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Juliana Wons,1 Isabel B Pfister,1,2 Stefano Anastasi,1 Sonja Steinhauer,1 Sophie-Alexia Niderprim,3 Justus G Garweg1,2,4 1Clinic for Vitreoretinal Disease, Berner Augenklinik, Bern, Switzerland; 2Swiss Eye Institute, Rotkreuz, Switzerland; 3Ophthalmology Private Practice, Langnau, Switzerland; 4Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, SwitzerlandCorrespondence: Justus G Garweg, Berner Augenklinik, Bremgartenstrasse 119, Bern, CH-3012, Switzerland, Tel +41 31 311 12 22, Fax +41 31 311 14 33, Email Justus.garweg@swiss-eye-institute.comPurpose: To compare the predictive value of macular perimetry and microperimetry for visual outcomes after vitrectomy with internal limiting membrane (ILM) peeling in full-thickness macular holes (MH).Methods: This retrospective, non-randomized case series refers to 100 eyes undergoing vitrectomy with ILM peeling. Best-corrected visual acuity (BCVA), standard 12° perimetry and microperimetry were perioperatively recorded. A possible predictive value of the preoperative findings on postoperative visual function (PVF) was assessed.Results: Independent of the preoperative minimal MH size (range: 55– 752 μm), all 100 MHs were closed. BCVA improved from 56.3 ± 12.8 to 74.8 ± 9.2 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters after six months and retinal fixation stability enhanced. We found a positive correlation between BCVA and macular sensitivity 6 months postoperatively in microperimetry (r = 0.48, p < 0.010) and 12° perimetry (r = 0.45, p < 0.014), as well as with mean defect (r = 0.48, p < 0.01 and r = 0.44, p < 0.017, respectively). A correlation between preoperative visual function indices and PVF was not established.Conclusion: Microperimetry and standard perimetry are equally suitable for describing perioperative retinal function in idiopathic MH. While the indices of both methods correlate comparably well with BCVA, they cannot predict PVF. This may be partially explained by the area covered by perimetry, compared to which the size of the MH is of inferior relevance.Keywords: central visual field, idiopathic full-thickness macular hole, microperimetry, peeling of the internal limiting membrane, vitrectomy

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)

BACKGROUND Periorbital necrotizing fasciitis (PNF) is a rare complication of bacterial infection, associated with irreversible inflammatory destruction of soft tissues like subcutaneous tissue and superficial fascia. PNF can cause visual loss, septic shock and death within hours to days. Since the infection progresses rapidly from a local disease to septic shock, prompt identification and decisive interventions are mandatory. AIM Considering pathophysiology, differential diagnosis, and treatment options, we report a case of PNF and its outcome.Methods: A 69 years old male with febrile periorbital swelling had been diagnosed with bilateral PNF, caused by dual infection with Streptococcus pyogenes (S. pyogenes) and Staphylococcus aureus (S. aureus) based on conjunctival swabs. RESULTS The superantigens produced by S. pyogenes have been identified as key to the rapid dissemination of infection and severity of systemic manifestations. CONCLUSIONS A combination of intravenous antibiotics and regular surgical debridements resulted in a beneficial outcome in our patient.

Zusammenfassung Hintergrund Immun-Checkpoint- und BRAF-/MEK-Inhibitoren (ICI) haben eine zentrale Stellung in der Krebstherapie eingenommen, da sie eine erhebliche Lebensverlängerung bei einer guten Verträglichkeit und Lebensqualität bewirken. Sie sind jedoch mit stoffklassenspezifischen, nicht toxischen immunologischen Nebenwirkungen, darunter auch Entstehung einer Uveitis, behaftet. In dieser Übersicht soll der aktuelle Kenntnisstand zu Wirkprinzip und systemischen und okulären Nebenwirkungen der ICI dargestellt werden. Methoden Dieser Übersicht liegt eine Literatursuche in PubMed, der Datenbank des National Institute of Health der USA (https://www.ncbi.nlm.nih.gov/pubmed) mit den Stichworten „uveitis“ AND „drug-induced“ AND/OR „immune checkpoint inhibitor“ zugrunde. Alle relevant erscheinenden Publikationen der letzten 5 Jahre wurden zusammen mit den darin zitierten Querverweisen ausgewertet. Ergebnisse Ein klassenspezifisches Phänomen der sonst gut verträglichen ICI ist ihre Fähigkeit, eine systemische und okuläre Autoimmunität auszulösen. Diese unterscheidet sich von toxischen Nebenwirkungen durch ihre Dosisunabhängigkeit. Okuläre Nebenwirkungen treten bei 3% der Patienten auf, wobei ein Melanom als Grunderkrankung und eine Therapie mit Pembrolizumab das Risiko um ein Mehrfaches erhöhen. Eine frühe Diagnose und systemische Steroidtherapie dieser potenziell lebensbedrohlichen Nebenwirkung erlauben in > 90% die Erhaltung der Sehfunktion und Lebensqualität, ohne die ICI-Therapie abzusetzen. Schlussfolgerung Das therapeutische Ansprechen von Malignomen auf ICI bezüglich des Überlebens und der Verträglichkeit, insbesondere bei Melanomen, lässt eine zunehmende Anwendung von ICI auch in Therapiekombinationen und damit eine Zunahme der immunologischen Komplikationen im klinischen Alltag erwarten. In Anbetracht einer Mortalität von unbehandelt bis zu 3% infolge immunvermittelter Nebenwirkungen an multiplen Organen ist eine rasche interdisziplinäre Abklärung und rechtzeitige aggressive Behandlung zwingend, führt aber meist auch zu erfreulichen funktionellen Ergebnissen.

