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Purpose: To investigate the influence of the selective Rho-kinase (ROCK) inhibitor, fasudil, on the mRNA level of proinflammatory factors and the retinal vascular development in mice with oxygen-induced retinopathy (OIR). Methods: C57BL/6J mice underwent standard protocol for OIR induction from postnatal days 7 to 12. Subsequently, they received a daily intraperitoneal injection of fasudil or sodium chloride from P12 to P16. Analyses were performed using vascular staining on retinal flat mounts, RNA expression by qPCR, and immunohistochemistry on paraffin sections. Results: On retinal flat mounts, the proportion of avascular area and tuft formation did not differ between the fasudil and NaCl group. Immunohistochemical staining revealed a less intense staining with inflammatory markers after fasudil. Nevertheless, there were no differences on RNA level between the two groups. Conclusions: In conclusion, our findings support that daily systemic application of fasudil does not decrease retinal neovascularization in rodents with oxygen-induced retinopathy. The results of our study together with the controversial results on the effects of different ROCK inhibitors from the literature makes it apparent that effects of ROCK inhibition are more complex, and further studies are necessary to analyze its potential therapeutic effects. [ABSTRACT FROM AUTHOR]

Purpose: To assess the influence of retinal macrophages and microglia on the formation of choroidal neovascularization (CNV). Therefore, we used a transgenic mouse (CD11b‐HSVTK) in which the application of ganciclovir (GCV) results in a depletion of CD11b+ cells. Methods: We first investigated if a local depletion of CD11b+ macrophages and microglia in the retina is feasible. In a second step, the influence of CD11b+ cell depletion on CNV formation was analysed. One eye of each CD11b‐HSVTK mouse was injected with GCV, and the fellow eye received sodium chloride solution (NaCl). Cell counting was performed at day 3 and 7 (one injection) or at day 14 and 21 (two injections). Choroidal neovascularization (CNV) was induced by argon laser and analysed at day 14. Results: The most effective CD11b+ cell depletion was achieved 7 days after a single injection and 14 days after two injections of GCV. After two injections of GCV, we found a significant reduction of CD11b+ cells in central (52 ± 23.9 cells/mm2) and peripheral retina (53 ± 20.6 cells/mm2); compared to eyes received NaCl (216 ± 49.0 and 210 ± 50.5 cells/mm2, p < 0.001, respectively). Regarding CNV areas, no statistical significance was found between the groups. Conclusion: The CD11b‐HSVTK mouse is a feasible model for a local depletion of CD11b+ cells in the retina. Nevertheless, only a partial depletion of CD11b+ cells could be achieved compared to baseline data without any intravitreal injections. Our results did not reveal a significant reduction in CNV areas. In the light of previous knowledge, the potential influence of systemic immune cells on CNV formation might be more relevant than expected. [ABSTRACT FROM AUTHOR]

Purpose: To investigate functional and anatomical results up to 12 months after Descemet’s membrane endothelial keratoplasty (DMEK) for Fuchs’ endothelial dystrophy (FED) versus bullous keratopathy (BK) in consideration of morphologic characteristics on host’s endothelium-Descemet’s membranes (EDM). Methods: In a prospective consecutive case series, 119 eyes underwent a primary DMEK for FED or BK. Intraoperatively obtained EDM were investigated immunohistologically. Clinical and morphological parameters were compared between FED and BK. Results: Overall, the 12-months best-corrected visual acuity (BCVA) was 0.14 logMAR, and 0.10 logMAR in eyes without vision-limiting comorbidities; thereby no differences were revealed between eyes with FED and BK up to 12 months postoperative (p = 0.186 and p = 0.095, respectively). Correspondingly, the mean central corneal thickness (CCT) measured 520 vs. 529 µm and the mean endothelial cell density (ECD) was 1743 vs. 1457 cells/mm2 for FED and BK, 12 months postoperative. Regarding CCT and ECD, no differences were observed between the groups (p = 0.181 and p = 0.112, respectively). The overall detachment rate was 40% (48/119). Comparing FED and BK the detachment rates did not differ, which were 41% vs. 39% and 43% vs. 35%, in pseudophakic eyes (p = 0.554 and p = 0.601, respectively). Yet, the distribution of recurring graft detachments differed between FED and BK; secondary re-detachments were more frequent in the FED group (7 cases). Regarding histologic investigations, a lower ECD was found in specimens with BK, no differences were revealed for EDM and anterior banded layer thicknesses. Immunohistologically, differences in the distribution of fibronectin and cytokeratin were observed. A rarification of matrix proteins was found in EDM complexes with FED. Conclusions: DMEK produces similar results for FED and BK. However, the postoperative course may differ with regard to the recurrence of secondary graft detachments that may be associated by histopathologic particularities. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the photochemical degradation of trypan blue (TB) and to identify decomposition products. Methods: Defined solution samples of TB and a mixture with lutein/zeaxanthin were exposed to blue light. Thermal degradation processes were ruled out using controls not subjected to irradiation. All samples were analyzed using optical microscopy, UV/Vis spectroscopy, matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and nuclear magnetic resonance (NMR) spectrometry. Degradation kinetics were determined based on changes in absorbance; intermediates were identified by analyzing mass differences of characteristic fragment ion peaks within the fragmentation patterns, and assignments were verified by NMR. Results: TB demonstrated a photochemical degradation, which can be triggered by lutein/zeaxanthin. Intermediates vary depending on the presence of lutein/zeaxanthin. The self-sensitized photodegradation of TB occurs under generation of dimethyl sulfate and presumed formation of phenol. In contrast, within the presence of lutein/zeaxanthin the decomposition of TB indicates the formation of methoxyamine and sulfonyl arin. Thermal degradation processes were not observed. Conclusions: TB demonstrated a photodegradation that may be triggered by lutein/zeaxanthin and results in the formation of cytotoxic decomposition products. Our findings contribute to understand degradation mechanisms of TB and may elucidate previous clinical and experimental observations of cellular toxicity after TB application. [ABSTRACT FROM AUTHOR]

