.6; P > 0.05). To achieve this, a mean of 7.7 (±1.2) injections and 4.4 (±1.6) clinic visits in the first year and 4.4 (±1.9) injections and 4.3 (±1.3) clinical visits per year thereafter were required. By 2 years of follow-up, 46.9% of patients reached a treatment interval of ≥12 weeks., Conclusions: By using a T&E regimen, patients with nAMD maintained stable visual function over 4 years in a real-world setting with a reasonable treatment burden., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the impact of inner limiting membrane peeling during vitrectomy for macula-involving retinal detachment on best-corrected visual acuity (VA)., Methods: Retrospective analysis of 89 eyes with primary macula-involving retinal detachment, which was undergoing vitrectomy, endolaser, retinotomy, endodrainage, and SF6 tamponade. Membrane-blue-assisted membrane peeling had been performed in 61 of the eyes (Group 1) but not in the other 28 (Group 2), which served as controls., Results: Age, lens status, and incidence of proliferative vitreoretinopathy 26.2% versus 39.3%; P = 0.23 in the 2 groups were comparable. The preoperative visual acuity (Early Treatment Diabetic Retinopathy Study letters) was 25.7 ± 27.9 in Group 1 and 28.8 ± 29.9 in Group 2 (P = 0.47). After surgery, these rose from 62.3 ± 30.5 (Group 1) and 34.2 ± 35.8 (Group 2) after 1 week (P = 0.090), through 83.1 ± 8.0 and 57.2 ± 32.4 at 1 month (P = 0.0005), to 92.1 ± 4.5 and 74.4 ± 23.1 Early Treatment Diabetic Retinopathy Study letters after 6 months (P = 0.0005). More than 6-month incidences of proliferative vitreoretinopathy (13.1% vs. 28.6%; P = 0.13) were similar, whereas the redetachment rate (9.8% vs. 32.1%; P = 0.014), the incidence of secondary epiretinal membranes (1.6% vs. 35.7%; P = 0.0005), and the revitrectomy rate were lower in group 1 (9.8% vs. 53.6%; P = 0.0005)., Conclusion: Inner limiting membrane peeling during vitrectomy for macula-involving retinal detachment may substantially contribute to the visual recovery, reducing the incidence of secondary epiretinal membrane formation.

Acute posterior and panuveitis mostly affect younger patients and affect both eyes in more than half of cases. Because of the severe consequences in the clinical course, rapid and broad differential diagnosis are critical steps. Permanent loss of vision after a delay in starting therapy and the initiation of ineffective treatment are both serious risks. The initial diagnostic classification is based on clinical presentation (anatomical localisation and type of inflammation) and clinical course and, secondarily, on the response to acute therapy. The aetiology is acute in as many as one third of cases. The most frequent acute posterior uveitis in immunocompetent persons is acute viral retinal necrosis. It is difficult to distinguish this clinically from Behçet uveitis, as long as there are no systemic manifestations. In patients with disease threatening the macula, high dose steroid therapy must be started no later than 24 hours after the start of antiviral and anti-parasitic acute therapy. Thus, misdiagnosis has therapeutic consequences. Moreover, the prognosis is favourably affected by aggressive treatment of acute posterior uveitis. Any delay in starting therapy increases infectious and inflammatory tissue damage, and increases the risk of involvement of the other eye and of other organs. On the other hand, the use of high doses of steroids, immunosuppressives and biological agents can lead to uncontrolled proliferation of the pathogen and relapses., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: Real-life studies on long-term functional outcome of anti-VEGF treatment for wet age-related macular degeneration (wAMD) are limited. We therefore assessed the 10-year outcomes in our patients., Methods: In this retrospective study, all patients with newly diagnosed wAMD that had received minimally three intravitreal injections between 2007 and 2012 and a follow-up of ≥48 months were included. Primary outcome measure was the evolution of best-corrected visual acuity (BCVA) over time. For qualitative, quantitative and longitudinal data, Pearson's chi 2 test, the Mann-Whitney U-test and Wilcoxon's signed-rank test were applied at a significance level of p < 0.05., Results: Of 267 eyes (219 patients) with newly diagnosed wAMD treated during this period, 104 eyes (104 patients) had been followed for at least 48 months and were included. Fifty-nine eyes (57.8%) after 7 years were still under active treatment, 29 eyes (25.0%) had interrupted treatment [mean follow-up 7.5 years (4.0-10.1; SD 1.6)], whereas 16 patients had died. BCVA stabilized at -7.3 to -11.9 letters after 3-10 years of follow-up with a mean of 2.8 injections (median; 3.0, SD 1.0; 1-5) and 5.1 visits per year. In two thirds of eyes, treatment was switched to aflibercept or corticosteroid combinations without bearing on functional outcomes. Thirty-seven percent (37%) of eyes maintained driving vision for up to 10 years., Conclusions: Beyond 3 years of treatment, functional stability was maintained for up to 10 years. Further improvement of long-term outcomes might have required a more intensive treatment in the early phase.

