The aim of this study was to compare the efficacy and safety profile of XEN microstent implantation with trabeculectomy (TET) in a comparable group of open-angle glaucoma cases in a retrospective, monocentric, single-surgeon setting. Each treatment group consisted of 100 eyes of 100 patients. At regular follow-up visits during the first 12 months after surgery, the following assessments were conducted and compared: intraocular pressure (IOP), number of IOP-lowering medications applied, best-corrected visual acuity (BCVA) and visual field testing. In both groups mean IOP was significantly reduced (p < 0.001). Mean IOP dropped from 24.8 ± 7.8 to 14.8 ± 4.0 mmHg in the TET and from 24.5 ± 6.7 to 16.6 ± 4.8 mmHg in the XEN group. The number of active compounds in the prescribed medication dropped from 3.3 ± 1.2 to 1.3 ± 1.4 in the TET and from 3.0 ± 1.1 to 1.4 ± 1.5 in the XEN group. BCVA and mean defect of static automated perimetry did not show a change of statistical significance in either group. Complications were more frequent after TET (p = 0.005) while postoperative needling was more frequent in the XEN group (p = 0.021). TET and XEN led to a significant reduction of IOP and IOP-lowering medication, while BCVA and visual field indices remained mostly unaltered over a 12-month postsurgical follow-up.

Survival of retinal ganglion cells (RGC) is compromised in several vision-threatening disorders such as ischemic and hypertensive retinopathies and glaucoma. Pigment epithelium-derived factor (PEDF) is a naturally occurring pleiotropic secreted factor in the retina. PEDF produced by retinal glial (Müller) cells is suspected to be an essential component of neuron-glial interactions especially for RGC, as it can protect this neuronal type from ischemia-induced cell death. Here we show that PEDF treatment can directly affect RGC survival in vitro. Using Müller cell-RGC-co-cultures we observed that activity of Müller-cell derived soluble mediators can attenuate hypoxia-induced damage and RGC loss. Finally, neutralizing the activity of PEDF in glia-conditioned media partially abolished the neuroprotective effect of glia, leading to an increased neuronal death in hypoxic condition. Altogether our results suggest that PEDF is crucially involved in the neuroprotective process of reactive Müller cells towards RGC.

Background: The pathogenesis of partial-thickness macular defects and the role of Müller glial cells in the development of such defects are not well understood. We document the morphological characteristics of various types of partial-thickness macular defects using spectral-domain optical coherence tomography, with the focus on tractional and degenerative lamellar holes, and discuss possible pathogenic mechanisms. Methods: A retrospective case series of 61 eyes of 61 patients with different types of partial-thickness macular defects is described. Results: Partial-thickness macular defects are caused by anteroposterior or tangential traction onto the fovea exerted by the partially detached posterior hyaloid and epiretinal membranes, respectively. Tractional elevation of the inner Müller cell layer of the foveola-without (outer lamellar holes, foveal pseudocysts) or with a disruption of this layer (tractional lamellar holes, macular pseudoholes)-produces an elevation of the inner layers of the foveal walls (nerve fiber layer to outer plexiform layer [OPL]) and a schisis between the OPL and Henle fiber layer (HFL). With the exception of outer lamellar holes, the (outer part of the) central outer nuclear layer and the external limiting membrane remain nondisrupted in the various types of partial-thickness defects. Degenerative lamellar holes are characterized by cavitations between the inner plexiform layer and HFL of the foveal walls; many cases have lamellar hole-associated epiretinal proliferation (LHEP). Proliferating cells of the disrupted Müller cell cone may contribute to the development of LHEP and fill the spaces left by degenerated photoreceptors in the foveal center. Conclusions: It is suggested that morphological characteristics of partial-thickness macular defects can be explained by the disruption of the (stalk of the) Müller cell cone in the foveola and the location of tissue layer interfaces with low mechanical stability: the boundary with no cellular connections between both Müller cell populations in the foveola, and the interface between the OPL and HFL in the foveal walls and parafovea. We propose that the development of the cavitations in degenerative lamellar holes is initiated by traction which produces a schisis between the OPL and HFL, and enlarged by a slow and chronic degeneration of Henle fibers and bipolar cells.

