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Susanna Friederike Koenig,1 Christoph Wolfgang Hirneiss2 1Moorfields Eye Hospital NHS Foundation Trust, London, EC1V 2PD, UK; 2Ludwig-Maximilians University, Eye Clinic, Campus Innenstadt, Munich, D-80336, GermanyCorrespondence: Susanna Friederike KoenigMoorfields Eye Hospital NHS Foundation Trust, 162 City Road, London, EC1V 2PD Email susanna.koenig@nhs.netPurpose: Lowering the intraocular pressure (IOP) in patients with primary open-angle glaucoma (POAG) with filtration surgery can induce morphological changes to the bulbus and structures of the retina. In this study, we have evaluated changes of Bruch’s membrane-based parameters and retinal nerve fiber layer (RNFL) derived by spectral-domain optical coherence tomography (SD-OCT) in eyes that have undergone glaucoma filtration surgery.Patients and Methods: SD-OCT imaging of the optic nerve head (ONH) and of the RNFL was performed in 54 eyes of 54 patients with medically uncontrolled POAG before and after IOP-lowering surgery (trabeculectomy or deep sclerectomy). The ONH parameter minimum rim width (MRW) and the size of the Bruch’s membrane opening (BMO-Area) were derived from 24 radial B-scans centered on the ONH.Results: The average preoperative IOP was 23.1 ± 7.5 mmHg. One month postoperatively, the average IOP decreased to 12.1 ± 4.6 mmHg (p < 0.01), which caused a significant increase in the thickness of neuroretinal rim. There was no significant change in the automatically detected BMO-Area (p = 0.32). The pressure-related increase in MRW correlated well with the postoperative IOP and cup-to-disc ratio (CDR). In regression analysis, the alteration in thickness of the neuroretinal rim could be well predicted in a model including CDR, change of IOP and mean deviation (MD) (R2 = 0.414, p < 0.001). RNFL showed a significant increase as well.Conclusion: IOP-lowering surgery in patients with medically uncontrolled POAG causes an increased thickness of the SD-OCT derived ONH parameters. The changes of the RNFL after surgery showed no significant correlations with IOP changes. In contrast to this, highly significant correlations of MRW values with the IOP could be observed. The BMO-Area remained completely stable A preferred use of RNFL for follow-up should be discussed.Keywords: glaucoma, optic nerve head, ONH, OCT, retinal nerve fiber layer, RNFL, Bruch’s membrane opening, BMO

Background: Persistent severe serous choroidal detachment is a rare complication after glaucoma surgery. Surgical treatment with choroidal fluid drainage through a scleral incision is an option in these cases. Combining this procedure with pars plana vitrectomy and gas endotamponade has potential advantages. In the following, the perioperative course of this surgical option in a small cohort will be presented., Methods: This is a retrospective cohort study of the postoperative course of ab externo drainage of persistent serous choroidal detachment (≥4 weeks) in combination with pars plana vitrectomy and gas endotamponade in six eyes of six patients after exhausting all conservative treatment options. Inclusion criterion was persistent hypotony with severe serous choroidal detachment after intraocular pressure (IOP) lowering surgery due to medically uncontrolled glaucoma. Eyes were evaluated according to resolution of choroidal detachment, change in IOP and visual acuity (VA), postdrainage complications, and need for further surgeries., Results: Before surgery, all patients presented with flat anterior chamber, decreased vision, and persistent choroidal detachment. The surgery itself was uneventful, but due to the complexity of the cases, tailoring the procedure to each patient's needs was required. Complete resolution of choroidal effusion was achieved by one month in 5 eyes and in 1 eye by month 3. There was an increase in average IOP from 5 (±2.1) mmHg before surgery to 11.3 (±3.7) mmHg and in VA from 1.7 (±0.8) to 1.2 (±0.6) logMAR. Five out of six patients required additional surgery, mainly to further increase the IOP even though choroidal detachment had already resolved., Conclusion: Ab externo choroidal fluid drainage combined with pars plana vitrectomy and gas endotamponade seems to be an effective and safe treatment option in persistent ocular hypotony. Although repeated surgeries might be necessary, large-scale prospective studies must be undertaken to provide corroborative evidence., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Susanna Friederike Koenig et al.)

