[Long-term outcome of macular neovascularization secondary to choroidal osteoma with and without intravitreal anti-VEGF(vascular endothelial growth factor)- treatment]. / Langzeitverlauf von makulären Neovaskularisationen bei chorioidalen Osteomen mit und ohne intravitreale Anti-VEGF(vascular endothelial growth factor)-Therapie.

BACKGROUND: Choroidal osteoma (CO) is a benign ossifying ocular tumor, which is unilateral in most cases. The CO may cause severe visual impairment, especially in the case of a secondary macular neovascularization (MNV). OBJECTIVE: Based on a case series of patients with MNV secondary to CO, the variability of the clinical course with and without intravitreal anti-vascular endothelial growth factor (VEGF) treatment is presented. METHODS: All patients diagnosed with secondary MNV due to CO between 2007 and 2023 were retrospectively assessed with respect to the clinical course. RESULTS: In this study 7 eyes of 5 patients (4 women, 1 man) were diagnosed with secondary MNV due to CO. Intravitreal anti-VEGF treatment was carried out in 2 patients with unilateral MNV and 1 patient was treated in both eyes for bilateral MNV. In another case with bilateral MNV, only 1 eye was treated because of fibrosis in the other eye. A further case with unilateral CO and MNV scars at the initial diagnosis was left untreated. Overall, in 3 out of 5 eyes treated with intravitreal VEGF inhibition stabilization or improvement of visual acuity could be achieved. CONCLUSION: In our case series intravitreal anti-VEGF treatment attained a functional stabilization or improvement in 3 out of 5 treated eyes. In one case of CO-associated MNV fibrosis rapidly developed without treatment. Therefore, the clarification for patients with CO about the lifelong risk for development of a secondary MNV is essential in individual cases for early treatment. As no standardized treatment scheme for intravitreal VEGF antibodies for CO-related MNV exists, the treatment is planned on an individual basis.

Comparability of input parameters in the German Retina.net ROP registry and the EU-ROP registry - An exemplary comparison between 2011 and 2021.

PURPOSE: The German Retina.net ROP registry and its Europe-wide successor, the EU-ROP registry, collect data from patients treated for ROP. This analysis compares input parameters of these two registries to establish a procedure for joint analyses of different registry data using exemplary datasets from the two registries. METHODS: Exemplary datasets from the two databases over a 1-year period each (German Retina.net ROP Registry, 2011, 22 infants; EU-ROP Registry, 2021, 44 infants) were compared. The parameters documented in the two databases were aligned and analysed regarding demographic parameters, treatment modalities, complications within first 24 h and retreatments. RESULTS: The current analysis showed that data can be aligned for joint analyses with some adjustments within the data structure. The registry with more detailed data collection (EU-ROP) needs to be reduced regarding granularity in order to align the different registries, as the registry with lower granularity determines the level of analyses that can be performed in a comparative approach. In the exemplary datasets, we observed that the overall most common ROP severity in both registries was zone II, 3+ (2011: 70.5%; 2021: 65%), with decreasing numbers of clock hours showing preretinal neovascularisations (2011: 10-12 clock hours in 29% of cases, 2021: 4-6 clock hours in 38%). The most prevalent treatment method was laser coagulation in 2011 (75%) and anti-VEGF therapy in 2021 (86.1%). Within the anti-VEGF group, all patients were treated with bevacizumab in 2011 and with ranibizumab in 2021. Retreatment rates were comparable in 2011 and 2021. CONCLUSION: Data from two different ROP registries can be aligned and jointly analysed. The analysis reveals a paradigm shift in treatment modalities, from predominantly laser to anti-VEGF, and within the anti-VEGF group from bevacizumab to ranibizumab in Germany. In addition, there was a trend towards earlier treatment in 2021.

Plant stem cell extract from Coffea canephora shows antioxidant, anti-inflammatory, and skin regenerative properties mediated by suppression of nuclear factor-κB.