Purpose: The model of oxygen-induced retinopathy (OIR) is widely used to analyze pathomechanisms in retinal neovascularization. Previous studies have shown that macrophages (MP) play a key role in vessel formation in OIR, the influence of microglia (MG) having been discussed. The aim of our study was to analyze the spatial and temporal distribution and activation of MP/MG expressing CD115 and CD11b during the process of neovascularization in OIR.Methods: We used MacGreen mice expressing the green fluorescence protein (GFP) under the promoter for CD115. CD115+ cells were investigated in vivo by scanning laser ophthalmoscopy at postnatal days (P) 17 and 21 in MacGreen mice with OIR (75% oxygen from P7 to P12), and were compared to MacGreen room-air controls. In addition MP/MG were examined ex vivo using immunohistochemistry for CD11b+ detection on retinal flatmounts at P14, P17, and P21 of wild type mice with OIR.Results: In-vivo imaging revealed the highest density of activated MP/MG in tuft areas at P17 of MacGreen mice with OIR. Tufts and regions with a high density of CD115+ cells were detected close to veins, rather to arteries. In peripheral, fully vascularized areas, the distribution of CD115+ cells in MacGreen mice with OIR was similar to MacGreen room-air controls. Correspondingly, immunohistochemical analyses of retinal flatmounts from wild type mice with OIR induction revealed that the number of CD11b+ cells significantly varies between vascular, avascular, and tuft areas as well as between the retinal layers. Activated CD11b+ cells were almost exclusively found in avascular areas and tufts of wild type mice with OIR induction; here, the proportion of activated cells related to the total number of CD11b+ cells remained stable over the course of time.Conclusions: Using two different approaches to monitor MP/MG cells, our findings demonstrated that MP/MG concentrate within pathologically vascularized areas during OIR. We were able to clarify that reactive changes of CD11b+ cell distribution to OIR primarily occur in the deep retinal layers. Furthermore, we found the highest proportion of activated CD11b+ cells in regions with pathologic neovascularization processes. Our findings support previous reports about activated MP/MG guiding revascularization in avascular areas and playing a key role in the formation and regression of neovascular tufts. [ABSTRACT FROM AUTHOR]

Objective: To investigate the incidence and risk factors for retinal detachment (RD) after cataract surgery or refractive lens exchange (RLE) in patients aged below 61 years. Methods: Retrospective medical chart review of 7,886 patients (13,925 eyes) who underwent cataract surgery or RLE. Patients aged below 61 years were selected. Age, gender, axial length, follow-up times, and the occurrence of RD were recorded. Additional characteristics documented for RD cases were: history of RD, preexisting retinal findings, laser capsulotomy, status of macula at RD, date and details of RD. Results: From a total of 421 patients (677 eyes) aged below 61 years 24 cases of RD were identified, resulting in an overall cumulative incidence per eyes of 3.55%. The mean follow-up time was 45 ± 32.8 months. Ninety-two % of all RDs occurred within 3.6 years from surgery. Axial length had a significant effect on the risk of RD after cataract/ RLE surgery (HR = 1.42, P = 0.0001, 95% CI 1.19–1.69). The highest incidence of RD occurred in the subgroup of 25 to 28.9 mm axial length (10.2%). With an increase in age of ten years, the hazard of postoperative RD was not significantly increased by a factor of 1.50 (P = 0.286, 95% CI 0.71–3.15). The highest incidence of RD occurred in patients aged 50–54 years (5.39%). Compared to females, males had an almost twofold not significant risk of postoperative RD (HR = 1.96, P = 0.123, 95% CI 0.83–4.63). None of the RD cases had a history of RD. Conclusions: Axial length is a significant risk factor for pseudophakic RD. The need for cataract surgery or RLE should be carefully considered in patients with axial lengths between 25 and 29 mm, aged 50–54 years, in males, and in case of preexisting retinal findings. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the influence of complement component C5a inhibition on laser-induced choroidal neovascularization (CNV) in mice using a C5a specific l-aptamer. Methods: In C57BL/6 J mice CNV was induced by argon-laser, C5a-inhibitor (NOX-D20) was intravitreally injected in three concentrations: 0.3, 3.0, and 30 mg/ml. The unPEGylated derivate (NOX-D20001) was applied at 3.0 mg/ml; the vehicle (5 % glucose) was injected in controls. Vascular leakage was evaluated using fluorescence angiography, CNV area was examined immunohistochemically. Activated immune cells surrounding the CNV lesion and potential cytotoxicity were analyzed. Results: Compared to controls, CNV areas were significantly reduced after NOX-D20 injection at a concentration of 0.3 and 3.0 mg/ml ( p = 0.042; p = 0.016). NOX-D20001 significantly decreased CNV leakage but not the area ( p = 0.007; p = 0.276). At a concentration of 30 mg/ml, NOX-D20 did not reveal significant effects on vascular leakage or CNV area ( p = 0.624; p = 0.121). The amount of CD11b positive cells was significantly reduced after treatment with 0.3 and 3.0 mg/ml NOX-D20 ( p = 0.027; p = 0.002). No adverse glial cell proliferation or increased apoptosis were observed at effective dosages. Conclusions: Our findings demonstrate that the targeted inhibition of complement component C5a reduces vascular leakage and neovascular area in laser-induced CNV in mice. NOX-D20 was proven to be an effective and safe agent that might be considered as a therapeutic candidate for CNV treatment. The deficiency of activated immune cells highlights promising new aspects in the pathology of choroidal neovascularization, and warrants further investigations. [ABSTRACT FROM AUTHOR]

