Modulation of Decellularized Lacrimal Gland Hydrogel Biodegradation by Genipin Crosslinking.

Purpose: Hydrogels derived from decellularized tissues are promising biomaterials in tissue engineering, but their rapid biodegradation can hinder in vitro cultivation. This study aimed to retard biodegradation of a hydrogel derived from porcine decellularized lacrimal glands (dLG-HG) by crosslinking with genipin to increase the mechanical stability without affecting the function and viability of lacrimal gland (LG)-associated cells. Methods: The effect of different genipin concentrations on dLG-HG stiffness was measured rheologically. Cell-dependent biodegradation was quantified over 10 days, and the impact on matrix metalloproteinase (MMP) activity was quantified by gelatin and collagen zymography. The viability of LG epithelial cells (EpCs), mesenchymal stem cells (MSCs), and endothelial cells (ECs) cultured on genipin-crosslinked dLG-HG was assessed after 10 days, and EpC secretory activity was analyzed by ß-hexosaminidase assay. Results: The 0.5-mM genipin increased the stiffness of dLG-HG by about 46%, and concentrations > 0.25 mM caused delayed cell-dependent biodegradation and reduced MMP activity. The viability of EpCs, MSCs, and ECs was not affected by genipin concentrations of up to 0.5 mM after 10 days. Moreover, up to 0.5-mM genipin did not negatively affect EpC secretory activity compared to control groups. Conclusions: A concentration of 0.5-mM genipin increased dLG-HG stiffness, and 0.25-mM genipin was sufficient to prevent MMP-dependent degradation. Importantly, concentrations of up to 0.5-mM genipin did not compromise the viability of LG-associated cells or the secretory activity of EpCs. Thus, crosslinking with genipin improves the properties of dLG-HG for use as a substrate in LG tissue engineering.

UV light-mediated corneal crosslinking as (lymph)angioregressive pretreatment to promote graft survival after subsequent high-risk corneal transplantation (CrossCornealVision): protocol for a multicenter, randomized controlled trial.

BACKGROUND: Good vision highly depends on the transparency of the cornea, which is the "windscreen" of the eye. In fact, corneal blindness due to transparency loss is the second most common cause of blindness worldwide, and corneal transplantation is the main cure. Importantly, the cornea is normally avascular but can secondarily be invaded by pathological (blood and lymphatic) vessels due to severe inflammation, and the survival prognosis of a corneal graft mainly depends on the preoperative vascular condition of the recipient's cornea. Whereas transplants placed into avascular recipient beds enjoy long-term survival rates of > 90%, survival rates significantly decrease in pathologically pre-vascularized, so-called high-risk recipients, which account for around 10% of all performed transplants in Germany and > 75% in lower and middle-income countries worldwide. METHODS: This parallel-grouped, open-randomized, multicenter, prospective controlled exploratory investigator-initiated trial (IIT) intends to improve graft survival by preconditioning pathologically vascularized recipient corneas by (lymph)angioregressive treatment before high-risk corneal transplantation. For this purpose, corneal crosslinking (CXL) will be used, which has been shown to potently regress corneal blood and lymphatic vessels. Prior to transplantation, patients will be randomized into 2 groups: (1) CXL (intervention) or (2) no pretreatment (control). CXL will be repeated once if insufficient reduction of corneal neovascularization should be observed. All patients (both groups) will then undergo corneal transplantation. In the intervention group, remaining blood vessels will be additionally regressed using fine needle diathermy (on the day of transplantation). Afterwards, the incidence of graft rejection episodes will be evaluated for 24 months (primary endpoint). Overall graft survival, as well as regression of corneal vessels and/or recurrence, among other factors, will be analyzed (secondary endpoints). DISCUSSION: Based on preclinical and early pilot clinical evidence, we want to test the novel concept of temporary (lymph)angioregressive pretreatment of high-risk eyes by CXL to promote subsequent corneal graft survival. So far, there is no evidence-based approach to reliably improve graft survival in the high-risk corneal transplantation setting available in clinical routine. If successful, this approach will be the first to promote graft survival in high-risk transplants. It will significantly improve vision and quality of life in patients suffering from corneal blindness. TRIAL REGISTRATION: ClinicalTrials.gov NCT05870566. Registered on 22 May 2023.