Plant cell cultures have become a promising production platform of bioactive compounds for biomedical and cosmetic uses in the last decades. However, the success so far has been limited. The study aimed to evaluate the effectiveness of this unique biotechnology process to obtain a bioactive stem cell extract of Coffea canephora (SCECC) with antioxidant, anti-inflammatory, and regenerative properties. Total phenolic and flavonoid contents were determined in the SCECC by spectrophotometry. The chemical composition of the extracts was characterized by mass spectrometry. Antioxidant activity was evaluated using the colorimetric methods of free radical scavenging 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and the ferric reducing ability of plasma (FRAP). The anti-inflammatory activity was determined in lipopolysaccharide-stimulated RAW 264.7 macrophages through the production of superoxide anion (O2•-), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and the activity of nuclear factor kappa B (NF-κB). Moreover, the ability of SCECC to stimulate the proliferation and migration of fibroblasts was assessed. Five compounds were tentatively identified, two flavonoids, two phenolic acids, and one sugar. High phenolic content and antioxidant activity were observed in the SCECC. SCECC promoted the proliferation and migration of fibroblasts and suppressed the pro-inflammatory mediators O2•-, NO, TNF-α, and IL-6 in a dose-dependent manner. Moreover, SCECC inhibited the NF-κB transcription factor. Therefore, we obtained evidence that the extract from C. canephora stem cells can be used as a natural agent against skin damage. Hence, it could be of interest in cosmetics for preventing skin aging.

Unexplained visual loss after primary pars-plana-vitrectomy with silicone oil tamponade in fovea-sparing retinal detachment.

BACKGROUND: To investigate the incidence and clinical characteristics of unexplained visual loss in patients with fovea-sparing rhegmatogenous retinal detachment (RRD) during or after silicone oil (SO) tamponade. METHODS: The medical charts of all patients with macula-on RRDs, who underwent pars-plana-vitrectomy (ppV) with SO tamponade were retrospectively assessed regarding unexplained visual loss (UVL) of ≥ 3 Snellen lines and alterations on optical coherence tomography (OCT) during or after SO tamponade. The clinical data analysed included visual acuity, surgical parameters, OCT images, duration of SO tamponade and the time point of visual decline. Cases with re-detachment or secondary causes of visual loss such as SO emulsification, epiretinal membranes or macular edema were excluded. RESULTS: Over a 15-year-period, 22 cases with macula-on RRD, which had primarily been treated with ppV and SO tamponade, met the inclusion criteria. In most eyes (n = 20; 91%), the RRD was caused by a giant retinal tear (GRT). In 11 of these 22 cases (50%), best-corrected visual acuity (BCVA) had dropped by at least 3 lines for no apparent reason. In these 11 cases, mean preoperative logMAR BCVA was 0.2 (SD 0.13; range 0-0.5), equal to Snellen's VA of 0.63, and mean postoperative logMAR BCVA 1.0 (SD 0.24; range 0.5-1.3), equal to Snellen's VA of 0.10. Visual decline occurred about 12 weeks postoperatively (SD 6.2; range 3-20 ) and comprised 8 lines (SD 2.3; range -11 to -4). SO was removed on average 139 (SD 50.0; range 88-271) days after the first ppV. In 9 cases visual decline occurred while the SO was in-situ. In 2 patients, BCVA decline was noted 2 weeks after SO removal. In all eyes, preoperative central foveal thickness (CFT) was 254 µm (SD 24.2), which decreased to 224 µm (SD 29.6) during SO tamponade and increased to 247 µm (SD 29.2) after SO removal, irrespective of the presence of UVL. The mean follow-up time was 20 months (SD 30.6) after SO removal. CONCLUSION: UVL after SO tamponade for macula-on RRD is more frequent than expected. The incidence in our case series was 50%. The mechanism of this phenomenon is still unknown. In general, vitreoretinal surgeons should thoroughly question the need for SO tamponade, inform their patients of possible UVL and remove SO as early as possible. TRIAL REGISTRATION: The study was approved by the local ethics committee on 6th of May 2022 (Ethikkommission der Universität Regensburg, Votum 22-2925-104) and was conducted in accordance with the ethical standards of the Declaration of Helsinki.

Plant stem cell extract from Coffea canephora shows antioxidant, anti-inflammatory, and skin regenerative properties mediated by suppression of nuclear factor-κB

