@article{DickKraussHillenkampetal.2017, author = {Dick, Julia and Krauß, Patrizia and Hillenkamp, Jost and Kohlmorgen, Britta and Schoen, Christoph}, title = {Postoperative Tropheryma whipplei endophthalmitis - a case report highlighting the additive value of molecular testing}, series = {JMM Case Reports}, volume = {4}, journal = {JMM Case Reports}, doi = {10.1099/jmmcr.0.005124}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158823}, pages = {e005124}, year = {2017}, abstract = {Introduction. Tropheryma whipplei is the causative agent of Whipple's disease. Gastrointestinal and lymphatic tissues are affected in the majority of cases, resulting in diarrhoea, malabsorption and fever. Here, we report a rare case of ocular manifestation in a patient lacking the typical Whipple symptoms. Case presentation. A 74-year-old Caucasian female presented with blurred vision in the right eye over a period of 1-2 months, accompanied by stinging pain and conjunctival hyperaemia for the last 2 days. Upon admission, visual acuity was hand motion in the affected eye. Ophthalmological examination showed typical signs of intraocular inflammation. Diagnostic and therapeutic pars plana vitrectomy including vitreous biopsy and intravitreal instillation of vancomycin and amikacin was performed within hours of initial presentation. Both microscopic analysis and microbial cultures of the vitreous biopsy remained negative for bacteria and fungi. The postoperative antibiotic regime included intravenous administration of ceftriaxone in combination with topical tobramycin and ofloxacin. Due to the empirical therapy the inflammation ceased and the patient was discharged after 5 days with cefpodoxime orally and local antibiotic and steroidal therapy. Meanwhile, the vitreous body had undergone testing by PCR for the eubacterial 16S rRNA gene, which was found to be positive. Analysis of the PCR product revealed a specific sequence of T. whipplei. Conclusion. In our patient, endophthalmitis was the first and only symptom of Morbus Whipple, while most patients with Whipple's disease suffer from severe gastrointestinal symptoms. 16S rDNA PCR should be considered for any intraocular infection when microscopy and standard culture methods remain negative.}, language = {en} } @article{BenAmiTongBhuiyanetal.2016, author = {Ben Ami, Tal and Tong, Yuehong and Bhuiyan, Alauddin and Huisingh, Carrie and Ablonczy, Zsolt and Ach, Thomas and Curcio, Christine A. and Smith, R. Theodore}, title = {Spatial and Spectral Characterization of Human Retinal Pigment Epithelium Fluorophore Families by Ex Vivo Hyperspectral Autofluorescence Imaging}, series = {Translational Vision Science \& Technology}, volume = {5}, journal = {Translational Vision Science \& Technology}, number = {3}, doi = {10.1167/tvst.5.3.5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168328}, pages = {5}, year = {2016}, abstract = {Purpose: Discovery of candidate spectra for abundant fluorophore families in human retinal pigment epithelium (RPE) by ex vivo hyperspectral imaging. Methods: Hyperspectral autofluorescence emission images were captured between 420 and 720 nm (10-nm intervals), at two excitation bands (436-460, 480-510 nm), from three locations (fovea, perifovea, near-periphery) in 20 normal RPE/Bruch's membrane (BrM) flatmounts. Mathematical factorization extracted a BrM spectrum (S0) and abundant lipofuscin/melanolipofuscin (LF/ML) spectra of RPE origin (S1, S2, S3) from each tissue. Results: Smooth spectra S1 to S3, with perinuclear localization consistent with LF/ML at all three retinal locations and both excitations in 14 eyes (84 datasets), were included in the analysis. The mean peak emissions of S0, S1, and S2 at λ\(_{ex}\) 436 nm were, respectively, 495 ± 14, 535 ± 17, and 576 ± 20 nm. S3 was generally trimodal, with peaks at either 580, 620, or 650 nm (peak mode, 650 nm). At λ\(_{ex}\) 480 nm, S0, S1, and S2 were red-shifted to 526 ± 9, 553 ± 10, and 588 ± 23 nm, and S3 was again trimodal (peak mode, 620 nm). S1 often split into two spectra, S1A and S1B. S3 strongly colocalized with melanin. There were no significant differences across age, sex, or retinal location. Conclusions: There appear to be at least three families of abundant RPE fluorophores that are ubiquitous across age, retinal location, and sex in this sample of healthy eyes. Further molecular characterization by imaging mass spectrometry and localization via super-resolution microscopy should elucidate normal and abnormal RPE physiology involving fluorophores. Translational Relevance: Our results help establish hyperspectral autofluorescence imaging of the human retinal pigment epithelium as a useful tool for investigating retinal health and disease.