Background: To describe cases of retinal vascular events shortly after administration of mRNA or adenoviral-vectored COVID-19 vaccines. Design: Retrospective, multicenter case series. Methods: Six cases of retinal vascular events shortly after receiving COVID-19 vaccines. Results: A 38-year-old, otherwise healthy male patient presented with branch retinal arterial occlusion four days after receiving his second dose of SARS-CoV-2 vaccination with Comirnaty® (BioNTech®, Mainz, Germany; Pfizer®, New York City, NY, USA). An 81-year-old female patient developed visual symptoms twelve days after the second dose of SARS-CoV-2 vaccination with Comirnaty® and was diagnosed with a combined arterial and venous occlusion in her right eye. A 40-year-old male patient noticed blurry vision five days after his first dose of SARS-CoV-2 vaccination with Comirnaty® and was diagnosed with venous stasis retinopathy in his left eye. A 67-year-old male was diagnosed with non-arteritic anterior ischemic optic neuropathy in his right eye four days after receiving the first dose of Vaxzevria® (AstraZeneca®, Cambridge, UK). A 32-year-old man presented with a sudden onset of a scotoma two days after receiving the second dose of SARS-CoV-2 vaccination with Spikevax® (Moderna, Cambridge, UK) and was diagnosed with a circumscribed nerve fiber infarction. A 21-year-old female patient developed an acute bilateral acute macular neuroretinopathy three days after receiving the first dose of SARS-CoV2-vaccine Vaxzevria® (AstraZeneca®, Cambridge, UK). Conclusion: This case series describes six cases of retinal vascular events shortly after receiving mRNA or adenoviral-vectored COVID-19 vaccines. The short time span between received vaccination and occurrence of the observed retinal vascular events raises the question of a direct correlation. Our case series adds to further reports of possible side effects with potential serious post-immunization complications of COVID-19 vaccinations.

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Aims To describe and compare the functional and anatomical outcomes of untreated and treated diabetic macular edema (DME) in eyes with very good baseline visual acuity (VA) in a real-world setting. Methods A 12-month, retrospective, multicenter, observational cohort study, including DME patients with baseline visual acuity (VA) ≤ 0.1 logMAR (≥ 20/25 Snellen) and central subfield thickness (CST) > 250 µm with intra- and/or subretinal fluid seen on optical coherence tomography. Results A total of 249 eyes were included, of which 155 were treated and 94 were non-treated during follow-up. Most eyes maintained vision (VA gain or VA loss < 5 letters) at 12 months (treated: 58.1%; non-treated: 73.4%). In non-treated eyes with stable VA within the first 6 months, VA was maintained throughout the follow-up in most cases (86.3%). In non-treated eyes with VA loss ≥ 5 letters within 6 months (36.7%), further observation led to worse visual outcome than treatment (− 4.2 vs. − 7.8 letters, p = 0.013). In eyes in which treatment was initiated at baseline ( n = 102), treatment with 8–12 anti-VEGF injections led to better visual outcome compared to treatment with less injections (− 0.3 ± 3.6 letters vs. − 3.8 ± 6.2 letters, p = 0.003). Conclusion In a real-world setting, the majority of DME patients with very good VA maintained vision at 12 months, regardless of whether the DME was treated or not. This study supports close observation of eyes with DME and very good VA with consideration of treatment when a one line drop in vision is observed.

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Neovascularization is a sight-threatening complication of ischemic proliferative retinopathies. Transforming growth factor (TGF)-β, a cytokine with multiple functions in the retina, participates in the control of pathological angiogenesis and neovascularization. Retinal glial (Müller) cells produce TGF-β2 under physiological and post-ischemic conditions. To characterize glial cell-derived mediators of angiogenesis regulation in glial-endothelial interactions in the retina, we co-cultured primary Müller cells and bovine microvascular retinal endothelial cells (BRECs). Müller cell-derived TGF-β2 was bound by the BRECs, which were found to express serine/threonine kinase TGF-β receptors, and stimulated TGF-β-dependent anti-proliferative signaling pathways. The proliferation of BRECs was attenuated by exogenous TGF-β2 as well as by the presence of Müller cell culture media. The following intracellular signaling mechanisms were found to be involved in the anti-angiogenic action of Müller cell-derived TGF-β2: (i) binding of TGF-β2 to BRECs is mediated by the type-II TGF-β receptor, leading to (ii) activation and phosphorylation of receptor-activated Smads; (iii) Müller cell-derived TGF-β2 activates Smad2 and Smad3 to (iv) attenuate the phosphorylation state of the MAP kinases, extracellular signal-regulated kinase (ERK)-1/-2. Neutralizing TGF-β or TGF-β type-II receptor or blocking the activation of Smads partially abrogated the effect of Müller cell-conditioned media on BRECs. Together, our data suggest that Müller cells release TGF-β2, inhibiting the proliferation of retinal endothelial cells via activation of Smad2/Smad3 and attenuation of ERK signaling. Given the context-dependent action of TGF-β2 on angiogenesis, our results may have implications for understanding the pathogenesis of retinal angiopathies, such as diabetic retinopathy, and the anti-angiogenic role of TGF-β therein.