Plant cell cultures have become a promising production platform of bioactive compounds for biomedical and cosmetic uses in the last decades. However, the success so far has been limited. The study aimed to evaluate the effectiveness of this unique biotechnology process to obtain a bioactive stem cell extract of Coffea canephora (SCECC) with antioxidant, anti-inflammatory, and regenerative properties. Total phenolic and flavonoid contents were determined in the SCECC by spectrophotometry. The chemical composition of the extracts was characterized by mass spectrometry. Antioxidant activity was evaluated using the colorimetric methods of free radical scavenging 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and the ferric reducing ability of plasma (FRAP). The anti-inflammatory activity was determined in lipopolysaccharide-stimulated RAW 264.7 macrophages through the production of superoxide anion (O2•-), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and the activity of nuclear factor kappa B (NF-κB). Moreover, the ability of SCECC to stimulate the proliferation and migration of fibroblasts was assessed. Five compounds were tentatively identified, two flavonoids, two phenolic acids, and one sugar. High phenolic content and antioxidant activity were observed in the SCECC. SCECC promoted the proliferation and migration of fibroblasts and suppressed the pro-inflammatory mediators O2•-, NO, TNF-α, and IL-6 in a dose-dependent manner. Moreover, SCECC inhibited the NF-κB transcription factor. Therefore, we obtained evidence that the extract from C. canephora stem cells can be used as a natural agent against skin damage. Hence, it could be of interest in cosmetics for preventing skin aging.

[Chordoma-An update]. / Chordome ­ Ein Update.

Chordomas are rare malignant tumors of the axial skeleton with notochordal differentiation. From a morphological point of view, chordomas display a broad spectrum ranging from the classical, conventional form not otherwise specified (NOS) to forms with hepatoid or renal carcinoma-like differentiation or even poorly or dedifferentiated variants. The detection of brachyury is highly characteristic, though not exclusive. The morphological differential diagnosis from a benign notochordal tumor (BNCT) requires integration of imaging since BNCT is limited to the vertebral bodies and is not osteolytic. Targeted therapy is a current research focus and cell lines as in vitro models are a precondition for the establishment and validation of this approach.

[Primary extra-axial chondroid chordoma of the anterior nasal septum: case report of a rare chordoma with literature review]. / Primäres extraaxiales chondroides Chordom des anterioren Nasenseptums: Fallbericht eines seltenen Chordoms mit Literaturübersicht.

An 87-year-old patient reported a nodular, progressively enlarging mass of the anterior nasal septum leading to partial obstruction of the nostrils. The tumor showed no infiltration of the subcutis, bone, or paranasal sinuses in imaging or intraoperatively. Histological examination revealed a chondroid tumor with lobular growth and physaliferous cell morphology. Immunohistochemistry revealed a brachyury-positive tumor without EWSR1 rearrangement, leading to the diagnosis of a chondroid chordoma. The reported case demonstrates the differential diagnostic considerations pertaining to this rare tumor, which can also have an untypical and very rare extra-axial location. Review of the literature identified 34 primary extraosseous chordomas of the nose, nasopharynx, and paranasal sinuses, and allowed the nasal chordoma presented herein to be included in this group of extra-axial chordomas.

[Anti-VEGF-therapy of fibrovascular and serous-vascularized pigment epithelial detachment in neovascular AMD : A retrospective five-year-analysis]. / Anti-VEGF-Therapie bei fibrovaskulärer und serös-vaskularisierter Pigmentepithelabhebung bei neovaskulärer AMD : Eine retrospektive Fünf-Jahres-Analyse.

BACKGROUND: Neovascular age-related macular degeneration (nAMD) is the most frequent cause of pigment epithelial detachment (PED). In the clinical routine the treatment of fibrovascular PED (fPED) and serous vascularized PED (svPED) with intravitreal vascular endothelial growth factor (VEGF) inhibitors has a restricted prognosis. OBJECTIVE: There are limited data on the long-term outcome of PED under anti-VEGF therapy. Therefore, this study recorded the course of treated PEDs in nAMD eyes over a period of 5 years. METHODS: All eyes with fPED or svPED that underwent anti-VEGF medication between 2006 and 2015 were retrospectively analyzed regarding the clinical course and the morphology seen on optical coherence tomography (OCT). The inclusion criteria were the detection of a PED on OCT, the angiographic verification of nAMD, a documented clinical history over 5 years and a good image quality. RESULTS: A total of 23 eyes from 22 patients met the inclusion criteria. After 5 years a significant deterioration of visual acuity (VA) was seen in all eyes (p = 0.007) and in the subgroup of cases with fPED (p = 0.045). In the eyes with svPED the decline of VA was not significant (p = 0.097). In the collective study group a statistically significant reduction of PED height (p = 0.006) and an increase of PED diameter was measured (p = 0.002). In the subgroup analysis the decrease of PED height and increase of PED diameter were significant for cases with svPED (p = 0.004, p = 0.013, respectively) but were not statistically significant for fPED eyes (height: p = 0.616; diameter: p = 0.097). In 17 (74%) eyes fibrosis or atrophy were seen on the final assessment of OCT images. DISCUSSION: After 5 years of anti-VEGF therapy for nAMD-associated PED the VA declined in half of the eyes and the OCT showed an unfavorable morphology in 3/4 of the cases. The average number of visits and injections was distinctly lower than in clinical trials and other real-life analyses. In summary, we observed an undertreatment with a worse functional and anatomical outcome in our clinical routine compared to other studies.