PURPOSE To compare the postoperative intraocular pressure (IOP) after ab interno trabeculectomy (AIT; trabectome surgery) alone or combined with cyclodialysis ab interno (AITC). PATIENTS AND METHODS Forty-three eyes with insufficiently controlled open-angle glaucoma were included in this consecutive case series. All eyes received AIT, combined with phacoemulsification and IOL-implantation in phakic instances, with or without additional cyclodialysis ab interno. Postoperative visual acuity, IOP, number of IOP-lowering medications and complications were registered over 12 months. RESULTS A total of 19 eyes (14 patients) received AIT and 24 (19 patients) received AITC. Both groups were comparable for baseline IOP (AIT: 19.7 ± 8.2 mmHg; AITC: 19.4 ± 6.8 mmHg; p = 0.96), there was a comparable IOP reduction after 6 months (AIT: - 3.8 ± 12.3, median (interquartile range (IQR)): - 3.8 (- 7.8-4.8) mmHg; AITC: - 4.9 ± 8.3, median (IQR): - 2.0 (- 10.8-2.0) mmHg; p = 0.95) and 12 months (AIT: - 4.3 ± 6.6, median (IQR): - 4.0 (- 8.0 to - 1.0) mmHg; AITC: - 3.7 ± 6.7, median (IQR): - 1.5 (- 5.5 to - 0.5) mmHg; p = 0.49). While final visual acuity was similar between the groups, they differed regarding topical IOP-lowering medications (baseline: AIT 2.9 ± 1.2 and AITC 2.9 ± 1.2; 1 year after surgery: AIT 2.6 ± 1.5 (p = 0.16) and AITC 1.3 ± 1.3; p

Finerenone is a potent and selective mineralocorticoid receptor (MR) antagonist that slowed progression of CKD and reduced risk of CV outcomes vs. placebo in patients with CKD and T2D in the FIDELIO-DKD and FIGARO-DKD phase 3 trials. MR overactivation is involved in DR pathogenesis. To evaluate potential benefits of oral finerenone on progression of DR, two studies of identical observational design (ReFineDR and DeFineDR) retrospectively collected data from patients with DR in FIDELIO-DKD/FIGARO-DKD at selected centers. Eligible patients had a routine ophthalmological examination showing NPDR in ≥1 eye performed 6 months prior to 1 month post-randomization in FIDELIO-DKD/FIGARO-DKD, and ≥1 subsequent ophthalmological assessment. Patients with advanced DR were excluded; inclusion was blinded to FIDELIO-DKD/FIGARO-DKD treatment assignment. Primary endpoint was occurrence of vision-threatening events (ASN, DME or PDR) at 2 years. Overall, 134 patients received finerenone and 1received placebo, of whom 68.7% and 71.8% had mild/moderate NPDR, 3.0% and 10.0% had severe NPDR, 27.6% and 15.5% had NPDR of unknown severity and 70.1% and 64.5% had HbA1c >7.5%, at baseline (mean HbA1c 8.25 [SD 1.41] and 8.18 [SD 1.34]) . At 2 years, 5 (3.7%) and 7 (6.4%) patients in the finerenone and placebo groups had a vision-threatening event in ≥1 eye (difference -0.026, 95% CI -0.082 to 0.029, p=0.3550) . The number of events increased after 2 years, with trends in Kaplan-Meier estimated cumulative incidence probabilities in favor of finerenone at 30 and 36 months (post hoc) . Results were generally consistent across components of the primary endpoint and subgroups with baseline HbA1c ≤ and >7.5%, UACR 30- Disclosure P.Rossing: Consultant; Astellas Pharma Inc., AstraZeneca, Bayer AG, Gilead Sciences, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Speaker's Bureau; Eli Lilly and Company. D.Finis: Employee; Bayer AG. S.Leal: Employee; Bayer Consumer Care AG. T.Schmelter: Employee; Bayer AG, Stock/Shareholder; Bayer AG. G.Bakris: Consultant; Alnylam Pharmaceuticals, Inc., AstraZeneca, DiaMedica Therapeutics, Inc., Horizon Therapeutics plc, Ionis Pharmaceuticals, Merck & Co., Inc., Other Relationship; Novo Nordisk. S.Anker: Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Novartis AG, Novo Nordisk, Vifor Pharma Management Ltd., Research Support; Abbott. J.G.Garweg: Advisory Panel; AbbVie Inc., Research Support; Roche Pharmaceuticals, Speaker's Bureau; Bayer AG, Novartis AG. T.Osonoi: Research Support; Bayer AG, Eli Lilly and Company, Gilead Sciences, Inc., Kowa Company, Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Speaker's Bureau; Novo Nordisk. B.Pitt: Advisory Panel; Merck & Co., Inc., Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Vifor Pharma Management Ltd. S.Rosas: Advisory Panel; AstraZeneca, Teladoc Health, Other Relationship; Bayer AG, Research Support; AstraZeneca, Bayer AG. L.M.Ruilope: Consultant; Bayer AG. D.Zhu: n/a. M.Brinker: Employee; Bayer AG.

Objective To assess the long-term visual outcomes in eyes with symptomatic diabetic macular oedema (DME) under intravitreal treatment (IVT) in a clinical routine setting. Methods Patients with newly diagnosed DME were included in this retrospective study if they had received at least three IVTs and a follow-up period ≥ 2 years. Due to altered treatment patterns since the approval of ranibizumab for DME in 2012, patients were subdivided according to their first IVT before 2013 (group 1) or thereafter (group 2). The primary outcome measure was the evolution of best-corrected visual acuity (BCVA) over time. Results Of 217 eyes (191 patients) with DME, 151 eyes (117 patients) fulfilled the inclusion criteria (63 eyes in the first period, 88 in the second period). Mean follow-up time was 7.9 ± 3.1 (group 1) and 4.1 ± 1.4 years (group 2; p p = 0.44), but not thereafter (after 2 years in group 1: + 4.4 ± 15.0, group 2: + 8.3 ± 13.0 ETDRS letters; p = 0.038). During the first year, group 1 patients received less clinical examinations (group 1: 6.6 ± 3.3, group 2: 7.5 ± 2.1; p = 0.007) and less injections (group 1: 3.6 ± 2.7, group 2: 6.1 ± 2.7; p Conclusion A greater visual gain, in response to more intensive treatment during the first year, was maintained for at least 5 years in group 2 subjects. Our data confirm that in a real-world setting, early intensive treatment results in satisfying long-term visual outcomes.