Purpose To investigate pathomechanisms involved in graft detachment after Descemet's membrane endothelial keratoplasty ( DMEK) and its clinical implications. Methods In a prospective case series, 30 eyes with Fuchs' endothelial dystrophy underwent DMEK. Intraoperatively obtained recipients' endothelium-Descemet's membranes ( EDMs) were investigated histologically and immunohistochemically. The postoperative donor graft status was categorized as attached or detached. Clinical and morphological parameters were analysed between the study groups. Results The detachment rate was 40% (12/30). There was no significant difference in postoperative visual acuity between the groups, but visual recovery was delayed in eyes with initially detached grafts. Gender, age, preoperative central corneal thickness or best corrected visual acuity did not influence the detachment rate. However, separation and disruption of the anterior banded layer ( ABL) were frequently observed in patients with graft detachment, and ABL thickness was identified as a significant predictor for graft detachment. The ABL thickness was 2.5 ± 0.9 μm and 3.5 ± 1.6 μm in patients with attached and detached grafts, respectively. Immunohistologically, a deficiency of fibronectin and cytokeratin was observed within the ABL of patients with detached grafts. In contrast, a complete removal of the EDM with residual stromal collagen fragments was observed in patients with adherent grafts. Conclusions Incomplete removal of the EDM, with residual ABL fragments on the recipients' corneal stroma, may be a risk factor for graft detachment after DMEK. The separation and disruption of the ABL might be promoted by a deficiency of matrix proteins, stronger biomechanical properties and a firm adherence to the posterior corneal stroma. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate commercially available 1- and 3-piece intraocular lenses (IOLs) with scanning electron microscopy (SEM). Setting: Department of Ophthalmology and Electron Microscopy Center, University Hospital Jena, Jena, Germany. Design: Experimental study. Methods: Seven +23.0 diopter IOLs of different design and material and from different manufacturers were chosen for a detailed assessment. Scanning electron microscopy was used at standardized magnifications to assess typical IOL characteristics. The particular focus was the optic edge, the optic surface, the haptic–optic junction, and the haptic. Results: All square-edged IOLs had a curvature radius of less than 10 μm, while the mean optic edge thickness ranged between 216 μm and 382 μm. A 360-degree square-edged boundary was present in all 3-piece IOLs and in a single 1-piece model. Relevant production remnants on the optic edge were observed in 1 case. Regarding the haptic, 3-piece IOLs had uniformly shaped fibers with a mean thickness of 177 μm ± 51 (SD) (range 116 to 220 μm). Chemical adhesives were used to attach the haptic in 1 case, where alterations of the IOL material were observed. In another case, the haptic fiber was press-fitted into the optic, which resulted in bulging of the optic profile. Inspection of surface characteristics showed wavelike patterns in 2 IOLs. Conclusions: Taking clinical relevance into account, all IOLs were of high manufacturing quality. Certain attention was paid in creating a sharp optic edge. Surface irregularities of 2 IOLs were attributed to the manufacturing technique. Methods for implementing the haptic–optic junction were diverse. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to develop surgical methods for the implantation of a wireless intraocular epiretinal retina implant (EPI RET3) in Göttingen minipigs. This animal model resembles closely the anatomical conditions in humans, and is thus suitable for investigating the EPI RET3 implant as designed for the application in humans. Methods: Phacoemulsification and vitrectomy was performed on the right eye of 16 Göttingen minipigs under general anesthesia. The implants, consisting of a receiver module and an electrode array connected via a flexible micro cable, were inserted through a corneoscleral incision. The receiver module was placed into the sulcus ciliaris and the electrode array was fixed onto the retina temporal to the optic disc with a retinal tack. Minipigs were monitored for intra- and postoperative ocular complications. Follow-up times were 3 (seven minipigs) and 12 weeks (nine minipigs). Results: Implantation was successfully performed in all 16 minipigs. The complete implantation surgery required on average 2 hours. Intraoperative findings were a minor hemorrhage of the anterior chamber angle in two eyes, one minor iris hemorrhage, and one minor punctiform retinal hemorrhage, which were all reversible. Postoperatively, the corneoscleral incision showed good wound healing in all eyes. Intraocular reactions included mainly fibrin exudation (six eyes) and formation of iris synechiae with the receiver module of the implants (three eyes). Conclusions: The performed implantation procedures of the intraocular EPI RET3 implant are feasible and reproducible within an acceptable surgical time. The development of inflammatory responses is a specific predisposition of the minipig following any intraocular intervention; nevertheless, the surgical techniques should be further improved to minimize procedure-related reactions. Our results provide a step towards the application of the EPI RET3 system in clinical studies. [ABSTRACT FROM AUTHOR]