}, 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} } @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{SchmidTarauRossietal.2018, author = {Schmid, Richard and Tarau, Ioana-Sandra and Rossi, Angela and Leonhardt, Stefan and Schwarz, Thomas and Schuerlein, Sebastian and Lotz, Christian and Hansmann, Jan}, title = {In Vivo-Like Culture Conditions in a Bioreactor Facilitate Improved Tissue Quality in Corneal Storage}, series = {Biotechnology Journal}, volume = {13}, journal = {Biotechnology Journal}, number = {1,1700344}, doi = {10.1002/biot.201700344}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228620}, pages = {1-7}, year = {2018}, abstract = {The cornea is the most-transplanted tissue worldwide. However, the availability and quality of grafts are limited due to the current methods of corneal storage. In this study, a dynamic bioreactor system is employed to enable the control of intraocular pressure and the culture at the air-liquid interface. Thereby, in vivo-like storage conditions are achieved. Different media combinations for endothelium and epithelium are tested in standard and dynamic conditions to enhance the viability of the tissue. In contrast to culture conditions used in eye banks, the combination of the bioreactor and biochrom medium 1 allows to preserve the corneal endothelium and the epithelium. Assessment of transparency, swelling, and the trans-epithelial-electrical-resistance (TEER) strengthens the impact of the in vivo-like tissue culture. For example, compared to corneas stored under static conditions, significantly lower optical densities and significantly higher TEER values were measured (p-value <0.05). Furthermore, healing of epithelial defects is enabled in the bioreactor, characterized by re-epithelialization and initiated stromal regeneration. Based on the obtained results, an easy-to-use 3D-printed bioreactor composed of only two parts was derived to translate the technology from the laboratory to the eye banks. This optimized bioreactor facilitates noninvasive microscopic monitoring. The improved storage conditions ameliorate the quality of corneal grafts and the storage time in the eye banks to increase availability and reduce re-grafting.}, language = {en} } @article{MuellerMeigen2016, author = {M{\"u}ller, Philipp L. and Meigen, Thomas}, title = {M-sequences in ophthalmic electrophysiology}, series = {Journal of Vision}, volume = {16}, journal = {Journal of Vision}, number = {1,15}, doi = {10.1167/16.1.15}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165796}, pages = {1-19}, year = {2016}, abstract = {The aim of this review is to use the multimedia aspects of a purely digital online publication to explain and illustrate the highly capable technique of m-sequences in multifocal ophthalmic electrophysiology. M-sequences have been successfully applied in clinical routines during the past 20 years. However, the underlying mathematical rationale is often daunting. These mathematical properties of m-sequences allow one not only to separate the responses from different fields but also to analyze adaptational effects and impacts of former events. By explaining the history, the formation, and the different aspects of application, a better comprehension of the technique is intended. With this review we aim to clarify the opportunities of m-sequences in order to motivate scientists to use m-sequences in their future research.