Juliana Wons,1,* Nadine Mihic,2,* Isabel B Pfister,1 Stefano Anastasi,1 Justus G Garweg,1,2 Markus Halberstadt3 1Swiss Eye Institute, Rotkreuz, and Berner Augenklinik am Lindenhofspital, Bern, Switzerland; 2Department of Ophthalmology, University of Bern, Bern, Switzerland; 3Private Practice for Ophthalmology, Flums, Switzerland*These authors contributed equally to this workCorrespondence: Markus HalberstadtAugenärzte Flums, Marktstrasse 21, Flums, 8890, SwitzerlandEmail augenaerzte-flums@hin.chPurpose: This study aimed to compare the effect of trabectome surgery in patients with and without intolerance to their medication and with preoperatively sufficiently controlled, insufficiently controlled, and uncontrolled intraocular pressure (IOP) on the surgical outcome.Patients and Methods: A total of 155 eyes (133 patients) with different forms of open angle glaucoma with or without intolerance to their glaucoma medication undergoing trabectome surgery alone (AIT) or combined with phacoemulsification (phaco-AIT) were included in this retrospective monocentric study. Patients were corresponding to IOP ≤ 18 mmHg (controlled but glaucoma progression or intolerance, group 1), 19– 26 mmHg (insufficiently controlled, group 2), and ≥ 26 mmHg (not controlled, group 3), respectively. Pre- and postoperative IOP and the number of IOP-lowering medications were registered over 12 months. Surgical success was defined as a postoperative IOP of ≤ 18mmHg and/or reduction of the topical treatment demand after 1 year.Results: Of the 155 included eyes, 79 received AIT and 76 received phaco-AIT. Sixty-nine eyes had a preoperatively sufficiently controlled IOP, 63 had an insufficiently controlled IOP, and 23 had an uncontrolled IOP. In all groups, the IOP significantly dropped by 6 and 12 months after surgery (p < 0.001). Surgical success war similar in all groups [47.8% (group 1), 38.1 (group 2) and 34.8% (group 3); p= 0.47]. The effect of AIT on IOP and glaucoma medication independent of intolerance to the anti-glaucoma medication and type of surgery (AIT/phaco-AIT).Conclusion: Independently of the preoperative IOP, a satisfying surgical success was achieved using AIT. In instances that do not qualify for filtrating surgery, trabectome surgery alone or in combination with phacoemulsification thus represents a safe and effective minimally invasive glaucoma surgery technique regardless of an intolerance to the topical medication.Keywords: glaucoma, ab interno trabeculectomy, trabectome, minimally-invasive glaucoma surgery, minimally-invasive glaucoma surgery, MIGS

To assess the efficacy of tumor necrosis factor-alpha inhibitors (TNFi) on uveitic macular edema (ME) unresponsive to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs).This multicenter retrospective study included patients with uveitic ME persisting despite csDMARDs. The effect of an additional TNFi on central retinal thickness (CRT), best corrected visual acuity (BCVA) and corticosteroid need was evaluated.Thirty-five eyes (26 patients, mean age 42.9 ± 15.2 years) were included. CRT decreased from 425 ± 137 µm to 294 ± 66 µm (The addition of a TNFi resulted in an improvement of CRT and BCVA for up to 4 years in uveitic ME but rescue treatments were needed for some patients.

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.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.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.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%.Immun-Checkpoint- und BRAF-/MEK-Inhibitoren (ICI) haben eine zentrale Stellung in der Krebstherapie eingenommen, da sie eine erhebliche Lebensverlängerung bei einer guten Verträglichkeit und Lebensqualität bewirken. Sie sind jedoch mit stoffklassenspezifischen, nicht toxischen immunologischen Nebenwirkungen, darunter auch Entstehung einer Uveitis, behaftet. In dieser Übersicht soll der aktuelle Kenntnisstand zu Wirkprinzip und systemischen und okulären Nebenwirkungen der ICI dargestellt werden.Dieser Übersicht liegt eine Literatursuche in PubMed, der Datenbank des National Institute of Health der USA (https://www.ncbi.nlm.nih.gov/pubmed) mit den Stichworten „uveitis“ AND „drug-induced“ AND/OR „immune checkpoint inhibitor“ zugrunde. Alle relevant erscheinenden Publikationen der letzten 5 Jahre wurden zusammen mit den darin zitierten Querverweisen ausgewertet.Ein klassenspezifisches Phänomen der sonst gut verträglichen ICI ist ihre Fähigkeit, eine systemische und okuläre Autoimmunität auszulösen. Diese unterscheidet sich von toxischen Nebenwirkungen durch ihre Dosisunabhängigkeit. Okuläre Nebenwirkungen treten bei 3% der Patienten auf, wobei ein Melanom als Grunderkrankung und eine Therapie mit Pembrolizumab das Risiko um ein Mehrfaches erhöhen. Eine frühe Diagnose und systemische Steroidtherapie dieser potenziell lebensbedrohlichen Nebenwirkung erlauben in 90% die Erhaltung der Sehfunktion und Lebensqualität, ohne die ICI-Therapie abzusetzen.Das therapeutische Ansprechen von Malignomen auf ICI bezüglich des Überlebens und der Verträglichkeit, insbesondere bei Melanomen, lässt eine zunehmende Anwendung von ICI auch in Therapiekombinationen und damit eine Zunahme der immunologischen Komplikationen im klinischen Alltag erwarten. In Anbetracht einer Mortalität von unbehandelt bis zu 3% infolge immunvermittelter Nebenwirkungen an multiplen Organen ist eine rasche interdisziplinäre Abklärung und rechtzeitige aggressive Behandlung zwingend, führt aber meist auch zu erfreulichen funktionellen Ergebnissen.