Purpose: To record the spectral transmittance curves of various ultraviolet (UV) and blue-light-filtering intraocular lenses (IOLs), evaluate their UV and blue-light-radiation– absorption capacities, and compare them with those of the natural crystalline lens. Setting: Department of Ophthalmology, Duisburg-Essen University, Essen, Germany. Methods: Eight IOLs from 6 manufacturers were evaluated. The transmittance of wavelengths from 200 nm to 800 nm was measured using a high-performance spectrophotometer with a diffuse transmittance accessory through a 1.5 mm aperture. Results: All assessed IOLs provided good UVC (200 to 280 nm) and UVB (280 to 320 nm) protection, but 2 IOLs lacked sufficient UVA (320 to 400 nm) protection. Major differences in the absorption capacities were observed in the blue-light range (400 to 500 nm). Conclusions: The absorption characteristics of some UV and blue-light-filtering IOLs resembled those of the crystalline lens, but some differed. Long-term clinical trials should be performed to determine how blue-blocking IOLs affect the risk for progression of age-related macular degeneration. [Copyright &y& Elsevier]

Brockmann, C., Mummert, R., Ruhberg, H. and Storch, V. 1999. Ultrastructural investigations of the female genital system of Epiperipatus biolleyi (Bouvier 1902) (Onychophora, Peripatidae). — Acta Zoologica (Stockholm) 80: 339–349. The female genital system of the neotropical peripatid Epiperipatus biolleyi was examined using transmission and scanning electron microscopy. Special attention is given to the two accessory organs of the paired oviducts: the receptacula seminis and the ovarian funnels (Ovarialtrichter). The latter occur only in the Peripatidae, whereas receptacula seminis may also be present in the Peripatopsidae, the only other family in the Onychophora. The ovarian funnels of E. biolleyi are thin-walled and closed from the haemocoel. This trait has also been reported from Epiperipatus trinidadensis, Macroperipatus torquatus, and Eoperipatus weldoni, whereas other peripatids have ovarian funnels which have been reported to open into the haemocoel. The occurrence of artificially opened ovarian funnels, caused by tissue rupture during specimen preparation, is discussed. The presence of spermatozoa both in the receptaculum seminis and in parts of the uterus of the female examined in this study supports the hypothesis that in E. biolleyi insemination of juvenile females occurs directly via the genital opening. The female contained one unstalked cleavage embryo in each uterus horn. Two features of the uterus were found to be unique to E. biolleyi: (1) a second cell layer overlying the uterine epithelium with a pronounced secretory activity (2) embryos are enclosed in a noncellular coat interspersed with numerous transport vesicles. [ABSTRACT FROM AUTHOR]

A large number of experiments have demonstrated that misleading postevent information may result in distortions of eyewitness performance. However, most studies have employed a quite specific piece of misinformation (the colour of a car, a type of a road sign) rather than more general postevent information. In the present experiment subjects viewed a film depicting a traffic accident and were subsequently informed that the car driver had or had not committed hit-and-run behaviour and that the motorcyclist had or had not been drinking. An additional control group received no information. In a subsequent interrogation subjects were asked to rate the amount of cause, responsibility and guilt attributable to the car driver and motorcyclist. Results showed that responsibility and guilt and the statements on the accident-related behaviour were influenced by the postevent information. In general, subjects who had received negative information about one of the persons involved attributed higher amounts of responsibility and guilt to them and provided more negative statement s concerning their behaviour. However, details that were not closely related to the accident were no significantly influenced by postevent information. The results are discussed in terms of schematic memory reports. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Intraocular Collision Tumour: Case Report and Literature Review," that was published in the 2013 issue.