}, language = {en} } @phdthesis{Glatzel2021, author = {Glatzel, Caroline}, title = {Ergebnisse einer neuen Filtrationsoperation im Vergleich zur konventionellen Trabekulektomie bei Glaukom}, doi = {10.25972/OPUS-16719}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167192}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Ziel: Die vorliegende Studie untersucht das Langzeitoutcome der filtrierenden Trabe- kulotomie (FTO) und vergleicht diese mit der konventionellen Trabekulektomie. Nach- dem in der Arbeit von Matlach et al. bereits gezeigt werden konnte, dass die filtrierende Trabekulotomie nach einem Jahr im Bezug auf die Augeninnendrucksenkung und das Auftreten von postoperativen Komplikationen mit der konventionellen Trabekulektomie vergleichbar ist (32), sollte in der vorliegenden Arbeit der Langzeiterfolg der beiden Ope- rationsmethoden miteinander verglichen werden. Untersucht wurde deshalb der intraoku- lare Druck, Langzeitkomplikationen, Folgeoperationen und der Visus nach eineinhalb und zwei Jahren. Methode: In einer Fall-Kontroll-Studie wurden 30 Patienten nach einer filtrierenden Tra- bekulotomie (prospektiv) mit 87 Patienten nach einer konventionellen Trabekulektomie (retrospektiv) verglichen. Alle Patienten waren zwischen 2007 und 2012 von demselben Operateur an der Augenklinik der Universit{\"a}t W{\"u}rzburg operiert worden. Eingeschlossen wurden Patienten mit prim{\"a}rem Offenwinkelglaukom, Pseudoexfoliationsglaukom und Pigmentdispersionsglaukom. Die Patienten waren nach Alter und intraokularem Druck (IOD) gematcht worden. Die Daten der vorliegenden Studie wurden an der Augenklink der Universit{\"a}t W{\"u}rzburg oder von den weiterbehandelnden niedergelassenen Augen{\"a}rz- ten mit Hilfe eines f{\"u}r diese Studie entworfenen Fragebogens erhoben. Endpunkt: Als prim{\"a}rer Endpunkt wurde ein Augeninnendruck von < 18 mmHg und eine Augeninnendrucksenkung um ≥ 30 \% des Ausgangswertes festgelegt. Wurden diese Kriterien ohne Medikamente erreicht, sprach man von einem „absoluten Erfolg" (com- plete-success), andernfalls von einem „relativen Erfolg" (qualified-success). Als sekund{\"a}re Endpunkte galten der intraokulare Druckverlauf, die Erfassung der Kom- plikationen, Folgeeingriffe, der Visusverlauf und die Medikation. Ergebnisse: Von den anfangs 117 eingeschlossenen Patienten konnten nach 2 Jahren die Daten von 95 Patienten (27 aus der FTO-Gruppe und 68 aus der TE-Gruppe) erhoben werden. Pr{\"a}operativ unterschieden sich die beiden Studiengruppen nicht signifikant im Bezug auf das Alter und den IOD, nach denen die Gruppen gematcht worden waren, den Visus (p= 0,60), das Geschlecht (p = 0,30) und die pr{\"a}operativ verwendeten Medikamente (p≥ 0,05). In der FTO-Gruppe lag die Zahl der Patienten mit Pigmentdispersionsglaukom (p= 0,02) und Pseudophakie (p = 0,02) schon pr{\"a}operativ deutlich {\"u}ber der der TE- Gruppe. Der IOD lag pr{\"a}operativ in beiden Operationsgruppen bei 23 mmHg (IQR 20- 27), wobei im Median 3,0 verschiedene augendrucksenkende Medikamente angewendet wurden. Der absolute Erfolg (complete-success) unterschied sich im Zeitraum der vorliegenden Studie zu keinem Zeitpunkt signifikant zwischen den Studiengruppen (p 18Mon. = 0,50 ; p 24Mon. = 0,067). Auch der relative Erfolg (qualified-success) unterschied sich zwischen den Gruppen nicht signifikant (p 18Mon. = 0,23 ; p 24Mon. = 0,60). Nach 2 Jahren erreichten 33,3 \% der FTO- und 56,7 \% der TE-Patienten einen absoluten Erfolg und 70,4 \% bzw. 77,6 \% einen relativen Erfolg. Der mediane postoperative IOD konnte auch 1,5 und 2 Jahre nach den Operationen sig- nifikant unter den pr{\"a}operativen IOD gesenkt werden (p < 0,001) und betrug nach 2 Jah- ren in der FTO-Gruppe 12,80 ± 3,79 mmHg und in der TE-Gruppe 11 mmHg (IQR 9- 13). Er unterschied sich auch zwischen beiden Gruppen zu keinem Zeitpunkt signifikant (p 18Mon. = 0,18 ; p 24Mon. = 0,12). Der mediane postoperative Visus unterschied sich 1,5 und 2 Jahre nach der OP zwischen den Gruppen nicht signifikant (p 1,5a = 0,11; p 2a = 0,77). In der FTO-Gruppe verschlech- terte sich der Visus der Patienten von 0,10 logMAR (0,79) nach 18 Monaten auf 0,20 logMAR (0,63) nach 24 Monaten. Der Visus in der TE-Gruppe blieb konstant (0,15 log- MAR). Insgesamt hatte sich der Visus der Patienten nach 1,5 und 2 Jahren im Vergleich zum pr{\"a}operativen Visus signifikant verschlechtert (p 1,5a = 0,02; p 2a = 0,00). Bei der separaten Auswertung der Patienten mit PEX-Glaukom konnte der IOD postope- rativ zu allen statistisch beurteilbaren Zeitpunkten signifikant unter den pr{\"a}operativen IOD gesenkt werden. Bei einem Vergleich zwischen den Gruppen lag der IOD der FTO- Gruppe einmalig {\"u}ber dem der TE-Gruppe. In den anderen F{\"a}llen traten keine signifikan- ten Druckunterschiede zwischen den Gruppen auf. Der postoperative Visus unterschied sich zu keinem Zeitpunkt, ob mit oder ohne Kunstlinse, im pr{\"a}- postoperativen Vergleich und zwischen den Gruppen. Die Anzahl der Wirkstoffklassen unterschied sich zwischen den Gruppen nicht signifi- kant. Reoperationen traten nach beiden Operationsmethoden so selten auf, sodass eine statistische Bewertung nicht m{\"o}glich war. Die Verteilung der Glaukomformen hatte sich auch nach 1,5 und 2 Jahren nicht ver{\"a}ndert. Die Zahl pseudophaker Patienten war im Beobachtungszeitraum auch in der TE-Gruppe stetig angestiegen, so dass sie sich nach 2 Jahren nicht mehr signifikant zwischen den Gruppen unterschied. Schlussfolgerung: Die FTO ist im Bezug auf den IOD, den Visus und die Erfolgsrate der TE {\"a}quivalent. Im Langzeitverlauf traten in der FTO Gruppe nicht mehr Komplikationen als nach TE auf. Nach 1 Jahr waren in der FTO-Gruppe signifikant mehr fr{\"u}he Komplikationen auf- getreten als in der TE. Nach 2 Jahren war die Rate an Komplikationen in den Gruppen nicht mehr signifikant unterschiedlich.}, subject = {Glaukom}, language = {de} } @article{BalasubramanianOthmanKampiketal.2017, author = {Balasubramanian, Srikkanth and Othman, Eman M. and Kampik, Daniel and Stopper, Helga and Hentschel, Ute and Ziebuhr, Wilma and Oelschlaeger, Tobias A. and Abdelmohsen, Usama R.}, title = {Marine sponge-derived Streptomyces sp SBT343 extract inhibits staphylococcal biofilm formation}, series = {Frontiers in Microbiology}, volume = {8}, journal = {Frontiers in Microbiology}, doi = {10.3389/fmicb.2017.00236}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171844}, year = {2017}, abstract = {Staphylococcus epidermidis and Staphylococcus aureus are opportunistic pathogens that cause nosocomial and chronic biofilm-associated infections. Indwelling medical devices and contact lenses are ideal ecological niches for formation of staphylococcal biofilms. Bacteria within biofilms are known to display reduced susceptibilities to antimicrobials and are protected from the host immune system. High rates of acquired antibiotic resistances in staphylococci and other biofilm-forming bacteria further hamper treatment options and highlight the need for new anti-biofilm strategies. Here, we aimed to evaluate the potential of marine sponge-derived actinomycetes in inhibiting biofilm formation of several strains of S. epidermidis, S. aureus, and Pseudomonas aeruginosa. Results from in vitro biofilm-formation assays, as well as scanning electron and confocal microscopy, revealed that an organic extract derived from the marine sponge-associated bacterium Streptomyces sp. SBT343 significantly inhibited staphylococcal biofilm formation on polystyrene, glass and contact lens surfaces, without affecting bacterial growth. The extract also displayed similar antagonistic effects towards the biofilm formation of other S. epidermidis and S. aureus strains tested but had no inhibitory effects towards Pseudomonas biofilms. Interestingly the extract, at lower effective concentrations, did not exhibit cytotoxic effects on mouse fibroblast, macrophage and human corneal epithelial cell lines. Chemical analysis by High Resolution Fourier Transform Mass Spectrometry (HRMS) of the Streptomyces sp. SBT343 extract proportion revealed its chemical richness and complexity. Preliminary physico-chemical characterization of the extract highlighted the heat-stable and non-proteinaceous nature of the active component(s). The combined data suggest that the Streptomyces sp. SBT343 extract selectively inhibits staphylococcal biofilm formation without interfering with bacterial cell viability. Due to absence of cell toxicity, the extract might represent a good starting material to develop a future remedy to block staphylococcal biofilm formation on contact lenses and thereby to prevent intractable contact lens-mediated ocular infections.