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 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.

Zusammenfassung Hintergrund Die okulare Toxoplasmose (OT) führt bei einem hohen Anteil der Patienten zu bleibenden Sehstörungen. Eine Kombination von Antibiotika und Kortikosteroiden verringert möglicherweise das Risiko einer dauerhaften Sehbehinderung und kann ein erneutes Auftreten verzögern. In dieser Übersicht fassen wir den aktuellen Kenntnisstand zur Rezidivprophylaxe der OT zusammen. Methode Grundlage dieser auf Expertenbewertung basierten Übersichtsarbeit bildet eine Literatursuche in PubMed mit den Schlüsselwörtern (MeSH terms) „human ocular toxoplasmosis“ oder „retinochoroiditis“ und „recurrence“ und „prophylaxis“ oder „prevention“. Unter den resultierenden Publikationen wurden Fallserien mit mehr als 20 Patienten, prospektive klinische Studien sowie Metaanalysen berücksichtigt, die innerhalb der letzten 25 Jahre publiziert wurden, außerdem darin erwähnte weitere Publikationen, und basierend auf der Erfahrung der Autoren bewertet. Ergebnisse Die Häufigkeit von Rezidiven unterscheidet sich nicht zwischen Lateinamerika, Nordamerika und Europa, liegt in den ersten beiden Jahren bei etwa 12 – 15% und nimmt danach ab, wobei Rezidive bis 49 Jahre nach einer aktiven Affektion beobachtet wurden. Nach 2 placebokontrollierten Doppelblindstudien aus Brasilien, wo besonders schwerwiegende Rezidive auftreten, kann eine Antibiotikaprophylaxe mit Trimethoprim 160 mg kombiniert mit Sulfamethoxazol 800 mg (Cotrim forte) 3-mal pro Woche über 12 Monate das Auftreten von Rezidiven über bis zu 3 Jahre von 22 auf 3% senken. Danach ist die Rezidivwahrscheinlichkeit so hoch wie bei Patienten, die keine Prophylaxe erhalten haben. Schlussfolgerung Rezidive können wirkungsvoll unterdrückt werden, wenn dies medizinisch indiziert ist, insbesondere bei zentraler Lage der Läsionen, unzureichender Immunkompetenz und häufigen Rezidiven. Die Prophylaxe sollte für mindestens 12 Monate durchgeführt werden, da das Rezidivrisiko in den ersten beiden Jahren am höchsten ist.

Macrophages are the main infiltrating immune cells in choroidal neovascularization (CNV), a hallmark of the human wet, or neovascular age-related macular degeneration (AMD). Due to their plasticity and ability to adapt to the local microenvironment in a tissue-dependent manner, macrophages display polar functional phenotypes characterized by their cell surface markers and their cytokine profiles. We found accumulation of hemoglobin-scavenging cluster of differentiation 163 (CD163)(+) macrophages in laser-induced CNV lesions and higher expression of CD163(+) monocytes in the peripheral blood on day 7 post injury in mice. In comparison, CD80(+) macrophages did not differ with laser-injury in young or aged mice and did not significantly change in the peripheral blood of CNV mice. We examined the percentages of CD163(+), CD206(+), and CD80(+) monocytes in the peripheral blood of patients with wet AMD, patients with dry AMD, and in age-matched individuals without AMD as controls. Percentages of peripheral blood CD163(+) monocytes in both dry AMD (P < .001) and wet AMD (P < .05) were higher than in age-matched non-AMD controls, while there was no difference between the groups in the percentages of peripheral CD206(+) and CD80(+) monocytes. Further, serum level of soluble CD163 (sCD163) was elevated only in patients with wet AMD (P < .05). An examination of 40 cytokine levels across the study groups revealed that anti-VEGF treated patients with wet AMD, who showed no exudative signs on the day of blood drawing had a cytokine profile that was similar to that of non-AMD individuals. These results indicate that CD163 could be further evaluated for its potential as a useful marker of disease activity in patients with neovascular AMD. Future studies will address the origin and potential mechanistic role of CD163(+) macrophages in wet AMD pathologies of angiogenesis and leakage of blood components.

Die tuberkulose Uveitis (TU) ist anfangs meist wenig akut, von geringen Sehstorungen begleitet und betrifft oft gesund wirkende jungere Patienten, sodass die Diagnose haufig primar verpasst wird. Ziel ist ein Update zu den therapeutischen Aspekten bei Verdacht auf TU. Anhand einer Literaturrecherche in PubMed zu den Stichworten wurden alle Studien, grosere Fallserien sowie Ubersichtsartikel der letzten 10 Jahre und darin zitierte Querverweise basierend auf der Expertise der Autoren ausgewertet. Wenn der Verdacht auf eine TU sich nicht erharten lasst, mussen Risiken und Nutzen der Therapie abgewogen werden. Das Ansprechen der Uveitis auf die antituberkulose Therapie (ATT) in 82 % ist ein wichtiger diagnostischer Hinweis. In Anbetracht dieser bemerkenswert guten Ansprechrate und vertretbarer Nebenwirkungen der ATT erscheint eine groszugige Indikationsstellung akzeptabel. Fehlendes Ansprechen oder eine paradoxe Verschlechterung der TU unter Therapie bei extrapulmonalen Tuberkulosemanifestationen sind vermutlich Ausdruck einer Hypersensitivitatsreaktion auf mykobakterielle Antigene und bedurfen einer zusatzlichen systemischen Steroidtherapie. Der Morbus Eales wird als vaskulitische Verlaufsform mit der TU assoziiert, spricht auf eine ATT nicht an und wird durch Lasertherapie der Ischamieareale behandelt. Eine TU tritt oft bei sonst gesunden Personen meist ohne extraokulare Manifestationen auf. Ein fruher Beginn der ATT moglichst vor einer systemischen Steroidtherapie ist entscheidend fur die langfristige funktionelle Erholung. Ein Therapieerfolg, definiert als Ausbleiben von Uveitisrezidiven innerhalb 6 Monaten nach Beendigung der Therapie ist damit in mindestens 82 % zu erwarten. Bei paradoxer Verschlechterung oder fehlendem Ansprechen ist zusatzlich eine Kontrolle der Entzundungsreaktion erforderlich.

