@article{WaxmanStrzalkowskaWangetal.2023, author = {Waxman, Susannah and Strzalkowska, Alicja and Wang, Chao and Loewen, Ralitsa and Dang, Yalong and Loewen, Nils A.}, title = {Tissue-engineered anterior segment eye cultures demonstrate hallmarks of conventional organ culture}, series = {Graefe's Archive for Clinical and Experimental Ophthalmology}, volume = {261}, journal = {Graefe's Archive for Clinical and Experimental Ophthalmology}, number = {5}, doi = {10.1007/s00417-022-05915-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323845}, pages = {1359-1368}, year = {2023}, abstract = {Background Glaucoma is a blinding disease largely caused by dysregulation of outflow through the trabecular meshwork (TM), resulting in elevated intraocular pressure (IOP). We hypothesized that transplanting TM cells into a decellularized, tissue-engineered anterior segment eye culture could restore the outflow structure and function. Methods Porcine eyes were decellularized with freeze-thaw cycles and perfusion of surfactant. We seeded control scaffolds with CrFK cells transduced with lentiviral vectors to stably express eGFP and compared them to scaffolds seeded with primary TM cells as well as to normal, unaltered eyes. We tracked the repopulation behavior, performed IOP maintenance challenges, and analyzed the histology. Results Transplanted cells localized to the TM and progressively infiltrated the extracellular matrix, reaching a distribution comparable to normal, unaltered eyes. After a perfusion rate challenge to mimic a glaucomatous pressure elevation, transplanted and normal eyes reestablished a normal intraocular pressure (transplanted = 16.5 ± 0.9 mmHg, normal = 16.9 ± 0.9). However, eyes reseeded with eGFP-expressing CrFK cells could not regulate IOP, remaining high and unstable (27.0 ± 6.2 mmHg) instead. Conclusion Tissue-engineered anterior segment scaffolds can serve as readily available, scalable ocular perfusion cultures. This could reduce dependency on scarce donor globes in outflow research and may allow engineering perfusion cultures with specific geno- and phenotypes.}, language = {en} } @article{GuggenbergerVogtSongetal.2023, author = {Guggenberger, Konstanze V. and Vogt, Marius L. and Song, Jae W. and Weng, Andreas M. and Fr{\"o}hlich, Matthias and Schmalzing, Marc and Venhoff, Nils and Hillenkamp, Jost and Pham, Mirko and Meckel, Stephan and Bley, Thorsten A.}, title = {Intraorbital findings in giant cell arteritis on black blood MRI}, series = {European Radiology}, volume = {33}, journal = {European Radiology}, number = {4}, doi = {10.1007/s00330-022-09256-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324978}, pages = {2529-2535}, year = {2023}, abstract = {Objective Blindness is a feared complication of giant cell arteritis (GCA). However, the spectrum of pathologic orbital imaging findings on magnetic resonance imaging (MRI) in GCA is not well understood. In this study, we assess inflammatory changes of intraorbital structures on black blood MRI (BB-MRI) in patients with GCA compared to age-matched controls. Methods In this multicenter case-control study, 106 subjects underwent BB-MRI. Fifty-six patients with clinically or histologically diagnosed GCA and 50 age-matched controls without clinical or laboratory evidence of vasculitis were included. All individuals were imaged on a 3-T MR scanner with a post-contrast compressed-sensing (CS) T1-weighted sampling perfection with application-optimized contrasts using different flip angle evolution (SPACE) BB-MRI sequence. Imaging results were correlated with available clinical symptoms. Results Eighteen of 56 GCA patients (32\%) showed inflammatory changes of at least one of the intraorbital structures. The most common finding was enhancement of at least one of the optic nerve sheaths (N = 13, 72\%). Vessel wall enhancement of the ophthalmic artery was unilateral in 8 and bilateral in 3 patients. Enhancement of the optic nerve was observed in one patient. There was no significant correlation between imaging features of inflammation and clinically reported orbital symptoms (p = 0.10). None of the age-matched control patients showed