Biomechanical aspects of the posteromedial split in bicondylar tibial plateau fractures-a finite-element investigation.

PURPOSE: To gain principal insight into fixation techniques of a posteromedial split fragment in bicondylar tibial plateau fractures. METHODS: A computer simulation was performed, applying the finite-element method (FEM) to compare four methods of fixation of the posteromedial split fragment: lateral plate (model 1), lateral plate and kickstand screw (model 2), lateral plate and two antero-posterior lag screws (model 3), and lateral and posteromedial plate (model 4). The displacement of the fragment and material stresses in implants and bone under 2500 N axial load were analyzed. RESULTS: Maximal displacement of the posteromedial split fragment of 2.8 mm was found with a sole lateral plate. An added kickstand screw decreased the displacement to 1.46 mm. Added lag screws improved stability by a factor 4, with a maximal displacement of 0.76 mm. The double-plate configuration revealed 0.27 mm, a decrease of the displacement by a factor 10 compared to model 1. An additional analysis of posteromedial fragment displacements with osteoporotic bone, simulated by dividing the elastic modulus of the bone by a factor 2, turned out to be of relevant impact. For model 1, the calculations did not converge. The influence of bone quality was found to be 70% in model 2, 60% in model 3, and 40% in model 4. CONCLUSIONS: The results indicate that the additional fixation of a posteromedial split fracture by plate osteosynthesis might be advantageous in bicondylar tibial plateau fractures treated with lateral plating. This might be even more important in patients with low bone quality.

[Unilateral retinal hemorrhage in infants-two cases of shaken baby syndrome?] / Unilaterale Netzhautblutungen bei Säuglingen ­ 2 Fälle von Schütteltrauma?

A 2.5-month-old boy and a 2-month-old girl were admitted to a pediatric intensive care unit with impaired consciousness. Both infants had subdural hemorrhages. Because of presumed non-accidental head injury (NAHI) funduscopy was performed, which revealed unilateral hemorrhage in both children. After intensive differential diagnostics NAHI was suspected in both cases and a forensic medical examination was initiated. This case series is important because it shows that unilateral retinal bleeding does not exclude NAHI.

[Outcome of pterygium excision after various surgical techniques-is excision with simple conjunctival closure still lege artis?] / Ergebnisse der Pterygiumchirurgie nach verschiedenen Operationstechniken ­ Ist die Exzision mit einfachem Bindehautverschluss noch lege artis?

BACKGROUND: There is no consensus about the best method for pterygium excision. Variable recurrence rates have been reported in the literature depending on the surgical technique. OBJECTIVE: To evaluate the postoperative outcome after pterygium excision depending on the preoperative extent of the pterygium and the surgical method. MATERIAL AND METHODS: A total of 109 patients (72 men, 37 women) who underwent 109 pterygium surgeries were retrospectively analyzed. In 87 cases postoperative data over a 5-year follow-up period were available. Besides recording the preoperative extent of the pterygium the functional outcome was analyzed and recurrence rates of the various techniques by simple excision with primary conjunctival closure (SE), conjunctival autograft (BHT) and amniotic membrane transplantation (AMT) were compared. RESULTS: Overall, recurrence was noted in 21 %. The recurrence rate of SE was 20 %. After BHT fewer recurrences (11 %) were seen than after AMT (39 %). After the intraoperative use of mitomycin C (MMC) more recurrences (31 %) occurred than without the use of MMC (17%). In 45 % of the cases delayed recurrence occurred after the first postoperative year. CONCLUSION: In our opinion the method of SE is not obsolete. Good results can be achieved with SE in pterygia with a small extent. The lowest recurrence rate was seen after BHT; therefore, BHT is the method of choice in general and especially for larger pterygia. The higher recurrence rate after intraoperative use of MMC is probably caused by selection bias. Regular follow-up examinations are required beyond the first postoperative year for timely detection of delayed recurrence.