The aim of this study was to compare neovascular age-related macular degeneration (nAMD) treatment outcomes between ophthalmological practices and a specialized macula clinic. In this case series, we included 347 treatment-naive eyes with nAMD (332 patients). All patients received intravitreal anti-VEGF treatment using ranibizumab or aflibercept at the discretion of the treating physician using a treat-and-extend protocol either by one of 28 practice-based ophthalmologists (group 1; n = 215 eyes) or at a macula clinic (group 2; n = 132 eyes) over 24 months. Baseline characteristics of the patients in the two groups, including age, initial BCVA (group 1 58.2 ± 18.5, group 2 60.8 ± 16.1 ETDRS letters; p = 0.32), and baseline CRT, were comparable. By end of the observation period, both groups presented similar BCVA (group 1 67.4 ± 19.3, group 2 66.8 ± 17.2 letters; p = 0.51), visual gains (group 1 7.8 ± 16.9, group 2 5.8 ± 14.4 letters; p = 0.11), CRT values (group 1 259.6 ± 80.5, group 2 277.4 ± 87.1 μm; p = 0.10), and number of injections (group 1 13.0 ± 4.5, group 2 11.6 ± 4.1 injections; p = 0.09), as well as portion of eyes with stable disease (absence of any intraretinal fluid and absence or stability of subretinal fluid and pigment epithelial detachment: group 1 78% (n = 128), group 2 75% (n = 95); p = 0.63). However, there was a significant difference regarding the number of examinations (group 1 12.8 ± 5.0, group 2 9.7 ± 3.1 visits; p = 0.0005). nAMD treatment delivered by practice-based ophthalmologists is reasonable regarding functional outcomes and reduces the indirect treatment burden, which is partially outweighed by significantly more clinical examinations in ophthalmological practices.

Brolucizumab is a single-chain variable antibody fragment (scVF) that specifically binds to VEGF-A. The results of two large phase III, multicentre, randomized clinical trials comparing intravitreal treatment with Brolucizumab and Aflibercept in neovascular age-related degeneration demonstrated its potency in the treatment of neovascular age-related macular degeneration (nAMD).The currently tested injected dose of 6 mg Brolucizumab results in a 11.2 - 13.3 times higher equivalent molar dose compared to Aflibercept 2 mg. Thus, it is conceivable that the effect of Brolucizumab in DME exceeds that of other currently used anti-VEGF agents with regards to effect durability; this was confirmed for nAMD in a phase I/II study.Approved anti-VEGF drugs have shown unprecedented success compared to laser treatment with regards to restoration of visual acuity and improvement of diabetic retinopathy severity scores for up to 5 years. The visual gains were sustained after the loading phase and a reduced number of injections were required after the first year independent of the treatment strategy. Compared to pan-retinal laser photocoagulation, the time to progression of DRP was markedly extended and was proven by better preservation of the visual field, prevention of severe vision loss, hemorrhagic complications, and the need for intraocular surgery.The ongoing prospective, randomized, phase III clinical studies in DME, KITE, and KESTREL aim to confirm the non-inferiority of Brolucizumab 6 mg compared to Aflibercept 2 mg on a functional and morphological level as well as durability effect over 2 years.Brolucizumab ist ein sogenanntes „Single-chain variable Antibody Fragment“ (scVF), das spezifisch an VEGF-A bindet. Zwei große randomisierte, klinische, multizentrische Phase-III-Studien haben die intravitreale Therapie mit Brolucizumab und Aflibercept bei feuchter altersbedingter Makuladegeneration verglichen und die Wirksamkeit von Brolucizumab bei dieser Erkrankung gezeigt.Mit einer intravitrealen Injektion von 6 mg Brolucizumab wird eine 11,2- bis 13,3-fach höhere molekulare Äquivalentdosis als mit Aflibercept 2 mg erreicht. Deshalb geht man davon aus, dass die Wirkdauer von Brolucizumab auch bei diabetischer Makulopathie (DME) länger ist als die von anderen derzeit eingesetzten Medikamenten, da sich dies in einer Phase-I/II-Studie bei feuchter AMD bereits betätigt hat.Die bisher zugelassenen Anti-VEGF-Medikamente haben eine weit über die Lasertherapie hinausgehende Wirkung bezüglich der Erholung des Visus und der Rückbildung diabetischer Netzhautveränderungen über bis zu 5 Jahre gezeigt. Der anfängliche Visusgewinn konnte trotz einer abnehmenden Zahl intravitrealer Injektionen unabhängig von der gewählten Behandlungsstrategie über das 1. Jahr hinaus erhalten werden. Gleichzeitig konnte im Vergleich zur panretinalen Laserkoagulation die Zeit bis zur Progression der diabetischen Retinopathie markant verlängert werden, ein deutlich besseres Gesichtsfeld erhalten, das Risiko eines schweren Visusverlustes und schwerer Komplikationen reduziert und das Risiko operativer Eingriffe deutlich gesenkt werden.Es ist zu erwarten, dass die laufenden randomisierten, klinischen Phase-III-Studien bei DME mit den Namen KITE und KESTREL die Noninferiorität von Brolucizumab 6 mg im Vergleich zu Aflibercept 2 mg bezüglich funktioneller und anatomischer Endpunkte über einen Zeitraum von bis zu 2 Jahren bestätigen.

Purpose: To assess the long-term anatomical and functional findings in patients with symptomatic vitreomacular traction (VMT), with or without full thickness macular hole (FTMH), after eye treatment with intravitreal ocriplasmin injection (IOI). Methods: This longitudinal case series includes 51 eyes from 51 symptomatic patients with VMT (

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.