Enhancement of lacrimal gland cell function by decellularized lacrimal gland derived hydrogel.

Sustainable treatment of aqueous deficient dry eye (ADDE) represents an unmet medical need and therefore requires new curative and regenerative approaches based on appropriatein vitromodels. Tissue specific hydrogels retain the individual biochemical composition of the extracellular matrix and thus promote the inherent cell´s physiological function. Hence, we created a decellularized lacrimal gland (LG) hydrogel (dLG-HG) meeting the requirements for a bioink as the basis of a LG model with potential forin vitroADDE studies. Varying hydrolysis durations were compared to obtain dLG-HG with best possible physical and ultrastructural properties while preserving the original biochemical composition. A particular focus was placed on dLG-HG´s impact on viability and functionality of LG associated cell types with relevance for a futurein vitromodel in comparison to the unspecific single component hydrogel collagen type-I (Col) and the common cell culture substrate Matrigel. Proliferation of LG epithelial cells (EpC), LG mesenchymal stem cells, and endothelial cells cultured on dLG-HG was enhanced compared to culture on Matrigel. Most importantly with respect to a functionalin vitromodel, the secretion capacity of EpC cultured on dLG-HG was higher than that of EpC cultured on Col or Matrigel. In addition to these promising cell related properties, a rapid matrix metalloproteinase-dependent biodegradation was observed, which on the one hand suggests a lively cell-matrix interaction, but on the other hand limits the cultivation period. Concluding, dLG-HG possesses decisive properties for the tissue engineering of a LGin vitromodel such as cytocompatibility and promotion of secretion, making it superior to unspecific cell culture substrates. However, deceleration of biodegradation should be addressed in future experiments.

High-Impact Actions to Reduce the Carbon Dioxide Footprint in an Ophthalmic Operation Room: A Narrative Review.

Germany's health care footprint accounts for 5.2% of the national emissions footprint which results in 0.71 tons of CO2 emission per capita. Thus, the health sector has a responsibility to take climate action. Surgery is a resource-intensive health care activity, requiring expensive equipment, sterilization procedures, advanced operative technologies, and obligatory life support systems. We spotlight the situation in a department of ophthalmology with frequent anesthesia services and highly standardized procedures. This narrative review discusses high-impact actions which result in a major reduction of the CO2 footprint according to the global road map for health care decarbonization, considering both the ophthalmic and anesthesiologic point of view.

Brillouin Spectroscopy in Ophthalmology. / Gegenwärtiger Stand der Brillouin-Spektroskopie in der Ophthalmologie.

BACKGROUND: Information about corneal biomechanics is crucial for achieving satisfactory outcomes after surgical corneal interventions, e.g., for astigmatic keratotomies, but also to identify corneas that are at risk for postoperative complications such as corneal ectasia. Hitherto, approaches to characterize corneal biomechanics in an in vivo setting have yielded only minor success, demonstrating the unmet medical need for a diagnostic technique to measure ocular biomechanics. OBJECTIVE: This review shall explain the mechanism of Brillouin spectroscopy and summarize the current scientific knowledge for ocular tissue. METHODS: PubMed research of relevant experimental and clinical publications, as well as reporting of own experience using Brillouin spectroscopy. RESULTS: Brillouin spectroscopy can measure different biomechanical moduli with a high spatial resolution. Currently, available devices are able to detect focal corneal weakening, e.g., in keratoconus, as well as stiffening after corneal cross-linking. Also, the mechanical properties of the crystalline can be measured. Corneal anisotropy and hydration, together with the dependence on the angle of the incident laser beam in Brillouin spectroscopy, are challenges in the precise interpretation of measured data. A clear advantage in the detection of subclinical keratoconus compared to corneal tomography, however, has not been shown yet. CONCLUSION: Brillouin spectroscopy is a technique to characterize biomechanical properties of ocular tissue in vivo. Published results confirm ex vivo data of ocular biomechanics; however, further improvements in the acquisition and interpretation of measured data are required until this technique can be used in a clinically viable setting.

Current Practice in the Treatment of Epithelial and Melanocytic Tumours with Interferon-α2b: A Survey of Tertiary Eye Centres in Germany.

