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Antony William,1 Sophia Kuehnel,1 Spyridon Dimopoulos,2 Jost Hillenkamp,1 Winfried Goebel1 1Department of Ophthalmology, University Eye Hospital Würzburg, Würzburg, Germany; 2Department of Ophthalmology, University Eye Hospital Tübingen, Tübingen, GermanyCorrespondence: Antony William, Department of Ophthalmology, University Hospital Würzburg, Josef–Schneider Straße 11, Würzburg, 97080, Germany, Tel +4993120120646, Email William_a@ukw.dePurpose: To analyse single-operation anatomical success (SOAS) of primary rhegmatogenous retinal detachment (RRD) repair by junior vitreoretinal surgeons guided by preoperative individual case selection by an experienced mentor vitreoretinal surgeon.Methods: Retrospective, single institute, observational study, included all patients who underwent standard pars plana vitrectomy (PPV) or combined encircling band (CB) and PPV and gas tamponade in the treatment of RRD from November 2021 to December 2022 were included. Preoperative selection for the surgery decision, whether standard PPV or combined CB & PPV was undertaken through the senior surgeon; according to the location and extensions of the RRD, number of retinal tears (RT) and lens status. We excluded patients with tractional retinal detachment, RD with proliferative vitreoretinopathy stage C, giant tears, trauma, previous scleral buckle, schisis RD and RD requiring silicone oil. The primary outcome measure was to evaluate the single-operation anatomic success (SOAS). Secondary outcome measures evaluated whether there was a statistical significant difference between both procedures.Results: Eighty-two eyes were included in the study. Forty-five eyes were selected for combined CB&PPV and 37 eyes for standard PPV. SOAS was achieved in 40 eyes (88.8%) in combined group and 35 eyes (94.5%) in standard PPV group. There was no statistically significant difference in the success rate between both operations, p = 0.65.Conclusion: Structured preoperative selection of standardized surgical techniques according to the degree of complexity of RD together with close supervision enables junior vitreoretinal surgeons in training to achieve re-attachment rates of more than 80% with both types of surgeries.Keywords: primary rhegmatogenous retinal detachment, RRD, pars plana vitrectomy, PPV, encircling band, CB

Antony William, Raoul Verma-Fuehring, Sophia Kuehnel, Dorothee Schwabe, Daniel Kampik, Winfried Goebel, Jost Hillenkamp Department of Ophthalmology, University Hospital Würzburg, Würzburg, GermanyCorrespondence: Antony William, Department of Ophthalmology, University Hospital Würzburg, Joseph–Schneider Straße 11, Würzburg, 97080, Germany, Tel +4993120120646, Email William_a@ukw.dePurpose: To evaluate the morphological macular changes and fluid dynamics under brolucizumab treatment in eyes refractory to previous anti–vascular endothelial growth factor (anti-VEGF) treatment for neovascular age-related macular degeneration (nAMD) compared with treatment-naive eyes.Methods: Retrospective study of all eyes treated with brolucizumab for nAMD between 2020 and 2021 with a fixed injection regimen and one year follow-up. Treatment-naive eyes (TN) were compared with eyes refractory to previous treatment with bevacizumab, ranibizumab, or aflibercept (RT). The primary outcome measure was change of best-corrected visual acuity (BCVA). Secondary outcome measures included foveal central thickness (FCT), presence of intra- or subretinal fluid (IRF, SRF) and presence of pigment epithelial detachment (PED) at any time point during treatment in both groups.Results: Seventeen TN eyes and 17 RT eyes were included. Mean BCVA and mean FCT in TN eyes had significantly improved after 3 months and continued to improve during treatment (p< 0.05 and p=0.001, respectively). In RT eyes, mean BCVA did not change significantly while mean FCT had improved after 3 months of treatment and remained stable thereafter. SRF or PED were more frequent in RT eyes compared with TN eyes (p=0.003 and p=0.005, respectively).Conclusion: After 3 months of treatment, the BCVA increased significantly only in TN eyes, while the FCT was significantly reduced in both groups. IRF appears to be similarly seen in both groups after the loading phase; however, SRF and PED appear to be more frequent in the RT eyes compared with TN eyes.Keywords: treatment naïve, TN, refractory treatment, RT

Abstract Background Female sperm storage has evolved independently multiple times among vertebrates to control reproduction in response to the environment. In internally fertilising amphibians, female salamanders store sperm in cloacal spermathecae, whereas among anurans sperm storage in oviducts is known only in tailed frogs. Facilitated through extensive field sampling following historical observations we tested for sperm storing structures in the female urogenital tract of fossorial, tropical caecilian amphibians. Findings In the oviparous Ichthyophis cf. kohtaoensis, aggregated sperm were present in a distinct region of the posterior oviduct but not in the cloaca in six out of seven vitellogenic females prior to oviposition. Spermatozoa were found most abundantly between the mucosal folds. In relation to the reproductive status decreased amounts of sperm were present in gravid females compared to pre-ovulatory females. Sperm were absent in females past oviposition. Conclusions Our findings indicate short-term oviductal sperm storage in the oviparous Ichthyophis cf. kohtaoensis. We assume that in female caecilians exhibiting high levels of parental investment sperm storage has evolved in order to optimally coordinate reproductive events and to increase fitness.