Purpose To compare the effect of adding a corticosteroid or switching to another anti-VEGF treatment in patients with exudative age-related macular degeneration (eAMD) with persisting intraretinal fluid on anti-VEGF monotherapy. Methods This retrospective, interventional case series involved 43 pseudophakic eyes with eAMD and persistent intraretinal fluid on anti-VEGF treatment that switched treatment to a combination of Ozurdex® or Triamcinolone and anti-VEGF therapy (group 1) or to another anti-VEGF agent (group 2). The number of injections, time to re-injection, change in central retinal thickness (CRT), and best-corrected visual acuity (BCVA) from 12 months prior to 12 months after switch to third-line therapy were defined as primary outcomes. Results Whereas the treatment demand was reduced (from 8.8±2.2 to 4.6±2.9 injections; p=0.001) and the re-injection interval extended in group 1 (from 1.5±0.4 months to 4.4±3.8 months; p=0.001), these parameters did not change in group 2 (7.4±1.6 to 7.3±2.2; p=0.90 and 1.7±0.3 months to 1.9±0.8 months; p=0.75). Mean CRT decreased from 455.7±30.1 and 427.6±36.0µm (groups 1 and 2, respectively) to 359.1±38.2 and 303.1±44.4µm (intergroup p=0.03). The mean baseline BCVA of 62.6±3.8 letters (group 1) and 63.0±1.9 letters (group 2) remained stable under therapy in both groups (intergroup p=0.67). Conclusion In eyes with eAMD with persistent intraretinal fluid on anti-VEGF monotherapy despite frequent re-injections, corticosteroids achieved a similar functional and morphological outcome over 12 months as switching to another anti-VEGF therapy, but with a reduced injection burden. In selected cases, corticosteroid treatment may thus be an option for third-line therapy in refractory exudative AMD.

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.

Purpose To examine vision-related quality of life in patients with diabetic macular edema (DME) treated with intravitreal aflibercept (EYLEA, Regeneron Pharmaceuticals, Inc, Tarrytown, NY). Design AQUA was a multicenter, open-label, single-arm, phase 4 study. Participants Adults 18 years of age or older with type 1 or 2 diabetes mellitus and DME. Methods Patients received intravitreal aflibercept 2 mg every 8 weeks for 52 weeks, after 5 initial doses every 4 weeks. Main Outcome Measures The primary outcome was the change in 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) total score from baseline to week 52. Secondary outcomes included the change in NEI VFQ-25 near and distant activities subscale scores, best-corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study [ETDRS] letters), and central retinal thickness (CRT) from baseline to week 52. Change in NEI VFQ-25 score at week 52 for better-seeing eyes (BSEs) and worse-seeing eyes (WSEs) also was evaluated. Results A total of 553 patients comprised the full analysis set, and 560 patients comprised the safety analysis set. At baseline, the mean NEI VFQ-25 total score was 70.12, mean BCVA was 61.5 ETDRS letters, and mean CRT was 464.81 μm. A mean of 8.8 injections were administered over 52 weeks. At week 52, the mean improvement from baseline in the NEI VFQ-25 total score was +6.11 (standard deviation [SD], 11.46); the corresponding improvements in near and distant activities were +11.37 (SD, 18.01) and +7.33 (SD, 17.32), respectively. Similarly, improvements in patients whose BSE and WSE were treated were 7.74 (SD, 13.59) and 5.48 (SD, 9.70), respectively. At week 52, mean change in BCVA was +10.0 ETDRS letters (SD, 8.0 ETDRS letters), and mean change in CRT was –175.38 μm (SD, 132.62 μm). Overall, 53.6% of patients reported treatment-emergent adverse events (TEAEs), of whom 26.8% experienced an ocular TEAE in the study eye. The most common serious ocular TEAE was endophthalmitis (0.5% [n = 3]). Five deaths (0.9%) were reported, but were not considered treatment related. Conclusions Intravitreal aflibercept was associated with clinically meaningful improvements in NEI VFQ-25 total score over 52 weeks in patients with DME; these were even more pronounced for near than for distant activities. Adverse events were consistent with the known safety profile of intravitreal aflibercept.

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.

ZusammenfassungDie breite Differenzialdiagnose der akuten posterioren und Panuveitis, die meist jüngere Individuen und in mehr als der Hälfte beide Augen betrifft, macht die rasche diagnostische Einordnung und die therapeutische Entscheidung wegen ihrer erheblichen Konsequenzen für den weiteren Verlauf zu kritischen Schritten. Das Risiko eines bleibenden Visusverlustes infolge eines verzögerten Therapiebeginns ist dabei ebenso bedeutsam wie das Einleiten einer nicht genügend wirksamen Therapie. Klinische Präsentation (anatomische Lokalisation und Entzündungstyp), Verlauf und sekundär das Ansprechen auf die Akuttherapie lassen eine erste diagnostische Eingrenzung zu, wobei eine infektiöse Ätiologie in bis zu einem Drittel der Fälle vorliegt. Die häufigste akute posteriore Uveitis bei immunkompetenten Patienten ist eine akute virale Netzhautnekrose. Diese lässt sich oft klinisch nicht sicher von einer Behçet-Uveitis unterscheiden, solange keine systemischen Manifestationen vorliegen. Bis zur definitiven diagnostischen Einordnung muss deshalb bei makulabedrohender Erkrankung spätestens 24 Stunden nach Beginn einer antiviralen und antiparasitären Akuttherapie eine hochdosierte Steroidtherapie begonnen werden. Den therapeutischen Konsequenzen der Fehleinschätzung der Erkrankung stehen prognostische Überlegungen gegenüber, die ein aggressives Vorgehen gerade bei akuten posterioren Uveitiden rechtfertigen: Jede Verzögerung des Therapiebeginns vermehrt die infektiöse und entzündliche Gewebsschädigung, erhöht das Risiko einer Affektion des Partnerauges und anderer Organe, wohingegen der Einsatz höherer Steroiddosen, Immunsuppressiva und Biologika zu unkontrollierter Erregerproliferation und zu Rezidiven führen kann.