any inflammatory changes of intraorbital structures. Conclusions BB-MRI revealed inflammatory findings in the orbits in up to 32\% of patients with GCA. Optic nerve sheath enhancement was the most common intraorbital inflammatory change on BB-MRI. MRI findings were independent of clinically reported orbital symptoms. Key Points • Up to 32\% of GCA patients shows signs of inflammation of intraorbital structures on BB-MRI. • Enhancement of the optic nerve sheath is the most common intraorbital finding in GCA patients on BB-MRI. • Features of inflammation of intraorbital structures are independent of clinically reported symptoms.}, language = {en} } @phdthesis{VermaFuehring2022, author = {Verma-F{\"u}hring, Raoul}, title = {Die Trabekulopunktion als Pr{\"a}diktiver Test f{\"u}r den Erfolg der Ab Interno Trabekulektomie im Schweineaugenmodell}, doi = {10.25972/OPUS-28263}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-282633}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {To investigate trabeculopuncture (TP) for predicting the outcome of ab interno trabeculectomy (AIT). Ex vivo porcine anterior segments were perfused and sequentially underwent two procedures, TP and AIT. We concluded that a 10\% reduction in IOP after TP can be used to predict the success (>20\% IOP decrease) of AIT in porcine eyes. As porcine eyes share many similarities with human eyes, our findings may have implications on the validity of this test as a predictor for surgical outcomes of AITs in humans.}, subject = {Glaukom}, language = {en} } @phdthesis{Dakroub2022, author = {Dakroub, Mohamad}, title = {Coarsened Exact Matching of Excisional to Plasma-Ablative Ab Interno Trabeculectomy}, doi = {10.25972/OPUS-29680}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-296805}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Abstract Purpose: To compare ab interno trabeculectomy by trabecular meshwork excision to plasma-mediated ablation in primary open-angle glaucoma. Methods: Retrospectively collected data of TrabEx+ (n=56) and Trabectome (n=99) were compared by coarsened exact matching to reduce confounding and matched based on baseline intraocular pressure and age. Primary outcomes were intraocular pressure and the number of glaucoma medications. Complications and the need for additional glaucoma surgery were assessed. Patients were followed for up to one year. Results: 53 TrabEx+ could be matched to Trabectome. Baseline intraocular pressure was 16.5 ± 4.6 mmHg in both; age was 73.7 ± 8.8 years and 71.5 ± 9.9 years in TrabEx+ and Trabectome, respectively. TrabEx+ were taking more medications than Trabectome (p<0.001). Intraocular pressure was reduced to 14.8±4.3 in TrabEx+ and 13.4±3.4 in Trabectome at 6 months, and to 14.9±6.0 (p=0.13) in TrabEx+ and to 14.1±3.8 mmHg (all p<0.05) in Trabectome at 12 months. Medications were reduced at both 6 and 12 months (p< 0.05). No differences were seen between both groups at 6 and 12 months. In TrabEx+, only one serious complication occurred, and two patients required further glaucoma surgery. Conclusion: Although both groups had a baseline intraocular pressure considered low for ab interno trabeculectomy, intraocular pressure and medications were reduced further at 6 and 12 months. Intraocular pressure reduction did not reach significance in TrabEx+ at 12 months. The inter-group comparison did not reveal any significant differences. Both had a low complication rate.}, subject = {Glaukom}, language = {en} } @article{BielmeierSchmittKleefeldtetal.2022, author = {Bielmeier, Christina B. and Schmitt, Sabrina I. and Kleefeldt, Nikolai and Boneva, Stefaniya K. and Schlecht, Anja and Vallon, Mario and Tamm, Ernst R. and Hillenkamp, Jost and Erg{\"u}n, S{\"u}leyman and Neueder, Andreas and Braunger, Barbara M.