Purposes: Coats disease is a rare retinal vascular disorder characterized by telangiectasia and exudation affecting predominantly young male. Due to its rareness, analyses of large cohorts over long periods are of particular importance to give a prognosis for the usually very young patients and their parents, especially with regard to required therapy. Methods: We retrospectively analyzed patients diagnosed with Coats disease and treated between May 1992 und March 2019. The minimum follow‐up was 12 months. We evaluated the interventional procedures with regard to the initial stage. Results: Seventy‐seven eyes of 75 patients were included in the analyses. Eighty‐one percent were male; mean age was 17.8 ± 18.2 years (range 1–71; median 10.0). Mean follow‐up time was 7.3 ± 5.6 years (range 1.1–21.4; median 6.5). In eyes with stage 1 (n = 2) only lasercoagulation (LC) was necessary. In stage 2A 65% (11/17) of eyes required LC, 30% (5/17) cryotherapie (CT), 25% (4/17) vitrectomy (VT) and 18% (3/17) ruthenium brachytherapy (RT) due to secondary vasoproliferative retinal tumor. In stage 2B 88% (29/33) were treated with LC, 30% (10/33) with CT, 21% (7/33) needed VT and 6% (2/33) RT. In 89% (8/9) of eyes staged 3A1 LC was necessary, in 100% (9/9) CT and in 44% (4/9) VT. Three eyes were staged 3A2 and all of them required VT, two additional LC and one additional CT. Similar results were seen in stage 3B (five eyes): in all eyes VT was performed, in 80% (4/5) LC and CT was done in addition. Four of six (66%) stage 4 eyes were enucleated, the 2 remaining received CT and VT or RT. We had 2 stage 5 eyes, thereof one required enucleation. Conclusion: Therapy in patients with Coats' disease strongly depends on the initial stage with less intense procedures in early stages. While most invasive treatment was necessary in stage 3, the rate of enucleation was, as expected, highest in stage 4. Therefore early diagnosis and immediate treatment is of highest priority to preserve the eye. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to identify predictors for the best-corrected visual acuity (BCVA), central corneal thickness (CCT), and the endothelial cell density (ECD) after primary Descemet's membrane endothelial keratoplasty (DMEK). Methods: In a prospective observational study, 108 eyes with Fuchs' endothelial dystrophy underwent a primary DMEK. Preoperative data, histologic parameters from host's Descemet's membrane, and follow-up data of the first eye were analyzed in regard to BCVA, CCT, and ECD, 12 months after surgery. Results: Overall, 12 months postoperative, the BCVA improved to 0.11 ± 0.11 logMAR, the CCT declined to 529 ± 42 µm, and the ECD measured 1675 ± 418 cells/mm2. A significant influence of the preoperative CCT on postoperative BCVAs and CCTs was observed (r = 0.299, p = 0.014 and r = 0.507, p < 0.001, respectively). Especially eyes with a CCT <625 µm demonstrated a better BCVA (0.05 ± 0.07 logMAR) than eyes with a CCT ≥625 µm (0.13 ± 0.11 logMAR, p = 0.002). Furthermore, the identification of eyes with an early visual restitution was possible by considering follow-up data of the first eye. A preoperative CCT ≥625 µm was also sensitive to identify eyes with a persistent corneal swelling. The anterior banded layer thickness, which was obtained histologically, correlated to the preoperative CCT and the frequency of graft detachments (r = 0.601, p = 0.023 and r = 0.652, p = 0.041, respectively). Furthermore, a graft's baseline ECD ≤2100 cells/mm2 was found to be a risk factor for an ECD deterioration under 1000 cells/mm2 (1.8% vs. 15.8%, p = 0.020). Conclusions: Simple clinical parameters, such as the preoperative CCT, the course of visual restitution of the first eye, and the graft's baseline ECD, are efficient predictors for relevant outcome parameters after DMEK and therefore may be used for stratification. Furthermore, our findings indicate that a DMEK should be performed in eyes with Fuchs' endothelial corneal dystrophy, if possible, before the CCT exceeds 625 µm to maintain good clinical results. [ABSTRACT FROM AUTHOR]

Anti-VEGF-directed therapies have been a milestone for treating retinal vascular diseases. Depletion of monocyte lineage cells suppresses pathological neovascularization in the oxygen-induced retinopathy mouse model. However, the question whether myeloid-derived VEGF-A expression is responsible for the pathogenesis in oxygen-induced retinopathy remained unknown. We analyzed LysMCre-driven myeloid cell-specific VEGF-A knockout mice as well as mice with complete depletion of circulating macrophages through clodronate-liposome treatment in the oxygen-induced retinopathy model by immunohistochemistry, qPCR, and flow cytometry. Furthermore, we analyzed VEGF-A mRNA expression in MIO-M1 cells alone and in co-culture with BV-2 cells in vitro . The myeloid cell-specific VEGF-A knockout did not change relative retinal VEGF-A mRNA levels, the relative avascular area or macrophage/granulocyte numbers in oxygen-induced retinopathy and under normoxic conditions. We observed an insignificantly attenuated pathology in systemically clodronate-liposome treated knockouts but evident VEGF-A expression in activated Müller cells on immunohistochemically stained sections. MIO-M1 cells had significantly higher expression levels of VEGF-A in co-culture with BV-2 cells compared to cultivating MIO-M1 cells alone. Our data show that myeloid-derived cells contribute to pathological neovascularization in oxygen-induced retinopathy through activation of VEGF-A expression in Müller cells. [ABSTRACT FROM AUTHOR]

Background: To investigate whether vaccination against SARS-CoV-2 is associated with the onset of retinal vascular occlusive disease (RVOD). Methods: In this multicentre study, data from patients with central and branch retinal vein occlusion (CRVO and BRVO), central and branch retinal artery occlusion (CRAO and BRAO), and anterior ischaemic optic neuropathy (AION) were retrospectively collected during a 2-month index period (1 June–31 July 2021) according to a defined protocol. The relation to any previous vaccination was documented for the consecutive case series. Numbers of RVOD and COVID-19 vaccination were investigated in a case-by-case analysis. A case–control study using age- and sex-matched controls from the general population (study participants from the Gutenberg Health Study) and an adjusted conditional logistic regression analysis was conducted. Results: Four hundred and twenty-one subjects presenting during the index period (61 days) were enrolled: one hundred and twenty-one patients with CRVO, seventy-five with BRVO, fifty-six with CRAO, sixty-five with BRAO, and one hundred and four with AION. Three hundred and thirty-two (78.9%) patients had been vaccinated before the onset of RVOD. The vaccines given were BNT162b2/BioNTech/Pfizer (n = 221), followed by ChadOx1/AstraZeneca (n = 57), mRNA-1273/Moderna (n = 21), and Ad26.COV2.S/Johnson & Johnson (n = 11; unknown n = 22). Our case–control analysis integrating population-based data from the GHS yielded no evidence of an increased risk after COVID-19 vaccination (OR = 0.93; 95% CI: 0.60–1.45, p = 0.75) in connection with a vaccination within a 4-week window. Conclusions: To date, there has been no evidence of any association between SARS-CoV-2 vaccination and a higher RVOD risk. [ABSTRACT FROM AUTHOR]