The aim of this paper is to summarise our own and to review published experience regarding the long-term outcome of intravitreal treatment for macular neovascularisation (MNV) secondary to Sorsby’s fundus dystrophy (SFD). A systematic literature search using the MeSH terms [Sorsby] and [anti-vascular endothelial growth factor (VEGF)] was conducted in NCBI/PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), ScienceDirect, Google Scholar and ClinicalTrials.gov to identify publications reporting anti-VEGF treatment outcomes in SFD. Treatment outcomes were extracted for this meta-analysis from 14 publications and an own patient reporting a total of 31 cases with a mean follow-up (FU) of 54 months. Both eyes were affected in ten (32.3%) instances. Heterogenous reporting limited the comparability of the outcomes. All papers in common, however, reported satisfied to excellent responses to anti-VEGF therapy if patients were diagnosed and treated immediately after onset of symptoms. Of 20 eyes, for which visual acuity was reported before and after treatment, five worsened and seven improved by more than 1 line, whereas eight eyes maintained their function by end of the follow up, and 11 eyes (55%) maintained a driving vision (Snellen VA ≥ 0.5). Of six eyes with a VA < 0.5, VA improved in one to VA ≥ 0.5, whereas of 14 eyes with an initial VA ≥ 0.5, this dropped to

Diabetic retinopathy (DR) is a sight-threatening late complication of diabetes mellitus (DM). Even though its pathophysiology has not been fully elucidated, several studies suggested a role for transforming growth factor- (TGF-) β, matrix metalloproteinases (MMPs), and tissue inhibitors of matrix metalloproteinase (TIMP) in the onset and progression of the disease. Consequently, the aim of this study was to analyze the concentrations of TGF-β1, TGF-β2, TGF-β3, MMP-3, MMP-9, and TIMP-1 in patients with different stages of DR in order to identify stage-specific changes in their concentrations during the progression of the disease. Serum and aqueous humor (AH) samples were collected during intraocular surgery, and eyes were classified into the following groups: healthy controls (n = 17), diabetic patients with non-apparent DR (n = 23), mild/moderate nonproliferative DR (NPDR) (n = 13), and advanced NPDR/proliferative DR (PDR) without vitreal hemorrhage (n = 14). None of the patients had been under anti-VEGF or laser treatment within six months prior to surgery. In the AH, TGF-β1 levels increased in advanced NPDR/PDR by a factor of 5.5 compared to the control group. Similarly, an increase in MMP-3 and TIMP-1 levels in the AH was evident in the later stages of DR, corresponding to a 7.7- and 2.4-fold increase compared to the control group, respectively, whereas serum levels of the studied proteins remained similar. In conclusion, increased concentrations of TGF-β1, MMP-3, and TIMP-1 in the AH, but not in the serum, in advanced NPDR/PDR indicate that the intraocular regulation for these cytokines is independent of the systemic one and suggest their involvement in the progression of DR.

Background: There is currently no clear evidence of the effectiveness of antibiotic therapy in acute ocular toxoplasmosis (OT), but its effect as a secondary prophylaxis is undisputed. The majority of uveitis specialists advocate treatment. This meta-analytic review aims to critically analyze determinants of treatment success and to update current treatment strategies for OT in order to explain this discrepancy. Methods: A systematic literature search was performed in NCBI/PubMed, Clinical Trials, Google Scholar and ScienceDirect to retrieve pro- and retrospective studies using the key terms “ocular toxoplasmosis” or “retinochoroiditis” and “immunocompetent” and “treatment” or “therapy” and “human.” Of these, larger case series and prospective clinical studies and cross references identified from meta-analyses were selected by a manual search, and primary and secondary outcome parameters were extracted. Results: Ten case series and clinical trials reported success parameters for treatment outcomes, and four additional for recurrence prophylaxis. Five treatment studies were randomized clinical trials, three comparative and two noncomparative case series. Though several outcome parameters were reported, five of them defined time to healing, four visual gain and one lesion size as primary and secondary outcome parameters, recurrence rate as a secondary outcome parameter was reported once. No conclusive evidence was found for an antibiotic treatment effect. Four prophylaxis studies addressed the prevention of recurrences after treatment. The primary outcome in all studies was the effect of treatment and prophylaxis on recurrences, and all four found a significant effect on the risk of and time to recurrences. Conclusions: Antibiotic treatment of OT aims at controlling parasite proliferation. The absence of an effect on visual acuity and time to healing is thus not surprising. The fact that time to and number of recurrences respond to recurrence of prophylaxis proves the antibiotic effect on parasite activity.

Purpose: The aim of this study was to evaluate the effect of switching treatment in eyes with neovascular age-related macular degeneration (nAMD) and treatment intervals of ≤6 weeks to brolucizumab. Methods: In this prospective series, eyes with persisting retinal fluid under aflibercept or ranibizumab every 4–6 weeks were switched to brolucizumab. Visual acuity (BCVA), reading acuity (RA), treatment intervals, central subfield thickness (CST), and the presence of intra- and subretinal fluid were recorded over 6 months. Results: Seven of 12 eyes completed the 6 month follow-up and received 4.4 ± 0.5 brolucizumab injections within 28.0 ± 2.8 weeks. Treatment intervals increased from 5.3 ± 0.9 weeks to 9.0 ± 2.8 weeks (95% confidence interval of extension (CI): 1.6 to 5.9). BCVA improved from 67.8 ± 7.2 to 72.2 ± 7.5 (95% CI: −0.3 to 9.1) ETDRS letters, RA improved from 0.48 ± 0.15 to 0.31 ± 0.17 LogRAD (95% CI: 0.03 to 0.25), and CST improved from 422.1 ± 97.3 to 353.6 ± 100.9 µm (95% CI: −19.9 to 157.1). Treatment was terminated early in five eyes (two intraocular inflammations with vascular occlusion without vision loss, one stroke, and two changes in the treatment plan). Conclusions: Improvement in visual performance and longer treatment intervals in our series over 6 months indicate the potential of brolucizumab to reduce the treatment burden in nAMD, while two instances of intraocular inflammation were encountered.