PURPOSE: To evaluate the standard of care, in particular the use of topical or subconjunctival interferon-α2b, in treating ocular surface squamous neoplasia or melanocytic tumours in tertiary eye centres in Germany. METHODS: A survey containing 14 questions was sent to 43 tertiary eye centres in Germany. The questions addressed the surgical and medical management of ocular surface squamous neoplasia and melanocytic tumours (primary acquired melanosis and malignant melanoma), as well as the clinical experiences and difficulties in prescribing off-label interferon-α2b eye drops and subconjunctival injections. RESULTS: Twenty-four tertiary eye centres responded to the survey. Eighty-three percent of centres had used interferon-α2b in their clinical practice and 25% prescribed it as the first-line cytostatic agent following surgical excision of ocular surface squamous neoplasia, while 10% would do so for melanocytic tumours. Correspondingly, the majority of respondents selected mitomycin C as their first-line agent. Side effects were uncommon with topical interferon-α2b eye drops but were more frequently reported after subconjunctival interferon-α2b injections. In total, eight centres had experience with interferon-α2b injections. The most significant obstacles perceived by ophthalmologists when prescribing interferon-α2b were its high cost and the reimbursement thereof. CONCLUSION: Off-label mitomycin C was the preferred adjuvant therapy for epithelial and melanocytic tumours, with interferon-α2b being the standard second-line option. Interferon-α2b has predominantly been used to treat ocular surface squamous neoplasia and, to a lesser extent, melanocytic tumours at German tertiary eye centres. Following its market withdrawal, supply shortages of interferon-α2b are likely to have a profound impact on patient care and their quality of life.

Evaluation of the Use of Intraoperative OCT in Routine Surgery: A Two-year Comparison. / Evaluation der Nutzung von intraoperativer OCT im operativen Alltag: ein 2-Jahres-Vergleich.

BACKGROUND: In recent years, an increasing number of surgical microscopes fitted with an OCT module (intraoperative OCT, iOCT) have become available, providing high-resolution images of the surgical site in real time. While a 2018 survey at our hospital showed that iOCT delivered an additional intraoperative benefit in only 2.4% of all operations, considering that the manufacturer had since revised the hardware and software, we conducted a second user evaluation of this technology. MATERIAL AND METHODS: Prospective monocentric analysis of the application and user-friendliness of an EnFocus Ultra-Deep OCT (Leica Microsystems) over a period of 25 (2018) and 20 working days (2021). A standardized questionnaire was used to assess the surgeons' use of iOCT and its influence on the surgical course. RESULTS: 118 operations were performed over a 25-day period in 2018 and 92 operations were performed over a 20-day period in 2021. In 2018, iOCT was used in 24.6% and in 2021 in 48.9% of all surgeries, with iOCT proving to be "critical" to the surgical course in 2.4% and 3.3% of cases, respectively, as assessed by the surgeons in both years. These were operations in which the intraocular view was limited, e.g., with decompensated cornea, vitreous hemorrhage, or after previous surgery, e.g., after penetrating keratoplasty. CONCLUSION: Further development of the user interface led to an improvement in usability, and the iOCT was used significantly more often. In both years, the iOCT proved to be critical for the course of the surgery in a comparably small number of operations, especially those involving complex situations.

The influence of a mineral oil cationic nanoemulsion or perfluorohexyloctane on the tear film lipid layer and higher order aberrations.