Aims To analyse morphologic alterations on posterior iris-claw intraocular lenses (IOL) after dislocation due to traumatic disenclavation. Methods Seven dislocated iris-claw IOLs were included in this observational study. Five posterior iris-claw IOLs were explanted after traumatic disenclavation and compared to two iris-claw IOLs with a history of spontaneous disenclavation. One original aphakic irisclaw IOL served as control. All IOLs underwent standardised examinations using light microscopy. Results All traumatically disenclaved iris-claw haptics presented decentred and twisted fixation arms. The average decentration on iris-claw haptics measured 23±11 mm in the surface plane and 103±43 mm on the edge profile; the axial twist of the fixation arms measured five angular degrees. Traumatically affected haptics were tilted (3/5) or did not provide an adequate closure (2/5), so that a reliable fixation on the iris stroma was not ensured. Morphologic alterations were significantly different after traumatic and spontaneous disenclavation. Spontaneously disenclaved IOLs and the original IOL demonstrated symmetric haptics with centred iris-claws and a sufficient closure. Conclusions Traumatically dislocated iris-claw IOLs presented considerable alterations on the affected haptics, which might not guarantee a reliable reenclavation. Therefore, we suggest an IOL replacement, instead of reenclavation, in cases of traumatic iris-claw disenclavation. [ABSTRACT FROM AUTHOR]

Background: The fixation of polyimide stimulator foils as the basic substrate of epiretinal prostheses by using retinal tacks may cause retinal or choroidal alterations such as retinal proliferations or choroidal neovascularizations. During the prospective trial for the semichronical testing of a wireless intraocular retinal implant (EPIRET3) we investigated alterations in angiographic findings during implantation and after explantation of the device, to detect potential vascular pathologies at the fixation site or elsewhere. Methods: As the final step of the implantation surgery in six blind patients, the stimulator was placed on the retinal surface using retinal tacks. For the detection of possible morphological or vascular alterations committed by the implant fluorescein angiography (FA) was performed 1 day before and 4 weeks after implantation surgery, as well as at the final visit 5 months after explantation. Results: Following implantation surgery funduscopy and FA did not reveal any evidence of either vascular pathologies or choroidal neovascularisations (CNV), in addition, no cystoid macular edema (CME) occurred after 4 weeks. At the 6-month follow-up visit, we found a mild epiretinal gliosis formation in four patients. In one patient a retinal break occurred during explantation, requiring a temporary silicone-oil endotamponade. At the final visit, we observed a focal proliferative vitreoretinopathy (PVR) reaction without activity, while there was no evidence for a CNV formation in that area. Conclusions: The FA findings confirm our previous results on the safety of the EPIRET3 system, which was tolerated in all patients but revealed a certain risk profile in regard to the stimulator fixation. While there was no evidence for newly occurred CME or CNV during the follow-up visits, nevertheless gliosis or even PVR reaction at the tack's fixation site suggests the need to develop alternative fixation procedures of epiretinal stimulators. [ABSTRACT FROM AUTHOR]

Aims/Purpose: Brachytherapy using ruthenium is an established procedure for the treatment of uveal melanomas, the most common malignant primary intraocular tumour in adults. The supplementary use of transpupillary thermotherapy (TTT) with brachytherapy is known as sandwich therapy. Due to the rarity of uveal melanomas, long‐term outcome of large cohorts treated by ruthenium brachytherapy with and without TTT is of special clinical and scientific interest. Methods: Based on a retrospective longitudinal study, patients with uveal melanoma who received treatment using ruthenium brachytherapy at the Department of Ophthalmology from 1994 to 2021, were analysed. The evaluation includes tumour height, visual acuity, radiation data, side effects, local recurrence, bulbus preservation and occurrence of metastasis. Results: Overall, 150 patients with medium sized uveal melanoma (tumour height >3.0 and ≤7.0 mm) who received ruthenium brachytherapy were included. The mean age of patients at diagnosis was 63.5 ± 12.9 years (median 65), the proportion of women was 60.0%. Tumours were located centrally in 48.7% of cases; ciliary body involvement was seen in 4%. Additive transpupillary thermotherapy (TTT) was performed in 70.7% of cases as part of a sandwich therapy. After therapy and a mean follow‐up of 68.0 ± 58.3 years tumours height was significantly reduced from 4.5 ± 1.1 to 1.4 ± 1.6 mm (p < 0.001). Visual acuity showed deterioration from 0.25 ± 0.43 to 1.0 ± 0.85 logMAR (p < 0.001) due to the large proportion of centrally located tumours. In 29.9% of cases no side effects requiring therapy occurred. Within the remaining cases cataracta complicata (41.3%) and radiation retinopathy (30.0%) were observed. Local tumour control was achieved in 86.0% of patients, in 91.3% of cases the ocular globe was preserved. Metastatic free survival was seen in 86.4% of patients. Conclusions: Brachytherapy using ruthenium plaque with and without TTT represents a safe procedure in the treatment of uveal melanomas over the last three decades. [ABSTRACT FROM AUTHOR]