}, title = {Deficiency in retinal TGFβ signaling aggravates neurodegeneration by modulating pro-apoptotic and MAP kinase pathways}, series = {International Journal of Molecular Sciences}, volume = {23}, journal = {International Journal of Molecular Sciences}, number = {5}, issn = {1422-0067}, doi = {10.3390/ijms23052626}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-283971}, year = {2022}, abstract = {Transforming growth factor β (TGFβ) signaling has manifold functions such as regulation of cell growth, differentiation, migration, and apoptosis. Moreover, there is increasing evidence that it also acts in a neuroprotective manner. We recently showed that TGFβ receptor type 2 (Tgfbr2) is upregulated in retinal neurons and M{\"u}ller cells during retinal degeneration. In this study we investigated if this upregulation of TGFβ signaling would have functional consequences in protecting retinal neurons. To this end, we analyzed the impact of TGFβ signaling on photoreceptor viability using mice with cell type-specific deletion of Tgfbr2 in retinal neurons and M{\"u}ller cells (Tgfbr2\(_{ΔOC}\)) in combination with a genetic model of photoreceptor degeneration (VPP). We examined retinal morphology and the degree of photoreceptor degeneration, as well as alterations of the retinal transcriptome. In summary, retinal morphology was not altered due to TGFβ signaling deficiency. In contrast, VPP-induced photoreceptor degeneration was drastically exacerbated in double mutant mice (Tgfbr2\(_{ΔOC}\); VPP) by induction of pro-apoptotic genes and dysregulation of the MAP kinase pathway. Therefore, TGFβ signaling in retinal neurons and M{\"u}ller cells exhibits a neuroprotective effect and might pose promising therapeutic options to attenuate photoreceptor degeneration in humans.}, language = {en} } @article{VermaFuehringDakroubHanetal.2022, author = {Verma-Fuehring, R. and Dakroub, M. and Han, H. and Hillenkamp, J. and Loewen, N. A.}, title = {Trabeculopuncture as a predictive test of distal outflow resistance in canal-based surgery}, series = {Scientific Reports}, volume = {12}, journal = {Scientific Reports}, doi = {10.1038/s41598-022-13990-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299740}, year = {2022}, abstract = {We investigated whether trabeculopuncture (TP) could detect distal outflow resistance to predict the outcome of canal-based glaucoma surgery such as ab interno trabeculectomy (AIT). These procedures have a high utilization in open angle glaucoma, but fail in eyes with an unidentified distal outflow resistance. We assigned 81 porcine eyes to two groups: trial (n = 42) and control (n = 39). At 24 h, four YAG-laser trabeculopunctures were placed nasally, followed by a 180° AIT at the same site at 48 h. The proportion of TP responders between both AIT groups was compared. Histology and outflow canalograms were determined. Both post-TP and post-AIT IOPs were lower than baseline IOP (p = 0.015 and p < 0.01, respectively). The success rates of TP and AIT were 69\% and 85.7\%, respectively. Sensitivity and specificity values of TP as predictive test for AIT success were 77.7\% and 83.3\%, respectively. The positive and negative predictive values were 96.6\% and 38.5\%, respectively. We conclude that a 10\% reduction in IOP after TP can be used as a predictor for the success (> 20\% IOP decrease) of 180° AIT in porcine eyes.}, language = {en} } @article{DakroubVermaFuehringAgorastouetal.2022, author = {Dakroub, Mohamad and Verma-Fuehring, Raoul and Agorastou, Vaia and Sch{\"o}n, Julian and Hillenkamp, Jost and Puppe, Frank and Loewen, Nils A.}, title = {Inter-eye correlation analysis of 24-h IOPs and glaucoma progression}, series = {Graefe's Archive for Clinical and Experimental Ophthalmology}, volume = {260}, journal = {Graefe's Archive for Clinical and Experimental Ophthalmology}, number = {10}, doi = {10.1007/s00417-022-05651-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323831}, pages = {3349-3356}, year = {2022}, abstract = {Purpose To determine whether 24-h IOP monitoring can be a predictor for glaucoma progression and to analyze the inter-eye relationship of IOP, perfusion, and progression parameters. Methods We extracted data from manually drawn IOP curves with HIOP-Reader, a software suite we developed. The relationship between measured IOPs and mean ocular perfusion pressures (MOPP) to retinal nerve fiber layer (RNFL) thickness was analyzed. We determined the ROC curves for peak IOP (T\(_{max}\)), average IOP(T\(_{avg}\)), IOP variation (IOP\(_{var}\)), and historical IOP cut-off levels to detect glaucoma progression (rate of RNFL loss). Bivariate analysis was also conducted to check for various inter-eye relationships. Results Two hundred seventeen eyes were included. The average IOP was 14.8 ± 3.5 mmHg, with a 24-h variation of 5.2 ± 2.9 mmHg. A total of 52\% of eyes with RNFL progression data showed disease progression. There was no significant difference in T\(_{max}\), T\(_{avg}\), and IOP\(_{var}\) between progressors and non-progressors (all p > 0.05). Except for T\(_{avg}\) and the temporal RNFL, there was no correlation between disease progression in any quadrant and T\(_{max}\), T\(_{avg}\), and IOP\(_{var}\). Twenty-four-hour and outpatient IOP variables had poor sensitivities and specificities in detecting disease progression. The correlation of inter-eye parameters was moderate; correlation with disease progression was weak. Conclusion In line with our previous study, IOP data obtained during a single visit (outpatient or inpatient monitoring) make for a poor diagnostic tool, no matter the method deployed. Glaucoma progression and perfusion pressure in left and right eyes correlated weakly to moderately with each other. Key messages What is known: ● Our prior study showed that manually obtained 24-hour inpatient IOP measurements in right eyes are poor predictors for glaucoma progression. The inter-eye relationship of 24-hour IOP parameters and disease progression on optical coherence tomography (OCT) has not been examined. What we found: ● 24-hour IOP profiles of left eyes from the same study were a poor diagnostic tool to detect worsening glaucoma. ● Significant inter-eye correlations of various strengths were found for all tested parameters}, language = {en} } @article{StrzalkowskaStrzalkowskiAlYousefetal.2021, author = {Strzalkowska, A. and Strzalkowski, P. and Al Yousef, Y. and Grehn, F. and Hillenkamp, J. and Loewen, Nils A.}, title = {Exact matching of trabectome-mediated ab interno trabeculectomy to conventional trabeculectomy with mitomycin C followed for 2 years}, series = {Graefe's Archive for Clinical and Experimental Ophthalmology}, volume = {259}, journal = {Graefe's Archive for Clinical and Experimental Ophthalmology}, issn = {0721-832X}, doi = {10.1007/s00417-020-05031-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235224}, pages = {963-970}, year = {2021}, abstract = {Purpose We used exact matching for a highly balanced comparison of ab interno trabeculectomy (AIT) with the trabectome to trabeculectomy with mitomycin C (TRAB). Methods A total of 5485 patients who underwent AIT were exact-matched to 196 TRAB patients by baseline intraocular pressure (IOP), number of glaucoma medications, and glaucoma type. Nearest-neighbor-matching was applied to age. Success was defined as a final IOP of less than 21 mmHg, IOP reduction of at least 20\% reduction from baseline, and no secondary surgical interventions. Outcomes were measured at 1, 3, 6, 12, 18, and 24 months. Results A total of 165 AIT could be matched to 165 TRAB. The mean baseline IOP was 22.3 ± 5.6 mmHg, and the baseline number of glaucoma medications was 2.7 ± 1.1 in both groups. At 24 months, IOP was reduced to 15.8 ± 5.2 mmHg in AIT and 12.4 ± 4.7 mmHg in TRAB. IOP was lower than baseline at all visits (p < 0.01) and lower in TRAB than AIT (p < 0.01). Glaucoma medications were reduced to 2.1 ± 1.3 in AIT and 0.2 ± 0.8 in TRAB. Compared to baseline, patients used fewer drops postoperatively (p < 0.01) and more infrequently in TRAB than in AIT (p > 0.01). Secondary surgical interventions had the highest impact on success and became necessary in 15 AIT and 59 TRAB patients. Thirty-two challenging events occurred in TRAB and none in AIT. Conclusion Both AIT and TRAB reduced IOP and medications. This reduction was more significant in TRAB but at the expense of four times as many secondary interventions.