PURPOSE: To prospectively assess the effect of a single and regular application of either a cationic nanoemulsion of mineral oil (CN) or perfluorohexyloctane (F6H8) on the lipid layer of the tear film and higher order aberrations (HOA) in patients with Dry Eye Disease (DED). METHODS: Fifty-seven patients with a lipid layer thickness (LLT) ≤ 75 interferometric colour units (ICU) were included in the study. In group A (20 patients) the effect of a single drop of F6H8 or CN on HOA and LLT was assessed immediately after application and up to two hours later. For long term effects (Group B) 37 patients applied CN or F6H8 five times a day for 12 weeks. Measurement of LLT, HOA, non-invasive-tear-break-up-time (NIBUT) and meibography were assessed prior to as well as at 4 weeks and 12 weeks after initiation of treatment. Our study is registered in the "German Clinical Trials Register" under the trial number: DRKS00028696. RESULTS: CN led to an increase of the LLT from 46.8 ± 16.9 ICU to 76.3 ± 23.5 ICU (p = 0.021) and to an increase of HOA from 0.43 ± 0.06 µm to 0.48 ± 0.08 µm immediately after application (p = 0.027). There was no correlation between the increase of LLT and HOA (r = -0.04; p = 0.90). In group B an increase of LLT was observed in the F6H8 group from 45.8 ± 8.8 ICU at baseline to 66.7 ± 19.5 ICU at 12 weeks (p = 0.002). No changes of HOA were measured throughout the observation period in group B. After 12 weeks CN increased NIBUT from 9.9 ± 5.3 seconds to 15.5 ± 5.6 seconds (p = 0.04). F6H8 increased NIBUT from 12.4 ± 5.9 seconds to 16.9 ± 4.7 seconds (p = 0.02) after 12 weeks. CONCLUSION: CN leads to a short-term increase in LLT and HOA, but only immediately after application. In contrast F6H8 does lead to an increase of LLT after regular long-term use but has no effect on HOA. The regular application of lipid-based products does not seem to decrease the quality of vision as measured in HOA. Instead, CN and F6H8, both are able to stabilize the tear film after regular application.

Use of Endoscopy in Keratoprostheses with Biological Haptics. / Endoskopieeinsatz bei Keratoprothesen mit biologischer Haptik.

INTRODUCTION: In severe ocular surface disease where penetrating keratoplasty cannot be successfully performed, implantation of a keratoprosthesis can achieve visual rehabilitation. Osteo-odonto-keratoprosthesis offers good tissue integration due to its biological haptics, resulting in a better survival rate and lower extrusion rate. Due to corneal opacity, which is often complete, assessing the potential visual acuity is challenging. Also, during implantation of a keratoprosthesis or during later intraocular revision surgery, there is a limited field of view of the peripheral retina or ciliary body region. This is due to the small size and central location of the prosthesis optics and the geometric conditions of the prosthetic haptics. These factors can complicate surgery. METHODS: Endoscopic video assistance was used in 7 eyes of 6 different patients (6 male, 2 female, mean age 66 ± 9 years). In 3 eyes the indication was for preoperative estimation of potential visual acuity during a 23 G vitrectomy. In 2 eyes it was used during implantation surgery itself, and in 2 eyes it was used during revision surgery and vitrectomy. An endoscope with semirigid optics and an image guidance system with 3,000 pixels and 70°field of view from PolyDiagnost was used, with a 23 G trocar system. RESULTS: Endoscopy was successfully applied in all eyes examined. In 1 of 3 eyes where endoscopy was performed to estimate the visual acuity potential, a keratoprosthesis was subsequently planned. In the other two eyes, the visual acuity potential was rated insufficient for future keratoprosthesis surgery. Detailed assessment of the retina and optic disc was limited to gross pathologies because of low image resolution. During implantation, it was possible to visualize correct positioning of the posterior haptic behind the host cornea. Retroprosthetic membranes could successfully be removed by endoscopy-assisted vitrectomy. CONCLUSION: Endoscopy assistance offers advantages in visualization both for determining the indication for KPro surgery, during implantation, and in the management of complications after implantation of a keratoprosthesis. Low resolution of the imaging system places limits on assessment capabilities. Although technical improvements and miniaturization may enhance its future capabilities, endoscopy in its current form is already a valuable addition in the context of keratoprosthesis surgery.

Descemet Membrane Endothelial Keratoplasty and Triple Descemet Membrane Endothelial Keratoplasty in Eyes With Macular Comorbidity.