Objectives: This study quantifies the effect of trabeculectomy on the rate of progression (RoP) of visual field (VF) damage utilising pre- and post-operative visual function as the outcome instead of surrogate outcomes of success., Methods: Clinical and VF data from 199 sequential patients who underwent trabeculectomy between 2015 and 2016 were extracted from the network of sites of Moorfields Eye Hospital NHS Foundation Trust. Of these, we analysed 80 eyes of 74 patients who met our inclusion criteria of at least three reliable VFs before and after surgery (false positive rate <15%). The change in mean RoP (dB/year) was tested using point-wise sensitivity values through a mixed effect model with random effects on both intercepts and slopes. A broken-stick regression of sensitivity over time, with a breakpoint at the day of surgery, modelled the individual change in RoP., Results: We analysed 10 [9,12] VFs per subject (Median [Interquartile Range]). At surgery, the age was 67 [57, 72] years, mean deviation was -10.84 [-14.7, -5.6] dB and the IOP was 18 [15, 20] mmHg. One year after surgery, the IOP was 10 [8,13] mmHg (p = 0.002). Mean RoP before surgery was -0.94 [-1.20, -0.69] dB/year (Mean [95% credible intervals]) and it was slowed down by 0.62 [0.26, 0.97] dB/year (p < 0.001) after surgery., Conclusions: Trabeculectomy leads to a significant reduction in the RoP of VF loss postoperatively., (© 2022. The Author(s).)

Purpose: Repeated intravitreal injections of methotrexate for proliferative vitreoretinopathy, a rare ocular condition that can cause vision loss, have shown beneficial effects in recent clinical studies. The purpose of this study was to develop a slow-release, long-term drug carrier composed of the polymer polylactide-co-glycolide and methotrexate that can be injected intravitreally., Methods: The required composition of the drug carrier was modeled using pharmacokinetic parameters based on current literature. Release kinetics were determined using an ocular pharmacokinetic model. Epiretinal PVR-membranes were harvested during pars plana vitrectomy and subsequently transferred to cell culture. The effect of the drug carrier on cell migration was investigated using time-lapse microscopy and a scratch-induced migration assay. The colorimetric WST-1-assay and a live-dead-assay were performed to determine viability, and the BrdU-assay was applied for proliferation., Results: The release profile showed an initial and a final burst of methotrexate with an intervening steady state that lasted 9-11 weeks. It showed inhibitory effects on pathobiological processes in human PVR-cells in vitro. Cell velocity in the time-lapse assay, migration in the scratch assay (p = 0.001), and proliferation in the BrdU assay (p = 0.027) were reduced after addition of the drug carrier. These effects occurred without causing a reduction in viability in the WST-1 assay (p > 0.99) and the live-dead assay., Conclusion: The methotrexate-loaded drug carrier can maintain a stable concentration for 9-11 weeks and influence the pathobiological process of PVR cells in vitro. Therefore, it represents a potential therapeutic orphan drug for PVR., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Efstathios Vounotrypidis reports a relationship with Bayer Corporation that includes: speaking and lecture fees. Efstathios Vounotrypidis reports a relationship with Novartis Pharmaceuticals Corporation that includes: speaking and lecture fees. Armin Wolf reports a relationship with Allergan Irvine that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Armin Wolf reports a relationship with Boehringer Ingelheim Corp USA that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Armin Wolf reports a relationship with Bayer Corporation that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Armin Wolf reports a relationship with Alimera Sciences Inc that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Armin Wolf reports a relationship with Novartis Pharmaceuticals Corporation that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Armin Wolf reports a relationship with Oertli Instrumente AG that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Armin Wolf reports a relationship with Roche SAS that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Armin Wolf reports a relationship with Carl Zeiss AG that includes: consulting or advisory and travel reimbursement., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: The aim of our prospective off-label, interventional clinical trial was to evaluate the efficacy and safety of the fluocinolone-loop-anchoring technique over two years in eyes with iris-lens diaphragm disruption and pseudophakic cystoid macular edema., Methods: In 10 eyes, scleral fixation of fluocinolone implant was performed. Main outcome measures were the development of best-corrected visual acuity (BCVA), central retinal thickness over 24 months, and general safety of the procedure., Results: A significant improvement to 0.57 ± 0.38 log MAR (Snellen 20/80) (range 0-1.30) was observed (P = 0.003) at 1 month. Further improvement to 0.45 ± 036 log MAR (Snellen 20/60) was observed until month 18 (P = 0.081). Mean central retinal thickness decreased by 22% from 601.6 ± 235.5 µm to 449.1 ± 128.9 µm at 1 month. In one patient, the implant has to be removed at Month 7 because of elevated intraocular pressure and one patient after globe rupture had a retinal redetachment at Month 4., Conclusion: In this study, we showed that the treatment of recalcitrant pseudophakic cystoid macular edema with scleral fixated fluocinolone implant in eyes with disruption of the iris-lens diaphragm provides good anatomical