Aims/Purpose: Formation of a full‐thickness macular hole (MH) after vitrectomy is extremely rare. Previous studies only included small numbers of cases. Aim of the present study was to describe course, functional prognosis and risk factors of secondary macular hole development following surgical treatment of a primary rhegmatogenous retinal detachment (RRD) in a large data set from two tertiary eye clinics. Methods: Formation of a full‐thickness macular hole (MH) after vitrectomy is extremely rare. Previous studies only included small numbers of cases. Aim of the present study was to describe course, functional prognosis and risk factors of secondary macular hole development following surgical treatment of a primary rhegmatogenous retinal detachment (RRD) in a large data set from two tertiary eye clinics. Results: Out of 9317 eyes following PPV 28 eyes (mean age 58.7 ± 9.6 yrs, 50% male, 60.7% right eyes) could be included. The interval between vitrectomy and MH formation was 46.9 ± 80.3 (range: 1–373) months. 15 eyes showed history of macular involving RRD, 7 macular sparing RRD. Sulphur‐hexafluoride (SF6) 20–25% was used as endotamponade in 18 cases for RRD repair, silicone oil (Sil5000® and Sil2000®) in 4 cases. Six cases were not assessable due to earlier external surgery. In secondary MH re‐PPV with SF6 20–25% endotamponade in 21 eyes (thereof with an ILM flap in 8 cases), Sil5000® in 6 eyes and Densiron® in one eye was performed. A primary closure rate of 88.2% with gas was achieved with a final best corrected visual acuity of 0.67 ± 0.99 logMAR. Degree of myopia, which correlated with functional results (p = 0.019) and earlier time of onset (p = 0.007), as well as timing of cataract surgery (p < 0.001) could be identified as risk factor for secondary MH development. Conclusions: Secondary MH after RRD repair is rare. In our study with the largest cohort studied so far, we can identify risk factors that lead to earlier MH formation. Myopia was shown to be a prognostic factor for functional outcome. [ABSTRACT FROM AUTHOR]

Microglia play a major role in retinal neovascularization and degeneration and are thus potential targets for therapeutic intervention. In vivo assessment of microglia behavior in disease models can provide important information to understand patho-mechanisms and develop therapeutic strategies. Although scanning laser ophthalmoscope (SLO) permits the monitoring of microglia in transgenic mice with microglia-specific GFP expression, there are fundamental limitations in reliable identification and quantification of activated cells. Therefore, we aimed to improve the SLO-based analysis of microglia using enhanced image processing with subsequent testing in laser-induced neovascularization (CNV). CNV was induced by argon laser in MacGreen mice. Microglia was visualized in vivo by SLO in the fundus auto-fluorescence (FAF) mode and verified ex vivo using retinal preparations. Three image processing algorithms based on different analysis of sequences of images were tested. The amount of recorded frames was limiting the effectiveness of the different algorithms. Best results from short recordings were obtained with a pixel averaging algorithm, further used to quantify spatial and temporal distribution of activated microglia in CNV. Morphologically, different microglia populations were detected in the inner and outer retinal layers. In CNV, the peak of microglia activation occurred in the inner layer at day 4 after laser, lacking an acute reaction. Besides, the spatial distribution of the activation changed by the time over the inner retina. No significant time and spatial changes were observed in the outer layer. An increase in laser power did not increase number of activated microglia. The SLO, in conjunction with enhanced image processing, is suitable for in vivo quantification of microglia activation. This surprisingly revealed that laser damage at the outer retina led to more reactive microglia in the inner retina, shedding light upon a new perspective to approach the immune response in the retina in vivo . [ABSTRACT FROM AUTHOR]

Background Retinal implants have been developed to treat blindness causing retinal degenerations such as Retinitis pigmentosa (RP). The retinal stimulators are covering only a small portion of the retina usually in its center. To restore not only central vision but also a useful visual field retinal stimulators need to cover a larger area of the retina. However, large area retinal stimulators are much more difficult to implant into an eye. Some basic questions concerning this challenge should be answered in a series of experiments. Methods Large area retinal stimulators were fabricated as flexible multielectrode arrays (MEAs) using silicon technology with polyimide as the basic material for the substrate. Electrodes were made of gold covered with reactively sputtered iridium oxide. Several prototype designs were considered and implanted into enucleated porcine eyes. The prototype MEAs were also used as recording devices. Results Large area retinal stimulator MEAs were fabricated with a diameter of 12 mm covering a visual angle of 37.6° in a normal sighted human eye. The structures were flexible enough to be implanted in a folded state through an insertion nozzle. The implants could be positioned onto the retinal surface and fixated here using a retinal tack. Recording of spontaneous activity of retinal neurons was possible in vitro using these devices. Conclusions Large flexible MEAs covering a wider area of the retina as current devices could be fabricated using silicon technology with polyimide as a base material. Principal surgical techniques were established to insert such large devices into an eye and the devices could also be used for recording of retinal neural activity. [ABSTRACT FROM AUTHOR]