Objective: To present two different phases of progression of Gass stage 1 foveolar detachment to lamellar or full-thickness macular holes revealed with spectral domain optical coherence tomography. Design: This is an observational study. Participants: The medical records of four patients (four eyes) with foveolar detachment that had evolved into stage 1 macular holes were compared. The patients manifested neither co-existing myopia nor any other ocular pathology. Methods: At each consultation, best-corrected visual acuity, dilated fundus examination, and spectral domain optical coherence tomography were performed to ascertain whether the foveolar detachment was associated with posterior vitreal detachment. Results: In two of the eyes, and at an early phase of the disease, an incomplete posterior vitreal detachment and vitreal adhesion at the head of the optic nerve were observed. In the other two cases, the traction was not antero-posterior but tangential and had been effected by thickening of the inner limiting membrane or by the presence of a discrete epiretinal membrane in the papillomacular area; the posterior vitreal detachment was complete. In the former two cases and in one of the latter, the foveolar detachments had progressed to full-thickness macular holes. The visual acuities were better in the latter than in the former two eyes. Conclusion: Two different pathological mechanisms appear to underlie the formation of macular holes: The optical coherence tomography–guided classification of Gass stage 1 macular hole as an antero-posterior traction with a triangular foveolar detachment has to be distinguished from a tangential traction and a complete posterior vitreal detachment. Tangential traction is typically associated with a more dome-shaped or irregular foveolar detachment and a hyper-reflective band at the vitreoretinal interface.

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 = p = 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.

Diabetic retinopathy (DR) is a sight-threatening late complication of diabetes mellitus (DM). Even though its pathophysiology has not been fully elucidated, several studies suggested a role for transforming growth factor- (TGF-) β, matrix metalloproteinases (MMPs), and tissue inhibitors of matrix metalloproteinase (TIMP) in the onset and progression of the disease. Consequently, the aim of this study was to analyze the concentrations of TGF-β1, TGF-β2, TGF-β3, MMP-3, MMP-9, and TIMP-1 in patients with different stages of DR in order to identify stage-specific changes in their concentrations during the progression of the disease. Serum and aqueous humor (AH) samples were collected during intraocular surgery, and eyes were classified into the following groups: healthy controls (n=17), diabetic patients with non-apparent DR (n=23), mild/moderate nonproliferative DR (NPDR) (n=13), and advanced NPDR/proliferative DR (PDR) without vitreal hemorrhage (n=14). None of the patients had been under anti-VEGF or laser treatment within six months prior to surgery. In the AH, TGF-β1 levels increased in advanced NPDR/PDR by a factor of 5.5 compared to the control group. Similarly, an increase in MMP-3 and TIMP-1 levels in the AH was evident in the later stages of DR, corresponding to a 7.7- and 2.4-fold increase compared to the control group, respectively, whereas serum levels of the studied proteins remained similar. In conclusion, increased concentrations of TGF-β1, MMP-3, and TIMP-1 in the AH, but not in the serum, in advanced NPDR/PDR indicate that the intraocular regulation for these cytokines is independent of the systemic one and suggest their involvement in the progression of DR.

Mario Deiss,1,* Cagdas Kaya,2,3,* Isabel B Pfister,2,3 Justus G Garweg1– 4 1University of Bern, Bern, Switzerland; 2Swiss Eye Institute, Rotkreuz, Switzerland; 3Berner Augenklinik am Lindenhofspital, Bern, Switzerland; 4Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland*These authors contributed equally to this workCorrespondence: Justus G GarwegBerner Augenklinik am Lindenhofspital, Bremgartenstrasse 119, Bern CH – 3012, SwitzerlandEmail justus.garweg@swiss-eye-institute.comBackground: To compare visual outcomes of vitrectomy with internal limiting membrane (ILM) peeling and failed SF6 gas tamponade requiring silicone oil (SO) in a second procedure with primary SO tamponade in fovea-involving retinal detachment (FiRD).Methods: Retrospective analysis of 82 eyes with retinal detachment and mild, but without advanced proliferative retinopathy (PVR ≥C2) requiring vitrectomy for FiRD. Group 1 comprised 23 eyes that underwent SF6 tamponade resulting in re-detachment requiring revision surgery with secondary SO tamponade. Based on the intraoperative findings, group 2 patients had primarily received SO as vitreal tamponade (n=59). Patients receiving a scleral buckle surgery or with advanced PVR as well as patients with underlying vascular diseases and uveitis were excluded.Results: Preoperative visual acuity (Early Treatment Diabetic Retinopathy Study letters) was 13.5 ± 19.1 in group 1 and 14.0 ± 18.3 in group 2 (p=0.44). Twelve months after first surgery for FiRD, visual acuity was 49.8 ± 19.8 in group 1 and 51.7 ± 18.7 letters in group 2 (p= 0.63). Re-detachment after SO removal requiring revision surgery developed in 17.4 (n=4) and 15.3% (n=9) cases.Conclusion: Our findings suggest that if retinal traction is completely relieved at the end of surgery, vitrectomy with ILM peeling and SF6 may, if successful, improve the functional outcomes in instances with visual potential, ie, a foveal detachment of short duration despite the presence of a mild to moderate PVR, but with the inherent increased risk of re-detachment requiring further intervention and the use of a SO tamponade. Hence, secondary SO installation during re-vitrectomy after failed primary reattachment surgery results in similar functional outcomes as primary oil filling.Keywords: internal limiting membrane, ILM peeling, macula-off, retinal detachment, silicone oil tamponade, vitrectomy