}, language = {en} } @article{LittsAchHammacketal.2016, author = {Litts, Katie M. and Ach, Thomas and Hammack, Kristen M. and Sloan, Kenneth R. and Zhang, Yuhua and Freund, K. Bailey and Curcio, Christine A.}, title = {Quantitative Analysis of Outer Retinal Tubulation in Age-Related Macular Degeneration From Spectral-Domain Optical Coherence Tomography and Histology}, series = {Investigative Ophthalmology \& Visual Science}, volume = {57}, journal = {Investigative Ophthalmology \& Visual Science}, doi = {10.1167/iovs.16-19262}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165532}, pages = {2647-2656}, year = {2016}, abstract = {Purpose: To assess outer retinal tubulation (ORT) morphology from spectral-domain optical coherence tomography (SD-OCT) volumes and donor eye histology, analyze ORT reflectivity, and estimate the number of cones surviving in ORT. Methods: In SD-OCT volumes from nine patients with advanced AMD, ORT was analyzed en face and in B-scans. The hyperreflective ORT border in cross-section was delineated and surface area calculated. Reflectivity was compared between ORT types (Closed, Open, Forming, and Branching). A flatmount retina from a donor with neovascular AMD was labeled to visualize the external limiting membrane that delimits ORT and allow measurements of cross-sectional cone area, center-to-center cone spacing, and cone density. The number of cones surviving in ORT was estimated. Results: By en face SD-OCT, ORT varies in complexity and shape. Outer retinal tubulation networks almost always contain Closed cross-sections. Spectral-domain OCT volumes containing almost exclusively Closed ORTs showed no significant direction-dependent differences in hyperreflective ORT border intensity. The surface areas of partial ORT assessed by SD-OCT volumes ranged from 0.16 to 1.76 mm2. From the flatmount retina, the average cross-sectional area of cone inner segments was 49.1 ± 7.9 μm2. The average cone spacing was 7.5 ± 0.6 μm. Outer retinal tubulation cone density was 20,351 cones/mm2. The estimated number of cones in ORT in a macula ranged from 26,399 to 186,833 cones, which is 6\% to 44\% of the cones present in a healthy macula. Conclusions: These first estimates for cone density and number of cones surviving in ORT suggest that ORT formation considerably distorts the photoreceptor mosaic. Results provide additional insight into the reflectivity characteristics and number of ORT cones observable in living patients by SD-OCT, as cones persist and disease progresses.}, language = {en} } @article{LotzSchmidRossietal.2016, author = {Lotz, Christian and Schmid, Freia F. and Rossi, Angela and Kurdyn, Szymon and Kampik, Daniel and De Wever, Bart and Walles, Heike and Groeber, Florian K.}, title = {Alternative Methods for the Replacement of Eye Irritation Testing}, series = {ALTEX - Alternatives to Animal Experimentation}, volume = {33}, journal = {ALTEX - Alternatives to Animal Experimentation}, number = {1}, doi = {10.14573/altex.1508241}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164444}, pages = {55-67}, year = {2016}, abstract = {In the last decades significant regulatory attempts were made to replace, refine and reduce animal testing to assess the risk of consumer products for the human eye. As the original in vivo Draize eye test is criticized for limited predictivity, costs and ethical issues, several animal-free test methods have been developed to categorize substances according to the global harmonized system (GHS) for eye irritation. This review summarizes the progress of alternative test methods for the assessment of eye irritation. Based on the corneal anatomy and current knowledge of the mechanisms causing eye irritation, different ex vivo and in vitro methods will be presented and discussed with regard to possible limitations and status of regulatory acceptance. In addition to established in vitro models, this review will also highlight emerging, full thickness cornea models that might be suited to predict all GHS categories.}, language = {en} }