and functional results with a reasonable safety profile over 24 months in eyes where pseudophakic cystoid macular edema is otherwise difficult to treat and often left untreated., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Purpose: The quality of life (QoL) of glaucoma patients is affected by many factors. In particular, patient activity is compromised by the chronicity of the disease. In this study, we evaluated the change in QoL and its impact on activities over a period of 8 years., Methods: A total of 43 patients with glaucomatous optic nerve damage were enrolled in this retrospective longitudinal observational study. Changes in intraocular pressure (IOP), best-corrected visual acuity (BCVA) and visual field (VF) parameters, number of IOP-lowering eye drops and IOP-lowering surgery were assessed over a period of 8 years. Assessment of QoL was obtained by patient-reported visual functioning using the Rasch-calibrated glaucoma activity limitation 9 (GAL-9) questionnaire at baseline and after 8 years., Results: The BCVA of the better eye changed from 0.16 ± 0.22 to 0.21 ± 0.14 logMAR, whereas there was a change from 0.27 ± 0.25 to 1.39 ± 1.1 logMAR in the worse eye. The VF parameter mean deviation (MD) of the better eye changed from -2.39 ± 4.55 dB to -4.83 ± 5.09 dB, while it altered significantly from -8.86 ± 5.86 dB to -12.05 ± 8.07 dB in the worse eye. Values of GAL‑9 changed from -2.39 ± 2.14 to -1.38 ± 2.78 (in the Rasch analysis, more negative values account for a better QoL), according to a sum score change from 79.17 ± 19.63 to 69.22 ± 27.95. This change showed a highly significant correlation with the MD at follow-up, especially with the worse eye (r = 0.43). The impact of the MD at follow-up on QoL could also be well predicted in a regression model., Conclusion: The QoL of glaucoma patients decreased significantly over time. Changes in the VF, particularly of the worse eye, have a great impact on reported functioning. Careful treatment, especially of the eye with greater glaucomatous damage, is mandatory., (© 2021. The Author(s).)

Among Xenopus Lef/Tcfs, XTcf-4 has an outstanding role. In early development it is located exclusively in the midbrain where it is essential for midbrain and isthmus development. In order to identify transcription factors responsible for the restriction of XTcf-4 expression we isolated a 3.8kb fragment of the XTcf-4 promoter. We found that this promoter fragment is sufficient to mimic endogenous XTcf-4 expression in the midbrain. Characterization of putative binding sites for en2 and pax2/5 revealed that en2, but not pax2/5 directly represses XTcf-4 promoter activity. Gain-of-function experiments in Xenopus embryos confirmed this en2-mediated repression. Loss-of-function experiments demonstrate that both en2 and pax2/5 are essential for endogenous XTcf-4 expression. The primary effect of pax2/5 depletion thereby appears to be a reduced en2 expression at neurula stages. Because en2 can compensate for the depletion of pax2/5, we assume a hierarchical regulation of gene expression in the midbrain/isthmus region with pax2/5 acting upstream of en2. Furthermore, since the XTcf-4 expression domain does not overlap with the expression domains of the isthmus marker genes en2 and pax2/5, we conclude that the knock-down of en2 and pax2/5 results in a downregulation of a paracrine growth factor regulating XTcf-4 expression. We found that the growth factor for this non-cell-autonomous effect of en2 and pax2/5 is wnt-1 acting on the -1437 Lef/Tcf binding site on the XTcf-4 promoter. We provide evidence that the main nuclear wnt transducer for the autoregulation of XTcf-4 is XTcf-1., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Coordinate-based, voxel-wise meta-analysis is an exciting recent addition to the human functional brain mapping literature. In view of the critical importance of selection criteria for any valid meta-analysis, a taxonomy of experimental design should be an important tool for aiding in the design of rigorous meta-analyses. The coding scheme of experimental designs developed for and implemented within the BrainMap database provides a candidate taxonomy. In this study, the BrainMap experimental-design taxonomy is described and evaluated by comparing taxonomy fields to data-filtering choices made by subject-matter experts carrying out meta-analyses of the functional imaging literature. Fifteen publications reporting a total of 46 voxel-wise meta-analyses were included in this assessment. Collectively these 46 meta-analyses pooled data from 351 publications, selected for experimental similarity within each meta-analysis. Filter implementations within BrainMap were graded by ease-of-use (A-C) and by stage-of-use (1-3). Quality filters and content filters were tabulated separately. Quality filters required for data entry into BrainMap were classed as mandatory (five filters), being above the use grading system. All authors spontaneously adopted the five mandatory filters in constructing their meta-analysis, indicating excellent agreement on data quality among authors and between authors and the BrainMap development team. Two non-mandatory quality filters (group size and imaging modality) were applied by all authors; both were Stage 1, Grade A filters. Field-of-view filters were the least-accessible quality filters (Stage 3, Grade C); two field-of-view filters were applied by six and four authors, respectively. Authors made a total of 115 content-filter choices. Of these, 78 (68%) were Stage 1, Grade A filters; 16 (14%) were Stage 2, Grade A; and 21 (18%) were Stage 2, Grade C. No author-applied filter was absent from the taxonomy.