PURPOSE: The aim of this study was to evaluate results after Descemet membrane endothelial keratoplasty (DMEK) and DMEK with cataract surgery (triple DMEK) in eyes with endothelial dysfunction and concomitant macular pathology. METHODS: A monocentric, prospective clinical observational study of patients who underwent DMEK or triple DMEK surgery at the Department of Ophthalmology, University Hospital Düsseldorf, Germany, from June 2013 to February 2016 was conducted. Sex, age, best-corrected visual acuity (BCVA), central corneal thickness, endothelial cell density, and central retinal thickness in the 1 millimeter zone were analyzed. RESULTS: A total of 209 eyes were included in the study. Forty-two eyes (20.1%) had vision-limiting concomitant maculopathies. These were age-related macular degeneration (n = 17, 8.1%), epiretinal gliosis (n = 13, 6.2%), chronic macular edema (n = 7, 3.3%), macular holes (n = 3, 1.4%), and macular scarring (n = 2, 1.0%). BCVA significantly increased in patients without maculopathy from 0.6 ± 0.33 logMAR to 0.1 ± 0.15 logMAR ( P < 0.001) and also in patients with maculopathy from 0.9 ± 0.38 logMAR to 0.27 ± 0.23 logMAR 12 months postoperatively ( P < 0.001). There was a significant central retinal thickness increase of 34.1 µm 6 weeks after triple DMEK in the central 1-mm zone ( P = 0.011). This increase was insignificant after DMEK. Postoperative macular edema occurred in 5.9% of cases after DMEK and 8.1% after triple DMEK, which was not significantly different. CONCLUSIONS: DMEK and triple DMEK significantly increase BCVA in eyes with concomitant maculopathy. Postoperative macular edema is a common disorder after lamellar keratoplasty; therefore, prophylactic treatment with nonsteroidal antiinflammatory drugs should be considered. Maculopathies did not predispose the development of postoperative macular edema.

[Diagnostics and treatment of organic intraorbital foreign bodies]. / Diagnostik und Therapie organischer intraorbitaler Fremdkörper.

BACKGROUND: Orbital injuries with organic foreign bodies are a clinical challenge as they can cause a variety of complications and sometimes lead to irreversible visual impairment. MATERIAL AND METHODS: We report five consecutive cases of patients with organic orbital foreign bodies who presented between 2012 and 2022. Documented parameters include age, gender, time of injury, mechanism of injury, best-corrected visual acuity (BCVA), presence of pain, restriction of motility, performed imaging, location and type of foreign body, treatment and complications. RESULTS: The mean patient age was 61.8 ± 32.3 years and the gender ratio was 4:1 (female:male). In 4 cases the injury had been reported on average 4.6 days (0/14 days min/max) previously. Best corrected visual acuity at first presentation was 0.5 ± 0.2 decimal and after a mean follow-up of 12.7 months (0.5/38 months min/max) at last presentation 0.67 ± 0.3 decimal (p = 0.2). The reason for initial presentation was pain (n = 3) and/or double vision (n = 2). All patients underwent computer tomography (CT). The diagnosis was confirmed in two cases by means of CT. In all five cases the foreign body material could be completely surgically removed, while one patient needed repeated surgery due to retained foreign body material. The organic foreign body material included wood (4) and wax (1). In two cases, a foreign body-induced infection was successfully treated with systemic antibiotics. There were no other complications. CONCLUSION: In orbital trauma a thorough wound exploration must be performed, especially if the mechanism of injury is uncertain and residual foreign bodies or a perforation injury cannot be excluded. The imaging of choice is CT, which may have to be performed again in the postoperative course.

Innovations in Corneal Crosslinking.

PURPOSE: Corneal Crosslinking (CXL) strengthens the keratoconus cornea and prevents further disease progression. Modified crosslinking protocols and different riboflavin solutions have been proposed to optimize the procedure and improve treatment success. METHODS: PubMed research of relevant publications and report of own experiences with different CXL protocols. RESULTS: Accelerated CXL shows comparable efficiency with shorter surgery time and similar complication rates. Customized CXL provides improved results with faster epithelial healing. CXL in a hyperoxic environment seems to be a safe and effective transepithelial alternative with presumably less complications and fewer side effects. Thin corneas (<400 µm) can be treated safely by corneal swelling using hypoosmolar riboflavin solutions and reducing the applied UV-energy. The combination of CXL with photorefractive keratectomy (PRK) can be considered in patients with contact lens intolerance improving visual acuity, however, with increased risk of visual loss compared to CXL alone. Two-Photon (2Ph) CXL is a promising new technology enabling three-dimensional CXL. DISCUSSION: Recently developed CXL protocols offer advantages over the standard "Dresden-protocol" and should be considered in patients with progressive keratectasia.

Total Full-Thickness Upper Eyelid Reconstruction: Combination of Mustardé Eyelid Switch Flap with a Bipedicled Periosteal and Tenzel Flap Technique.