Background: Pseudoexfoliation syndrome (PEXS) may go along with capsular bag shrinkage and luxation. In the present study, we focus on an association of isoforms of TGF-β with capsular bag luxation., Methods: Aqueous humor was collected intraoperatively from 20 healthy controls and from 73 otherwise healthy patients with PEXS [PEXS without complications (PEX, n = 33), late PEXS with glaucoma (PEXG, n = 30) and with IOL and capsular bag luxation (PEXL, n = 10)]. The concentrations of TGF-β1, TGF-β2 and TGF-β3 were compared using the Bio-Plex® multiplex beads system based on the non-parametric Kruskal-Wallis H test (p < 0.01)., Results: Concentrations of TGF-β 1, TGF-β 2 and TGF-β 3 were higher in the sub-groups PEX and PEXG than in controls (TGF-β 1; p = 0.009 and 0.0005; TGF-β 2; p = 0.002 and 0.005 and TGF-β 3; 0.0005 and 0.0005; respectively), whereas for TGF β2, no significant difference between controls and PEXL was revealed (p = 1.0). TGF-β2 concentrations were elevated in a similar degree in early PEX and PEXG, but not in PEXL compared to controls (p = 0.002). The concentrations of of TGF-β 1 and TGF-β 3 increased in parallel with the progression of disease. The levels of TGF-β 3, however, did not attain pathophysiological levels (>100 pg/ml) in any group., Conclusions: A stage-dependent increase in the concentrations of TGF-β1 and TGF-β3, but not of TGF-β2, accords to the shrinkage of the capsular bag. This could increase the tension on the zonular fibers and contribute to luxation of the capsular bag.

Objective: In many case series, anatomical but not functional improvements have been documented after a switch in therapy from ranibizumab to aflibercept. We wished to compare the outcomes of eyes that had undergone a switch in therapy from ranibizumab to aflibercept because of a high treatment demand or for other reasons., Design: Retrospective comparative case series., Participants: Patients (≥50 years of age) undergoing treatment for neovascular age-related macular degeneration in a routine clinical setting., Methods: Eyes monitored for ≥10 months after switch in intravitreal therapy from ranibizumab to aflibercept were allocated to one of 2 groups: eyes with high treatment demand because of insufficient response to ranibizumab (persisting intraretinal fluid or injection frequency of ≤6 weeks [group 1, n = 34]) and eyes in which the switch had been instigated for other reasons (n = 94)., Main Outcome Measures: Annual number of injections before and after the switch in therapy., Results: Patients were of comparable ages at the time of diagnosis. The follow-up time before switching, but not thereafter, was shorter in group 1 than in group 2 (P = 0.001). Visual acuity and central retinal thickness did not change appreciably during the follow-up period. The annual number of injections was higher under ranibizumab than under aflibercept in group 1 (9.1±2.2 injections vs. 5.7±2.2 injections; P = 0.0005) but not in group 2 (4.9±2.0 injections vs. 4.6±1.8 injections; P = 0.24). After the switch from ranibizumab to aflibercept, the eyes in group 1 required more injections than did those in group 2 (P = 0.007). The time that elapsed to a reinjection differed between the 2 groups under treatment with ranibizumab (P = 0.0005) as well as under that with aflibercept (P = 0.007)., Conclusion: After the switch in therapy from ranibizumab to aflibercept, visual acuity remained stable for >12 months in both groups. Nevertheless, eyes that required frequent reinjections under ranibizumab also had a higher treatment demand under aflibercept., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To review published data pertaining to the clinical experience with a dexamethasone intravitreal implant (Ozurdex®) with a view to establishing a clinically based therapeutic regime., Methods: A PubMed search using the MeSH terms "retinal vein occlusion" and either "pathophysiology" or "dexamethasone intravitreal implant" was undertaken for manuscripts published until August 2015. The analysis included studies involving minimally 15 patients under a prospective design or 30 under a retrospective design, a minimal