Aims: For the purpose of visual rehabilitation of subjects with photoreceptor degeneration, an implantable microelectronic device for epiretinal stimulation was developed. Our study aimed to show whether implantation and explantation could be conducted safely and to investigate tissue compatibility. Methods: The device was implanted in 5 Göttinger minipigs. Four weeks later, the implant was surgical- ly removed. Histopathological examination that followed aimed at detecting inflammatory or proliferative changes. Stains used were hematoxylin and eosin, leukocyte common antigen, CD68 and glial fibrillary acidic protein. A grinding technique was used to visualize the retinal tissue in conjunction with the retinal tacks. Results: The implantation of the devices was successful in all cases. The explantation was complicated by intraoperative hemorrhages. Complete explantation could only be achieved after modifying the implantation strategy. Histopathology revealed a mild degree of cystic disaggregation of the retina. Immunohistochemically, an increased glial fibrillary acidic protein expression of Müller cells was found, which shows a moderate glial cell activation. Inflammatory cells were absent. Using the grinding technique, tissue adjacent to the retinal tacks showed a mild gliosis. Discussion: The viability of implantation and explantation of the implant in minipigs has been shown. The absence of immunoreactive cells or a considerable glial reaction suggest that the device may be considered safe and suitable for further implantation in humans. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: To compare keratocyte loss in the corneal stroma after laser-assisted subepithelial keratectomy (LASEK) and photorefractive keratectomy (PRK) in rabbits.Setting: Department of Ophthalmology, University of Essen, Essen, and the Institute of Anatomy, University of Bochum, Bochum, Germany.Methods: Laser-assisted subepithelial keratectomy and PRK were performed in rabbits and studied 1, 3, 10, and 20 days after surgery. Excimer photoablation was done unilaterally with a 6.0 mm ablation zone and an 80 μm depth, equivalent to -6.0 diopters. Keratocyte death was analyzed using DNA fragmentation-detecting terminal deoxynucleotidyl transferase deoxy-UTR-nick end labeling (TUNEL) assay and transmission electron microscopy.Results: Numerous TUNEL-positive keratocytes occurred 1 day after PRK; the number decreased significantly after 3 days. After LASEK, significantly fewer TUNEL-positive keratocytes were noted at the early time points (P<.001 at 1 day; P≤.05 at 3 days). At 10 days, the number of TUNEL-positive keratocytes decreased in both groups but remained significantly higher after PRK than after LASEK (P<.001). Twenty days after both procedures, no significant signs of keratocyte death were found in the corneal stroma. Transmission electron microscopy revealed few apoptotic keratocytes after LASEK. After PRK, apoptotic keratocytes, characterized by chromatin condensation, apoptotic bodies, and cell shrinkage, were scattered in the stroma. The ultrastructural findings confirmed the results obtained with the TUNEL assay.Conclusions: Laser-assisted subepithelial keratectomy induced significantly less apoptotic keratocyte death than PRK and promoted wound healing in the acute phase after photoablation. This procedure may offer the possibility of treating higher myopia with a decreased risk for developing wound healing-related complications known to occur after PRK. [Copyright &y& Elsevier]

: PurposeTo evaluate and compare the efficacy of oral clorazepate dipotassium (Tranxilium®) and intravenous midazolam (Dormicum®) as premedication agents in retrobulbar anesthesia and clear corneal phacoemulsification with intraocular lens (IOL) implantation.: SettingDepartment of Ophthalmology, University of Essen, Essen, Germany.: MethodsIn a prospective clinical trial, 97 consecutive patients (97 eyes) having phacoemulsification with implantation of a foldable IOL were randomized to 2 groups. The first group received 10 mg oral clorazepate dipotassium and the second group, 1 mg intravenous midazolam. The surgeon''s subjective experience of patients'' cooperation during retrobulbar anesthesia and after surgery was measured on a 5-point Likert scale. The duration of surgery and rate of complications were documented. One day after surgery, the patients'' subjective comfort during cataract surgery was evaluated using a 5-point Likert scale and the best corrected visual acuity was determined.: ResultsThe level of anterograde amnesia tended to be higher in the midazolam group than in the clorazepate dipotassium group (4% versus 0% for anesthesia administration; 14% versus 4% for surgery), but the difference between groups was not significant. There were no significant differences in patient cooperation or complications during surgery. Patient satisfaction scores were not significantly different between the groups (P<.14); however, patients in the midazolam group expected to have significantly less pain during surgery (P<.04). The rate of potential visual acuity recovery was similar between groups.: ConclusionsAnterograde amnesia occurred more frequently and patients expected less pain before surgery with midazolam. Both anesthetic agents provided safe and effective premedication for retrobulbar anesthesia in clear corneal cataract surgery. [Copyright &y& Elsevier]

Background: Retinal implants have been developed to treat blindness causing retinal degenerations such as Retinitis pigmentosa (RP). The retinal stimulators are covering only a small portion of the retina usually in its center. To restore not only central vision but also a useful visual field retinal stimulators need to cover a larger area of the retina. However, large area retinal stimulators are much more difficult to implant into an eye. Some basic questions concerning this challenge should be answered in a series of experiments.Methods: Large area retinal stimulators were fabricated as flexible multielectrode arrays (MEAs) using silicon technology with polyimide as the basic material for the substrate. Electrodes were made of gold covered with reactively sputtered iridium oxide. Several prototype designs were considered and implanted into enucleated porcine eyes. The prototype MEAs were also used as recording devices.Results: Large area retinal stimulator MEAs were fabricated with a diameter of 12 mm covering a visual angle of 37.6° in a normal sighted human eye. The structures were flexible enough to be implanted in a folded state through an insertion nozzle. The implants could be positioned onto the retinal surface and fixated here using a retinal tack. Recording of spontaneous activity of retinal neurons was possible in vitro using these devices.Conclusions: Large flexible MEAs covering a wider area of the retina as current devices could be fabricated using silicon technology with polyimide as a base material. Principal surgical techniques were established to insert such large devices into an eye and the devices could also be used for recording of retinal neural activity. [ABSTRACT FROM AUTHOR]