Intravitreal anti-VEGF treatment for choroidal neovascularization secondary to traumatic choroidal rupture.

BACKGROUND: So far only single cases with short follow-up have been reported on the use of intravitreal anti-VEGF for traumatic choroidal neovascularizations (CNV). This paper reports a large case series of patients with CNV secondary to choroidal rupture after ocular trauma receiving intravitreal anti-VEGF (vascular endothelial growth factor) injections. METHODS: Fifty-four patients with unilateral choroidal rupture after ocular trauma diagnosed between 2000 and 2016 were retrospectively evaluated. Eleven patients with CNV secondary to choroidal rupture were identified. Five eyes with traumatic secondary CNV were treated with anti-VEGF and were systematically analysed. The other 4 patients with inactive CNV underwent watchful observation. RESULTS: Four men and one woman with a mean age of 29 years (SD 12.4; range 19-45) had intravitreal anti-VEGF therapy for traumatic CNV. Another 4 patients with a mean age of 37 years (SD 6.6; range 31-46) presented with inactive CNV and did not receive specific treatment. In all 9 cases the mean interval between the ocular trauma and the diagnosis of CNV was 5.7 months (SD 4.75; range 2-12). In the treatment group per eye 4.2 injections (SD 3.2; range 1-8) were given on average. Four eyes were treated with bevacizumab and one eye with ranibizumab. Regression of CNV was noted in all eyes. In 4 eyes visual acuity (VA) improved, one eye kept stable visual acuity. CONCLUSIONS: Here, we present the up to now largest case series of traumatic CNV membranes treated with anti-VEGF injections with a mean follow-up period of 5 years. Intravitreal anti-VEGF therapy seems to be safe and effective for secondary CNV after choroidal rupture. Compared to exudative age-related macular degeneration fewer injections are needed to control the disease. TRIAL REGISTRATION: Retrospective registration with local ethics committee on 21 March 2019. Trial registration number is 19-1368-104.

S-Nitrosothiol Signaling Is involved in Regulating Hydrogen Peroxide Metabolism of Zinc-Stressed Arabidopsis.

Accumulation of heavy metals such as zinc (Zn) disturbs the metabolism of reactive oxygen (e.g. hydrogen peroxide, H2O2) and nitrogen species (e.g. nitric oxide, NO; S-nitrosoglutathione, GSNO) in plant cells; however, their signal interactions are not well understood. Therefore, this study examines the interplay between H2O2 metabolism and GSNO signaling in Arabidopsis. Comparing the Zn tolerance of the wild type (WT), GSNO reductase (GSNOR) overexpressor 35S::FLAG-GSNOR1 and GSNOR-deficient gsnor1-3, we observed relative Zn tolerance of gsnor1-3, which was not accompanied by altered Zn accumulation capacity. Moreover, in gsnor1-3 plants Zn did not induce NO/S-nitrosothiol (SNO) signaling, possibly due to the enhanced activity of NADPH-dependent thioredoxin reductase. In WT and 35S::FLAG-GSNOR1, GSNOR was inactivated by Zn, and Zn-induced H2O2 is directly involved in the GSNOR activity loss. In WT seedlings, Zn resulted in a slight intensification of protein nitration detected by Western blot and protein S-nitrosation observed by resin-assisted capture of SNO proteins (RSNO-RAC). LC-MS/MS analyses indicate that Zn induces the S-nitrosation of ascorbate peroxidase 1. Our data collectively show that Zn-induced H2O2 may influence its own level, which involves GSNOR inactivation-triggered SNO signaling. These data provide new evidence for the interplay between H2O2 and SNO signaling in Arabidopsis plants affected by metal stress.

[H3F3A mutated multicentric giant cell tumor of bone : A very rare primary bone disease]. / H3F3A-mutierter multifokaler Riesenzelltumor des Knochens : Eine äußerst seltene primär ossäre Erkrankung.

This article presents the case of a metachronic multicentric giant cell tumor of bone (GCTB). The patient obtained his first diagnosis of GCTB in the left humerus at the age of 47 years. Furthermore, he suffered from a GCTB in the head of his 4th left metacarpal bone and from a recurrence of the latter. All tumors carried the characteristic H3F3A mutation, which was proven by Sanger sequencing and a mutation specific antibody. The case is the first description of a multicentric H3F3A mutated GCTB.