follow up of 6 months, and at least 2 intravitreal Ozurdex® injections per eye., Results: In the vast majority of eyes, satisfactory outcomes were achieved with retreatment intervals of between 3 and 5 months. Initial evidence indicates a similar efficacy compared to anti-VEGF therapies as a first-line treatment. Safety concerns associated with the long-term and repeated use of Ozurdex® are not borne out by clinical findings: its implantation is not associated with a sustained increase in intraocular pressure (IOP) over time or with the number of applications., Conclusion: Compared with anti-VEGF therapies, the burden of retreatment is reduced. In patients with chronic macular edema not responsive to repetitive anti-VEGF therapies, the outcome after dexamethasone implant treatment is encouraging. However, these results are achieved at the expense of side effects typically associated with steroids: in up to 20 % of the Ozurdex®-treated patients, an elevation in IOP, which could be medically controlled in the majority of cases, and cataract formation or progression was observed.

Because proliferative vitreoretinopathy cannot be effectively treated, its prevention is indispensable for the success of surgery for retinal detachment. The elaboration of preventive and therapeutic strategies depends upon the identification of patients who are genetically predisposed to develop the disease, as well as upon an understanding of the biological process involved and the role of local factors, such as the status of the uveovascular barrier. Detachment of the retina or vitreous activates glia to release cytokines and ATP, which not only protect the neuroretina but also promote inflammation, retinal ischemia, cell proliferation, and tissue remodeling. The vitreal microenvironment favors cellular de-differentiation and proliferation of cells with nonspecific nutritional requirements. This may render a pharmacological inhibition of their growth difficult without causing damage to the pharmacologically vulnerable neuroretina. Moreover, reattachment of the retina relies upon the local induction of a controlled wound-healing response involving macrophages and proliferating glia. Hence, the functional outcome of proliferative vitreoretinopathy will be determined by the equilibrium established between protective and destructive repair mechanisms, which will be influenced by the location and the degree of damage to the photoreceptor cells that is induced by peri-retinal gliosis., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Viral infections of Herpes origin are the most commonly encountered ones in man. The most important member of this family is the Herpes simplex virus (HSV), two varieties of which are known to exist: HSV-1 affects predominantly the upper half of the body, whereas HSV-2 is associated mainly with diseases of the urogenital tract. In the immunocompetent host, viral replication is usually confined to cutaneous and mucocutaneous sites, invasion of subcutaneous tissues being impeded by an early onset of non-specific defence mechanisms. These are rapidly complemented by the specific, mainly cellular, immune response., Patients: Epithelial dendritic keratitis is the first symptomatic clinical finding, and after several recurrences, the corneal stroma may become involved. This condition of herpetic stromal keratitis (HSK), which, in contrast to the epithelial one, is believed to be directed by a predominantly immunopathological process, is one of the leading causes of infectious blindness in developed countries., Results: The mechanisms underlying HSK, and the establishment of viral latency and reactivation are poorly understood. But on the basis of studies with mice as well as clinical immunohistological observations, evidence is now accumulating in support of a cell-mediated mechanism being responsible for corneal destruction., Conclusion: Our present knowledge of the pathogenesis of herpetic keratitis is incomplete. The different pathophysiological aspects reflecting our current understanding, such as that of a virally induced autoimmune disease, form the basis of accepted clinical treatment concepts.