Reconstruction of the bony socket after orbital exenteration is a matter of much debate. Prompt defect closure with a microvascular flap is desirable but involves a major surgical procedure and hence, places considerable burden on the patient. The new surgical technique presented here permits a technically simpler wound closure with fewer complications after orbital exenteration., Methods: Between May 2014 and June 2022 in the ENT department of Regensburg University, nine patients underwent exenteration and reconstruction with a pericranial flap. The flap was raised via a broken line incision in the forehead or endoscopically, incised in a roughly croissant-like shape, then introduced into the orbit through a tunnel in the eyebrow. A retrospective analysis of the patients and considerations about determining the size, shape, and vascular supply of the flap are presented., Results: Flap healing was uncomplicated in all cases. Only 6 weeks after surgery, the flap was stable, making it possible to start adjuvant therapy and prosthetic rehabilitation swiftly. The flap is adapted to the near cone-shape of the orbit. The mean (± standard deviation) surface area of the measured orbits is (39.58 ± 3.32) cm 2 . The territory of the angular artery provides the periosteal flap arterial blood supply. Venous drainage is via venous networks surrounding the artery., Conclusions: Use of the pericranial flap makes it possible to close the orbital cavity promptly with minimal donor site defect and a short operating time, thereby minimizing the surgical risk and speeding up physical and psychological recovery., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Maternal stress, especially during early pregnancy, predisposes offspring to neuropsychiatric disorders. We hypothesized that maternal psychosocial stress (MPS) during pregnancy affects fetal structural neurodevelopment depending on the gestational age of exposure. Fetal sheep brains were harvested at 130 days gestation (dG, term 150 dG) from ewes frequently isolated from flock-mates during early gestation (first and second trimester; n  = 10) or late gestation (third trimester; n  = 10), or from control flock-mates ( n  = 8). Immunohistochemistry for formation of neuronal processes, myelination, synaptic density, cell proliferation and programed cell death was performed on brain tissue sections. Sections of the cortical gray matter, the hippocampal CA3 region and the superficial, subcortical and deep white matter were examined morphometrically. Stress effects depended on the brain region and time of exposure. Stress during early gestation but not during late gestation reduced the amount of neuronal processes in the cerebral cortex and hippocampus by 36.9 ± 10.1% ( p  < 0.05, mean ± SEM) and 36.9 ± 15.8% ( p  < 0.05), respectively, accompanied by a decrease in synaptic density in the cerebral cortex and hippocampus by 39.8 ± 23.1% ( p  < 0.05) and 32.9 ± 13.4% ( p  < 0.01). Myelination was decreased in white matter layers on average by 44.8 ± 11.7% ( p  < 0.05) accompanied by reduced (glial) cell proliferation in the deep white matter by 83.6 ± 12.4% ( p  < 0.05). In contrast, stress during the third trimester had no effect in any brain region. Chronic MPS during the first and second trimester induced prolonged effects on neuronal network and myelin formation which might contribute to disturbed neurobehavioral, cognitive and motor development in offspring of stressed mothers.Lay summaryMany women are exposed to stressful events during pregnancy. Maternal stress especially during early pregnancy predisposes for offspring's neuropsychiatric disorders. In our sheep study, we show that disturbance of fetal brain development is a potential mechanism and is worst during 1st and 2nd trimester.

Background: In glioblastoma multiforme (GBM), the serine protease urokinase plasminogen activator (uPA), and matrix metalloproteases (MMP-2/MMP-9) contribute to its invasive growth pattern, which is the major obstacle to successful surgical treatment., Materials and Methods: The expression of uPA was determined in monolayers and spheroids of the rodent GBM cell line C6 by immunohistochemistry and polymerase chain reaction (PCR). The longitudinal expression of proteases was studied in orthotopically implanted spheroids by semi-quantitative immunohistochemistry (IHC) in Sprague Dawley rats (n=40). The tumor volume was monitored by magnetic resonance imaging (MRI)., Results: In vitro, the GBM cell line C6 expresses high levels of uPA. In vivo, a continuous increase of uPA, uPA-receptor (uPAR), MMP-2, and MMP-9 expression was found in the infiltration zone. uPA was located exclusively in the infiltration zone and in the vascular basal layers. The mean tumor volume 23 days after implantation was 3.2 mm3., Conclusion: uPA, uPAR, MMP-2 and MMP-9 play an important role in GBM growth. Blockade of uPA and interruption of the proteolytic cascade could become a useful tool in the therapy of GBM.

Background: Non-participation of General Practitioners (GPs) hampers primary care research. Using existing network structures can improve participation, but may introduce sampling effects., Objectives: To examine the role of network-based recruitment and other determinants of participation, and to estimate effects of sampling and non-participation on generalizability., Methods: For a study of quality of care assessment, we recruited GPs from a regionally defined population and a GP network. Effects of sampling and non-participation were analysed by comparing characteristics between participants, target samples, and reference data for all German GPs. Factors influencing study participation were assessed in multiple logistic regression., Results: Compared to the regional sample, network GPs were more likely to complete survey questionnaires (92% versus 69%) and to participate in the study (66% versus 23%). Compared to national reference data, study participants from both populations were younger, had a higher level of professional training, and included more men. These differences were already present in the network target sample, but were largely attributable to selective participation in the regional sample. Network membership remained the strongest determinant of participation in multiple logistic regression (odds ratio 5.01; 95% confidence interval 2.53-9.91). A younger age, higher professional training, and membership in the German Society of General Practice were also predictive of participation., Conclusions: Although network-based recruitment of GPs increases participation rates, sample effects are similar in size and direction as effects of non-participation in the regionally defined population. Careful analysis of participants based on publicly available data is therefore crucial for the assessment of generalizability.