}, language = {en} } @article{WaltherZimmermannTheuersbacheretal.2021, author = {Walther, Grit and Zimmermann, Anna and Theuersbacher, Johanna and Kaerger, Kerstin and Lilienfeld-Toal, Marie von and Roth, Mathias and Kampik, Daniel and Geerling, Gerd and Kurzai, Oliver}, title = {Eye infections caused by filamentous fungi: spectrum and antifungal susceptibility of the prevailing agents in Germany}, series = {Journal of Fungi}, volume = {7}, journal = {Journal of Fungi}, number = {7}, issn = {2309-608X}, doi = {10.3390/jof7070511}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241810}, year = {2021}, abstract = {Fungal eye infections can lead to loss of vision and blindness. The disease is most prevalent in the tropics, although case numbers in moderate climates are increasing as well. This study aimed to determine the dominating filamentous fungi causing eye infections in Germany and their antifungal susceptibility profiles in order to improve treatment, including cases with unidentified pathogenic fungi. As such, we studied all filamentous fungi isolated from the eye or associated materials that were sent to the NRZMyk between 2014 and 2020. All strains were molecularly identified and antifungal susceptibility testing according to the EUCAST protocol was performed for common species. In total, 242 strains of 66 species were received. Fusarium was the dominating genus, followed by Aspergillus, Purpureocillium, Alternaria, and Scedosporium. The most prevalent species in eye samples were Fusarium petroliphilum, F. keratoplasticum, and F. solani of the Fusarium solani species complex. The spectrum of species comprises less susceptible taxa for amphotericin B, natamycin, and azoles, including voriconazole. Natamycin is effective for most species but not for Aspergillus flavus or Purpureocillium spp. Some strains of F. solani show MICs higher than 16 mg/L. Our data underline the importance of species identification for correct treatment.}, language = {en} } @article{WabbelsFrickeSchittkowskietal.2021, author = {Wabbels, Bettina and Fricke, Julia and Schittkowski, Michael and Gr{\"a}f, Michael and Lorenz, Birgit and Bau, Viktoria and Nentwich, Martin M. and Atili, Abed and Eckstein, Anja and Sturm, Veit and Beisse, Christina and Sterker, Ina and Neppert, Birte and Mauschitz, Matthias M.}, title = {Yokoyama procedure for esotropia associated with high myopia: real-world data from a large-scale multicentre analysis}, series = {Acta Ophthalmologica}, volume = {99}, journal = {Acta Ophthalmologica}, number = {8}, doi = {10.1111/aos.14808}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239939}, pages = {e1340 -- e1347}, year = {2021}, abstract = {Purpose High myopic patients may develop strabismus due to globe dislocation out of the normal extraocular muscle cone. Surgical correction of this strabismus type is possible by joining the superior and lateral rectus muscles without the need for a scleral suture called the Yokoyama procedure. Data from large patient samples and the evaluation of a potential effect of an additional medial rectus recession (MRR) have been lacking so far. Methods We pooled retrospective patient data of 14 departments of ophthalmology in Germany and Switzerland and analysed determinants of postoperative results using multivariable regression models. Results We included 133 patients (mean age: 59.7 ± 13.4 years, surgery between 2008 and 2017) with a mean preoperative esotropia (both Yokoyama with and without MRR) of 23.8°±4.6°. The angle of preoperative esotropia increased with age. The postoperative esotropia was 8.7° ± 9.9°, and six patients were overcorrected. While preoperative esotropia was highly associated with postoperative results, we found no association of additional MRR with any of our postoperative outcome measures. The Yokoyama procedure had a higher absolute effect in patients with higher preoperative esotropia. Conclusion Our study confirms the positive effect of the Yokoyama procedure on strabismus due to high myopia in large-scale real-world data. In some cases, MRR may be needed because of muscle contracture, although additional MRR statistically did not affect the postoperative outcome. In patients with bilateral high myopic strabismus, correction of both eyes seems beneficial. The effect size of the Yokoyama procedure appears to be mainly driven by preoperative esotropia.}, language = {en} }