INTRODUCTION: In recent decades, two techniques for large full-thickness upper eyelid reconstruction have been described, the Cutler-Beard lid sharing flap and the Mustardé eyelid switch flap. In the literature, modifications are being introduced to improve those techniques. Here, we present our approach for the reconstruction of total full-thickness upper eyelid defects and compare it with these established upper lid reconstruction techniques. METHODS: Three patients presented with upper eyelid tumors and required extensive excision resulting in total full-thickness upper eyelid defects. Reconstruction consisted of a two-stage procedure: a Mustardé eyelid switch flap was performed followed by division of the rotation flap and lateral canthoplasty using a periosteal bipedicled flap and Tenzel flap. Patients were followed-up every 3 months for at least 1 year. During every preoperative and postoperative check-up, palpebral fissure height, levator function, margin reflex distance, and presence of lagophthalmos were measured. RESULTS: Histopathological examination revealed a Merkel cell carcinoma in two cases and a Basal cell carcinoma in one case. Postoperatively, all patients showed a stable reconstructed upper eyelid with preserved motility and satisfying aesthetic results when compared to the fellow eye. In one case, a lagophthalmos of 1.5 mm was observed, which was treated conservatively to prevent exposure keratopathy. CONCLUSION: The eyelid switch flap combined with a bipedicled periosteal and a Tenzel flap is a good alternative for the reconstruction of total upper eyelid defects with the advantage of leaving the contralateral eye untouched. It achieves satisfying anatomical results, including an upper eyelid margin with eyelashes and well-matched skin color.

Descemet Membrane Endothelial Keratoplasty in Combination with Pars Plana Vitrectomy in Complex Eyes for Enhanced Gas Tamponades. / Descemet-Membran-Endothel-Keratoplastik in Kombination mit Pars-plana-Vitrektomie in komplexen Augen zur extensiven Gastamponade.

BACKGROUND: DMEK is well-established to treat endothelial corneal diseases. The procedure involves the use of an anterior chamber gastamponade to attach the graft. In eyes after lense extraction, fistulating glaucoma surgery or with large iris defects the gas tamponade is often lost postoperatively in the vitreous cavity or subconjunctival. We are reporting on three cases below, in which simultaneous anterior and posterior chamber gas tamponade were inserted with a combination of DMEK and 23-G pars plana vitrectomy (ppV). CASE DESCRIPTIONS: In the first case, a 70-year-old man experienced complete gas dislocation into the vitreous cavity early on after DMEK, resulting in re-bubbling being carried out in combination with 23-G ppV. In the second case, DMEK was immediately combined with ppV for an 80-year-old man who had an Ahmed glaucoma implant, and for a 61-year-old woman, our third case, who had traumatic aphakia. In all three cases, the vitreous cavity and anterior chamber were filled with 20% SF 6 as much as possible. In the second case, it was necessary to perform a re-bubbling due to partial graft dehiscence that occurred on the fifth day post-DMEK. The intraocular pressure in all three cases remained compensated postoperatively, and visual acuity increased despite the complex pre-existing conditions that had limited vision prior. DISCUSSION: The combined endotamponade of the anterior and posterior chambers while performing DMEK with 23-G ppV can extend the gas endotamponade in patients whose eyes have a complex medical history, and can thus ensure successful graft adherence.

Preserflo MicroShunt: Efficacy and Endothelial Cell Density.

PRCIS: A main safety concern associated with new glaucoma implants is corneal endothelial cell loss, which could even be observed in already established procedures. PURPOSE: The purpose of this study was to evaluate the efficacy and corneal safety, especially corneal endothelial cell loss (ECL), after Preserflo MicroShunt implantation. METHODS: A monocentric, prospective clinical observational study of patients with a follow-up of at least 12 months who underwent Preserflo MicroShunt implantation at the Department of Ophthalmology, University Hospital of Düsseldorf, Germany, between January 2020 and October 2021. Endothelial cell density (ECD), the distance between the tip of the implant and the corneal endothelium, and the success of the surgery were analyzed. RESULTS: In total, 14 eyes of 12 patients were included. After a mean follow-up of 20±2.7 months intraocular pressure was significantly reduced by 8.2 mm Hg (P=0.0041); in 28.6% of patients, a revision surgery was necessary. Reduction of preoperative and follow-up ECD was not statistically significant (ECL of 45 cells/mm2, ECDpreoperative=2074±703.6 cells/mm2, ECDlast follow-up=2029±742.3 cells/mm2, P=0.42). A longer intracameral shunt tube length correlated significantly with a higher distance between the shunt tip and corneal endothelium (r=0.61, P=0.036). CONCLUSIONS: Preserflo MicroShunt effectively lowered intraocular pressure without substantial ECL after a minimum follow-up period of 17 months.

S2k Guideline for the diagnosis and treatment of mucous membrane pemphigoid.

Mucous membrane pemphigoid (MMP) is a pemphigoid disease with predominant mucous membrane involvement. It mainly affects the mucous membranes of the mouth, eyes, nose and pharynx, but also the larynx, trachea, esophagus, genital and perianal regions. The manifestation of the disease covers a wide spectrum from gingival erythema and single oral lesions to severe tracheal strictures that obstruct breathing and conjunctival scarring with marked visual impairment and, not infrequently, blindness. In addition to a clinical picture of predominant mucosal involvement, diagnosis is based on direct immunofluorescence of a peri-lesional biopsy and serology. The main target antigen is BP180 (collagen XVII), and reactivity with laminin 332 is associated with malignancy in approximately 25 % of MMP patients. The treatment of MMP is challenging. On the one hand, due to the involvement of different mucous membranes, good interdisciplinary cooperation is required; on the other hand, due to the rarity of the disease, no randomized controlled clinical trials are available. The aim of this guideline is to present the clinical picture, including severity and scoring systems, and to give guidance for diagnosing and treating this complex disease. In MMP, interdisciplinary cooperation plays an essential role as well as the prompt diagnosis and initiation of adequate therapy in order to avoid irreversible damage to the mucous membranes with serious complications.

[Conjunctival reconstruction-State of the art of regenerative treatment forms beyond the limbus]. / Bindehautrekonstruktion ­ Status quo regenerativer Therapieformen jenseits des Limbus.

BACKGROUND: The demands on conjunctival replacement tissues are high: they need to be elastic, clinically compatible, surgically feasible and support goblet cell growth. OBJECTIVE: This article provides an overview of currently applied conjunctival replacement tissues and those under investigation. METHOD: Current publications on clinically applied conjunctival replacement tissues and substrates which are the subject of scientific research and those already tested in animal models are presented and discussed. RESULTS: Replacement tissues in clinical use are autologous and allogenic conjunctiva, nasal and oral mucous membranes, amniotic membrane and decellularized tissues. Autologous conjunctiva shows good results but is not suitable for large defects due to limited availability. In these cases autologous nasal and oral mucous membranes can be used; however, success is limited in cases of autoimmune diseases. Amniotic membranes are frequently applied clinically but goblet cell growth is limited. Different decellularized tissues are used clinically and goblet cell growth was found in vivo. Robust comparative studies are not yet available. Biological matrices such as fibrin, collagen, elastin, gelatin or hyaluronate and synthetic tissues from the group of polyesters are being investigated in the laboratory and in animal models. These studies show good epithelialization and goblet cell growth in vivo. CONCLUSION: Transplantation of conjunctiva, nasal and oral mucous membranes and amniotic membranes show satisfactory clinical results but exhibit individual weaknesses. Further studies in animal models and clinical settings are required to further evaluate the benefits of other matrices, such as cell-free tissues or other biological and synthetic matrices.

[Regenerative medicine for the corneal epithelium : Cell therapy from bench to bedside]. / Regenerative Medizin für das Hornhautepithel : Zelltherapie in Wissenschaft und Klinik.

In the case of thermal or caustic burns of the ocular surface, loss of limbal epithelial stem cells leads to compromised self-renewal of the corneal epithelium. This results in permanent loss of vision. In these situations, transplantation of cultured limbal epithelial cells on an amniotic membrane or fibrin gel as substrate (Holoclar®) can help to regenerate the corneal surface. The required cells are obtained from the healthy partner eye, if available. Adult stem cells from other parts of the body potentially serve as alternative cell sources: hair follicles, oral mucosa, mesenchymal stromal cells, or induced pluripotent stem cells (originally, e.g., skin fibroblasts). The reprogramming of such cells can be achieved with the help of transcription factors. In addition, work is being done on biosynthetic or synthetic matrices, which not only serve as substrate material for the transplantation but also support the functional properties of these cells (self-renewal, corneal epithelial-typical phenotype).